Melanin-specific life-history strategies.

Abstract The maintenance of genetic variation is a long-standing issue because the adaptive value of life-history strategies associated with each genetic variant is usually unknown. However, evidence for the coexistence of alternative evolutionary fixed strategies at the population level remains scarce. Because in the tawny owl (Strix aluco) heritable melanin-based coloration shows different physiological and behavioral norms of reaction, we investigated whether coloration is associated with investment in maintenance and reproduction. Light melanic owls had lower adult survival compared to dark melanic conspecifics, and color variation was related to the trade-off between offspring number and quality. When we experimentally enlarged brood size, light melanic males produced more fledglings but in poorer condition, and they were less often recruited in the local breeding population than those of darker melanic conspecifics. Our results also suggest that dark melanic males allocate a constant effort to raise their brood independently of environmental conditions, whereas lighter melanic males finely adjust reproductive effort in relation to changes in environmental conditions. Color traits can therefore be associated with life-history strategies, and stochastic environmental perturbation can temporarily favor one phenotype over others. The existence of fixed strategies implies that some phenotypes can sometimes display a "maladapted" strategy. Long-term population monitoring is therefore vital for a full understanding of how different genotypes deal with trade-offs.

Spatiotemporal adaptive multiscale multiphysics simulations of two-phase flow

We present a spatiotemporal adaptive multiscale algorithm, which is based on the Multiscale Finite Volume method. The algorithm offers a very efficient framework to deal with multiphysics problems and to couple regions with different spatial resolution. We employ the method to simulate two-phase flow through porous media. At the fine scale, we consider a pore-scale description of the flow based on the Volume Of Fluid method. In order to construct a global problem that describes the coarse-scale behavior, the equations are averaged numerically with respect to auxiliary control volumes, and a Darcy-like coarse-scale model is obtained. The space adaptivity is based on the idea that a fine-scale description is only required in the front region, whereas the resolution can be coarsened elsewhere. Temporal adaptivity relies on the fact that the fine-scale and the coarse-scale problems can be solved with different temporal resolution (longer time steps can be used at the coarse scale). By simulating drainage under unstable flow conditions, we show that the method is able to capture the coarse-scale behavior outside the front region and to reproduce complex fluid patterns in the front region.

Stab wounds in a Swiss emergency department: a series of 80 consecutive cases.

Background: Interpersonal violence is a worldwide social reality which seems to increasingly affect even the safest of countries, such as Switzerland. In this country, road traffic accidents, as well as professional and recreational activities, are the main providers of trauma-related injuries. The incidence of penetrative trauma related to stab wounds seems to be regularly increasing in our ED. The question arises of whether our strategies in trauma management are adapted to deal efficiently with these injuries.Methods: To answer this question, the study analysed patients admitted for intentional penetrative injuries in a tertiary urban emergency department (ED) during a 23 month period. Demographics, conditions of the assault, injury type and treatments applied were analysed.Results: Eighty patients admitted due to an intentional penetrating trauma accounted for 0.2% of the surgical practice of our ED. The assault occurred equally in a public or a private context, mainly affecting young males during the night and the weekend. Sixty six patients (83%) were treated as out-patients. Only 10 patients needed surgery. None of them required damage control surgery. No patient died and the mean hospital stay was 5.5 days.Conclusions: The prevalence of stab wounds in Switzerland is low. These injuries rarely need complex, surgical procedures. Observational strategies should be considered according to the patient status.

The dysfunction of T follicular helper cells.

PURPOSE OF REVIEW: T follicular helper (Tfh) cells play a critical role as providers of B-cell help and dysfunction in Tfh/B-cell interactions can lead to autoimmunity or immunodeficiency. These observations have generated a great deal of interest in understanding how these cells are affected during HIV infection and how their functional changes might affect antibody responses. RECENT FINDINGS: Recent studies have shown that HIV/simian immunodeficiency virus (SIV) infection affects both Tfh-cell frequency and function and suggest that Tfh-cell perturbations might contribute to the relative inefficiency of HIV-infected individuals to generate broadly neutralizing antibodies (bNAbs). SUMMARY: The present review will highlight these recent findings addressing the role of Tfh cells in HIV infection as well as the impact HIV infection has on Tfh and circulating memory Tfh (cTfh) cell frequency and function.

