Analyse des taux de renvoi entre médecins praticiens: une revue de la littérature. [Analysis of referral rate between medical practitioners: a review of the literature].

The authors are discussing the results of the international literature with regards to referrals between ambulatory physicians. There are still few studies on this problem and the methodologies used are often too different to make valid comparisons. However, the earned results suggest more questions than they give answers to the determinants of the referral process. This can be explained by the multidimensionality of factors which are involved in the decision to refer a patient to another practitioner, particularly by the complex interaction between the characteristics of each patient, practitioner and the sanitary system itself.

Analysis of hemoglobin-based oxygen carriers by CE-UV/Vis and CE-ESI-TOF/MS.

Blood doping involves the use of products that enhance the uptake, transport, or delivery of oxygen to the blood. One approach uses artificial oxygen carriers, known as hemoglobin-based oxygen carriers (HBOCs). This study describes an analytical strategy based on CE for detecting intact HBOCs in plasma samples collected for doping control. On-capillary detection was performed by UV/Vis at 415 nm, which offered detection selectivity for hemoproteins (such as hemoglobin and HBOCs). On-line ESI-MS detection with a TOF analyzer was further used to provide accurate masses on CE peaks and to confirm the presence of HBOCs. An immunodepletion sample preparation step was mandatory prior to analysis, in order to remove most abundant proteins that interfered with CE separation and altered the ESI process. This analytical method was successfully applied to plasma samples enriched with Oxyglobin, a commercially available HBOC used for veterinary purposes. Detection limits of 0.20 and 0.45 g/dL were achieved in plasma for CE-UV/Vis at 415 nm and CE-ESI-TOF/MS, respectively.

Proteomic analysis of Intercept-treated platelets.

In the past decades, transfusion medicine has been driven by the quest for increased safety against transfusion-transmitted infections, mainly by better donor selection and by the development of improved serological and nucleic-acid-based screening assays. Recently, pathogen reduction technologies became available and started to be implemented in several countries, with the primary goal to fight against bacterial contamination of blood products, a rare but dramatic event against which there was no definitive measure. Though pathogen reduction technologies represent a quantum leap in transfusion safety, the biomedical efficacy of platelet concentrates (PCs) treated with various pathogen reduction techniques has been recently questioned by clinical studies. Here, a gel-based proteomic analysis of PCs (n=5), Intercept-treated or untreated, from pooled buffy-coat (10 donors per PC) at Days 1, 2 and 8, shows that the Intercept process that is the most widespread pathogen reduction technique to date, has relatively low impact on the proteome of treated platelets: the process induces modifications of DJ-1 protein, glutaredoxin 5, and G(i)alpha 2 protein. As for the impact of storage, chloride intracellular channel protein 4 (CLIC4) and actin increased independently of Intercept treatment during storage. Whereas alteration of the DJ-1 protein and glutaredoxin 5 points out an oxidative stress-associated lesion, modification of G(i)alpha2 directly connects a possible Intercept-associated lesion to haemostatic properties of Intercept-treated platelets. This article is part of a Special Issue entitled: Integrated omics.

Discrete analysis of dividend payments in a non-life insurance portfolio

The process of free reserves in a non-life insurance portfolio as defined in the classical model of risk theory is modified by the introduction of dividend policies that set maximum levels for the accumulation of reserves. The first part of the work formulates the quantification of the dividend payments via the expectation of their current value under diferent hypotheses. The second part presents a solution based on a system of linear equations for discrete dividend payments in the case of a constant dividend barrier, illustrated by solving a specific case.

Interactive readings of children's literature in day care: Microgenetic analysis of the semiopictorial construction.

