VictorJuiz/thesis huggingface dataset:
The Involvement of Cortical Inhibition, Plasticity, and Excitability in the Neurobiology and Treatment of Late-Life Depression
Keywords: Inhibitory neurotransmission
Late-life depression
Membrane excitability
Neuroplasticity
Transcranial magnetic stimulation
Venlafaxine

Several lines of evidence indicate that the pathophysiology of depression includes altered inhibitory and excitatory neurotransmission in the cortex. Most studies to date, however, have focused on younger and mid-life adults with depression. Advancing age has widespread effects on the structure and function of the brain, and late-life depression is often characterized by unique clinical features, including executive dysfunction and high relapse rates. Thus, the pathophysiology of depression may differ in older adults. This work aimed to uncover how neurophysiological mechanisms driven by inhibitory and excitatory neurotransmission are involved in the pathophysiology and treatment of late-life depression. We combined single-pulse and paired-pulse transcranial magnetic stimulation (TMS) with electromyography to measure inhibition, plasticity, and excitability in the motor cortex of older adults with depression. TMS measures were collected prior to treatment initiation, and after 1 week and 12 weeks of treatment with venlafaxine. We also measured cognitive functioning pre-treatment, and depressive symptom severity pre- and post-treatment. We hypothesized that TMS measures would be abnormal in older adults with depression compared to healthy controls, and that these TMS measures would be associated with executive dysfunction and treatment outcomes in late-life depression. First, compared to younger healthy controls, we observed similar reductions in GABAA receptor-mediated cortical inhibition in older and younger adults with depression, and older healthy controls, suggesting overlapping cortical inhibition deficits in advancing age and depression across the lifespan. Second, we found a specific relationship between worse executive function and heightened cortical plasticity in older adults with depression. Third, cortical inhibition and plasticity were not found to change after 1 or 12 weeks of venlafaxine treatment, regardless of clinical response to treatment, suggesting that conventional pharmacotherapy may not target abnormalities in these motor cortical processes in late-life depression. Lastly, we demonstrated that pre-treatment single-pulse TMS measures of cortical excitability were predictive of response and non-response to venlafaxine treatment. Together, these findings highlight the importance of biological aging to the neurobiology of late-life depression, and clarify the unique roles that cortical inhibition, plasticity, and excitability each play in late-life depression pathophysiology, cognitive functioning, and treatment outcomes.
Corrosion Behaviour of Electrodeposited Nanocrystalline Nickel (Ni) and Nickel-Iron (NiFe) Alloys Compared to their Polycrystalline Coarse-Grained Counterparts
Keywords: Corrosion
Electrodeposition
Nanomaterials
Passivity
Polarization
XPS

The corrosion behaviour of electrodeposited nanocrystalline Ni, 85Ni-15Fe, 80Ni-20Fe and 45Ni-55Fe was assessed in sulfate electrolytes and compared to their coarse-grained counterparts. The effect of grain size reduction on the corrosion behaviour of Ni and NiFe alloys was minimal, in particular at increasingly oxidizing conditions (i.e. increased anodic potential, increased pH), whereby the contribution of sulfur impurities (present in higher concentration in the nanostructured materials) was minimized. The consideration of other microstructural factors, in addition to grain size reduction, was critical in the appropriate interpretation of the corrosion performance.In acidic sulfate electrolytes, similar active-passive-transpassive polarization behaviour was observed, regardless of grain size. Differences in the region of active dissolution (e.g. enhanced current densities, increased passivation potential) were ascribed to the effects of sulfur impurities rather than grain size reduction; the nanomaterials contained increased sulfur due to additives used during their electrodeposition. Once passive, slightly enhanced passive current densities were observed with grain size reduction and attributed to differences in their passive film, as characterized using parallel angle-resolved X-ray photoelectron spectroscopy (PARXPS) to obtain non-destructive depth profiles. Regardless of grain size, the passive film of NiFe alloys consisted of inner Ni and Fe oxides, and an outer Ni hydroxide, with the relative Ni:Fe ratio remaining stoichiometric, relative to the bulk alloy composition; however, thicker passive films formed on nanostructured NiFe, as well as a higher concentration of Ni³⁺ in the form of defective Ni oxide. The slightly enhanced passive current densities with grain size reduction observed in Ni-rich NiFe were attributed to the influence of a defective Ni oxide. The cathodic stability of the passive film (i.e. Flade potential) was similar regardless of grain size, with only a minor increase that could be ascribed to grain size effects, as assessed using open circuit potential decay. Grain size reduction also impacted the corrosion morphology, leading to a more uniform topology with finer roughness. During transpassive dissolution, grain size reduction in Ni resulted in the delocalization of corrosion attack, from localized intergranular (coarse-grained) to more uniform (nanocrystalline).
Cellular and Molecular Mechanisms of Endothelial Dysfunction in Diabetic Cardiomyopathy
Keywords: Diabetes
Diastolic dysfunction
Endothelial cell
Extracellular vesicles
microRNA
Microvasculature

