<p>Tissue engineering of biomimetic skeletal muscle may lead to development of new therapies for myogenic repair and generation of improved in vitro models for studies of muscle function, regeneration, and disease. For the optimal therapeutic and in vitro results, engineered muscle should recreate the force-generating and regenerative capacities of native muscle, enabled respectively by its two main cellular constituents, the mature myofibers and satellite cells (SCs). Still, after 20 years of research, engineered muscle tissues fall short of mimicking contractile function and self-repair capacity of native skeletal muscle. To overcome this limitation, we set the thesis goals to: 1) generate a highly functional, self-regenerative engineered skeletal muscle and 2) explore mechanisms governing its formation and regeneration in vitro and survival and vascularization in vivo.</p><p>By studying myogenic progenitors isolated from neonatal rats, we first discovered advantages of using an adherent cell fraction for engineering of skeletal muscles with robust structure and function and the formation of a SC pool. Specifically, when synergized with dynamic culture conditions, the use of adherent cells yielded muscle constructs capable of replicating the contractile output of native neonatal muscle, generating >40 mN/mm2 of specific force. Moreover, tissue structure and cellular heterogeneity of engineered muscle constructs closely resembled those of native muscle, consisting of aligned, striated myofibers embedded in a matrix of basal lamina proteins and SCs that resided in native-like niches. Importantly, we identified rapid formation of myofibers early during engineered muscle culture as a critical condition leading to SC homing and conversion to a quiescent, non-proliferative state. The SCs retained natural regenerative capacity and activated, proliferated, and differentiated to rebuild damaged myofibers and recover contractile function within 10 days after the muscle was injured by cardiotoxin (CTX). The resulting regenerative response was directly dependent on the abundance of SCs in the engineered muscle that we varied by expanding starting cell population under different levels of basic fibroblast growth factor (bFGF), an inhibitor of myogenic differentiation. Using a dorsal skinfold window chamber model in nude mice, we further demonstrated that within 2 weeks after implantation, initially avascular engineered muscle underwent robust vascularization and perfusion and exhibited improved structure and contractile function beyond what was achievable in vitro. </p><p>To enhance translational value of our approach, we transitioned to use of adult rat myogenic cells, but found that despite similar function to that of neonatal constructs, adult-derived muscle lacked regenerative capacity. Using a novel platform for live monitoring of calcium transients during construct culture, we rapidly screened for potential enhancers of regeneration to establish that many known pro-regenerative soluble factors were ineffective in stimulating in vitro engineered muscle recovery from CTX injury. This led us to introduce bone marrow-derived macrophages (BMDMs), an established non-myogenic contributor to muscle repair, to the adult-derived constructs and to demonstrate remarkable recovery of force generation (>80%) and muscle mass (>70%) following CTX injury. Mechanistically, while similar patterns of early SC activation and proliferation upon injury were observed in engineered muscles with and without BMDMs, a significant decrease in injury-induced apoptosis occurred only in the presence of BMDMs. The importance of preventing apoptosis was further demonstrated by showing that application of caspase inhibitor (Q-VD-OPh) yielded myofiber regrowth and functional recovery post-injury. Gene expression analysis suggested muscle-secreted tumor necrosis factor-α (TNFα) as a potential inducer of apoptosis as common for muscle degeneration in diseases and aging in vivo. Finally, we showed that BMDM incorporation in engineered muscle enhanced its growth, angiogenesis, and function following implantation in the dorsal window chambers in nude mice.</p><p>In summary, this thesis describes novel strategies to engineer highly contractile and regenerative skeletal muscle tissues starting from neonatal or adult rat myogenic cells. We find that age-dependent differences of myogenic cells distinctly affect the self-repair capacity but not contractile function of engineered muscle. Adult, but not neonatal, myogenic progenitors appear to require co-culture with other cells, such as bone marrow-derived macrophages, to allow robust muscle regeneration in vitro and rapid vascularization in vivo. Regarding the established roles of immune system cells in the repair of various muscle and non-muscle tissues, we expect that our work will stimulate the future applications of immune cells as pro-regenerative or anti-inflammatory constituents of engineered tissue grafts. Furthermore, we expect that rodent studies in this thesis will inspire successful engineering of biomimetic human muscle tissues for use in regenerative therapy and drug discovery applications.</p> / Dissertation

