NCube/papyrus huggingface dataset:
Évaluation pharmacoéconomique des thérapies efficaces et dispendieuses en prévention des maladies cardiovasculaires

Cardiovascular diseases (CVD) have a high prevalence worldwide and are considered the second leading cause of death in the Canadian population. Statins are recognized to be the gold standard treatment in the prevention of CVD. However, statins are not suitable for all patients, potentially because of side effects and lack of efficacy. With the advancement of science, new therapies are emerging in the cardiovascular field. Inhibitors of proprotein convertase subtilisin-kexin type 9 (iPCSK9) have been shown to be effective in reducing cardiovascular events. However, these therapies are expensive. This article-based thesis aims to explore the pharmacoeconomics of expensive therapies that have demonstrated significant clinical efficacy in the preventive treatment of CVD. Pharmacoeconomics is an evaluation tool for decision-makers with the objective of optimizing the use of human and financial resources. In the first publication, we evaluated the maximum effectiveness of lipid-lowering therapy from cardiovascular risk grids. According to our results, this maximum expected benefit fluctuates between 0.46 and 0.66. In the second publication, we estimated the effectiveness of an expensive therapy. At the time of our second publication, the results of the randomized controlled trial evaluating the clinical efficacy of iPCSK9 had not been published yet. Therefore, we used a Markov model to estimate the necessary clinical efficacy of PCSK9 inhibitors to reach two arbitrarily selected willingness-to-pay (WTP) thresholds. Our results showed that an efficacy of 0.58 and 0.78 were necessary to reach WTP thresholds of $50,000 and $100,000 per quality-adjusted life years respectively. Once the clinical efficacy of iPCSK9 was published, we evaluated their cost-utility. This was the object of our third article and a new simulation method named Discretely Integrated Condition was used. Our results suggested that at the current price, the PCSK9 inhibitors were not cost-effective. Following the results presented in this article-based thesis, it would be of interest to integrate the option of a hypothetical genetic test into the pharmacoeconomic model. This genetic test would be able to identify good responders in order to optimize the treatment of each individual patient.

Keyphrases: Markov, Pharmacoeconomic evaluation, Health economics, Cardiovascular diseases, Discretely integrated condition event, Statins, PCSK9 inhibitors
Influence of the transcription factor Ikaros on neutrophil response during acute inflammation

Neutrophils are critical for acute inflammatory responses initiated by infection or tissue injury. Multiple inflammatory genes and signaling pathways are activated rapidly to regulate neutrophil functions. Ikaros is a critical transcription factor involved in the regulation of myeloid cells differentiation. Transcription analysis of the hematopoietic cells in the absence of Ikaros indicates differences in expression of genes encoding signaling factors. However, the impact of Ikaros on signaling mechanisms in myeloid cells during inflammation remains to be defined. The aim of this study was to define whether the lack of Ikaros expression could perturb signaling and thereby, neutrophil function/response during inflammation.  We studied purified neutrophils from the bone marrow of WT and Ikaros+/- mice. We found that the expression level of Ikaros is important and governs neutrophil apoptosis, NETosis, myeloperoxidase activity and ROS production in response to bacterial DNA. We also performed in vivo experiments using a mouse model of severe pneumonia. We show that partial deletion of Ikaros (Ikaros+/- mice) is associated with impaired elimination of bacteria. To define how the crippled expression of Ikaros could affect signaling in neutrophils, we performed a high-throughput microarray to identify variations in protein kinase activity. The microarray data suggest that multiple signaling pathways, including the P38 MAPK pathway, could be affected by Ikaros. Accordingly, we employed selective kinase inhibitors to further define the importance of these kinases in neutrophil function. Finally, our results indicate the critical role of Ikaros in the regulation of Toll Like Receptor 4 and 9 as well as the cytosolic DNA sensor IFI204 in neutrophils. This study provides novel information on the role of Ikaros in the regulation of neutrophil functions and a rational basis for the development of novel therapeutic approaches targeting Ikaros for the treatment of patients with infections, and sepsis in particular.

