Gentamicin Improves the Activities of Daptomycin and Vancomycin against Enterococcus faecalis In Vitro and in an Experimental Foreign-Body Infection Model.

For enterococcal implant-associated infections, the optimal treatment regimen has not been defined. We investigated the activity of daptomycin, vancomycin, and gentamicin (and their combinations) against Enterococcus faecalis in vitro and in a foreign-body infection model. Antimicrobial activity was investigated by time-kill and growth-related heat production studies (microcalorimetry) as well as with a guinea pig model using subcutaneously implanted cages. Infection was established by percutaneous injection of E. faecalis in the cage. Antibiotic treatment for 4 days was started 3 h after infection. Cages were removed 5 days after end of treatment to determine the cure rate. The MIC, the minimal bactericidal concentration (MBC) in the logarithmic phase, and the MBC in the stationary phase were 1.25, 5, and >20 μg/ml for daptomycin, 1, >64, and >64 μg/ml for vancomycin, and 16, 32, and 4 μg/ml for gentamicin, respectively. In vitro, gentamicin at subinhibitory concentrations improved the activity against E. faecalis when combined with daptomycin or vancomycin in the logarithmic and stationary phases. In the animal model, daptomycin cured 25%, vancomycin 17%, and gentamicin 50% of infected cages. In combination with gentamicin, the cure rate for daptomycin increased to 55% and that of vancomycin increased to 33%. In conclusion, daptomycin was more active than vancomycin against adherent E. faecalis, and its activity was further improved by the addition of gentamicin. Despite a short duration of infection (3 h), the cure rates did not exceed 55%, highlighting the difficulty of eradicating E. faecalis from implants already in the early stage of implant-associated infection.

Emotion expression in body action and posture

Emotion communication research strongly focuses on the face and voice as expressive modalities, leaving the rest of the body relatively understudied. Contrary to the early assumption that body movement only indicates emotional intensity, recent studies show that body movement and posture also convey emotion specific information. However, a deeper understanding of the underlying mechanisms is hampered by a lack of production studies informed by a theoretical framework. In this research we adopted the Body Action and Posture (BAP) coding system to examine the types and patterns of body movement that are employed by 10 professional actors to portray a set of 12 emotions. We investigated to what extent these expression patterns support explicit or implicit predictions from basic emotion theory, bi-dimensional theory, and componential appraisal theory. The overall results showed partial support for the different theoretical approaches. They revealed that several patterns of body movement systematically occur in portrayals of specific emotions, allowing emotion differentiation. While a few emotions were prototypically encoded by one particular pattern, most emotions were variably expressed by multiple patterns, many of which can be explained as reflecting functional components of emotion such as modes of appraisal and action readiness. It is concluded that further work in this largely underdeveloped area should be guided by an appropriate theoretical framework to allow a more systematic design of experiments and clear hypothesis testing.

Insulin secretion is regulated by the glucose-dependent production of islet beta cell macrophage migration inhibitory factor.

Macrophage migration inhibitory factor (MIF), originally identified as a cytokine secreted by T lymphocytes, was found recently to be both a pituitary hormone and a mediator released by immune cells in response to glucocorticoid stimulation. We report here that the insulin-secreting beta cell of the islets of Langerhans expresses MIF and that its production is regulated by glucose in a time- and concentration-dependent manner. MIF and insulin colocalize by immunocytochemistry within the secretory granules of the pancreatic islet beta cells, and once released, MIF appears to regulate insulin release in an autocrine fashion. In perifusion studies performed with isolated rat islets, immunoneutralization of MIF reduced the first and second phase of the glucose-induced insulin secretion response by 39% and 31%, respectively. Conversely, exogenously added recombinant MIF was found to potentiate insulin release. Constitutive expression of MIF antisense RNA in the insulin-secreting INS-1 cell line inhibited MIF protein synthesis and decreased significantly glucose-induced insulin release. MIF is therefore a glucose-dependent, islet cell product that regulates insulin secretion in a positive manner and may play an important role in carbohydrate metabolism.

Febuxostat, an Inhibitor of Xanthine Oxidase, Suppresses Lipopolysaccharide-Induced MCP-1 Production via MAPK Phosphatase-1-Mediated Inactivation of JNK.