Problématique : Bien que l’implantation réussie des services de liaison à la suite d’une fracture (Fracture Liaison Services – FLS) soit essentielle afin de soutenir leur efficacité à prévenir la survenue d’autres fractures de fragilité (FF), l’implantation des FLS a été peu étudiée. Objectifs : Évaluer l’implantation d’un FLS par l’analyse des facteurs influençant : 1) le degré d’implantation du FLS ; et 2) l’adhésion des participants aux recommandations du FLS. Méthodologie: Une étude de cas multiples avec un devis mixte imbriqué à prédominance qualitative a été menée de 2013 à 2015 afin d’identifier les facteurs influençant l’implantation du FLS dans 3 régions du Québec (Canada) : Estrie, Montréal et Lanaudière. Le degré d’implantation a été déterminé selon la mise en œuvre de 7 composantes du FLS : 1) la nomination d’un coordonnateur, 2) la formation en première ligne sur les FF, 3) l’identification de patients avec une FF, 4) l’investigation de leur FF, 5) la communication avec leur médecin de famille, 6) la référence en prévention des chutes et 7) la prescription d’une médication. Les données ont été recueillies au moyen de la base de données des participants du FLS, des comptes rendus des réunions du comité d’implantation et d’entrevues avec des parties prenantes : comité d’implantation, coordonnateurs, orthopédistes et membres de l’équipe d’orthopédie. Les comptes rendus et les verbatim d’entrevues ont fait l’objet d’une analyse guidée par le Cadre consolidé pour la recherche sur l’implantation. Un devis mixte séquentiel explicatif a ensuite été utilisé afin d’identifier les facteurs influençant l’adhésion des participants aux recommandations concernant : 1) la médication; 2) les habitudes de vie (vitamine D, calcium et activité physique); et 3) la prévention des chutes. Des caractéristiques des participants ont été modélisées pour estimer la probabilité d’adhérer aux recommandations du FLS et des entrevues ont été réalisées avec des participants afin d’approfondir ces résultats. Résultats : Au cours de la période d’implantation analysée de 30 mois, un coordonnateur a été nominé dans chaque région et des formations sur les FF ont été données. Un total de 457 patients ont été identifiés et ont accepté de participer au FLS. Parmi les participants, 376 (82%) ont été investigués pour leur risque de FF, la communication avec leur médecin a été établie pour 456 (98%), 299 (65%) ont initié une médication et 158 (35%) ont été référés en prévention des chutes. L’initiation de la médication et la référence en prévention des chutes ont significativement varié entre les régions. L’analyse des 39 comptes rendus et des 10 entrevues a montré que des caractéristiques des coordonnateurs ont facilité l’implantation des composantes du FLS alors que l'accès difficile à des activités de prévention des chutes a nui à l’implantation. La connaissance de leur diagnostic d'ostéoporose (n=106/354) a augmenté la probabilité des participants d’adhérer à la médication (OR=2,47; IC 95% 1,47-3,93) et à la vitamine D (OR=2,34; IC 95% 1,23-4,46). Paradoxalement, cela a diminué leur probabilité d’adhérer à l’activité physique (OR=0,45; IC 95% 0,25-0,81). Les entrevues avec les participants (n=16) ont montré que l’éducation centrée sur le patient les aidait à mieux comprendre que leur FF était causée par l’ostéoporose et que le soutien à l’autogestion facilitait la mise en place de stratégies pour adhérer aux recommandations du FLS. Conclusion : Cette étude met en évidence l'importance du rôle du coordonnateur pour promouvoir l’implantation réussie des composantes d'un FLS, faciliter la compréhension que le patient se fait de sa maladie et le soutenir dans la gestion de ses soins à la suite d’une FF, tout en favorisant l’intégration du continuum de soins et services du patient visant à prévenir la survenue d’autres FF. / Abstract : Background: Although Fracture Liaison Services (FLSs) are clinically- and cost-effective to prevent subsequent fragility fractures (FF), their rigorous implementation is essential to support their effectiveness. Despite the emergence of FLS, few studies have analysed their implementation. Objectives: Evaluate the factors influencing: 1) the degree of implementation of a FLS components; and 2) the adoption to the FLS recommendations by participants. Methodology: A multiple case study using a quantitative approach embedded within a predominantly qualitative method was firstly