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Development of Well-Defined, Bench-Stable Ni-NHC Precatalysts for Challenging C-N Bond Formation Reactions
No full textTransition-metal-catalyzed C-N bond formation represents one of the most powerful synthetic methods for constructing aromatic amines and nitrogen-containing heterocycles. While palladium has historically dominated this field, nickel has recently emerged as a sustainable and cost-effective alternative due to its earth abundance, unique redox flexibility, and capacity to engage in both two-electron and single-electron processes. However, despite its potential, the development of well-defined, air- and moisture-stable nickel complexes capable of promoting challenging amination reactions remains limited. This thesis describes the systematic design, synthesis, and catalytic evaluation of new generations of bench-stable Ni-NHC precatalysts that overcome longstanding challenges in nickel-catalyzed C-N cross-coupling. The work focused on enhancing catalyst stability and reactivity through rational modification of the NHC ligand's steric and electronic properties.
A first-generation Ni-NHC-IPr complex synthesized by Organ group shown to promote the amination of aryl chlorides under mild conditions while maintaining excellent air and moisture stability. The reactivity is consistent with in-situ reduction of Ni(II) to a catalytically active Ni(0) species operating through a conventional Ni(0)/Ni(II) cycle. Although its activity diminished with sterically hindered or electronically deactivated substrates, the results confirmed that well-defined Ni-NHC complexes can serve as reliable precatalysts for cross-coupling applications. Interestingly, an unusual halide reactivity trend was observed: aryl chlorides afforded higher yields than their bromide or iodide analogues. This behavior was attributed to catalyst poisoning by bromide and iodide species, which divert the Ni complex off-cycle and terminate productive catalysis. These findings emphasize the distinctive oxidative-addition behavior of the Ni-NHC system and the critical role of halide identity in determining catalytic efficiency and stability.
Building on these results, the Ni-NHC-IPr complex was further explored under visible-light irradiation in combination with an iridium-based photoredox co-catalyst. The resulting dual [Ni]/[Ir] system enabled cross-coupling under milder conditions via high-valent Ni(I)/Ni(III) intermediates, accelerating reductive elimination. This photochemically assisted platform demonstrated enhanced performance with select substrates, highlighting the potential of redox modulation to extend nickel's reactivity window. However, the need for an external photosensitizer and diminished performance with demanding substrates underscore the need for further refinement. To advance catalyst performance, a range of sterically and electronically tuned NHC ligands, including IPent, IHept, IPr^*OMe, IPr^Cl, IPent^Cl, and IHept^Cl, were developed and incorporated into new generations of Ni-NHC complexes. Comparative catalytic studies revealed that increasing ligand bulk accelerates reductive elimination against B-hydride elimination but can also hinder substrate coordination, highlighting the need for fine steric balance. Backbone chlorination enhanced reactivity and selectivity in certain reactions but did not universally improve yields. The introduction of π-allyl ligands replaced the bulky stabilizing ligand with a more compact π-allyl group, opening greater coordination flexibility to accommodate bulkier NHC ligands on nickel; however, this modification came at the expense of reduced air stability.
Collectively, this work establishes a comprehensive framework for the development of well-defined Ni-NHC precatalysts that are not only bench-stable but also tunable across electronic and steric dimensions to meet diverse synthetic challenges. Through rational ligand design and systematic evaluation, it delivers a versatile platform for promoting challenging C-N bond formation with reliable performance under mild conditions, advancing both mechanistic understanding and practical applicability, and ultimately bridging the gap between academic discovery and industrial application
Collagen-Like Peptide Nanoparticles for Methylglyoxal Trapping
No full textCardiovascular diseases (CVDs) remain the leading global cause of death, with myocardial infarction (MI) a major contributor. Following MI, toxic metabolites like methylglyoxal (MG), a glycolysis byproduct, accumulates and increases formation of advanced glycation end-products (AGEs), inducing protein crosslinking, tissue stiffening, and signaling dysregulation, ultimately contributing to cardiac dysfunction.