Type 2 diabetes (T2D) is associated with cardiac microvascular dysfunction, which is thought to contribute to the development of diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF). The molecular mechanisms responsible for HFpEF remain unclear, and no effective diagnostics or main-stay treatments are available. To gain insight into biomarkers and disease mechanisms we measured the microRNA content of circulating extracellular vesicles (EVs) during pathogenesis in two animal models of T2D-associated HFpEF (i.e., obese mouse [Lepr-/-] and lean rat [Goto Kakizaki]). We found that miR-30d and miR-30e were increased prior to echocardiographic evidence of diastolic dysfunction in T2D mice, and they were also elevated in T2D rats with established diastolic dysfunction. These microRNAs may serve as biomarkers of cardiac microvascular dysfunction as they are upregulated in the endothelial cells (ECs) of the left ventricle of the heart, but not other organs. Furthermore, the miR-30 family is secreted in response to activation of senescence pathways, a characteristic feature of diabetic ECs. Assessment of pathways regulated by miR-30d/e revealed a large number of target genes involved in fatty acid biosynthesis and metabolism. Importantly, over-expression of miR-30e in ECs increased fatty acid oxidation and the production of reactive oxygen species, while inhibiting the miR-30 family decreased fatty acid oxidation. Additionally, miR-30e over-expression synergized with fatty acid exposure to dramatically down-regulate the expression of eNOS, an important regulator of microvascular and cardiomyocyte function. Thus, miR-30d/e may represent early biomarkers of diastolic dysfunction that reflect altered fatty acid metabolism and microvascular dysfunction in the heart. Furthermore, the pathways regulated by miR-30 may represent therapeutic targets for diabetes-associated HFpEF.
Secondary Prevention of Anal Cancer among Men living with HIV: Acceptability and Suitability of Anal Pap Cytology and HPV DNA Type Testing
Keywords: Anal cancer
Cancer screening
HIV
Human papillomavirus
Men living with HIV

