VictorJuiz/thesis huggingface dataset:
Investigating Nutritional Status in Moderate to Severe Alzheimer's Disease Patients Enrolled in a Randomized Controlled Trial with Nabilone

Nutritional status is of great clinical significance in Alzheimer’s disease (AD) patients as malnutrition can increase risk of morbidity, mortality and severity of neuropsychiatric symptoms. Due to a lack of pharmacological treatments for malnutrition, we investigate the use of nabilone, a synthetic cannabinoid, for the improvement of nutritional status. Patients were recruited from a clinical trial in AD patients with clinically significant agitation. Patients treated with nabilone did not have improved nutritional status over time as assessed by the Mini Nutritional Assessment-Short Form (b=-0.020 (95%CI -0.27 to 0.23), p=0.87) and body mass index (b=0.020 (95%CI -0.13 to 0.17), p=0.79). Safety outcomes did not significantly differ with respect to nutrition for patients receiving nabilone treatment. By identifying efficacious interventions to manage nutrition in an at-risk population, there may be potential to improve quality of life for AD patients.

Advisor: Lanctôt, Krista L
The Glaciolacustrine Sediment Record of Cariboo Lake, BC: Implications for Holocene Fluvial and Glacial Watershed Dynamics

Cariboo Lake is a glacier-fed lake located in the Cariboo Mountains of eastern-central British Columbia. Fine clastic sediments produced in the glaciated headwaters of the Cariboo Lake watershed provide the main source of sediment to the lake. Sediment delivery into Cariboo Lake is primarily governed by overflow currents of suspended clastic sediments from the main Cariboo River. Sediments deposited in deep basins over 30 m deep are characterized by couplets of coarse grained laminae, followed by fine grained sediments and are inferred to be annually laminated varves. Inflow of clastic sediments to Cariboo Lake has remained high enough to produce annual varves for the past two millennia. Down-core trends in varve thickness, grain size, and percent organics from Cariboo Lake sediment archives reveal changes that corresponded to climate fluctuations over the past two millennia.

Keywords: Climate Proxy
Fluvial Geomorphology
Glacier Retreat
Glaciolacustrine
Holocene
Watershed Dynamics
Advisor: Desloges, Joseph R
A High Throughput Device for Clonogenic Assays and Radiobiology Research

The gold standard tool for conducting in vitro radiobiology research is the clonogenic assay. The assay measures a cell’s ability to survive a therapy and is widely used when studying the effects of radiation and radiation sensitizing drugs. The standard clonogenic assay is a time consuming and labour intensive protocol which produces a single measurement with little context to the behaviours of the cells. A system was developed to perform high throughput clonogenic assays using a robotic well plate irradiator and a robotic live cell imaging system. The high throughput system conducts automated multi dose radiation delivery to a single well plate and can monitor the growth of cells into colonies. The system was tested by conducting high throughput clonogenic assays of HCT116 and FaDu cells using 384 well plates. This thesis describes the algorithms and methods used to conduct automated high throughput clonogenic assay on a robotic platform.

Keywords: cancer
Clonogenic assay
high thoughput
hypoxia
radiation
Radiobiology
Advisor: Jaffray, David A
Extending the Capabilities of Terrestrial Target Tracking Spacecraft

Autonomous terrestrial target tracking is performed by many communications and Earth observation missions to track ground-fixed targets. The DAUNTLESS platform, under development by the Space Flight Laboratory will employ novel attitude trajectory generation schemes to achieve high-performance ground target tracking for a wide range of targets, across a wide range of potential orbits. The development of the guidance and control algorithms employed by this platform and their implementation on-board a prototype mission will be presented in detail. In addition, this thesis will present the development of an end-of-life spacecraft deorbit maneuver, and the associated attitude and orbit control challenges. These engineering problems will be discussed as focal points in the broader context of attitude and orbital control system development for microsatellites. Particular attention will be given to the use of modern numerical optimization approaches as a means to achieve robust solutions for complex multi-variable problems.