Collagen-like peptides (CLPs) offer a versatile strategy for cardiac repair. Here, we designed CLPs containing arginine motifs optimized for MG scavenging. Spectroscopy and in vitro studies confirmed collagen-like behaviour and MG-trapping activity without exogenous molecules.
To enhance delivery, we developed self-assembled nanoparticles (NPs) from Fmoc-tyrosine and Fmoc-tryptophan, crosslinked via photopolymerization using Irgacure-2959. These NPs showed stability under purification, processing, and storage. Encapsulation efficiency (EE) studies better efficiency in phosphate buffer, achieving EE up to 72% EE (83.9 ug peptide/ 0.31 mg NPs).
Together, this highlights the potential of our MG-trapping peptide delivered via NPs as a potential therapeutic for post-MI cardiac repair
A mixed methods process evaluation of a collaborative outpatient palliative care clinic for patients with end-stage liver disease
No full textAbstract Background Patients with end-stage liver disease (ESLD) have significant symptoms and limited prognosis, yet receive less palliative care (PC) than patients with cancer. The optimal outpatient PC model for patients with ESLD remains unclear. Objective We used process evaluation methodology to evaluate a novel PC clinic for patients with ESLD in Ottawa, Canada. Design We conducted a convergent parallel mixed methods study, informed by a logic model and process evaluation framework co-designed with a caregiver partner. Qualitative inputs included semi-structured interviews conducted with patients, family caregivers, as well as PC and hepatology clinicians, and analyzed using applied thematic analysis. Quantitative inputs included data collected through a retrospective chart review, analyzing healthcare utilization up to six months before and after consultation. Participants Interviews conducted with eight healthcare providers (HCPs) and 13 patients and caregivers. Chart review performed for 46 patients seen in the clinic between October 2020 and June 2023. Intervention An outpatient PC hepatology collaboration clinic, led by specialist PC physicians. Approach Qualitative and quantitative data were analyzed independently and then triangulated for overall interpretation. Key results The evaluation demonstrated the achievement of the outcomes in the logic model and process evaluation domains. Interviews highlighted high satisfaction among HCPs, patients, and caregivers, and effective collaboration between the PC and hepatology teams. Perceived barriers include the burden of in-person appointments. Quantitative results indicated decreased acute healthcare utilization in the six months following PC consultation compared to the six months prior. Over 50% of the deceased patients died outside of the hospital. Conclusion The early outpatient PC clinic provides high-quality, collaborative care for patients with ESLD; study findings suggest an association with reduced acute healthcare utilization and increased likelihood of death occurring outside the hospital. This model represents a promising approach for PC in ESLD and other non-malignant illnesses
Moving Beyond 'Better than Prison': How 'Alternatives to Imprisonment' are Experienced by Criminalized People and Staff
No full textThis doctoral dissertation explores the experiences of criminalized people and workers of initiatives that the Canadian federal government considers to be 'alternatives to incarceration'. Within the context of a penal paradox in which there are increased prison builds alongside stated efforts to address racism and colonialism within the penal system, it is important to examine the possibilities and pitfalls of initiatives said to be 'alternatives to incarceration'. Rooted in abolition geography and an abolitionist reform approach, this study explores how wards and workers of these initiatives experience care/support and coercion/control from staff and community-based 'correctional' institutions more broadly. The results indicate that although wards experience some benefits within these so-called alternatives to imprisonment, these initiatives are often experienced as extensions of the carceral structure, replicating many of the conditions and constraints of prison itself. Although these initiatives were often described as 'better than prison', the participants offered many suggestions for how to improve 'alternatives to imprisonment' and/or create new ones that address harms and/or meet basic needs of those who have been criminalized which would allow them to flourish, while decreasing or eliminating criminalization
Effects of patient decision aids used pre-consult or in-consult on patient-clinician communication - secondary analysis of a systematic review with meta-analysis
