title: Size Matters: Reduction of Nuclear-Size Related Uncertainties in Atomic Spectroscopy

contributor:
Burgess, Clifford
Physics and Astronomy

subject:
Atomic Spectroscopy
Effective Field Theory
Renormalization
Non-perturbative effects

abstract: This work details how to use the Point-Particle Effective Field Theory (PPEFT) framework to make predictions for the nuclear-size contributions to spectroscopic transitions of atoms without the overbearing large uncertainties generally associated with such effects. After a lightning review of Quantum Field Theories, Effective Field Theories and their model-building algorithms, the backbones of the PPEFT formalism are laid down by considering the low-energy effective theories of lumps. Then, by drawing an analogy between a certain type of lumps and a freely propagating point-particle we build a PPEFT for nuclei, which we gradually couple to gauge and fermionic fields. We find that the consequences of having a nucleus in our theory are captured by a set of new near-nucleus boundary conditions its action implies for the surrounding fields, set up on a Gaussian spherical boundary with arbitrary radius, $\epsilon$. Afterwards, we use this formalism to derive the effects of the finite size of the nucleus on bound-state energies in terms of Renormalization Group (RG)-invariant parameters that characterize the running of the PPEFT couplings in $\epsilon$, implied by these new boundary conditions in order to keep physical quantities independent of this fictitious scale. Surprisingly, when comparing to formulae from the literature that express these same energy shifts in terms of nuclear moments there always appear to be fewer RG-invariants than moments. By fitting these handful of parameters using experimental data we then reduce the errors in nuclear-size effect predictions for other transitions by writing them in terms of differences between spectroscopic measurements and their corresponding energy differences predicted by those bound-state Quantum Electrodynamics calculations that assume nuclei to be point-like. Finally, we apply this algorithm to the systems: ${}^4_2 {\rm He}^+$, $\mu \, {}^4_2 {\rm He}^+$, H, and $\mu$H, where we make such predictions.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: The finite size of the nucleus shifts the bound-state energy of electrons (or muons) in atoms. Although these effects had been captured through a large number of nuclear-model independent ``nuclear moments'' closely related to the extent of the nucleus in the past, they introduce large uncertainties into theoretical predictions, which hinders testing fundamental subatomic processes in spectroscopic measurements. In this work it is shown that there is a more manageable number of parameters that control these effects because the above moments always appear in specific combinations. This allows for trading these combinations for differences between experimental values and their theoretically expected ones that assume the nucleus to have no size, which is the key in making predictions for atomic transitions that do not suffer from the large nuclear errors. A large set of such predictions are made for Hydrogen and the principles are applied to its muonic cousin as well.


title: Factors Affecting the Morphology and Composition of MOF Crystals

contributor:
Shiping, Zhu
Filipe, Carlos
Chemical Engineering

abstract:
Porous materials have become a subject of great scientific interest in recent decades due to their broad range of applications, and their ability to interact with atoms, ions, and molecules both on the surface and throughout the bulk of a material. Among porous materials, zeolites and activated carbons have been the most intensively researched. However, in last two decades, a new class of porous materials known as metal-organic frameworks (MOFs) has drawn great attention from researchers.
Metal-organic frameworks (MOFs), also known as coordination polymers, are porous crystalline materials that were first synthesized in 1999; since that time, these materials have attracted significant interest due to their attractive properties.
This class of porous materials generally consists of crystalline compounds that are built from metal ions or metal ion clusters, which act as connectors and organic linkers. The synthesis of an MOF is dependent on the chemical structures and properties of all of its constituent components, with a huge range of network topologies (i.e., one-, two-, and three- dimensional topologies) having been developed since the first MOFs were reported. In addition, the ability to change ligands allows a variety of organic linkers with different functional groups to be introduced to the network. Furthermore, pore size, pore shape, functionality, and network topology can all be tuned, thus allowing the properties of an MOF to be adjusted to suit a particular application. Most reported MOFs were synthesised via solvothermal and hydrothermal methods using organic solvent or water as a medium and high temperatures. To avoid the longer reaction times usually required for these methods, researchers have developed new methods, such as microwave/ultrasound-assisted process, which allow MOFs to be synthesized in only a few minutes.   Aside from the above-noted methods, other commonly used methods include electrochemical methods, mechanochemical methods, and synthesis under solvent-free conditions, among others.
Although researchers have become interested in MOFs due to the huge number of different MOFs that can be synthesized using relatively simple preparation methods, the root of interest in MOFs is due to their unique properties. Unlike other porous materials such as activated carbons and zeolites, MOFs offer thermal and chemical stability, ordered structure with various reactive sites, tunable pore properties, ultra-low densities, and large internal surface areas of up to 7000 m2g-1. As a result of these properties, MOFs have emerged as an interesting class of materials with various applications. One of the most commonly researched MOF applications is for the storage of gases (methane and hydrogen). In particular, MOFs are well-suited for hydrogen storage due to their high surface areas and low densities.  Similarly, MOFs have also been examined as good candidates for hydrogen storage due to their high surface areas and pore volumes. Furthermore, adjustable pore sizes and controllable surface properties, along with high surface areas, make MOFs ideal candidates for gas separation applications. Some of the other most commonly investigated MOF applications include their use as drug delivery systems, as chemical sensors,  for catalysis, and for air purification.
Even though MOFs possess unique properties, the study of their potential is often limited due to the form in which they are produced, which is most often a powder. To overcome this problem, researchers have attempted to fabricate MOFs as membranes, as well as attempted to deposit them onto cost-effective polymeric substrates or ceramics, to name a few notable formats.  One attractive approach that has been garnering more attention is the fabrication of composites using MOFs and cellulose based materials.
The manipulation of the size and shape of the crystals is important because it can help determine the physical properties of the final material and enable specific applications. Given the recent surge in interest on attaching MOFs to various surfaces, we examine potential approaches to controlling the morphology of MOF-assemblies. In addition, we grew MOF crystals using natural substrates, and attempted to manipulate their shape by altering some of the initial parameters. Furthermore, since it is always desirable to discover new MOFs, we modified well-known MOFs by introducing another metal into the framework to examine how doing so affects the morphology of the parent MOF.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Carpal Tunnel Pathomechanics: Vascular Dynamics, Tissue Kinematics, & Nerve Function

contributor:
Keir, Peter
Kinesiology

subject: Carpal Tunnel Syndrome

abstract: Carpal tunnel syndrome (CTS) is a common peripheral compression neuropathy which is often idiopathic in etiology.  There is evidence that the development of CTS may result from circulatory disturbances.  The purpose of this thesis was to improve our understanding of the vascular component to the development and progression of CTS.  Ultrasound allowed for non-invasive investigation of median nerve intraneural blood flow and morphology, tissue stiffness, and mechanics of the flexor digitorum superficialis (FDS) tendon and its adjacent subsynovial connective tissue (SSCT).  Nerve conduction study (NCS) allowed for investigation of median nerve function.  Three studies were completed, two with patients and one involving healthy participants, to investigate the relationship between local blood flow and carpal tunnel tissue function, morphology, and mechanics.  Nerve function, intraneural blood flow, individual FDS and SSCT displacements, and measures of shear strain (relative FDS-SSCT displacement and shear strain index (SSI)) were quantified in CTS patients (Chapter 2).  These patients were followed-up six months later and the measures were repeated (Chapter 3), allowing me to determine the prognostic value of ultrasound measures.  Results from these two studies suggested a high interdependency among intraneural blood flow velocity, nerve function, and FDS-SSCT relative displacement and SSI.  Intraneural blood flow velocity, peak FDS-SSCT relative displacement, and SSI were also significant predictors of median nerve function at 6-months follow-up.  To directly investigate the effects of circulatory disturbances, temporary partial ischemia of the carpal tunnel was induced in healthy participants through a 30-minute occlusion protocol (Chapter 4).  Partial ischemia immediately decreased intraneural blood flow velocity.  Nerve dysfunction, and increased SSI and relative displacement were observed soon after.  This thesis clearly demonstrates the interrelationship among median nerve vascular dynamics, tendon-SSCT kinematics, and nerve function.  Altered nerve blood flow may be a driver in the development of CTS.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Carpal tunnel syndrome (CTS) is due to compression of the median nerve as it passes through the carpal tunnel which is located at the base of the palm.  Nerve compression leads to nerve dysfunction, resulting in symptoms of tingling, numbness and weakness of the hand.  The purpose of this thesis was to improve our understanding of the effects of altered blood flow on the development of CTS.  I conducted three unique studies to investigate the relationship among nerve blood flow, nerve function, and motion of the tendons and connective tissue within the carpal tunnel.  The use of ultrasound allowed for real-time, non-invasive investigation of function in these tissues.  Results from these three studies clearly demonstrate the interrelationship between nerve function, tendon-connective tissue motion and adequate nerve blood flow.  These findings have implications for individuals with cardiovascular conditions and for people working under conditions that may compromise normal blood flow.


title: Interactive effects of wastewater effluent and hypoxia on the metabolic physiology and health of mummichog killifish (Fundulus heteroclitus)

contributor:
Scott, Graham
Biology

subject: Pollution

subject: Respirometry

subject: Pharmaceuticals and personal care products

subject: Aerobic metabolism

subject: Metabolic depression

abstract: This thesis is organized in “sandwich” format, as recommended by my supervisory committee. It consists of three main chapters. Chapter one is a general introduction and outlines the background information leading to the objectives and hypotheses of my thesis research. Chapter two is a manuscript prepared for submission to a peer-reviewed scientific journal. Chapter three is an overview of the major findings of this thesis, their implications in fish physiology and ecotoxicology, including suggestions of future directions of research. Appendix A contains data from an additional series of experiments that were conducted during my thesis but are not included as a full data chapter. It will be prepared for publication after my defence.

