30921 research outputs found
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Health-related quality of life in hereditary angioedema patients treated with subcutaneous C1 inhibitor (C1-INH) therapy in Canada
Full text linkBackground: Hereditary angioedema (HAE) therapies have demonstrated improvements in clinical symptoms and health-related quality of life (HR-QoL) in patients with HAE. Specific causes for improvement in HR-QoL have not been sufficiently explored in Canada.
Objective: To understand patient perspectives on the burden of HAE and their experiences taking subcutaneous plasma-derived C1 inhibitor concentrate (SC-pdC1INH), and to investigate changes in HR-QoL domains which include physical, mental, emotional, functional, social, and medical well-being.
Methods: A qualitative research design was employed using telephone interviews from May to July 2023 and a quantitative self-administered Angioedema QoL questionnaire (AE-QoL), which has a recall period of 4 weeks. A conceptual map was generated from the interviews that illustrated HR-QoL domains most important to patients.
Results: This study included 20 patients (50% female; mean age of 51 years; 85% HAE Type 1/2). Patients reported more controlled HAE since starting SC-pdC1INH, with fewer attacks (85%) and even no/nearly no attacks (60%) in the past year. Patients reported emotional benefits (reduced stress/anxiety regarding potential attacks [75%], and increased confidence in managing HAE [95%]). Positive impacts also included increased productivity/less missed days from work/school (40%) and improved physical ability/well-being (50%). The total mean AE-QoL Score was 34 (range 0–87; SD 24.9), indicating a small effect of HAE on HR-QoL in the 4-week pre-interview period.
Conclusion: Overall, patients on long-term prophylaxis with SC-pdC1INH reported improvements in many HR-QoL domains, but most significantly relief of stress and anxiety associated with HAE, and improvement in social and physical well-being
Locating tip-of-the-tongue in lexical retrieval
Full text linkTip-of-the-tongue states (TOTs) commonly occur when a word cannot be retrieved, despite the conviction that it is known and will emerge imminently. Past research has probed access to target information during TOTs, but these tasks typically use definitions, common knowledge questions, or pictures to cue recall. This mimics naturalistic language use, but this semantic input creates challenges for observing the retrieval of semantic information. In Experiment 1a (N = 85), participants studied a list of uncommon words before completing a cued-recall task using vague clues to elicit TOTs thus limiting semantic input. When recall failed, participants rated their mental state before attempting to pick a semantic associate in a 4AFC task. In Experiment 1b (N = 88) recall was cued by presenting one item from studied word pairs, providing no direct information about the targets. The proportion of associate choice was significantly higher after reporting TOTs compared to forgetting in Experiment 1a but not 1b. The latter design was replicated in Experiments 2 (N = 90) and 3 (N = 86) using phonological and orthographic associate words, respectively. Finally, Experiment 4 (N = 86) included a semantic, phonological, and orthographic associate in the 4AFC task to place all three modalities in mutual competition. The results showed that TOTs benefited only phonology in isolation, but orthography was preferred when more lexical information was accessible. The experimental data provided a basis to evaluate a computational model of lexical retrieval, with the aim of simulating the observed recall and TOT phenomena. The model’s lexicon included vector representations for the semantic, phonological, and orthographic relationships between 52,176 English words. Lexical retrieval required an initial semantic step which acted as a gate to the phonological and orthographic features of the word. Simulations of the empirical results using the same experimental stimuli showed promise, but the model struggled to capture the recall and 4AFC outcomes with a single set of parameters. Adaptations are proposed to better capture the progress of TOTs over time and the shift in attention from semantics towards phonology and orthography as retrieval unfolds.February 202
Evaluation of the Canadian CRA tool in caries-free children <6yrs
Full text linkIntroduction: The Canadian Caries Risk Assessment (CRA) Tool is a six-item screening tool used to identify risk level for future caries development in children <6 years. The purpose of this study was to determine whether baseline CRA tool scores in caries-free children <6 years of age can predict future
caries development.
