Mesures visant à freiner la hausse des coûts dans l’assurance obligatoire des soins : rapport du groupe d'experts

La santé est un des ingrédients fondamentaux du bien-être humain. On peut escompter que l’élévation du niveau de vie, la multiplication des maladies chroniques et le risque croissant de multimorbidité dû à l’évolution démographique entraînent une hausse des coûts de la santé imputable à plusieurs facteurs. Au total, ces coûts sont passés de 37,5 milliards de francs en 1996 à 77,8 milliards en 2015, tandis que ceux de l'AOS ont grimpé de 10,8 à 27,5 milliards de francs. Notons qu'au cours de cette période en question, l’importance économique a augmenté non seulement en termes absolus mais également rapporté au produit intérieur brut (PIB), indice qui mesure la performance économique d’un pays. Alors que les coûts globaux de la santé représentaient, en 1996, 9,2 % du PIB par année, ce pourcentage était supérieur à 12 en 2015. En comparaison avec la croissance démographique, les coûts des soins de santé ont également augmenté de façon disproportionnée: la progression des prestations nettes dans l’AOS est en effet de 4 % environ par assuré en moyenne, soit 3,5 % déduction faite de l’inflation. Certes, les bases de données ne sont pas parfaites, mais le faisceau d’indices pointant une tendance à l’accélération de la hausse des coûts est incontestable. Pour tenter de la freiner, une intervention politique s’impose de plus en plus, si bien que les mesures de nature à permettre au système de santé de rester financièrement viable sur la durée, tant pour les payeurs de primes que les pouvoirs publics, gagnent en importance. Les mesures envisagées dans le présent rapport visent en particulier à éviter que des prestations médicales inutiles et évitables soient fournies et, partant, à contribuer à freiner la hausse des coûts. (Contexte

Causes of mortality in laying hens in different housing systems in 2001 to 2004

<p>Abstract</p> <p>Background</p> <p>The husbandry systems for laying hens were changed in Sweden during the years 2001 – 2004, and an increase in the number of submissions for necropsy from laying hen farms was noted. Hence, this study was initiated to compare causes of mortality in different housing systems for commercial laying hens during this change.</p> <p>Methods</p> <p>Based on results from routine necropsies of 914 laying hens performed at the National Veterinary Institute (SVA) in Uppsala, Sweden between 2001 and 2004, a retrospective study on the occurrence of diseases and cannibalism, i.e., pecking leading to mortality, in different housing systems was carried out. Using the number of disease outbreaks in caged flocks as the baseline, the expected number of flocks with a certain category of disease in the other housing systems was estimated having regard to the total number of birds in the population. Whether the actual number of flocks significantly exceeded the expected number was determined using a Poisson distribution for the variance of the baseline number, a continuity correction and the exact value for the Poisson distribution function in Excel 2000.</p> <p>Results</p> <p>Common causes of mortality in necropsied laying hens included colibacillosis, erysipelas, coccidiosis, red mite infestation, lymphoid leukosis and cannibalism. Less common diagnoses were Newcastle Disease, pasteurellosis and botulism. Considering the size of the populations in the different housing systems, a larger proportion of laying hens than expected was submitted for necropsy from litter-based systems and free range production compared to hens in cages (<it>P </it>< 0.001). The study showed a significantly higher occurrence of bacterial and parasitic diseases and cannibalism in laying hens kept in litter-based housing systems and free-range systems than in hens kept in cages (<it>P </it>< 0.001). The occurrence of viral diseases was significantly higher in indoor litter-based housing systems than in cages (<it>P </it>< 0.001).</p> <p>Conclusion</p> <p>The results of the present study indicated that during 2001–2004 laying hens housed in litter-based housing systems, with or without access to outdoor areas, were at higher risk of infectious diseases and cannibalistic behaviour compared to laying hens in cages. Future research should focus on finding suitable prophylactic measures, including efficient biosecurity routines, to reduce the risk of infectious diseases and cannibalism in litter-based housing systems for laying hens.</p

Crystal Structure of the Minimalist Max-E47 Protein Chimera

Max-E47 is a protein chimera generated from the fusion of the DNA-binding basic region of Max and the dimerization region of E47, both members of the basic region/helix-loop-helix (bHLH) superfamily of transcription factors. Like native Max, Max-E47 binds with high affinity and specificity to the E-box site, 5′-CACGTG, both in vivo and in vitro. We have determined the crystal structure of Max-E47 at 1.7 Å resolution, and found that it associates to form a well-structured dimer even in the absence of its cognate DNA. Analytical ultracentrifugation confirms that Max-E47 is dimeric even at low micromolar concentrations, indicating that the Max-E47 dimer is stable in the absence of DNA. Circular dichroism analysis demonstrates that both non-specific DNA and the E-box site induce similar levels of helical secondary structure in Max-E47. These results suggest that Max-E47 may bind to the E-box following the two-step mechanism proposed for other bHLH proteins. In this mechanism, a rapid step where protein binds to DNA without sequence specificity is followed by a slow step where specific protein:DNA interactions are fine-tuned, leading to sequence-specific recognition. Collectively, these results show that the designed Max-E47 protein chimera behaves both structurally and functionally like its native counterparts