Excess reactive oxygen species (ROS) formation can trigger various pathological conditions such as inflammation, in which xanthine oxidase (XO) is one major enzymatic source of ROS. Although XO has been reported to play essential roles in inflammatory conditions, the molecular mechanisms underlying the involvement of XO in inflammatory pathways remain unclear. Febuxostat, a selective and potent inhibitor of XO, effectively inhibits not only the generation of uric acid but also the formation of ROS. In this study, therefore, we examined the effects of febuxostat on lipopolysaccharide (LPS)-mediated inflammatory responses. Here we show that febuxostat suppresses LPS-induced MCP-1 production and mRNA expression via activating MAPK phosphatase-1 (MKP-1) which, in turn, leads to dephosphorylation and inactivation of JNK in macrophages. Moreover, these effects of febuxostat are mediated by inhibiting XO-mediated intracellular ROS production. Taken together, our data suggest that XO mediates LPS-induced phosphorylation of JNK through ROS production and MKP-1 inactivation, leading to MCP-1 production in macrophages. These studies may bring new insights into the novel role of XO in regulating inflammatory process through MAPK phosphatase, and demonstrate the potential use of XO inhibitor in modulating the inflammatory processes.

Dynamics of phonological-phonetic encoding in word production: Evidence from diverging ERPs between stroke patients and controls.

While the dynamics of lexical-semantic and lexical-phonological encoding in word production have been investigated in several event-related potential (ERP) studies, the estimated time course of phonological-phonetic encoding is the result of rather indirect evidence. We investigated the dynamics of phonological-phonetic encoding combining ERP analyses covering the entire encoding process in picture naming and word reading tasks by comparing ERP modulations in eight brain-damaged speakers presenting impaired phonological-phonetic encoding relative to 16 healthy controls. ERPs diverged between groups in terms of local waveform amplitude and global topography at ∼400ms after stimulus onset in the picture naming task and at ∼320-350ms in word reading and sustained until 100ms before articulation onset. These divergences appeared in later time windows than those found in patients with underlying lexical-semantic and lexical-phonological impairment in previous studies, providing evidence that phonological-phonetic encoding is engaged around 400ms in picture naming and around 330ms in word reading.

La gestion des services environnementaux: entre règles et régulation négociée. Six études de cas de services forestiers pour la production d'eau potable dans trois pays