Keywords: attitude and orbital control systems
deorbit
microsatellites
spacecraft dynamics
target tracking
trajectory planning
Advisor: Zee, Robert E
Liu, Hugh HT
The Impact of a Childhood Cancer Diagnosis on their Mother's Mental Healthcare Use

The impact of a child’s cancer diagnosis on a mother’s mental health is unclear. We assembled a population-based cohort of mothers of children diagnosed with cancer and captured all mental health-related visits using healthcare administrative data. The primary outcome assessed rate of low severity mental health visits after cancer diagnosis. Secondary outcomes included time to severe mental health event (ED visit, hospitalization, suicide), and specific severe psychiatric diagnoses. When compared to 26,950 controls, 5,418 childhood cancer mothers had higher rates of outpatient mental health visits (rate ratio 1.4, p

Keywords: Cancer
Healthcare
Mental health
Mother
Oncology
Pediatric
Advisor: Gupta, Sumit
Glucose Derangements and Brain Function in Neonatal Encephalopathy

Hypoglycemia and hyperglycemia are common in neonates with encephalopathy and may be independently associated with unfavourable outcomes. This thesis describes how glucose derangements detected with continuous interstitial glucose monitoring commenced soon after birth are associated with brain function on amplitude-integrated electroencephalography (aEEG) and continuous EEG (cEEG) in the context of neonatal encephalopathy. We hypothesize that hypoglycemia, hyperglycemia and glucose variability in neonatal encephalopathy are associated with abnormal brain background activity and increased electrographic seizures on aEEG and cEEG. In neonates with encephalopathy, epochs of hyperglycemia, but not hypoglycemia, were common and temporally associated with worse aEEG background scores, less sleep-wake cycling, and more electrographic seizures, including after adjusting for clinical markers of hypoxia-ischemia. Epochs of hyperglycemia also were associated with worse cEEG background scores, including after adjusting for hypoxia-ischemia severity. Our data support the hypothesis that proactive avoidance of hyperglycemia may be a neuroprotective strategy in infants with neonatal encephalopathy.

Keywords: Amplitude-integrated electroencephalography (aEEG)
Continuous electroencephalography (cEEG)
Glucose variability
Hyperglycemia
Hypoglycemia
Neonatal neurology
Advisor: Tam, Emily W.Y.
Hahn, Cecil D.
Health Care Providers' Perspectives of Uncertainty in Newborn Screening

There is a paucity of research exploring the issues of uncertainty in the context of newborn screening and metabolic care. This work explores these issues of uncertainty through qualitative description. Semi-structured telephone interviews were conducted with health care providers at specialized metabolic centers across Canada. Data was coded and thematically analyzed. This study found that health care providers experience personal, practical, diagnostic, prognostic, and therapeutic issues of uncertainty when managing the care of patients affected by mild hyperphenylalaninemia (MHP), very long chain acyl CoA dehydrogenase (VLCAD) deficiency, medium chain acyl CoA dehydrogenase (MCAD) deficiency, and partial biotinidase deficiency. Heath care providers described nosological inadequacy as a source of uncertainty when managing 3-methylcrotonyl CoA (3-MCC) deficiency. Participants emphasized caution, while avoiding overmedicalization, when managing medical uncertainty. Providers indicated that greater communication and consensus is required across care centers, which may open a dialogue for a pan-Canadian newborn screening strategy.

Keywords: Health care providers
Medicalization
Metabolic disease
Newborn
Screening
Uncertainty
Advisor: Hayeems, Robin
Assaying the Microbiome During Critical Illness

Critical illness is associated with large-scale perturbations in the gut microbiota. We compared four sample types in intensive care unit patients – rectal, nares, and antecubital swabs, and stool – using 16S rRNA gene sequencing. Stool was obtained in 31% of attempts, while swabs were reliably obtained (≥97% of attempts). Although not compositionally identical, rectal swabs captured microbiota perturbations in critically ill patients similar to those previously described using stool. Additionally, potentially informative changes in the gut microbiome occurring during late-onset sepsis in an ICU were captured using shotgun metagenomic sequencing of rectal swabs. Initiation of empiric antibiotic therapy was associated with compositional collapse of the gut microbiome within 24 hours, with Pseudomonas aeruginosa becoming the dominant community member and acquiring genomic variants in resistance-associated loci. Overall, rectal swabs were easily obtained and captured compositional and metagenomic perturbations common during critical illness, demonstrating their potential utility for microbiome analysis in this population.

