Train-the-trainer: E-learning zur Förderung einer praxisorientiertem Vermittlung von evidenzbasierter Medizin

Hintergrund: Trotz ihrer Etablierung als essentieller Bestandteil der medizinischen Weiter-/Fortbildung werden europa- wie schweizweit kaum Kurse in evidenzbasierter Medizin (ebm) angeboten, die - integriert im klinischen Alltag - gezielt Fertigkeiten in ebm vermitteln. Noch grössere Defizite finden sich bei ebm- Weiterbildungsmöglichkeiten für klinische Ausbilder (z.B. Oberärzte). Als Weiterführung eines EU-finanzierten, klinisch integrierten E-learning- Programms für Weiterbildungsassistenten (www.ebm-unity.org) entwickelte eine europäische Gruppe von medical educators gezielt für Ausbilder ein e-learning-Curriculum zur Vermittlung von ebm im Rahmen der klinischen Weiterbildung. Methode: Die Entwicklung des Curriculums umfasst folgende Schritte: Beschreibung von Lernzielen, Identifikation von klinisch relevanten Lernumgebungen, Entwicklung von Lerninhalten und exemplarischen didaktischen Strategien, zugeschnitten auf die jeweilige Lernumgebungen, Design von web-basierten Selbst-Lernsequenzen mit Möglichkeiten zur Selbstevaluation, Erstellung eines Handbuchs. Ergebnisse: Lernziele des Tutoren-Lehrgangs sind der Erwerb von Fertigkeiten zur Vermittlung der 5 klassischen ebm-Schritte: PICO- (Patient-Intervention-Comparison-Outcome)-Fragen, Literatursuche, kritische Literaturbewertung, Übertragung der Ergebnisse im eigenen Setting und Implementierung). Die Lehrbeispiele zeigen angehenden ebm-Tutoren, wie sich typische klinische Situationen wie z.B. Stationsvisite, Ambulanzsprechstunde, Journalclub, offizielle Konferenzen, Audit oder das klinische Assessment von Weiterbildungsassistenten gezielt für die Vermittlung von ebm nutzen lassen. Kurze E-Learning-Module mit exemplarischen «real-life»-Video-Clips erlauben flexibles Lernen zugeschnitten auf das knappe Zeitkontingent von Ärzten. Eine Selbst-Evaluation ermöglicht die Überprüfung der gelernten Inhalte. Die Pilotierung des Tutoren-Lehrgangs mit klinisch tätigen Tutoren sowie die Übersetzung des Moduls in weitere Sprachen sind derzeit in Vorbereitung. chlussfolgerung: Der modulare Train-the-Trainer-Kurs zur Vermittlung von ebm im klinischen Alltag schliesst eine wichtige Lücke in der Dissemination von klinischer ebm. Webbasierte Beispiele mit kurzen Sequenzen demonstrieren typische Situationen zur Vermittlung der ebm-Kernfertigkeiten und bieten medical educators wie Oberärzten einen niedrigschwelligen Einstieg in «ebm» am Krankenbett. Langfristiges Ziel ist eine europäische Qualifikation für ebm- Learning und -Teaching in der Fort- und Weiterbildung. Nach Abschluss der Evaluation steht das Curriculum interessierten Personen und Gruppen unter «not-for-profit»-Bedingungen zur Verfügung. Auskünfte erhältlich von rkunz@uhbs.ch. Finanziert durch die Europäische Kommission - Leonardo da Vinci Programme - Transfer of Innovation - Pilot Project for Lifelong Learn- ing 2007 und das Schweizerische Staatssekretariat für Bildung und Forschung.