Cette thèse est construite en quatre parties : trois annexes qui présentent six études de cas (env. 800 pages), précédées par une analyse transversale, plus synthétique (env. 150 pages), dont traite ce résumé. Chaque annexe contient une synthèse détaillée des études de cas. Cette thèse aborde la « gestion des ressources naturelles » en affirmant d'emblée que l'appellation est inappropriée, car ce ne sont pas les ressources qui sont gérées, mais leurs usages. Il s'agit donc d'identifier et d'analyser ce qui influence les comportements humains en lien avec la ressource. Cette affirmation fonde la perspective des sciences sociales sur la gestion des ressources naturelles, dans laquelle s'inscrit cette thèse. L'approche néo-institutionnaliste considère que les usages sont influencés par des institutions, qui sont elles-mêmes influencées par les usagers. Ces institutions sont des constructions humaines qui composent le contexte institutionnel dans lequel les acteurs décident de leurs usages (abattre un arbre, prélever de l'eau, etc.). Les usages des ressources ne sont donc jamais libres et il s'agit de comprendre comment ces règles du jeu influencent les pratiques. Elles sont nombreuses, interdépendantes et forment la trame sur laquelle se décident les usages. Pour saisir cette complexité, l'auteur applique le cadre d'analyse des régimes institutionnels des ressources (RIR) qui se limite à l'analyse de deux types de droits d'usages : ceux issues des règles de la propriété (titres de propriété, servitudes, etc.) et ceux issus des politiques publiques (lois, ordonnances, etc.). Le RIR permet d'identifier un « régime institutionnel », spécifique à la ressource étudiée, dont les évolutions peuvent être comparées dans le temps ou entre plusieurs lieux. Dans cette recherche, ce cadre d'analyse a été appliqué au même objet - la gestion forestière dans les zones de captage d'eau souterraine destinée au réseau public - dans trois pays : en France, en Suisse et en Indonésie. Trois années de recherche de terrain ont permis à l'auteur de s'intéresser non seulement aux règles prédéterminées (la réglementation), mais aussi aux règles effectivement activées sur le terrain (la régulation) par les acteurs rencontrés. Les études de cas montrent que les règles prévues sont inégalement activées et que les acteurs privilégient parfois la négociation directe pour résoudre leurs rivalités d'usages, à la place d'invoquer leurs droits acquis. Ce constat conduit l'auteur à proposer un élargissement de la focale du RIR, qui constitue le coeur de sa thèse. On ne s'intéresse plus seulement à ce qui « est » régulé, mais aussi à ce qui ne l'« est pas » et qui échappe à l'application classique du RIR. Ce renversement de perspective est crucial pour comprendre les usages concrets des ressources dans les régimes peu intégrés, où les pratiques s'expliquent davantage par la marge de manoeuvre laissée aux acteurs que par les règles prédéterminées. Cette relecture, testée avec succès dans cette thèse, permet d'intégrer la marge de manoeuvre à l'analyse au moyen du RIR. Elle se concrétise par l'identification des lacunes et incohérences dans les régimes institutionnels étudiés. Le champ d'application du RIR s'en trouve élargi et sa vulgarisation pour des non-spécialistes est facilitée, notamment pour les environnementalistes. La complémentarité entre les approches s'en trouve renforcée. Les résultats montrent deux choses : premièrement les acteurs disposent toujours d'une marge de manoeuvre pour négocier des régulations ponctuelles, qui sont autant d'alternatives à l'application des règles prévues. Deuxièmement, la conclusion d'accords issus de la négociation bi-/multilatérale dépend directement de la marge de manoeuvre laissée par le contexte institutionnel. Ceci explique pourquoi la négociation entre les propriétaires forestiers et les exploitants de captages s'imposent en Indonésie, est envisageable en France, mais n'aboutit pas en Suisse. Les nombreuses tentatives infructueuses de mise en oeuvre de solutions négociées, notamment sous forme de paiements pour services environnementaux (PSE), trouvent ici une explication. - This thesis (written in French) is built in four parts: three annexes that present six case studies (approx. 800 pages), preceded by a transverse, more conceptual analysis (approx. 150 pages), which this summary is about. Each annexe contains a detailed summary of the case studies. 'Natural resource management' is an inappropriate designation because it is not the resources that are managed but the uses made of them, therefore this thesis addresses the identification and analysis of the influences on human behaviour in relation to the resource. This statement roots the social sciences perspective on the management of natural resources, in which this thesis fits. A neoinstitutionalist approach considers that the uses are influenced by institutions, which are themselves influenced by users. These institutions are human constructions that form the institutional context in which the actors decide on the use of resources (felling a tree, collecting water, etc.). Thus, the uses of resources are never independent from institutional influences and it becomes necessary to understand how these rules of the game affect practices. They are numerous, interrelated and form the basis for the uses of resources. To understand this complexity, the author applies the institutional regime resource framework (IRR) which limits the analysis to two types of use rights: those resulting from the property rights (deeds, easements, etc.) and those from public policies (laws, ordinances, etc.). The IRR identifies an 'institutional regime', specific to the resource, from which developments can be compared over time or between several places. In this research, this analytical framework has been applied to the same topic - forest management in the recharging areas of groundwater piped for public supply - in three countries: France, Switzerland and Indonesia. Three years of field research allow the author to look not only at predetermined rules (rules), but also at regulations that are actually activated on the ground (rules-in-use). The case studies show that the predetermined rules are unevenly applied and that sometimes actors favour direct negotiation to resolve their rivalry of uses, instead of invoking their vested rights. From this observation the author proposes an enlargement of the IRR's scope, forming the core of his thesis. The interest covers not only what 'is' regulated, but what 'is not' and so is beyond the classical application of the IRR. This shift in perspective is crucial to understand the concrete uses of resources in poorly integrated regimes, where practices are explained by the margin of manoeuvre left to the actors rather than predetermined rules. This reinterpretation, tested successfully in this research, allows the margin of manoeuvre to be integrated in the analysis using the IRR and is made concrete by the identification of gaps and inconsistencies in the investigated institutional context. The new interpretation of the IRR in this thesis complements and enhances its classical application. In particular, its use and understanding by non-specialists, especially environmentalists, is facilitated. The results show two things: first the actors always have leeway to negotiate ad hoc regulations, which are alternatives to the application of the predefined rules. Second, the conclusion of bi/multilateral negotiated agreements depends directly on the leeway left by the institutional context. This explains why the negotiation between forest owners and operators of water catchments is needed in Indonesia, is possible in France, but does not succeed in Switzerland. This offers an explanation for many unsuccessful attempts to implement negotiated solutions, notably payments for environmental services (PES).