Quantitative morphometry analysis of the fetal brain using clinical MR imaging

In vivo fetal magnetic resonance imaging provides aunique approach for the study of early human braindevelopment [1]. In utero cerebral morphometry couldpotentially be used as a marker of the cerebralmaturation and help to distinguish between normal andabnormal development in ambiguous situations. However,this quantitative approach is a major challenge becauseof the movement of the fetus inside the amniotic cavity,the poor spatial resolution provided by very fast MRIsequences and the partial volume effect. Extensiveefforts are made to deal with the reconstruction ofhigh-resolution 3D fetal volumes based on severalacquisitions with lower resolution [2,3,4]. Frameworkswere developed for the segmentation of specific regionsof the fetal brain such as posterior fossa, brainstem orgerminal matrix [5,6], or for the entire brain tissue[7,8], applying the Expectation-Maximization MarkovRandom Field (EM-MRF) framework. However, many of theseprevious works focused on the young fetus (i.e. before 24weeks) and use anatomical atlas priors to segment thedifferent tissue or regions. As most of the gyraldevelopment takes place after the 24th week, acomprehensive and clinically meaningful study of thefetal brain should not dismiss the third trimester ofgestation. To cope with the rapidly changing appearanceof the developing brain, some authors proposed a dynamicatlas [8]. To our opinion, this approach however faces arisk of circularity: each brain will be analyzed /deformed using the template of its biological age,potentially biasing the effective developmental delay.Here, we expand our previous work [9] to proposepost-processing pipeline without prior that allow acomprehensive set of morphometric measurement devoted toclinical application. Data set & Methods: Prenatal MRimaging was performed with a 1-T system (GE MedicalSystems, Milwaukee) using single shot fast spin echo(ssFSE) sequences (TR 7000 ms, TE 180 ms, FOV 40 x 40 cm,slice thickness 5.4mm, in plane spatial resolution1.09mm). For each fetus, 6 axial volumes shifted by 1 mmwere acquired under motherâeuro?s sedation (about 1min pervolume). First, each volume is segmentedsemi-automatically using region-growing algorithms toextract fetal brain from surrounding maternal tissues.Inhomogeneity intensity correction [10] and linearintensity normalization are then performed. Brain tissues(CSF, GM and WM) are then segmented based on thelow-resolution volumes as presented in [9]. Ahigh-resolution image with isotropic voxel size of 1.09mm is created as proposed in [2] and using B-splines forthe scattered data interpolation [11]. Basal gangliasegmentation is performed using a levet setimplementation on the high-resolution volume [12]. Theresulting white matter image is then binarized and givenas an input in FreeSurfer software(http://surfer.nmr.mgh.harvard.edu) to providetopologically accurate three-dimensional reconstructionsof the fetal brain according to the local intensitygradient. References: [1] Guibaud, Prenatal Diagnosis29(4) (2009). [2] Rousseau, Acad. Rad. 13(9), 2006. [3]Jiang, IEEE TMI 2007. [4] Warfield IADB, MICCAI 2009. [5]Claude, IEEE Trans. Bio. Eng. 51(4) 2004. [6] Habas,MICCAI 2008. [7] Bertelsen, ISMRM 2009. [8] Habas,Neuroimage 53(2) 2010. [9] Bach Cuadra, IADB, MICCAI2009. [10] Styner, IEEE TMI 19(39 (2000). [11] Lee, IEEETrans. Visual. And Comp. Graph. 3(3), 1997. [12] BachCuadra, ISMRM 2010.

On y voit rien. Le recours aux sources de presse pour l'analyse des mobilisations protestataires

