NCube/papyrus huggingface dataset:
L’identification et la remédiation des difficultés de raisonnement clinique en
médecine (État des pratiques, recherche d’outils et processus pour soutenir les cliniciens
enseignants)

CONTEXT: Clinical reasoning is central to medical practice. However, we lack tools to identify and objectify the difficulties of clinical reasoning, and there are relatively few descriptions of remediation methods defined. Much work remains to be done to better understand how the problems manifest themselves in the clinical reasoning of students in training, but also to make these concepts more accessible to teachers.Then this will improve the quality of the identification process difficulties, and allow considering targeted and effective remediations.PURPOSE: This research is based on the one hand, around the objectification and understanding of current practices of clinical teachers, on the other hand, around the construction and implementation of tools and processes to facilitate the process of diagnosis and remediation of difficulties in clinical reasoning. METHODOLOGY: A qualitative research, mainly using the methods of participatory action research has been relevant to achieving our goals. The research consists of four steps: 1. An exploratory study 2. The construction and implementation of a first tool in three clinical settings 3. The development of a taxonomy of difficulties in clinical reasoning and the construction of a new tool. 4. The development of a comprehensive approach to support and train clinical teachers RESULTS: Teachers have a quick perception, but still global and intuitive, of the potential difficulties of clinical reasoning residents. This perception does not necessarily move into pedagogical terms. We observed the absence of organized and structured pedagogical processes to manage these difficulties. This seems to project the clinical teachers in a zone of discomfort, by confronting them with a lack of control and uncertainty about their educational activities. The categorization of clinical reasoning difficulties that we have built allows identifying the problems as they occur in everyday clinical supervision. This tool, however, needs to be integrated into a larger process. CONCLUSION: It is necessary to develop a comprehensive approach that includes faculty development process, implementation tools, vulgarization of the theory, and teacher training.

Keyphrases: Clinical reasoning process, Clinical reasoning difficulties, Clinical teacher
Modulation of Endothelin-1 and Insulin-like Growth Factor Type 1-induced Signaling by Curcumin in A-10 Vascular Smooth Muscle Cells

Cardiovascular diseases (CVDs), including hypertension and atherosclerosis, are associated with vascular functional and structural changes. Some of the cellular events underlying these processes include aberrant vascular smooth muscle cell (VSMC) proliferation, hypertrophy and migration. Endothelin-1 (ET-1) has been implicated in the pathogenesis of vascular abnormalities through the hyperactivation of key components of growth promoting and proliferative signaling pathways, including MAPKs and PI3-K/PKB. Vascular oxidative stress has also been suggested to play an intermediary role in mediating ET-1-induced pathophysiological effects. Interference with ET-1-induced signaling may therefore serve as a potential therapeutic strategy against the progression of cardiovascular disorders. There is presently a surge of interest in the use of plant-derived phytochemicals for the treatment of various diseases. Curcumin, the main constituent of the spice turmeric, exhibits multiple biological properties, amongst them, antioxidant, anti-proliferative and cardioprotective properties. However, the molecular mechanisms of its cardiovascular protective action remain obscure. Therefore, in the present studies, we investigated the effectiveness of curcumin to inhibit ET-1-induced signaling events in VSMC. Curcumin inhibited ET-1-induced as well as IGF-1-induced phosphorylation of IGF-1R, PKB, c-Raf and ERK1/2, in VSMC. Furthermore, curcumin inhibited the expression of transcription factor early growth response-1 (Egr-1) induced by ET-1 and IGF-1, in VSMC. In summary, these results demonstrate that curcumin is a potent inhibitor of ET-1 and IGF-1-induced mitogenic and proliferative signaling events in VSMC, suggesting that the ability of curcumin to attenuate these effects may contribute as potential mechanism for its cardiovascular protective response.

Keyphrases: ERK1/2, IGF-1, IGF-1R, PKB, Egr-1, Curcumin, Endothelin-1 (ET-1), Extracellular signal-regulated kinase 1/2  (ERK1/2), Vascular smooth muscle cells (VSMC), Insulin-like growth factor type 1 (IGF-1), Insulin-like growth factor type 1 receptor (IGF-1R), Protein kinase B (PKB), Early growth response -1 (Egr-1)
La notion de contrainte excessive : seule limite à l’obligation
d’accommodement

The obligation of reasonable accommodation has been the object of much discussion during the last decade, in Quebec and elsewhere in Canada. Since this issue was first broached by the Supreme Court of Canada in 1985, the courts and tribunals have had many occasions to render decisions on the topic. Starting at the onset with a very vague and indistinct legal concept, decision makers have since sought to define the concept of reasonable accommodation through studying its only limit: undue hardship. It is now accepted that the employers must adapt work and workplaces to enable disabled workers with an access to employment without discrimination. Trade unions, just like employees aimed by a request for accommodation, also both have the obligation to collaborate in the search of measurements of rectification. This Master’s thesis proposes a jurisprudential study of the concepts of reasonable accommodation and undue hardship. Our analysis will relate to the decisions of the judicial and administrative tribunals rendered in Quebec between 1999 and 2010. The present study has for main objective to analyze the extent of the concept of undue hardship and to define it clearly and with precision.

