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The Role of Mitochondrial Dynamics in Muscle Stem Cell Quiescence and Cell Cycle Re-Entry
No full textBalanced stem cell fate decisions are essential for the maintenance and regeneration of tissues across the lifespan. The mitochondrial fusion protein OPA1 and mitochondrial shape changes are essential contributors to balanced fate decisions, however the full mechanistic scope of their signalling abilities are not fully known. Here, using OPA1-deficient and OPA1-overexpressing muscle stem cells (MuSCs), we show that mitochondrial shape changes alter the metabolome of MuSCs. These OPA1-regulated metabolites possess distinct abilities to alter MuSC progression and fate. Furthermore, OPA1 expression and mitochondrial shape alters the ratio of alpha-ketoglutarate (aKG) to succinate, and this ratio dictates the decisions to self-renew or commit. Manipulation of this ratio in vitro is sufficient to alter the fate of MuSCs by modifying mitochondrial shape and altering the expression of key stemness and myogenic genes. In addition, we find that committed and self-renewed MuSCs have opposing gene expression profiles indicative of differential [aKG]:[succinate] ratios. Lastly, in OPA1-deficient mice, in vivo restoration of this ratio prevents MuSC depletion and preserves the stem cell pool after injury and decreases precocious commitment and differentiation. Our studies present a novel role for mitochondrial shape as a signalling mechanism to guide MuSC progression and fate
Piano Performance and Identification of Melodic Contour and Pitch of Prelingually Deaf Children with Cochlear Implants After Three Months of Formal Music Instruction
No full textSignificant developments in cochlear implant design have been made in the past two decades, with clearer speech and music perception serving as the main research foci (Advanced Bionics, 2009). However, poor spectral resolution produces an inadequate representation of the pitch information crucial for music appreciation (Chen, 2012; Galvin, Fu, & Shannon, 2009; Jung et al., 2012). Several studies suggest that daily exposure and practice are positively correlated factors for the effective music instruction of pediatric cochlear implant recipients (children CI users), enhancing their ability to recognize, enjoy, and reproduce music (Comeau, Koravand, & Markovic, 2017; Lo, Looi, Thompson et al., 2020). However, no studies have yet focused on teaching music outcomes and then assessing those taught skills to children CI users. Amid the plethora of research on music therapy for children CI users, no individual formal teaching methods have yet been proposed to investigate the outcomes of teaching classical music on piano. This thesis main goal was a comparative study of children CI users and NH children's piano performances, identification of melody, rhythm, and pitch discrimination after three months of individual formal piano training using a multi-sensory (auditory, visual, and tactile) approach and a customized aural modeling (no notation reading) teaching method with familiar songs. This study included 10 children CI users and 10 NH children aged 4 to 9 with no prior formal music training. The results indicate that in familiar song recognition tests, and MBEMA melody and rhythm tests, children CI users improved on their accuracy after the three months of piano lessons. Also, children CI users have reported enjoyment in practice and music listening overall
Applying an implementation science lens to understand physician-level variation in patient length of stay in internal medicine
No full textAbstract Background & objectives Length of Stay (LoS) is a critical quality metric and focus of improvement efforts in healthcare. Successfully managing LoS depends on understanding the drivers of variation amenable to change. This study aims to (1) characterize physician-level variation in LoS; (2) identify physician actions associated with LoS; and (3) explore the individual-, team-, and hospital-level factors influencing this variation to generate hypotheses for further study. Methods This mixed-methods comparative case study approach examined six General Internal Medicine (GIM) departments in Toronto, Ontario. Physician-level variation in LoS was calculated using a random-intercept negative binomial regression model and sensitivity analysis. Semi-structured interviews and ethnographic observations were conducted and analyzed using the AACTT Framework (Action-Actor-Context-Target-Time), the Consolidated Framework for Implementation Research (CFIR), and the Theoretical Domains Frameworks (TDF). Hospitals