abstract: Hypoxia often occurs in aquatic ecosystems that receive effluent from municipal wastewater treatment plants (WWTP). WWTP effluent contains contaminants that could disrupt the complex physiological pathways fish use to cope with hypoxia (e.g., pharmaceuticals, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons), but the effects of WWTP effluent on the physiological responses of fish to chronic hypoxia is poorly understood. We exposed mummichog killifish (Fundulus heteroclitus) to hypoxia (5 and 2 kPa O2) and/or WWTP effluent for 21 days in a full factorial design. We then measured hypoxia tolerance, whole-animal metabolism, gill morphology, haematology, and tissue metabolites. In clean water, killifish responded to chronic hypoxia with improvements in hypoxia tolerance – increases in time to loss of equilibrium at 0.5 kPa (tLOE) and decreases in critical O2 tension (Pcrit) – in association with increased gill surface area as a result of regression of the interlamellar cell mass (ILCM). Concurrent exposure to wastewater attenuated the increases in tLOE and gill remodeling in chronic hypoxia, and nearly depleted brain glycogen stores. Therefore, exposure to WWTP effluent can disrupt the physiological mechanisms fish use to cope with chronic hypoxia and impair hypoxia tolerance. My research suggests that the combination of stressors near WWTPs can have interactive effects on the physiology and health of fish.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Low oxygen conditions, known as ‘hypoxia’, frequently occur in aquatic ecosystems that receive municipal wastewater treatment plant (WWTP) effluent. WWTP effluent is a continuous and complex source of pollution, including contaminants that can disrupt fish physiology, affecting their ability to cope with stressors, like hypoxia. The effects of WWTP effluent on the responses of fish to chronic hypoxia are poorly understood. To address this research gap, I examined the effects of hypoxia and WWTP effluent on chronically exposed mummichog killifish. I provide evidence that combined exposure to hypoxia and wastewater affected hypoxia tolerance, gill structure, and depleted energy stores in the brain. My thesis demonstrates that WWTP effluent can disrupt mechanisms that fish use to cope with chronic hypoxia and impair hypoxia tolerance. These findings contribute to the existing body of work that documents the interactive effects of combined stressors in effluent-dominated ecosystems on the physiology and health of fish.


title: Pharmacogenetics of Methadone Maintenance Treatment Outcomes in Opioid Use Disorder Patients

contributor:
Samaan, Zainab
Neuroscience

subject:
genetics
methadone
opioid use disorder
treatment outcome

abstract:
Background: Opioid use disorder (OUD) has been an increasing concern in Canada as mortality rates continue to rise. Though OUD treatments, such as methadone maintenance treatment (MMT), reduce its burden, they could potentially cause harm due to OUD’s variance in severity and presentation across individuals. It is hypothesized that genetic variants such as single nucleotide polymorphisms (SNPs) could predispose patients to respond differently to MMT. In addition, sex differences have been observed in opioid use patterns, treatment outcomes, and genetic make-up. As such, this thesis aims to identify significant SNPs associated with treatment outcomes in genome-wide association studies, and test biologically relevant SNPs with MMT outcomes of interest, while highlighting sex differences. This is achieved through a systematic review protocol, a systematic review, and a candidate gene study.
Methods: A protocol was prepared for the planning of the first ever systematic review of genome-wide significant findings of medication-assisted treatment outcomes for OUD patients. The systematic review assessed the literature findings and study qualities, narratively summarizing significant associations. Next, a candidate gene study analyzed the association between SNPs in OPRM1 and CYP2B6 genes, and continued opioid use, relapse, and methadone dose within an ancestrally European sample (n=1226). Sex-stratified and sex-interaction analyses were also conducted.
Results: The systematic review included 5 studies and qualitatively assessed 43 unique genetic variants. The candidate gene study showed no significant associations between the selected OPRM1 and CYP2B6 SNPs and outcomes of interest. While no significant differences between the sexes were observed, rs73568641 and rs3745274 showed near significance associations in only one sex, females, and males, respectively.
Discussion: Through the study of genetic variants associated with treatment outcomes in the literature and our sample of ancestrally European individuals on MMT, we were able to highlight gaps in pharmacogenetics research and identify areas of focus for future studies.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Recently, opioid use disorder (OUD) has been declared a national crisis in Canada. OUD treatments are helpful in reducing opioid use and adverse events. However, their dosing and metabolism in patients can impact continued opioid use, relapse, or treatment dose changes. Due to the variability in response between individuals, there might be a genetic basis to treatment outcomes. This thesis explores which genetic variants reported in previous studies are involved in OUD treatment outcomes. Then, it tests select genetic variants in OPRM1 and CYP2B6 genes to see if they are linked to specific outcomes in an Ontario population and tries to identify if these associations differ by sex. No significant associations were found, though associations in males and females had near-significant results in one sex but not the other. Despite suggesting sex’s possible involvement in treatment outcomes, more research is necessary to confirm these findings.


title: Longitudinal Data Clustering Via Kernel Mixture Models

contributor:
McNicholas, Paul
Statistics

subject:
kernel mixture model
longitudinal data clustering

abstract: Kernel mixture models are proposed to cluster univariate, independent multivariate and dependent bivariate longitudinal data. The Gaussian distribution in finite mixture models is replaced by the Gaussian and gamma kernel functions, and the expectation-maximization algorithm is used to estimate bandwidths and compute log-likelihood scores. For dependent bivariate longitudinal data, the bivariate Gaussian copula is used to reveal the correlation between two attributes. After that, we use AIC, BIC and ICL to select the best model. In addition, we also introduce a kernel distance-based clustering method to compare with the kernel mixture models. A simulation is performed to illustrate the performance of this mixture model, and results show that the gamma kernel mixture model performs better than the kernel distance-based clustering method based on misclassification rates. Finally, these two models are applied to COVID-19 data, and sixty countries are classified into ten clusters based on growth rates and death rates.

abstract: Thesis

abstract: Master of Science (MSc)


title: CHARACTERIZATION OF CYCLIC MOTOR PATTERNS AND HAUSTRAL ACTIVITIES IN THE HUMAN COLON BY HIGH-RESOLUTION MANOMETRY

title: CYCLIC MOTOR PATTERNS AND HAUSTRAL  ACTIVITY IN THE HUMAN COLON

contributor:
Huizinga, Jan
Medical Sciences

subject:
colonic motility
cyclic motor patterns
haustral activity
high-resolution colonic manometry
rectal pressure waves
interstitial cells of cajal
sphincter of O'Beirne

abstract: This thesis focuses on the characterization of rhythmic activity in the colon of healthy subjects and patients diagnosed with refractory constipation; this activity is mediated by pacemaker cells in the gastrointestinal system, the Interstitial cells of Cajal (ICC). The myogenic activity described are the cyclic motor patterns (CMP) and haustral activity; characterization of these motor patterns in healthy subjects provided control values for the subsequent comparison in patients. Frequency analysis of CMP revealed a novel high-frequency activity (7-15cpm) unrelated to the breathing artefact. Three categories of cyclic motor patterns were observed: (1) CMP following mass peristaltic events (HAPW); (2) those that occur in isolation of other colonic motor patterns (HAPW) in the colon; and (3) low-frequency (2-6cpm), prominently retrograde rhythmic activity in the rectum. CMP were scarcely present in majority of the patients; however, elevated retrograde CMP in the distal colon and rectum in some patients plays a role in retarding flow of colonic content. A detailed characterization of haustral activity (comprised of 2 boundaries and the activity within a haustrum) is reported for the first time using high-resolution colonic manometry. Furthermore, we find that over expression of haustral boundary activity in patients serves as a disproportionate hindrance in colonic transit. An in-depth methodology is developed for the identification and subsequent analysis of haustral activity and CMP; this provides transparency in the data acquisition and analysis. Lastly, a sphincter at the rectosigmoid junction, sphincter of O’Beirne is presented in a patient case report. The persistent presence and paradoxical contractions of this sphincter served to impede flow colonic content, an important factor contributing to the pathophysiology of severe refractory constipation.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Colonic manometry tests and measures strength and coordination of colonic muscles contractions. This tool was used to understand the rhythmic colonic motor patterns and their contribution to motility in healthy subjects and patients with constipation. Rhythmic activity in the gut is mediated by pacemaker cells, Interstitial cells of Cajal (ICC). We present a detailed characterization of ICC-mediated rhythmic activity that (1) occurs in the small pouches making up the colon (haustra) and (2) is greater than 5cm along the length of the colon (cyclic motor patterns-CMP).CMP possess high-frequency activity (7-15cpm), in addition to activity observed in the low-frequency range (2-6cpm). Activity in the haustra, or haustral activity, is comprised of 2 boundaries with activity within these bounds (intra-haustral activity); the overexpression in patients serves to retard flow of colonic content. Sphincter of O’Beirne is the last haustral boundary at the rectosigmoid junction; its persistent presence was characterized in a patient with refractory constipation.


