VictorJuiz/thesis huggingface dataset:
The role of sensorimotor information in endpoint error detection: A focus on limb-target regulation processes
Keywords: efferent
forward model
motor control
proprioception
robotic guidance
vision

Our planned limb trajectories often require amendments to achieve accurate movement endpoints. Several studies have demonstrated the importance of visual feedback for online error detection and correction processes, but the importance of proprioceptive feedback and motor efference remains unclear. The current study investigated the role of proprioception and efference in movement endpoint error detection during reaching movements. Participants were required to judge endpoint errors of reaching movements to a visual target. The available sources of sensorimotor information were manipulated across one control and three experimental conditions that either did or did not involve efferent information and proprioceptive feedback. Results showed that participants had better endpoint error judgements when both efferent commands and proprioceptive feedback were available compared to when only vision was available. Therefore, both efferent information and proprioception appear to be important for online limb-target regulation processes.
Tele-Mindfulness for Dementia's Family Caregivers: a Randomized Trial with a Usual Care Control Group
Keywords: Caregiver
Dementia
Mindfulness

Caring for a family member with dementia is associated with chronic stress which can have negative effects on caregivers’ mental and physical health. Mindfulness-based interventions have been proposed to improve psychological outcomes in caregivers. The purpose of this study was to evaluate the feasibility and effectiveness of live online mindfulness (tele-MBCT) program for caregivers of people with dementia. 26 family caregivers were randomly assigned to a tele-MBCT intervention or control group. Intervention participants attended eight weekly live online training and practiced at home. All participants completed surveys at baseline, post-intervention and 4-week follow-up. Majority of participants completed the study. Intervention group reported high satisfaction with the intervention and the online delivery method. Pre-Post improvement in self-compassion and coping strategies in the intervention group were noted. Tele-MBCT is a feasible intervention and may improve psychological outcomes and adaptive coping in dementia’s family caregivers. A larger controlled trial is warranted.
Exploring Patient-centred Care for Women with Ductal Carcinoma in situ
Keywords: ductal carcinoma in situ
patient-centred care
qualitative research

Introduction: Ductal carcinoma in situ (DCIS) patients report poor healthcare experiences. Research shows that patient-centred care (PCC) improves healthcare experiences and outcomes. This study explored how to support PCC for DCIS. Methods: Purposive sampling was used to recruit clinicians and DCIS patients. Clinicians were interviewed by telephone and patients by focus groups. Data was collected via qualitative methods. Data was analyzed and described using a 6-domain PCC framework. Findings from clinician and patients were analyzed independently then compared to determine whether PCC was addressed. Results: Forty-six clinicians from six provinces were interviewed. Clinicians reported variability across all 6 PCC domains including how they described DCIS and whether they engaged patients in decision making. Thirty-five women from five provinces reported variable understanding and experiences of communication with clinicians. Overall, all PCC domains were not adequately addressed. Conclusions: Experiences of women with DCIS could be improved by employing developments that support PCC.
Teachers' Beliefs About Gender Differences in Single-Sex Classrooms
Keywords: Biological or Sex-Based Differences
Gender
Gender Inclusive
Learning Differences
Professional Development
Sex

Some argue that girls’ and boys’ education should be based on biological differences between learners, while other studies argue that sex-based instruction problematically dismisses or ignores issues of gender. Using a qualitative design, this study addresses two main research questions concerning teachers’ beliefs about the salience of gender in their single-sex classrooms, and how teachers’ beliefs about gender shape their pedagogy. The 6 participating teachers were selected randomly from private, single-sex schools in the Greater Toronto Area. The results show teachers did not take a firm stance on “gender exploitive” (i.e., working with dominant gender constructions and stereotypes) or “gender transformative” (i.e., working against and to challenge dominant gender constructions and stereotypes) pedagogies and shared experiences that both reinforced and challenged gender norms. Conclusions drawn support the need for further professional development to build teacher capacity to effectively respond and address gender and gender issues in their classrooms.
Comparing Hospital Performance with Competing Risk Quality Indicators through Inverse Probability Weighting and the Fine and Gray Model
Keywords: competing risks
direct standardization
Fine and Gray model
inverse probability weighting
quality-of-care comparisons

