Discrimination génétique lors de la pré-embauche : élaboration d'une politique d'encadrement

"Mémoire présenté à la Faculté des études supérieures En vue de l'obtention du grade de maîtrise en droit"

Le financement de la haute technologie dans le système de santé : le cas de la pharmacogénomique

L’exercice d’allocation de ressources en santé, relevant du Ministère de la santé, se voit fortement influencé autant par les besoins variés de la population que par les exigences des intervenants en santé. Quel rôle ces différents intérêts peuvent-ils jouer dans l’intégration de nouvelles technologies dans la distribution des soins de santé ? La pharmacogénomique, branche émergente de la pharmacologie intégrant les données issues du projet génome humain au processus de développement du médicament, est perçue comme une technologie qui permettrait de personnaliser la médecine. Son intégration aux processus de développement ou de prescription de médicaments promet de minimiser l’apparition d’effets secondaires néfastes découlant de la prise de médicaments. Serait-il alors judicieux pour le gouvernement du Québec, considérant la conjoncture actuelle d’allocation de ressources, d’investir dans la pharmacogénomique en tant que nouvel outil de développement du médicament ou nouveau mode pronostic de médication pour sa population ? Nous aborderons cette question à l’aide de critères de sélection dictés par Caulfield et ses collaborateurs (2001)[1] pour évaluer la pertinence de l’investissement public dans la mise sur pied d’un test génétique, soit l’acceptabilité, l’utilité, la non-malfaisance et la présence d’un bénéfice clair – à coût raisonnable – pour la population. La génomique avoisinant la génétique, ces facteurs s’avèrent applicables dans notre discussion.

Phénomène de biohype dans des articles scientifiques rapportant des résultats issus de recherches cliniques en nutrigénétique/nutrigénomique : caractérisation et perception des chercheurs

Le développement de la nutrigénétique/nutrigénomique (NGx) a suscité de nombreuses attentes puisque les retombées qui lui sont associées s’avèrent potentiellement bénéfiques autant pour les individus en santé que pour les individus malades. De grandes attentes avaient également été associées au Projet de décryptage du Génome Humain (PGH). Aujourd’hui, seules quelques attentes de celles envisagées se sont concrétisées. Le PGH a donc évolué dans un contexte marqué par du biohype, soit la promotion d’attentes exagérées, voir irréalistes. Étant donné l’importance des attentes associées avec le développement de la NGx et des limites méthodologiques auxquelles fait encore face la recherche clinique conduite dans ce domaine, l’objectif principal de cette thèse est de déterminer si les publications scientifiques rapportant des résultats de recherches cliniques effectuées en NGx contribuent à l’émergence d’un phénomène de biohype. Plus spécifiquement, il s’agira également de documenter la perception des chercheurs oeuvrant dans le domaine de la NGx du phénomène de biohype, d’identifier certains facteurs qui pourraient expliquer son émergence dans la littérature scientifique propre à ce domaine et de proposer des pistes d’actions pour limiter les risques associés à ce phénomène. Nous avons tout d’abord procédé à une analyse documentaire d’articles scientifiques rapportant des résultats issus de recherches cliniques en NGx. Celle-ci nous a révélé que plusieurs bénéfices étaient promus dans cette littérature alors même que les limites méthodologiques n’étaient pas d’emblée présentées et discutées. Cette observation nous portait à croire que ces bénéfices étant potentiellement prématurés. Nous avons ensuite voulu valider notre constat auprès des chercheurs œuvrant principalement dans le domaine de la NGx. Cette enquête nous a permis de constater que les chercheurs étaient généralement en accord avec les bénéfices que nous avons recensés dans les articles scientifiques. Toutefois, ils n’envisageaient pas leur concrétisation à moyen terme. Par ailleurs, cette enquête nous a également révélé que les limitations méthodologiques actuellement rencontrées dans la conduite de recherches cliniques soulevaient des doutes quant à la faisabilité des bénéfices promut dans les articles scientifiques. Ces données viennent confirmer notre observation à savoir qu’un phénomène de biohype serait réellement en émergence dans les articles scientifiques rapportant des résultats de recherches cliniques en NGx. Outre des informations concernant les publics ciblés par les chercheurs et les éléments que doivent contenir un article scientifique, cette enquête nous a également aidés à mieux comprendre les avantages associés à la promotion de bénéfices. Selon la majorité des chercheurs interrogés, la promotion de bénéfices dans un article scientifique augmenterait les chances d’un manuscrit d’être publié et favoriserait la continuité du financement du domaine de recherche. Cette activité étant caractérisée par un environnement compétitif, la promotion de bénéfices semble être une avenue à envisager pour se démarquer. Quoique la promotion de bénéfices prématurés ou exagérés ne soit pas considérée comme de l’inconduite scientifique, elle peut causer entre autres un affaiblissement du sentiment de confiance entre le public et les chercheurs et ultimement, contrevenir à la continuité d’une saine activité de recherche. À la lumière de ces données, nous croyons qu’une des stratégies qui permettrait de prévenir l’apparition des risques associés au phénomène de biohype serait de sensibiliser les chercheurs et les éditeurs de journaux scientifiques à ces derniers. Plus particulièrement, nous encourageons l’intégration de lignes directrices portant sur la gestion du biohype dans les codes de conduites qui ont été mis en place pour favoriser les bonnes pratiques en recherche.