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

The N-terminal methionine is a major determinant of the DNA binding specificity of MEF-2C

Members of the MEF-2 family of transcriptional regulators positively modulate the activity of basic helix-loop-helix proteins in both myogenic and neurogenic cell lineages. Previous work had shown that MEF-2C(2–117), a protein fragment comprising the dimerization and DNA-binding domains of MEF-2C but lacking the N-terminal methionine, bound to AT-rich DNA sequences with high affinity. MEF-2C(2–117) did not discriminate between different AT-rich sequences. We now report the in vitro DNA binding properties of a MEF-2C fragment containing the N-terminal methionine. Measurements of the apparent dissociation constants of the complexes of GG-MEF-2C(1–117) revealed that different AT-rich sequences are bound with different affinities; in particular MEF site containing DNA (CTATAAATAG) is bound preferentially to DNA containing a SRF site (CATAAATG). Strikingly, when the shorter AT run consisted of six alternating thymines and adenines, almost wild-type affinity was observed. Irrespective of the particular DNA sequence, all circular dichroism spectra of the DNA complexes of GG-MEF-2C(1–117) were superimposable and characterized by an identical maximal ellipticity at 269.5 nm, suggesting similar DNA conformations. Bending analysis by circular permutation assay revealed that on complex formation MEF-2C(2–117) induced cognate DNA to bend by 49°, while heterologous DNA remained unbent. In the presence of the N-terminal methionine, however, all DNA sequences were bent by 70°. The above results suggest an important function for the N-terminal methionine in properly orientating MEF-2C on the DNA

High level expression in soluble form, one step purification, and characterization of the DNA binding domain of MEF-2C

Members of the MEF-2 family of transcription factors act as coregulators of basic helix–loop–helix (BHLH) proteins in the control of lineage specific gene expression in many cell types through direct interaction between the respective DNA binding domains. To make possible a thorough biochemical, biophysical, and structural characterization of the properties of myocyte enhancer factor (MEF) proteins and of their interactions with BHLH-proteins, a simple system for high level expression and rapid purification of myocyte enhancer factor-2C (MEF-2C) was developed. A T7 expression system was used to produce in high yield inEscherichia colian N-terminal fragment of MEF-2C comprising both the MADS box and the MEF domain. Purification by a single round of cation-exchange chromatography on a Resource-S HPLC column at elevated pH afforded an essentially pure protein. Recombinant MEF-2C(1–117) bound with high affinity to the MEF consensus DNA binding site (CTATAAATAG). Mutations in this sequence that replaced adenines with thymine or vice versa did not significantly alter the affinity for MEF-2C(1–117). The introduction of G–C pairs into the core of the MEF-site, however, dramatically increased the concentration of MEF-2C(1–117) needed for half maximal DNA binding. We propose an explanation of the DNA binding specificity of MEF-2C based on the intrinsic bending properties of the unbound DNA

Influence of fair and supportive leadership behavior on commitment and organizational citizenship behaviour

This study examines the influence of fair and supportive leadership behavior on employees’ self-reported organizational citizenship behavior (OCB). The model tested assumes that the impact of fair and supportive leadership on OCB is mediated by employees’ commitment to the organization as well as their commitment to their supervisor. A total of 260 bank employees completed a questionnaire in which they rated their supervisor’s behavior, the two commitment foci (organization and supervisor) and the degree to which they engaged in OCB. As a whole, results of structural equation modelling provide support for the hypotheses and indicate that fostering fair and supportive leadership can be worthwhile for organizations

High affinity binding of MEF-2C correlates with DNA bending.

To regulate lineage-specific gene expression in many cell types, members of the myocyte enhancer factor-2 (MEF-2) family of transcription factors cooperate with basic helix-loop-helix (bHLH) proteins, which show only limited intrinsic DNA binding specificity. We investigated the DNA binding properties of MEF-2C in vitro and show that the inherent bendability of the MEF site is one of the principal structural characteristics recognized by MEF-2C. Measurements of the apparent dissociation constants of MEF-2C complexes with several DNA sequences revealed that MEF-2C bound with high affinity to DNA sequences containing a MEF site. Mutations in the MEF site which did not affect the bendability of the DNA changed the free energy of binding only marginally. However, reducing the intrinsic bendability of the DNA binding site through an AA-->GC substitution increased the half-maximal binding concentration of MEF-2C by almost one order of magnitude. Electrophoretic mobility shift assays revealed markedly reduced MEF-2C binding to DNA containing 2,6-diaminopurine. On binding to MEF-2C the maximum ellipticity at 275 nm in the CD spectrum of DNA containing a MEF site was red shifted by 4 nm and its intensity reduced significantly, while a slight blue shift of <1 nm was observed for a mutant DNA sequence with reduced bendability (AA-->GC). Bending analysis by circular permutation assay revealed that the DNA in the cognate complex was bent by 49 degrees , while the DNA in the complex with the mutant oligonucleotide was largely unbent