title: Development of Robust Biofunctional Interfaces for Applications in Selfcleaning Surfaces, Lab-Ona-Chip Systems, and Diagnostics

contributor:
Didar, Tohid
Mechanical Engineering

subject:
Biofunctionalization
Biosensors
Microfluidics
biomolecule immobilization

abstract:
Biofunctional interfaces capable of anchoring biomolecules and nanoparticles of interest onto a platform are the key components of many biomedical assays, clinical pathologies, as well as antibacterial and antiviral surfaces. In an ideal biofunctional surface, bio-entities and particles are covalently immobilized on a substrate in order to provide robustness and long-term stability. Nonetheless, most of the reported covalent immobilization strategies incorporate complex wet-chemical steps and long incubation times hindering their implementation for mass production and commercialization. Another essential factor in the biointerface preparation, specially with regard to biosensors and diagnostic applications, is utilization of an efficient and durable blocking agent that can inhibit non-specific adsorption of biomolecules thereby enhancing the sensitivity of sensors by diminishing the level of background noise. Many of the commonly used blocking agents lack proper prevention of non-specific adsorption in complex fluids. In addition, most of these agents are physically attached to surfaces making them unreliable for long-term usage in harsh environments (i.e. where shear stresses above 50 dyn/cm2 or strong washing buffers are involved).
This thesis presents novel and versatile strategies to covalently immobilize nanoparticles and biomolecules on substrates. The new surface coating techniques are first implemented for robust attachment of TiO2 nanoparticles onto ceramic tiles providing self-cleaning properties. Further, we utilize similar strategies to covalently immobilize proteins and culture cells in microfluidic channels either as a full surface coating or as micropatterns of interest. The new strategies allow us to obtain adhesion of ~ 400 cells/mm2 in microfluidic channels after only 1-day incubation, which is not achievable by the conventional methods. Moreover, we show the possibility of covalently micropatterning of biomolecules on lubricant-infused surfaces (LISs) so as to attain a new class of biofunctional LISs. By integration of these surfaces into a biosensing platform, we are able to detect interleukin 6 (IL-6) in a complex biofluid of human whole plasma with a limit of detection (LOD) of 0.5 pg.mL-1. This LOD is significantly lower than the smallest reported IL-6 LOD in plasma, 23 pg mL-1, using a complex electrochemical system. The higher sensitivity of our developed biosensor can be attributed to the distinguish capability of biofunctional LISs in preventing non-specific adhesion of biomolecules compared to other blocking agents.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: The key goal of this thesis is to provide new strategies for preparation of robust and durable biointerfaces that could be employed for many biomedical devices such as self-cleaning coatings, microfluidics, point-of-care diagnostics, biomedical assays, and biosensors in order to enhance their efficiency, sensitivity, and precision. The introduced surface biofunctionalization methods are straightforward to use and do not require multiple wet-chemistry steps and incubation times, making them suitable for mass production and high throughput demands. Moreover, the introduced surface coating strategies allow for creation of antibody/protein micro-patterns covalently bound onto a biomolecule-repellent surface. The repellent property of the surfaces is resulted from infusion of an FDA-approved lubricant into the surface of a chemically modified substrate. While the surface repellency can effectively prevent non-specific adhesion of biomolecules, the patterned antibodies can locally capture the desired analyte, making them a great candidate for biosensing.


title: The Response of Mobile Applications to Crisis in Canada

contributor:
Lokker, Cynthia
eHealth

abstract: When  a  crisis  strikes,  technology  allows  information  to  move  quickly.  By leveraging mobile technology, mobile applications (apps) can serve as a reliable way to ensure rapid communication. This thesis evaluated mobile apps created for two crises: the COVID-19 pandemic and the Indigenous Mental Health crisis.  Through the completion of two independent scoping reviews on each topic, apps were collected, analyzed and assessed in a double-blind nature, including results from both grey and scientific literature searches. The results of these scoping reviews were compiled to create an overall report on the capability of these apps to address each crisis respectively. The results indicate that while apps can be quickly developed and made available on application stores in order to help mount  a  rapid  response  to  crises,  many  do  not  fit  the  needs  of  users  and  none  can completely cater to a crisis within one app. Further research is required to provide evidence of effectiveness, acceptability and usabilityof these apps. Innovation and collaboration between  key  stakeholders,  government,  health  care  organizations  and  application developers will be essential to address the identified gaps and facilitate the creation of successful apps for use in either crisis.

abstract: Thesis

abstract: Masters of Health Informatics (MHI)


title: Methodological and Statistical Issues in the Design and Analysis of Stratified Cluster Randomized Trials

contributor: Clinical Health Sciences (Health Research Methodology)

abstract:
Background and Objectives
While the number of adopting stratified cluster randomized trials (CRTs) is
increasing, we have limited knowledge about the methodological and statistical issues
pertaining to this design.
Our objectives were to (i) survey the literature to assess the methodological and
statistical issues and quality of reporting of stratified CRTs; (ii) examine the sensitivity of
methods for analyzing data from stratified CRTs; (iii) evaluate the performance of methods
for analyzing continuous data from stratified CRTs.
Methods
We conducted a systematic survey and identified the stratified CRTs from the
database MEDLINE. Data were abstracted on several methodological and statistical issues
including sample size, randomization, and method of analysis. Two empirical studies were
conducted to examine the robustness of methods for analyzing continuous and count data
from stratified CRTs. Furthermore, a simulation study was performed to evaluate the
performance of methods for analyzing continuous data from stratified CRTs under different
scenarios including number of clusters, and cluster sizes.Results and Conclusions
There was significant deficiency in reporting and analysis of data from stratified
CRTs. The majority of the studies did not adjust the primary method for both clustering
and stratification to assess the intervention effect.
The results from the empirical studies indicated that the methods for analyzing
continuous and count data yielded similar conclusions. However, these methods varied in
terms of magnitude of the effect sizes and widths of the 95% confidence intervals (CIs).
Moreover, these studies demonstrated that, widths of the 95% CIs were narrower, and pvalues
were lower when adjusted for stratification compared to without adjusted for
stratification.
The results from the simulation study showed that, performance of all methods
improved as the number of clusters and cluster sizes increases. However, the performance
of these methods deteriorated as the value of intra-cluster correlation coefficient (ICC)
increases. Generalized estimating equations (GEE) and meta-regression yielded type I error
rate of approximately 10% for small number of clusters. Meta-regression was the least
powerful and efficient method compared to GEE, mixed-effects, and cluster-level linear
regression methods.
The contributions of this thesis will guide the researchers to make informed
decision about assessing the intervention effect and reporting of stratified CRTs.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Cryptic genetic variation and its contribution to genetic assimilation in natural populations of Drosophila melanogaster

title: CGV and genetic assimilation in Drosophila melanogaster

contributor:
Dworkin, Ian
Biology

abstract: Over 65 years ago, Waddington demonstrated phenotypically plastic traits can evolve to become constitutive, a process he termed genetic assimilation. Experiments demonstrated genetic assimilation evolves rapidly, with the response in large part due to segregating genetic variation only expressed in rare/novel environments, but otherwise phenotypically cryptic. Despite previous work suggesting a substantial role of cryptic genetic variation contributing to the evolution of genetic assimilation, some have argued for a prominent role for new mutations of large effect concurrent with selection. Less concerned by the relative contribution of CGV or new variants, Waddington aimed to test the role of canalization, an evolved form of robustness. While canalization has been extensively studied, its role in the evolution of genetic assimilation is disputed, in part because explicit tests of evolved robustness are lacking. To address these questions, we recreated Waddington’s selection experiments on an environmentally sensitive change in Drosophila wing morphology (crossvein development), using many independently evolved replicate lineages. Using these we show that 1) CGV has potentially pleiotropic and fitness consequences in natural populations and may not be always be “cryptic”. 2) CGV, but not new variants of large effect are largely responsible for the evolved response demonstrated using both genomic and genetic approaches. 3) Using both environmental manipulations and mutagenesis of the evolved lineages that there is no evidence for evolved changes in canalization contributing to genetic assimilation.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Investigations of the heterogeneity of host-associated bacteria during respiratory infections

contributor:
Surette, Michael G
Biochemistry and Biomedical Sciences

abstract:
Respiratory infections are a leading cause of mortality and morbidity worldwide and will continue to be prevalent in the coming decades. The burden associated with acute respiratory infection is mostly due to the high prevalence of pneumonia, including hospital-acquired pneumonia. Respiratory infections are diverse with respect to clinical features, population targeted, etiology, treatment options, and development of potential complications. Several factors such as the difficulty to identify the etiology of acute respiratory infections and subsequent inappropriate therapeutic plans contribute to the complexity of treating respiratory infections, and to the development of potential complications such as pleural empyema, bacteremia and sepsis. As such, further study of the microbes entering the respiratory tract as potential pathogens or contributing to disease outcome is required.
In this thesis, I have investigated the microbiome of the critically ill as part of the PROSPECT study (NCT02462590) which examines probiotics as a prophylactic treatment to reduce ventilator-associated pneumonia in the intensive care unit (ICU). Using 16S rRNA gene profiling, we identified a novel association between hospital mortality and low microbial α-diversity observed in the lower respiratory tract. Interestingly, this microbial signature was readily identifiable within days of patient admission to the ICU. I also carried out quality control on the probiotic (Lactobacillus rhamnosus GG) and investigated the microbiology of adverse events with possible involvement of the probiotic. We demonstrated that the patients enrolled in the PROSPECT study received a constant dose of the probiotic and that 70 % of the placebo used in this study contains no bacteria where the remaining capsules recovered a modest number of non-pathogenic bacteria. Moreover, our results showed that rare adverse events associated with the probiotic consumption could occur, though several events were potentially due to bedside contamination not infection.
Additionally, I performed a comparative genomic study of 151 isolates of the Streptococcus Anginosus/Milleri group which represents under-reported respiratory pathogens that may commonly be associated with pneumonia complications such as pleural empyema. This investigation has shown that these isolates are genetically heterogenous, where diversity was observed by the presence and identity of specialized genes and genomic features (e.g. prophages, antimicrobial resistance genes, and biosynthetic gene clusters). Moreover, we further characterized two phenotypically distinct isolates recovered from a single pleural empyema aspirate. The difference in morphotype was the consequence of the presence of a single mutation in a gene involved in exopolysaccharide production.
Taken together, this work characterized the heterogeneity associated with respiratory infections. This heterogeneity, from the microbial community, bacterial group, and isolate level, contributes to the challenge of identifying but also treating respiratory infections such as pneumonia and pleural empyema.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: From preschool to school-age: physical activity, physical literacy and health