Production of an affinity-purified antibody against an aldehyde-treated neurofilament protein for use in immunocytochemistry.

Fixation enhances cellular morphology and reduces loss of molecules during tissue processing. Antibodies against fixation-resistant epitopes are very useful, because they allow an immunocytochemical detection in tissue of better preserved morphology. However, fixatives can alter antigenicity and adversely affect the result of immunohistochemical procedures. To address this problem, this study examined the feasibility of generating antibodies to a paraformaldehyde-fixed antigen for use in immunohistochemical procedures. The large subunit of neurofilament proteins was selected for this study. Crude neurofilament proteins were isolated and separated by SDS-polyacrylamide gel electrophoresis. The large subunit of neurofilaments (NF-H) was electroeluted from the electrophoresis gel and exposed to paraformaldehyde, and used for immunization of a rabbit. The rabbit antiserum was affinity purified on CNBr-sepharose immobilized neurofilament proteins. On Western blots, the antibody reacted with the NF-H protein in a phosphorylation-dependent manner. In aldehyde-fixed cerebellum, the antibody strongly stained axons. In contrast, in alcohol-fixed cryostat sections the immunocytochemical detection was substantially reduced. The procedure presented in this study, involving a simple pretreatment of the immunogen, allows for the generation of an antibody that may be used in immunohistochemical studies where localization of the immunogen may be reduced or even lost by aldehyde fixation.

Assessing multiple sclerosis activity: is the in vitro production of tumor necrosis factor-alpha, interleukins 2, 6, 4, and 10, and immunoglobulin G of value?

Tumor necrosis factor (TNF) alpha, interleukins (IL) 2, 4, 6, and 10, and IgG oligoclonal bands (IgG OB) in vitro production was assessed, after whole-blood stimulation with lipopolysaccharide or concanavalin A, in 61 patients presenting with relapsing-remitting, relapsing-progressive, or chronic progressive multiple sclerosis. Multiple sclerosis patients were receiving no treatment or azathioprine (AZA), cyclosporin, cyclophosphamide, subcutaneous interferon (IFN) beta 1 a, or corticosteroids (CST). Statistical correlations significantly showed that: (a) AZA lowers TNF-alpha (P = 0.002) and increases IL-4 production (P = 0.0024), and IFN-beta 1 a increases TNF-alpha and decreases IL-4 levels; (b) CST has a negative effect on TNF-alpha, IL-6, and IL-4 synthesis; and (c) AZA, IFN-beta 1 a, and CST diminish IgG OB synthesis (P = 0.001). Although our study of the dynamics of TNF-alpha, IL-2, IL-4, IL-6, and IL-10 in vitro production generally found no statistically significant correlations (partly explained by the limited number of values in the various groups), IL-6 was shown to drop during the periods surrounding relapse (P = 0.05) in the absence of treatment, while TNF-alpha (P = 0.04) and IL-6 (P < 0.05) dropped before exacerbation in the presence of AZA. In vitro production of TNF-alpha was closely and positively correlated with that of IL-6, independently of clinical features. The enhanced production of IL-10 detected before or at relapse with AZA and IFN-beta 1 a (trends) may interfere with initiation of the immune reaction and with the development of new CNS lesions. Some discrepancies with previously published results stress the difficulties in studying the state of stimulation of different populations of leukocytes by using a variety of in vitro stimuli and in establishing a correlation between mRNA studies and the amount of final or active protein produced.

Discovery of amino acid variants in the human glucose-dependent insulinotropic polypeptide (GIP) receptor: the impact on the pancreatic beta cell responses and functional expression studies in Chinese hamster fibroblast cells.