Methods: Baseline and follow-up CRA tool scores were obtained as part of routine care from preschool children attending three publicly funded dental clinics in Winnipeg. Data for this study were restricted to children who were caries-free at baseline. Charts of children who had returned for follow-up one year later were then reviewed to determine the proportion developing caries, as evidenced by new carious lesions (including white spot lesions). Statistical analyses included descriptive statistics along with bivariate analyses. A p value ≤ 0.05 was significant.
Results: A total of 145 children were caries-free at baseline, of which, 96 returned and had completed follow-up data. The mean total CRA score significantly increased from baseline to follow-up (1.9 ± 1.0 vs. 2.4 ± 1.9, p = 0.005). While not statistically significant, not brushing teeth twice daily (OR = 1.89, 95% CI = 0.72-4.90, p = 0.19) and low family income (OR = 1.73, 95% CI = 0.65-4.57, p = 0.27) were the strongest indicators of caries development by follow-up. The CRA tool was found to have a sensitivity and specificity for baseline CRA rating and the development of new caries at follow-up of 30.4% and
75.3%, respectively, indicating a low sensitivity but high specificity.
Conclusions: The CRA tool has a high potential of identifying low risk children who truly do not develop future caries. This research emphasizes the use of CRA tools in preventive pediatric dentistry to improve children’s oral health and maintain a caries-free state
Indigenous-led housing and education systems transformation: a case study of the Wikiwin – University education partnership with York Factory First Nation
Full text linkHousing and education disparities exist between Canadians and First Nation reserve communities. These inequities may explain the worse health and education outcomes for First Nation people living on reserves. This study investigates whether community-led post-secondary education improves the holistic well-being of the student interns engaged in the Wikiwin program of the York Factory First Nation (YFFN)-University of Manitoba education partnership. A longitudinal survey was conducted between 2023 and 2025 for all 20 Wikiwin students. This longitudinal survey had an 85% return rate (n=17) among the 20 Indigenous students in the Wikiwin (means "home" in Ininew) program. I analyzed a paired t-test of the pre-survey and the post-survey (n=17). Wikiwin students had statistically significantly (p < 0.05) higher satisfaction with most human, financial and social assets, but not their physical assets, after a year or more in the program.
The Wikiwin program made a difference at the individual and community levels, with the Wikiwin partnership bringing an $8.4 million grant to YFFN. This grant built, with local labour, four different housing prototypes, a student dormitory, and a trades training centre, towards creating a local housing and education ecosystem. Wikiwin students benefited from this earn-as-you-learn program, taking in-person and distance university courses in their YFFN community of York Landing and homebuilding internships. The Wikiwin post-secondary education program built local housing and youth capacity in pursuit of the YFFN goal of “bringing education home.”February 202
What is and what could be: listening to student perspectives to reconceptualize care in correctional education
Full text linkThis research reconceptualizes care in correctional education. Based on experiences and ideas shared by formerly incarcerated students, the research defines a more detailed concept of care than what existing literature provides. Based on what men shared, relationships are the foundation of caring teaching experiences, which includes an awareness of students’ past and current experiences, understanding their learning needs, providing persistent encouragement, and expanding their learning experiences beyond academics into personal exploration and growth. The research uses conceptual frameworks guided by anticolonial theories, Indigenous philosophies of learning, and the relationship between control and care. While traditionally, dominant attitudes in corrections view relationships with incarcerated people as dangerous liabilities, this research suggests actively building relationships with students is fundamental for educational growth. Ultimately, the research concludes that care in correctional education requires a comprehensive view and requires the teacher to find the relational midpoint where they can offer caring support while providing structure for students and maintaining professional boundaries.February 202
Designing an on-campus student housing as a support for cultural adaptation
Full text linkThis practicum looks at how on-campus housing can better support the cultural adaptation of
international students, especially as Canadian universities continue to welcome a growing and
diverse student population. University College Residence at the University of Manitoba, built in
1964, serves as the focus of this study.