No full textAbstract Background Patient decision aids (PtDAs) provide benefits and risks of options for a specific decision, and help patients clarify their values. This study examined whether the timing of PtDA use—before (pre-consult) or during (in-consult) the clinical encounter—affects patient-clinician communication. Methods We conducted a secondary analysis of 209 randomized controlled trials (RCTs) in the 2024 Cochrane review of PtDAs compared to usual care. Eligible studies measured patient-clinician communication using observer-, patient- or clinician-reported instruments. Results Thirty-six RCTs met inclusion criteria, reporting on communication outcomes: 21 evaluated pre-consult PtDAs and 15 in-consult PtDAs. Pre-consult PtDAs commonly addressed screening and treatment decisions, often using digital formats. In-consult PtDAs focused on treatment and were mostly paper-based. For pre-consult PtDAs, 68.6% of patients discussed the decision with their clinician versus 50.2% in usual care (p < 0.001), though no difference was found for patient-reported SDM-Q-9 scores. In-consult PtDAs significantly improved communication measured by the observer-rated OPTION12 instrument. Conclusions The effects of PtDAs varied by timing and measurement approach, with in-consult PtDAs potentially offering more structured support for shared decision making. No studies directly compared pre- and in-consult PtDAs. Future research should directly compare these approaches and use consistent communication measures
Parlons sciences ensemble : une recherche collaborative sur la place du dialogue en classe de sciences au secondaire en milieu minoritaire francophone dans l’Est ontarien
No full textCette thèse explore la place du dialogue dans l’enseignement des sciences au secondaire, en contexte minoritaire francophone ontarien. Elle accorde une attention particulière aux conditions d’émergence du dialogue exploratoire (exploratory talk) en groupe-classe, une forme d’interaction où les élèves expriment, justifient et construisent leurs idées de manière collaborative et raisonnée (Mercer, 1996). Mobilisant successivement la théorie des représentations sociales (Abric, 2001; Jodelet, 1989) et les cadres de l’enseignement dialogique (Alexander, 2020; Boyd, 2023) et de la sociolinguistique critique (Dalley, 2008a), cette recherche collaborative (Desgagné et al., 2001) a été réalisée avec trois membres du personnel enseignant expérimentés d’une école de l’Est ontarien. Elle s’appuie sur un corpus constitué d’enregistrements de leçons et de rencontres collaboratives, au sein desquelles la chercheuse et les membres du personnel enseignant ont analysé et discuté, de manière réflexive, des moments clés tirés des pratiques observées. Particulièrement attentive aux dimensions langagières, identitaires et épistémologiques du dialogue en sciences, cette étude met en lumière les défis propres à un milieu où le français est à la fois langue d’enseignement et langue minoritaire. Elle explore ainsi les tensions entre les normes linguistiques institutionnelles et les répertoires pluriels des élèves, révélant la complexité de concilier inclusion langagière, posture enseignante et visée épistémique dans l’enseignement des sciences.
Inspirée par une approche interprétative soucieuse de rendre compte de la complexité du terrain, cette thèse s’appuie sur deux analyses inductives et complémentaires, chacune en cohérence avec les tensions identifiées, les questions soulevées et les dynamiques linguistiques observées dans les pratiques enseignantes. Ce choix méthodologique s’inscrit dans une logique interprétative où l’analyse émerge en partie de la rencontre entre des moments empiriquement significatifs et des cadres théoriques qui s’ajustent au fil de l’interaction avec les données (Snell et Lefstein, 2015).
La première analyse adopte une approche centrée sur les représentations sociales du personnel enseignant à l’égard des compétences langagières des élèves et de leur capacité à participer à un dialogue scientifique en contexte minoritaire francophone. Elle repose sur une démarche inductive interprétative fondée sur les échanges lors de la première rencontre collaborative. En cohérence avec la problématique générale de la thèse, cette analyse mobilise un cadre conceptuel axé sur les représentations sociales (Jodelet, 1989 ; Abric, 2001) et une perspective sociolinguistique critique attentive aux normes langagières implicites (Dalley, 2008a). L’analyse, réalisée à partir des discours des personnes enseignantes sur les habiletés langagières de leurs élèves, met en lumière les tensions entre les conceptions normatives du français scolaire et la possibilité de créer un espace dialogique inclusif, tout en soulignant les obstacles structurels et symboliques à l’émergence du dialogue exploratoire en groupe-classe.