Keyphrases: Ikaros, Neutrophil, Acute Inflammation, Innate Immunity, Singling
dSTRIPAK régule les fonctions catalytiques et non-catalytiques de la kinase Ste20 Slik

Many cellular and molecular mechanisms are involved in the structural changes (morphogenesis) taking place during embryonic development. Indeed, the cytoskeleton is dynamically modified by intracellular signaling cascades, controlling cell morphogenesis  during division or epithelial organization. Signal transduction mechanisms establishes homeostasis during morphogenetic processes. The cell cortex, composed by plasma membrane and underlying cytoskeleton meshwork, is responsible for integrating cell shape changes and organizing structural elements required for intercellular communication. The composition of the cell cortex is thus constantly changing in response to morphogenetic needs. However, the signaling network controlling this cortical plasticity is still unclear.  This work has identified a new signaling pathway involved in cell cortex organization. The laboratories of Dr Carréno and Dr Hipfner use Drosophila as a model organism to study cell and tissue morphogenesis. Dr Carréno and Dr Hipfner had previously found that Ste20 Slik kinase was responsible for dMoesin activation by phosphorylation. dMoesin acts as a cross-linker between the cytoskeleton and the plasma membrane. This way, activation of dMoesin by Slik controls cortical stability during mitosis and epithelial integrity in Drosophila. This research project found that dSTRIPAK phosphatase activity promotes cortical localization of Slik in order to activate dMoesin at the plasma membrane. In addition, it showed that dSTRIPAK, as Slik and dMoesin, controls mitotic morphogenesis and epithelial tissue integrity.  On top of that, Dr Hipfner has previously shown that Slik induces growth signaling at distance and independently of its catalytic activity. My research has led to the discovery that Slik is located along specialized signaling filopodia, called cytonemes. In addition, our data showed that Slik lengthens cytonemes, while dSTRIPAK is necessary for their biogenesis and signaling function. Slik and dSTRIPAK thus control tissue growth during the embryonic development of Drosophila. We have not determined the molecular mechanisms involved in the formation of cytonemes by dSTRIPAK/Slik yet.  Together, our research projects led to the discovery that the dSTRIPAK complex regulates the catalytic and non-catalytic functions of Slik. We have thus identified a new signaling pathway controlling cell and tissue morphogenesis, through the cytoskeleton and intercellular communication. These processes are essential for maintaining homeostasis during embryogenesis. However, alteration of these morphogenetic processes can cause tumorigenesis. Our research might lead to the exploration of new anti-cancer therapeutic avenues.

Keyphrases: STRIPAK, Sterile20 kinase Slik, Morphogenesis, Mitosis, Cytoskeleton, Plasma membrane, dMoesin (ERM), Cell cortex, kinase Sterile20 Slik
La dominance mycorhizienne en tant que facteur local déterminant des processus écologiques forestiers

Mycorrhizas, which involve plants and fungi, are probably the most important and widespread mutual symbioses in terrestrial ecosystems. Since most trees form arbuscular mycorrhizas or ectomycorrhizas that are ecophysiologically distinct from each other, it is useful to characterize forests according to their mycorrhizal dominance in order to measure their respective impacts on ecological processes. The objective of this thesis is to quantify the impacts of forest mycorrhizal dominance on the abiotic and biotic properties of the soil, which influence at the local scale two associated processes: the decomposition of organic matter and the maintenance of plant diversity. The forests studied have opposite mycorrhizal dominance exhibit distinct soil physico-chemical properties and microbial communities, but more similar vertical distribution patterns of microorganisms than expected. Decomposition is favored by organic matter in the upper soil layers, but also by the presence of the fungal network, especially when ectomycorrhizas predominate, illustrating the importance of the local environmental context. Establishment of arbuscular mycorrhizal tree may be limited by the combination of abiotic and biotic edaphic factors of the boreal forest, which is ectomycorrhizal-dominated, in contrast to forests with shared dominance between arbuscular mycorrhizas and ectomycorrhizas, where tree species diversity is favored at the community level. This thesis demonstrates the decisive role, at the local scale, played by mycorrhizal dominance on ecological processes, and raises the importance of soil biotic and abiotic heterogeneity to better understand the functioning of terrestrial ecosystems.