with the lowest and highest physician-level variation in LoS were compared. Results Physician-level variation in LoS ranged from 1.7 to 7.0%, which—though modest numerically—represents meaningful differences in physician decision-making not explained by patient complexity, and no significant hospital-level effect was observed. Qualitative analysis from 12 observations and 67 interviews (32 GIM physicians and residents, 35 nurses and other health professionals) identified eight discrete physician actions influencing LoS, along with five individual-level factors and five team- and hospital-level factors. The nature of these factors was different when comparing hospitals with the lowest and highest variation. Organizational culture and perceptions of the patient population shaped physician perceptions of their professional role, while GIM departmental culture, structural characteristics, and communication networks informed physician beliefs about team capabilities and consequences of action (or inaction). Conclusion This study highlights the complex interplay between physician actions and factors influencing physician-level variation in LoS. Interventions that target physicians but do not attend to team and hospital factors are likely insufficient to achieve sustained improvements in LoS. Aligning individual-level feedback and environmental restructuring with organizational values and needs of the patient population may offer a more promising approach to sustained improvement
Violence, politique et société : Étude sociologique de la violence armée en Haïti
No full textCette thèse de maîtrise porte sur la violence des gangs en Haïti. À travers des jeunes appartenant aux gangs, l'étude propose de comprendre la violence armée dans le contexte haïtien actuel, telle que vécue et pensée par les acteurs eux-mêmes. En partant des concepts de « mépris » et de « désolation », la recherche montre que les gangs s'apparentent à une « communauté de souffrants » dont les membres partagent les mêmes expériences de désespoir. Ainsi, l'étude révèle que les groupes armés illégaux sont davantage envisagés par les jeunes marginalisés du pays comme un moyen leur permettant d'accéder à une condition sociale valorisante, et à la capacité de construire leur vie, au-delà des contraintes. Néanmoins, si ces groupes forment une telle communauté, ils ne s'organisent pas autour d'un projet commun visant à modifier l'état des choses. L'analyse suggère donc, faute de mieux, de voir dans la violence armée une forme de « lutte des places ». Outre cela, ce travail interroge également les mécanismes de pouvoir dans les territoires contrôlés par les groupes armés illégaux. Les résultats soutiennent que ces groupes font régner une sorte d'« ordre normatif » de substitution à celui de l'État, et exercent une domination totale établie par la violence dans les quartiers contrôlés. Par cette domination, le chef de gang s'érige en tant que souverain, et acquiert un droit de vie et de mort sur ses soldats et la population locale
Corporate Social Advocacy Within Sport Organizations: The Case Study of the International Olympic Committee and the Toronto Raptors
No full textHistory has shown that social movements can catalyze institutional transformation and influence organizational policies (Heydari, 2023). Movements such as #BlackLivesMatter and #MeToo- digitally born movement, decentralized, and hashtag-driven- that enabled rapid global mobilization through social media. have not only reshaped public discussion on racism, gender-based violence, and systemic inequality but have also permeated the sports world, prompting organizations and athletes to assume more active advocacy roles. Drawing from these developments and the belief that sport organizations have a responsibility to champion human rights (O'Brien et al., 2016), this dissertation explores Corporate Social Advocacy (CSA) practices within two influential sport organizations: The International Olympic Committee (IOC) and the Toronto Raptors.
The research investigates whether and how these organizations integrate CSA practices into their operations related to communication practices, and stakeholder engagement. A multi-method qualitative approach was employed, including on-line archival analysis of IOC documents sourced through the Wayback Machine, semi-structured interviews with IOC and Toronto Raptors advocacy experts. The findings reveal that both organizations have addressed societal issues - such as climate change, gender equality, refugee inclusion, LGBTQ+ rights, and anti-racism - through mission-aligned CSA efforts; a CSA approach that was revealed in this study.
