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Type d'Item : Item , Understanding the Consequences of Deficient Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1) Expression in Congenital Myasthenic Syndromes (CMS) and Elucidating New Therapeutic Strategies(Université d'Ottawa / University of Ottawa, 2026-08-04) Holland, Stephen Henry; Lochmüller, HannsCongenital myasthenic syndromes (CMS) are early onset, inheritable neuromuscular disorders caused by mutations in proteins required for neuromuscular junction (NMJ) development, maintenance, function, and motor endplate organization. Clinically, CMS are heterogeneous but typically manifest as fatigable weakness affecting facial, bulbar, ocular, respiratory, limb, and/or girdle muscles, with severity ranging from transient to permanent impairment depending on the underlying genetic defect. More than 40 genes have been implicated in CMS pathogenesis. Among these, glutamine–fructose 6 phosphate transaminase 1 (GFPT1) encodes the rate limiting enzyme of the hexosamine biosynthetic pathway (HBP). Biallelic GFPT1 mutations cause a limb girdle predominant CMS, yet the molecular basis of disease and effective treatments remain poorly understood. We hypothesized that GFPT1 deficiency generates a hypoglycosylated cellular environment that impairs neuromuscular function. Using integrated biochemical, proteomic, and functional analyses, we define the molecular consequences of GFPT1 deficiency. We demonstrate that GFPT1 CMS is a bona fide glycosylation disorder marked by impaired N linked glycosylation and altered protein O GlcNAcylation. Notably, we identify the first mis glycosylated peptide in GFPT1 CMS, located within the δ subunit of the acetylcholine receptor (AChR), providing direct evidence that reduced HBP flux disrupts glycoprotein maturation essential for NMJ transmission. Building on this mechanistic insight, we establish two metabolic strategies that restore glycosylation: galactose supplementation, which partially rescues muscle protein glycosylation, normalizes NMJ and skeletal muscle morphology, and improves behavioral outcomes; and AMDH2 knockdown, which increases O GlcNAcylation in GFPT1 deficient cellular models. Collectively, this work defines the first molecular signature of mis glycosylation in GFPT1 CMS, establishes two therapeutic strategies to restore glycan homeostasis, and identifies serglycin as a potential biomarker. These discoveries advance the mechanistic understanding of glycosylation dependent neuromuscular disease and lay the groundwork for targeted therapeutic development in GFPT1 CMS and related disorders.Type d'Item : Item , Structural Performance and Damage Evaluation of Corroded Infill Slabs from the Champlain Bridge After 60 years in Service(Université d'Ottawa / University of Ottawa, 2026-08-04) Tawil, Dana; Martín-Pérez, Beatriz; Noël, Martin; Sanchez, Leandro F. M.The rapid deterioration of aging civil infrastructure represents a critical challenge for global transportation networks. While extensive research has focused on the performance of reinforced and prestressed concrete (PC) members subjected to laboratory-accelerated corrosion, there remains a fundamental disconnect between these controlled simulations and the complex, long-term degradation observed in field-aged structures. This doctoral research bridges this gap through a comprehensive multi-scale forensic and structural evaluation of roadway infill slabs extracted from the former Champlain Bridge in Montreal, Canada, after 57 years of aggressive environmental exposure. The research program integrates high-resolution non-destructive testing (NDT), forensic material characterization of 975 individual prestressing wires, and destructive testing of 15 full-scale slab panels under realistic boundary conditions. Material-scale analysis identifies a robust ductility transition threshold at approximately 3% mass loss, beyond which the ultimate strain capacity of parallel-wire tendons significantly deteriorates, independent of gauge length or prior loading history. At the structural scale, the research reveals a fundamental divergence in performance that is independent of average material degradation. Experimental results demonstrate a significant "capacity spread" at low corrosion levels. Specifically, specimens with nearly identical average mass-loss values exhibited ultimate load capacities varying by over 140% (160.1 kN to 384.3 kN). This disparity is identified as a consequence of localized interface conditions rather than distributed section loss. The forensic investigation confirms that grout integrity is a governing factor influencing the ultimate limit state. While solid grout coverage ensures ductile flexural behavior, crumbled or powdery grout leads to a more variable structural response. Such deterioration can trigger a premature transition to brittle shear failure. However, it can also facilitate bond-slip mechanisms that redistribute stresses and activate arching action. As demonstrated in the numerical investigation, this shift in the load-carrying mechanism can result in higher ultimate load capacities. The experimental findings are further validated through nonlinear finite element (FE) modelling, which successfully isolates the "ductility gap" caused by bond-slip mechanisms. The results prove that simplified evaluation metrics relying on average section loss, which is the current industry standard for large-scale bridge inventories, can lead to unconservative safety estimates. This thesis contributes a performance-based framework for the assessment of aging PC infrastructure, advocating for the prioritization of grout integrity and localized bond-penalty factors in national design codes. By integrating the assessment of volumetric steel loss with the governing physics of the tendon-concrete interface, this work provides bridge owners with a data-driven methodology to ensure the continued safety and reliability of aging transportation networks.Type d'Item : Item , Threading Through School Exclusion: Sense of School Belonging and Absenteeism of Children with Autism Spectrum Disorder(Université d'Ottawa / University of Ottawa, 2026-08-04) Ozturk, Mina; Whitley, JessicaSchool