Detection of millimetric deformation using a terrestrial laser scanner: experiment and application to a rockfall event

Abstract. Terrestrial laser scanning (TLS) is one of the most promising surveying techniques for rockslope characteriza- tion and monitoring. Landslide and rockfall movements can be detected by means of comparison of sequential scans. One of the most pressing challenges of natural hazards is com- bined temporal and spatial prediction of rockfall. An outdoor experiment was performed to ascertain whether the TLS in- strumental error is small enough to enable detection of pre- cursory displacements of millimetric magnitude. This con- sists of a known displacement of three objects relative to a stable surface. Results show that millimetric changes cannot be detected by the analysis of the unprocessed datasets. Dis- placement measurement are improved considerably by ap- plying Nearest Neighbour (NN) averaging, which reduces the error (1σ ) up to a factor of 6. This technique was ap- plied to displacements prior to the April 2007 rockfall event at Castellfollit de la Roca, Spain. The maximum precursory displacement measured was 45 mm, approximately 2.5 times the standard deviation of the model comparison, hampering the distinction between actual displacement and instrumen- tal error using conventional methodologies. Encouragingly, the precursory displacement was clearly detected by apply- ing the NN averaging method. These results show that mil- limetric displacements prior to failure can be detected using TLS.

Évaluation d'une nouvelle méthode pour l'essai de stérilité des préparations pharmaceutiques

Introduction : Au CHUV, les contrôles microbiologiques des préparations pharmaceutiques stériles produites par la pharmacie de l'hôpital se basent sur l'essai de stérilité de la Pharmacopée Européenne. Avant 2000, une méthode en circuit ouvert était utilisée, puis, dès l'année 2000, une nouvelle méthode développée par H. Ing du service de pharmacie des HUG a été adoptée (méthode « Ing »). Cette dernière permet d'opérer en circuit fermé et de filtrer le milieu de culture. De plus, elle utilise du matériel bon marché (trousse de perfusion, filtres à usage unique). Objectifs : Le présent travail avait pour but : 1) l'évaluation préliminaire de cette méthode (validation). 2) l'évaluation du bénéfice apporté en terme d'incidence de faux positifs sur les préparations stériles filtrables. Matériel et méthode : La validation a été effectuée en analysant des flexs de NaCl 0.9% préalablement inoculés avec 10-100 CFU de 6 souches microbiennes décrites dans la Pharmacopée pour le test de validation, ainsi qu'un flex « contrôle » non inoculé. Le bénéfice de la méthode a été évalué à partir des résultats des essais de routine effectués au laboratoire. Un taux de faux positifs imputable à chaque méthode a ainsi pu être déterminé (i.e. croissance microbienne due à une contamination lors de l'essai et non à une contamination initiale de la préparation pharmaceutique) et la comparaison a été effectuée à l'aide du test statistique de Fisher. Résultats : Une croissance a été observée dans toutes les préparations préalablement inoculées par des micro-organismes. La méthode a donc pu être implantée dans le laboratoire pour les analyses de routine dès février 2000. L'analyse rétrospective des résultats des essais de stérilité effectués sur une période de plus de 4 ans (2 ans avec l'ancienne méthode (système ouvert) et de presque 3 ans avec la nouvelle méthode) montre que l'ancienne méthode produisait un taux de faux positifs de 1.57 %, alors que ce taux n'est que de 0.21% avec la méthode « Ing ». Cette dernière se caractérise donc par un taux de faux positifs significativement plus bas que celui de l'ancienne méthode (p < 0.0001). Conclusion : La méthode « Ing » constitue une technique bien adaptée à l'essai de stérilité pour l'hôpital, suffisamment sensible et conforme aux recommandations de la Pharmacopée. En maintenant le produit dans un espace clos, elle permet de diminuer les risques de contamination susceptibles de se produire lors de l'essai.

A randomized trial of spiritual assessment of outpatients with schizophrenia: Patients' and clinicians' experience

Objective: Recovery-oriented care for patients with schizophrenia involves consideration of cultural issues, such as religion and spirituality. However, there is evidence that psychiatrists rarely address such topics. This study examined acceptance of a spiritual assessment by patients and clinicians, suggestions for treatment that arose from the assessment, and patient outcomes-in terms of treatment compliance and satisfaction with care (as measured by treatment alliance). Methods: Outpatients with psychosis were randomly assigned to two groups: an intervention group that received traditional treatment and a religious and spiritual assessment (N=40) and a control group that received only traditional treatment (N=38). Eight psychiatrists were trained to administer the assessment to their established and stable patients. After each administration, the psychiatrist attended a supervision session with a psychiatrist and a psychologist of religion. Baseline and three-month data were collected. Results: The spiritual assessment was well accepted by patients. During supervision, psychiatrists reported potential clinical uses for the assessment information for 67% of patients. No between-group differences in medication adherence and satisfaction with care were found at three months, although patients in the in- tervention group had significantly better appointment attendance dur- ing the follow-up period. Their interest in discussing religion and spirituality with their psychiatrists remained high. The process was not as well accepted by psychiatrists. Conclusions: Spiritual assessment can raise important clinical issues in the treatment of patients with chronic schizophrenia. Cultural factors, such as religion and spirituality, should be considered early in clinical training, because many clinicians are not at ease addressing such topics with patients.