The IOC's practices demonstrate a values-based approach rooted in sustainability and human rights, with advocacy communicated via digital platforms and global partnerships. Interviews with IOC experts confirmed that CSA is embedded in the organization's operations, despite cultural challenges and differing international perspectives. Similarly, the Toronto Raptors exhibit a CSA orientation, leveraging their platform to promote equity, health advocacy, youth engagement, and inclusivity. Their initiatives - often developed through cross-departmental collaboration and community partnerships - emphasize authenticity and data-driven decision-making wit implementing CSA practices.
The findings illustrate that CSA in sport is not limited to branding or reputation management but functions as a legitimate governance and strategic communication tool. The dissertation makes a significant theoretical contribution by introducing the concept of mission-aligned CSA - advocacy practices rooted in an organization's core values and operational goals. It challenges traditional CSA models focused on profit motives by demonstrating how non-profit and value-driven organizations can lead advocacy in ways that promote social change. The research also refines CSA theory by integrating elements such as public relations, policy influencing, emphasizing stakeholder engagement, cultural sensitivity, and resource mobilization. Additionally, the study outlines various communication channels that sport organizations can use to share their CSA initiatives with stakeholders. Ultimately, this study contributes to CSA scholarship by proposing a flexible, context-sensitive CSA framework that captures both the opportunities and complexities of implementing advocacy within sport management contexts
A Reinforcement Learning and Recommendation-Based Approach to Content Caching Optimization in Vehicular Networks
No full textEdge caching for the Internet of Vehicles (IoVs) has emerged as one of the most active research areas in computer networks, aiming to alleviate network congestion and reduce latency by deploying content caching and computational capabilities at Roadside Units (RSU). Given the high mobility of vehicles and the diversity of content requests, RSUs require caching strategies that ensure both high accuracy and content diversity. RSUs naturally act as in network caches consistent with the Information Centric Networking (ICN) paradigm. To address these challenges, we propose a proactive caching strategy named (GCN) based Recommender System and Deep Reinforcement Learning Caching (GCNR-DRL). This approach integrates a GCN-based recommender system with deep reinforcement learning to predict vehicles’ content demands and dynamically optimize caching decisions. The reinforcement learning agent captures the complex spatial temporal dynamics of vehicular networks and the intricate relationships between vehicles and content items, enabling precise cache replacement actions that significantly reduce transmission delays and mitigate network congestion during peak traffic hours.
Furthermore, we extend our work by introducing an innovative method that hierarchically learns recommendation and caching strategies using an Actor-Critic reinforcement learning framework. This method couples a cache controller with a pervehicle recommender. By jointly optimizing recommendation and caching decisions, the HiCaRe-RL approach further improves cache hit ratios, reduces latency, and lowers link load compared to existing strategies. By combining predictive power with adaptive caching decisions, our methods effectively enhance content dissemination efficiency in highly dynamic vehicular environments. The ability of GNN-based models to learn latent representations of vehicular interactions, coupled with reinforcement learning’s adaptability, makes these approaches highly suitable for real world IoV scenarios.