Keyphrases: Interactions plantes-sols, Plant-soil interactions, Microbial biodiversity, Saprotrophic fungi, Northern broadleaf temperate forest, Temperate-boreal ecotone, Sugar maple, American beech, Boreal forest, Carbon cycle, Climate change
Sexual desire, sexual behaviour and sexual distress in committed couples

Despite the central role they play in sexuality, sexual desire and sexual behaviour remain poorly understood in committed couples. The paucity of empirical results in this area contributes to the distance between research and clinical practice, and negatively impacts the quality of care offered to the many couples seeking help for sexual desire issues – the most common complaint in sex therapy.  The objective of the three articles in this doctoral research was to help address this gap by studying sexual desire within a relational perspective, working from the assumption that each partner’s wellbeing was influenced by that of the other partner, and that this influence was mediated in part by the couples’ sexual behaviour. Results from this research suggest that positive interactions during sex, such as self- and other-approach motives and genital and affective behaviours, are associated with greater sexual satisfaction and intimacy (study 1). In contrast, sexual difficulties such as low sexual desire are associated with restrictions in sexual behaviour and sexual dissatisfaction (study 2), and asynchronies between partners such as sexual desire discrepancy are associated with sexual distress (study 3). Furthermore, the third study begins to establish a direction and span to these associations, by suggesting that issues with sexual desire discrepancy are predictive of sexual distress from one day to the next, and that these daily associations are mirrored by more distal associations spanning a year or more. These results are consistent with recent research on emotional regulation in sexuality, and more specifically, with proposals that sexual desire plays a regulatory role in the couple, mediated by variations in sexual behaviour.  It is hoped that, beyond these conceptual contributions, this research will be of use to clinicians. In particular, these results support the use of therapies that focus on everyday interactions between partners to help couples struggling with sexual desire issues.

Keyphrases: Sexual desire, Sexual behaviour, Sexual distress, sexual satisfaction, sexual desire discrepancy
Étude fondamentale des interactions plasma-graphène dans les plasmas Argon/B2H6

The research realized in this PhD thesis focuses on the understanding of plasma-graphene interactions during exposure of polycrystalline graphene films to a low-pressure argon RF plasma containing diborane (B2H6). A particular attention is devoted to the kinetics driving the damage formation dynamics. In the case of a continuous, argon plasma, the absence of energy threshold for the production of ion-induced damage is demonstrated. This is explained by two-step etching, facilitated by the high number density of charged species in the H-mode of RF plasmas. Raman characterization of plasma-treated graphene films shows a wide distribution over the small area surveyed. In order to link these fluctuations to the initial state of graphene, Raman imaging (RIMA) is adapted to extract quantitative data on the state of graphene before and after plasma treatment. Subsequently, the temporal study of argon RF plasmas in the pulsed regime makes it possible to find operating conditions with a drastically reduced fluence of charged species compared to the continuous regime; in combination with RIMA studies, this allows temporally- and spatially-resolved investigations of plasma-graphene interactions. For the first time, a preferential self-healing of ion-irradiation damage at grain boundaries of graphene films is experimentally demonstrated. Moreover, by using several electrical and optical diagnostics of the argon plasma in the pulsed regime, it is possible to determine operating conditions in which either the ions, the metastables or the VUV photons emitted by the resonant states become the main energy vectors. From these experiments, the respective roles of each of these species in the physics of plasma-graphene interactions could be highlighted. Finally, the introduction of 5% of diborane into the argon plasma induces a radical modification of the physicochemical properties of the plasma. Exposure of graphene films to this highly reactive plasma reveals high boron incorporation with minimal ion and hydrogen damage.