Accidentes de trabajo y enfermedades laborales de los mineros de socavón en Boyacá, Cundinamarca y Norte de Santander

RESUMEN. Introducción: la minería a cielo abierto y la subterránea, presentan altas cifras de lesiones asociadas a esta industria a nivel internacional. Países como Australia, algunos de Europa y Estados Unidos tienen avances en seguridad minera, tanto en lesiones fatales como no mortales; sin embargo, otros países no muestran el mismo desarrollo, ejemplo de ello son algunos países de África, China y países de Suramérica. Colombia, muestra un paupérrimo avance en seguridad minera, agravado por ausencia de registros de calidad para establecer políticas en salud y seguridad minera. Objetivo: describir los accidentes de trabajo (AT) y enfermedades laborales (EL) de dichos trabajadores y sus relaciones con tiempo de exposición y oficio. Metodología: estudio transversal con 476 trabajadores del el sector de minería. Se indago sobre los AT y EL de los mineros de socavón en los departamentos de Boyacá, Cundinamarca y Norte de Santander. Se realizó análisis estadístico con medidas de tendencia central y dispersión, estimación de prevalencia de AT y EL y pruebas de asociación Chi-cuadrado para identificar factores relacionados con las variables. Para las estimaciones de parámetros se empleó un nivel de confianza del 95% y las pruebas de asociación un nivel α de 0,05. Resultados: La edad en años de los trabajadores varió entre 20 y 76 años con una media general de 43 ± 10. La antigüedad laboral en años varió entre 10 y 57 años con una media general de 19,3±9,1. Los trabajadores con mayor promedio de antigüedad laboral fueron los de Cundinamarca (valor_p< 0.000). La incidencia de AT fue de 52,3%, IC (95% 47,7% – 56,9%) en los tres departamentos, siendo mayor en Boyacá. Las regiones anatómicas más comprometidas fueron miembros inferiores 32,2%, miembros superiores 26,9%, la cabeza y espalda con 9,9% respectivamente. La enfermedad laboral que más se diagnosticó, fue hernia de disco. Conclusiones: Este estudio muestra la magnitud del problema de la accidentalidad observada en los tres departamentos; la distribución de los accidentes en el sector minero, según la región anatómica, el tipo de lesión y su agente causal, esto será insumo para ayudar a la elaboración de políticas públicas, a nivel empresarial, de las Administradoras de Riesgos Laborales (ARL) y otros actores del Sistema de gestión de la Seguridad y Salud en el Trabajo (SGSST). Palabras clave: minería, exposición profesional, accidentes de trabajo, enfermedad laboral, Colombia.