La deuxième analyse se concentre sur une étude de cas portant sur une leçon de sciences coplanifiée et coanimée par une équipe enseignante-chercheuse dans le cadre de la recherche collaborative. Elle repose sur des enregistrements dans la classe de l’enseignante et des réflexions faites à posteriori avec tous les membres de l’équipe de la recherche collaborative. Alors que la première analyse explorait des représentations sociales exprimées en début de projet, celle-ci s’intéresse à la mise en œuvre concrète d’un espace dialogique et les effets de cette transformation sur les interactions en classe. Elle analyse les gestes discursifs, le recadrage de la posture dialogique de l’enseignante et les réactions des élèves qui en découlent. Le cadre théorique mobilisé s’appuie sur les travaux en enseignement dialogique (Alexander, 2020; Boyd, 2023), en interaction didactique (Mercer et Hodgkinson, 2008; Scott et al., 2006) et sur une perspective sociolinguistique inspirée des recherches de Dalley (2008a). Cette approche permet d’analyser la légitimation des répertoires pluriels en classe de sciences et de rendre compte des conditions concrètes de mise en œuvre du dialogue, ainsi que des tensions épistémologiques et sociolinguistiques inhérentes au contexte minoritaire francophone canadien.
D’après les résultats de ces analyses, la posture épistémologique de la personne enseignante, qu’elle soit objectiviste et transmissive ou dialogique et coconstructive, a un impact significatif sur la nature et la fonction du dialogue en classe de sciences. En contexte minoritaire francophone, cette posture est étroitement liée aux conceptions langagières qui conditionnent la participation des élèves et leur accès aux savoirs. Suivant Dalley (2008a), cette thèse propose que l’ouverture à un dialogue authentique, en particulier dans les contextes francophones minoritaires, puisse non seulement enrichir les apprentissages scientifiques, mais aussi favoriser une appropriation plus inclusive et linguistiquement plurielle des savoirs scientifiques.
This dissertation explores the role of dialogue in secondary science education in a francophone minority context. It pays particular attention to the conditions under which exploratory talk emerges in whole-class settings, which involves students expressing, justifying, and collaboratively building their ideas through reasoned dialogue (Mercer, 1996). Grounded in the theory of social representations (Abric, 2001; Jodelet, 1989), the frameworks of dialogic teaching (Alexander, 2020; Boyd, 2023), and critical sociolinguistics (Dalley, 2008a), this collaborative research project (Desgagné et al., 2001) was conducted with three experienced science teachers in a secondary school in Eastern Ontario. The research draws on the analysis of recorded lessons and collaborative meetings in which the researcher and teachers jointly analyzed and reflectively discussed key moments drawn from classroom practice.
Particularly attentive to the linguistic, identity-related, and epistemological dimensions of dialogue in science, this study highlights the specific challenges faced in a context where French is both the language of instruction and a minority language. It examines the tensions between institutional linguistic norms and students’ plural repertoires, revealing the complexity of reconciling linguistic inclusion, teaching stance, and epistemic purpose in science education.
Guided by an interpretive approach attentive to the complexity of the field, two complementary inductive analyses were conducted, each aligned with the tensions identified, the questions raised, and the observed linguistic dynamics in teachers’ practices. In this approach, the analysis partially emerges from the interplay between empirically salient moments and theoretical frameworks that are refined through interaction with sensitizing data (Snell and Lefstein, 2015).
