Conflict and co-operation in ant societies

Cette thèse se propose d?étudier les forces évolutives qui influencent la bal- ance entre coopération et conflit. Deux exemples sont analysés en détail, les sociétés d?insectes et l?association entre la fourmi Formica exsecta et son sym- bionte intracellulaire Wolbachia. Chacune de ces deux associations animales est caractérisée par la coexistence de coopération et de conflit. Les colonies d?insectes sociaux sont un exemple typique de coopération. Néanmoins, la détermination haplodiploïde du sexe crée des apparentements asymétriques entre les membres de la colonie qui se traduisent par des con- flits entre reines et ouvrières. Un des conflits les plus importants porte sur le sexe-ratio, l?investissement optimal en sexués males et femelles étant équilibré pour la reine, mais biaisé en faveur des femelles pour les ouvrières. Jusqu?ici, les modèles étudiant ce conflit se basaient uniquement sur les asymétries d?ap- parentement. La première partie de cette thèse (Chapitres 1 et 2) propose d?introduire dans des modèles de sexe-ratio les mécanismes proximaux utilisés par les deux parties pour influencer le sexe-ratio. Ces mécanismes, par leurs ef- fets négatifs sur la productivité de la colonie, peuvent entraîner des déviations importantes du sexe-ratio par rapport à la valeur prédite par des modèles clas- siques. De plus, la prise en compte de ces mécanismes nous permet d?étudier dans quelle mesure les parties opposées sont sélectionnées pour influencer le sexe-ratio. Enfin, les modèles génèrent des prédictions quant à l?issue du con- flit, c?est-à-dire un compromis où reines et ouvrières partagent le contrôle de l?investissement. La seconde partie du travail porte sur l?infection de la fourmi Formica ex- secta par le symbionte cytoplasmique Wolbachia. Ce symbionte, présent chez un grand nombre d?espèces d?Arthropodes, est transmis maternellement. Afin de se répandre dans la population d?hôtes, Wolbachia manipule la physiolo- gie reproductive de l?organisme qui l?abrite. Le Chapitre 3 décrit une étude consacrée aux variations du sexe-ratio produit dans des colonies de fourmis? en fonction de la présence ou de l?absence de Wolbachia. Le Chapitre 4 étudie l?association entre les lignées du symbionte et les haplotypes mitochondriaux des hôtes. L?étude de l?association entre les deux éléments maternellement transmis est d?un intérêt particulier chez Formica exsecta car le taux de migra- tion femelle très faible engendre une forte strucure génétique mitochondriale.

Skin permeation and metabolism of di(2-ethylhexyl) phthalate (DEHP).

Phthalates are suspected to be endocrine disruptors. Di(2-ethylhexyl) phthalate (DEHP) is assumed to have low dermal absorption; however, previous in vitro skin permeation studies have shown large permeation differences. Our aims were to determine DEHP permeation parameters and assess extent of skin DEHP metabolism among workers highly exposed to these lipophilic, low volatile substances. Surgically removed skin from patients undergoing abdominoplasty was immediately dermatomed (800 μm) and mounted on flow-through diffusion cells (1.77 cm(2)) operating at 32°C with cell culture media (aqueous solution) as the reservoir liquid. The cells were dosed either with neat DEHP or emulsified in aqueous solution (166 μg/ml). Samples were analysed by HPLC-MS/MS. DEHP permeated human viable skin only as the metabolite MEHP (100%) after 8h of exposure. Human skin was able to further oxidize MEHP to 5-oxo-MEHP. Neat DEHP applied to the skin hardly permeated skin while the aqueous solution readily permeated skin measured in both cases as concentration of MEHP in the receptor liquid. DEHP pass through human skin, detected as MEHP only when emulsified in aqueous solution, and to a far lesser degree when applied neat to the skin. Using results from older in vitro skin permeation studies with non-viable skin may underestimate skin exposures. Our results are in overall agreement with newer phthalate skin permeation studies.

Two mechanisms of caspase 9 processing in double-stranded RNA- and virus-triggered apoptosis.

Viral double-stranded RNA (dsRNA) is a ubiquitous intracellular "alert signal" used by cells to detect viral infection and to mount anti-viral responses. DsRNA triggers a rapid (complete within 2-4 h) apoptosis in the highly-susceptible HeLa cell line. Here, we demonstrate that the apical event in this apoptotic cascade is the activation of procaspase 8. Downstream of caspase 8, the apoptotic signaling cascade bifurcates into a mitochondria-independent caspase 8/caspase 3 arm and a mitochondria-dependent, caspase 8/Bid/Bax/Bak/cytochrome c arm. Both arms impinge upon, and activate, procaspase 9 via two different cleavage sites within the procaspase 9 molecule (D330 and D315, respectively). This is the first in vivo demonstration that the "effector" caspase 3 plays an "initiator" role in the regulation of caspase 9. The dsRNA-induced apoptosis is potentiated by the inhibition of protein synthesis, whose role is to accelerate the execution of all apoptosis steps downstream of, and including, the activation of caspase 8. Thus, efficient apoptosis in response to viral dsRNA results from the co-operation of the two major apical caspases (8 and 9) and the dsRNA-activated protein kinase R (PKR)/ribonuclease L (RNase L) system that is essential for the inhibition of protein synthesis in response to viral infection.