Associação entre a aptidão cardiorrespiratória e a circunferência da cintura, pressão arterial, e glicemia em adolescentes

A relação entre aptidão cardiorrespiratória e um menor perfil de risco cardiovascular tem sido demonstrado em crianças e adolescentes (Janssen & Leblanc, 2010; 2006; Kriemler et al., 2008). Objetivo: verificar a associação entre o consumo máximo de oxigénio ( 2max) e a circunferência da cintura (CC), pressão arterial sistólica (PAS), pressão arterial diastólica (PAD) e glicemia em adolescentes utilizando a base de dados do projeto Rastresaúde. Método: este ro eto tin a co o ob etivo ava iar os rinci ais indicadores de sa de cardiovascu ar e inc u a as vari veis 2max A A e ice ia. ontudo nesse ro eto o 2max tinha sido obtido através do chester step test (CST) ue não estava va idado ara ado escentes. este sentido oi rea i ado u estudo re i inar co o ob etivo de estudar a associação entre va ores do 2max estimados utilizando o CST e o teste do Vaivém que está validado para adolescentes (Leger, Mercier, Gadoury, & Lambert, 1988). Pretendíamos com este objetivo poder eventualmente utilizar, os va ores do 2max da referida base de dados. endo-se veri icado u a associação estatistica ente si ni icativa orte e ositiva entre os va ores de 2max obtidos utilizando o CST e o teste Vaivém para o sexo masculino, r=0,92, p<0,05 e para o sexo feminino, r=0,78, p<0,05 decidimo-nos e a uti i ação da base de dados do astresa de. este sentido a re erida base de dados oi uti i ada ara investi ar a associação do 2max com a CC, PAS, PAD e glicemia em adolescentes. Resultados: verificou-se nos indivíduos do sexo feminino uma associação inversa e estatistica ente si ni icativa entre o 2max e a A r - 1 5 entre o 2max e a A r - 1 5 e entre o 2max e a CC, r=-0,182, p< 5. ara os indiv duos do se o ascu ino veri icou-se u a associação inversa e estatistica ente si ni icativa a enas entre o 2max e a CC, r=-0,229, p<0,05 sendo que todas as associações encontradas foram consideradas fracas, r<0,3 (Field, 2005). Conclusão: os resultados do estudo sugerem uma associação inversa entre o 2max e a PAS, PAD e CC em adolescentes do sexo feminino e entre 2max e a CC em adolescentes do sexo masculino. Dada a escassez de estudos e derivado ao aumento da prevalência dos fatores de risco associados às doenças cardiovasculares na infância e adolescência é relevante realizar mais estudos na população jovem.

British Nutrition Foundation annual lecture: chips with everything? Nutritional genomics and the application of diet in disease prevention

The development of high throughput techniques ('chip' technology) for measurement of gene expression and gene polymorphisms (genomics), and techniques for measuring global protein expression (proteomics) and metabolite profile (metabolomics) are revolutionising life science research, including research in human nutrition. In particular, the ability to undertake large-scale genotyping and to identify gene polymorphisms that determine risk of chronic disease (candidate genes) could enable definition of an individual's risk at an early age. However, the search for candidate genes has proven to be more complex, and their identification more elusive, than previously thought. This is largely due to the fact that much of the variability in risk results from interactions between the genome and environmental exposures. Whilst the former is now very well defined via the Human Genome Project, the latter (e.g. diet, toxins, physical activity) are poorly characterised, resulting in inability to account for their confounding effects in most large-scale candidate gene studies. The polygenic nature of most chronic diseases offers further complexity, requiring very large studies to disentangle relatively weak impacts of large numbers of potential 'risk' genes. The efficacy of diet as a preventative strategy could also be considerably increased by better information concerning gene polymorphisms that determine variability in responsiveness to specific diet and nutrient changes. Much of the limited available data are based on retrospective genotyping using stored samples from previously conducted intervention trials. Prospective studies are now needed to provide data that can be used as the basis for provision of individualised dietary advice and development of food products that optimise disease prevention. Application of the new technologies in nutrition research offers considerable potential for development of new knowledge and could greatly advance the role of diet as a preventative disease strategy in the 21st century. Given the potential economic and social benefits offered, funding for research in this area needs greater recognition, and a stronger strategic focus, than is presently the case. Application of genomics in human health offers considerable ethical and societal as well as scientific challenges. Economic determinants of health care provision are more likely to resolve such issues than scientific developments or altruistic concerns for human health.