In line with educational issues involved in emergent literacy practices in preschool, in particular those concerning comprehension processes, this paper focuses on picture-based narrative comprehension during an interactive reading session of a wordless picture book, involving a group of children aged three and their teacher. Children are asked to make inferences about the meaning and outcome of the story, a procedure which gradually elicits their responses on how events link together, thus enhancing their capacity to use prior and implicit knowledge to build the story meaning. Moreover, this study highlights the importance of interaction for developing comprehension. Data collected was analysed following didactic microgenesis, an analytical approach showing that knowledge built during interaction depends on the joint construction of a zone of common meaning by which teacher and children try to adjust to each other. In order to help the process of merging different meanings of the story built online, a text written by researchers, following the narrative structure of the story, was read by the teacher after the picture-based reading. This led us to examine through interactional analysis which semiotic cues were used during recall on the following day, as an additional measure of knowledge construction.

A Statistical Analysis of Iowa Premature Concrete Pavement Deterioration, Supplementary Study, HR-1063, 1997

This supplementary project has been undertaken as an effort to continue work previously completed in the Pooled Fund Study of Premature Concrete Pavement Deterioration. As such, it shares the objective of "Identifying the variables that are present in those pavements exhibiting premature deterioration," by collecting additional data and performing statistical analysis of those data. The approach and philosophy of this work are identical to that followed in the above project, and the Pooled Fund Study Final Report provides a detailed description of this process. This project has involved the collection of data for additional sites in the state of Iowa. These sites have then been added to sites collected in the original study, and statistical analysis has been performed on the entire set. It is hoped that this will have two major effects. First, using data from only one state allows for the analysis of a larger set of independent variables with a greater degree of commonality than was possible in the multi-state study, since the data are not limited by state to state differences in data collection and retention. Second, more data on additional sites will increase the degrees of freedom in the model and hopefully add confidence to the results.

Statistical Analysis of Highway Needs Condition Data: Manual vs. Automated, TR-494

This project examines similarities and differences between the automated condition data collected on and off county paved roads and the manual condition data collected by Iowa Department of Transportation (DOT) staff in 2000 and 2001. Also, the researchers will provide staff support to the advisory committee in exploring other options to the highway need process. The results show that the automated condition data can be used in a converted highway needs process with no major differences between the two methods. Even though the foundation rating difference was significant, the foundation rating weighting factor in HWYNEEDS is minimal and should not have a major impact. In terms of RUTF formula based distribution, the results clearly show the superiority of the condition-based analysis compared to the non-condition based. That correlation can be further enhanced by adding more distress variables to the analysis.

The social disembedding of business theory and practice. A (neo-)institutional analysis of the homo economicus and corporate social responsibility, and the inherent responsibility of business scholars

Aim Structure of the Thesis In the first article, I focus on the context in which the Homo Economicus was constructed - i.e., the conception of economic actors as fully rational, informed, egocentric, and profit-maximizing. I argue that the Homo Economicus theory was developed in a specific societal context with specific (partly tacit) values and norms. These norms have implicitly influenced the behavior of economic actors and have framed the interpretation of the Homo Economicus. Different factors however have weakened this implicit influence of the broader societal values and norms on economic actors. The result is an unbridled interpretation and application of the values and norms of the Homo Economicus in the business environment, and perhaps also in the broader society. In the second article, I show that the morality of many economic actors relies on isomorphism, i.e., the attempt to fit into the group by adopting the moral norms surrounding them. In consequence, if the norms prevailing in a specific group or context (such as a specific region or a specific industry) change, it can be expected that actors with an 'isomorphism morality' will also adapt their ethical thinking and their behavior -for the 'better' or for the 'worse'. The article further describes the process through which corporations could emancipate from the ethical norms prevailing in the broader society, and therefore develop an institution with specific norms and values. These norms mainly rely on mainstream business theories praising the economic actor's self-interest and neglecting moral reasoning. Moreover, because of isomorphism morality, many economic actors have changed their perception of ethics, and have abandoned the values prevailing in the broader society in order to adopt those of the economic theory. Finally, isomorphism morality also implies that these economic actors will change their morality again if the institutional context changes. The third article highlights the role and responsibility of business scholars in promoting a systematic reflection and self-critique of the business system and develops alternative models to fill the moral void of the business institution and its inherent legitimacy crisis. Indeed, the current business institution relies on assumptions such as scientific neutrality and specialization, which seem at least partly challenged by two factors. First, self-fulfilling prophecy provides scholars with an important (even if sometimes undesired) normative influence over practical life. Second, the increasing complexity of today's (socio-political) world and interactions between the different elements constituting our society question the strong specialization of science. For instance, economic theories are not unrelated to psychology or sociology, and economic actors influence socio-political structures and processes, e.g., through lobbying (Dobbs, 2006; Rondinelli, 2002), or through marketing which changes not only the way we consume, but more generally tries to instill a specific lifestyle (Cova, 2004; M. K. Hogg & Michell, 1996; McCracken, 1988; Muniz & O'Guinn, 2001). In consequence, business scholars are key actors in shaping both tomorrow's economic world and its broader context. A greater awareness of this influence might be a first step toward an increased feeling of civic responsibility and accountability for the models and theories developed or taught in business schools.