Aujourd'hui la PEA est devenue la méthode la plus employée dans le champ des études de mobilisation. Toutefois, il est frappant que les limites, nombreuses, de cette méthode, demeurent peu explorées, malgré une abondante littérature critique. C'est à ces questions des biais propres aux sources de presse dans le cadre de la PEA et aux moyens de les explorer que ce working paper se consacre. Nous commencerons par montrer, en deux temps, comment la question de la systématicité gagne à être explorée à partir d'enquêtes qualitatives, en nous appuyant sur un travail inédit mené naguère auprès du journal Le Monde, dans le cadre d'une recherche collective sur les transformations de l'activisme environnemental en Europe, dont les données seront comparées avec des sources de police, le dépouillement des dépêches de l'Agence France-Presse sur six mois, et surtout une série d'interviews avec des journalistes spécialisés dans l'environnement. L'on revient dans un second temps à la question de la sélectivité des sources en tentant de montrer comment dans toute une série de circonstances et pour toute une série de groupes, les luttes ne sauraient se réduire ni aux événements protestataires ni à un appel à l'Etat ou à l'opinion. L'on espère ainsi proposer des moyens de se garder d'un défaut commun à tout conventionnalisme méthodologique qui, ici comme ailleurs, frappe la recherche, soit la réitération de mesures conventionnelles ayant pour effet de les institutionnaliser en dehors de toute réflexion sur leur pertinence. Protest Events Analysis (PEA) has by no doubts become one the most used method in the field of social movement research. Yet, the numerous biases of that method have not been explored completely, despite a rich litterature. Our paper first proposes a discussion of the systematicity of biases, based on an empirical research on environmental journalists in various French newspapers and Agence France press. Secondly, we deal with the question of selectivity of biases. Finally, we propose some methodological recommendations in order to improve our understanding of social movements and to avoid methodological conventionalism.

From dialysis to transplantation, illness experience and patients' concerns about future: A longitudinal qualitative study

Background: Transplantation is the treatment of choice when compared to dialysis. Long-term evolution of patients is rarely comprehensively described. Thirty end-stage renal disease patient's experience of illness was explored from registration for transplantation until twenty-four months after transplantation. Methods: Longitudinal semi-structured interviews were conducted, and qualitative discourse analysis performed. Findings: Before transplantation loss of quality of life (QOL), emotional fragility related to dialysis constraints were reported, and increased with waiting-time. Six months after transplantation, recovered freedom was described but acute rejection, and life-dependency to immunosuppressants generated concerns. After twelve months, long-term survival of the graft, and possible return-to-dialysis were mentioned. After twenty months graft's dysfunction, co-morbidities, immunosuppressants side effects rose concerns even though QOL persisted. Most patients report positive transformations after transplantation, which are related to graft survival and limited co-morbidities. Discussion: As time passes, patients deal with changing illness constraints, and contemplate with anxiety possible new return to dialysis and/or transplantation.

Extension of Murray's law using a non-Newtonian model of blood flow.

BACKGROUND: So far, none of the existing methods on Murray's law deal with the non-Newtonian behavior of blood flow although the non-Newtonian approach for blood flow modelling looks more accurate. MODELING: In the present paper, Murray's law which is applicable to an arterial bifurcation, is generalized to a non-Newtonian blood flow model (power-law model). When the vessel size reaches the capillary limitation, blood can be modeled using a non-Newtonian constitutive equation. It is assumed two different constraints in addition to the pumping power: the volume constraint or the surface constraint (related to the internal surface of the vessel). For a seek of generality, the relationships are given for an arbitrary number of daughter vessels. It is shown that for a cost function including the volume constraint, classical Murray's law remains valid (i.e. SigmaR(c) = cste with c = 3 is verified and is independent of n, the dimensionless index in the viscosity equation; R being the radius of the vessel). On the contrary, for a cost function including the surface constraint, different values of c may be calculated depending on the value of n. RESULTS: We find that c varies for blood from 2.42 to 3 depending on the constraint and the fluid properties. For the Newtonian model, the surface constraint leads to c = 2.5. The cost function (based on the surface constraint) can be related to entropy generation, by dividing it by the temperature. CONCLUSION: It is demonstrated that the entropy generated in all the daughter vessels is greater than the entropy generated in the parent vessel. Furthermore, it is shown that the difference of entropy generation between the parent and daughter vessels is smaller for a non-Newtonian fluid than for a Newtonian fluid.