Keyphrases: Discrimination, Reasonnable accommodation, Undue hardship, Law, Labour, Discrimination, Human rights
Mutations esthétiques, mais continuité technique dans l'oeuvre de Pierre Boulez

Pierre Boulez’s musical compositions are one of the most important compositions in the second half of the twentieth century. They moved a lot between 1945 and 2008 together with his written works, in which his thought deals successively with the different aspects of his language : the theory between 1948 and 1963, then the esthetics between 1963 and 1995.  Studying only the officially accepted works is not sufficient to understand this evolution, the issues and the outlines of Boulez’s music. It was necessary to study all the compositions of secondary importance - even if they were not finished or recognized - and all the successive versions of each work ; that’s why all these sources had to be collected and analyzed. It has been contractually intended since 1986 that the Paul Sacher Foundation in Basel should have Boulez’s archives, however many sources, sketches, manuscripts and mails are still scattered or lost. That is what happened to some early works and some recent works that have not been registered in the Foundation yet.  This doctoral dissertation is above all a work of analysis. From the viewpoint of the works that have already been done, I chose to restrict my study to the compositions of two periods – 1945-1949 and then 1965-2008 – which are extreme and representative of the evolution of Boulez’s esthetic and composition. According to the sources’ availability, I favored an approach called “poïétique inductive” – to take up again the idea of “tripartition” – within the context of music semiology as it was elaborated by Jean Molino1 and Jean-Jacques Nattiez2 in the middle of the seventies, that is to say by studying only the available scores – Répons, Initiale, Incises and sur Incises- or an approach called “poïetique externe”, that is to say by reconstituting with sketches processes of composition (early works, Dérives 2, Domaines, Dialogue de l’ombre double, Anthèmes, Anthèmes 2).  The first part of this doctoral dissertation deals with Boulez’s esthetic evolutions. The two analyses in the second part – devoted to Domaines/Dialogue de l’ombre double and Anthèmes/Anthèmes 2 – aim at demonstrating in the light of the sketches the complexity and the rigour of Boulez’s reasoning when he composes, although the constituents seem apparently simple. I hope that this work will contribute to making clearer the gradual construction of Boulez’s language and the perception of his works.

Keyphrases: Boulez, analyse, music of the twentieth century, analysis, genetics, sketches
Les solidarités familiales à l’épreuve de la migration : enquête auprès de couples de Marocains à Montréal

In what follows, we take a look at the situation of immigrant families’ native from Morocco. By mobilizing notions such as ‘family solidarities’ (Pitrou, 1978; Dandurand and Ouellette, 1992), transnationalism (Glick Schiller and al., 1992 and 1995) as well as the work on existing links between social networks and conjugal roles modifications, we examine the impact of migration on three aspects: (1) the family dynamics, (2) the conjugal role redefinition and (3) the preservation of family relations in spite of the geographical distance. On the basis of 6 semi-directed interviews with Moroccan couples established in Quebec for at least two years, we noticed how the family relations and solidarities are remodelled to mitigate the distance and how friendships take a whole new function.

Keyphrases: immigration, Immigration, Conjugal roles, Transnationalism, Family solidarities, Social networks, Quebec, Morocco
L’information de localisation à Montréal : une exploration

This master’s thesis is an exploratory research on localization experiences lived in Montreal’s urban space by subjects in relation to ‘location’ information. Localization is a spatial orientation process where a place’s location in space is a problem to be solved. This exploration is based on a theorization of information proposed by Bateson (1972) as well as on a development of the concept of apparatus (dispositif) by Belin (2002) and Agamben (2007) following Foucault’s; localization being an exploratory empirical concept. The localization process is investigated regarding its media character: location information is a medium that, being a result and a cause of action, shapes this process that is driven by effort. An ethnomethodological fieldwork is enacted by empirical observations and qualitative interviews that permit to identify certain conditions that make possible, in everyday life, relations between location information, urban space and a subject. Being mostly lived regarding actual, future or past movements, localization is thus conceptualized as wayfinding: the act of determining which path or trajectory to follow to get from point A to point B. This master’s thesis is actually an open problematization that aims to explore and identify some issues that are at the heart of localization processes in Montreal’s urban space. If “[t]he human act par excellence”, as put forward by André Leroi-Gouhran (1993 [1965]) “is perhaps not so much the creation of tools as the domestication of time and space” (p. 313), the fact that we dwell in a certain time and in a certain space is a problematic relation of trust (confiance) in itself. The living and the non-living inhabit spaces that are continuously transformed by their mutual determination. Starting from the observation that the built environment is deploying itself while being produced and developed (aménagé) in dispositions where some of our gestures are delegated, is it possible to consider being free without trusting?