Quality-of-care comparisons have been a growing interest for government and healthcare stakeholders to identify specific areas of improvement among healthcare institutions. Causal inference methods can be adapted to obtain fairer comparisons between institutions and provide better evidence of quality-of-care. Two methods that can be used to adjust for differences in patient case-mix between providers are direct standardization using an outcome regression model and inverse probability weighting via the propensity score. Assuming the models are correctly specified, both generate unbiased estimators of expected quality-of-care outcomes. For competing risk time-to-event outcomes, the semiparametric Fine-and-Gray model can be used, while the nonparametric cumulative incidence estimator can be modified to accommodate inverse probability weights. We formulate potential cumulative incidence estimators based on these two methods and assess their performance through simulation studies. Furthermore, we apply both methods to rank and identify outliers for Ontario hospitals by their 5-year second cancer cumulative incidence.
Designing a wearable sensor system to monitor the internal mechanism of a stance phase control passive prosthetic knee
Keywords: amputee
biomechanics
design
gait
knee joint
prosthesis

Prosthetic knees aim to improve mobility for above-knee amputees, but studies that quantify the performance of prosthetic knee controllers are limited. Further, most studies about the performance of prosthetic knees are often limited to a controlled environment, so information from gait studies that inform design decisions may be misleading. Therefore, the objective of this project was to further develop a wearable gait analysis tool that quantitatively measures performance of a prosthetic knee. The idea of collecting empirical data and inputting it into a computational model for design improvements was motivated through a literature review. Moreover, a fully wearable gait analysis tool and 4 finite output states were developed. Both were validated through collection of data from walking trials with able-bodied participants. The further development of this tool has shown the potential for a wearable gait analysis tool that can be used in a variety of environmental conditions, to inform design decisions.
Association Between Inflammatory Markers and Neurocognitive Flexibility Among Adolescents with and without Bipolar Disorder
Keywords: Bipolar Disorder
Cognition
Inflammation
Neurocognition
Youth

Imbalances between pro-to anti-inflammatory markers have been implicated in the pathogenesis of bipolar disorder (BD). In adults with BD, inflammatory markers are negatively associated with neurocognitive functioning. This relationship has not been investigated in BD adolescents. Serum levels of five inflammatory markers [interleukin (IL)-1B, IL-6, IL-10, C-reactive protein (CRP) and tumor necrosis factor (TNF)] were examined in 63 adolescents with BD (31 symptomatic, 32 euthymic) and 60 healthy controls (HC). Neurocognitive flexibility was assessed via the CANTAB intra/extradimensional shift (IED) task. In symptomatic BD adolescents, but not asymptomatic BD or HC, lower IL-6/IL-10 ratio was significantly associated with poorer performance on the IED task. These results suggest that balanced pro- to anti-inflammatory ratios are associated with better neurocognitive flexibility in symptomatic BD adolescents. Neuroimaging studies are warranted to examine the neurophysiologic processes that underlie these findings.
Using 16 versus 256 channels to map microbubble activity in a brain-therapeutic ultrasound application: an in-system comparison of two digitizers
Keywords: acoustic imaging
clinical engineering
focused ultrasound
signal processing

Information provided by the nonlinear re-radiation of acoustic energy from a microbubble population can be used to calibrate treatment pressures in brain-therapeutic ultrasound applications. In this thesis, the in-system performance of the AlazarTech ATS9416 16 channel digitizer is compared against two 128-channel Ultrasonix SonixDAQ digitizers using the time exposure acoustics (TEA) algorithm to map bubble activity. Using the ATS9416, real-time ultrasonic source and bubble reconstruction was achieved using a CPU implementation of TEA, though the lowered channel count decreased the sensitivity to subharmonic microbubble activity. An in-system signal-to-noise ratio (SNR) comparison between the digitizers found that amplifier gain had the strongest impact on SNR rather than any difference between the digitizers themselves; a more direct comparison may only be possible with the addition of hardware anti-aliasing filters and amplifiers to the ATS9416.
Nursing, Power, and Gender in Interprofessional Collaboration
Keywords: gender
hierarchy
Interprofessional collaboration
medicine
nursing
occupational closure

