Opening The Fortress : the work of public gaze on the Swiss asylum reality

The Fortress (La Forteresse) is a 2008 documentary film by Fernand Melgar that reports the Swiss asylum reality from a distant but committed point of view. The documentary describes the life of asylum seekers awaiting in a federal centre the decision to grant them-or not-refugee status. It subtly raises the issue of the role that "textual realities", grasped from the spectator's point of view, play in the production of public discourses. Most of all, it subtly poses the question of the (Swiss) spectator as an actor of the asylum policy, in the context of a semi-direct democracy. After evoking the notion of sensible experience for linking spectatorship to politics, we look at how the documentary invites its model spectator to accept the film's moral premises. Furthermore, focusing on the Swiss public sphere, we deliver an account of the reception by empirical spectators, notably by a group of leftist activists that tend to subvert Melgar's intentions. This two-fold analysis leads us to exhibit that, in a context of discursive struggles, The Fortress generates an original space of deliberation and experience, which appeals to the public to exercise their political agency on asylum policy without being constricted by an antagonist framework.

Identification of novel HIV restriction factors

To efficiently replicate within mammalian cells, viruses have to manoeuvre through complex host mechanisms, hijacking a network of host proteins to achieve successful propagation. To prevent this invasion, cells have evolved over time to efficiently block the incursing pathogen by direct or indirect targeting. Human immunodeficiency virus (HIV) is a retrovirus of major global public health issue. In the last decade, extensive focus on innate immune proteins has been given, and particularly restriction factors, proteins inhibiting HIV replication by affecting various stages of the viral cycle. Because of the importance of developing new HIV therapies that are associated with reduced side effects and resistances, there is an urge to understand the antiviral response against HIV. Using common features of known restriction factors as a signature to identify new anti-HIV factors, candidates were identified. Particularly multiple members of the apolipoproteins L (APOL) family were found. Cotransfection experiments confirmed very potent inhibitory effects on HIV-1 expression. Further characterization of APOL6, the best candidate, was carried out. APOL6 was not able to inhibit HIV specifically but rather inhibited any gene-encoded DNA that was cotransfected and therefore APOL6 does not classify as a bona fide restriction factor. In addition, we were able to map the activity of APOL6 to the MAD domain and mainly to residue 174. We also found that other members of the family identified in the screen, APOL1 and 3, could have similar mechanism of action as APOL6. Finally, although the complete mechanism of action of APOL6 has yet to be elucidated, it might be blocked during transfections, potentially improving transfection of primary cells. -- Pour se répliquer efficacement dans les cellules de mammifères, les virus doivent manoeuvrer à travers des mécanismes cellulaires complexes et détourner un réseau de protéines de l'hôte. Pour empêcher cette invasion, les gènes de l'hôte ont évolué dans le temps pour cibler efficacement, directement ou indirectement, l'agent pathogène. Le virus de l'immunodéficience humaine (VIH) est un rétrovirus de problème majeur de santé publique mondiale, mais le faible risque de transmission du virus pourrait être expliqué par la présence d'un système antiviral de l'hôte qui, en cas d'échec, conduit à une infection productive. Durant la dernière décennie, il y a eu un intérêt spécial porté sur les protéines immunitaires innées appelé facteurs de restriction présentant des effets inhibiteurs puissants sur la réplication du VIH en affectant différentes étapes du cycle viral. En raison de l'importance de la recherche de nouvelles thérapies anti-VIH associées à des effets secondaires et des résistances réduites comparé aux traitements actuels, il existe un besoin de comprendre la réponse antivirale innée contre le VIH. Basé sur des caractéristiques communes des facteurs de restriction connus, nous avons proposé d'identifier de nouveaux facteurs anti-VIH. Nous avons trouvé une famille de protéines, les apolipoprotéines L (APOL) montrant les effets inhibiteurs très puissants contre l'expression du VIH-1 dans des expériences de co-transfection. Nous avons décidé d'approfondir le rôle de ces protéines dans l'immunité innée et de se concentrer sur le meilleur candidat APOL6. Nous avons en outre établi qu'APOL6 n'a pas d'activité anti-virale spécifique et donc pas classé comme un facteur de bonne foi de restriction. Par ailleurs, APOL6 est capable d'inhiber fortement l'expression de tout Plasmide cotransfecté. En outre, nous avons été en mesure de cartographier l'activité d'APOL6 au domaine MAD et principalement au résidu 174. Nous avons également constaté que d'autres membres de la famille identifiés dans l'étude, APOL1 et 3, pourraient avoir le même mécanisme d'action qu'APOL6. Enfin, bien que le mécanisme d'action complet d'APOL6 reste à être élucidé, il pourrait être d'une importance biotechnologique car il pourrait potentiellement faciliter la transfection de cellules primaires après l'inhibition d'APOL6.