The risk of anal cancer is magnitudes higher among men living HIV than the general population. To contribute to an evidence-base in support of anal cancer screening guidelines, this dissertation evaluates the acceptability of screening among men living with HIV and sets the foundation for work examining the suitability of anal cytology and HPV DNA type testing for screening this population. A sample of 1677 men living with HIV enrolled in the Ontario HIV Treatment Network Cohort study completed a questionnaire module on HPV, its associated diseases, and their prevention in 2016-2017. Three objectives examined acceptability of anal cancer screening by 1) quantifying prevalence of screening, 2) examining the role of past screening on beliefs and willingness to be screened, and 3) evaluating facilitators to screening, HPV knowledge and self-perceived risk for anal cancer. In this sample, disparities in anal cancer screening were observed, wherein men from some racialized groups and heterosexual men were less likely to have discussed screening or to have been screened. The vast majority (90%) of men, however, were willing to undergo screening in the future. Positive beliefs regarding screening were associated with higher willingness. Behavioural intention does not ensure uptake, however, and factors such as health literacy and perceived susceptibility can influence men’s participation. Half of the study sample were unaware of HPV and the majority (73%) felt they had no or low chance of getting anal cancer. Specific risk-focused knowledge was associated with higher perceptions of risk. Findings will inform community-led health literacy efforts to improve participation in anal cancer screening. The final objective provides methodological guidance for the analysis of screening studies when verification of screening results is not possible for all participants. This simulation study assessed the utility of statistical methods to account for verification bias that arises in these scenarios. Findings suggest multiple imputation may be most suitable for handling complex missing data scenarios common to screening studies. This work will inform the analysis of data from a forthcoming anal cancer screening study to determine the best algorithm by which to screen for anal cancer among men living with HIV.
Optimization and Mechanistic Exploration of Intravenous Human Immunoglobulin G for Treatment of Traumatic Cervical Spinal Cord Injury
Keywords: Immunomodulation
Immunosuppression
Intravenous human immunoglobulin G
Neuroinflammation
Neutrophils
Spinal cord injury

Spinal cord injury (SCI) causes devastating functional impairments and socioeconomic consequences for patients and family members. The pathology is characterized by an initial physical trauma which is amplified by secondary injury mechanisms including vascular and inflammatory processes. The blood-spinal cord-barrier (BSCB) consists of pericytes, astrocytes and endothelial cells, which collectively form the neurovascular unit (NVU). After SCI, a compromised BSCB enables peripheral immune cells to enter the injury site. This inflammatory response has polarizing effects. While immune cells are beneficial by secreting growth factors that promote regeneration after SCI, they also propagate injury when sterilizing the injured area. Thus, immunomodulation is becoming the preferred clinical intervention to immunosuppression when resolving neuroinflammation. Approved by regulatory authorities as an immunomodulatory therapy, intravenous human immunoglobulin G (IVIg) may be suitable for treating SCI. While prior work has suggested a possible beneficial role for IVIg in the treatment of acute SCI, the clinical translation of this work has been hindered by critical knowledge gaps including uncertainty around mechanism of action, the optimal dosing and the post-injury therapeutic window. Therefore, this thesis aims to use a clinically relevant rat model of SCI to provide insights into the optimal dose, therapeutic time window and mechanism of action. My work determined that the optimal therapeutic dose of IVIg is 2g/kg and that beneficial effects were maintained when administered up to 4 hours post-SCI. My work showed that IVIg binds to BSCB cells, strengthening the BSCB and reducing neutrophil infiltration at 24 hours post-SCI. This is associated with long-term motor and sensory recovery and spinal cord tissue preservation. Immunomodulatory effects mediated by IVIg (2g/kg) might be explained in two-fold, where human immunoglobulin G (hIgG) antagonizes neutrophil infiltration into the spinal cord by co-localizing with endothelial cell ligands that mediate neutrophil extravasation. Moreover, IVIg traffics neutrophils to the spleen by increasing expression of neutrophil chemoattractants in spleen and sera. In conclusion, this work demonstrates that IVIg might be a suitable treatment for SCI with potential for clinical translation. IVIg (2g/kg) enhances short-term and long-term benefits after SCI by modulating local and systemic neuroinflammatory cascades.
Structural properties of the human cerebral cortex in health and disease
Keywords: Cerebral cortex
Cortical thickness
cortical surface area
MRI
magnetic resonance imaging
Neurodevelopment
Psychiatry
Transcriptomics