Role of glutathione deficit in the disconnectivity syndrome in schizophrenia: from pathogenetic mechanisms to therapeutic interventions

In the cerebrospinal fluid of 26 drug-naive schizophrenics (DSM-III- R), we observed that the level of glutathione ([GSH]) and of its metabolite γ-Glu-Gln was decreased by 27% and 16% respectively. Using a new in-vivo method based on magnetic resonance spec- troscopy, [GSH] was measured in the medial prefrontal cortex of 18 schizophrenics and found to be 52 % lower than in controls (n = 20). This is consistent with the recently observed decreased mRNA levels in fibroblasts of patients (n=32) of the two GSH synthesizing en- zymes (glutathione synthetase (GSS), and glutamate-cysteine ligase M (GCLM) the modulatory subunit of glutamate-cysteine ligase). Moreover, the level of GCLM expression in fibroblasts correlates neg- atively with the psychopathology (positive, general and some nega- tive symptoms). Thus, the observed difference in gene expression is not only the cause of low brain [GSH], but is also related to the sever- ity of symptoms, suggesting that fibroblasts are adequate surrogate for brain tissue. A hypothesis was proposed, based on a central role of GSH in the pathophysiology of schizophrenia. GSH is an important endogenous redox regulator and neuroactive substance. GSH is pro- tecting cells from damage by reactive oxygen species generated, among others, by the metabolism of dopamine. A GSH deficit-in- duced oxidative stress would lead to lipid peroxidation and micro-le- sions in the surrounding of catecholamine terminals, affecting the synaptic contacts on dendritic spines of cortical neurones, where ex- citatory glutamatergic terminals converge with dopaminergic ones. This would lead to spines degeneration and abnormal nervous con- nections or structural disconnectivity, possibly responsible for posi- tive, perceptive and cognitive symptoms of schizophrenia. In addi- tion, a GSH deficit could also lead to a functional disconnectivity by depressing NMDA neurotransmission, in analogy to phencyclidine effects. Present experimental biochemical, cell biological and behav- ioral data are consistent with the proposed mechanism: decreasing pharmacologically [GSH] in experimental models, with or without blocking DA uptake (GBR12909), induces morphological and behav- ioral changes similar to those observed in patients. Dendritic spines: (a) In neuronal cultures, low [GSH] and DA induce decreased density of neural processes; (b) In developing rats (p5-p16), [GSH] deficit and GBR induce a decrease in normal spines in prefrontal pyramids and in GABA-parvalbumine but not of -calretinine immunoreactivity in anterior cingulate. NMDA-dependant synaptic plasticity: GSH deple- I/13 tion in hippocampal slices impairs long-term potentiation. Develop- ing rats with low [GSH] and GBR have deficit in olfactory integration and in object recognition which appears earlier in males than fe- males, in analogy to the delay of the psychosis onset between man and woman. In summary, a deficit of GSH and/or GSH-related enzymes during early development could constitute a major vulnerability fac- tor in schizophrenia.

The enterprise face to the environmental challenge: straddling the fence between social responsibility and penal responsibility

This contribution aims to analyse how to incur companies' criminal liability when they violate environmental protection globally. In Switzerland, companies' criminal liability has already been provided for to fight against money launder- ing (Article 102 CP). Could a similar liability be incurred, in Switzerland, for companies that infringe environmental protection? This is what our contribution is all about. Since the company is at the heart of our subject, the point is to see to what extent criminal liability could be transposed to cases of violation by companies of the environmental principles promoted by the CSR concept.

Subjective mental time: the functional architecture of projecting the self to past and future.