title: Physical activity and physical literacy in childhood

contributor:
Timmons, Brian W.
Kinesiology

subject:
Physical activity
Physical literacy
Pediatrics
Exercise Science

abstract:
Physical activity is associated with a host of health benefits across childhood. Despite this, most children are not engaging in enough physical activity to achieve health benefits, and there is growing evidence that lifelong physical activity habits may be established in childhood. Theories suggest that physical literacy may be associated with health benefits due to its reciprocal relationship with physical activity participation. The associations between physical literacy, physical activity and health in children remain largely unstudied. The purpose of this thesis was to explore the relationships between physical literacy, physical activity and health across early and middle childhood.
The first study assessed the measurement properties of the Physical Literacy Assessment for Youth Tools, an assessment battery for physical literacy. We determined that this assessment had acceptable internal consistency, construct validity, and offered unique perspectives of a child’s physical literacy. We then determined that physical literacy was associated favourably with body composition, blood pressure, quality of life, and aerobic fitness in school-age children. Moderate-to-vigorous physical activity mediated the associations between physical literacy and aerobic fitness. Finally, the third study observed that physical activity trajectories from preschool to school-age were associated with school-age physical literacy.
These results highlight the importance of physical literacy in childhood, given its associations with physical activity and health indicators. Physical literacy was associated with favourable health indicators, supporting its position as a determinant of health. The participants in the lowest physical activity trajectory groups had the lowest physical literacy. These finds suggest that physical activity across early and middle childhood may play a formative role in the development of physical literacy. Future work should determine if these results are applicable to other age groups, such as early years or adolescents, and if changes in physical activity over time are associated with changes in physical literacy over time.

abstract: Thesis

abstract: Doctor of Science  (PhD)

abstract: Kids who are active every day will be healthier that those who aren’t. Unfortunately, most Canadian kids are not active enough to be healthy. We still don’t really know why some kids are active and some kids aren’t active. We think that physical literacy might be the missing piece to help kids be more active as they grow. This thesis studied the links between physical literacy, physical activity and health in kids. We found that we could measure physical literacy well in school-age kids. We also found that physical literacy was linked to health in kids. Kids who were the most active as they grew had the highest physical literacy. We saw that boys were more active than girls as they grew. Kids should start being active as preschoolers to help develop physical literacy. We need more programs and activities for kids to be more active to help develop physical literacy.


title: Ceramic membrane nanofiltration for industrial wastewater treatment – a comparison with conventional polymer membranes & data-driven modeling of organic compounds removal

contributor:
Latulippe, David
Mhaskar, Prashant
Chemical Engineering

subject:
Nanofiltration
Industrial Wastewater

abstract: Industrial wastewater treatment using conventional treatment technologies is becoming challenging day-by-day due to presence of ‘newer’ refractory compounds, lower treatment efficiencies and stricter environmental laws. Combination of conventional treatment techniques with modern treatment technologies like membrane filtration or advanced oxidation processes (AOPs) has shown promise in achieving high efficiencies. In this work we have worked towards development of a membrane nanofiltration unit to treat coagulation-flocculation pretreated IWW from a specialized treatment facility. More specifically, state-of-the-art TiO2 ceramic NF membranes with low molecular weight cut off (MWCO) (200, 450, 750, 8500 Da) purchased from Inopor Gmbh were tested on 6 different IWW samples due to their superior chemical stability, higher flux and high fouling resistance along with 3 commercial polymer NF membranes (NF90, NFX, NFS) for comparison purposes. Additionally, wastewater characterization dataset including composition analysis using Gas-chromatography Mass-spectroscopy (GC-MS) is leveraged to build data driven models for membrane performance prediction. ‘200 Da’ ceramic NF membrane was able to reject significant COD with an average rejection of 77% and 60% for two IWW samples with permeate flux between 5-15 LMH at 100-120 psi trans-membrane pressure (TMP). ‘200-Da’ membrane was also found to achieve more flux than ‘450 Da’ membrane while rejecting more COD at the same time. ‘200 Da’ membrane also showed lower flux decline than polymer membranes. Additionally, the ceramic NF membranes were found to be easily chemically cleanable restoring wastewater flux after fouling. Since polymer NF membranes were found to reject at higher COD rejection efficiencies (60-90%) and permeate flux, further improvement in ceramic membranes is needed to treat at higher efficiencies. 200 Da, NF90 and NFX membranes were found to be promising to reduce COD below target (600 mg/L) and should be studied further for this application.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: Conventional technologies for Industrial wastewater (IWW) treatment include biological treatment, coagulation, flocculation, adsorption and filtration. Many industries produce IWW with high concentration of biologically toxic organics ruling out the option of biological treatment. Moreover, with stricter regulatory laws in place for effluent discharge, adoption of new treatment technologies is needed. Nanofiltration (NF) is one such treatment technology that has seen a lot of growth in the past decade since its advent in 1980s. Polymer nanofiltration has been successfully used in applications such as dye removal in textile industry, as a pre-treatment method in desalination plants, for organic solvent nanofiltration in pharmaceutical industry and many more. More recent development of ceramic nanofiltration membranes has seen a lot of interest from researchers around the world due to their superior physical and chemical robustness, fouling resistant properties and higher permeability as compared to polymer NF membranes, though only a small amount of ceramic NF membranes are applied in industrial projects. To this end, we have conducted laboratory scale testing of 4 state of the art ceramic NF membranes on multiple real industrial wastewater samples collected from a specialized IWW treatment plant, along with 3 polymer NF membranes for comparison purposes. Additionally, a data-driven modeling approach leveraging the wastewater composition dataset is shown. The models can be used to predict % rejection of an unseen compound based on its chemical properties and provide insights into complex interactions between compounds and the membrane.


title: New Understanding for New Antibiotics: Bacterial Nutrient Stress and Drug Efflux

contributor:
Brown, Eric
Biochemistry and Biomedical Sciences

abstract: The dramatic decline in the discovery and development of novel antibiotics has been met with an exponential increase in antibiotic-resistant pathogenic bacteria. Calls for new chemical matter have been paradoxically answered with the withdrawal of multinational pharmaceutical companies from the field of antibiotic discovery and development. Nevertheless, scientific challenges have also been a major contributor to a lean antibiotic pipeline. Renewed efforts to gain a deeper understanding of the bacterial physiology, which governs growth and survival, are urgently needed. To this end, I have examined two important avenues with relevance to the field of new antibiotic discovery using Escherichia coli as a model: 1) a systems analysis of the interactions of essential functions under nutrient stress and 2) a physicochemical and structural analysis of small molecules to identify properties that influence Gram-negative activity and efflux susceptibility. I tackled the first aim by systematically combining 45 chemical probes that target essential cellular processes. I revealed a highly connected network of 186 interactions, of which 81 were synergistic and 105 were antagonistic. The network highlighted new connectivity between housekeeping functions and nutrient metabolism. I approached the second aim by screening ~314,000 diverse synthetic compounds for inhibitors of an efflux-deficient E. coli strain. I identified about 4,500 actives, of which approximately 84% showed high susceptibility to efflux. Using a machine learning approach, I assessed the physicochemical space occupied by these 4,500 inhibitors and determined that hydrophobic and planar small molecules with low molecular stability exhibited antibacterial activity only in efflux-compromised E. coli. Further, compounds with reduced branching and compactness showed increased susceptibility to efflux. Within this dataset, I also identified some compound series highlighting structural variations that have a large impact on efflux susceptibility. In all, the work provides new insights into an emerging target in antibiotic drug discovery, namely nutrient stress, and uncovers some physicochemical properties and structural motifs that contribute to antibacterial activity and efflux susceptibility of small molecules.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Use of magnetic resonance imaging to assess tibiofemoral cartilage behaviour following loading: a multi-disciplinary evaluation of cartilage mechanics

contributor:
Maly, Monica R.
Keir, Peter J.
Kinesiology

abstract:
Understanding articular cartilage mechanics is imperative to gain insight into tissue tolerances and loads, and how these may change with disease.  This thesis used a multi-disciplinary approach to quantify cartilage mechanics using magnetic resonance imaging (MRI), a non-invasive tool for the evaluation of soft tissues.  Study 1 (Chapter 2) outlined an in vivo study that aimed to identify the effect of 1) running; 2) biological sex; and 3) their interaction on tibial and femoral cartilage thickness changes following running using Statistical Parametric Mapping (SPM).  Running caused deformation in all knee compartments, and especially in the lateral tibia (p < 0.0001).  Females had thinner cartilage than males (p < 0.009).  Finally, clusters indicating an interaction of Running and Sex were identifi ed on the posterior lateral tibia, suggesting females experienced greater cartilage deformation than males (p < 0.012). Studies 2 and 3 (Chapters 3 and 4) integrated MRI and biomechanical datasets to explore
the loading environment at the knee. Study 2 investigated the effect of daily cumulative knee load (measured using musculoskeletal modeling and accelerometry) on cartilage response (change in morphology, composition) following running in women.  This cumulative loading metric was related to tibial volume change (F(4, 14) = 4:68, p = 0.013, R2 = 0.50), suggesting a potential cartilage conditioning effect.  Study 3 outlined the use of an ex vivo porcine stifle model to build a 3D voxelwise statistical map exploring the relationship between cartilage mechanical properties (measured via automated indentation mapping) and cartilage outcomes from MRI (cartilage thickness, T2 change) following static loading.  No signi ficant relationships were identi fied; however, this novel integration of indentation mapping and MRI cartilage outcomes shows utility moving forward.  Overall, this thesis characterizes cartilage response to biomechanical load using novel tools derived by integrating engineering, biomechanics, and imaging.  Together this work provides an exciting opportunity to explore and quantify spatial relationships between mechanical properties and cartilage MRI outcomes.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
This thesis used a multi-disciplinary approach to characterize articular cartilage mechanics
in the knee joint.  First, the deformation of knee cartilage following running was quantifi ed using magnetic resonance imaging (MRI), and the effects of 1) running; 2) biological sex; and 3) their interaction were explored using a statistical mapping procedure.  Second, daily cumulative knee load (or total load incurred by the knee joint over a day) was related to knee cartilage deformation (via MRI) following running in women.  Third, a pig knee model was used to develop a 3D statistical model predicting cartilage mechanical properties from MRI-derived cartilage metrics.  This thesis integrated elements of engineering, biomechanics, and medical imaging to derive novel evaluation techniques for the cartilage of the knee joint.  This work builds a critical foundation for future development of statistical models that can assist with the assessment of cartilage health and disease management.