Keyphrases: Information, Disposition, Exploration, Wayfinding, Medium, Effort, Confiance, Location, Localization, Everyday life, Trust, Delegation
Influence et usage de la mémoire dans la vision officielle française de
l’Allemagne réunifiée (1989-1995)

This dissertation analyzes references to history and, a fortiori, to memory in the official French discourse during and after German unification. Partly because of history, the definitive end of the post-war years and the return of German diplomatic sovereignty caused concern in France, and revived the resolve to contain German influence in the European community. In order to understand the role played by memory in French diplomacy, this dissertation assesses how French leaders used the past as an instrument of foreign policy, and to what extent it influenced the French vision of German unification. It shows that the understanding of the past complies, in all its expressions, with France’s European policy. Furthermore, it confirms that France seized this turning point to structure a European space appealing to the universalist principles stemming from the French Revolution, which, it was hoped, would henceforth be carried by the French-German couple. The invention of tradition and the metaphoric use of the past echo a concern to foster Franco-German reconciliation and are essential to the creation of an historical patriotism on which to build a common European civic and legal identity. Entirely oriented towards the promotion and justification of the European future, official memory distorts some historical facts in order to exorcise the present of a cumbersome past. Rather than an end in itself but a means deferring to the national interest, this representation of the past shows the limits of the official memory.

Keyphrases: France, Official memory, National identity, German Reunification, Foreign policy, International relations, Germany, European identity
La quétiapine dans le traitement des troubles liés à l’utilisation de substances psychoactives

Background: Substance use disorders (SUDs) are associated with a variety of psychiatric disorders and mood and behavioral instability. Growing evidence suggests that the atypical antipsychotic quetiapine may be useful in the treatment of SUDs. The primary objective of the current open-label trial was to examine the effects of quetiapine on SUD outcomes in patients entering detoxification. Methods: Thirty-three nonpsychosis SUD patients participated. Patients received quetiapine for a 12-week beginning in detoxification. Craving, quantities used and psychiatric symptoms were evaluated on baseline and at end point. Results: Out of 33 recruited patients, 26 completed > 9 weeks of treatment. Last observation carried forward (LOCF) analyses revealed that craving, SUD severity and quantities used improved during the study. Psychiatric and depressive symptoms also improved. Conclusions: Our results cannot be attributed per se to the pharmacological effects of quetiapine owing to the open-label design of the study, the small sample size involved and the fact that patients were involved in an intensive therapy program. Nevertheless, our results indicate that quetiapine may be helpful for the treatment of SUD patients entering detoxification. Controlled studies are warranted to determine whether these results are quetiapine-related.

Keyphrases: atypical antipsychotic, detoxification, psychiatric symptom, quetiapine, substance use disorders
Évaluation de la fréquence des micronoyaux et du potentiel clastogène et/ou aneugène du benzo-a-pyrène suite à une exposition in vitro des lymphocytes humains

Benzo-a-pyrene (BaP) is a known human carcinogen, contaminating all spheres of our environment. In human cells, BaP can induce various genotoxic effects on DNA, such as micronuclei (MNs) and chromosomal aberrations (CAs). MNs and CAs are measured in human lymphocytes in vitro exposed to low BaP concentrations, taken from 20 young healthy non-smoking subjects. Following BaP exposure, MN frequency increases significantly and shows a non-linear dose-response curve, suggesting the induction of detoxification process and/or DNA repair. Also, interindividual and sex differences in BaP-induced genotoxic damages are present. CA test shows that chromosome breaks increase significantly in cells exposed to BaP even at low concentrations. Combined to the observed MN frequency increase, our results confirm the clastogenic properties of BaP, as already reported in literature. In addition, fluorescence in situ hybridization (FISH) on MN using a pancentromeric probe is done to assess MN content. FISH reveals that most BaP-induced MNs contain centromeres, and specifically three or more centromeres. This difference is significant when compared to the unexposed condition, and suggest presence of an aneugenic effect.  Clastogenic effect of BaP is associated with initiation step of carcinogenesis, while the aneugenic effect would link it with cancer progression. These results could be particularly important because exposure to BaP and other member of its chemical class usually last for decades (smoking, air pollution, etc.), and need to be confirm in future studies.