Keyphrases: interactions plasma-graphène, synergie, plasma-surface interactions, polycrystalline graphene, synergy effects, self-healing at grain boundaries
Modification de films de graphène dans la post-décharge en flux de plasmas micro-ondes d’azote à pression réduite

This thesis project deals with the treatment of graphene films in the flowing afterglow of microwave nitrogen plasmas at reduced pressure. Various surface contamination considerations were found to be crucial for this work. For example, in the presence of hydrocarbons, the treatments in the different regions of the afterglow show distinct damage production, nitrogen incorporation and contaminant functionalization profiles. The aggressive treatment offered by the early afterglow results in the formation of amorphous graphene-hydrocarbon complexes responsible for a sharp increase in the nitrogen content (up to 49%) at moderate disorders (D: G = 1.3). For the treatments in the late afterglow, the hydrocarbons act as a protective layer, allowing a monotonic incorporation (up to 18%) with very low damage (D: G < 0.3). Nitrogenous species are found to be weakly bound so that transfer to an SiO2 substrate generates a significant loss (>80%) of the nitrogen content. Considerations of surface inhomogeneity of graphene films have motivated the development of a new analysis method of Raman maps obtained by hyperspectral imager. The study of Raman spectra at growth domain versus grain boundary has revealed a self-healing mechanism of grain boundaries linked to the anisotropy of the migration of carbon adatoms at the surface. The accumulation of these at grain boundaries leads to an emission of atoms responsible for the annihilation of Frenkel pairs. In nitrogenous plasmas, this mechanism is also found to be responsible for the selective incorporation of nitrogen into the growth domains of the graphene. For amorphous graphene, selective doping fades as the transport of carbon adatoms to grain boundaries, and therefore the accumulation essential to the self-healing process, becomes impeded. Finally, the surface recombination of nitrogen atoms and the de-excitation of metastable N2(A) are identified as the main agents defect generation in the nitrogen flowing afterglow. An incorporation model involving the formation of damage and adsorption of nitrogen atoms is proposed. In the presence of oxidizing species in the nitrogen afterglow, damage formation remains limited by populations of N and N2(A).

Keyphrases: reduced pressure plasmas, nitrogen flowing afterglow, spectroscopic plasmas diagnostics, graphene, material characterisation
The art of post-truth in quantum cryptography

Quantum Key Establishment (QKD) enables two distant parties Alice and Bob to establish a common random secret key known only to the two of them (i.e., unknown to Eve and anyone else). The common secret key is information-theoretically secure. Later, Alice and Bob may use this key to transmit messages securely, for example as a one-time pad. The QKD protocol guarantees the confidentiality of the key from an information-theoretic perspective against an adversary Eve who is only limited by the laws of quantum theory and can act only on the signals as they pass through the classical and quantum channels. But what if Eve has the extra power to coerce Alice and/or Bob after the successful execution of the QKD protocol forcing either both or only one of them to reveal all their private information (possibly also after one or several (classical) ciphertexts encrypted with that key have been transmitted between Alice and Bob) then Eve could go through the protocol and obtain the key (hence also the message)? Can Alice and Bob deny establishment of the key plausibly by revealing fake private information and hence also a fake key? Do QKD protocols guarantee deniability for free in this case? In this Thesis, we investigate this conundrum. In the rest of this document, we take an information-theoretic perspective on deniability in quantum key establishment protocols. We rigorously formalize different levels and flavours of deniability depending on which party is coerced, what the adversary may ask, what is the size of the fake set that surreptitious parties can pretend to be established, when the parties should decide on the fake key(s), and what is the coercer’s tolerance to less likely events and possibly also computational assumptions. We then rigorously define a general class of QKD protocols, based on an almost-perfect quantum channel, and prove that any QKD protocol that belongs to this class satisfies the most general flavour of deniability, i.e.,universal deniability. Moreover, we define a broad class of QKD protocols, which we call prepare-and-measure, and prove that these protocols are not deniable in any level or flavour. Moreover, we define a class of QKD protocols, which we refer to as fuzzy prepare-andmeasure, that provides a certain level of deniability conditioned on Eve being fair. Furthermore, we propose a hybrid protocol under which any QKD protocol can be at most existentially deniable. Finally, we define a class of QKD protocols, which we refer to as mono-deniable, which is either Alice or Bob (but not both) deniable.