Effective corporate governance : experimental evidence on international auditors'judgments and the contribution of financial accounting education

1 Summary This dissertation deals with two major aspects of corporate governance that grew in importance during the last years: the internal audit function and financial accounting education. In three essays, I contribute to research on these topics which are embedded in the broader corporate governance literature. The first two essays consist of experimental investigations of internal auditors' judgments. They deal with two research issues for which accounting research lacks evidence: The effectiveness of internal controls and the potentially conflicting role of the internal audit function between management and the audit committee. The findings of the first two essays contribute to the literature on internal auditors' judgment and the role of the internal audit function as a major cornerstone of corporate governance. The third essay theoretically examines a broader issue but also relates to the overall research question of this dissertation: What contributes to effective corporate governance? This last essay takes the perspective that the root for quality corporate governance is appropriate financial accounting education. r develop a public interest approach to accounting education that contributes to the literature on adequate accounting education with respect to corporate governance and accounting harmonization. The increasing importance of both the internal audit function and accounting education for corporate governance can be explained by the same recent fundamental changes that still affect accounting research and practice. First, the Sarbanes-Oxley Act of 2002 (SOX, 2002) and the 8th EU Directive (EU, 2006) have led to a bigger role for the internal audit function in corporate governance. Their implications regarding the implementation of audit committees and their oversight over internal controls are extensive. As a consequence, the internal audit function has become increasingly important for corporate governance and serves a new master (i.e. the audit committee) within the company in addition to management. Second, the SOX (2002) and the 8th EU Directive introduced additional internal control mechanisms that are expected to contribute to the reliability of financial information. As a consequence, the internal audit function is expected to contribute to a greater extent to the reliability of financial statements. Therefore, effective internal control mechanisms that strengthen objective judgments and independence become important. This is especially true when external- auditors rely on the work of internal auditors in the context of the International Standard on Auditing (ISA) 610 and the equivalent US Statement on Auditing Standards (SAS) 65 (see IFAC, 2009 and AICPA, 1990). Third, the harmonization of international reporting standards is increasingly promoted by means of a principles-based approach. It is the leading approach since a study of the SEC (2003) that was required by the SOX (2002) in section 108(d) was in favor of this approach. As a result, the Financial Accounting Standards Board (FASB) and the International Accounting Standards Board (IASB) commit themselves to the development of compatible accounting standards based on a principles-based approach. Moreover, since the Norwalk Agreement of 2002, the two standard setters have developed exposure drafts for a common conceptual framework that will be the basis for accounting harmonization. The new .framework will be in favor of fair value measurement and accounting for real-world economic phenomena. These changes in terms of standard setting lead to a trend towards more professional judgment in the accounting process. They affect internal and external auditors, accountants, and managers in general. As a consequence, a new competency set for preparers and users of financial statements is required. The basil for this new competency set is adequate accounting education (Schipper, 2003). These three issues which affect corporate governance are the initial point of this dissertation and constitute its motivation. Two broad questions motivated a scientific examination in three essays: 1) What are major aspects to be examined regarding the new role of the internal audit function? 2) How should major changes in standard setting affect financial accounting education? The first question became apparent due to two published literature reviews by Gramling et al. (2004) and Cohen, Krishnamoorthy & Wright (2004). These studies raise various questions for future research that are still relevant and which motivate the first two essays of my dissertation. In the first essay, I focus on the role of the internal audit function as one cornerstone of corporate governance and its potentially conflicting role of serving both management and the audit committee (IIA, 2003). In an experimental study, I provide evidence on the challenges for internal auditors in their role as servant for two masters -the audit committee and management -and how this influences internal auditors' judgment (Gramling et al. 2004; Cohen, Krishnamoorthy & Wright, 2004). I ask if there is an expectation gap between what internal auditors should provide for corporate governance in theory compared to what internal auditors are able to provide in practice. In particular, I focus on the effect of serving two masters on the internal auditor's independence. I argue that