Comprehensive experimental results demonstrate that both GCN-based Recommender System and Deep Reinforcement Learning Caching (GCNRDRL) and the HiCaRe-RL method outperform traditional caching strategies. Our investigations underscore the potential of leveraging advanced GNN-based models and reinforcement learning techniques to drive efficient content placement and network resource management in dynamic IoV environments
A randomised controlled trial comparing epinephrine and dexamethasone to placebo in the treatment of infants with bronchiolitis (BIPED study): a statistical analysis plan
No full textAbstract Background Bronchiolitis is a common lung infection that affects infants and young children. While most children can be treated at home, some require hospitalisation where supportive care, such as fluids and oxygen, is the suggested treatment. Bronchiolitis is the leading cause of infant hospitalisation in developed countries and exerts a significant burden on the healthcare system. The aim of the Bronchiolitis in Infants Placebo Versus Epinephrine and Dexamethasone (BIPED) study is to evaluate the effects of a combination of epinephrine and dexamethasone, given during initial presentation at the emergency department, on hospitalisation for bronchiolitis. This article outlines the statistical analysis plan (SAP) for the BIPED study. The BIPED study is a Phase III, multi-centre, randomised, controlled, double-blinded superiority, placebo-controlled trial to determine whether the combination of epinephrine and dexamethasone is successful in reducing hospitalisation for bronchiolitis up to 7 days following presentation at an emergency department with bronchiolitis. The secondary outcomes include hospital admissions for bronchiolitis at the emergency department enrolment visit, and all-cause hospital admissions, health care provider visits and health care-related costs in the 21 days following enrolment. The safety outcomes are gastrointestinal bleeding, serious bacterial infection, severe varicella and death. Discussion The BIPED study will provide evidence on whether a combination of epinephrine and dexamethasone reduces hospitalisation in infants following presentation to the emergency department with bronchiolitis. These data will be analyzed using this SAP, submitted before the data became available for analysis, to reduce the risk of bias in our reported outcomes. Trial registration ClinicalTrials.gov NCT03567473. Registered on June 25, 2018
Forming the South Asian Diaspora: The Use of Instagram as an Identity and Community Building Platform
No full textAs social media becomes increasingly embedded in our lives, this thesis focuses on a specific niche within the expansive and ever-evolving social media landscape. Through digital ethnographic research and semi-structured interviews with participants, the study examines how South Asian diasporic leftist activists in Canada and the United States strive to build community and identity on Instagram. By creating a space on the platform to express what they describe as their authentic selves, these activists, primarily women from regions they identify as either South Asian or SWANA (South West Asian and North African), share their artistic endeavours, whether through photography, curated to achieve aesthetic appeal or captured by themselves, as well as written works and other forms of creative expression. Their work is deeply intertwined with their identities; as women of colour and feminists, they leverage their platforms to address issues that impact them and their communities, fostering a space that elevates marginalized voices through online techniques. In Chapter One, I examine how Instagram has developed and evolved into its current form, focusing on the role of users, other key stakeholders, and competition from other social media platforms in capturing engagement and attention. In Chapter Two, I explore how activists present themselves on this platform, create communities through activism, and challenge stereotypes and Islamophobia. Additionally, I analyze the backlash these activists face and how it serves as a tool to contest narratives surrounding their own identities. Finally, using the ongoing war in Gaza in 2023 as a case study, I investigate how these activists mobilized discussions around this genocide and the challenges they encountered in striving to be seen as virtuous advocates. I will conclude this thesis by discussing the intricacies of conducting research online, including its benefits and the potential negative impacts on users, particularly researchers. --
