Targeting Notch signaling in pancreatic cancer.

IMPORTANCE OF THE FIELD: With some 220,000 new cases/year in the world, pancreatic adenocarcinoma is the fourth highest cause of death by cancers. Among newly diagnosed patients about 210,000 will die within 9 months following diagnosis. Therefore, effective adjuncts to current treatment strategies are necessary. Because embryological signaling pathways are upregulated in pancreatic adenocarcinoma, they represent potential targets for future therapies. AREAS COVERED IN THIS REVIEW: Our aim is to present the Notch pathway, and to describe its involvement in pancreatic pathophysiology/carcinogenesis. This pathway appeared as a prime target for pancreatic cancer therapy. In the light of the crosstalk of Notch with other survival/embryologic pathways, drugs affecting more than one pathway may have to be combined. WHAT THE READER WILL GAIN: Drugs against gamma-secretases could thus serve in cancer treatment and can be combined with drugs targeting survival pathways interplaying with Notch such as Hedgehog. TAKE HOME MESSAGE: Downregulation of Notch contributes to the inhibition and apoptosis of pancreatic cancer cells whereas Hedgehog inhibition will allow for enhanced delivery of drugs to the tumor. Both pathway inhibitors appear to have synergistic effects for future therapeutics for pancreatic adenocarcinoma, once safety issues of compounds are overcome.

Using plan analysis in psychotherapeutic case formulation of borderline personality disorder.

A comprehensive understanding of the patient's problems is essential for a constructive therapeutic behaviour, especially in borderline personality disorder (BPD) where difficult interpersonal patterns are persistent. In these circumstances, the use of an integrative case formulation approach such as Plan Analysis, developed by K. Grawe and F. Caspar, can be of help for therapy planning. The focus here is on instrumental relations between behaviours and the hypothetical Plans and motives 'behind' those behaviours. The present qualitative study aimed at setting a prototypical Plan structure for n = 15 patients presenting a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of BPD using Plan Analysis. The first psychotherapeutic session of every outpatient was video-taped and evaluated according to the Plan Analysis procedure. Inter-rater reliability was established between two independent raters and was considered sufficient. The detailed prototypical Plan structure of BPD showed two main tendencies: first, the important presence of support-seeking among these patients and second, the will to be in control and to protect oneself. This study confirms the existence of several core similarities in the functioning of patients with BPD. These findings are in line with earlier studies and expand the latter with the aim of contributing to the understanding of BPD psychopathology. Clinical implications are discussed. Copyright © 2011 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Plan Analysis can especially be of help with patients who have difficult interpersonal patterns, as those presenting with BPD. Two tendencies were found within BPD patients: (1) support-seeking and (2) control and self-protecting Plans. Further research using Plan Analysis should focus on the identification and detail of emotions within BPD.

The role of magma rheology during emplacement of the Listino Suite, Adamello Massif, Italy

This thesis studies individual and contextual antecedents of anti-immigrant attitudes by drawing on intergroup threat and contact, social representation, and value theories. As an alternative to previous multilevel research on the topic, it aims to articulate levels of analysis by putting forward a Person x Context Interaction approach. Moreover, rather than focussing exclusively on the impact of a large immigrant proportion, by introducing ideological climates, it develops and examines the normative societal context in which individuals are embedded. The studies largely draw on cross-sectional survey data across Swiss municipalities (Studies 1 to 3) and European countries (Study 4), but are complemented by elite discourses (Study 5) and online collected survey data (Study 6). Study 1 distinguishes between valued and devalued immigrants, thereby shedding light on the impact of immigrant proportion on intergroup contact and threat. Study 2 focuses on the link between immigrant proportion and attitudes towards the Muslim veil by examining its joint impact with conservative ideologies on the individual and municipality level. Aiming to explain threat related to immigrants, the interplay between immigrant proportion and ideological climates is studied across Swiss municipalities (Study 3) and European countries (Study 4). In addition, by adopting a Person x Context Interaction approach, it is investigated whether a context galvanizes individuals already prone to viewing immigrants as threatening, or mobilizes those generally least likely to express prejudice. Finally, to better understand the role political elites play in fuelling ideological climates, the official discourses on the 2011 England riots are analysed (Study 5). With online survey data collected during the riots, it is then shown that once endorsed, threat-eliciting climates are likely to mobilize negative ethnic diversity attitudes in the larger population (Study 6). Overall, this thesis proposes an integrative approach to studying anti-immigrant attitudes and discusses theoretical and methodological implications. - La présente thèse se penche sur les antécédents individuels et contextuels des attitudes négatives envers les immigré e s, en combinant les théories de la menace intergroupe, du contact, des représentations sociales et des valeurs. Elle a plus précisément pour but d'articuler différents niveaux d'analyse à travers une approche insistant sur les interactions entre Individu et Contexte. Ce faisant, elle propose une alternative aux recherches précédentes sur le thème, basées sur une perspective multiniveau plus « classique ». Au lieu de se pencher uniquement sur l'impact de la présence de populations immigrées dans un lieu donné, la recherche réalisée a par ailleurs développé et étudié le concept de climat idéologique, à savoir le contexte normatif au sein duquel les individus sont plongés au quotidien. Les études composant cette thèse se basent essentiellement sur des données d'enquête de grande échelle, récoltées dans diverses municipalités Suisses (Etudes 1 à 3) ou divers pays Européens (Etude 4). Elles sont complétées par l'analyse de discours politiques (Etude 5) et de données récoltées sur internet (Etude 6). Distinguant entre immigré-e'S valorisé-e s et dévalorisé-e-s, l'Etude 1 a eu pour but de mettre en lumière l'impact de la présence d'immigré e s sur le contact et la menace intergroupes. L'Etude 2 a, quant à elle, examiné si la présence d'immigré e s interagit avec les idéologies conservatrices, tant au niveau individuel que municipal, pour expliquer les attitudes envers le voile. Dans le même ordre idée, les études suivantes ont mis en exergue les effets conjoints de la présence d'immigré-e s et du climat idéologique au niveau des municipalités suisses (Etude 3) ou des pays Européens (Etude 4). En s'intéressant aux interactions entre Individu et Contexte, ces études ont en particulier cherché à observer dans quelle mesure ce dernier pouvait galvaniser les attitudes de personnes qui avaient déjà tendance à percevoir les immigré e s comme une menace ou, au contraire, mobiliser des individus desquels on n'attendrait pas de telles attitudes. Pour finir, les dernières études ont eu pour but de mettre en lumière la manière dont les élites politiques alimentent les climats idéologiques. Dans ce but, l'Etude 5 a analysé les discours officiels donnés pendant les émeutes qui ont secoué Londres en 2011, alors que l'Etude 6 a démontré comment le fait d'être en accord avec le message de menace véhiculé par ces discours avait poussé des individus égalitaires à exprimer des attitudes négatives envers la diversité ethnique. Dans l'ensemble, la présente thèse propose donc une approche intégrative d'étudier les attitudes négatives envers les immigré-e-s, et en discute les implications théoriques et méthodologiques.