conducted between 2013 and 2015 in 3 regions of the province of Quebec (Canada): the Eastern Townships, Montreal, and Lanaudiere. The degree of implementation was determined according to 7 FLS components: 1) the employment of a coordinator, 2) the training on FF to primary care providers, 3) the identification of FF patients, 4) the investigation of their FF, 5) the communication with their family physician, 6) the referral to a fall prevention activity, and 7) the prescription of a medication. Data were collected through the FSL participant database, implementation committee meeting minutes, and interviews with stakeholders (i.e. implementation committee, coordinators, orthopaedic surgeons and members of orthopaedic teams). The Consolidated Framework for Implementation Research guided analysis of meeting minutes and interview verbatim. An explanatory sequential mixed methods design was secondly used to identify factors influencing the adoption of FLS recommendations by participants regarding: 1) medication; 2) lifestyle habits (vitamin D, calcium and physical activity); and 3) fall prevention. Participants' characteristics were modeled to estimate the likelihood of adopting FSL recommendations, and interviews were conducted with FLS participants to deepen these results. Results: During the 30-month implementation period analyzed, a coordinator was nominated in each region and FF training was provided. A total of 457 patients were identified and agreed to participate in the FSL. Of the participants, 376 (82%) were investigated for their risk of FF, a communication with their physician was established for 456 (98%), 299 (65%) initiated medication and 158 (35%) were referred for fall prevention. The referral to fall prevention activities and the prescription of medications varied significantly between regions. The analysis of the minutes of 39 meetings and 10 verbatim showed that some coordinator characteristics facilitated the implementation of FLS components whereas the problematic access to fall prevention activities impeded the implementation. Participant knowledge of their diagnosis of osteoporosis (n=106/354) increased the likelihood of adopting medication (OR=2.47, 95% CI 1.47-3.93) and vitamin D (OR=2.34, 95% CI 1.23-4.46). Paradoxically, this decreased their likelihood of adopting physical activity (OR=0.45, 95% CI 0.25-0.81). Interviews with participants (n=16) showed that patientcentered education helped them to understand that their FF was caused by osteoporosis, and that self-management support facilitated the development of strategies to adopt FLS recommendations. Conclusion: This study highlights the importance of the role of the coordinator in promoting the successful implementation of FSL components, facilitating patient understanding of its disease, and supporting self-management of FF, while fostering the integration of the patient's continuum of care and services that aim to prevent the occurrence of subsequent FFs.

Notre recherche vise à identifier les facteurs critiques du succès de l’implantation de l’Entreprise Risk Management (ERM). À cette fin, nous avons élaboré un modèle, c’est-à-dire une sorte de cadre de référence susceptible d’améliorer nos connaissances des déterminants de succès dans l’implantation de l’ERM, d’une part, et de guider les entreprises impliquées dans cette implantation, d’autre part. Étant donné le caractère holistique de l’ERM, nous avons adopté une approche systémique. Cette dernière nous a permis : 1) de conceptualiser les enjeux associés à l’implantation de l’ERM comme un tout au sens d’identifier les éléments et leurs attributs; 2) de déterminer les relations entre les éléments; 3) et de tenir compte de la dynamique de la gestion intégrée des risques que préconise l’ERM. Comme cadre théorique général, nous avons eu recours à la théorie sociotechnique, ce qui a orienté notre réflexion vers des construits : pilotage stratégique, implication des acteurs, parrainage de la direction, adaptation structurelle et climat organisationnel, du côté social, et capacité d’intégration des connaissances, capacité TI et capacité de changement, du côté des aspects techniques. L’approche de notre recherche est exploratoire avec un design d’étude corrélationnel et une recherche par enquête. Les données ont été collectées entre le 2 décembre 2012 et le 28 février 2013, par l’intermédiaire d’un questionnaire électronique. Nous avons procédé à la réduction des données à l’aide d’une analyse factorielle exploratoire. Pour la modélisation statistique proprement dite, nous avons eu recours aux équations structurelles par la méthode des moindres carrés partiels. Pour ce, nous avons utilisé le logiciel SmartPLS. Les résultats sont satisfaisants et nous ont permis : a) de déceler des problèmes dans l’opérationnalisation de certains