Polyarthrite rhumatoïde et grossesse [Rheumatoid arthritis and pregnancy]

Rheumatoid arthritis occurs frequently in women in childbearing years. With the improvement of the treatments, more patients with rheumatoid arthritis consider a pregnancy. Close co-operation between the physician and the obstetrician caring for the mother and the foetus is necessary. The disease should be well controlled at the time of the conception, although an amelioration of rheumatoid arthritis occurs in about 75% of pregnancies, in the first trimester. Some medications can be used during pregnancy and lactation. There is no indication of any adverse effects of rheumatoid arthritis on pregnancy outcome. The mother needs to be followed up regularly after delivery because of the high risk of post-partum flare.

Accompagnement thérapeutique : le chemin du suivi à long terme [Patient education: the way for long-term follow up]

L'éducation thérapeutique du patient est maintenant parfaitement intégrée dans les soins. Son champ d'application se situe essentiellement dans le domaine des maladies chroniques pour l'acquisition de compétences dans la gestion du traitement, en coopération avec les professionnels. En médecine ambulatoire, patients et soignants se heurtent actuellement aux difficultés du suivi avec sa part d'incertitude, lassitude et de pression économique. La médecine fondée sur les preuves (EBM) et les différents modèles en psychologie de la santé ne nous éclairent que partiellement le chemin. Un nouveau type de démarche réflexive est en train d'émerger. Cette réflexion devrait placer en son centre la notion de relation thérapeutique : entre science et existence. Nous résumons ici ce processus réflexif en cours d'une équipe interdisciplinaire regroupant sciences humaines, art et médecine. Therapeutic education is now perfectly integrated in caring and medicine. Its field of application is primarily in chronic diseases for the acquisition of competences in the management of treatments, in co-operation with health professionals. In ambulatory medicine, patients and health professionals are currently running up against the difficulties of the long-term follow-up with its part of uncertainty, lassitude and economic pressure. EBM and the various models of health psychology light us only partially the way. A new type of reflexive step is emerging. This way of thinking should place in its center the concept of therapeutic relation: between science and being. We summarize here our reflexive process in the course of an interdisciplinary team gathering social sciences, art and medicine

The evolution of helping and harming on graphs: the return of the inclusive fitness effect.

Evolutionary graph theory has been proposed as providing new fundamental rules for the evolution of co-operation and altruism. But how do these results relate to those of inclusive fitness theory? Here, we carry out a retrospective analysis of the models for the evolution of helping on graphs of Ohtsuki et al. [Nature (2006) 441, 502] and Ohtsuki & Nowak [Proc. R. Soc. Lond. Ser. B Biol. Sci (2006) 273, 2249]. We show that it is possible to translate evolutionary graph theory models into classical kin selection models without disturbing at all the mathematics describing the net effect of selection on helping. Model analysis further demonstrates that costly helping evolves on graphs through limited dispersal and overlapping generations. These two factors are well known to promote relatedness between interacting individuals in spatially structured populations. By allowing more than one individual to live at each node of the graph and by allowing interactions to vary with the distance between nodes, our inclusive fitness model allows us to consider a wider range of biological scenarios leading to the evolution of both helping and harming behaviours on graphs.

How many diagnosis fields are needed to capture safety events in administrative data? Findings and recommendations from the WHO ICD-11 Topic Advisory Group on Quality and Safety

OBJECTIVE: As part of the WHO ICD-11 development initiative, the Topic Advisory Group on Quality and Safety explores meta-features of morbidity data sets, such as the optimal number of secondary diagnosis fields. DESIGN: The Health Care Quality Indicators Project of the Organization for Economic Co-Operation and Development collected Patient Safety Indicator (PSI) information from administrative hospital data of 19-20 countries in 2009 and 2011. We investigated whether three countries that expanded their data systems to include more secondary diagnosis fields showed increased PSI rates compared with six countries that did not. Furthermore, administrative hospital data from six of these countries and two American states, California (2011) and Florida (2010), were analysed for distributions of coded patient safety events across diagnosis fields. RESULTS: Among the participating countries, increasing the number of diagnosis fields was not associated with any overall increase in PSI rates. However, high proportions of PSI-related diagnoses appeared beyond the sixth secondary diagnosis field. The distribution of three PSI-related ICD codes was similar in California and Florida: 89-90% of central venous catheter infections and 97-99% of retained foreign bodies and accidental punctures or lacerations were captured within 15 secondary diagnosis fields. CONCLUSIONS: Six to nine secondary diagnosis fields are inadequate for comparing complication rates using hospital administrative data; at least 15 (and perhaps more with ICD-11) are recommended to fully characterize clinical outcomes. Increasing the number of fields should improve the international and intra-national comparability of data for epidemiologic and health services research, utilization analyses and quality of care assessment.