Abstract Human experience takes place in the line of mental time (MT) created through 'self-projection' of oneself to different time-points in the past or future. Here we manipulated self-projection in MT not only with respect to one's life events but also with respect to one's faces from different past and future time-points. Behavioural and event-related functional magnetic resonance imaging activity showed three independent effects characterized by (i) similarity between past recollection and future imagination, (ii) facilitation of judgements related to the future as compared with the past, and (iii) facilitation of judgements related to time-points distant from the present. These effects were found with respect to faces and events, and also suggest that brain mechanisms of MT are independent of whether actual life episodes have to be re-experienced or pre-experienced, recruiting a common cerebral network including the anteromedial temporal, posterior parietal, inferior frontal, temporo-parietal and insular cortices. These behavioural and neural data suggest that self-projection in time is a fundamental aspect of MT, relying on neural structures encoding memory, mental imagery and self.

Etude de la toxicité hépatique de la cocaïne associée à de l'alcool: Effets de l'éthanol sur le métabolisme de la cocaïne dan les hépatocytes de rat en suspension et dans un modèle enzymatique humain

Le but essentiel de notre travail a été d?étudier la capacité du foie, premier organe de métabolisation des xénobiotiques, à dégrader la cocaïne en présence d?éthanol, à l?aide de deux modèles expérimentaux, à savoir un modèle cellulaire (les hépatocytes de rat en suspension) et un modèle acellulaire (modèle reconstitué in vitro à partir d?enzymes purifiées de foie humain). La première partie a pour objectifs de rechercher les voies de métabolisation de la cocaïne qui sont inhibées et / ou stimulées en présence d?éthanol, sur hépatocytes isolés de rat. Dans ce but, une méthode originale permettant de séparer et de quantifier simultanément la cocaïne, le cocaéthylène et huit de leurs métabolites respectifs a été développée par Chromatographie Phase Gazeuse couplée à la Spectrométrie de Masse (CPG / SM). Nos résultats préliminaires indiquent que l?éthanol aux trois concentrations testées (20, 40 et 80 mM) n?a aucun effet sur la cinétique de métabolisation de la cocaïne. Notre étude confirme que l?addition d?éthanol à des cellules hépatiques de rat en suspension supplémentées en cocaïne résulte en la formation précoce de benzoylecgonine et de cocaéthylène. L?apparition retardée d?ecgonine méthyl ester démontre l?activation d?une deuxième voie de détoxification. La production tardive d?ecgonine indique une dégradation de la benzoylecgonine et de l?ecgonine méthyl ester. De plus, la voie d?oxydation intervenant dans l?induction du stress oxydant en produisant de la norcocaïne est tardivement stimulée. Enfin, notre étude montre une métabolisation complète de la concentration initiale en éthanol par les hépatocytes de rat en suspension. La deuxième partie a pour but de déterminer s?il existe d?autres enzymes que les carboxylesterases formes 1 et 2 humaines ayant une capacité à métaboliser la cocaïne seule ou associée à de l?éthanol. Pour ce faire, une méthode de micropurification par chromatographie liquide (Smart System®) a été mise au point. Dans le cadre de nos dosages in situ de la cocaïne, du cocaéthylène, de la benzoylecgonine, de l?acide benzoïque et de la lidocaïne, une technique par Chromatographie Liquide Haute Performance couplée à une Détection par Barrette de Diode (CLHP / DBD) et une méthode de dosage de l?éthanol par Chromatographie Phase Gazeuse couplée à une Détection par Ionisation de Flamme équipée d?un injecteur à espace de tête (espace de tête CPG / DIF) ont été développées. La procédure de purification nous a permis de suspecter la présence d?autres enzymes que les carboxylesterases formes 1 et 2 de foie humain impliquées dans le métabolisme de la cocaïne et déjà isolées. A partir d?un modèle enzymatique reconstitué in vitro, nos résultats préliminaires indiquent que d?autres esterases que les formes 1 et 2 de foie humain sont impliquées dans l?élimination de la cocaïne, produisant benzoylecgonine et ecgonine méthyl ester. De plus, nous avons montré que les sensibilités de ces enzymes à l?éthanol sont variables.<br/><br/>The main purpose of our work was to study the ability of the liver, as the first organ to metabolise xenobiotic substances, to degrade cocaine in the presence of ethanol. In order to do this, we used two experimental models, namely a cellular model (rat liver cells in suspension) and an a-cellular model (model reconstructed in vitro from purified human liver enzymes). The purpose of the first part of our study was to look for cocaine metabolising processes which were inhibited and / or stimulated by the presence of ethanol, in isolated rat liver cells. With this aim in mind, an original method for simultaneously separating and quantifying cocaine, cocaethylene and eight of their respective metabolites was developed by Vapour Phase Chromatography coupled with Mass Spectrometry (VPC / MS). Our preliminary results point out that ethanol at three tested concentrations (20, 40 et 80 mM) have no effect on the kinetic of metabolisation of cocaine. Our study confirms that the addition of alcohol to rat liver cells in suspension, supplemented with cocaine, results in the premature formation of ecgonine benzoyl ester and cocaethylene. The delayed appearance of ecgonine methyl ester shows that a second detoxification process is activated. The delayed production of ecgonine indicates a degradation of the ecgonine benzoyl ester and the ecgonine methyl ester. Moreover, the oxidising process which occurs during the induction of the oxidising stress, producing norcocaine, is stimulated at a late stage. Finally, our study shows the complete metabolisation of the initial alcohol concentration by the rat liver cells in suspension. The second part consisted in determining if enzymes other than human carboxylesterases 1 and 2, able to metabolise cocaine on its own or with alcohol, existed. To do this, a micropurification method us ing liquid phase chromatography (Smart System®) was developed. A technique based on High Performance Liquid Chromatography coupled with a Diode Array Detection (HPLC / DAD) in the in situ proportioning of cocaine, cocaethylene, ecgonine benzoyl ester, benzoic acid and lidocaine, and a method for proportioning alcohol by quantifying the head space using Vapour Phase Chromatography coupled with a Flame Ionisation Detection (head space VPC / FID) were used. The purification procedure pointed to the presence of enzymes other than the human liver carboxylesterases, forms 1 and 2, involved in the metabolism of cocaine and already isolated. The preliminary results drawn from an enzymatic model reconstructed in vitro indicate that human liver carboxylesterases, other than forms 1 and 2, are involved in the elimination of cocaine, producing ecgonine benzoyl ester and ecgonine methyl ester. Moreover, we have shown that the sensitivity of these enzymes to alcohol is variable.