Using a combination of literature review, precedent studies, site analysis, and programming, the
practicum explores how the design of shared spaces and private living areas can influence students’
sense of belonging and well-being. The research shows that small design decisions, like the
placement of social spaces, the flexibility of room layouts, or the availability of culturally
responsive amenities, can significantly affect the student experience and ease the adaptation
process.
The final proposal brings these insights together in a retrofit design of University College
Residence. The goal is to create an environment that feels welcoming, inclusive, and supportive
of different cultural lifestyles, while still encouraging meaningful interactions between students.
By rethinking how shared and private spaces work together, this practicum shows how interior
design can contribute to a more student-centred and culturally responsive housing model on
campus.February 202
Investigating genetic and epigenetic vulnerabilities in the retinoic acid signaling network including those found in rare neurodevelopmental disorders sharing comorbidities with fetal alcohol spectrum disorder
No full textFetal Alcohol Spectrum Disorder (FASD) is one of the most common neurodevelopmental disorders (NDD) worldwide. Retinoic acid (RA), the active signaling metabolite of vitamin A (retinol), guides embryogenesis by mediating gene expression. Prenatal alcohol exposure (PAE) inhibits RA synthesis at early development resulting in RA deficiency. In a focused review of disorders that share comorbidities with FASD, we noted many are rare genetic NDDs and congenital disorders of glycosylation (CDG) that share phenotypic and molecular features with FASD, suggesting they may be novel targets of EtOH teratogenesis. Consistent with many other PAE targets, we noted many rare NDD and CDG genes are also RA-regulated. We hypothesized genetic and epigenetic changes that alter the function of the RA and EtOH metabolism or downstream RA-dependent developmental signaling networks would increase the risk of the development of FASD. In line with our hypothesis, we found 65 new potential PAE risk and resilience alleles within these pathways in a human FASD cohort. Notably, RA/EtOH metabolic and rare NDD signaling pathways both harbored 15 PAE risk variants, making them the most heavily impacted targets. In line with these findings, using EtOH exposed and RA deficient Xenopus laevis embryos, 95% of the dysregulated genes perturbed by RA deficiency were perturbed also dysregulated following in EtOH exposed embryos, and comprised 41% of the overall EtOH disrupted genes. Early/mid gastrulation is the most developmental stage vulnerable to EtOH-induced RA-deficiency, harboring a significant number of genes showing transcriptomic dysregulation. Interestingly, while transcriptomic dysregulation normalized by late gastrulation, many EtOH-induced epigenetic changes did not correct and accumulated during development. The causative genes of rare NDD and CDG were also dysregulated following PAE-induced RA deficiency. Together, this work shows EtOH-induced RA-deficiency is a major mechanism of PAE and highlights new molecular targets underlying FASD outcomes, including the novel roles of NDD and CDG genes and pathways in PAE. We hope that the PAE targets identified in this work will facilitate earlier FASD diagnosis and access to care that are known to prevent secondary disabilities associated with FASD that can change the life course for children with FASD.February 202
Clonal evolution distances: biologically motivated distances for comparing cancer clonal trees
Full text linkCancer evolution is driven by the accumulation of mutations in tumor cells, creating ge- netically diverse subclones. Clonal trees are useful for representing this evolutionary history, but existing distance methods often assume unique labels and no mutation loss—assumptions that rarely hold in real data from modern sequencing technologies.
In this thesis, we present the Clonal Evolution Distance (CED), a biologically motivated metric for comparing clonal trees that supports multi-labeled nodes, repeated mutations, and mutation loss, while following the principle that once a mutation is lost, it cannot be regained. CED is defined as the minimum total weight of deletion, rearrangement, and insertion operations required to transform one tree into another, where weights reflect the number of nodes affected. We show that computing exact CED is NP-hard.
