NCube/papyrus huggingface dataset:
Développement d’un modèle in vitro de la barrière hémato-encéphalique

The blood-brain barrier (BBB), a central nervous system structure, is found in the cerebral capillaries. It represents a major obstacle for the drugs that have to reach the brain in order to exercise their pharmacological effect. In the early stages of the drug development, in vitro cell models are used to evaluate the brain permeability of new drugs. Models assembled using primary endothelial cells (ECs) isolated from mouse brain capillaries are of particular interest for research, as for their ease of obtaining and relevance for the drug screening. Thus, the goal of this project was to build and characterize a primary mouse monolayer model. At the same time, a murine b.End3 cell line monolayer model was investigated. The evaluation of these models was based on the TEER and fluorescent marker permeability values, as well as on the presence of the BBB hallmark proteins. The model validation was established by the correlation of the permeability data obtained with the in vitro model and the data obtained in mice (in vivo). As a result, the primary mouse model showed superior monolayer integrity and higher expression of the tight junction and membrane transporter proteins when compared with the bEnd.3 cell line model. The in vitro/in vivo correlation of the primary model resulted in r2 = 0.765 compared to the bEnd.3 model with r2 = 0.019. This research work shows that the primary monolayer mouse model is a simple and reliable model for predicting the drug permeability across the BBB.

Keyphrases: corrélation IVIVC, logBB, Blood-brain barrier, mouse brain microvascular endothelial cells, primary cell culture, bEnd.3 cell line, drug permeability, log BB, drug screening, IVIVC, in vivo permeability, Transwell®-type model
La signalisation du Brain-Derived Neurotrophic Factor et ses récepteurs dans les plaquettes

The Brain-Derived Neutrophic Factor (BDNF) is a growth factor that was initially discovered in the brain. BDNF has both an autocrine and a paracrine role in neurons and its release and signaling mechanisms have been extensively studied in the central nervous system. Surprisingly, large quantities of BDNF have been reported in circulation, where it is essentially stored in platelets with concentrations reaching 100-1000-fold those of neurons. Despite this abundance, the function of BDNF in platelet biology has not been explored. Thus, this project sought to investigate the effect of BDNF on platelet function and the mechanisms underlying platelet responses to BDNF. In washed platelets, BDNF induced complete biphasic platelet aggregation that in part relied on amplification from secondary mediators. The low-affinity agonist neurotrophin-4 and an activating antibody raised against the canonical BDNF receptor TrkB induced similar platelet responses, implicating TrkB. Platelets express, both at their surface and in their intracellular compartment, a truncated form of TrkB lacking a tyrosine kinase domain. The BDNF-induced aggregation of washed platelets was prevented by inhibitors of the Rac1, PKC, and PI3K/Akt. Platelets exposed to BDNF secreted pro-angiogenic and pro-inflammatory cytokines, which may play a role in maintaining vascular homeostasis. Finally, in platelet-rich plasma, exogenous BDNF failed to induce aggregation and BDNF immunoprecipitates contained α2-macroglobulin immunoreactivity. Hence, platelets are rich in BDNF, which induce platelet aggregation via TrkB activation. The restriction of BDNF bioavailablility by plasma protein binding may serve to target BDNF-mediated platelet activation to sites of vascular injury.

Keyphrases: BDNF, Platelets, Aggregation, TrkB, Tyrosine kinase, Signaling
Le développement de l’autonomie professionnelle d’infirmières nouvellement diplômées sur une unité de soins intensifs