À mesure que les réseaux sociaux deviennent de plus en plus ancrés dans nos vies, cette thèse se concentre sur une niche spécifique dans le paysage expansif et en constante évolution des médias sociaux. Au moyen d'une recherche ethnographique numérique et d'entretiens semi-structurés avec les participant·e·s, l'étude examine comment les militants de gauche de la diaspora sud-asiatique au Canada et aux États-Unis s'efforcent de construire une communauté et une identité sur Instagram. En créant un espace sur la plateforme pour exprimer ce qu'ils décrivent comme leur « moi authentique », ces militants, principalement des femmes originaires de régions qu'ils identifient comme étant soit sud-asiatiques, soit SWANA (South West Asian and North African), partagent leurs efforts artistiques, que ce soit par le biais de la photographie, conçue pour atteindre un attrait esthétique ou capturée par eux-mêmes, ainsi que des œuvres écrites et d'autres formes d'expression créative. Leur travail est profondément lié à leurs identités ; en tant que femmes racisées et féministes, elles utilisent leurs plateformes pour aborder des enjeux qui les concernent elles-mêmes et leurs communautés, créant un espace qui valorise les voix marginalisées grâce à des pratiques en ligne. Dans le premier chapitre, j'examine comment Instagram s'est développé et transformé jusqu'à sa forme actuelle, en me concentrant sur le rôle des utilisateur·rice·s, d'autres acteurs clés, ainsi que sur la concurrence d'autres plateformes sociales dans la captation de l'engagement et de l'attention. Dans le deuxième chapitre, j'explore comment les activistes se présentent sur cette plateforme, créent des communautés d'activisme, et remettent en question les stéréotypes et l'islamophobie. J'analyse également les réactions négatives auxquelles ces activistes sont confrontées, et comment ces retours deviennent des outils leur permettant de contester les récits entourant leurs propres identités. Enfin, en utilisant la guerre en cours à Gaza en 2023 comme étude de cas, j'examine comment ces activistes ont mobilisé des discussions autour de ce génocide et les défis auxquels elles ont été confrontées dans leur quête pour être perçues comme des défenseures légitimes. Je conclurai cette thèse en discutant des subtilités de la recherche en ligne, y compris ses avantages et les impacts potentiellement négatifs sur les utilisateur·rice·s, en particulier les chercheur·e·s
Coenrollment of critically ill patients in PROSPECT: characteristics and association with treatment efficacy and safety
No full textAbstract Introduction Coenrollment is the enrollment of one participant into more than one study. While coenrollment can enhance research efficiency, it theoretically may result in treatment interactions that distort effect estimates. This study aimed to explore the sensitivity of safety and efficacy outcomes to coenrollment in an international, blinded randomized controlled trial evaluating probiotic use in critically ill patients (PROSPECT: Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial; [NCT02462590]). Methods In this planned secondary analysis of PROSPECT, we performed Cox proportional hazards analyses to assess the sensitivity of the treatment effect of probiotics to coenrollment on the primary outcome of ventilator-associated pneumonia. Secondarily, we examined the characteristics of coenrolled patients, studies, and centers using descriptive statistics, explored factors associated with coenrollment via a multilevel logistic regression model, and conducted Fisher’s exact tests to evaluate the difference in adverse event rates (defined as Lactobacillus species from a sterile site or cultured as the sole or predominant organism from a nonsterile site) by coenrollment status. Results Of 2650 PROSPECT participants recruited across 44 centers, 568 patients (21.4%) were coenrolled a total of 680 times across 115 studies. Coenrollment did not modify the effect of probiotics on the primary outcome of ventilator-associated pneumonia (p = 0.630). Patients who were coenrolled in any other study had a higher rate of adverse events compared to non-coenrolled patients (p = 0.011); however, post hoc testing found no difference in adverse events between patients coenrolled specifically into at least one other randomized controlled trial and patients who were not coenrolled into another randomized controlled trial (i.e., coenrolled into an observational study or not coenrolled at all; p = 0.126). Multivariable analyses found more severely ill patients (p = 0.038) and patients from centers with a longer PROSPECT recruitment period (p = 0.047) were more likely to be coenrolled. Conclusion In this international, blinded trial, one-fifth of patients enrolled were coenrolled in at least one other study, which had no influence on the effect of probiotics on the primary outcome. Coenrolled patients were more likely to have higher disease severity, and to be recruited from a center with a longer history of participation in PROSPECT. Trial registration The PROSPECT trial was registered in ClinicalTrials.gov NCT02462590. Registered on June 2015
Properties of Arithmetic Universes and Locoi
No full textIn this thesis, we study two kinds of categories: locoi, which are lextensive categories with list objects, and arithmetic universes, which are pretoposes with list objects. We show three main results: first, if is a locos, then the list object functor : → is a polynomial functor. Second, if is a locos, then the full subcategory Fin() of finite objects is a Boolean topos. Third, if is an arithmetic universe, then the free extension of by an object is the category [Finₛ, ] of indexed copresheaves on the internal category Finₛ of finite sets in