In vivo magnetic resonance imaging (MRI) has shown profound structural differences in the human cerebral cortex – varying across regions – during development, aging, and in clinical conditions such as mental illness. The neurobiology underlying these MRI-derived structural variations remains largely unknown. Herein, we develop a novel bioinformatics approach to probe the underlying biological processes behind structural variations of the cerebral cortex by integrating single-cell and bulk transcriptomics with MRI-derived measures. This approach was first applied to a multi-modal dataset linking biophysical MR properties in cortical tissue, commonly used to index tissue microstructure, with shared and unique cellular elements of pyramidal neurons and oligodendrocytes. Then, using an independent dataset, we link microstructural change in the cerebral cortex during adolescence with intra-cortical myelination. Finally, this approach was used to probe the neurobiological and developmental origins of cortical thickness and surface area in psychiatric disorders. Group differences in cortical thickness were quantified in individuals with mental illness (n=28,321), namely attention-deficit/hyperactivity disorder (ADHD), autism spectrum (ASD), bipolar (BD), major depressive (MDD), obsessive-compulsive (OCD), and schizophrenia (SCZ). There was a shared profile in group differences of thickness among the six disorders and was associated with pyramidal-specific expression. Co-expression analysis of genes implicated in thickness differences revealed two clusters: a prenatal cluster involved in neurodevelopmental processes and 2) a postnatal cluster involved in synaptic activity/plasticity. Next, we investigated group differences in cortical surface area – a phenotype largely determined during gestation – in those with ADHD, ASD, BD, MDD, SCZ, and high psychopathology (n=27,359). Group differences in area were predominantly in transmodal association cortices, and associated with inter-regional profiles of fetal gene-expression specific to proliferative cells, namely radial glia and intermediate progenitor cells, and differentiated cells, namely excitatory neurons, endothelial and mural cells. We also show that these cell types intersect with genes associated with known pre-/perinatal risk factors for mental illness. Taken together, these findings support a model of mental illness, whereby deviations in neurodevelopment confer vulnerability later in life, and subsequent postnatal perturbations contribute to clinical manifestation. Ultimately, this body of work provides an analytical framework to explain variations within the human cerebral cortex.
Novel Operation and Maintenance Practices for Permeable Pavements
Keywords: Chloride
low impact development
Maintenance
permeable pavement
PICP
Smart Infrastructure

This thesis investigates several opportunities for operation and maintenance to improve the performance of permeable pavements by testing strategies to rejuvenate old pavements, improve winter stormwater quality, and enhance stormwater infiltration. Testing of pre-treatment maintenance followed by street sweeping on mature permeable interlocking concrete pavement parking lots in 2016 revealed that pre-treatment with pressure wash significantly improves the effectiveness of vacuum sweeping. Pavement age and usage were found to affect the restoration of surface infiltration significantly. Older pavements and high traffic areas were considerably more challenging to restore for both control and test groups. Power brushing gave inconclusive results across test groups. Chloride concentrations in surface runoff and zero-exfiltration permeable pavement effluent were measured between Jan 2016 to May 2017 and compared with concentration in runoff from a conventional asphalt pavement. Runoff from asphalt generated large spikes in chloride concentration over 21,800 mg/L. However, when combined with the flashier runoff hydrograph, these high instantaneous chloride levels, lasting a few hours, resulted in less exposure to elevated concentrations. Permeable pavements, in contrast, attenuated peak chloride concentrations during winter. Furthermore, chloride was retained only temporarily and flushed from the pavement reservoir during spring melt, suggesting that attenuated chloride release from permeable pavement effluent is unlikely throughout the summer or fall months. Smart adaptive operation of PICP underdrains was tested to increase stormwater infiltration on low permeability soils. This unique study is the first demonstration of ‘smart’ operations for permeable pavements. The three-year evaluation, 2016-2018, confirmed that extended detention of stormwater could allow permeable pavements to control and infiltrate excess stormwater run-on and increase the probability of managing extreme events in non-run-on situations. The study also noted that high volume reductions could be achieved even when low permeability soils are present on site. Overall, the thesis bridges the gap between theory and practice by guiding how to improve operation and maintenance techniques for permeable pavements. This research aims to benefit permeable pavement manufacturers, suppliers, and installers in Canada by highlighting opportunities to improve permeable pavements' environmental benefits and management practices.
Culture and Family Relationships: Examining Young Sibling Conflict, and European and South Asian Canadian Mothers
Keywords: culture
marital conflict
parent-child relationship
sibling conflict
South-Asian

