VictorJuiz/thesis huggingface dataset:
Exploring Clinical and Biological Subtypes of Isocitrate Dehydrogenase Mutant Gliomas
Keywords: 2-hydroxyglutarate
Brain Cancer
Epigenetics
Glioma
Isocitrate Dehydrogenase
Metabolism

Malignant gliomas are the most common primary brain tumours in adults. Due to their diffuse nature and significant inter- and intra-tumoural heterogeneity, conventional therapies fail to prolong patient life expectancy beyond 12-15 months upon diagnosis. Isocitrate dehydrogenase (IDH) mutations are critical early genetic alterations in glioma and confer a significantly improved prognosis. We sought to establish the importance of IDH mutations in glioma through three approaches. We show an overall support from the Neuro-Oncology field for the recent integration of IDH mutation in the World Health Organization diagnostic criteria for gliomas. Next, we report clinical utility in utilizing the oncometabolite, 2-hydroxyglutarate as a surrogate biomarker for IDH mutation detection. Lastly, we report distinct metabolic, clinical and epigenetic profiles in a cohort of IDH mutated lower grade gliomas, that “mimic” high grade glioblastoma. Our results support the clinical importance of IDH mutation and provide novel insights on its underlying biology.
What Matters to the Kids? Perspectives of Children with ASD on Weight and their Bodies
Keywords: Autism Spectrum Disorder
Body Image
Disability
Health Care
Obesity
Weight Management

Introduction: Overweight and obesity (OW/OB) affects children with Autism Spectrum Disorder (ASD) at high rates, often compromising their health. Objective: To advance an understanding of OW/OB in relation to children with disabilities. Methods: 1. Applied a socioecological lens to examine risk factors for OW/OB for children with disabilities. 2. A scoping review of weight-management programs for children with disabilities. 3. Qualitative interviews with children with ASD. Results: Numerous actors beyond the individual child must be considered when supporting children with disabilities and OW/OB. While weight-management programs for this population are scarce, existing programs can be accommodated to include children with disabilities. Children with ASD were mostly unconcerned about their weight, view their bodies positively, and value being physically active. Discussion: Health care providers must critically examine their assumptions about weight. This work promotes shifting focus from weight and body size to health and growth to promote child- centered care.
Exploring the Needs of Cancer Survivors When Returning to or Staying in the Workforce
Keywords: Cancer
Rehabilitation
Return-to-work
Support

Cancer survivors have strong personal desires to resume work to feel productive and meet financial needs. However, they may be faced with physical and psychological challenges. This research aims to: examine cancer survivors’ perspectives on supports needed when returning to work; investigate sex and gender differences when returning to work; and explore demographic and employment factors that may influence this process. An exploratory qualitative design was used. The study had two phases: focus groups and one-on-one semi-structured interviews. Inductive thematic analysis was used to analyze the data. The total sample includes 15 participants, 87% female and 13% male. Key themes include: changing perspectives on self and work; managing work and social systems; determining disclosure and accommodation; and the importance of supports for return to work and daily life. This study informs cancer rehabilitation research by developing an understanding of the supports needed to help cancer survivors return to work successfully.
Risk Stratification for Prevention of Venous Thromboembolism in Hospitalized Medical Patients: Can thromboprophylaxis be safely restricted to limit costs?
Keywords: Cost
Deep Vein Thrombosis
Medical Patients
Pulmonary Embolism
Risk Assessment Models
Venous Thromboembolism

The objectives of this study were to estimate and compare the economic and clinical outcomes of using risk assessment models (RAMs) to support decision-making on thromboprophylaxis compared to the current standard of practice (SOP) in hospitalized medical patients at Sunnybrook Health Sciences Centre (SHSC). The Padua Prediction Score (PPS) and the Improve Risk Score (IRS), were applied to 199 general internal medicine (GIM) patients during three samples of one-week GIM admissions at SHSC. The predicted rate of hospital associated venous thromboembolism (HA-VTE) and the quality of life in GIM patients at SHSC identified as low risk of HA-VTE, was not significantly different after one year with RAM-directed thromboprophylaxis compared to SOP-directed thromboprophylaxis. Additionally, the use of RAMs had a significant potential annual cost savings of more than $200,000. Prospective evaluation is required to establish the feasibility and usability of RAMs and the safety of reducing the rate of thromboprophylaxis.
Chemical Exchange Saturation Transfer MRI for Detection of Cell Death in Breast Cancer Xenografts
Keywords: Breast cancer
Cell death
CEST
Chemotherapy
MRI
Response monitoring

Detecting cell death after chemotherapy could help optimize treatment regimens and improve outcomes. Breast cancer xenografts (MDA-MB-231) were scanned before and after chemotherapy to investigate parameters of chemical exchange saturation transfer (CEST) MRI that can differentiate regions of cell death from viable tumour. The CEST effect at 0.5 μT saturation amplitude was measured using the magnetization transfer ratio (MTR) at 1.8 and -3.3 ppm frequency offsets. An MTR cutoff of 0.12 at 1.8 ppm was able differentiate between viable tumour and cell death regions (p
A Novel Evaluation of Alcohol Sensitivity in the Context of the Acquired Preparedness Model
Keywords: acquired preparedness
alcohol
expectancy
impulsivity
learning theory
subjective response

