VictorJuiz/thesis huggingface dataset:
Continuity of Care, Emergency Department Visits and Readmission in Adolescents with Psychiatric Disorders: A Retrospective Cohort Study using Propensity Score Matching

Objective: To determine whether continuity of care (COC) reduces emergency department (ED) visits and/or readmission in adolescents with psychiatric disorders. Methods: A retrospective cohort of adolescents discharged with psychiatric disorder between April 1, 2002 and March 1, 2004 was identified using hospital administrative databases. Good COC was defined as at least one aftercare contact in 30 days. Confounding by patient characteristics was adjusted for by propensity-score-matching of good and poor COC adolescents. Cox PH was used to analyze time to outcome. Results: 48.77% of adolescents had good COC. 38.39% of adolescents had ED visit or readmission in the year post-discharge. Good COC increased risk of readmission (HR = 1.38 (1.14 – 1.66)), but not of ED visits (HR = 1.14 (0.95 – 1.37)). Conclusions: COC increased risk of readmission by 38% but did not increase risk of ED visits. These findings are contextualized. Implications to adolescent mental health service delivery are discussed.

Keywords: child
adolescent
mental health
psychiatric disorders
mental health services
epidemiology
continuity of care
aftercare
hospitalization
psychiatric hospitalization
emergency services, psychiatric
emergency department visits
health status disparities
health services utilization
observational studies
follow-up studies
propensity scores
Bias
Advisor: To, Teresa
Prostate Cancer and Alpha-linolenic Acid

The objectives were to 1) conduct a meta-analysis to assess the association between alpha-linolenic acid (ALA) and prostate cancer; 2) analyze a trial of ALA on coronary heart disease with PSA as a post hoc outcome; 3) assess the effect of trial serum and also ALA directly on LNCaP cell growth. 1) The ALA meta-analysis of prospective and case-control studies showed no overall effect on prostate cancer. However, removal of one study from the analysis of prospective studies changed the result to a significant protective effect (RR=0.91; 95%CI:0.83,0.99). 2) No significant treatment difference was seen in the change in PSA in the randomized controlled trial. 3) The ALA treatment serum from the clinical trial did not affect LNCaP cell growth. However, ALA decreased LNCaP cell growth in a dose dependent manner when added to cell culture. The results provide no positive evidence for an effect of ALA on prostate cancer.

Keywords: prostate cancer
alpha-linolenic acid
omega-3 fatty acid
n-3 fatty acid
prostate specific antigen
LNCaP cell
Advisor: Jenkins, David J. A.
The Role of Dimerization by Escherichia coli HypB in Hydrogenase Biosynthesis

Nickel insertion into the [NiFe]-hydrogenase requires the accessory protein HypB, which is a GTPase. The GTPase domain of Escherichia coli (E. coli) HypB undergoes dimerization in the presence of GTP. To determine the role of HypB dimerization in hydrogenase biosynthesis, a double mutation L242A/L246A was introduced into full-length E. coli HypB, and the protein was expressed and characterized both in vitro and in vivo. Gel filtration experiments demonstrated that L242A/L246A HypB was monomeric as expected. The inability of L242A/L246A HypB to dimerize does not abolish its GTPase activity and the monomeric L242A/L246A HypB has a similar Ni(II)-binding behavior as that of wild type HypB. Upon the expression of L242A/L246A HypB in vivo the hydrogenase activity is approximately half of the activity of the wild-type control. These experimental results suggest that dimerization of HypB does have a, but not critical, role in hydrogenase biosynthesis.

Keywords: Escherichia coli
HypB
Dimerization
Hydrogenase
Advisor: Zamble, Deborah
Actin Tyrosine Phosphorylation in Microcysts of Polysphondylium pallidum

High osmolarity causes amoebae of the cellular slime mould Polysphondylium pallidum to individually encyst, forming microcysts. During microcyst differentiation, actin is tyrosine phosphorylated. Tyrosine phosphorylation of actin is independent of encystment conditions and occurs during the final stages of microcyst formation. During microcyst germination, actin undergoes dephosphorylation prior to amoebal emergence. Renewed phosphorylation of actin in germinating microcysts can be triggered by increasing the osmolarity of the medium which inhibits emergence. Immunofluorescence reveals that actin is dispersed throughout the cytoplasm in dormant microcysts. Following the onset of germination, actin is observed around vesicles where it co-localizes with phosphotyrosine. Prior to emergence, actin localizes to patches near the cell surface. Increasing osmolarity disrupts this localization and causes actin to redistribute throughout the cytoplasm, a situation similar to that observed in dormant microcysts. Together, these results indicate an association between actin tyrosine phosphorylation, organization of the actin cytoskeleton, and microcyst dormancy.