Keywords: Critically Illness
Late-onset infections
Microbiome
Sepsis
Advisor: Coburn, Bryan
Shrinking Horizon, Scenario-based Optimal Liquidation with Lower Partial Moments Criteria

A quasi-multi-period model for optimal position liquidation in the presence of market impact is proposed. Two features distinguish the approach from alternatives. First, a shrinking horizon framework is implemented to update intraday parameters by incorporating new information while maintaining standard non-anticipativity constraints. The method is data-driven, numerically tractable, and reactive to the market. Second, lower partial moments, a downside risk measure, is used which captures traders’ increased risk aversion to losses better than symmetric risk measures. The performance of the proposed strategies is tested using historical, high-frequency New York Stock Exchange (NYSE) data. The proposed strategies outperform their benchmark on days with unfavorable market conditions, strongly supporting the use of lower partial moments as a risk measure. Additionally, results validate the use of a shrinking horizon framework as an adaptive, tractable alternative to dynamic programming for trading.

Keywords: Intraday Trading
Lower Partial Moments
Optimal Liquidation
Shrinking Horizon
Stochastic Programming
Advisor: Kwon, Roy H.
Identifying CD36 as a Receptor for Albumin Transcytosis by Dermal Microvascular Endothelial Cells

Albumin is the most abundant serum protein. Under basal physiological conditions, the movement of albumin in and out of the vasculature occurs by transcytosis. Little is known regarding the mechanism of albumin transcytosis and its variability across tissue beds. Using a novel TIRF microscopy-based assay, in this present study I have shown that albumin transcytosis is saturable in dermal (HDMECs) but not in lung microvascular endothelial cells (HPMECs). I have identified the scavenger receptor CD36 as necessary for albumin transcytosis across HDMECs, in contrast to HPMECs where macropinocytosis dominates. Mutations in the apical bundle of CD36 prevented albumin internalization. A modified Miles assay in mice with an endothelial CD36 deficiency exhibited lower basal permeability to albumin. These mice also developed a smaller subcutaneous fat layer despite comparable body weights and circulating FA levels as wild-type animals. These findings shed light on the mechanism and functional importance of albumin transcytosis.

Keywords: Albumin
CD36
Endothelial Cells
Microvasculature
Transcytosis
Advisor: Lee, Warren
The Effect of Diagnostic Terminology on Cognitive, Emotional, and Somatic Outcomes Following Mild Traumatic Brain Injury

Although used interchangeably to represent similar acute injury characteristics, mild traumatic brain injury (mTBI) and concussion may result in different functional outcomes. This investigation sought to determine whether varying diagnostic terminology resulted in differences in perceived cognitive, emotional, somatic symptom sequalae, and expected recovery time. A total of 108 university students were randomly assigned to one of three conditions: concussion (n=31), mTBI (n=44), or undiagnosed injury (n=33), and were instructed to simulate on a battery of cognitive, emotional, and somatic measures. There were no differences between the mTBI and concussion groups on cognitive (d=.09), emotional (d=.09), and somatic (d=.09) variables; however, the mTBI group perceived greater cognitive (d=.15), emotional (d=.33), and somatic (d=.28) consequences compared to the no diagnosis group. These findings provide preliminary support for the potential iatrogenic effects that may arise as a result of providing participants with a list of common brain injury symptoms.

Keywords: Concussion
Diagnostic Terminology
Mild Traumatic Brain Injury
Advisor: Zakzanis, Konstantine K
Bagby, R Michael
Anatomical and Behavioural Characterization of Dpr-Interacting Protein Beta in Drosophila melanogaster

The mammalian limbic system has many important biological functions. During development, the limbic-system associated membrane protein (LSAMP) plays a crucial role by ensuring proper neuronal connectivity within the system. Similarly, the LSAMP homologue in the Drosophila, the Dpr-interacting protein beta (DIP-β), is believed to assist in neuronal formation during the development of the fly central nervous system. Other data suggests that DIP-β even regulates social interactions. Researchers have only more recently begun investigating DIP-β however, and DIP-β remains to be extensively studied. Thus, the aim of this project was to fully characterize DIP-β expression in the brain and the behaviour of DIP-β mutants, to obtain a better understanding of DIP-β function. DIP-β’s predominant expression in the optic lobes and regions in the central brain, along with changes in behavioural rhythmicity observed in DIP-β mutants, suggests DIP-β may be associated with clock mechanisms.