title: Cardiorespiratory Optimized Guided-Breathing for Post-Stress Recovery in a Group Setting

contributor:
Trainor, Laurel J
Psychology

subject: Biofeedback, HRV, GSR

abstract: Stress is the feeling of emotional strain in response to a perceived threat that disturbs the homeostasis and affects our health and well-being. Short-term stress has some beneficial effects such as improving alertness and performance and boosting memory, but prolonged stress responses can have deleterious effects on human health, including tissue damage and disease. Thus regulating stress levels is important for dealing with difficult situations to mitigate negative impacts. Prevailing approaches to treating stress have some limitations and drawbacks. Slow breathing/Resonant frequency breathing or HRV biofeedback and Music Therapy are some of the widely used methods for dealing with stress and anxiety. These methods are thought to stimulate the vagus nerve that promotes autonomic balance and hence reduce symptoms of stress. The current study investigated the effects of relaxing music and Slow breathing/Resonance frequency breathing on heart rate variability and respiration as well as on subjective measures of perceived stress. Although relaxing techniques are often administered in group classes, research studies in groups are rare. To our knowledge, this is the first study to investigate the effects of music listening and slow breathing in reducing stress evoked by watching a stressful movie in a group setting. The study sought to evaluate the effectiveness of the aforementioned interventions in reducing stress, measured by psychophysiological and self-report measures. Thirty-two participants were recruited and randomly assigned to two groups (Music, Breathing). We hypothesized that after watching the stressful movie, the Breathing group would show greater physiological and self-report changes marking greater stress reduction compared to the Music group. Results indicated that slow Breathing affected perceived stress as well as HRV, whereas Music affected perceived stress, but had no significant effect on HRV. Also, results indicated that Slow Breathing and not Music reduced the complexity of heart and respiration signals. Moreover, the study found that respiration and heart rhythm synchronized maximally during slow breathing. The results suggest that the interventions studied in this research can be used as an effective stress reduction tool in a group setting.

abstract: Thesis

abstract: Master of Science (MSc)


title: Chemical thermoplasticization of lignocellulosic fibers by reactive extrusion

contributor:
Thompson, Michael
Chemical Engineering

subject: Renewable Thermoplastic Lignocellulose

abstract:
Cellulosic thermoplastics are anticipated as promising replacements to petroleum-based thermoplastics, but their high manufacturing costs have limited wide-spread application. The primary objectives of this thesis were to use low-cost lignocellulose, practically forestry waste, as the raw material rather than more expensive purified cellulose in the preparation of new plastics and, consequently, to develop an economical reactive process focused on diminishing the use of expensive solvents in the thermoplasticization of lignocellulose.
The thermoplasticization of lignocellulosic fibers started by developing a high solids content (60 wt%) twin-screw extrusion technique to defibrillate the raw material for the subsequent chemical modification. By this approach, the received lignocellulosic fibers showed improving handling as a feedstock for extrusion as well as chemical accessibility. To effectively wet the lignocellulosic fibers for chemical modification and avoid using expensive and largely ineffective solvents, a low-cost additive was derived by mimicking aspects of an ionic liquid using benzethonium chloride (hyamine) and sulfuric acid. The effectiveness of the hyamine/sulfuric acid wetting agent was demonstrated initially in a bench-top method where the additive also became chemically bonded to the lignocellulose and strongly contributed to its thermoplasticity. During acetylation, this new and low-cost wetting/functionalizing agent converted the lignocellulosic fibers into a compression-moldable thermoplastic. The molar ratio of benzethonium chloride to sulfuric acid was found to be the most significant variable to determine grafting behaviour as well as degradation of the polymer chains.
Subsequently, this new modification chemistry was translated over to the environment of a twin-screw extruder to devise a continuous, greener method of thermoplasticization for lignocellulose. The new reactive extrusion process had a short reaction time of 45-90 s and yet showed a good tendency for producing a flowable thermoplastic suitable for melt molding without plasticizers. A notable benefit to the method was the moldable lignocellulosic bioplastic maintained the excellent stiffness inherent to cellulose. Moreover, by the reactive extrusion method, the properties of the lignocellulosic thermoplastics were found to be tunable with the selected esterifying agents (butyric anhydride versus acetyl anhydride) and the molar ratio of benzethonium chloride to sulfuric acid. A statistical analysis based on a Design of Experiment method revealed details on desirable extrusion conditions.
The project concluded with improvements to the high solids-content process was exploring the novel concept of a recycle stream for reactive extrusion. The excessive esterifying agent content used in the initial studies was necessary to lubricate the fibrous mass inside the extruder else it would jam the process. This meant that the extrudate left the extruder with an unnecessary amount of reactant and required costly cleaning. The idea of recycling a portion of the newly made cellulosic thermoplastic was to add a natural lubricant and thereby lower the content of the esterifying agent in the extruder. Under optimal recycling conditions, a significant 50% decline in reactant was possible without decreasing the degree of modification or harming the thermoplasticity of the modified lignocellulose.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
Wood biomass is the most abundant renewable material on the planet and comprises polymer chains like plastics. These polymer chains in wood biomass are locked by strong bonds, which limits their mobility. It is for this reason that wood biomass can not “melt” like commercial plastics such as polyethylene, and thus limits its application in the manufacture of objects with complex shapes. Using chemical modifiers to react with the wood biomass can unlock those bonds among the chains and convert it into a “meltable” thermoplastic. The current preparation of thermoplastics from wood biomass is very costly because of using expensive purified cellulose and solvents to assist the reaction.
This thesis describes the development of an economical reactive process for converting less purified wood biomass into thermoplastics. It used low-cost lignocellulose, practically forestry waste, and discovered a low-cost but effective reaction method for using less expensive reactants. Finally, a rapid mechanically assisted reaction process (called reactive extrusion) was adopted based on the new chemistry to convert the lignocellulose biomass with significantly fewer reactants than needed in a batch system.


title: Variational data assimilation for the shallow water equations with applications to tsunami wave prediction

contributor:
Kevlahan, Nicholas
Computational Engineering and Science

subject: tsunami, shallow water equations, data assimilation, bathymetry, adjoint, sensitivity analysis

abstract:
Accurate prediction of tsunami waves requires complete boundary and initial condition
data, coupled with the appropriate mathematical model. However, necessary
data is often missing or inaccurate, and may not have sufficient resolution
to capture the dynamics of such nonlinear waves accurately. In this thesis we
demonstrate that variational data assimilation for the continuous shallow water
equations (SWE) is a feasible approach for recovering both initial conditions and
bathymetry data from sparse observations. Using a Sadourny finite-difference finite
volume discretisation for our numerical implementation, we show that convergence
to true initial conditions can be achieved for sparse observations arranged in multiple
configurations, for both isotropic and anisotropic initial conditions, and with
realistic bathymetry data in two dimensions. We demonstrate that for the 1-D
SWE, convergence to exact bathymetry is improved by including a low-pass filter
in the data assimilation algorithm designed to remove scale-scale noise, and with
a larger number of observations. A necessary condition for a relative L2 error less
than 10% in bathymetry reconstruction is that the amplitude of the initial conditions
be less than 1% of the bathymetry height. We perform Second Order Adjoint
Sensitivity Analysis and Global Sensitivity Analysis to comprehensively assess the
sensitivity of the surface wave to errors in the bathymetry and perturbations in
the observations. By demonstrating low sensitivity of the surface wave to the reconstruction
error, we found that reconstructing the bathymetry with a relative
error of about 10% is sufficiently accurate for surface wave modelling in most cases.
These idealised results with simplified 2-D and 1-D geometry are intended to be
a first step towards more physically realistic settings, and can be used in tsunami
modelling to (i) maximise accuracy of tsunami prediction through sufficiently accurate
reconstruction of the necessary data, (ii) attain a priori knowledge of how
different bathymetry and initial conditions can affect the surface wave error, and
(iii) provide insight on how these can be mitigated through optimal configuration
of the observations.