The barriers in transition-to-practice for newly graduated nurses on intensive care units has been well documented. Independent professional practice is, in particular, one of the barriers shared by newly graduated nurses integrating an intensive care unit. This research aims to explore the perceptions of newly graduated nurses and preceptors regarding the professional autonomy development of the newly graduated nurses in a nursing residency program on intensive care units. Nursing residency programs were developed in order to facilitate transition-to-practice of newly graduated nurses. In these programs, the evaluation that assesses clinical competence development can be primarily based on the newly graduated nurse’s autonomy. However, few studies focus on the development of professional autonomy of newly graduated nurses. As study framework, a model that includes Benner's stages of clinical competence (1982), Tardif's competency assessment approach (2006) and a definition of professional autonomy as suggested by Létourneau (2017) is proposed. By conducting a descriptive exploratory study, semi-structured individual interviews collected the data from newly graduated nurses (n=6), while preceptors (n= 4) shared their perceptions during focus groups. Content analysis by Van der Maren (1996) was used for data analysis. The results include the barriers encountered in the early career of the newly graduated nurses in critical care setting, a definition of professional autonomy and the influences of the newly graduated nurses’ professional autonomy development. The influences of the newly graduated nurses’ professional autonomy development and the definition of professional autonomy have been linked in a concept map. Considering these findings, implications for practice, research, education and management in nursing were made.

Keyphrases: newly graduated nurses, professional autonomy development, professional transition-to-practice, intensive care unit, preceptors
Des personnes à part entière? Ethnographie auprès de résidents atteints de troubles neurocognitifs majeurs au stade avancé en centre d'hébergement

The thesis focuses on the daily lives of people with Alzheimer's or other types of dementia, who have reached the very advanced stages (no longer able to express themselves verbally) and who reside in long-term care homes (CHSLD). Mobilizing an interactionist framework, the thesis revolves around the concept of personhood, trying to grasp if and how these vulnerable residents are considered as persons in their own right. The proposed conceptualization of personhood includes three dimensions: recognition of a status as a person; the recognition of a unique individual identity; and the adaptation of the intervention approach, centered on the person. Methodology is based on an 18-month ethnographic approach that draws on 3 main sources of data: 1) participant observation in the form of individual pairing to 8 residents, totaling nearly 200 hours; 2) photographic documentation of accompanied residents and their daily lives (more than 80 photos); as well as 3) semi-structured interviews with 7 relatives and 13 staff members. Results highlight an organizational context marked by insufficient staffing and increased workload, a reality that translates into scarce social contacts outside the episodes of care for residents with severe Alzheimer's. The personhood of these residents are deeply impressed by the uncertainty and ambivalence of the people around them (relatives and staff members) about their status as a person - and even as "living". The thesis proposes a typology of identity in advanced dementia, which comes in various combinations of "pre-dementia identity" (the person we have always known) and "current identity", which is marked by losses but which can also reveal to attentive observers very unique personality and needs. The thesis contributes to theoretical knowledge around the concept of personhood in advanced dementia and to rethink possible interventions with these residents in terms of individual support and presence. It also addresses the issue of the end of life of these citizens, particularly in connection with the ongoing social reflections around the access of incapable people to medical assistance in dying.

Keyphrases: Alzheimer, Personhood, Dementia, Long term care, Identity, End-of-life, Ethnography
Longitudinal effects of an optic nerve injury on visual behaviour

Disease or trauma to the visual system can cause long-term damage and severe visual deficits. However, recent research has turned to neural plasticity as a means to recover functional vision despite anatomical damage. To understand the involvement of neural plasticity and reorganization following a deficit, the present thesis investigated the spontaneous recovery of visual functions over time using behavioural tests in mice. Specifically, a partial optic nerve crush (pONC) was induced with two injury intensities, while still allowing for residual vision from surviving retinal cells. Behavioural assessments of visual functions included the optomotor reflex test, which measured the mouse’s tracking reflex in response to moving sinusoidal gratings, while the visual cliff test evaluated depth avoidance behaviour by simulating a cliff to observe the animal’s perception of depth. The tests were performed once before the injury, then at multiple time points up to 28 days. Retinal ganglion cell survival was subsequently quantified. Results showed that the high-intensity pONC led to a complete loss of visual acuity and depth avoidance, with no improvement in the following 28 days, whereas the low-intensity pONC showed a partial recovery. There were fewer surviving cells after the high-intensity pONC, especially in proximal regions. These results show evidence of spontaneous recovery of visual functions, but only with a certain amount of cell survival.