Advisor: Levine, Joel
Evaluating the Unique Associations Between Personality Psychopathology and Heterogeneous Eating Pathology Symptoms

This study examined unique associations between pathological personality facets and heterogeneous eating pathology symptoms (e.g., restriction, purging, binge eating). Participants were 570 community adults (247 women) recruited through MTurk. The Personality Inventory for DSM-5 measured pathological personality facets. Indicators from two eating pathology scales were used to measure latent and dimensional eating pathology symptoms as opposed to categorical diagnostic constructs. Three structural equation models (exploratory, theoretical, and empirical) were tested for each eating pathology symptom. The empirical model was considered the most parsimonious of the three models for all three symptoms. Unique associations were found; higher rigid perfectionism, lower perseveration, and higher deceitfulness were uniquely associated with restriction whereas lower attention seeking and higher perceptual dysregulation were uniquely associated with purging. Higher impulsivity and anxiousness were uniquely associated with binge eating. Researchers are encouraged to examine dimensional and heterogeneous eating pathology symptoms when exploring associations with personality.

Keywords: eating pathology
Personality Inventory for DSM-5
personality psychopathology
Advisor: Bagby, Michael
Altered CD8+ T cell function in Ankylosing Spondylitis: The role of perforin in enhanced inflammatory profiles

Ankylosing Spondylitis (AS) is an autoimmune disease of still unknown pathogenesis and disease mechanism. Currently the most well-known genetic factor associated with AS is one specific human leukocyte antigen, HLA-B27, but it still remains unclear how exactly HLA-B27 contributes to AS. Class I major histocompatibility complex (MHC I) molecules such as HLA-B27 are essential for the function of cytotoxic lymphocytes (CTL). Therefore, it is of interest to address whether CTL have any pathological contribution to the disease process in AS. In this study, I have explored one aspect of this question using several clinical and laboratory approaches. I have found that AS patients tend to have a reduction in perforin, which is an important protein for CTL cytotoxicity. Further studies suggested that perforin deficiency might cause over-activation of CTL and subsequent secretion of inflammatory cytokines. My study has provided a novel idea regarding AS disease mechanism, and provides a new potential direction for AS therapy in the future.

Keywords: Ankylosing Spondylitis
Arthritis
CD8 T cell
Immunology
Inflmmation
Perforin
Advisor: Inman, Robert D
Patient Expectations in the Treatment of Depression: The Role of Outcome Expectancy in Therapeutic Change across Psychotherapy versus Pharmacotherapy

The present study extended previous research on outcome expectancy by exploring its temporal dynamics, as well its relation to depression improvement in two different treatment modalities. A sample of 104 patients with depression were randomized to receive either cognitive behavioural therapy (CBT) or pharmacotherapy for 16 weeks. Outcome expectancy was measured throughout treatment using the Depression Change Expectancy Scale (DCES), a measure comprising two subscales assessing pessimistic versus optimistic expectancies. Results corroborated the role of pre-treatment expectancy on treatment response in CBT. Moreover, associations between mid-treatment expectancy and treatment response were seen in pharmacotherapy. Notably, the associative patterns between expectancy and depression in CBT differed as a function of expectancy valence (i.e., pessimistic versus optimistic). Results support a possible mediational role of expectancy across different treatments for MDD. Future studies incorporating larger sample sizes and more frequent assessments of during-treatment expectancy will be needed to validate these results.

Advisor: Quilty, Lena C
Bagby, R. Michael
Visualization of Fluid Dynamics in Nanoporous Media for Unconventional Hydrocarbon Recovery

Evaporation at the nanoscale is critical to hydrocarbon production from nanoporous shale, a process that has reshaped global energy supply. However, there is a lack of understanding pertaining to phase change of hydrocarbons trapped in nanopores. This thesis develops and applies nanofluidics for the direct study of evaporation as relevant to shale oil and gas. Onset and dynamics of propane evaporation are studied in two-dimensional nanomodel. With sub-10 nm confinement, evaporation is vapor transport dominated with the Knudsen flow effect twice the viscous flow effect. A nanomodel is also developed that couples the inherent heterogeneity in shale pore sizes (100 nm pores gated by 5 nm-pores) to study vaporization of ternary hydrocarbons. Distinct spatio-temporal dynamics of vaporization are observed as a function of superheat. Results are compared to a vapor transport model. The differences highlight the inherent complexity of multi-component fluids in multi-scale geometries at the heart of unconventional resources.

