Autonomie et consentement éclairé à la participation aux biobanques : entre fondements philosophiques de l’éthique de la recherche et de l'éthique de la santé publique

Ce mémoire de maîtrise tente de répondre à la question suivante : quelle est la valeur de l’autonomie dans le domaine de la recherche biomédicale, et plus particulièrement dans le contexte des biobanques? Pour éclairer cette question, nous étudierons le concept d’autonomie dans deux domaines d’éthique appliquée : l’éthique de la recherche et l’éthique de la santé publique. Depuis la deuxième moitié du XXe siècle, le respect de l’autonomie individuelle est un principe programmatique de l’éthique de la recherche. Or, sa conceptualisation a été accusée d’être trop individualiste pour répondre aux enjeux qui caractérisent la recherche en santé d’aujourd’hui. En éthique de la santé publique, au contraire, l’autonomie individuelle prend une place moins prépondérante et fait droit à des dimensions sociopolitiques de l’autonomie qui ont été négligées par le domaine de l’éthique de la recherche. Ces dimensions mettent en lumière le rôle des institutions dans la promotion de l’autonomie tout comme l’importance pour les individus d’avoir la possibilité de participer à l’élaboration des politiques de santé qui les concernent pour réaliser leur autonomie. Le cas de la recherche en contexte de biobanques sera l’occasion d’appliquer ces différentes conceptualisations de l’autonomie à un domaine de recherche en pleine expansion qui se situe au carrefour de l’éthique de la recherche et de l’éthique de la santé publique.This master's thesis attempts to answer the following question: what is the value of autonomy in biomedical research, and more particularly in the context of biobanks? To answer this question, we will study the concept of autonomy in two areas of applied ethics: research ethics and public health ethics. Since the second half of the 20th century, respect for individual autonomy has been a programmatic principle of research ethics. However, many authors consider this conceptualization to be too individualistic to respond to the challenges that characterize health research today. In public health ethics, on the contrary, individual autonomy takes a less preponderant role and acknowledges some socio-political dimensions of autonomy that have been neglected by the field of research ethics. These dimensions highlight the role of institutions in promoting autonomy as well as the need for individuals to have the opportunity to participate in the development of health policies in order to achieve their autonomy. Finally, the case study of biobanks will provide an opportunity to apply these different conceptualizations of autonomy to a rapidly expanding field of research located at the crossroads between research ethics and public health

Alteration in vascular function due to high intravascular pressure: arterial stiffness and the role of beta-adrenoceptors

Background: Hypertension-induced arterial stiffness is associated with high risks of morbidity and mortality. The sympathetic nervous system plays an important role in the control of cardiovascular function through beta-adrenoceptors (β-AR). The involvement of β-AR in the control of arterial stiffness in a state of hypertension and normotension was examined. Methods: Pulse wave velocity (PWV) was assessed within a narrow range of blood pressures in isoflurane-anaesthetized 13-14-week-old male spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats. Results: Baseline PWV was higher in SH (9.2±0.9 m/s) compared to WKY rats (6.7±0.4 m/s). The stimulation of β₂- but not β₃-AR reduced PWV in SH rats despite comparable reductions in blood pressure. Sodium nitroprusside infusions initiated a dose-dependent reduction of PWV in SH rats. Conclusion: The evidence suggests that a reduction in central vascular tone may play a key role in decreasing elevated PWV independently from reduction in blood pressure in a state of hypertension

Production du cannabis médical (Cannabis sativa L.) cultivé en hydroponie : impact de N, P et K sur la croissance, productivité et qualité