Keyphrases: Edited Truth, Deniability, Quantum Key Establishment
Révéler par l’art les enjeux politiques et matériels de l’économie : la monnaie, la dette, le profit et la valeur vus à travers les matières premières dans trois performances de Marta Minujín (1985, 1996, 2017)

This thesis revisits a number of major economic themes through an in-depth analysis of three works of art. It seeks to interrogate the prevailing conception of the contemporary economy as an abstract domain detached from political concerns—a conception commonly found in art historical texts. The first chapter of this thesis reassesses the definition of the economy. I identify a set of theoretical principles that serve to legitimate the idea that economic objectives are neutral. In the second chapter, I build a theoretical framework at the crossroads of several bodies of thought in the social sciences and humanities, in view of putting forward a renewed conception of the economy, anchored in political and material considerations. I then turn to my analysis of three performances by Argentinian artist Marta Minujín. Taking a cue from the artist's approach, I use raw materials as a prism of analysis and reflection. I combine novel comparative analyses of works of art with a fresh re-examination of key moments in the history of capitalism, drawing on recent literature on world-systems analysis and ecological economics, among others. I also present extensive reflections on a number of important economic concepts, namely money, debt, profit and value. In so doing, I expose the polysemic nature of Minujín’s performances and highlight their capacity to reveal recurring political, territorial and material dynamics undergirding the economy. I explore the ways in which Minujín’s works overturn the traditional hierarchy of economic subordination all the while revealing its historical roots and present-day manifestations. Lastly, I show how Marta Minujín’s performances highlight and challenge the consensual deals and arrangements that guarantee economic profit-making.

Keyphrases: art, Marta Minujín, performance, economy, Marta Minujín, capitalism, performance, raw materials
La dévotion au Saint Frère André à l’Oratoire Saint-Joseph du Mont-Royal : ethnographie d’une religiosité populaire contemporaine

The religious landscape in Quebec has changed profoundly, even though the disaffection of the Catholic churches, some forms of devotion remain important, especially the devotion to Saint Brother André. Canonized by Pope Benedict XVI in October 2010, Saint Brother André is the first Canadian-born male Saint. He is responsible for the construction of Saint Joseph’s Oratory, the largest shrine dedicated to Saint Joseph in the world, and he is an important figure in Quebec. According to the Sanctuary’s data, every year, two million visitors visit the Oratory. These visitors have several profiles, they are either devout people from Montreal or the surrounding area, religious tourists, or pilgrims. This thesis deals with the devotion to Saint Brother André at the Saint Joseph Oratory of Mount Royal. The main objective is to understand the expressions and practices of this popular devotion as well as the experience lived by the devotees in this place of pilgrimage, using an ethnographic approach, which is based on a combined archival study of prayer intentions collected at the Oratory during the years 2010 and 2018. The ten observations made in the five places of prayer dedicated to Saint Brother André, the fifty interviews conducted with devotees and the study of about a hundred prayer intentions highlight the relationship of trust and friendship that people have with the Saint. This relationship is sustained by the perception of manifestations attributed to the divine, such as healing miracles, apparitions, and visions that, for the devotees, testify to the existence of an exchange of goods of charity between Heaven and Earth. This thesis shows the importance of the role of intercessor of Saint Brother André in the collective memory of Quebec, as evidenced by the historical relations that many families have developed with the Saint. Prayer is the first place of the encounter, the vehicle through which the devotees meet and communicate with Saint Brother André. As for devotional practices, they are expressed in many forms: relics, devotional spaces, statues, objects of piety, oil of Saint Joseph, images, worship, pilgrimages, etc. Since popular devotion is not controlled by the religious institution, it gives free rein to spontaneous religious expressions both in rituals and in votive writing.

Keyphrases: Saint, Intercession, Miracle, Devotion, Pilgrimage, Shrine, Saint, Prayer, Intercession, Miracle, Relics, Healing, Spiritual experience