The use of proteomics to identify novel therapeutic targets for the treatment of disease

The completion of the Human Genome Project has revealed a multitude of potential avenues for the identification of therapeutic targets. Extensive sequence information enables the identification of novel genes but does not facilitate a thorough understanding of how changes in gene expression control the molecular mechanisms underlying the development and regulation of a cell or the progression of disease. Proteomics encompasses the study of proteins expressed by a population of cells, and evaluates changes in protein expression, post-translational modifications, protein interactions, protein structure and splice variants, all of which are imperative for a complete understanding of protein function within the cell. From the outset, proteomics has been used to compare the protein profiles of cells in healthy and diseased states and as such can be used to identify proteins associated with disease development and progression. These candidate proteins might provide novel targets for new therapeutic agents or aid the development of assays for disease biomarkers. This review provides an overview of the current proteomic techniques available and focuses on their application in the search for novel therapeutic targets for the treatment of disease.

An insight into the public acceptance of nutrigenomic-based personalised nutrition.

It is predicted that non-communicable diseases will account for over 73 % of global mortality in 2020. Given that the majority of these deaths occur in developed countries such as the UK, and that up to 80 % of chronic disease could be prevented through improvements in diet and lifestyle, it is imperative that dietary guidelines and disease prevention strategies are reviewed in order to improve their efficacy. Since the completion of the human genome project our understanding of complex interactions between environmental factors such as diet and genes has progressed considerably, as has the potential to individualise diets using dietary, phenotypic and genotypic data. Thus, there is an ambition for dietary interventions to move away from population-based guidance towards 'personalised nutrition'. The present paper reviews current evidence for the public acceptance of genetic testing and personalised nutrition in disease prevention. Health and clear consumer benefits have been identified as key motivators in the uptake of genetic testing, with individuals reporting personal experience of disease, such as those with specific symptoms, being more willing to undergo genetic testing for the purpose of personalised nutrition. This greater perceived susceptibility to disease may also improve motivation to change behaviour which is a key barrier in the success of any nutrition intervention. Several consumer concerns have been identified in the literature which should be addressed before the introduction of a nutrigenomic-based personalised nutrition service. Future research should focus on the efficacy and implementation of nutrigenomic-based personalised nutrition.

Adaptive climate change governance for urban resilience

Climate change poses new challenges to cities and new flexible forms of governance are required that are able to take into account the uncertainty and abruptness of changes. The purpose of this paper is to discuss adaptive climate change governance for urban resilience. This paper identifies and reviews three traditions of literature on the idea of transitions and transformations, and assesses to what extent the transitions encompass elements of adaptive governance. This paper uses the open source Urban Transitions Project database to assess how urban experiments take into account principles of adaptive governance. The results show that: the experiments give no explicit information of ecological knowledge; the leadership of cities is primarily from local authorities; and evidence of partnerships and anticipatory or planned adaptation is limited or absent. The analysis shows that neither technological, political nor ecological solutions alone are sufficient to further our understanding of the analytical aspects of transition thinking in urban climate governance. In conclusion, the paper argues that the future research agenda for urban climate governance needs to explore further the links between the three traditions in order to better identify contradictions, complementarities or compatibilities, and what this means in practice for creating and assessing urban experiments.