The Impact of Cooperation on R&D, Innovation andProductivity: an Analysis of Spanish Manufacturing and Services Firms

This paper investigates relationships between cooperation, R&D, innovation and productivity in Spanish firms. It uses a large sample of firm-level micro-data and applies an extended structural model that aims to explain the effects of cooperation on R&D investment, of R&D investment on output innovation, and of innovation on firms’ productivity levels. It also analyses the determinants of R&D cooperation. Firms’ technology level is taken into account in order to analyse the differences between high-tech and low-tech firms, both in the industrial and service sectors. The database used was the Technological Innovation Panel (PITEC) for the period 2004-2010. Empirical results show that firms which cooperate in innovative activities are more likely to invest in R&D in subsequent years. As expected, R&D investment has a positive impact on the probability of generating an innovation, in terms of both product and process, for manufacturing firms. Finally, innovation output has a positive impact on firms’ productivity, being greater in process innovations.

Characterization of the effect of mammary gland irridiation on experimental brest cancer progression and analysis of the implicated mechanisms

SUMMARY Radiotherapy is commonly and efficiently used to treat solid cancer in the clinic. Experimental evidence however suggests that radiation can promote tumor progression by inducing chronic modifications of the tumor microenvironment. Clinically, these observations are highly relevant to aggressive tumoral lesions relapsing after radiation therapy, a leading cause of patients' death. The investigation and understanding of the biological mechanisms implicated in the malignant progression of post-radiation relapses are therefore of major importance. Here we used a syngeneic (immunocompetent) breast cancer orthotopic xenograft model, to show that local irradiation of the mammary gland promotes the appearance of an invasive and metastatic tumor phenotype. Previous studies in our laboratory revealed that inhibition of tumor-induced angiogenesis and consequent increase in tumor hypoxia promotes metastasis formation through the activation of pro-invasive programs in the tumor cells. Our results extend these observations suggesting that mammary gland irradiation induces the recruitment of CD11b+ cells to both the primary tumor and the lungs at pre-metastatic stages through the hypoxia-dependent induction of Kit-ligand (KITL) expression in primary tumors. Abrogation of KITL expression in tumor cells prevented CD11 b+ cells accumulation in both the primary tumor and lungs and significantly reduced metastases of tumors growing in irradiated mammary gland. Importantly, irradiated mammary gland enhanced tumor-induced mobilization of circulating CD11b+cKit+ myelomonocytic cells through a HIF1- and KITL-dependent process. By cell transfer experiments, mobilized circulating CD11b+cKit+ cells were shown to supply both tumor- and lungs infiltrating CD11b+ cells. Using a blocking antibody against cKit (the KITL receptor), the mobilization of CD11b+cKit+ ceils was prevented as well as lung metastases derived from tumors growing in irradiated mammary gland. Taken together, these results indicate that tumors growing in a pre-irradiated mammary gland partially promote their malignant progression through the distant mobilization of circulating myelomonocytic precursor cells. They identify KITL inhibition and/or cKit receptor neutralization as potentially promising therapeutic approaches for post-radiation relapses. RESUME La radiothérapie est largement utilisée comme traitement de choix de nombreux types de cancers. L'agressivité des récidives tumorales observée en clinique après radiothérapie suggère cependant que le recours à l'irradiation pourrait dans certains cas accélérer