abstract: Thesis

abstract: Candidate in Philosophy


title: Thermal and Hydraulic Performance of Finned Tube Heat Exchangers

contributor:
Ching, Chan Y.
Mechanical Engineering

subject:
Plain fin and tube heat exchanger
Bypass flow
Partially ducted heat exchanger
heat transfer correlation
friction factor correlation

abstract:
This study numerically examines the heat transfer and pressure drop performance of finned tube heat exchangers with staggered and inline tube layout for a range of tube pitch. The first part of the thesis considers the case where the heat exchanger is placed in fully ducted airflow. The simulations indicate that the performance reduced considerably for the staggered tube layout with an increase in the tube pitch, but a minimal difference for the inline tube arrangement. The effects of other geometrical parameters like fin pitch and the number of tube rows are then presented. Finally, a correlation for fin and tube heat exchangers with inline tube layout is proposed based on 280 simulations for 70 different configurations. The proposed heat transfer correlation can describe the database within ±8% discrepancy while the friction factor correlation can correlate the dataset within a ±10% discrepancy. The mean deviations for heat transfer and friction factor correlations are 4.3% and 5.4%.
An important factor that influences the performance of flat plate and finned tube heat exchangers is when there is bypass flow around the heat exchanger. The next section of this thesis numerically investigates the partially ducted inline fin and tube heat exchanger with side bypass. The effects of the side clearance and the Reynolds number on the heat transfer and the pressure drop performance of the heat exchanger are presented. The simulations indicate that the heat transfer performance depreciates by more than 25% for infinite side clearance. The study then compares the pressure difference observed for entry, exit and the friction pressure drop with the various correlations available in the literature. Finally, the heat transfer and pressure drop performance for staggered and inline tube layouts are compared.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Group 3 Metal Complexes of Rigid Neutral and Monoanionic Pincer Ligands

contributor:
Emslie, David
Chemistry

subject:
rare earth
rare earth cations
pincer ligands
olefin polymerization
intramolecular hydroamination
imidazol-2-imine
phosphinimine
cyclometallation
rare earth dications
rare earth alkyl complexes

abstract:
The synthesis of a rigid 4,5-bis(triphenylphosphinimino)-2,7-di-tert-butyl-9,9-dimethylxanthene (Ph3PN)2XT (1) ligand is outlined, along with a modified synthesis for previously reported 1,8-bis(triphenylphosphinimino)naphthalene (Ph3PN)2NAP (3). Reaction of neutral (Ph3PN)2XT with [Y(CH2SiMe3)3(THF)2] resulted in double cyclometallation, yielding the base-free monoalkyl complex, [({Ph2(C6H4)PN}2XT)Y(CH2SiMe3)] (2). Layering a concentrated THF solution of 2 with hexanes at −28 °C afforded THF-coordinated [({Ph2(C6H4)PN}2XT) Y(CH2SiMe3)(THF)]·2THF (2-THF·2THF), with a distorted pentagonal bipyramidal geometry and approximately meridional coordination of the pentadentate {Ph2(C6H4)PN}2XT dianion. Similarly, (Ph3PN)2NAP reacted with [Y(CH2SiMe3)3(THF)2] to afford a THF-coordinated monoalkyl complex, [{(Ph2(C6H4)PN)2NAP}Y(CH2SiMe3)(THF)] (4-THF). Layering a DME solution of 4-THF with hexanes at −28 °C afforded X-ray quality crystals of [{(Ph2(C6H4)PN)2NAP}Y(CH2SiMe3)(κ2-DME)]·hexane (4-DME·hexane), with a highly distorted pentagonal bipyramidal geometry and a facial coordination mode of the tetradentate {Ph2(C6H4)PN}2NAP dianion

	The synthesis of a rigid 4,5-bis(1,3-diisopropylimidazol-2-imine)-2,7,9,9-tetramethylacridan H(AII2) ligand (5) was achieved via a Buchwald-Hartwig cross-coupling reaction.  Reaction of the proligand H(AII2) with  [M(CH2SiMe3)3(THF)2] (M = Y(6), Sc(8)) yielded the base free dialkyl complexes [(AII2)Y(CH2SiMe3)2] (6) and [(AII2)Sc(CH2SiMe3)2] (8). The reaction of 6 with one equivalent of [CPh3][B(C6F5)4] yielded [(AII2)Y(CH2SiMe3)][B(C6F5)4] (7) in-situ. Complex 7 proved to be a potent intramolecular hydroamination catalyst for a variety of aminoalkane substrates.
	The attempted synthesis of 4,5-bis(1,3-diisopropylimidazol-2-imine)-2,7-di-tert-butyl-9,9-dimethylxanthene (XII2) via the Staudinger reaction resulted in the isolation of the triazene intermediate 4,5-bis(1,3-diisopropylimidazol-2-yliedene{triazene})-2,7-di-tert-butyl-9,9-dimethylxanthene XIA2 (9). Reaction of XIA2 with one equivalent of [Y(CH2SiMe3)3(THF)2] led to the isolation of [(XIA2)Y(CH2SiMe3)3] (10).  Synthesis of XII2 (11) was achieved via a Buchwald-Hartwig cross-coupling reaction. Reaction of XII2 with one equivalent of YCl3(THF)3.5 resulted in the isolation of [(XII2)YCl3] (12). In contrast, the reaction of XII2 with one equivalent of [Y(CH2SiMe3)3(THF)2] led to several unidentified products. Reaction of XII2 with 1 equivalent of [H(Et2O)2][B(C6F5)4] led to the isolation of the precursor [H(XII)2][B(C6F5)4] (13). The reaction of 13 with 1.1 equivalents of [M(CH2SiMe3)3(THF)2] (M = {Y(14), Sc(15)} led to the isolation of the monocationic  [(XII)2M(CH2SiMe3)2][B(C6F5)4] complexes.  The reaction of [(XII)2Sc(CH2SiMe3)2][B(C6F5)4] with 1.1 equivalents of B(C6F5)3 led to the abstraction of a methyl anion from the silicon center, with concomitant migration of the remaining alkyl group to the positively charged silicon, forming a new CH2SiMe2CH2SiMe3 alkyl group. This process is accompanied by MeB(C6F5)3 anion formation, forming a contact ion pair to afford the dicationic species [(XII)2Sc(CH2SiMe3)][MeB(C6F5)3][B(C6F5)4] 16.  In contrast, the reaction of 15 with 1.3 equivalents of [CPh3][B(C6F5)4] in the presence of 5 equivalents of toluene resulted in the synthesis of [(XII)2Sc(CH2SiMe3)(ɳx-toluene)][B(C6F5)4]2 17 in-situ. Complex 17 is a highly potent ethylene polymerization catalyst with an activity of 868 kg/mol·atm·h. The reaction of 15 with [HNMe2Ph][B(C6F5)4] led to the cyclometallation of the resulting NMe2Ph byproduct to yield [(XII2)Sc(C6H4NMe2)][B(C6F5)4]2 (18) in-situ.
The synthesis of a rigid, asymmetric 4-(1,3-diisopropylimidazol-2-imine)-5-(2,6-diisopropylanilido)- 2,7-di-tert-butyl-9,9-dimethylxanthene XAI (19) ligand was achieved by a two step Buchwald-Hartwig cross-coupling reaction with initial cross coupling of 1,3-diisopropylimidazol-2-imine followed by the cross-coupling of 2,6-diisoproylaniline. The reaction of XAI with 1.1 equivalents of [Y(CH2SiMe3)3(THF)2] yielded [(XAI)Y(CH2SiMe3)2] (20).    Subsequent reaction of [(XAI)Y(CH2SiMe3)2] with 1 equivalent of [CPh3][B(C6F5)4] in the presence of 10 equivalents of toluene resulted in the synthesis of the toluene coordinated [(XAI)Y(CH2SiMe3)(ɳx-toluene)][B(C6F5)4] (21) complex. Similar to 7, complex 21 was highly active for intramolecular hydroamination of various substrates.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: Cationic group 3 alkyl complexes are underreported in comparison to analogous group 4 complexes. The scarcity of these complexes can be attributed to their propensity to engage in undesirable reactions such as ligand redistribution and cyclometallation. To increase the thermal stability of such complexes, design features, such as carefully positioned steric bulk and ligand rigidity are beneficial. Additionally, such ligands must also have considerable donor ability, in order to stabilize inherently electron deficient cationic metal centers. This work details the synthesis of a variety of neutral and monoanionic ligands that incorporate the aforementioned design features, which were utilized in the successful synthesis of a variety of neutral, monocationic and extremely rare dicationic group 3 alkyl complexes. The cationic monoalkyl complex in this work proved to be a highly potent intramolecular hydroamination catalyst. Furthermore, a rare dicationic scandium complex was highly active for ethylene polymerization


title: Contesting the Crisis - CUPE, the CAW, and Third Way Neoliberalism in Ontario from 2003-2013

contributor:
Storey, Robert
Sociology

abstract:
This research uses Gramscian claims about culture and resistance to assess the radical potential
of trade unions under neoliberalism. Using a comparative case study, this research examines the
implications of chosen strategies of resistance deployed by the leading public- and private-sector
unions (Canadian Union of Public Employees – CUPE, and Canadian Auto Workers – CAW,
respectively) during the pre- and post-Great Recession phases of the McGuinty Liberal
government in Ontario. The key contributions of this work are relevant for the fields of political
sociology, political economy, and labour studies. In the field of political sociology, this work
finds that contesting hegemonic governance strategies requires both a resistance against
opportunities for integration and incorporation and the articulation of and organization around
radical and non-sectionalist (systemic) alternatives. Second, this work demonstrates how political economic considerations are contested both structurally and culturally through both
organizational-institutional and ideological-symbolic interventions. Finally, this research holds
implications for strategies of union renewal by analyzing the capacities and limitations of certain
strategic interventions in the lead-up and aftermath of a large-scale economic crisis.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: A New Switch-Count Reduction Configuration and New Control Strategies for Regenerative Cascaded H-Bridge Medium Voltage Motor Drives

contributor:
Narimani, Mehdi
Electrical and Computer Engineering

subject:
Medium Voltage Motor Drives
Cascaded H-Bridge Multilevel Inverters
Regeneration
Switch-count reduction
Fundamental frequency ends