Keywords: Evaporation
Knudsen flow
Nanofluidics
Nanoporous
Shale
Advisor: Sinton, David
The Role of the Arabidopsis HOP2 Protein in Promoting Homologous Chromosome Interactions and Blocking Nonhomologous Interactions

The Homologous Pairing Protein 2 (HOP2) is important for its role in reciprocal genetic exchange in meiosis. It is thought to operate as a part of the double-strand break (DSB) repair pathway. Recent models give two potential roles for HOP2: it acts to promote interactions between homologous chromosomes, and it acts to block interactions between non-homologous chromosomes. The goal of my study was to see if the HOP2 protein acted to block non-homologous interactions by analyzing its role in haploid plants. Haploid hop2-1 mutants were analyzed by light and fluorescent microscopy and compared with haploid WT plants. Like WT haploids, hop2-1 mutants showed univalents in early meiosis. However, unlike WT haploid plants, hop2-1 haploid mutants showed large amounts of DNA fragmentation and chromosomal bridging in anaphase and metaphase for both Meiosis I and Meiosis II. This suggests that HOP2 acts to block non-homologous interactions.

Keywords: Chromosome
Homology
HOP2
Meiosis
Pairing
Advisor: Hasenkampf, Clare
Apolipoprotein E polymorphism and hippocampal atrophy across the spectrum of Alzheimer’s disease and dementia with Lewy bodies

Apolipoprotein E ɛ4-allele (APOE-ε4) is a major susceptibility factor across the spectrum of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). The characterization of this shared risk using neuroimaging and clinicopathological phenotypes is desirable for biomarker development. In this thesis, we first conduct a systematic literature review to synthesize current knowledge on the relationship between APOE-ε4 and hippocampal volumes in AD. We then study 298 patients (AD=250, DLB=48; 38 pathology-confirmed) to explore the association of APOE-ε4 with hippocampal volumes, irrespective of clinical diagnosis. Across the AD/DLB spectrum, (1) hippocampal volumes were smaller with increasing APOE-ε4 dosage, (2) learning performance was associated with hippocampal volumes only among APOE-ε4 carriers, (3) APOE-ε4 carriers performed worse on long-delay word-recall. Hippocampal volumes were also inversely related to APOE-ε4 dosage within the AD and DLB groups. We provide evidence that APOE-ε4 is linked to hippocampal atrophy across the AD/DLB spectrum, possibly via shared neurodegenerative mechanisms.

Keywords: Alzheimer's disease
Apolipoprotein E
Dementia with Lewy bodies
Endophenotype
Hippocampus
Magnetic Resonance Imaging
Advisor: Masellis, Mario
Black, Sandra E
Optimized Analysis of the Lung Allograft Microbiota from Bronchoalveolar Lavage Fluid

Introduction: Use of bronchoalveolar lavage fluid (BALF) for analysis of the allograft microbiota in lung transplant recipients (LTR) by culture-independent analysis poses specific challenges due to its highly variable bacterial density. Approach: We developed a methodology to analyze low-density BALF using a serially diluted mock community and BALF from uninfected LTR. Methods/Results: A mock microbial community was used to establish the properties of true-positive taxa and contaminants in BALF. Contaminants had an inverse relationship with input bacterial density. Concentrating samples increased the bacterial density and the ratio of community taxa (signal) to contaminants (noise), whereas DNase treatment decreased density and signal:noise. Systematic removal of contaminants had an important impact on microbiota-inflammation correlations in BALF. Conclusions: There is an inverse relationship between microbial density and the proportion of contaminants within microbial communities across the density range of BALF. This study has implications for the analysis and interpretation of BALF microbiota.

Keywords: Allograft microbiota
Bronchoalveolar Lavage Fluid
Lung Transplant
Microbiome
Advisor: Coburn, Bryan