Le cannabis médical et récréatif (Cannabis sativa L.) est une industrie en pleine expansion au Canada depuis sa légalisation en octobre 2018. Cependant, le peu de connaissance scientifique sur la fertilisation est un enjeu important pour les producteurs afin d'obtenir de meilleurs rendements et d'offrir un produit de qualité. Cela se traduit souvent par une fertilisation excessive ou non adaptée à cette espèce, ce qui impacte la qualité des produits et engendre des coûts plus élevés de production. Le but de cette étude était donc, dans un premier temps, de caractériser les taux de prélèvement des éléments nutritifs du Cannabis sativa lors de la phase de floraison et, dans un second temps, de déterminer pour un génotype l'effet de N, P et K sur la croissance, la productivité et la qualité des inflorescences. Pour ce faire, nous avons réalisé deux expériences. La première expérience s'est déroulée chez un producteur autorisé (IsoCanMed Inc.) utilisant des tours verticales aéroponiques et où deux doses de N (150 et 250 ppm) ont été comparées et l'absorption minérale des plantes caractérisée au cours de la phase de floraison, et ce, pour 2 cycles de production par niveau d'azote. La deuxième expérience s'est tenue dans une serre de l'Université Laval et a permis d'étudier les effets de cinq concentrations de P (25, 50, 100, 150 et 200 ppm) et deux concentrations de K (175 et 250 ppm) pour des plantes cultivées dans un système hydroponique en eau profonde. Nos résultats ont démontré qu'une concentration élevée en N (> 150 ppm) a entrainé une surcroissance des plantes (hauteur des plantes), a diminué la teneur en THC des inflorescences (-9,5%), mais a permis d'augmenter la biomasse florale (+29%) d'un des deux génotypes étudiés. Des concentrations supérieures à 25 ppm de P et 175 ppm de K n'ont toutefois pas amélioré la productivité et la qualité des inflorescences. Les résultats obtenus ainsi que la caractérisation des taux d'absorption des éléments nutritifs au cours du développement de la plante nous ont permis de suggérer une fertilisation de référence en N, P et K pour des plantes en phase de floraison et cultivées dans un système hydroponique. Il serait toutefois intéressant de poursuivre ces travaux avec un plus grand nombre de phénotypes et sous différentes conditions lumineuses.Drug-type cannabis (Cannabis sativa L.) in a booming industry following its legalization in Canada in 2018. However, few scientific studies on the optimal fertilization is a main challenge for producers who aim to harvest high yields with a high cannabinoid content. Thus, this often results in the overuse of fertilizers or not well adapted fertilization that impact the quality and the cost of production. Thus, the aim of this study was to characterize the nutrient plant uptake during the flowering phase and to determine the impact of N, P and K on growth, productivity, and quality of the inflorescence. The first experiment was done within a plant factory at a licensed producer (IsoCanMed Inc.) who uses vertical aeroponic towers. Two levels of N (150 and 250 ppm) were used in two cycles for each treatment to identify their impact on Cannabis and to characterize the nutrient uptake throughout the flowering phase. The second experiment was conducted in a greenhouse located at Laval University in order to test five (25, 50, 100, 150 and 200 ppm) and two (175 and 250 ppm) concentrations of P and K, respectively, by using a deep-water system. Based on our results, N fertilization above 150 ppm resulted in an overgrowth (plant height), a reduction in THC content in the inflorescences (-9.5%), but an improvement in floral biomass productivity (+29%) for one genotype. Concentrations above 25 ppm P and 175 ppm K, however, did not improve the productivity and the quality of the inflorescences. The results obtained as well as the characterization of the absorption rates of nutrients during the development of the plant allowed us to suggest a reference N, P and K fertilization for flowering plants grown in a hydroponic system. However, it would be interesting to continue this work with a larger number of phenotypes and under different light conditions