construits, b) de valider certaines des hypothèses, c) de tirer des conclusions que nous avons ventilées au début. Ces résultats nous ont aussi montré qu’il y avait d’autres facteurs qu’il n’était pas nécessaire de considérer dans une telle implantation. De manière générale, la recherche répond à notre question de recherche : « Quels sont les facteurs critiques du succès de l’implantation de l’ERM? ». Il en ressort aussi des contributions théoriques et pratiques. En ce qui a trait aux contributions théoriques, en premier lieu, notre étude contribue à une meilleure compréhension des facteurs de succès de l’implantation de l’ERM, car elle permet d’identifier de manière empirique les facteurs : Pilotage Stratégique, Implications des Acteurs, Parrainage de la Direction, Adaptation Structurelles, Capacité TI et Capacité de Changement Organisationnelle. En second lieu, notre recherche se distingue des études antérieures sur l’ERM également, car elle contribue à développer une perspective théorique relative à l’ERM en proposant de considérer l’ERM comme étant une innovation administrative et technologique, d’une part, et comme un système sociotechnique, d’autre part. En ce qui a trait aux contributions pratiques, les résultats empiriques suggèrent 1) que les gestionnaires accordent une attention importante au soutien de la haute direction avant de s’engager dans l’adoption et l’implantation de l’ERM; 2) que l’implantation réussie de l’ERM ne dépend pas uniquement de la disponibilité des ressources techniques physiques et humaines, les gestionnaires doivent s’assurer d’intégrer les processus opérationnels et technologiques. / Abstract : Our research aims to identify the critical success factors for the implementation of the Enterprise Risk Management (ERM). To this end, we have developed a model, meaning a kind of framework to improve our knowledge of the determinants of success in implementing ERM, on the one hand and guide companies involved in this implementation, on another hand. Given the holistic nature of the ERM, we have adopted a systemic approach, which allowed us to: 1) to conceptualize the issues associated with the implementation of ERM as a whole in the sense of identifying the elements and their attributes; 2) to determine the relationship between the elements; 3) and take into account the dynamics of integrated risk management advocated by the ERM. As a general theoretical framework, we used the socio-technical theory, which guided our thinking towards the variables: strategic management, stakeholder involvement, sponsorship management, structural adjustment and organizational climate, on the social side, and capacity integration of knowledge, IT capability and capacity for change, on the side of the technical aspects. The approach of this research is exploratory with a design of correlation study and survey research. Data collection was done between December 2, 2012 and February 28, 2013, via an electronic questionnaire. We performed data reduction using an exploratory factor analysis. For the statistical modeling, we used Structural Equations Modeling (SEM) technique with Partial Least Squares (PLS) as the method. For this, we used the SmartPLS software. The results are satisfactory and allowed us to: a) identify problems in the application of some variables, b) validate some of the hypothesis, c) to confirm some 8 ideas which we have in the beginning. These results also showed that there were other factors that it was not necessary to consider in such implementation. In general, the research responds to our research question: "What are the critical success factors for the implementation of the ERM?". It also gives some theoretical and practical contributions. Concerning the theoretical contributions, in the first place, our study contributes to a better understanding of the factors of successful implementation of ERM, as it allows to identify empirically the follow factors: Strategic Driving, Employee Implication, Board Implication, Structure Adaptation, IT Capacity and Change Capacity. Second, our research differs from previous studies on the ERM because it helps to develop a theoretical perspective on the ERM proposing to consider the ERM as an administrative and technological innovation on the one hand, and as a sociotechnical system, on the other hand. Moreover, in respect to practical contributions, empirical results suggest 1) Members of the board and senior managers are supposed to understand the importance of giving support for the implementation team even before engaging in the adoption and implementation of ERM; 2) the successful implementation of ERM does not depend only on the availability of physical, technical and human resources, Senior managers should be engaged in the integration of operational and technological processes.