This research explores how power and gender are used to construct professional hierarchies between nurses and physicians and therefore influence interprofessional collaboration. Through directed content analysis and constant comparison analysis, I analysed top-cited articles about interprofessional collaboration involving nurses and physicians and contextualized the relationship between gender and professional hierarchies with Witz’s occupational closure theory. In my first theme, The invisibility of gender, most authors considered gender incidentally or not at all. In my second theme, Interprofessional hierarchies in nursing work are reinforced by gendered strategies, nurses jockeyed for power by ‘playing the game’, a usurpationary strategy. Physicians used exclusionary and demarcationary strategies, as interprofessional collaboration represented a threat to their hegemonic control over health care. Despite the enduring presence of gendered strategies, gender gradually slid from analytic view. Gender is not recognized in most research as an avenue of potential hegemony that impinges on effective interprofessional collaboration.
Conversations with Young Two-Spirit, Trans and Queer Indigenous People About the Term Two-Spirit
Keywords: Indigenous
queer
trans
two-spirit
youth

Since the coining of the term in 1990, two-spirit has been used with increasing frequency in reference to Indigenous LGBTQ people; however, there is rarely explicit discussion of to whom the term two-spirit refers. The word is often simultaneously used as both an umbrella term for all Indigenous people with complex genders or sexualities, and with the specific, literal understanding that two-spirit means someone who has two spirits. This thesis discusses findings from a series of qualitative interviews with young trans, queer and two-spirit Indigenous people living in Toronto. Exploring the ways in which participants understand the term two-spirit to be a meaningful and complex signifier for a range of ways of being in the world, this paper does not seek to define the term two-spirit; rather, following the direction of research participants, the thesis instead seeks to trouble the idea that articulating a definition of two-spirit is a worthwhile undertaking.
Leveraging Smart Card Intelligence to Improve Transit Planning: A Case Study of PRESTO in the Greater Toronto and Hamilton Region
Keywords: geographic information systems
key performance indicators
planning
PRESTO
smart cards
transit

While smart cards are primarily designed to automate fare collection, the transaction records contain rich intelligence. This thesis demonstrates the capabilities of smart card analytics in the Greater Toronto and Hamilton Area (GTHA), using data from the PRESTO smart card system. The case studies involve Hamilton Street Railway (HSR), GO Transit (GO), Burlington Transit, and the Toronto Transit Commission (TTC). Methods are demonstrated for: geocoding PRESTO transactions, reconstructing trips, visualizing passenger flows, spatial clustering of passenger groups, computing route level transfer volume matrices, and quantifying transfer delays. The results underscore PRESTO’s superior capability in providing longitudinal transit demand profiles, which can be leveraged to develop enhanced Key Performance Indicators (KPIs) that measure the transit travel experience from the lens of passengers. As PRESTO cards will become ubiquitous in the GTHA, this study addresses the pressing need to demonstrate the value of PRESTO analysis to improve the practice of transit planning.
Targeting Antioxidant Systems to Treat Pancreatic Cancer
Keywords: Antioxidants
Cancer Therapy
Glutathione
Pancreatic Cancer
Thioredoxin

Pancreatic cancer has the worst prognosis of all cancers. Pancreatic tumours are characterized by excessive oxidative stress that may provide a unique vulnerability to target in the development of new therapeutic strategies. I investigated a novel combination therapy targeting the two main intracellular antioxidant systems, glutathione and thioredoxin. Buthionine sulfoximine (BSO) targets glutathione synthesis and auranofin targets thioredoxin recycling. These drugs have been tested in human clinical trials and are strong candidates for repurposing in cancer therapy. I found that BSO potentiated auranofin’s cytotoxic effects in vitro. Furthermore, the combination augmented oxidative stress in cells. Auranofin engaged its target TrxR in vitro at concentrations causing cell death. I also assessed the biodistribution of auranofin in vivo and observed a preferential accumulation in the stroma 24 hours after treatment. Overall, I conclude that this treatment strategy can be effective against pancreatic cancer and deserves attention for future development.
Genomic Variants Associated with Pseudomonas aeruginosa Eradication Failure in Cystic Fibrosis
Keywords: cystic fibrosis
eradication failure
genome-wide association study
gwas
Pseudomonas aeruginosa
tobramycin