belonging is increasingly recognized as a key component of students' academic, social, and emotional wellbeing. While previous research has documented elevated rates of absenteeism and exclusion among Autistic students, less is known about how these experiences relate to students' sense of belonging to school, particularly from caregiver perspectives. The purpose of this mixed-methods study was to address the gap in the literature regarding school exclusion of Autistic students by exploring the relationships between school belonging, absenteeism, family- and school-related factors. Data were drawn from an Ontario-wide survey exploring the experiences of K-12 Autistic students during the 2022-2023 academic year, in which 232 parents/caregivers reported on school belonging, attendance patterns, and exclusion. Findings were integrated using a weaving approach to provide a more comprehensive understanding of participants' school experiences. Quantitative analyses included correlational and linear regression analyses, while qualitative open-ended responses from 129 caregivers were interpreted using content analysis. Significant relationships emerged between school belonging, absenteeism, and class placement, with lower rates of school absence and more inclusive educational placements being associated with greater school belonging among Autistic students. Qualitative findings highlighted themes related to insufficient staffing, inadequate supports and accommodations, systemic barriers, school-based practices limiting attendance, social exclusion, inconsistent school-home communication, and the broader impacts of school experiences on families. Findings underscore the importance of inclusive education and appropriate supports in school environments to strengthen school belonging among Autistic students.Type d'Item : Item , Changes in food literacy following a one-week experiential culinary education intervention in school-age children(2026-05-29) Jeha, Karissa; Vincent, Coralie; Giroux, IsabelleAbstract Background Food literacy is a multidimensional construct encompassing the knowledge, skills, and attitudes needed to make informed food choices and support healthy eating. Food literacy education is important for fostering lifelong positive eating behaviours. However, evidence on intensive experiential, culinary education interventions for school-aged children remains limited. The objective of this study was to assess changes in food literacy skills following a one-week experiential culinary education intervention among school-aged children attending a university-based culinary summer camp. Methods A theory-informed, child-centered culinary intervention was developed using a competency-based framework to support structured skill development. A single-arm, baseline-to-endpoint study design was used to evaluate change in food literacy skills among children aged 8–12 attending a one-week culinary summer camp. Food literacy skills were assessed using an observational scoring rubric informed by a competency framework and the Experiential Learning Theory, measuring six domains: autonomy, ease and safety, measuring, hygiene, working with others, and confidence. Each domain was scored on a 12-point scale, with higher scores indicating greater skill proficiency. Paired-samples t-tests were conducted to evaluate changes. Effect sizes (Cohen’s dz) and 95% confidence intervals were calculated. Results Eighty-eight children participated in the culinary intervention. Significant improvements were observed across all six food literacy domains following the intervention (p< .001). Mean score increases ranged from 1.46 to 2.47 points, with effect sizes ranging from moderate to large (dz = 0.62–1.36), indicating meaningful improvements in observed food literacy skills over the one-week period. Improvements were particularly notable for the ease and safety, measuring, and confidence domains. Conclusions This intensive experiential culinary education intervention was associated with significant improvements in food literacy skills among school-aged children. These findings support the potential of immersive, skills-based food literacy programs and highlight the value of experiential learning approaches for supporting children’s food literacy development.Type d'Item : Item , Cardiac function in zebrafish embryos is linked to an androgen receptor-adrenomedullin-proepicardium axis(2026-07-30) Duong Phu, Max; Guerrero Samanidis, Alessandra; Laibacher, Sabrina; Burczyk, Martina; Alkhars, Yara; Janovic, Ana; Al Madhoun, Ashraf; Skerjanc, Ilona S.; Burkhalter, Martin D.; Philipp, MelanieAbstract Background Congenital heart defects (CHDs) comprise the most common congenital malformation affecting nearly 1% of all newborns. In individuals with sex chromosome aneuploidy syndromes, however, the prevalence reaches up to 50% of all livebirths. One commonality to these syndromes is a marked reduction in sex hormones, particularly androgens. Androgen receptor (Ar) insufficiency represents a culprit in the pathophysiology of adult onset cardiovascular disease and arrhythmia, but there are no reports regarding Ar function during heart development. This is surprising as androgens along with its nuclear receptor exist already during early development, even before gonads develop and become functional. Methods We evaluated the role of the Ar during vertebrate heart development by generating loss-of function in zebrafish embryos via pharmacological inhibition, transient CRISPR/Cas9 treatment, or interference of splicing as well as murine cell culture. Results Attenuation of Ar function in zebrafish embryos prevents normal cardiac morphology and physiology as apparent by edema, bradycardia and arrhythmia. Molecularly, we identified increased abundance of adrenomedullin (Adm) 2a as a likely cause for the observed defects. Cellularly, these phenomena may be linked to impaired formation of proepicardial cells, which are reported to intermingle with cells of the conduction system and influence cardiac pacing. Conclusions A disrupted Ar – Adm2 axis possibly contributes to the increased frequency of CHD in individuals suffering from sex chromosome aneuploidy syndrome.