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In this chapter, we examine the multiple dimensions of declarations of fertility in-tention in order to provide a critical reading of currently used indicators of the childbearing decision-making process. Using a qualitative approach, we pay atten-tion to the complexity of the process through which individuals make (or fail to make) plans regarding their reproductive future. The data are a series of compara-ble in-depth interviews conducted in a number of European countries with varying fertility levels, and differing normative and institutional contexts. First, we ana-lyze the meanings that respondents attribute to their childbearing intentions, pay-ing particular attention to uncertain intentions that are often underanalyzed. Se-cond, we study the ways in which individuals vary in holding to their intentions over time, and consider why they might change their minds, even over relatively short periods of time. Third, we examine how several aspects of the larger social context (attitudes towards having children, family policy, norms related to the di-vision of labor, norms about the timing of children) shape fertility intentions.

Fingerprint identification: advances since the 2009 National Research Council report

"This paper will discuss the major developments in the area of fingerprint" "identification that followed the publication of the National Research Council (NRC, of the US National Academies of Sciences) report in 2009 entitled: Strengthening Forensic Science in the United States: A Path Forward. The report portrayed an image of a field of expertise used for decades without the necessary scientific research-based underpinning. The advances since the report and the needs in selected areas of fingerprinting will be detailed. It includes the measurement of the accuracy, reliability, repeatability and reproducibility of the conclusions offered by fingerprint experts. The paper will also pay attention to the development of statistical models allow- ing assessment of fingerprint comparisons. As a corollary of these developments, the next challenge is to reconcile a traditional practice domi- nated by deterministic conclusions with the probabilistic logic of any statistical model. There is a call for greater candour and fingerprint experts will need to communicate differently on the strengths and limitations of their findings. Their testimony will have to go beyond the blunt assertion" "of the uniqueness of fingerprints or the opinion delivered ispe dixit."