Keywords: actin
dormancy
germination
microcyst
Polysphondylium
tyrosine phosphorylation
cytoskeleton
encystation
osmolarity
slime mould
Advisor: O'Day, Danton H.
The Thermal Grill Illusion of Pain: Characterizing Differences in Response across Body Sites

The simultaneous application of interlaced innocuous warm and cool stimuli (a thermal grill stimulus, TGS) can elicit sensations of burning heat (the Thermal Grill Illusion, TGI). The TGS is thought to alter the central interactions between somatosensory sub-modalities (i.e. cold-inhibition of pain). Previous psychophysical findings point to body site differences in perceptual thermal thresholds. The primary objective of this study was to evaluate whether, using the same TGS, a TGI can be elicited at body sites other than the upper extremity. The present findings indicate that the TGI can be induced at the palm, back, calf, and foot. Pain and unpleasantness in response to the TGS were more frequent and intense following stimulation of the palm and back than the calf and foot. Lower cold pain thresholds were associated with lower pain intensity ratings in response to the TGS. These two findings may reflect differences in central integrative processes.

Keywords: somatosensory
psychophysics
temperature
Advisor: Dostrovsky, Jonathan O.
Hunter, Judith
The Role of Discoidin Domain Receptor 1 (Ddr1) on Macrophages in Adhesion and Cytokine Production

Atherosclerosis is an inflammatory disease of the cardiovascular system. Discoidin domain receptor 1 is a receptor tyrosine kinase that binds collagens. Previous work in our lab has shown that deleting DDR1 in a mouse model results in attenuation of atherosclerosis, with fewer macrophages in the plaque. The aim of this study was to determine what changes in macrophage behaviour due to the lack of DDR1 was attenuating plaque development. In order to carry out experiments, primary mouse peritoneal macrophages were used. DDR1-deficient macrophages adhered significantly less to type IV collagen and fibronectin compared to DDR1-expressing cells. In addition, when plated on type IV collagen and fibronectin, DDR1-deficient macrophages produced decreased levels of MCP-1 protein, a cytokine known to be important in plaque development, particularly in leukocyte recruitment to plaque. These results suggest that DDR1 is an important mediator in macrophage adhesion to matrix and macrophage cytokine production

Keywords: DDR1
Macrophage
Advisor: Bendeck, Michelle
The Quantity and Structural Quality of SP-A and SP-D Present in the Airways of Influenza-infected Patients

Influenza A virus (IAV) is a major cause of morbidity and mortality worldwide. Surfactant proteins A and D (SP-A and SP-D) are important lung innate immune proteins and have been shown in vitro and in mice to both neutralize and enhance the clearance of various IAV strains. In this study we hypothesized that SP-A and SP-D levels will be lower in human bronchoalveolar lavage (BAL) fluids from patients who have tested positive for influenza, as well as bacterial or fungal pathogens compared to controls. We have found that patients who have detectable IAV, bacteria or fungus have lower levels of SP-A and SP-D as detected by western blot analysis and enzyme-linked immunosorbent assay (ELISA) when compared to controls. Also, we found minor differences in the oligomerization and no differences in the glycosylation of SP-A and SP-D among BALs that detected the proteins on a Western blot.

Keywords: Influenza
SP-A
SP-D
Advisor: Palaniyar, Nades
The Effects of Bilingualism on Attention and Memory: Do Bilingual Advantages in Attention Lead to Disadvantages in Memory?

Recent evidence suggests that the task of managing a bilingual individual’s two languages is carried out by general attentional mechanisms. Researchers have found evidence for bilingual advantages in attention, specifically on tasks that involve inhibiting irrelevant information, which are believed to stem from lifelong practice at inhibiting the language system not currently in use. In the present study we hypothesized that, since bilinguals are better at inhibiting irrelevant information, they should show memory disadvantages if previously irrelevant information becomes relevant. 12 bilingual and 12 monolingual participants (age range:19-27) were tested in an eye tracking paradigm where the relational manipulation effect (the tendency to direct more viewing to manipulated regions of previously viewed scenes) was used to access memory for scenes that had been presented as distractors during a study block. No differences in memory were observed. However, we observed a significant difference in general viewing patterns between the two language groups, such that bilinguals made significantly shorter fixations.