Due to the strong association between chronic Pseudomonas aeruginosa (PA) lung infection and morbidity/mortality in individuals with cystic fibrosis (CF), antibiotic eradication therapy (AET) is the standard treatment in patients with new-onset PA infections. However, for reasons that remain poorly understood, AET fails and PA is able to persist in up to 40% of individuals with new-onset PA infections. We sought to identify the genetic basis of PA persistence in new-onset infections through the application of genome-wide association approaches to a collection of PA isolates from pediatric CF patients with new-onset infections. We identified a hypothetical protein and 3 SNPs associated with AET failure. One SNP was in a bacteriophage integrase, and the other two were upstream of virulence-related proteins. These results suggest that regulation of PA virulence may play a role in AET failure and that PA persistence may be the result of multiple, independent pathways.
The Use of Endogenous and Synthetic Cannabinoids in Prostate Cancer Therapy
Keywords: anandamide
cannabinoid receptor
cannabinoids
cell cycle
prostate cancer
WIN 55
212-2

Cannabinoids are mainly used as an antiemetic and for cancer-related pain, however, studies have implicated an anti-proliferative role in various cancer models. This thesis examines the therapeutic potential of cannabinoids anandamide and WIN55,212-2 in prostate cancer. In vitro studies on prostate cancer cells showed that the cannabinoids significantly reduce proliferation, migration, invasion, and induce apoptosis in a dose-dependent manner. Inhibition of cannabinoid receptor 2 resulted in a reversal of the anti-proliferative effects. Cell cycle analysis revealed that WIN55,212-2 caused arrest in G1/2 phases, and mechanistic studies demonstrated that these effects were mediated through alterations in key cell cycle regulators. Based on these studies, the effect of WIN55,212-2 was assessed using a xenograft model, resulting in a reduction in tumor volume compared to control. Evidence from this thesis provides a framework for future studies and provides a more in-depth understanding of the potential benefit of cannabinoid use in prostate cancer.
The Role of Neutrophil Extracellular Traps in Lung Transplantation
Keywords: Large animal model
Lung transplantation
Neutrophil extracellular trap

Neutrophil extracellular traps (NETs) are a product of the innate immune response. This thesis hypothesized that NETs are produced in response to various forms of lung transplant-related injury, and that the concentration of NETs in the lung predicts lung function. NETs were measured in the lungs and in EVLP perfusate in various models of porcine lung transplant-related injury and ex vivo lung perfusion (EVLP), as well as in clinical EVLP and recipient bronchial wash samples. NETs were detected in porcine models of lung injury. NET concentration in porcine EVLP perfusate increased over time and varied according to lung injury. In clinical perfusate, NETs were significantly correlated with recipient days on the ventilator and length of stay in the ICU. This thesis demonstrates that NETs are present in lungs at various stages throughout the transplantation process, and that NETs in donor lungs could be used for predicting recipient outcomes.
CHARACTERIZING AQP9: A REGULATOR OF EPIPHYSEAL PLATE CHONDROCYTE PROLIFERATION, HYPERTROPHY, AND LONG BONE GROWTH
Keywords: aquaporin
bone
channelome
chondrocyte
endochondral ossification
epiphyseal plate