abstract: Cascaded H-bridge (CHB) multilevel inverters have significant popularity with motor drives applications due to their modularity, scalability, and reliability. Typical CHB inverters employ diode rectifiers that allow unidirectional power flow from the grid to the load. To capture and utilize the regenerated energy in regenerative applications, regenerative CHB drives were introduced with two-level voltage source converters in the front end to allow bidirectional energy flow. This solution is accompanied by challenges of high number of switches and control circuits, high switching power losses, and massive dimensions. Recently, developing more economic versions of regenerative cascaded H-bridge drives has become one of the hottest topics in power electronics research. In this thesis work, two solutions are proposed for more energy efficient and economic regenerative CHB drives. The first solution is a proposed power cell configuration that reduces the number of switches per cell by two. Additionally, phase alternation connection method and carrier phase-shifting techniques are introduced to address the challenges of the presented configuration. The switch-count reduction reduces the system’s complexity, switches’ cost, and footprint. The second proposed solution is a new controller to operate the front-end converters as fundamental frequency ends (FFEs). The proposed controller is employed in both the conventional regenerative cascaded H-bridge and the proposed reduced switch-count configuration. This solution minimizes the switching power losses, and results in more compact and economic design, with higher DC-link utilization. Theoretical analysis and simulation studies of both proposed solutions show promising performance and capability to be applied as energy-efficient and cost effective regenerative CHB motor drives. Experimental validation of the proposed reduced switch-count configuration is presented for STATCOM operation of a scaled-down 7-Level regenerative CHB drive system. The future work of this thesis includes experimental validation of the proposed FFE controller, and operation of the system with regenerative motor load.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Prediction, Detection, and Management of Myocardial Injury After Noncardiac Surgery

contributor:
Devereaux, Philip James
Health Research Methodology

subject:
Myocardial injury
Noncardiac surgery

abstract: Myocardial injury after noncardiac surgery (MINS) is common in patients undergoing inpatient noncardiac surgery and has been shown to adversely impact short- and long-term patient prognosis.  Most MINS events are asymptomatic and systematic troponin measurement early after surgery is of paramount importance to detect these events.  The largest study to determine thresholds and prognostic importance of MINS used troponin T and high-sensitivity troponin T.  There is limited information on how to diagnose MINS using high-sensitivity troponin I (hsTnI).  How to predict who is at higher risk of MINS and would benefit the most from troponin monitoring, and how to manage patients who suffer a MINS are also areas that need further research.  This thesis presents studies that inform on these knowledge gaps. Chapter 2 describes the result of a large prospective cohort of patients undergoing noncardiac surgery which determined the utility of preoperative N-Terminal pro-B type Natriuretic Peptide to predict 30-day MINS and vascular death, in addition to clinical evaluation.  Chapter 3 uses data collected as part of a large prospective cohort with a nested biobank to determine thresholds of hsTnI that can predict major cardiovascular events in patients who underwent noncardiac surgery and be used to diagnosis MINS using hsTnI.  Chapter 4 details the methods of an international, multicentre, randomized placebo-controlled trial (MANAGE Trial) determining the impact of dabigatran, a blood thinner, and using a partial factorial design, of omeprazole, a gastric acid reducing drug, on the occurrence of major vascular and upper gastrointestinal events in patients who suffered a MINS and are followed for up to 2 years.  Chapter 5 presents the results of the omeprazole component of the MANAGE Trial.  Chapter 6 discusses the key findings of the thesis and future research directions.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Damage to the heart muscle occurring after a noncardiac surgery, called myocardial injury after noncardiac surgery (MINS), occurs frequently and negatively impacts patient’s short- and long-term health and survival.  Most patients who suffer a MINS do not present symptoms suggestive of heart problems.  Blood tests obtained after surgery measuring troponins, a marker of heart damage, is necessary to detect which patients are having MINS.  Different troponin tests are available, including a test called high-sensitivity troponin I, for which there is limited information on how to diagnose MINS using this test. How to predict who is at higher risk of MINS and how to treat patients who suffered a MINS are also areas that need further research. This thesis presents studies that inform on these knowledge gaps.


title: Modeling and Improvement of DC-link Capacitor Lifetime in a Regenerative Cascaded H-bridge Motor Drive

subject:
Regenerative motor drives
DC-link capacitor lifetime

abstract: Motor drives represent electric equipment used for speed control of electric motors. Varieties of industrial applications, such as assembly, pumps, fans etc., require motors and they consume huge amount of electric energy. Compared with traditional motor drives, which can only send energy from grid to motor, a regenerative motor drive can achieve bi-directional power flow control between motors and utility grid. Regenerative motor drives are excellent candidates for reducing power loss in motor-related applications. One of the most essential parts of a regenerative motor drive power cell is dc-link capacitors. They create suitable dc-link voltages and smooth the voltage waveforms. Reliability, or lifetime of dc-link capacitors highly affect power cell lifetime, and power loss in dc-link capacitor is also another issue that worth noticing. This thesis focuses on the lifetime modeling and lifetime improvement of dc-link capacitors in a regenerative cascaded H-bridge medium-voltage motor drive. The lifetime modeling bases itself on the mechanisms of dominant lifetime stresses in practical operations. A proposed method is used to reduce a dominant current harmonic component in dc-link capacitors. With the proposed lifetime model and harmonic-reduction method, dc-link capacitor lifetime improvement can be anticipated in this motor drive model. Less power losses in those dc-link capacitor banks can also be achieved.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Inheriting Justice:Reading Myself Through an Erased History

contributor:
Joseph, Ameil
Social Work

subject:
Activism
Intellectual Disability
Masie Cartwright
Vulnerability
Social Change
Social Work
History of Disability

abstract: The over-arching goal of this project is to instill hope for activists and social workers, while simultaneously exploring the narrative of my Great-Grandmother, Mrs. Marguerite Emily Cartwright, whose activist story has never truly been told.  Through the use of storytelling and thematic analysis, this research will present the reader with an opportunity to explore the tools and strategies that one woman used to make a profound and lasting influence on disability services, the study of disability and persons with disabilities throughout Ontario in the 1940’s and onwards.  The Study of Disability, Disability Studies and Social Justice Studies, along with storytelling literature, are both broad albeit unique areas of knowledge. This unique thesis is based on the analysis of my family’s archives of Mrs. Cartwright’s activism, through original journal entries and newspaper clippings, along with letters and personal correspondences Mrs. Cartwright wrote to prominent North American politicians, offering a window into the mind of the activist herself. Through the use of storytelling and thematic analysis, this paper explores how the themes of wielding personal power, inheriting a moral sense of justice, and the history of disability services in Ontario contributed to the telling of Mrs. Cartwright’s untold story. An analysis of Mrs. Cartwright’s activist strategies demonstrated the intersectionality of disability, critical theory, feminism and justice studies, and the use of self in advocacy. Lastly, I discuss how my own sense of social justice, epistemology and practice of social work has been impacted by the telling of this story.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: Pacifist Theology and the Problem of Mennonite Violence in Miriam Toews’ Women Talking and Casey Plett’s Little Fish

contributor:
Kehler, Grace
English and Cultural Studies

subject:
Mennonite Literature
Pacifist Theology
Miriam Toews
Casey Plett

abstract: This paper examines how the Mennonite theology of pacifism has enacted, perpetuated, and allowed for violence against particularly marginalized groups such as women and the LGBTQ+ community. Through studying contemporary Mennonite literature, this paper attempts to discover how this literature reveals this violence, shows it to be working, and attempts to redeem the Mennonite faith and pacifism itself as positive in the world.

abstract: Thesis

abstract: Master of Arts (MA)


title: Evaluating the Success of Ontario Roadside Restorations - An Ecosystem Approach

contributor:
Dudley, Susan
Biology

subject: restoration grassland roadside monitoring diversity bee

abstract: Ecological restoration, or assisting the recovery of damaged ecosystems, is recognized as a crucial activity for reversing biodiversity loss across the globe. Roadside rights-of-way may be suitable areas for the restoration of endangered grassland communities, because they occupy significant areas of underutilized land, are managed as early successional plant communities, and may serve as corridors for wildlife movement and gene flow. However, though many roadside restoration projects have been undertaken in North America, few studies have evaluated their long-term success and most monitoring is narrow in scope. True restoration includes restoring an appropriate species composition, vegetation structure and ecosystem functions, and thus these ecosystem components must be measured when evaluating success. I assessed the plant community, bee community, soil carbon and plant-fungal relationships at roadside restorations of various ages along three major highways in Southern Ontario and compared these measures to unrestored roadsides and reference sites. I found that roadside restorations successfully increased native plant richness, though not to the level of a remnant grassland. Bee communities varied mostly by highway rather than site type, though bee abundance was positively correlated with plant diversity and bare ground. Soil carbon in roadside sites was similar to that of a remnant grassland but did not differ among restored and control sites. Plant growth response to arbuscular mycorrhizal fungi collected from roadside sites varied depending on the site and showed a weak negative correlation with site age. Taken together, these results suggest that roadside restoration can benefit some ecosystem components, but simply seeding native plants along roadsides may not be sufficient for improving ecosystem function. This study highlights the importance of evaluating success in a comprehensive manner that includes multiple ecosystem components.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Ecological restoration is crucial for reversing global biodiversity loss. Roadsides may be suitable for the restoration of grassland ecosystems, but few studies have comprehensively evaluated the long-term success of roadside restorations. I assessed the plant community, bee community, soil carbon and plant-fungal relationships at roadside restorations along three Southern Ontario highways and compared these measures to unrestored roadsides and a remnant grassland. Restoration increased native plant diversity, though not to remnant levels. Bee communities varied mostly by highway, though bee abundance was positively correlated with plant diversity. Soil carbon in roadside sites was similar to the remnant but did not differ among restored and unrestored sites. Plant response to soil fungi collected from roadside sites varied significantly by site. Thus, roadside restoration can benefit some ecosystem components, but more intervention may be required to restore ecosystem function. This study highlights the importance of evaluating restoration success in a comprehensive manner.