The first analysis adopts a focus on teachers’ social representations regarding students’ language skills and their ability to participate in scientific dialogue within a francophone minority setting. Based on exchanges from the project’s initial collaborative meeting, this inductive, interpretive analysis draws on a conceptual framework rooted in social representations theory (Jodelet, 1989; Abric, 2001) and a critical sociolinguistic perspective attentive to implicit language norms. The analysis highlights tensions between normative conceptions of academic French and the possibility of an inclusive dialogic space. This initial focus helps to uncover both structural and symbolic barriers to the emergence of exploratory dialogue, based on how teachers speak about their students’ linguistic capacities.
The second analysis presents a case study of a science lesson co-planned and co-taught by a teacher-researcher team within the collaborative framework. It is based on classroom recordings and post-lesson reflections with teaching staff. While the previous chapter focused on the social representations expressed early in the project, this analysis examines the concrete enactment of a dialogic space through discursive moves, a reframing of the teacher’s stance, and the student responses these moves provoke. The conceptual framework here builds on work in dialogic teaching (Alexander, 2020; Boyd, 2023), didactic interaction (Mercer et Hodgkinson, 2008; Scott et al., 2006), and a sociolinguistic perspective inspired by Dalley (2008a), which enables an analysis of how hybrid repertoires are legitimized in the science classroom. This second focus adopts an interactional and situated perspective that sheds light on the concrete conditions for implementing dialogue in class, as well as the epistemological and sociolinguistic tensions it entails in a Canadian francophone minority context.
The findings of this dissertation indicate that the teacher’s epistemological stance, whether objectivist and transmissive or dialogic and coconstructive, profoundly shapes the nature and function of dialogue in science classrooms. In francophone minority contexts, this stance is closely tied to underlying language ideologies that influence student participation and access to knowledge. The study suggests that fostering authentic dialogue, particularly in minority settings, can not only deepen learning but also support a more inclusive and linguistically plural appropriation of scientific knowledge
#notforkids: alcohol, vaping, and cannabis marketing by social media influencers popular with children and adolescents on YouTube, Instagram, and TikTok and policy implications
No full textAbstract Background Despite the popularity of social media among children and adolescents, there is comparatively little research on social media influencer marketing, particularly in the context of harmful products. The purpose of this study was to examine the frequency of advertisements for alcohol, vaping, and cannabis products/brands promoted by social media influencers popular with Canadian children and adolescents on YouTube, Instagram, and TikTok and analyze the marketing techniques used. Methods The top 9 influencers among Canadian children (10–12 years) and top 8 among Canadian adolescents (13–17 years) were identified from the 2021 International Food Policy Study. A subset of posts on YouTube, Instagram, and TikTok between June 1, 2021, and May 31, 2022, were examined for alcohol, vaping, and cannabis marketing. The frequency of marketing instances for each commodity was determined by age group and platform. Results We found no cannabis or vaping marketing. Influencers popular with children made 25 posts with alcohol marketing on Instagram and YouTube, showcasing 34 products/brands, while influencers popular with adolescents made 9 posts with alcohol marketing, featuring 16 alcohol products/brands. TikTok posts did not feature any alcohol products. Among influencers popular with children, YouTube accounted for most alcohol-related posts (72%), with beer being the most promoted (47%). Among influencers popular with adolescents, posts were mostly on Instagram (78%), with spirits being the most promoted (75%). Most posts across both age groups showed the product. Songs/music and appeals to fun/cool were the most common marketing techniques among influencers popular with children and adolescents, respectively. Conclusions Alcohol marketing that is appealing to children and adolescents is restricted in Canada, though they are likely exposed to such marketing ostensibly directed to adults. Further regulation, monitoring, and compliance assessments are warranted
Molecular and Cellular Characterization of Synovial Joint Tissues: Insights into Subsynovial Adipose Tissue, Cell-Type Heterogeneity, and Osteoarthritis