Aquaporin-9 (AQP9) is a membrane channel protein suspected to regulate growth in the epiphyseal plate. As long bone defects often possess limited non-surgical options, novel factors underlying bone growth must be continuously explored to advance effective treatments. I hypothesized that Aqp9 is an important epiphyseal plate chondrocyte channel regulating the process of endochondral ossification. In this study, Aqp9 -/- mouse long bones compared to wildtype mouse long bones showed a neonatal hindlimb-specific acceleration of growth followed by reduced length in the juvenile age. Analysis of Aqp9 -/- epiphyseal plates and chondrocytes showed an early disposition for proliferation and aversion from hypertrophy, suggesting that Aqp9 may function similarly to genes such as Col10a1 and Mmp13. This study provides insight into chondrocyte membrane channel proteins and their regulation of the growing epiphyseal plate, demonstrating that Aqp9 may be a novel therapeutic target for the non-invasive intervention of leg length discrepancies.
Resveratrol Effect on Oral Inflammatory Load in Chronic Periodontitis: A Pilot Study
Keywords: Periodontitis
Resveratrol

Chronic periodontitis is an inflammatory disease that diminishes tooth-supporting structures and is dependent on neutrophil recruitment and oxidative stress. An anti-oxidant, resveratrol (3, 4’, 5-trihydroxystilbene) blocks neutrophil recruitment and oxidative bursts. Thus, resveratrol can help lessen oral inflammatory load (OIL), thereby reducing clinical manifestations of periodontitis. It was hypothesized that OIL will be further reduced in periodontitis patients treated with SRP plus resveratrol, compared to SRP alone. A randomized triple-blind clinical trial was conducted. By measuring clinical parameters, oral neutrophil numbers, and neutrophil phenotypes, it was demonstrated that, while not statistically significant, resveratrol treatment further reduced OIL. Importantly, patients treated with resveratrol demonstrated earlier responses to treatment compared to those on placebo. This pilot study demonstrated the potential benefits of resveratrol, as an adjunctive treatment to SRP. Further research should be conducted with larger cohorts to examine the benefits of resveratrol in patients with periodontal diseases, particularly those with co-morbidities.
Evaluating the Glycogenic Activity and Therapeutic Capacity of PPP1R3D in a Mouse Model of Lafora Disease
Keywords: glycogen
glycogen targeting subunit
lafora bodies
Lafora disease
neurology
PPP1R3D

Lafora disease (LD) is an intractable, neurodegenerative epilepsy caused by loss-of-function mutations in the EPM2A or EPM2B genes. Central to LD is the accumulation of malstructured glycogen (Lafora bodies; LB) in neurons, a consequence of dysregulated glycogen synthesis. Glycogen synthase catalyzes glycogen formation and is activated by dephosphorylation. The latter is mediated by glycogen-targeting subunits of protein phosphatase 1, including PTG (R5) and R6, known formally as PPP1R3D, both abundantly expressed in brain. PTG knockout in LD mice rescues LD, including near-complete disappearance of LB and neurodegeneration. I examined whether the same could be achieved with R6 knockout. Despite significant brain glycogen and LB reductions in R6-deficient-Epm2a-/- mice, substantial amounts of LB remained and neurodegeneration was not rescued. This partial effect remains unexplained. Future experiments to resolve the difference with PTG will shed important light on both LB formation and Lafora disease, and brain glycogen metabolism.
A Reverse Genetics Approach to Examining Drosophila Social Interaction Networks (SINs)
Keywords: DIP‑B
Drosophila melanogaster
Group size
Olfactory sensilla
Social context
Social network

Social network analysis is a powerful tool for understanding the underlying mechanisms that regulate the evolution of sociality. The social behaviour of individuals manifests in non-random inter-individual social interactions, including cooperation in foraging, mating, and competition. These interactions comprise the social network of the population, affecting group-level processes such as information flow and disease transmission. Social network structure is quantifiable; therefore, understanding the reciprocal relationship between these processes and network structure could provide insight into the fitness consequences of various social behaviour strategies, and why they persist within the population. Most studies which utilize the network approach rely on observational data of animal populations. These studies are limited because researchers are unable to manipulate the genetic and social environment. Therefore, the objective of my thesis is to provide insight into how social interaction network (SIN) structure is affected by genetic mechanisms and social context using the model organism Drosophila melanogaster.