The importance of egg size for the diversity of salmonids

Understanding the origin and nature of intra specific biodiversity enables us to better conserve and manage animal populations. Biological diversity is seen at different scales and for different traits such as behavior, morphology, physiology, and life history. Behavior is especially important since behavioral changes are believed to precede changes in morphology or physiology among fishes. Salmonids display great diversity in terms of behavior, life histories and morphology within and among populations. Thus, differentiation among populations and morphs has been related to the evolution of new species. Various genetic, environmental and ecological factors have been shown to be important for segregation of morphs, including competition for food or other resources, phenotypic plasticity and sexual selection. Recently, it has been suggested that the importance of epigenetic and maternal effects for intra specific diversity have been underestimated. I studied the short- and long-term effects of egg size on development, behavior, body growth and physiology in Arctic charr Salvelinus alpinus and steelhead trout Oncorhynchus mykiss. I also examined how domestication can affect egg size. Egg size was smaller in domesticated fish populations after accounting for female body size and age. Egg size was negatively correlated with embryonic development before hatching, i.e. embryos in small eggs developed more rapidly. At emergence, egg size was positively correlated with length and weight of first feeding progeny. Juveniles coming from larger eggs tended to feed more at the surface whereas juveniles coming from smaller eggs fed more on the bottom. These relationships and effects of egg size on embryos and first feeding fish were observed in both species in laboratory conditions. In Arctic charr there was a higher energy content per egg in larger eggs in both aquaculture and wild populations, and the total energy content per egg varied among populations. Behavior of Arctic charr at first feeding was affected by egg size, social environment and their interaction. At 300 days post fertilization, fish coming from different egg sizes differed in morphology and behavior: larger fish coming from larger eggs fed more at the surface than smaller fish coming from smaller eggs. Independently of their genetic origin large and small juveniles, coming respectively from large and small eggs, differed in body shape. This was most clearly seen in head and body morphology, e.g. larger fish were overall slimmer than smaller fish. The influence of egg size on behavior and morphology of Arctic charr varied with female parentage, indicating strong maternal x genetic interactions. In steelhead trout, both origin of fish and egg size were related with body growth of yearling fish reared under laboratory conditions: hatchery juveniles coming from small eggs were larger than wild juveniles coming from small eggs. Both were in turn larger than hatchery and wild juveniles coming from large eggs. Hatchery progeny showed lower osmo-regulatory status compared to wild progeny but nevertheless preferentially chose salt water. This study presents novel findings that demonstrate that variability in egg size is an important source of phenotypic variation in fishes. My results support the hypothesis that females experiencing relatively high growth rate as juveniles produce a large number of small eggs as adults and that such a reduction in egg size happens rapidly, i.e. in only one generation in domestication. I discuss the implications of egg size for evolution of fishes and, especially how diversity created by egg size can influence diversification and speciation of fishes

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Variation in the magnitude of morphological and dietary differences between individuals among populations of small benthic Arctic charr in relation to ecological factors

The early stages of intraspecific diversity are important for the evolution of diversification and speciation. Early stages of diversification can be seen in individual specialization, where individuals consume only a portion of the diet of the population as a whole, and how such specialization is related to phenotypic diversity within populations. Here, we study the strength of the relationship between morphological and dietary distances among individuals in eighteen populations of Icelandic small benthic charr. We furthermore studied if the strength of the relationship could be related to variation in local ecological factors these populations inhabit. In all the populations studied, there was a clear relationship between morphological and dietary distances, indicating that fish that had similar morphology were at the same time-consuming similar food items. Our findings show a systematic variation in the relationship between morphology and diet at early stages of diversification in a highly specialized small benthic charr morph. The results show the importance of fine scale comparisons within populations and furthermore the value that systematic comparisons among populations under parallel evolution can contribute toward our increased understanding of evolutionary and ecological processes.The project was supported by the Brock Doctoral Scholarship, University of Guelph and a graduate student grant from the Icelandic Science Foundation to BKK. Hólar University College also generously funded this project.Peer Reviewe

Re-identification of individuals from images using spot constellations : a case study in Arctic charr (Salvelinus alpinus)

The long-term monitoring of Arctic charr in lava caves is funded by the Icelandic Research Fund, RANNÍS (research grant nos. 120227 and 162893). E.A.M. was supported by the Icelandic Research Fund, RANNÍS (grant no. 162893) and NERC research grant awarded to M.B.M. (grant no. NE/R011109/1). M.B.M. was supported by a University Research Fellowship from the Royal Society (London). C.A.L. and B.K.K. were supported by Hólar University, Iceland. The Titan Xp GPU used for this research was donated to K.T. by the NVIDIA Corporation.The ability to re-identify individuals is fundamental to the individual-based studies that are required to estimate many important ecological and evolutionary parameters in wild populations. Traditional methods of marking individuals and tracking them through time can be invasive and imperfect, which can affect these estimates and create uncertainties for population management. Here we present a photographic re-identification method that uses spot constellations in images to match specimens through time. Photographs of Arctic charr (Salvelinus alpinus) were used as a case study. Classical computer vision techniques were compared with new deep-learning techniques for masks and spot extraction. We found that a U-Net approach trained on a small set of human-annotated photographs performed substantially better than a baseline feature engineering approach. For matching the spot constellations, two algorithms were adapted, and, depending on whether a fully or semi-automated set-up is preferred, we show how either one or a combination of these algorithms can be implemented. Within our case study, our pipeline both successfully identified unmarked individuals from photographs alone and re-identified individuals that had lost tags, resulting in an approximately 4 our multi-step pipeline involves little human supervision and could be applied to many organisms.Publisher PDFPeer reviewe