The two incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are insulinotropic factors released from the small intestine to the blood stream in response to oral glucose ingestion. The insulinotropic effect of GLP-1 is maintained in patients with Type II (non-insulin-dependent) diabetes mellitus, whereas, for unknown reasons, the effect of GIP is diminished or lacking. We defined the exon-intron boundaries of the human GIP receptor, made a mutational analysis of the gene and identified two amino acid substitutions, A207 V and E354Q. In an association study of 227 Caucasian Type II diabetic patients and 224 matched glucose tolerant control subjects, the allelic frequency of the A207 V polymorphism was 1.1% in Type II diabetic patients and 0.7% in control subjects (p = 0.48), whereas the allelic frequency of the codon 354 polymorphism was 24.9% in Type II diabetic patients versus 23.2% in control subjects. Interestingly, the glucose tolerant subjects (6% of the population) who were homozygous for the codon 354 variant had on average a 14% decrease in fasting serum C-peptide concentration (p = 0.01) and an 11% decrease in the same variable 30 min after an oral glucose load (p = 0.03) compared with subjects with the wild-type receptor. Investigation of the function of the two GIP receptor variants in Chinese hamster fibroblasts showed, however, that the GIP-induced cAMP formation and the binding of GIP to cells expressing the variant receptors were not different from the findings in cells expressing the wildtype GIP receptor. In conclusion, amino acid variants in the GIP receptor are not associated with random Type II diabetes in patients of Danish Caucasian origin or with altered GIP binding and GIP-induced cAMP production when stably transfected in Chinese hamster fibroblasts. The finding of an association between homozygosity for the codon 354 variant and reduced fasting and post oral glucose tolerance test (OGTT) serum C-peptide concentrations, however, calls for further investigations and could suggest that GIP even in the fasting state regulates the beta-cell secretory response.

The C76R transmembrane activator and calcium modulator cyclophilin ligand interactor mutation disrupts antibody production and B-cell homeostasis in heterozygous and homozygous mice.

BackgroundMutations in TNFRSF13B, the gene encoding transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI), are found in 10% of patients with common variable immunodeficiency. However, the most commonly detected mutation is the heterozygous change C104R, which is also found in 0.5% to 1% of healthy subjects. The contribution of the C104R mutation to the B-cell defects observed in patients with common variable immunodeficiency therefore remains unclear.ObjectiveWe sought to define the functional consequences of the C104R mutation on B-cell function.MethodsWe performed in vitro studies of TACI C104R expression and signaling. A knock-in mouse with the equivalent mutation murine TACI (mTACI) C76R was generated as a physiologically relevant model of human disease. We examined homozygous and heterozygous C76R mutant mice alongside wild-type littermates and studied specific B-cell lineages and antibody responses to T cell-independent and T cell-dependent challenge.ResultsC104R expression and ligand binding are significantly diminished when the mutant protein is expressed in 293T cells or in patients' cell lines. This leads to defective nuclear factor κB activation, which is proportionally restored by reintroduction of wild-type TACI. Mice heterozygous and homozygous for mTACI C76R exhibit significant B-cell dysfunction with splenomegaly, marginal zone B-cell expansion, diminished immunoglobulin production and serological responses to T cell-independent antigen, and abnormal immunoglobulin synthesis.ConclusionsThese data show that the C104R mutation and its murine equivalent, C76R, can significantly disrupt TACI function, probably through haploinsufficiency. Furthermore, the heterozygous C76R mutation alone is sufficient to disturb B-cell function with lymphoproliferation and immunoglobulin production defects.

Production of recombinant TRAIL and TRAIL receptor: Fc chimeric proteins.

The tumor necrosis factor (TNF)/TNF receptor (TNFR) families of ligands and receptors are implicated in a variety of physiological and pathological processes and regulate cellular functions as diverse as proliferation, differentiation, and death. Recombinant forms of these ligands and receptors can act to agonize or antagonize these functions and are therefore useful for laboratory studies and may have clinical applications. A protocol is presented for the expression and purification of dimeric soluble receptors fused to the Fc portion of human IgG1 and of soluble, N-terminally Flag-tagged ligands. Soluble recombinant proteins are easier to handle than membrane-bound proteins and the use of tags greatly facilitates their detection and purification. In addition, some tags may provide enhanced biological activity to the recombinant proteins (mainly by oligomerization and stabilization effects) and facilitate their functional characterization. Expression in bacterial (for selected ligands) and eukaryotic expression systems (for ligands and receptors) was performed using M15 pREP4 bacteria and human embryonic kidney 293 cells, respectively. The yield of purified protein is about 1 mg/liter for the mammalian expression system and several milligrams per liter for the bacterial expression system. Protocols are given for a specific ligand-receptor pair, namely TRAIL (Apo-2L) and TRAIL receptor 2 (DR5), but can be applied to other ligands and receptors of the TNF family.