title: THYMIC STROMAL LYMPHOPOIETIN EXPRESSION IN NASAL EPITHELIAL CELLS OF ALLERGIC ASTHMATICS

contributor:
Denburg, Judah
Medical Sciences

subject:
asthma
allergy
thymis stromal lymphopoietin
rs1837253
nasal epithelial cells

abstract: Thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine, has a critical role in the development of allergic inflammatory responses and have been implicated in type 2 allergic disease, including asthma, allergic rhinitis, and atopic dermatitis. Genetic polymorphisms in the TSLP gene are among the most commonly cited variants associated with asthma and allergic disease, however, the functional effects of these polymorphism are not fully understood. The objective of this study was to investigate the role of a TSLP polymorphism in the Th2 inflammatory responses of the nasal epithelium, as well as in responding to nasal allergen provocation and intranasal corticosteroid treatment. We cultured nasal epithelial cells from allergic asthmatic subjects and examined cytokine and chemokine secretions and gene expression profiles in response to polyinosinic:polycytidylic acid treatment. To explore the functional consequences of the rs1837253 polymorphism we analyzed the two TSLP gene isoforms, as they have shown dichotomous effects, however, no associations were found between rs1837253 genotype and the expression of TSLP and gene isoforms. We did not find any associations of TSLP or cytokine production between genotypes, or in relation to response to nasal allergen challenge or corticosteroid treatment. Exploration of local and systemic effects of the rs1837253 SNP did not show any differences in response to INCS treatment in vitro or ex vivo. We did demonstrate that nasal epithelial cell-derived factors are capable of stimulating eosinophil/basophil colony forming units in the absence and presence of exogenous IL-3. Overall, the results indicate a role of the nasal epithelium in driving eosinophil/basophil differentiation and highlight the complexity of gene-environment interactions and the mechanisms of asthma and allergic inflammation.

abstract: Thesis

abstract: Master of Science (MSc)


title: Incorporating Observational Gas Data into Simulations of Embedded Star Clusters

contributor:
Sills, Alison
Physics and Astronomy

subject:
Astrophysics
Simulation
Star Clusters

abstract: Realistic star cluster simulations that dynamically evolve embedded star clusters require an accurate treatment of the stars, gas and their interaction. We present and validate a novel technique which creates an initial gas density distribution based on observational gas column density data. We consider two approaches to this technique where the first is based on randomly sampling from the original gas density distribution and the second assigns one particle to represent the gas in each observed image pixel. To create a three-dimensional distribution, we consider two estimates of cloud depth where one is a constant value and the second involves variable depths calculated using image processing techniques based on density features seen in the plane of the sky. We apply these methods to evolve the Carina region using initial stellar positions derived from the MYSTiX catalogue and gas data from the Herschel Hi-GAL survey. We evolve the stars using an N-body code and the gas using a smoothed-particle hydrodynamics code which are coupled through the AMUSE framework. We analyzed our results using dendrograms to describe the gas distribution over time and the DBSCAN clustering algorithm to track the clustering of stars over time. We model the gas using an adiabatic ideal gas equation of state and find that increasing the initial gas velocity dispersion prevents gas from accumulating and therefore could hinder future star formation. We also find that the stars, initially in subclusters spatially (not necessarily bound), tend to merge together to form one large cluster regardless of the initial conditions of the gas. It is only after the subclusters have merged that the initial conditions of the gas start to have a noticeable effect on the structure of the star cluster. Of the two approaches to our novel technique, the second approach leads to more accurate and realistic results. The second approach also has a significant effect on the stars as the subclusters merge together approximately 1 Myr earlier compared to the first approach. Therefore the choice of initial gas conditions affects the dynamical evolution of star cluster systems and being able to incorporate observational gas data leads to the increasingly accurate dynamical evolution of such systems.

abstract: Thesis

abstract: Master of Science (MSc)


title: Assessment of Social Cognition by Site of Lesion in Adults with Traumatic Brain Injury Using the Visual Social Inference Test

contributor:
Turkstra, Lyn
Neuroscience

subject:
Social cognition
Traumatic Brain Injury
Theory of mind
Frontal lobe lesions
Video social inference test (VSIT)

abstract:
Individuals with Traumatic Brain Injury (TBI) exhibit impaired performance on social cognition and theory of mind (ToM) measures, like the Video Social Inference Test (VSIT). The frontal lobe, being the primary region involved in higher level cognitive functions mediates the neural mechanisms involved in social cognition and ToM abilities, according to studies on brain and behaviour. The goal of this study was to examine if individuals with TBI who did not damage their frontal lobe would perform differently on the VSIT than individuals with TBI who did. This study was a secondary analysis of documented imaging data and VSIT scores obtained from 51 adults with moderate-to-severe TBI (23 females). A comparison was made between scores obtained on the VSIT between participants with and without frontal lobe lesions. The results indicated that there was no significant difference between the two groups, in other words, site of lesion in participants with TBI did not predict performance on the VSIT. The results suggest that while the VSIT may yield critical information about social cognition, it is not sensitive to individual site of lesion. There is evidence that aspects of social cognition are impaired in this clinical population, however, most research in this area is obstructed by the complex nature of TBI neuropathology in addition to small heterogenous samples involved in studies. Further research in this area is required in order to reveal and enhance our understanding of social cognition deficits following TBI.
	Keywords: social cognition, traumatic brain injury, theory of mind, frontal lobe lesions, video social inference test

abstract: Thesis

abstract: Master of Science (MSc)


title: Comparative cognition between social and non-social cichlids

contributor:
Balshine, Sigal
Psychology

subject: Cooperation Cognition Group-living Learning Memory Teleosts

abstract:
Cooperation often draws on cognition (i.e. learning and memory) in order to
track cooperative partners and their contributions, resolve conflict between partners,
improve coordination between partners, and enhance strategic-decision making.
Learning and memory are also vital to resolve what is frequently a spatial and temporal
mismatch between performing a cooperative act and receiving any kind of benefit in
return. In this thesis, I compared cognitive abilities between three cooperative and
group-living cichlid fishes from the Lamprologini tribe of Lake Tanganyika
Neolamprologus pulcher, Neolamprologus multifasciatus, and Julidochromis ornatus
with three of their close relatives that are not cooperative and never form groups
Telmatochromis temporalis, Altolamprologus compressiceps, and Neolamprologus
tretocephalus. This thesis aims to address whether the evolution of cooperation
coincided with the evolution of sophisticated cognition in these fishes. In Chapter 2, I
present evidence that both cooperative and non-cooperative cichlids are able to
recognize familiar individuals and have similar numerical abilities. In Chapter 3, I
show that performance when learning to navigate a maze, arguably a more general
cognitive ability, was equivalent across cooperative and non-cooperative species, with
comparable scores in terms of time to maze completion, number of mistakes and
inhibitory control. In Chapter 4, I report on the results of a literature review where I
quantified the growing interest in the field of fish cognition research, outline the
current practices and pitfalls (heavy use of captive bred individuals and a reliance on
lab-based research) and suggest how to bring more ecological relevance to the field. Taken together, the results of my thesis improve our understanding of how social
factors like group-living and cooperation modulate cognitive abilities, and detail the
current trajectory of the field of fish cognition.

abstract: Thesis

abstract: Master of Science (MSc)


title: Optimizing the Presentation of Indirect Evidence for Clinical Practice Guideline Panels That Use the Grade Approach for Decision-Making

contributor:
Brozek, Jan
Health Research Methodology

subject:
GRADE
Guidelines
Indirect Evidence

abstract: While many clinical practice guidelines that use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach have ample published evidence to support their recommendations, certain situations (e.g. rare, rapidly emerging, or understudied diseases) may be limiting. As a result, it is common for guideline developers to seek out indirect evidence from other areas to fill in these evidence gaps. The GRADE evidence-to-decision (EtD) framework, which offers a structured and transparent development process for guidelines, includes additional research evidence domains (e.g. feasibility, acceptability, equity) for panels to consider in their decision-making process. This confluence of both considerations of indirect information and increasing literature domain sources to draw from when making decisions weighs on the simplicity of literature presentation. Herein, firstly, we described an example of specific decision-rules for including indirect evidence and the implications of the rules for presenting results to decision-makers. Secondly, we provided a comprehensive overview of how guideline developers currently report economic information across GRADE evidence-to-decision frameworks. Lastly, we ranked the most important study characteristics suggested in the literature by economists to consider as decision-rules when assessing indirectness (transferability) of economic evaluations chosen as research evidence in a GRADE guideline. We conclude that developers, with the help of their panels, should work to establish and report clear decision-rules and the rationale for indirect evidence that they select for their clinical practice guidelines. This has the potential to simplify the presentation of indirect evidence for panels and developers, as well as, to reduce decision-making confusion, time demands and guideline funder costs.

abstract: Thesis

abstract: Candidate in Philosophy

abstract:
While many clinical practice guidelines have ample published evidence to support their recommendations, certain situations (e.g. rare, rapidly emerging, or understudied diseases) may be limiting the available literature. As a result, it is common for guideline developers to seek out indirect evidence from other, but related areas, to fill in these evidence gaps. Selection of available indirect evidence may be better than basing decisions on no evidence, in particular in situations of clinical equipoise. However, including all potentially relevant indirect evidence may represent an overuse of evidence. Indirect evidence refers to information sources with related populations, interventions, outcomes or comparisons, which could reasonably be extrapolated; but, are not entirely specific to the research topic at hand. This confluence of both indirect information considerations and desire by many for increasing literature sources to draw from weighs on the simplicity of an overall summary of literature presented during a guideline recommendation decision-making process. Herein, firstly, we described an example of explicit decision-rules for including indirect evidence that were specific and the implications of the rules for presenting results to decision-makers. Secondly, we provided a comprehensive overview of how guideline developers currently report economic information across guideline frameworks, in particular with respect to indirectness. Lastly, we described the most important study characteristics suggested by economists to consider as decision-rules when assessing economic evaluations for use as research evidence in a guideline.
This work presents important concepts for guideline developers to consider when choosing indirect evidence sources in their clinical practice guidelines. Our findings have the potential to simplify the presentation of indirect evidence for guideline panels and developers, as well as, to reduce decision-making confusion, time demands and guideline funder costs.