Comparative modular analysis of gene expression in vertebrate development

The focus of my PhD research was the concept of modularity. In the last 15 years, modularity has become a classic term in different fields of biology. On the conceptual level, a module is a set of interacting elements that remain mostly independent from the elements outside of the module. I used modular analysis techniques to study gene expression evolution in vertebrates. In particular, I identified ``natural'' modules of gene expression in mouse and human, and I showed that expression of organ-specific and system-specific genes tends to be conserved between such distance vertebrates as mammals and fishes. Also with a modular approach, I studied patterns of developmental constraints on transcriptome evolution. I showed that none of the two commonly accepted models of the evolution of embryonic development (``evo-devo'') are exclusively valid. In particular, I found that the conservation of the sequences of regulatory regions is highest during mid-development of zebrafish, and thus it supports the ``hourglass model''. In contrast, events of gene duplication and new gene introduction are most rare in early development, which supports the ``early conservation model''. In addition to the biological insights on transcriptome evolution, I have also discussed in detail the advantages of modular approaches in large-scale data analysis. Moreover, I re-analyzed several studies (published in high-ranking journals), and showed that their conclusions do not hold out under a detailed analysis. This demonstrates that complex analysis of high-throughput data requires a co-operation between biologists, bioinformaticians, and statisticians.

Unlicensed and off-label drug use in a Swiss paediatric university hospital.

BACKGROUND: Many medicines used in newborns, infants, children and adolescents are not licensed ("unlicensed") or are prescribed outside the terms of the marketing authorization ("off-label"). Several studies have shown that this is a common practice in various healthcare settings in the USA, Europe and Australia, but data are scarce in Switzerland. OBJECTIVES: The aim of our prospective study was to determine the proportion of unlicensed or off-label prescriptions in paediatric patients. METHODS: This pilot study was conducted prospectively over a six month period in the department of paediatrics of a university hospital. RESULTS: Sixty patients aged from three days to 14 years were included in the study. A total of 483 prescriptions were written for the patients. More than half of all prescriptions (247; 51%) followed the terms of the marketing authorization. 114 (24%) were unlicensed and 122 (25%) off-label. All patients received at least one unlicensed or offlabel medicine. CONCLUSION: The use of unlicensed or off-label medicines to treat children was found to be common. Co-operation between the pharmaceutical industry, national regulatory authorities, clinical researchers, healthcare professionals and parents is required in order to ensure that children do not remain "therapeutic orphans".

Die Schweizer Gemeinden im Wandel : Konvergenz oder Divergenz?

Switzerland is currently going through a phase of political restructuring. The numerous reform activities at the beginning of the twenty-first century leave almost no area of political life untouched. The reforms are particularly abundant in the 2′867 municipalities, spanning from amalgamations, intermunicipal co-operation, New Public Management, to reforms of the political systems. Accounting for the fact that there are big socio-economic differences between the municipalities as well as their political systems, we investigate whether the municipalities are headed for divergence or convergence as a result of these reforms. The empirical results are derived from three surveys of the local authorities conducted in 1988, 1994, and 1998. The results indicate that the communes do convergence in regard to their administrative and political structure. However, the convergence appears to be limited to the single cantons and observable only among certain types of municipalities.

A course on collaboration between social workers and general practitioners during their vocational training

The educational programme reported was an experiment in the vocational training scheme of the department of General Practice, Erasmus University, Rotterdam, Holland, and is now part of the course. The programme focused on the training in team function (co-operation) given to trainee GPs and social workers. It became clear that both groups during their professional training develop markedly different attitudes and views about patient (client) care. These differences form a fundamental handicap in any discussion about teamwork. During the programme the students were made aware of this divergence of viewpoint and were taught how to handle these resulting handicaps and, if possible, to eliminate them.

The evolution of judgement bias in indirect reciprocity.

Indirect reciprocity is a form of reciprocity where help is given to individuals based on their reputation. In indirect reciprocity, bad acts (such as not helping) reduce an individual's reputation while good acts (such as helping) increase an individual's reputation. Studies of indirect reciprocity assume that good acts and bad acts are weighted equally when assessing the reputation of an individual. As different information can be processed in different ways, this is not likely to be the case, and it is possible that an individual could bias an actor's reputation by putting more weight to acts of defection (not helping) than acts of co-operation (helping) or vice versa. We term this difference 'judgement bias', and build an individual-based model of image scoring to investigate the conditions under which it may evolve. We find that, if the benefits of co-operation are small, judgement bias is weighted towards acts perceived to be bad; if the benefits are high, the reverse is true. Our result is consistent under both scoring and standing strategies, and we find that allowing judgement bias to evolve increases the level of co-operation in the population.