independence is hardly achievable if the internal audit function serves two masters with conflicting priorities. The second essay provides evidence on the effectiveness of accountability as an internal control mechanism. In general, internal control mechanisms based on accountability were enforced by the SOX (2002) and the 8th EU Directive. Subsequently, many companies introduced sub-certification processes that should contribute to an objective judgment process. Thus, these mechanisms are important to strengthen the reliability of financial statements. Based on a need for evidence on the effectiveness of internal control mechanisms (Brennan & Solomon, 2008; Gramling et al. 2004; Cohen, Krishnamoorthy & Wright, 2004; Solomon & Trotman, 2003), I designed an experiment to examine the joint effect of accountability and obedience pressure in an internal audit setting. I argue that obedience pressure potentially can lead to a negative influence on accountants' objectivity (e.g. DeZoort & Lord, 1997) whereas accountability can mitigate this negative effect. My second main research question - How should major changes in standard setting affect financial accounting education? - is investigated in the third essay. It is motivated by the observation during my PhD that many conferences deal with the topic of accounting education but very little is published about what needs to be done. Moreover, the Endings in the first two essays of this thesis and their literature review suggest that financial accounting education can contribute significantly to quality corporate governance as argued elsewhere (Schipper, 2003; Boyce, 2004; Ghoshal, 2005). In the third essay of this thesis, I therefore focus on approaches to financial accounting education that account for the changes in standard setting and also contribute to corporate governance and accounting harmonization. I argue that the competency set that is required in practice changes due to major changes in standard setting. As the major contribution of the third article, I develop a public interest approach for financial accounting education. The major findings of this dissertation can be summarized as follows. The first essay provides evidence to an important research question raised by Gramling et al. (2004, p. 240): "If the audit committee and management have different visions for the corporate governance role of the IAF, which vision will dominate?" According to the results of the first essay, internal auditors do follow the priorities of either management or the audit committee based on the guidance provided by the Chief Audit executive. The study's results question whether the independence of the internal audit function is actually achievable. My findings contribute to research on internal auditors' judgment and the internal audit function's independence in the broader frame of corporate governance. The results are also important for practice because independence is a major justification for a positive contribution of the internal audit function to corporate governance. The major findings of the second essay indicate that the duty to sign work results - a means of holding people accountable -mitigates the negative effect of obedience pressure on reliability. Hence, I found evidence that control .mechanisms relying on certifications may enhance the reliability of financial information. These findings contribute to the literature on the effectiveness of internal control mechanisms. They are also important in the light of sub-certification processes that resulted from the Sarbanes-Oxley Act and the 8th EU Directive. The third essay contributes to the literature by developing a measurement framework that accounts for the consequences of major trends in standard setting. Moreovér, it shows how these trends affect the required .competency set of people dealing with accounting issues. Based on this work, my main contribution is the development of a public interest approach for the design of adequate financial accounting curricula. 2 Serving two masters: Experimental evidence on the independence of internal auditors Abstract Twenty nine internal auditors participated in a study that examines the independence of internal auditors in their potentially competing roles of serving two masters: the audit committee and management. Our main hypothesis suggests that internal auditors' independence is not achievable in an institutional setting in which internal auditors are accountable to two different parties with potentially differing priorities. We test our hypothesis in an experiment in which the treatment consisted of two different instructions of the Chief audit executive; one stressing the priority of management (cost reduction) and one stressing the priority of the audit committee (effectiveness). Internal auditors had to evaluate internal controls and their inherent costs of different processes which varied in their degree of task complexity. Our main results indicate that internal auditors' evaluation of the processes is significantly different when task complexity is high. Our findings suggest that internal auditors do follow the priorities of either management or the audit committee depending on the instructions of a superior internal auditor. The study's results question whether the independence of the internal audit function is actually achievable. With our findings, we contribute to research on internal auditors' judgment and the internal audit function's independence in the frame of corporate governance.