la progression tumorale. De récents travaux expérimentaux ont en effet permis d'appuyer cette hypothèse, en montrant notamment l'effet néfaste des modifications chroniques de l'environnement induites par l'irradiation sur la progression tumorale. A l'aide d'un modèle murin syngénique orthotopique de cancer de sein, nous avons pu montrer que l'irradiation locale de la glande mammaire facilite l'invasion et la dissémination métastatique des cellules tumorales en favorisant le recrutement de cellules myéloïdes CD11 b+ vers la tumeur primaire et les poumons à un stade pré-métastatique. Comme mécanisme impliqué dans le recrutement des cellules CD11b+, nous avons pu observer après irradiation locale de la glande mammaire une expression augmentée de Kit-ligand (KITL) dans la tumeur (induite par l'hypoxie) ainsi que la mobilisation de cellules myéloïdes circulantes exprimant le récepteur cKit et précurseurs des cellules CD11b+ infiltrant la tumeur et les poumons. En empêchant la mobilisation par la tumeur de cellules circulantes cKit+ par des approches à la fois génétique et pharmacologique nous avons pu prévenir l'accumulation de cellules myéloïdes CD11 b+ dans la tumeur primaire et les poumons ainsi que la dissémination métastatique induites par' l'irradiation de la glande mammaire. De façon générale, ces résultats montrent que la progression agressive des tumeurs qui se développent dans un environnement irradié repose à la fois sur l'expression tumorale de KITL et la mobilisation de cellules myéloïdes précurseurs cKit*. Ils auront permis d'identifier KITL et/ou cKit comme des cibles thérapeutiques potentielles intéressantes pour le traitement des récidives tumorales après radiothérapie.

The Impact of Cooperation on R&D, Innovation and Productivity: an Analysis of Spanish Manufacturing and Services Firms

This paper investigates relationships between cooperation, R&D, innovation and productivity in Spanish firms. It uses a large sample of firm-level micro-data and applies an extended structural model that aims to explain the effects of cooperation on R&D investment, of R&D investment on output innovation, and of innovation on firms’ productivity levels. It also analyses the determinants of R&D cooperation. Firms’ technology level is taken into account in order to analyse the differences between high-tech and low-tech firms, both in the industrial and service sectors. The database used was the Technological Innovation Panel (PITEC) for the period 2004-2010. Empirical results show that firms which cooperate in innovative activities are more likely to invest in R&D in subsequent years. As expected, R&D investment has a positive impact on the probability of generating an innovation, in terms of both product and process, for manufacturing firms. Finally, innovation output has a positive impact on firms’ productivity, being greater in process innovations. Keywords: innovation sources; productivity; R&D Cooperation

Gas analysis of exhumed cadavers buried for 30 years: a case report about long time alteration.

Due to important alteration caused by long time decomposition, the gases in human bodies buried for more than a year have not been investigated. For the first time, the results of gas analysis sampled from bodies recently exhumed after 30 years are presented. Adipocere formation has prevented the bodies from too important alteration, and gaseous areas were identified. The sampling was performed with airtight syringes assisted by multi-detector computed tomography (MDCT) in those specific areas. The important amount of methane (CH4), coupled to weak amounts of hydrogen (H2) and carbon dioxide (CO2), usual gaseous alteration indicators, have permitted to confirm methanogenesis mechanism for long period of alteration. H2 and CO2 produced during the first stages of the alteration process were consumed through anaerobic oxidation by methanogenic bacteria, generating CH4.