Mechanisms of Antifungal Drug Resistance.

Antifungal therapy is a central component of patient management for acute and chronic mycoses. Yet, treatment choices are restricted because of the sparse number of antifungal drug classes. Clinical management of fungal diseases is further compromised by the emergence of antifungal drug resistance, which eliminates available drug classes as treatment options. Once considered a rare occurrence, antifungal drug resistance is on the rise in many high-risk medical centers. Most concerning is the evolution of multidrug- resistant organisms refractory to several different classes of antifungal agents, especially among common Candida species. The mechanisms responsible are mostly shared by both resistant strains displaying inherently reduced susceptibility and those acquiring resistance during therapy. The molecular mechanisms include altered drug affinity and target abundance, reduced intracellular drug levels caused by efflux pumps, and formation of biofilms. New insights into genetic factors regulating these mechanisms, as well as cellular factors important for stress adaptation, provide a foundation to better understand the emergence of antifungal drug resistance.

Endocrine causes of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed.

Co-evolution of Policy Sectors: Health Care and Public Health in five Countries

Cette thèse analyse la co-évolution de deux secteurs dans la politique de la santé: santé publique (public health) et soins aux malades (health care). En d'autres termes, la relation entre les dimensions curative et préventive de la politique de la santé et leur développement dans la durée. Une telle recherche est nécessaire car les problèmes de la santé sont complexes et ont besoin de solutions coordonnées. De plus, les dépenses de la santé ont augmenté sans arrt durant les dernières décennies. Un moyen de réduire une future augmentation des dépenses pourrait consister en davantage d'investissement dans des mesures préventives. En relation avec cette idée, ma recherche analyse les politiques de la santé publique et les soins aux malades de cinq pays: Allemagne, Angleterre, Australie, Etats-Unis et Suisse. En m'appuyant sur la littérature secondaire, des statistiques descriptives et des entretiens avec des experts et des politiciens, j'analyse la relation entre les deux secteurs depuis la fin du dix-neuvième siècle. En particulier, je me focalise sur la relation des deux champs sur trois niveaux: institutions, acteurs et politiques. Mes résultats montrent les similitudes et les différences d'évolution entre les cinq pays. D'un c^oté, lorsque la profession médicale est politiquement active et que le pays consiste en une fédération centralisée ou en un gouvernement unitaire, les deux secteurs sont intégrés au niveau institutionnel, ralliant les professions et groupes d'intérêt des deux secteurs la cause commune dans une activité politique. Par contre, dans tous les pays, les deux secteurs ont co-évolué vers une complémentarité malgré de la politisation des professions et la centralisation du gouvernement. Ces résultats sont intéressants pour la science politique en général car ils soulignent l'importance des professions pour le développement institutionnel et proposent un cadre pour l'analyse de la co-évolution des politiques publiques en général. -- This Ph.D. thesis analyzes the co-evolution of the health care and the public health sectors. In other words, the relation between preventive and curative health policy and its evolution over time. Such research is necessary, because current health problems are complex and might need coordinated solutions. What is more, health expenditures have increased continuously in the last decades. One way to slow down further increase in health spending could be to invest more in preventative health policies. Therefore, I am connecting individual health care and public health into a common analysis, taking Australia, Germany, Switzerland, the UK and the U.S. as examples. Based on secondary literature, descriptive statistics and interviews with experts and policymakers, I am analyzing how the two sectors' relations co-evolved between the late nineteenth and the early twenty-first century. Specifically, I am researching how health care and public health were related on the levels of institutions, actors and policies. My results show that there are differences and similarities in the co-evolution of policy sectors between these countries. On the one hand, when the medical profession was politically active and the country a centralized federation or a unitary state, there was institutional integration and common political advocacy of the sectors' interest groups and professions. On the other hand, in all countries, both sectors co-evolved towards complementarity, irrespectively of the politicization of professions and centralization of government. These findings are interesting for the political science literature at large, because they underline the importance of professions for institutional development and propose an analytical framework for analyzing the co-evolution of policy sectors in general.