Nouvelles recommandations de l'ESH/ESC: des changements en douceur pour le malade hypertendu [New recommendations of the ESH/ESC: smooth changes for the hypertensive patient].

The last recommendations of the European Society of Hypertension and the European Society of Cardiology made available deal with the diagnosis and the treatment of arterial hypertension. They point to the importance of both 24-hour ambulatory blood pressure monitoring and home blood pressure measurement. They also underscore the importance of stratifying cardiovascular risk and of controlling strictly blood pressure using hygienic measures and antihypertensive drugs, either as monotherapy or combination therapy.

Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes.

Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells.

Development of a harmonised method for the profiling of amphetamine

Résumé : Cette thèse de doctorat est le fruit d'un projet de recherche européen financé par le quatrième programme cadre de la Commission Européenne (DG XII, Standards, Measurement and Testing). Ce projet, dénommé SMT-CT98-2277, a été financé pour la partie suisse par l'Office Fédéral de l'Education et de la Science (OFES, Berne, Suisse). Le but de ce projet était de développer une méthode harmonisée et collaborativement testée pour le profilage des impuretés de l'amphétamine illicite par chromatographie capillaire en phase gazeuse. Le travail a été divisé en sept phases majeures qui concernaient la synthèse de l'amphétamine, l'identification d'impuretés, l'optimisation de la préparation de l'échantillon et du système chromatographique, la variabilité des résultats, l'investigation de méthodes mathématiques pour la classification et la comparaison de profils et finalement l'application de la méthode à des réels échantillons illicites. La méthode résultant de ce travail n'a pas seulement montré que les données étaient interchangeables entre laboratoires mais aussi qu'elle était supérieure en de nombreux points aux méthodes préalablement publiées dans la littérature scientifique. Abstract : This Ph.D. thesis was carried out in parallel to an European project funded by the fourth framework program of the European Commission (DG XII, Standards, Measurement and Testing). This project, named SMT-CT98-2277 was funded, for the Swiss part, by the Federal Office of Education and Science (OFES, Bern, Switzerland). The aim of the project was to develop a harmonised, collaboratively tested method for the impurity profiling of illicit amphetamine by capillary gas chromatography. The work was divided into seven main tasks which deal with the synthesis of amphetamine, identification of impurities, optimization of sample preparation and of the chromatographic system, variability of the results, investigation of numerical methods for the classification and comparison of profiles and finally application of the methodology to real illicit samples. The resulting method has not only shown to produce interchangeable data between different laboratories but was also found to be superior in many aspects to previously published methods.

Quelle perception ont les médecins de famille en Suisse de leur rôle dans la prévention et la promotion de la santé? : comprendre les barrières à l'implémentation