Activation of GPER-1 estradiol receptor downregulates production of testosterone in isolated rat Leydig cells and adult human testis.

PURPOSE: Estradiol (E2) modulates testicular functions including steroidogenesis, but the mechanisms of E2 signaling in human testis are poorly understood. GPER-1 (GPR30), a G protein-coupled membrane receptor, mediates rapid genomic and non-genomic response to estrogens. The aim of this study was to evaluate GPER-1 expression in the testis, and its role in estradiol dependent regulation of steroidogenesis in isolated rat Leydig cells and human testis. MATERIALS AND METHODS: Isolated Leydig cells (LC) from adult rats and human testicular tissue were used in this study. Expression and localization studies of GPER-1 were performed with qRT-PCR, immunofluorescence, immunohistochemistry and Western Blot. Luteinizing Hormone (LH) -stimulated, isolated LC were incubated with estradiol, G-1 (GPER-1-selective agonist), and estrogen receptor antagonist ICI 182,780. Testosterone production was measured with radioimmunoassay. LC viability after incubation with G-1 was measured using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. RESULTS: GPER-1 mRNA is abundantly expressed in rat LC and human testis. Co-localization experiments showed high expression levels of GPER-1 protein in LC. E2-dependent activation of GPER-1 lowers testosterone production in isolated rats LCs and in human testis, with statistically and clinically significant drops in testosterone production by 20-30% as compared to estradiol-naïve LC. The exposure to G-1 does not affect viability of isolated LCs. CONCLUSIONS: Our results indicate that activation of GPER-1 lowers testosterone levels in the rat and human testis. The expression of GPER-1 in human testis, which lack ERα, makes it an exciting target for developing new agents affecting testosterone production in men.

Transforming growth factor beta 1 production by CD4+ CD25+ regulatory T cells in peripheral blood mononuclear cells from healthy subjects stimulated with Leishmania guyanensis.

Transforming growth factor beta (TGF-beta) has been shown to be a central immunomodulator used by leishmaniae to escape effective mechanisms of protection in human and murine infections with these parasites. However, all the information is derived from studies of established infection, while little is known about TGF-beta production in response to Leishmania stimulation in healthy subjects. In this study, TGF-beta1 production was demonstrated in peripheral blood mononuclear cells from healthy subjects never exposed to leishmaniae in response to live Leishmania guyanensis, and the TGF-beta1-producing cells were described as a distinct subpopulation of CD4(+) CD25(+) regulatory T cells. The suppressive properties of CD4(+) CD25(+) T cells were demonstrated in vitro by their inhibition of production of interleukin 2 (IL-2) and IL-10 by CD4(+) CD25(-) T cells in the presence of either anti-CD3 or L. guyanensis. Although neutralization of TGF-beta1 did not reverse the suppressive activity of CD4(+) CD25(+) T cells activated by anti-CD3, it reversed the suppressive activity of CD4(+) CD25(+) T cells activated by L. guyanensis. Altogether our data demonstrated that TGF-beta1 is involved in the suppressive activity of L. guyanensis-stimulated CD4(+) CD25(+) T cells from healthy controls.

Dexamethasone therapy and endogenous cortisol production in severe pediatric head injury.

A prospective randomised study was performed on 25 children aged 1.4 to 15.8 years with severe head injury (Glasgow Coma Scale less than or equal to 7) to determine the clinical effectiveness and the impact on endogenous cortisol production of high-dose steroid therapy. Thirteen patients (group 1) received dexamethasone 1 mg/kg/day during the first 3 days and 12 (group 2) not. All patients were treated with a standardized regimen. Urinary free cortisol was measured by radioimmunoassay, and the clinical data were recorded at hourly intervals. Outcome was assessed 6 months later using the Glasgow Outcome Scale. We found a higher frequency of bacterial pneumonias in the dexamethasone-treated patients (7/13 versus 2/12). Group 1 showed a suppression of endogenous cortisol production from day 1 to day 6. In group 2, mean free cortisol was up to 5-fold higher than under basal conditions. The results in group 2 showed that the endogenous steroid production reacts adequately to the stress of severe head injury. It probably is sufficient to elicit maximum glucocorticoid effects. There was no other statistically significant difference in the clinical and laboratory data between the two groups. We conclude that dexamethasone in high doses suppresses endogenous cortisol production up to 6 days and may increase the risk of bacterial infection without affecting the outcome or the clinical and laboratory data.