No full textOsteoarthritis (OA) is a chronic degenerative joint disease that affects nearly 15% of Canadians, with an estimated healthcare cost exceeding $11 billion annually by 2031. Current regenerative strategies primarily focus on mesenchymal stem cells (MSCs); however, the precise identity of joint-resident stem cells and their responses to physiological changes remain poorly understood. This thesis addresses this gap through a multi-level investigation of joint tissues in human and animal models. First, we examined surgical samples of human sub-synovial adipose tissue (ssAT) of the hip to distinguish cellular and molecular changes associated with OA from those of normal aging. Using immunohistochemistry and targeted transcriptomics, we demonstrated that OA is characterized by increased mesenchymal stem/progenitor cell content, vascular remodeling, and immune dysregulation, in contrast to the more subtle changes associated with normal aging. To further characterize joint tissue heterogeneity, we generated a comprehensive single-cell atlas of the murine postnatal joint by integrating publicly available single-cell datasets with a spatial transcriptomics dataset produced in this work. This atlas highlights the distinct cellular populations and transcriptional programs underlying joint maintenance and disease susceptibility. Building on these insights, we identified Tbx18 as a putative marker of joint-resident cells and performed lineage tracing combined with three-dimensional (3D) confocal imaging in mice. We show that Tbx18⁺ cells populate the synovium, meniscus, articular cartilage, and tendons, where they remain quiescent under homeostasis but become activated following injury. Collectively, this work highlights the ssAT as an active contributor to OA pathogenesis, establishes the first integrated atlas of the postnatal joint, and identifies Tbx18 as a powerful surrogate marker for studying all tissues in the joints. These findings provide new insights into the biology of joint tissues and lay the groundwork for stem cell–based regenerative strategies in orthopedic disease
Unravelling the complexities of end-of-life critical care interventions: what drives medico-legal complaints to physicians?
No full textAbstract Background This study sought to describe the key medico-legal issues associated with end-of-life critical care interventions in Canada. We explored the most common themes of a disagreement between patients or substitute decision makers (SDM) and treating physicians related to intervention decisions, and complaints against physicians, that were identified and criticised by peer experts as contributing to medico-legal risk. Methods A national repository was retrospectively searched for cases involving end-of-life care that were supported by the Canadian Medical Protective Association (CMPA) between 2018 and 2022. The study involved patients admitted to surgical and medical intensive and critical care units, emergency departments and residents in long term care settings. The frequencies and proportions of the top risk factors leading to medico-legal risks and the most frequent allegations were calculated by exploring factors that contributed to each incident. Results We identified 93 eligible cases, involving 142 physicians. Family medicine was the most frequent specialty named in 32% of the cases. The median age of 93 unique patients was 78 years. Common reasons for complaints were communication breakdown between a physician and a patient/SDM and deficient assessment. The most frequent contributing factors criticised by peer experts were communication breakdown between a physician and a patient/SDM and inadequate documentation. Conclusions The most common omission identified by peer experts involved a physician’s communication with a patient/SDM. Physicians may reduce their medico-legal risk by exploring effective techniques for optimal communication to improve understanding in end-of-life discussions, with the goal of high-quality patient care
Effects of Chronic Cortisol Elevation on Cardiac Structure and Function in Zebrafish (Danio rerio)
No full textCardiac deformities are increasingly reported in farmed salmonid fishes. Pathological cardiac hypertrophy is dysfunctional remodelling that includes enlargement of the ventricle and compact myocardium, as well as fibrotic collagen deposition. The current study investigated the effect of chronic cortisol elevation, as a proxy for chronic stress, on zebrafish (Danio rerio) heart structure and function. Compact myocardium thickness and heart size increased in wildtype zebrafish exposed to waterborne cortisol treatment. However, pro-hypertrophic molecular markers did not differ in transcript abundance between treatment groups. Measures of cardiac function were not affected by cortisol exposure, nor was swimming performance. Zebrafish lacking functional expression of the glucocorticoid receptor (GR-KO) had hearts that were smaller and with thinner walls relative to body mass than wildtype fish. However, cardiac function and swimming performance in GR-KO fish were comparable to those of matched wildtype fish. Collectively, these data indicate that the zebrafish heart is capable of maintaining function even as morphology changes