Introduction: The importance of health promotion and prevention and the potential of general practitioners (GPs) to conduct individual prevention procedures have been demonstrated in several studies. Clinical recommendations for screening and prevention activities, an important condition for success, are published regularly, but their implementation into daily practice does not necessarily follow. Information is lacking about the actual conditions of how prevention is carried out on a daily basis by Swiss GPs, about their perceptions and needs, their attitudes and the present barriers they face. Such information is essential for the development of new tools and programs targeting better implementation of clinical recommendations for prevention in primary care in Switzerland. Objectives: The objectives of the study were to analyze how Swiss GPs perceive their role in prevention by obtaining information regarding the following issues: What do disease prevention and health promotion mean to them? What are the current incentives and barriers they face? What are their ideas and suggestions to deal with these barriers? What are their needs and expectations regarding prevention guidelines and tools? Methods: We conducted a qualitative research project using focus groups to examine the questions mentioned above. A total of 13 focus groups took place including GPs from eight cantons: five groups in German- speaking Switzerland and eight in French- speaking Switzerland. Each group was composed of 4-11 GPs, making in total 102 participants, who were paid expenses to cover their participation. The sessions were audio-recorded and transcribed verbatim. Data analysis: Content analysis of the transcriptions began by classifying the data according to a typology, the first level of which was developed in line with the structure of the interview guide. This typology was extended by successively regrouping similar statements. Synopsis and interpretation was then performed on each category thus obtained. This research report is based on the results from the French-speaking cantons. Results: Physicians perceive a change in their role as a consequence of changes in society and the health system. They emphasize the importance of a personalized and long lasting relationship between the family doctor and his/her patient; a privileged position allowing them to perform individualized prevention activities, considered to be more effective, as they are appropriate to the specific situation and needs of the patient. They point out their need for training and for better information concerning prevention and health promotion interventions, and stress difficulties arising from the lack of a clear political signal conferring them with a mandate for prevention. -- INTRODUCTION L'importance de la prévention et de la promotion de la santé et le potentiel des médecins de famillea à mettre en oeuvre des mesures individuelles de prévention, de dépistage et de conseils, a été démontrée dans plusieurs études. Régulièrement durant les dernières années, de nombreuses associations médicales ont publié des recommandations cliniques concernant les activités de dépistage et de prévention qui sont une condition essentielle pour le succès, mais ne sont pas forcément appliquées de manière systématique dans la pratique médicale quotidienne. Des contraintes spécifiques contribuent à l'écart entre le désir des médecins de pratiquer une médecine préventive et la réalité d'un cabinet médical. Nous n'avons que peu de données sur les conditions actuelles dans lesquelles la prévention et la promotion de la santé sont réalisées par les médecins de famille suisses dans leur travail quotidien. Des informations précises et représentatives sur leurs perceptions et leurs besoins, leurs attitudes et les contraintes auxquelles ils sont confrontés manquent. Or ces données sont essentielles dans le développement de nouveaux outils et programmes visant une meilleure implémentation des recommandations cliniques dans le domaine de la prévention et la promotion de la santé dans la médecine de famille en Suisse. OBJECTIFS Le développement de concepts pour une prévention systématique ainsi que d'outils adéquats, tout comme l'amélioration des conditions qui permettent une implémentation à grande échelle, implique, avant tout, l'analyse de la perception que les médecins de famille suisses ont de leur rôle dans la prévention. Par conséquent, cette étude a eu pour objectif d'obtenir des informations concernant les questions suivantes : ? Que signifient la prévention et la promotion de la santé pour les médecins de famille suisses ? ? Quelles sont leurs incitations et les barrières rencontrées ? ? Quelles sont leurs idées et leurs suggestions pour faire face à ces contraintes ? ? Quels sont leurs besoins et leurs attentes concernant les outils pour la prévention ? METHODES Nous avons mené un projet de recherche qualitative en utilisant la technique des focus groups pour examiner les questions mentionnées ci-dessus. Une telle technique de collecte de données est particulièrement adaptée à un domaine où l'on connaît mal les perceptions des parties prenantes. Nous avons mené 13 focus groups au total, comprenant des médecins issus de huit cantons: cinq groupes ont eu lieu en Suisse alémanique et huit groupes en Suisse romande. Chaque groupe était composé de 4 à 11 médecins de famille, avec au total 102 participants qui ont été défrayés pour leur participation. Les séances ont été audio-enregistrées et transcrites. ANALYSE DES DONNEES L'analyse du contenu des transcriptions a commencé par la classification des données selon une typologie dont le premier niveau a été développé à partir de la structure de la grille d'entretiens. Cette typologie a été affinée et élargie en regroupant successivement des propos similaires. Une synthèse a été effectuée pour chaque catégorie. Ce rapport est basé sur les résultats de l'analyse des données des cantons francophones. RESULTATS Les médecins perçoivent un changement de leur rôle dans une société et dans un système de santé qui évoluent. Ils soulignent l'importance de la relation personnalisée et durable du médecin de famille avec son patient, atout précieux, qui leur permet de réaliser des activités de prévention individualisées et adaptées à la situation et aux besoins du patient, considérées plus efficaces. Afin de surmonter leur doutes et découragement par rapport aux interventions de prévention, ils pointent la nécessité d'une formation aux nouvelles connaissances en prévention et promotion de la santé et d'une meilleure information aux médecins quant à leur efficacité et importance. Ils montrent le besoin d'un signal clair des politiques par rapport à l'attribution de ce mandat aux médecins de famille et de leur reconnaissance en tant qu'acteur de prévention dans le système de santé.

Intervention de la pensée représentative de futurs enseignant-e-s dans leurs prises de position envers l'intégration scolaire