What does your neighbourhood say about you? : a study of life expectancy in 1.3 million Swiss neighbourhoods

BACKGROUND: Switzerland had the highest life expectancy at 82.8 years among the Organisation for Economic Co-operation and Development (OECD) countries in 2011. Geographical variation of life expectancy and its relation to the socioeconomic position of neighbourhoods are, however, not well understood. METHODS: We analysed the Swiss National Cohort, which linked the 2000 census with mortality records 2000-2008 to estimate life expectancy across neighbourhoods. A neighbourhood index of socioeconomic position (SEP) based on the median rent, education and occupation of household heads and crowding was calculated for 1.3 million overlapping neighbourhoods of 50 households. We used skew-normal regression models, including the index and additionally marital status, education, nationality, religion and occupation to calculate crude and adjusted estimates of life expectancy at age 30 years. RESULTS: Based on over 4.5 million individuals and over 400,000 deaths, estimates of life expectancy at age 30 in neighbourhoods ranged from 46.9 to 54.2 years in men and from 53.5 to 57.2 years in women. The correlation between life expectancy and neighbourhood SEP was strong (r=0.95 in men and r=0.94 women, both p values <0.0001). In a comparison of the lowest with the highest percentile of neighbourhood SEP, the crude difference in life expectancy from skew-normal regression was 4.5 years in men and 2.5 years in women. The corresponding adjusted differences were 2.8 and 1.9 years, respectively (all p values <0.0001). CONCLUSIONS: Although life expectancy is high in Switzerland, there is substantial geographical variation and life expectancy is strongly associated with the social standing of neighbourhoods.

Towards actionable international comparisons of health system performance: expert revision of the OECD framework and quality indicators.

OBJECTIVE: To review and update the conceptual framework, indicator content and research priorities of the Organisation for Economic Cooperation and Development's (OECD) Health Care Quality Indicators (HCQI) project, after a decade of collaborative work. DESIGN: A structured assessment was carried out using a modified Delphi approach, followed by a consensus meeting, to assess the suite of HCQI for international comparisons, agree on revisions to the original framework and set priorities for research and development. SETTING: International group of countries participating to OECD projects. PARTICIPANTS: Members of the OECD HCQI expert group. RESULTS: A reference matrix, based on a revised performance framework, was used to map and assess all seventy HCQI routinely calculated by the OECD expert group. A total of 21 indicators were agreed to be excluded, due to the following concerns: (i) relevance, (ii) international comparability, particularly where heterogeneous coding practices might induce bias, (iii) feasibility, when the number of countries able to report was limited and the added value did not justify sustained effort and (iv) actionability, for indicators that were unlikely to improve on the basis of targeted policy interventions. CONCLUSIONS: The revised OECD framework for HCQI represents a new milestone of a long-standing international collaboration among a group of countries committed to building common ground for performance measurement. The expert group believes that the continuation of this work is paramount to provide decision makers with a validated toolbox to directly act on quality improvement strategies.

Institutional legacies, employment and professional integration of non EU/EEA doctors in France

Internationally, policies for attracting highly-skilled migrants have become the guidelines mainly used by the Organisation for Economic Co-operation and Development (OECD) countries. Governments are implementing specific procedures to capture and facilitate their mobility. However, all professions are not equal when it comes to welcoming highly-skilled migrants. The medical profession, as a protective market, is one of these. Taking the case of non-EU/EEA doctors in France, this paper shows that the medical profession defined as the closed labour market, remains the most controversial in terms of professional integration of migrants, protectionist barriers to migrant competition and challenge of medical shortage. Based on the path-dependency approach, this paper argues that non-EU/EEA doctors' issues in France derive from a complex historical process of interaction between standards settled in the past, particularly the historical power of medical corporatism, the unexpected long-term effects of French hospital reforms of 1958, and budgetary pressures. Theoretically, this paper shows two significant findings. Firstly, the French medical system has undergone a series of transformations unthinkable in the strict sense of a path-dependence approach: an opening of the medical profession to foreign physicians in the context of the Europeanisation of public policy, acceptance of non-EU/EEA doctors in a context of medical shortage and budgetary pressures. Secondly, there is no change of the overall paradigm: significantly, the recruitment policies of non-EU/EEA doctors continue to highlight the imprint of the past and reveal a significant persistence of prejudices. Non-EU/EEA doctors are not considered legitimate doctors even if they have the qualifications of physicians which are legitimate in their country and which can be recognised in other receiving countries.