Keyphrases: Visual Recovery, Behaviour, Visual Deficit
Étude longitudinale d’un modèle murin de dystonie progressive causée par un gain de fonction du récepteur bêta de l’acide rétinoïque

We previously described several patients with a severe and progressive form of early-onset dystonia who carried de novo mutations in the retinoic acid receptor beta gene (RARB). RARB is a transcription factor that is activated upon binding to retinoic acid (RA), whose signaling is required for proper development of the brain. Transfection studies indicate that these de novo mutations increase RARB transcriptional activity, suggesting that they confer a gain-of-function (GOF) propriety to the protein. Dystonia is typically explained by some dysfunction of the striatum, a region where RARB is predominantly expressed. Interestingly, loss of Rarb function in mice leads to a reduction of striatonigral neurons and motor abnormalities, suggesting a disruption in early development of striatal circuits. We hypothesized that the motor impairment of patients with RARB GOF mutations is caused by increased RARB signaling in the striatum, possibly disrupting homeostatic control of the same pathways as those affected by decreased Rarb signaling. Using CRISPR-Cas9 technology, we generated mice carrying the mutation p.R394C, which is homologous to the GOF mutation p.R387C found in several patients. These RarbR394C/+ mice show locomotor impairments reminiscent of that of other mouse models of dystonia, along with a decreased striatopallidal neuronal population. Our data suggest that GOF mutations in RARB induce dystonia by disrupting striatal dopaminergic signaling necessary for functional equilibrium. This work might also shed light on common neurodegenerative disorders of the basal ganglia including Huntington’s and Parkinson’s disease, in which RA and RARB signaling appear to be compromised.

Keyphrases: Striatum, Retinoic acid, Dystonia, Gain-of-function, De novo mutation
Création d'un univers fictif cohérent en musique: la narrativité non linéaire au sein d'un corpus d'oeuvres

This thesis is the outcome of five years of doctoral studies at the University of Montreal. It presents the theory behind a cycle of eleven autonomous narrative instrumental pieces, following the definition of cycle as defined by researcher Anne Besson in her book “D’Asimov à Tolkien : cycles et séries dans la littérature de genre.”  The goal was to create a coherent and unified fictional universe that explores the concept of narrative chronology in music. The pieces were composed in a different order than the one in which the events of the story occur. It allows us to explore the idea of prequel and sequel in music. Originally composed for the concert hall, for ensembles ranging from chamber music to symphonic orchestras, they were afterwards adapted to be recorded and edited in a studio, allowing the composer to explore an array of new compositional techniques.  Presenting many theoretical concepts such as narrativity (in general and pertaining specifically to music), the cyclic concept in a body of works and also the definition of a fictional universe, this thesis will analyze these eleven works while suggesting possible solutions for bringing processes that occur frequently in literature and film to the world of music.

Keyphrases: Composition, Music, Cycle of works, Fictional universe, Narrativity, Analysis, Chronology
Notes de programme : une histoire, des pratiques et de nouveaux usages numériques