Keywords: Bilingualism
Bilingual advantage
Attention
Memory
Advisor: Ryan, Jennifer D.
Wnt Signaling in Human Neural Stem Cells and Brain Tumour Stem Cells

We sought to determine whether activation of the Wnt signaling pathway altered the function of hNSCs in vitro. We took three approaches to activate Wnt signaling: Wnt3a, constitutively stabilized β-catenin (ΔN90), and the GSK3 inhibitor BIO. While Wnt3a and ΔN90 had no effect on proliferation in both stem cell (+EGF/FGF) and differentiating (-EGF/FGF) conditions, BIO reduced proliferation in both. All methods of Wnt signaling activation promoted neuronal lineage commitment during hNSC differentiation. Furthermore, BIO was able to induce mild neuronal differentiation in stem cell conditions, suggesting that GSK3-inhibition interferes with several pathways to regulate hNSC fate decisions. We also probed BTSC function using BIO-mediated GSK3 inhibition. We found that in stem cell conditions, BIO was able to induce neuronal differentiation, decrease proliferation, and induce cell cycle arrest. Together this data suggests that GSK3-inhibition, possibly through activation of Wnt signaling, may offer a novel mechanism for the differentiation treatment of glioblastomas.

Keywords: Wnt Signaling
Neural Stem Cells
Cancer Stem Cells
Brain Tumour
Advisor: Dirks, Peter Benjamin
Preeclampsia in HIV Positive Pregnant Women on Highly Active Anti-retroviral Therapy: A Matched Cohort Study

Background: Some studies have suggested that the risk of preeclampsia in HIV positive pregnant women has increased since the use of HAART became routine. There is also a concern that HIV positive women on HAART have a higher risk of adverse fetal outcomes compared to HIV negative women. Methods: In this matched retrospective cohort study, the risk of preeclampsia and adverse fetal outcomes was examined in 91 HIV positive pregnant women receiving HAART and 273 HIV negative pregnant women. Multivariate logistic regression models were used to adjust for confounding factors. Results: The risk of preeclampsia and preterm birth did not differ significantly between HIV positive and HIV negative women. HIV treated with HAART was an independent predictor for giving birth to a low birthweight baby. Conclusions: HIV positive women on HAART do not have a higher risk of preeclampsia. They do however have a higher risk for lower birthweight infants.

Keywords: Human immunodeficiency virus
preeclampsia
Highly Active Anti Retroviral Therapy
low birthweight
pregnancy
Advisor: Murphy, Kellie
Prediciting the corrosion and stress corrosion performance of copper in anaerobic sulfide solution

Stress corrosion cracking (SCC) susceptibility of the phosphorus de-oxidized copper has been evaluated in synthetic seawater polluted by sulfides using slow strain rate test (SSRT). The effect of concentration of sulfide, temperature, and applied cathodic and anodic potentials on the final strain values and maximum stress were also studied. No cracks were found under the tested conditions. The final strain and maximum stress values decreased but not significantly, with increase in the temperature, applied anodic potential and sulfide concentration. The observed effect is due to the section reduction by uniform corrosion. Lateral cross section and microscopic examination of the fractured specimen ruled out the existence of the localized corrosion. Electrochemical measurements showed that the Cu2S film is not a protective film and also exhibits a mass transfer limitation to the inward diffusion of the sulfides. Based on these results the reasons for the absence of cracking are also discussed.

Keywords: stress corrosion cracking
sulfide corrosion of copper
Advisor: Newman, Roger C.
The Therapeutic Effects of the Combined Use of American Ginseng (Panax Quinquefolius L.) Extract and Korean Red Ginseng (Panax Ginseng C.A. Meyer) Extract in the Management of Type 2 Diabetes Mellitus and Cardiovascular Risk Factors

Combination therapy has proven to be a popular treatment strategy for tighter diabetes control. Since the preliminary evidence is suggestive of complementary actions of American (AG) and Korean Red Ginseng (KRG) in improving glycemia, this project was designed to investigate the therapeutic potential of AG and KRG in combination. Following a randomized, double-blind, placebo-controlled parallel design in a population with diabetes at two centres, the combined use of AG and KRG for 12 weeks was safe, but did not significantly affect glycemic control, blood lipids or blood pressure. However, there was a trend toward lower glycated hemoglobin by 0.7% (p=0.1) and office systolic blood pressure by 5 mm Hg (p=0.052) compared to placebo. These findings encourage further investigation of the mechanism and roles of AG, KRG and their effective components. They also highlight limitations in ginseng research and the need to impose strict regulations to facilitate its standardization.