A realistic Computed Tomography simulator for small motion analysis of cerebral aneurysms.

This paper describes a realistic simulator for the Computed Tomography (CT) scan process for motion analysis. In fact, we are currently developing a new framework to find small motion from the CT scan. In order to prove the fidelity of this framework, or potentially any other algorithm, we present in this paper a simulator to simulate the whole CT acquisition process with a priori known parameters. In other words, it is a digital phantom for the motion analysis that can be used to compare the results of any related algorithm with the ground-truth realistic analytical model. Such a simulator can be used by the community to test different algorithms in the biomedical imaging domain. The most important features of this simulator are its different considerations to simulate the best the real acquisition process and its generality.

Comprehensive analysis of proteins secreted by dermatophytes in a protein medium which to some extent mimic "in vivo" growth parameters

RESUME : Les dermatophytes sont les agents infectieux les plus fréquents responsables de la plupart des mycoses superficielles chez les humains et chez les animaux. Ces infections, dermatophytoses, également appelées tineas ou teignes, sont fréquentes et causent des problèmes de santé publique au niveau mondial. La capacité d'envahir et de progresser au sein des structures kératinisées est probablement liée à la sécrétion de différentes enzymes kératinolytiques, qui sont considérées comme la principale caractéristique liée à la pathogénicité de ces champignons. L'objectif de ma thèse a été premièrement de progresser dans l'identification et la caractérisation des nouvelles protéines sécrétées, afin de mieux comprendre a) la capacité globale des dermatophytes à envahir les structures kératinisées, et b) les différences dans la virulence et la spécificité d'hôte que présentent les espèces étudiées .Pour progresser dans l'identification et la caractérisation de ces nouvelles protéines, les secretomes de six espèces de dermatophytes (Trichophyton rubrum, Trichophyton violaceum, Trichophyton soudanense, Trichophyton equinum, Arthroderma vanbreuseghemii et Trichophyton tonsurans) ont été étudiés. Bien qu'il y ait un niveau globalement élevé de similitude entre les protéases sécrétées, les différentes espèces de dermatophytes sécrètent des profiles protéiques distincts lorsqu'elles sont cultivées dans les mêmes conditions de culture, et donc une signature spécifique a pu être associé à chaque espèce. Ces profiles ont été un outil avantageux pour identifier et cartographier les protéines orthologues aux six espèces et ont aussi permit la discrimination d'espèces très proches comme T. tonsurans et T. equinum qui ne peuvent pas être différenciées par l'ADN ribosomal. Ce travail également présente ce que l'on croit être la première identification global des protéines sécrétées par les dermatophytes dans des conditions de culture que incitent l'activité protéolytique extracellulaire. Ce catalogue de protéines, comprenant des endo- and exo- proteases, autres hydrolases, oxydoreductases et des protéines avec fonction inconnue, représente probablement le spectre d'enzymes qui permettent la dégradation des tissus kératinisés en composés qui peuvent être assimilés par le champignon. Les résultats suggèrent qu'un changement écologique pourrait être associé à une expression différentielle des gènes codant les protéines sécrétées, en particulier, les protéases, plutôt qu'à des divergences génétiques au niveau des gènes codant les protéines orthologues. Une sécrétion différentielle des protéines par les dermatophytes pourrait également être responsable de la variabilité inflammatoire qui causent ces agents infectieux chez les différents hôtes. Par conséquent, les protéines identifiées ici sont également importantes pour faire la lumière sur la réponse immunitaire de l'hôte au cours du processus infectieux. SUMMARY : Dermatophytes are the most common infectious agents responsible for superficial mycosis in humans and animals. Dermatophytoses, also called tineas or ringworm, are frequent and cause public health problems worldwide. The secretion of different keratinolytic enzymes is believed to be a key pathogenicity-related characteristic of these fungi. The aim of this work was first to progress in the identification and characterization of novel secreted proteins, in order to better understand a) the overall capability of dermatophytes to invade keratinised structures, and b) differences in virulence and host-specificity of the investigated species. To progress in the identification and characterization of novel proteins, the secretomes from Trichophyton rubrum, Trichophyton violaceum, Trichophyton soudanense, Trichophyton equinum, Arthroderma vanbreuseghemii and Trichophyton tonsurans were studied. Although there is a high global level of similarity among the secreted proteases, different dermatophyte species produce distinct patterns of proteins when grown in the same culture medium, and so a specific signature could be associated to each species. These patterns were useful to identify and map orthologous proteins among the six species, as well as to discriminate the closely related species T. tonsurans and T. equinum, which cannot be differentiated by ribosomal DNA. This work also presents the first in-depth identification of the major proteins secreted by dermatophytes growing under conditions promoting extracellular proteolytic activity. This catalogue of proteins, which include several endo- and exo- proteases, other hydrolases, oxydoreductases, and proteins of unknown function, probably represents the spectrum of enzymes that allow the degradation of keratinized tissues into compounds which can be assimilated by the fungus. The results suggest that ecological switching could be related to a differential expression of genes encoding secreted proteins, particularly, proteases, rather than genetic divergences of the genes encoding orthologous proteins. Differential secretion of proteins by Dermatophyte species could also be responsible for the variable inflammation caused by the infectious agent within the host. Therefore, the proteins here identified are also important to shed light into the immune response of the host during the infection process.