Keyphrases: Progression, Cancer, Genotoxicity, Chromosome aberrations, Fluorescence in situ hybridization (FISH), Pancentromeric probe, Centromeres, Non-linear dose-response curve, Interindividual differences, Sex differences, Progression, Cancer
Impact de la maladie du greffon contre l’hôte sur la reconstitution immunitaire suite à une greffe de moelle osseuse allogénique

Allogeneic hematopoietic stem cell transplantation (SCT) is an effective treatment for numerous types of haematological malignancies. However, graft-versus-host disease (GVHD) remains the major cause of morbidity and mortality following SCT. GVHD is associated with poor immune reconstitution and its adverse effect on T cell regeneration greatly exaggerates the immunodeficiency normally associated with SCT. As a result, patients experiencing GVHD present deficit in T cells that can last for several years.   Our laboratory has demonstrated that elevated systemic IL-7 found during lymphopenia can interfere with the capacity of dendritic cells (DC) to support the homeostatic proliferation (HP) of CD4+ T cells. Since IL-7 levels are also elevated during GVHD, we hypothesized that IL-7 signaling in DC could also contribute to diminished T cell reconstitution in this setting. We used the well describe GVHD mouse model C57BL/6 (B6) into B6D2F1 to study the contribution of IL-7 signalling in DC on CD4+ T cell regeneration during GVHD. To regenerate a peripheral niche permissive for CD4+ T cells HP, we transplanted B6D2F1 mice with bone marrow (BM) from B6 IL-7Rα-/- mice. Finally, GVHD was induced with 1x106 of alloreactive B6 T cells. In control mice transplanted with IL-7Rα-/- BM cells, CD4+ T cells HP is efficiently supported. In contrast, CD4+ HP is completely abrogated in GVHD mice despite the presence of a peripheral niche that does not signal IL-7. Loss of CD4+ HP during GVHD was associated with diminished number of DC. Using an in vivo cytotoxic assay, we demonstrated that B6 DC can be eliminated by alloreactive B6 T cells when these cells developed into B6D2F1 hosts.  In conclusion, our data demonstrates that the immunosuppression associated with GVHD is in part related to the elimination of donor-derived DC by donor alloreactive T cells.  Therefore, we postulate that loss of DC, and not IL-7 signaling in DC, represents the limiting factor that contains CD4+ HP during GVHD.

Keyphrases: GVHD, GVHD, immune reconstitution, lymphocyte T CD4+, CD4+ T cells, dendritic cells, homeostatic proliferation
Étude fonctionnelle de l’opéron fimbriaire stg de Salmonella enterica sérovar Typhi

Salmonella enterica serovar Typhi (S. Typhi) causes typhoid fever in humans and is considered as an important health problem. Most of our knowledge on the pathogenesis of this bacterium comes from an enteric fever model in mice caused by serovar Typhimurium. Few studies have examined the virulence factors unique to serovar Typhi or the possibility that pseudogenes harbored in its genome may be functional. stg fimbriae are found only within the serovar Typhi genome and contain a premature TAA stop codon in the stgC gene encoding the usher responsible for the assembly of fimbrial subunits at the bacterial surface. Thus, the stg fimbria has been classified among the list of non-functional pseudogenes. The objectives of this study were to assess the involvement of stg fimbriae during interaction with human cells, and then to evaluate the importance of the stgC pseudogene in fimbrial biogenesis.  First, stg transcription was evaluated using a lacZ fusion. Despite low expression levels generally observed in rich medium, growth in minimal medium promoted transcription of the operon. Complete deletion of the stgABCD fimbrial operon from S. Typhi was performed by allelic exchange and was complemented on a plasmid. It has been shown that the presence of stg in S. Typhi, S. Typhimurium and E. coli contributes to increased adherence to human epithelial cells. In addition, the fimbriae seem to act as an anti-phagocytic structure during the interaction with macrophages. Thus, the stg operon appears to be functional despite its premature codon, as phenotypes were observed. The second part of this study involved testing the role of the stgC pseudogene in fimbrial biogenesis. Different variants of the operon were generated, cloned into an arabinose inducible vector, and then transformed into afimbriated E. coli strain ORN172. Translocation of the StgD subunit to the cell surface of the different mutants was evaluated using Western blot. This experiment demonstrated that stgC is essential for export of the StgD subunit to the cell surface. The addition of a 6-histidine tag at the C-terminal end of StgC confirmed the complete translation of the gene, despite the premature TAA stop codon. Peptide sequencing revealed the insertion of a tyrosine at this codon. A translational fusion with the green fluorescent protein demonstrated that approximately 0.8% of the mRNA can be translated to allow full production of the usher.  This project allowed characterization of a virulence factor unique to S. Typhi and is a step closer towards better understanding of its pathogenesis mechanisms. This is the first demonstration in bacteria of the functionality of a gene which is interrupted by a premature TAA stop codon.

Keyphrases: Fimbriae, Stg, Salmonella enterica serovar Typhi, Pathogenesis, Pseudogene