In the past two decades, international recommendations have made inclusive education a priority issue. Many countries have adopted school policies inciting players to question their representations about the duties and purposes of schooling and their role therein. In Switzerland, a new national and cantonal framework defines the integration of students with disabilities or special educational needs in the regular classroom as a priority. However, progress in this area is modest and many researchers are left wondering how teachers could be better prepared to meet the special needs of some students. Initial training is thus seen as essential in bringing pre-service teachers to develop open attitudes toward students with disabilities or special educational needs. While many studies have examined the role of training in building professional attitudes, very few deal with teacher representations of inclusive education, let alone those of future teachers. Our research focuses on two samples of pre-service teachers in the beginning, middle or end of their initial training. 261 pre-service teachers for primary education and 212 pre-service teachers for secondaiy education are involved in the study. The research aims to highlight the role of their representative thinking in building their attitudes towards inclusive education. Our results show that objectification remains essentialist and focuses on the prototypes of the most publicized disabilities. They also showed the weakness of the training system as perceived by future teachers. Even though they have maintained or strengthened positive attitudes towards integration, most leave their training with a reinforced sense of apprehension when faced with the disabilities or special educational needs that they expect to encounter in their future work. Although pre-service teachers consider their training insufficient, it nevertheless positively influences their attitudes toward integration. In particular, greater internship practice, however modest it may be, has a significant effect on attitudes of future teachers by increasing their perception of competence and confidence. -- Ces deux dernières décennies, les recommandations internationales ont fait de l'inclusion scolaire une thématique prioritaire. De nombreux pays ont adopté des politiques scolaires obligeant les acteurs scolaires à interroger leurs représentations des missions de l'école et leur rôle au sein de celle-ci. En Suisse, un nouveau cadre national et cantonal a défini comme prioritaire l'intégration dans l'école ordinaire des élèves en situation de handicap ou ayant des besoins éducatifs particuliers. Or, les avancées en la matière restent modestes et de nombreux chercheurs se questionnent sur la manière dont les enseignant-e-s pourraient être mieux préparés à répondre aux besoins éducatifs particuliers de certains élèves. La formation initiale est ainsi perçue comme essentielle pour amener les futurs enseignant-e-s pour développer des attitudes ouvertes envers les élèves en situation de handicap ou ayant des besoins éducatifs particuliers. Si beaucoup d'études portent sur le rôle de la formation dans la construction d'attitudes professionnelles, très peu traitent des représentations des enseignant-e-s à l'égard de l'intégration scolaire et encore moins de celles des futurs enseignant-e-s. Notre recherche porte sur deux populations de futurs enseignant-e-s en début, au milieu ou en fin de formation. Elles sont composées respectivement de 261 étudiant-e-s se destinant à l'enseignement primaire et de 212 étudiant-e-s se destinant à l'enseignement secondaire. La recherche vise à mettre en évidence l'intervention de leur pensée représentative dans leurs prises de position envers l'intégration scolaire. Nos résultats montrent que l'objectivation reste essentialiste et se focalise sur les prototypes de situations de handicap les plus médiatisés. Nos résultats font également fait apparaître la faiblesse du dispositif de formation tel que perçu les futurs enseignant-e-s. Quand bien même ont-ils conservé ou renforcé des attitudes favorables à l'intégration, ils quittent pour la plupart leur formation avec une appréhension renforcée à l'égard des situations de handicap ou de besoins éducatifs particuliers qu'ils s'attendent à rencontrer dans leur future pratique. Bien que la formation soit jugée insuffisante par les étudiant-e-s, elle oriente néanmoins favorablement leurs prises de position envers l'intégration des élèves concernés. En particulier, une plus grande pratique de stage, si modeste soit-elle, a un effet important sur ces prises de position par l'augmentation du sentiment de compétence et la perception d'assurance des futurs enseignant-e-s.

A single epidermal stem cell strategy for safe ex vivo gene therapy.

There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells before they are transplanted. To address this, we have developed a strategy that permits transplantation of a clonal population of genetically corrected autologous stem cells that meet stringent selection criteria and the principle of precaution. As a proof of concept, we have stably transduced epidermal stem cells (holoclones) obtained from a patient suffering from recessive dystrophic epidermolysis bullosa. Holoclones were infected with self-inactivating retroviruses bearing a COL7A1 cDNA and cloned before the progeny of individual stem cells were characterised using a number of criteria. Clonal analysis revealed a great deal of heterogeneity among transduced stem cells in their capacity to produce functional type VII collagen (COLVII). Selected transduced stem cells transplanted onto immunodeficient mice regenerated a non-blistering epidermis for months and produced a functional COLVII. Safety was assessed by determining the sites of proviral integration, rearrangements and hit genes and by whole-genome sequencing. The progeny of the selected stem cells also had a diploid karyotype, was not tumorigenic and did not disseminate after long-term transplantation onto immunodeficient mice. In conclusion, a clonal strategy is a powerful and efficient means of by-passing the heterogeneity of a transduced stem cell population. It guarantees a safe and homogenous medicinal product, fulfilling the principle of precaution and the requirements of regulatory affairs. Furthermore, a clonal strategy makes it possible to envision exciting gene-editing technologies like zinc finger nucleases, TALENs and homologous recombination for next-generation gene therapy.