Sugarcane Phosphoribosyl Pyrophosphate Synthetase: Molecular Characterization of a Phosphate-independent PRS

Phosphoribosyl pyrophosphate synthetase (PRS-EC:2.7.6.1) is an important enzyme present in several metabolic pathways, thus forming a complex family of isoenzymes. However, plant PRS enzymes have not been extensively investigated. In this study, a sugarcane prs gene has been characterized from the Sugar Cane Expressed Sequence Tag Genome Project. This gene contains a 984-bp open reading frame encoding a 328-amino acid protein. The predicted amino acid sequence has 77% and 78% amino acid sequence identity to Arabidopsis thaliana and Spinacia oleracea PRS4, respectively. The assignment of sugarcane PRS as a phosphate-independent PRS isoenzyme (Class II PRS) is verified following enzyme assay and phylogenetic reconstruction of PRS homologues. To gain further insight into the structural framework of the phosphate independence of sugarcane PRS, a molecular model is described. This model reveals the formation of two conserved domains elucidating the structural features involved in sugarcane PRS phosphate independence. The recombinant PRS retains secondary structure elements and a quaternary arrangement consistent with known PRS homologues, based on circular dichroism measurements.

Transcriptome analysis of Taenia solium cysticerci using Open Reading Frame ESTs (ORESTES)

Background: Human infection by the pork tapeworm Taenia solium affects more than 50 million people worldwide, particularly in underdeveloped and developing countries. Cysticercosis which arises from larval encystation can be life threatening and difficult to treat. Here, we investigate for the first time the transcriptome of the clinically relevant cysticerci larval form. Results: Using Expressed Sequence Tags (ESTs) produced by the ORESTES method, a total of 1,520 high quality ESTs were generated from 20 ORESTES cDNA mini-libraries and its analysis revealed fragments of genes with promising applications including 51 ESTs matching antigens previously described in other species, as well as 113 sequences representing proteins with potential extracellular localization, with obvious applications for immune-diagnosis or vaccine development. Conclusion: The set of sequences described here will contribute to deciphering the expression profile of this important parasite and will be informative for the genome assembly and annotation, as well as for studies of intra- and inter-specific sequence variability. Genes of interest for developing new diagnostic and therapeutic tools are described and discussed.

The manufacturing industry in Brazil in the era of global value chains

This article presents a comprehensive and detailed overview of the international trade performance of the manufacturing industry in Brazil over the last decades, emphasizing its participation in Global Value Chains. It uses information from recent available global inputoutput tables such as WIOD (World Input-output database) and TIVA (Trade in Value Added, OECD) as well as complementary information from the GTAP 8 (Global Trade Analysis Project) database. The calculation of a broad set of value added type indicators allows a precise contextualization of the ongoing structural changes in the Brazilian industry, highlighting the relative isolation of its manufacturing sector from the most relevant international supply chains. This article also proposes a public policy discussion, presenting two case studies: the first one related to trade facilitation and the second one to preferential trade agreements. The main conclusions are twofold: first, the reduction of time delays at customs in Brazil may significantly improve the trade performance of its manufacturing industry, specially for the more capital intensive sectors which are generally the ones with greater potential to connection to global value chains; second, the extension of the concept of a “preferential trade partner” to the context of the global unbundling of production may pave the way to future trade policy in Brazil, particularly in the mapping of those partners whose bilateral trade relations with Brazil should receive greater priority by policy makers.

The manufacturing industry in Brazil in the era of global value chains

This article presents a comprehensive and detailed overview of the international trade performance of the manufacturing industry in Brazil over the last decades, emphasizing its participation in Global Value Chains. It uses information from recent available global inputoutput tables such as WIOD (World Input-output database) and TIVA (Trade in Value Added, OECD) as well as complementary information from the GTAP 8 (Global Trade Analysis Project) database. The calculation of a broad set of value added type indicators allows a precise contextualization of the ongoing structural changes in the Brazilian industry, highlighting the relative isolation of its manufacturing sector from the most relevant international supply chains. This article also proposes a public policy discussion, presenting two case studies: the first one related to trade facilitation and the second one to preferential trade agreements. The main conclusions are twofold: first, the reduction of time delays at customs in Brazil may significantly improve the trade performance of its manufacturing industry, specially for the more capital intensive sectors which are generally the ones with greater potential to connection to global value chains; second, the extension of the concept of a “preferential trade partner” to the context of the global unbundling of production may pave the way to future trade policy in Brazil, particularly in the mapping of those partners whose bilateral trade relations with Brazil should receive greater priority by policy makers