Since their appearance in the mid-nineteenth century, program notes, sometimes containing detailed information on the works that are about to be performed, have continued to meet audiences needs during concerts. They respond to a wide range of needs: providing intelligible comprehension tools for laymen and laywomen, who discover the music of the past and of the present, while arousing the curiosity of well-accustomed listeners, who increase their knowledge and cultivation. This goes for program notes as well as other music appreciation tools, torn between the desire to make classical music accessible to all and, on the other hand, the rigorous approach to musicology that is expected from connoisseurs. In this thesis, we combine both theory and practice. In addition to an inquiry, conducted in October 2017 as part of three concert nights at the Orchestre symphonique de Montréal (hereafter, OSM) – an inquiry which gives us an idea of how program notes are regarded by concert audiences –, we will display a series of short open educational videos that we produced for the OSM, during the 2015-2016 season. The work necessary for these new digital tools is partly based on the analysis of a large body of former program notes from which we have identified a number of trends and specific cases. The results of the inquiry show that the OSM’s audience, far from being homogeneous, is made up of listeners who bear very different expectations. According to many, the program notes are considered appropriate for one’s concert experience. However, they may also spring critical reactions among concertgoers: either too detailed, tedious for some, or somewhat dull for others. Although audience members have different musical backgrounds and scales of knowledge, both novices and connoisseurs seem to share a common interest in the music itself, which needs to be explained through means of analysis. This interest is being fulfilled by program notes, in line with the requirements of musicological research. The question remains: how can one describe a work of music in order to meet the needs of everyone? In this thesis, we try to find appropriate answers to this matter.

Keyphrases: Program notes, Listening guides, Popularization, Music appreciation, Open education, Public outreach, Elite culture, Cultivation, Médiation culturelle
Générateurs de nombres aléatoires modulo un grand entier, dont l’uniformité est assurée

This thesis is about linear random number generators with a large integer modulus. It is essential to be able to check that a generator has good properties in Monte-Carlo simulation. The generator family studied here produces points that possess a well known lattice structure that can be studied to assess the uniformity of these generators. The present work is motivated by the update of the LatMRG software which studies the lattice structure of the aforementioned generators.  This thesis first presents the different types of generators the software considers. It explains how they can be used to produce random numbers and how to study their period length. It then presents equivalences between some members of this family that are used to simplify LatMRG.  It then covers the lattice structure. The thesis describes what it is and how to characterize it. It describes the characterization of the lattice structure for the considered generators. From that, it presents a few algorithms that extract information on the uniformity of generators.  At last, the thesis describes the LatMRG software. LatMRG contains both an executable program and a library. The thesis presents both their purpose and their functionalities. It describes upgrades of the software that aim to simplify its usage. Along with the software description are a few examples that serve to illustrate the flexibility and future research avenues.

Keyphrases: random numbers, lattice structure, rng, Monte-Carlo simulation
L’évolution du terme « Métis » chez le Conseil national des Autochtones du Canada et l’Alliance laurentienne des Métis et Indiens sans statut entre 1971 et 1982

Between 1876 and 1982, Métis were excluded from federal Indian policy, as they were not recognized as indigenous owing to the discriminatory and assimilationist clauses within the Indian Act. However, numerous spaces emerged for the recognition of the indigenous nature of the rights and identities of Métis and non-status Indians (MNSI) amid the creation of the Native Council of Canada in 1971 and the repatriation of the Canadian constitution in 1982. Among these were the creation of MNSI representative organizations across the country, the funding of historical and legal research for land claims, and lastly, the recognition of Métis rights as an Aboriginal people within the constitution.  Within the scope of these spaces and the pressing context of land claims and constitutional repatriation, the NCC and the Laurentian Alliance of Metis and non-status Indians (LAMNSI) highlighted different ideas and definitions on the rights and identities of MNSI people in Canada in order to be recognized by the state. For this reason, the CNAC valued an ethno-national concept of Métis that was centered around the Red River community. Consequently, LAMNSI argued that there was no such thing as a Métis Nation in Quebec or in eastern Canada. Instead, LAMNSI affirmed that its members belonged to the historical, cultural and familial realities of the First Nations.