Keywords: American Ginseng
Diabetes
Korean Red Ginseng
Ginseng
Type 2 Diabetes
Cardiovascular
HbA1c
Combination Therapy
Ginseng Extract
Diabetes Management
Cardiovascular Risk Factors
Advisor: Vuksan, Vladimir
A Cost of Illness Study of Generalized Anxiety DisorderI in Canada

Background: Economic evaluations of generalized anxiety disorder (GAD) have been limited to ≤18 months. A decision model was developed; quantifying the lifetime cost-of-illness (COI) of GAD. Methods: An incidence-based Markov-model was developed using TreeAge® software, reflecting 9 health-states (HS): physician-assessed patients (3HS), maintenance therapies(4HS), discontinuation(1HS) and death(1HS). Onset probability (ages 18-80) determined model entry. Canadian Psychiatric Association (CPA) guidelines determined pharmaco-therapy, with revisions/validation by an expert panel. Response, remission based on pooled-analysis of CPA-cited evidence. Remaining clinical rates, absenteeism and hospitalization retrieved from literature. Direct (clinician, pharmacotherapy, hospitalization) and indirect costs (wage rate) retrieved from government publications. Results discounted at 5%. Results: The mean COI was 2008 Canadian $31,213(SD=$9,100)/patient; 96% attributed to absenteeism. Mean age=31years, discontinued treatment=85% by 2nd year, treatment discontinuation duration, 14(SD=9) years. CONCLUSION: GAD is a costly disease with a lifetime COI<$32k/patient; absenteeism exerts a significant impact. Limited prospective data contributes to uncertainty of estimate.

Keywords: Cost of Illess
Anxiety
Model
Advisor: Einarson, Thomas Ray
Making Conformance Work: Constructing Accessibility Standards Compliance

Web Content Accessibility Guidelines (WCAG) and the Accessible Rich Internet Applications (WAI-ARIA) constitute core accessibility resources for Web designers and developers. To explore their deployment, I conduct interviews with 10 practitioners who use WCAG and WAI-ARIA in their work. Using techniques derived from grounded theory and situational analysis, I develop the concept of conformance work. Conformance work refers to how designers and developers develop harmonized interpretations of WAI-ARIA and WCAG, and the Websites these specifications are meant to instruct. Conformance work is the upstream work designers and developers engage in to invest categories such as “standards compliance” and “Web accessibility” with meaning.

Keywords: Infrastructure
WCAG
WAI-ARIA
Advisor: Hockema, Stephen
A Task’s Cognitive Demands Influence Self-reported Performance Variances Throughout The Day

Chronotype describes the daily rhythm of an individual’s performance capability as it changes through the day. It is defined using the Horne-Östberg Morningness-Eveningness Questionnaire (MEQ) which assesses time-of-day preference; or the Munich ChronoType Questionnaire (MCTQ) which indicates sleep timing parameters. My hypothesis was that chronotype predominantly reflects an individual’s perceived daily rhythm in executive function. We tested this by comparing MEQ and MCTQ with the University of Toronto Inventory of Morningness and Eveningness (UTIME) Questionnaire which examines performance on scenarios requiring cognitive, physical, and/or emotional responses. Highest correlations were found between MEQ and UTIME tasks with high executive demand. The same UTIME tasks were also correlated with MCTQ (mid-sleep, free days), although the correlations were consistently lower than UTIME versus MEQ. Correlations among UTIME tasks and MCTQ (mid-sleep, workdays) were not linked to executive demand. Chronotype appears to reflect the perception of peak executive ability independently of sleep pattern.