To reduce complexity, we propose a semi-metric, that uses biologically informed path pairing and tie-breaking. Possible applications include comparing trees from different methods, datasets, or time points, and evaluating robustness with partial sequencing data.February 202
Examining <i>Escherichia coli</i> outer membrane vesicles for their antimicrobial properties, cell fusion, and applications as antimicrobial resistance cargo delivery vehicles
No full textOuter membrane vesicles (OMVs) are naturally formed secretions of portions of Gram-negative bacterial membranes that play a role in antimicrobial resistance (AMR) and many other cellular activities, and also have potential as biotechnological drug delivery tools. To fully realize OMVs as drug delivery tools, this thesis examined three related projects, each focused on different aspects of OMV formation, roles in AMR, OMV fusion (using enhanced green fluorescent protein; eGFP), and AMR cargo delivery in E. coli K-12 BW25113 (WT).
In Chapter 3, two different OMV isolation ultradiafiltration methods were compared: stirred cell (SC) and tangential flow filtration (TFF), using E. coli WT and its hypervesiculating mutant ΔtolA to determine which technique was most efficient for producing the highest OMV yields. These results showed that the TFF produced 3-fold faster isolation rates of ΔtolA-OMVs and a 1-log10 fold increase in WT-OMV yields compared to SC.
In Chapter 4, OMVs from a colistin (COL) adapted E. coli isolate (COLR) were studied to determine if the antimicrobial properties of COLR-OMVs, when supplemented to live E. coli WT, were due to COL drug carryover in the vesicles. COLR-OMVs without added COL during growth had no antimicrobial activity when supplemented to WT cells, suggesting COL carryover was the cause; both COLR-OMVs ± COL had unique morphologies.
In Chapter 5, Aim 1, OMVs were isolated from WT and ΔtolA transformants expressing Tat secretion signal His6-tagged SiriusGFP (an enhanced green fluorescent protein; eGFP) to determine OMV-cell fluorescent transfer to non-fluorescent WT cells. Here, we show that ΔtolA Tat-His6-SiriusGFP-OMV transfer to E. coli WT cells occurs quickly (tolA transformants as a ß-lactamase-inhibiting cargo in OMVs. Unfortunately, BLIP transfer to OMVs was undetectable, and further studies are needed to improve BLIP secretion and expression.
Overall, the results from this study showed that not all OMV isolation techniques are created equal, COL adaptation/addition has ramifications on OMV morphology and antimicrobial characteristics, and finally, eGFP cargo-to-cell fusion experiments occur quickly in E. coli.February 202
Mathematical and statistical modelling during a pandemic event
Full text linkThis thesis addresses challenges in epidemiological research through innovative methodological approaches across multiple domains.
It begins by presenting a novel approach to conducting a comprehensive literature review on COVID-19 epidemiological modelling. Given the vast volume of research, traditional manual methods proved insufficient. To address this, we employed a data-driven methodology using natural language processing (NLP) techniques to systematically analyze and synthesize key findings in the field.
One focus is on COVID-19 transmission in Alberta, where the transition from time-dependent to constant parameters improved the clarity of intervention scenario analyses. Findings highlight the critical role of social distancing and strategic testing in controlling disease spread, offering practical insights for public health decision-making.
Another key focus is infectious disease variant interactions, introducing the concept of "practical coexistence'' to examine how initial infection levels and reproduction numbers influence variant dynamics. The analysis of Alpha and Gamma variants in Alberta and British Columbia reveals the impacts of containment strategies on variant spread.
Additionally, the thesis develops a Python package for temporal network analysis, applying innovative techniques to transportation networks. By examining air travel and urban bike-sharing systems, the research illuminates complex network adaptability and resilience which has implications for pandemic preparedness.
Ultimately, the work emphasizes the critical role of interdisciplinary collaboration, modelling flexibility, and comprehensive intervention strategies in addressing future public health challenges.February 202