Keyphrases: Métis, Constitution, Non-status Indians, Laurentian Alliance of Metis and non-status Indians, Native Council of Canada, Identity, Indigenous, Land claims
Émotions lumineuses : la poésie de la lumière en mouvement

This thesis, presented as a research-creation project, sounds the power of the light and the shadow in movement. Inspired by the writings of Henri Alekan and Fabrice Revault d’Allonnes, we will point out a work method used to shape the light, that rests upon two essential steps: the first step is called éclairement, and calls on a hiérarchisation of the light sources. The second step is one of lumination, that is equivalent to a dramatisation of the light. The method, considered in a classico-baroque context, will open the door to some analysis of the light’s variations. We will explore two techniques used by cinematographers: the conception of a light «path», and the changement à vue. We will study these two techniques through the work of various cinematographers, such as Vittorio Storaro and Darius Khondji. We will apply these two techniques in a creation that is linked to this thesis, to better comprehend the subtleties of the light in movement, and understand the difficulties that come along with the practice of cinematography. Thus, the creation will be a true exploration for me, and a practical and theoretical learning process about the possibilities and the complexity of light and shadow. This stammering and hesitating approach intends to understand the poetic potential of the light and the shadow.

Keyphrases: Lumination, Éclairement, Hiérarchisation, Dramatisation, Baroque, Light, Shadow, Lighting, Poetry, Resonances
Intervention de pratique réflexive auprès de préceptrices pour accompagner 
le développement du raisonnement clinique infirmier des débutantes aux soins intensifs

Clinical nursing reasoning is a springboard to the safe delivery of quality care and services (Goudreau, Boyer, et Létourneau, 2014). Preceptorship programs have been designed to facilitate the development of clinical reasoning of beginner nurses. However, these programs do not necessarily provide the full opportunity to support the professional development of nurse preceptors . As it has been pointed out in scientific literature and demonstrated during the internship, nurse preceptors need support in fostering the development of clinical nursing reasoning. As part of a master’s degree in nursing, a reflective practice intervention was developed and tested with preceptors from an intensive care unit, in order to better equip them to support the development of clinical reasoning for beginners. This reflective practice intervention guided by the reflexion model of Huard et al. (2016) and Knowles' andragogical principles (1984), consisted of four activities, three of which were in the form of an interactive discussion group. This reflective practice intervention enabled the preceptors to become more aware of their preceptorial practice to potentiate the opportunities for the development of clinical reasoning for beginner nurses in intensive care. This reflective group practice intervention appears to have been an effective professional development strategy, which should be more widely recognized in clinical settings to improve and enhance the quality of care. Continuous professional development activities through reflective practice place each learner at the center of their learning and aim not only to support the preceptors, but also to contribute indirectly to the advancement of the nursing profession.

Keyphrases: Formation continue
Perceptions des membres de l’équipe interprofessionnelle face à la présence de la famille lors de la réanimation d’un proche

Background. Cardiopulmonary resuscitation is emotionally charged for the members of the interprofessional team, but also for the patient's family. The family wants to be present with their loved one at this critical time. However, this inclusion of the family is not widespread in the hospital environment today. Different perceptions and barriers emanate from this practice. Aim. Identify the perceptions of interprofessional team members regarding the presence of the family during emergency department resuscitation maneuvers in order to promote this practice. Methodology. An integrative review of the literature according to the method of Whittemore and Knafl (2005) was conducted. Scientific articles were retrieved from the Cumulative Index to Nursing Information and Allied Health Literature (CINAHL), PsycINFO, Medline, Web of Science, Cochrane and Joanna Briggs Institute (JBI) databases. Results. Of the 1,910 potential articles identified, 23 writings were included. The integrative review highlights many benefits and risks perceived by nurses and physicians regarding the inclusion of the family during resuscitation maneuvers. One of the perceived benefits is that the family provides emotional support to the patient. Family presence also strengthens the family/caregiver bond. Factors affecting the interprofessional team's level of confidence in the inclusion of the family were also identified. However, the lack of studies on the perception of all members of the interprofessional team regarding the inclusion of families when resuscitating a loved one was noted. Conclusion. The results of this integrative review of the literature provide a starting point for reflection on the development of a model of care organization aimed at improving practices by promoting the inclusion of families.

Keyphrases: Nurses, Health professionals, Resuscitation, Emergency, Family, Integrative review