Economics of public governance with strategic production of information: four essays

SUMMARY This paper analyses the outcomes of the EEA and bilateral agreements vote at the level of the 3025 communities of the Swiss Confederation by simultaneously modelling the vote and the participation decisions. Regressions include economic and political factors. The economic variables are the aggregated shares of people employed in the losing, Winning and neutral sectors, according to BRUNETTI, JAGGI and WEDER (1998) classification, Which follows a Ricardo-Viner logic, and the average education levels, which follows a Heckscher-Ohlin approach. The political factors are those used in the recent literature. The results are extremely precise and consistent. Most of the variables have the predicted sign and are significant at the l % level. More than 80 % of the communities' vote variance is explained by the model, substantially reducing the residuals when compared to former studies. The political variables do have the expected signs and are significant as Well. Our results underline the importance of the interaction between electoral choice and participation decisions as well as the importance of simultaneously dealing with those issues. Eventually they reveal the electorate's high level of information and rationality. ZUSAMMENFASSUNG Unser Beitrag analysiert in einem Model, welches gleichzeitig die Stimm- ("ja" oder "nein") und Partizipationsentscheidung einbezieht, den Ausgang der Abstimmungen über den Beitritt zum EWR und über die bilateralen Verträge für die 3025 Gemeinden der Schweiz. Die Regressionsgleichungen beinhalten ökonomische und politische Variabeln. Die ökonomischen Variabeln beinhalten die Anteile an sektoriellen Arbeitsplatzen, die, wie in BRUNETTI, JAGGIl.1I1d WEDER (1998), in Gewinner, Verlierer und Neutrale aufgeteilt Wurden, gemäß dem Model von Ricardo-Viner, und das durchschnittliche Ausbildungsniveau, gemäß dem Model von Heckscher-Ohlin. Die politischen Variabeln sind die in der gegenwärtigen Literatur üblichen. Unsere Resultate sind bemerkenswert präzise und kohärent. Die meisten Variabeln haben das von der Theorie vorausgesagte Vorzeichen und sind hoch signifikant (l%). Mehr als 80% der Varianz der Stimmabgabe in den Gemeinden wird durch das Modell erklärt, was, im Vergleich mit früheren Arbeiten, die unerklärten Residuen Wesentlich verkleinert. Die politischen Variabeln haben auch die erwarteten Vorzeichen und sind signifikant. Unsere Resultate unterstreichen die Bedeutung der Interaktion zwischen der Stimm- und der Partizipationsentscheidung, und die Bedeutung diese gleichzeitig zu behandeln. Letztendlich, belegen sie den hohen lnformationsgrad und die hohe Rationalität der Stimmbürger. RESUME Le présent article analyse les résultats des votations sur l'EEE et sur les accords bilatéraux au niveau des 3025 communes de la Confédération en modélisant simultanément les décisions de vote ("oui" ou "non") et de participation. Les régressions incluent des déterminants économiques et politiques. Les déterminants économiques sont les parts d'emploi sectoriels agrégées en perdants, gagnants et neutres selon la classification de BRUNETTI, JAGGI ET WEDER (1998), suivant la logique du modèle Ricardo-Viner, et les niveaux de diplômes moyens, suivant celle du modèle Heckscher-Ohlin. Les déterminants politiques suivent de près ceux utilisés dans la littérature récente. Les résultats sont remarquablement précis et cohérents. La plupart des variables ont les signes prédits par les modèles et sont significatives a 1%. Plus de 80% de la variance du vote par commune sont expliqués par le modèle, faisant substantiellement reculer la part résiduelle par rapport aux travaux précédents. Les variables politiques ont aussi les signes attendus et sont aussi significatives. Nos résultats soulignent l'importance de l'interaction entre choix électoraux et décisions de participation et l'importance de les traiter simultanément. Enfin, ils mettent en lumière les niveaux élevés d'information et de rationalité de l'électorat.