Multivariate analysis of morphology, behaviour, growth and developmental timing in hybrids brings new insights into the divergence of sympatric Arctic charr morphs

This work was fully funded by the Icelandic Centre of Research, RANNÍS (Icelandic Research Fund grant no.173802-051).Background: Studying the development of fitness related traits in hybrids from populations diverging in sympatry is a fundamental approach to understand the processes of speciation. However, such traits are often affected by covariance structures that complicate the comprehension of these processes, especially because the interactive relationships between traits of different nature (e.g. morphology, behaviour, life-history) remain largely unknown in this context. In a common garden setup, we conducted an extensive examination of a large suit of traits putatively involved in the divergence of two morphs of Arctic charr (Salvelinus alpinus), and investigated the consequences of potential patterns of trait covariance on the phenotype of their hybrids. These traits were measured along ontogeny and involved growth, yolk sac resorption, developmental timing (hatching and the onset of exogeneous feeding), head morphology and feeding behaviour. Results: Growth trajectories provided the strongest signal of phenotypic divergence between the two charr. Strikingly, the first-generation hybrids did not show intermediate nor delayed growth but were similar to the smallest morph, suggesting parental biases in the inheritance of growth patterns. However, we did not observe extensive multivariate trait differences  between the two morphs and their hybrids. Growth was linked to head morphology (suggesting that morphological variations in early juveniles relate to simple allometric effects) but this was the only strong signal of covariance observed between all the measured traits. Furthermore, we did not report evidence for differences in overall phenotypic variance between morphs, nor for enhanced phenotypic variability in their hybrids. Conclusion: Our study shed light on the multivariate aspect of development in a context of adaptive divergence. The lack of evidence for the integration of most traits into a single covariance structure suggested that phenotypic constraints may not always favour nor impede divergence toward ecological niches differing in numerous physical and ecological variables, as observed in the respective habitats of the two charr. Likewise, the role of hybridization as a disruptive agent of trait covariance may not necessarily be significant in the evolution of populations undergoing resource polymorphism.Publisher PDFPeer reviewe

Patterns, processes, and conservation management consequences of intraspecific diversity, illustrated by fishes from recently glaciated lakes

Patterns in phenotypic and genotypic diversity within many species are becoming increasingly apparent, although there remain many species for which such patterns have yet to be described adequately. Fishes from recently glaciated ecosystems are likely to be particularly rich in intraspecific diversity, yet current conservation management strategies are, in many parts of the world, particularly in Europe, conventionally and overwhelmingly focused on species, regardless of competing species concepts, and appropriate policies for managing diversity at a sub-specific level still have to be developed. Occasional attempts to protect certain vulnerable ecotypes and proposed alternative units of conservation (e.g. ‘Pragmatic Species’ or ‘Evolutionarily Significant Units’) reinforce the conventional primacy of contemporary expressed patterns of variation. Intraspecific phenotypic and genotypic patterns are ultimately the result of complex processes of divergence; conservation approaches that focus on the products of evolution largely ignore the processes that generate and maintain those patterns. Policies that acknowledge the continuation of evolution, the derivation of novel diversity over often very short time spans and the role of environment in initiating and perpetuating these processes are poorly integrated into management strategy. To address possible deficits, where intraspecific diversity is not addressed in management practice, we believe it to be important first to characterize hidden genetic and phenotypic diversity, which may intimate eco-evolutionary processes, initially among species of high conservation status. A second step should be to use an approach to intraspecific diversity that illuminates the ultimate processes and mechanisms that bring about that diversity, which also concedes the central role of the environment and affords adequate protection to the ecosystems that drive these processes, such as the United Nations Convention on Biological Diversity (CBD) Ecosystems approach