The acquired preparedness model (APM) posits that the relationships between impulsivity and alcohol misuse are indirectly influenced through the biased acquisition of positive versus negative expectancies for the effects of alcohol. The present study assessed whether self-reported sensitivity to the lower dose/stimulant and heavier dose/sedative effects of alcohol would indirectly influence the impulsivity-expectancy relationship and drinking quantity and problems. Structural equation modeling was performed on cross-sectional, self-report data from 300 young adult heavy drinkers. Alcohol sensitivity was unrelated to impulsivity or alcohol expectancies, but each variable had unique associations with drinking outcomes, suggesting that alcohol sensitivity does not contribute to the APM. Lower alcohol sensitivity was directly associated with drinking outcomes. There were also positive, indirect effects in the traditional APM between impulsivity and drinking variables via positive and negative expectancies. Future research should try to replicate the model in a longitudinal sample to confirm temporal sequencing of relationships.
Effects of final irrigation with CHX and EDTA based irrigant combined with detergents οn the surface of dentin using surface analytical methods
Keywords: chlorhexidine
parachloroanaline(PCA)
precipitate
sodium hypochlorite
TOF-SIMS
XPS

This study evaluated the formation of precipitate or parachloroanaline (PCA) on the root canal dentin surface after irrigation with NaOCl and final irrigation with Smear OFF using of Time-of-Flight Secondary-Ion-Mass-Spectrometry (TOF-SIMS) surface analysis and X- Ray Photoelectron spectroscopy (XPS). Dentin blocks from human maxillary molars were used and the dentinal tubules were exposed in a perpendicular orientation. The blocks were divided in CHX group: Irrigation with 6% NaOCl 17% EDTA 6 % NaOCl and 2% CHX, Smear OFF group: Irrigation with 6% NaOCl and Smear OFF. TOF – SIMS and XPS analysis of the blocks followed. Precipitation with PCA and occlusion of the dentinal tubules were noted on the surface of the dentin in the control group (CHX). No precipitate or PCA were detected on the surface of dentin in the experimental group (Smear OFF) and the dentinal tubules were open.
The Glaciolacustrine Sediment Record of Cariboo Lake, BC: Implications for Holocene Fluvial and Glacial Watershed Dynamics
Keywords: Climate Proxy
Fluvial Geomorphology
Glacier Retreat
Glaciolacustrine
Holocene
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.
A High Throughput Device for Clonogenic Assays and Radiobiology Research
Keywords: cancer
Clonogenic assay
high thoughput
hypoxia
radiation
Radiobiology

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.
Extending the Capabilities of Terrestrial Target Tracking Spacecraft
Keywords: attitude and orbital control systems
deorbit
microsatellites
spacecraft dynamics
target tracking
trajectory planning

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.
The Impact of a Childhood Cancer Diagnosis on their Mother's Mental Healthcare Use
Keywords: Cancer
Healthcare
Mental health
Mother
Oncology
Pediatric

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
Glucose Derangements and Brain Function in Neonatal Encephalopathy
Keywords: Amplitude-integrated electroencephalography (aEEG)
Continuous electroencephalography (cEEG)
Glucose variability
Hyperglycemia
Hypoglycemia
Neonatal neurology

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.
Health Care Providers' Perspectives of Uncertainty in Newborn Screening
Keywords: Health care providers
Medicalization
Metabolic disease
Newborn
Screening
Uncertainty

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.
Assaying the Microbiome During Critical Illness
Keywords: Critically Illness
Late-onset infections
Microbiome
Sepsis

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.
Shrinking Horizon, Scenario-based Optimal Liquidation with Lower Partial Moments Criteria
Keywords: Intraday Trading
Lower Partial Moments
Optimal Liquidation
Shrinking Horizon
Stochastic Programming

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.
Identifying CD36 as a Receptor for Albumin Transcytosis by Dermal Microvascular Endothelial Cells
Keywords: Albumin
CD36
Endothelial Cells
Microvasculature
Transcytosis

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.
The Effect of Diagnostic Terminology on Cognitive, Emotional, and Somatic Outcomes Following Mild Traumatic Brain Injury
Keywords: Concussion
Diagnostic Terminology
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.
Evaluating the Unique Associations Between Personality Psychopathology and Heterogeneous Eating Pathology Symptoms
Keywords: eating pathology
Personality Inventory for DSM-5
personality psychopathology

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.
Altered CD8+ T cell function in Ankylosing Spondylitis: The role of perforin in enhanced inflammatory profiles
Keywords: Ankylosing Spondylitis
Arthritis
CD8 T cell
Immunology
Inflmmation
Perforin

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.
Visualization of Fluid Dynamics in Nanoporous Media for Unconventional Hydrocarbon Recovery
Keywords: Evaporation
Knudsen flow
Nanofluidics
Nanoporous
Shale

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.