Association of car ownership and physical activity across the spectrum of human development : Modeling the Epidemiologic Transition Study (METS).

BACKGROUND: Variations in physical activity (PA) across nations may be driven by socioeconomic position. As national incomes increase, car ownership becomes within reach of more individuals. This report characterizes associations between car ownership and PA in African-origin populations across 5 sites at different levels of economic development and with different transportation infrastructures: US, Seychelles, Jamaica, South Africa, and Ghana. METHODS: Twenty-five hundred adults, ages 25-45, were enrolled in the study. A total of 2,101 subjects had valid accelerometer-based PA measures (reported as average daily duration of moderate to vigorous PA, MVPA) and complete socioeconomic information. Our primary exposure of interest was whether the household owned a car. We adjusted for socioeconomic position using household income and ownership of common goods. RESULTS: Overall, PA levels did not vary largely between sites, with highest levels in South Africa, lowest in the US. Across all sites, greater PA was consistently associated with male gender, fewer years of education, manual occupations, lower income, and owning fewer material goods. We found heterogeneity across sites in car ownership: after adjustment for confounders, car owners in the US had 24.3 fewer minutes of MVPA compared to non-car owners in the US (20.7 vs. 45.1 minutes/day of MVPA); in the non-US sites, car-owners had an average of 9.7 fewer minutes of MVPA than non-car owners (24.9 vs. 34.6 minutes/day of MVPA). CONCLUSIONS: PA levels are similar across all study sites except Jamaica, despite very different levels of socioeconomic development. Not owning a car in the US is associated with especially high levels of MVPA. As car ownership becomes prevalent in the developing world, strategies to promote alternative forms of active transit may become important.

Quality of Qualitative Research in the Health Sciences : Analysis of the Common Criteria Present in 58 Assessment Guidelines by Expert Users

The number of qualitative research methods has grown substantially over the last twenty years, both in social sciences and, more recently, in the health sciences. This growth came with questions on the quality criteria needed to evaluate this work, and numerous guidelines were published. The latters include many discrepancies though, both in their vocabulary and construction. Many expert evaluators decry the absence of consensual and reliable evaluation tools. The authors present the results of an evaluation of 58 existing guidelines in 4 major health science fields (medicine and epidemiology; nursing and health education; social sciences and public health; psychology / psychiatry, research methods and organization) by expert users (article reviewers, experts allocating funds, editors, etc.). The results propose a toolbox containing 12 consensual criteria with the definitions given by expert users. They also indicate in which disciplinary field each type of criteria is known to be more or less essential. Nevertheless, the authors highlight the limitations of the criteria comparability, as soon as one focuses on their specific definitions. They conclude that each criterion in the toolbox must be explained to come to broader consensus and identify definitions that are consensual to all the fields examined and easily operational.

Differences in pandemic influenza vaccination policies for pregnant women in Europe.