The overall aim of this thesis is to explore experiences and self-reported outcomes from Transcatheter Aortic Valve Implantation, TAVI, among people with severe aortic stenosis. The thesis includes four studies. Study I-II are based on interviews performed the day before TAVI and Qualitative Concept Analysis was used for analysis. Study III is based on interviews at six months’ follow-up and Grounded Theory was used for analysis. Study IV is quantitative and based on questionnaires at baseline and at six months’ follow-up. Nonparametric, descriptive statistics were used for the analysis. Study I described the vulnerable situation for patients with severe aortic stenosis before TAVI. They were facing death and at the same time struggling to cope with their symptoms and to maintain independent. TAVI offered hope but also caused uncertainty about the new method. Study II focused on the patients’ decision-making process. Three patterns were identified; ambivalent, obedient, and reconciled. The ambivalent patient is unsure of the value of treatment and aware of the risks; the obedient patient is unsure of the value of one's own decision and wants to leave the decision to others; the reconciled patient has reached a point where there is no choice anymore and is always sure that the decision to undergo TAVI is right. Study III offered a deeper understanding of the TAVI trajectory. A journey of balancing between hope and life-struggle was the core category of the analysis. Before TAVI patients felt threatened, but also experienced hope. The rehabilitation phase was described as demanding and depressing or surprisingly simple. At the six months’ followup patients described being pleased to return to life, however, many were still struggling with limitations. Study IV focused on quantifying the symptom burden, function and health related quality of life before and after TAVI. The results were reflected against that of patients treated with open surgery. Self-rated function and health related quality of life increased and symptoms were reduced at follow-up, but breathlessness and fatigue were still common. Conclusively, TAVI patients are struggling with limitations, both because of their comorbidities and because of their valve disease which also poses a threat to their lives. TAVI gives an opportunity to survive, to stay independent and to increase quality of life. To feel and preserve hope is essential for patients’ wellbeing, both before and during the recovery process.

Structural and optical properties of ZnO nanostructures synthesized by low energy ion implantation technique were examined. ZnO molecular ions were implanted into Si/SiO2 substrates at room temperature and then furnace annealed under different temperatures and environments. In all as-implanted samples only Zn nanostructures with varying diameters distributed into the Si/SiO2 matrices were observed. No trace of ZnO was found. The distributions of Zn nanostructures in Si/SiO2 closely matched results from Stopping and Range of Ions in Matter (SRIM) simulations. During annealing at 750 oC, Zn diffused both toward and away from the surface of the substrate and combine with oxygen to form ZnO nanostructures. At higher annealing temperatures ZnO bonding started to break down and transfer to zinc silicate (Zn2SiO4), and at 900 oC the ZnO was completely converted into Zn2SiO4. The average sizes of Zn/ZnO nanostructures depended on the ion fluence. If the fluence increased the average sizes of nanostructures also increased and vice versa. For room temperature photoluminescence (RT-PL), band-edge emission in the ultraviolet (UV) region was observed from all samples annealed at 700 oC/750 oC and were slightly blue shifted as compare to bulk ZnO. Donor-bound exciton (D,X) and acceptor-bound exciton (A,X) transitions were observed in low temperature photoluminescence (PL). The lifetime of both donor-bound excitonic emission (D, X) and acceptor-bound excitonic emission (A, X) were found to be in the picosecond (ps) range.

Symptomatic aortic stenosis (AS) is an increasing phenomenon as more adults live longer. The gold standard for treating AS is surgical aortic valve replacement (SAVR). Frequently, as older individuals with AS often have multiple comorbidities, a SAVR is determined to be too high risk. Therefore, a less invasive treatment option is available, namely a transcatheter aortic valve implantation (TAVI) or transcatheter aortic valve replacement (TAVR). Such biomedical procedures have encouraged life extension and the decision to intervene commonplace with the aging population. Without an intervention, significant debilitating symptoms affect a person's quality of life (QoL). Multiple quantitative studies evaluating QoL before and after a TAVI have been performed. However QoL has multiple attributes and is not a single construct. By limiting practice to these defined QoL measures, we exclude the human experience and what values individuals describe as important to them. The dilemma in the present medical model is influenced by two paradigms, evidence based medicine and patient centered medicine. Some people opt not to have a TAVI. This study aims to understand what it is like living with aortic stenosis as perceived by the participant and to gain a more meaningful understanding of why some individuals with AS choose not to have this procedure performed. Using a convenience sample of patients who declined a TAVI, a telephone interview with the person focused on their perceived QoL and the implications determining not to pursue a TAVI. In this qualitative phenomenological design, open-ended questions included: 1) What is it like to live with Aortic Stenosis. 2) Why did you choose not to have the TAVI? Interviews will explore emerging themes. Advanced practice nurses are in ideal positions for performing research to gain greater insight on the complexity of people's health choices. As the incidence of AS occurs more frequently in the increasing aged population, TAVI offers a treatment option for those patients who are symptomatic with AS and are not surgical candidates. However, health care providers should focus on the illness, not the disease, and explore the patients' biopsychosocial values with their medical needs. The information gathered in this study will help guide heath care providers with offering holistic health care incorporating both paradigms of evidence based practice and patient centered medicine options on treatment for people with symptomatic AS.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

No description available.

Call number: LD2668 .T4 1986 Y36 / Master of Science / Physics