Keywords: Performance
Time-of-day preference
Morningness
Eveningness
Executive function
Cognitive
Physical
Emotional
Sleep
Advisor: Ralph, Martin
The Annotative Practices of Graduate Students: Tensions & Negotiations Fostering an Epistemic Practice

This research explores the annotation and note-taking practices of graduate students and reports on the sets of activities, habits, objects, tools and methods that define the practice. In particular, this empirical study focuses on understanding the integration of annotation practices within larger scholarly processes. This study therefore aims to describe and analyze annotation not only as material externalities of the research process, but also as crucial epistemic practices allowing students to progress from one research activity to the other. Interviews are supplemented by document collection and analyzed using a multi-perspectival framework. The findings describe an annotation lifecycle and suggest a new model of the scholarly process using annotation practices as units of analysis. The study further discusses annotation as a primitive epistemic practice and examines the productive tensions fostering the student’s progress towards her goals. This research finally proposes requirements for future tools supporting scholarly practice.

Keywords: Annotation
Note-Taking
Scholarly Process
Epistemic Practice
Digital Textuality
Annotation Lifecycle
Scholarly Primitives
Reading and Writing
Advisor: Ratto, Matthew
Characterization of a Novel Interaction Between Septins and the Adenomatous Polyposis Coli Tumor Suppressor.

Septins are evolutionarily conserved proteins with roles in chromosome congression and segregation, cytokinesis and microtubule destabilization. Septins form homo- and hetero-oligomeric complexes, which are thought to act as dynamic scaffolds. We identified SEPT2/9/11/10 as novel interacting partners of adenomatous polyposis coli (APC), a bona fide tumor suppressor. Since septins and APC have similar roles and knockdown phenotypes, I sought to determine if they work together to perform their cellular functions. I showed that APC co-immunoprecipitates with endogenous septins in colon cancer cell lines. Using siRNA, I found that SEPT2 and APC may function within the same pathway to regulate DNA congression and segregation. Co-depleting SEPT9 with APC slightly alleviates the chromosome congression and segregation defects caused by siAPC alone. siSEPT9 increased abscission times, which was rescued by co-depleting APC. Future studies should elucidate the significance of the rescue data obtained upon APC and SEPT9 co-depletion and APC’s interactions with SEPT10/11.

Keywords: septins
APC
knockdown
abscission
Advisor: Trimble, William S.
Should Hepatitis B Screening Be Added to the United States Immigration Medical Exam? A Cost-utility Model

Hepatitis B virus (HBV) infection is a global leading cause of death as a result of its role in the development of cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). In industrialized nations such as the United States, chronic hepatitis B infection represents a significant and disproportionate disease burden among the foreign-born population. A Markov cohort decision model was developed to determine the cost-effectiveness of HBV screening among new immigrants for the purposes of early detection and treatment, as compared to usual care. The incremental cost-effectiveness ratio for the screening strategy was $45,570 per quality adjusted life year saved. Given the potential for health gains for the immigrant cohort as well as the economic attractiveness of the intervention, some consideration should be given to the addition of a universal HBV screening program to U.S. immigration policy.

Keywords: hepatitis B
economic evaluation
cost-utility
Markov model
immigration
screening
Advisor: Hoch, Jeffrey
Khan, Kamran
Dietary Chemoprevention Agent Sulforaphane Inhibits Growth, Survival and Tumorigenic Activity in Human Neuroblastoma

Objective: To evaluate the anti-tumor and histone deacetylase (HDAC) inhibitory activity of the dietary isothiocyanate, sulforaphane (SFN) in the paediatric cancer,neuroblastoma (NB). Materials and Methods: NB cell line (NUB-7), fibroblasts (FLF; negative control) and MCF-7 (positive control), were treated with SFN for up to 7 days and effects on growth, cytotoxicity, differentiation and tumorigenicity assessed. HDAC inhibition was determined by histone (H3/ H4) acetylation. Results: 10 μM SFN significantly decreased in vitro growth and survival of NUB-7 to 10.22 ± 0.71% (p < 0.001) with no significant effect on FLF. SFN induced G1, G2 and S phase cell cycle arrests and stimulated H3/H4 histone acetylation. SFN markedly decreased NUB-7 clonogenicity and tumorigenicity in vivo. Conclusion: Results suggest that low dose SFN reduces proliferation, survival and tumorigenicity of NB NUB-7. As a dietary factor of negligible intrinsic toxicity SFN is a promising therapeutic agent for the treatment of NB.

Keywords: Neuroblastoma
Sulforaphane
Apotosis
Cell cycle arrest
Differentiation
Dietary Compond
chemoprevention
Tumorigenic activity
Advisor: Yeger, Herman