Mothers are salient influencers of their children’s development, and the strength of their influence is contingent on cultural values and beliefs. Cross-cultural research has primarily investigated parental relationships and their associations with individual child behaviour. The unique contribution of this thesis is the cross-cultural examination of three dyadic relationships in the family: the sibling, parent-child, and marital relationships. Data was drawn from Kids, Family Places. Two hundred and seventy-three Canadian families (222 European and 51 South Asian) were included. There was data from a total of 546 siblings (i.e., 273 dyads). Observational measures of interaction between young sibling dyads were collected in the home, and mothers reported on negative and positive qualities of their parenting, and conflict in their marriage. Cross-culturally equivalent measures of parenting and marital conflict were first established using structural equation modelling. Establishing measurement equivalence was an important component as it allowed for meaningful mean comparisons of the constructs between European and South Asian Canadian mothers. Mean differences were examined with t-tests and there was evidence of cultural variation in parenting and marital conflict patterns. South Asian Canadian mothers reported more negativity with both of their children and positivity with their younger 18-month-old, and lower frequency of destructive marital conflict, than European Canadian mothers. Sibling conflict (aggression and hostility) was investigated in the context of positive parenting and constructive marital conflict, their interaction, and culture. Culture was examined as a moderator on the association of sibling conflict with positive parenting and constructive marital conflict using multilevel modelling. As expected, sibling conflict was found to be negatively predicted by positive parenting. This association was attenuated by the frequency of constructive marital conflict. Consistent with literature, culture moderated the negative association of positive parenting on sibling conflict. Specifically, positive parenting was more strongly associated with sibling conflict in European Canadian than in South Asian families. These findings are discussed in the context of values and beliefs associated with conflict and cooperation amongst individualistic Western cultures and collectivistic Eastern cultures such as the South Asian community.
Towards an Automatic Caption Quality Assessment Model Reflecting the Subjective Views of Deaf, and Hard of Hearing Audiences
Keywords: Active learning
Broadcasting
Closed Captioning
Human Factors
Quality assessment
Signal Detection Theory

Closed Captioning (CC) was designed to serve Deaf and Hard of Hearing viewers, but the quality of CC has been assessed without much inclusion of these primary consumer groups. Currently, caption quality is mostly measured using arithmetic counts based on “errors” between the original spoken words and the caption text. A method to assess the quality of CC that includes the subjective perspective of D/HoH viewers could provide descriptive evaluations and ratings reflective to hearing conditions. Furthermore, using machine learning algorithms based on subjective ratings from D and HoH audiences could automate the process of assessment while reflecting human subjective assessment. Towards the goal of automatic caption quality assessment based on target consumer group perspectives, three studies were conducted to: 1) determine the potential of neural network prediction model feasibility; 2) generate a probability model of human caption quality assessment using the Signal Detection Theory framework; 3) construct and train neural networks to represent human quality assessors using Active Learning; and 4) carry out a benchmarking analysis to compare the newly developed assessment system with existing measures. The main findings from the studies include: 1) statistically significant difference in subjective assessment between D and HoH audiences; 2) correlation between caption error sensitivity and the perceived quality ratings on captions; 3) empirical evidence of the relationship between the values of the four quality factors (Delay, Speed, Number of missing words, and Caption paraphrasing) and the subjective quality rating; 4) use of Signal Detection Theory for modeling D and HoH audience error detection behaviour from watching CC; 5) implementation of Caption quality Assessment Intelligence System (CAIS) which can automatically rate the quality of CC by replicating human subjective assessment on various captions. The main contributions of this research are: 1) the development of a quality assessment neural network model for Closed Captioning which includes Deaf and Hard of Hearing viewer’s subjective opinions; 2) the development of probability decision models for Deaf and Hard of Hearing viewers based on caption error detection; and 3) provision of additional quantitative evidence of subjective difference between Deaf and Hard of Hearing groups.