BACKGROUND: An important component of the policy to deal with the H1N1 pandemic in 2009 was to develop and implement vaccination. Since pregnant women were found to be at particular risk of severe morbidity and mortality, the World Health Organization and the European Centers for Disease Control advised vaccinating pregnant women, regardless of trimester of pregnancy. This study reports a survey of vaccination policies for pregnant women in European countries. METHODS: Questionnaires were sent to European competent authorities of 27 countries via the European Medicines Agency and to leaders of registries of European Surveillance of Congenital Anomalies in 21 countries. RESULTS: Replies were received for 24 out of 32 European countries of which 20 had an official pandemic vaccination policy. These 20 countries all had a policy targeting pregnant women. For two of the four countries without official pandemic vaccination policies, some vaccination of pregnant women took place. In 12 out of 20 countries the policy was to vaccinate only second and third trimester pregnant women and in 8 out of 20 countries the policy was to vaccinate pregnant women regardless of trimester of pregnancy. Seven different vaccines were used for pregnant women, of which four contained adjuvants. Few countries had mechanisms to monitor the number of vaccinations given specifically to pregnant women over time. Vaccination uptake varied. CONCLUSIONS: Differences in pandemic vaccination policy and practice might relate to variation in perception of vaccine efficacy and safety, operational issues related to vaccine manufacturing and procurement, and vaccination campaign systems. Increased monitoring of pandemic influenza vaccine coverage of pregnant women is recommended to enable evaluation of the vaccine safety in pregnancy and pandemic vaccination campaign effectiveness.

Carotenoid-based colours reflect the stress response in the common lizard.

Under chronic stress, carotenoid-based colouration has often been shown to fade. However, the ecological and physiological mechanisms that govern colouration still remain largely unknown. Colour changes may be directly induced by the stressor (for example through reduced carotenoid intake) or due to the activation of the physiological stress response (PSR, e.g. due to increased blood corticosterone concentrations). Here, we tested whether blood corticosterone concentration affected carotenoid-based colouration, and whether a trade-off between colouration and PSR existed. Using the common lizard (Lacerta vivipara), we correlatively and experimentally showed that elevated blood corticosterone levels are associated with increased redness of the lizard's belly. In this study, the effects of corticosterone did not depend on carotenoid ingestion, indicating the absence of a trade-off between colouration and PSR for carotenoids. While carotenoid ingestion increased blood carotenoid concentration, colouration was not modified. This suggests that carotenoid-based colouration of common lizards is not severely limited by dietary carotenoid intake. Together with earlier studies, these findings suggest that the common lizard's carotenoid-based colouration may be a composite trait, consisting of fixed (e.g. genetic) and environmentally elements, the latter reflecting the lizard's PSR.

Current and future trens in the quality control of pharmaceuticals and biopharmaticals : impacts on Cost of Goods Sold (COGS)

[Summary] 2. Roles of quality control in the pharmaceutical and biopharmaceutical industries. - 2.1. Pharmaceutical industry. - 2.2. Biopharmaceutical industry. - 2.3. Policy and regulatory. - 2.3.1. The US Food and Drug Administration (FDA). - 2.3.2. The European Medicine Agency (EMEA). - 2.3.3. The Japanese Ministry of Work, Labor and Welfare (MHLW). - 2.3.4. The Swiss Agency for Therapeutic Products (Swissmedic). - 2.3.5. The International Conference on Harmonization (ICH). - - 3. Types of testing. - 3.1. Microbiological purity tests. - 3.2. Physiochemical tests. - 3.3. Critical to quality steps. - 3.3.1. API starting materials and excipients. - 3.3.2. Intermediates. - 3.3.3. APIs (drug substances) and final drug product. - 3.3.4. Primary and secondary packaging materials fro drug products. - - 4. Manufacturing cost and quality control. - 4.1.1. Pharmaceutical manufacturing cost breakdown. - 4.1.2. Biopharmaceutical manufacturing cost breakdown. - 4.2. Batch failure / rejection / rework / recalls. - - 5. Future trends in the quality control of pharmaceuticals and biopharmaceuticals. - 5.1. Rapid and real time testing. - 5.1.1. Physio-chemicals testing. - 5.1.2. Rapid microbiology methods