Auditory cues support place navigation in rats when associated with a visual cue.

Rats, like other crepuscular animals, have excellent auditory capacities and they discriminate well between different sounds [Heffner HE, Heffner RS, Hearing in two cricetid rodents: wood rats (Neotoma floridana) and grasshopper mouse (Onychomys leucogaster). J Comp Psychol 1985;99(3):275-88]. However, most experimental literature concerning spatial orientation almost exclusively emphasizes the use of visual landmarks [Cressant A, Muller RU, Poucet B. Failure of centrally placed objects to control the firing fields of hippocampal place cells. J Neurosci 1997;17(7):2531-42; and Goodridge JP, Taube JS. Preferential use of the landmark navigational system by head direction cells in rats. Behav Neurosci 1995;109(1):49-61]. To address the important issue of whether rats are able to achieve a place navigation task relative to auditory beacons, we designed a place learning task in the water maze. We controlled cue availability by conducting the experiment in total darkness. Three auditory cues did not allow place navigation whereas three visual cues in the same positions did support place navigation. One auditory beacon directly associated with the goal location did not support taxon navigation (a beacon strategy allowing the animal to find the goal just by swimming toward the cue). Replacing the auditory beacons by one single visual beacon did support taxon navigation. A multimodal configuration of two auditory cues and one visual cue allowed correct place navigation. The deletion of the two auditory or of the one visual cue did disrupt the spatial performance. Thus rats can combine information from different sensory modalities to achieve a place navigation task. In particular, auditory cues support place navigation when associated with a visual one.

Central line sepsis in intensive care units : overview and update

Catheter-related infection remains a leading cause of nosocomial infections, particularly in intensive care units. It includes colonization of the device, skin exit-site infection and device- or catheter-related bloodstream infection. The latter represents the most frequent life-threatening associated complication of central venous catheter use and is associated with significant patient morbidity, mortality and extra hospital costs. The incidence of catheter-related bloodstream infection ranges from 2 to 14 episodes per 1000 catheter-days. On average, microbiologically-documented device-related bloodstream infections complicate from three to five per 100 central venous line uses, but they only represent the visible part of the iceberg and most clinical sepsis are nowadays considered to be catheter-related. We briefly review the pathophysiology of infection, highlighting the importance of the skin insertion site and of intravenous line hub as principal sources of colonization. Principles of therapy are reviewed. Several preventive approaches are also discussed, in particular the possible benefit of recently developed impregnated catheters. Finally, the potential positive impact of a multimodal global preventive strategy based on strict application of hygienic rules is presented.

La fonction de la carte géographique : approche épistémologique ternaire

Under the referential of a ternary logic, with the two orthogonal concepts of information/signification, mediated by the third-included, the diagonal organizer of the cartographic communication, this article aims to cladify the pragmatical aspects of the map functionnality as a communication object. The interaction beween the meaning of its information and the information reciprocally contained in its signification, within a specified context and pertinence, implies a strong level of redundancy shared by producers and users of the map, a same system of scientific and ideological values to pass on the cartographic message. We are far from the objective cartographer who would fade away so to let the facts speaks "objectively" by themselves.

Élaboration et évaluation de produits géotouristiques. Propositions méthodologiques

Lors de l'élaboration de produits géotouristiques, l'essentiel de l'attention est portée au site et au support: panneau, brochure ou appareil mobile. C'est du moins ce qui ressort ces dernières années des colloques scientifiques consacrés au géotourisme. Bien qu'essentielles, les considérations relatives aux processus de médiation ou aux approches méthodologiques pour la valorisation géotouristique demeurent rares. Cet article tente une formalisation du processus d'élaboration des produits géotouristiques. Quatre domaines sont identifiés - le public, le site, le contenu et le support - qui soulèvent une série de questions. Leur résolution vise à obtenir un produit de médiation cohérent, base nécessaire à une entreprise didactique. Est-ce que la réalisation est adaptée au site et à ses particularités, intéresse le public, est structurée de manière à rendre possible la transmission d'un message ? Sur cette même base est présentée une ébauche de méthode d'évaluation des produits, portant à la fois sur la qualité scientifique et la qualité de la démarche didactique. L'importance d'évaluations complémentaires sur la réelle efficacité didactique et les retombées socio-économiques de ces produits est signalée. L?ensemble de ces démarches vise à augmenter la qualité générale des produits géotouristiques et à leur permettre d?atteindre leurs buts didactiques ou de sensibilisation.