Molecular Analysis of the PTEN Gene in a Choroidal Schwannoma in the Context of a Hamartomatous Syndrome

Purpose: To investigate the molecular involvement of PTEN, a tumor suppressor gene, in a case of cellular pigmented choroidal Schwannoma in a patient with hamartomatous syndrome due to heterozygous PTEN germline mutation. Methods: Histopathological, immunohistochemical, and electron microscopy analyses were performed by standard procedures. Paraffin-embedded samples of normal and tumor eye tissues were collected and DNA was extracted. A 145 bp region flanking the heterozygous c.406T>C mutation in exon 5 of PTEN was amplified by PCR and sequenced. To evaluate the allelic status of PTEN in the tumor sample, we cloned different PCR products in E. coli using a TA cloning procedure. Results: Histopathology demonstrated a posterior choroidal mass measuring 1.3 x 1.6 x 1.4 cm. The tumor was composed by fascicles of spindle cells with wavy cytoplasm. No Verrocay bodies could be identified. Scattered histiocytes with clear cytoplasm were present. By immunohistochemistry, the cells were expressing S100 and focally Melan A proteins. Pericellular type IV collagen could be demonstrated. Interlacing cytoplasmic processes covered by thick basement membrane could be found by electron microscopy as well as few premelanosomes. Moderate PTEN expression by immunohistochemistry was identified in some cells. As expected, the germline mutation could be detected by DNA sequencing in both the paraffin-embedded normal and tumor eye tissues. Analysis of 33 E. coli colonies bearing clones from the tumor eye tissue DNA surprisingly revealed that most of them contained the PTEN wild-type allele (29 vs. 4, Fisher's test p-value = 0.002). Conclusions: This is the first reported case of choroidal cellular Schwannoma arising in the context of a PTEN hamartomatous syndrome. Allelic analysis of PTEN in the tumor suggests a statistically-significant partial loss of heterozygozity in favor of the wild-type allele. Our findings are in clear contrast with what is usually observed in cancer tissues, for which mutated alleles of tumor suppressor genes are usually brought to homozygosity. Similar results were previously reported in human non-Hodgkin's lymphomas, displaying an overexpression of the wild-type form of the tumor suppressor gene p53. We are in the process of investigating additional DNA derived from other fresh and paraffin-embedded tissues from the patient, in order to gain insights on the molecular bases of PTEN involvement in this rare choroidal Schwannoma.