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Purpose: This report describes the essential steps in the development, implementation, evaluation and quality assurance of the written part of the Swiss Federal Licensing Examination for Human Medicine (FLE) and the insights gained since its introduction in 2011.Methods: Based on existing scientific evidence, international expertise, and experience gained from previous examinations, the FLE is developed by experts from all five medical faculties in Switzerland with the support of the Institute for Medical Education and is held simultaneously at five locations. The exam organisers document and review every examination held and continuously optimise the processes; they have summarised the results in this report.Results: The essential steps comprise the development, revision and translation of questions; construction of the exam and production of materials; candidate preparation; implementation and analysis. The quality assurance measures consist of guideline coherence in the development of the questions and implementation of the exam, revision processes, construction of the exam based on the national blueprint, multiphase review of the translations and exam material, and statistical analysis of the exam and the comments from candidates. The intensive collaboration, especially on the part of representatives from all the participating faculties and a central coordination unit, which provides methodological support throughout and oversees the analysis of the exam, has proven successful. Successfully completed examinations and reliable results in the eleven examinations so far implemented represent the outcomes of the quality assurance measures. Significant insights in recent years are the importance of appreciating the work of those involved and the central organisation of exam development, thus ensuring the long-term success of the process.Conclusion: Common guidelines and workshops, quality assurance measures accompanied by the continuous improvement of all processes, Zielsetzung: Dieser Bericht beschreibt die zentralen Schritte der Erstellung, Durchführung, Auswertung und Qualitätssicherung des schriftlichen Teils der eidgenössischen Prüfung Humanmedizin (Schweizer Staatsexamen) sowie die seit deren Einführung 2011 gewonnenen Erkenntnisse.Methodik: Die eidgenössische Prüfung wird auf Basis vorhandener wissenschaftlicher Evidenz, internationaler Expertise sowie Erfahrungen aus vorhergehenden Prüfungen durch Experten aller fünf Medizinischen Fakultäten der Schweiz mit Unterstützung des Instituts für medizinische Lehre erstellt und gleichzeitig an fünf Standorten durchgeführt. Die Prüfungsorganisatoren dokumentieren und reflektieren jede Prüfungsdurchführung, optimieren die Prozesse kontinuierlich und haben die Ergebnisse in diesem Bericht zusammengefasst. Ergebnisse: Die zentralen Schritte umfassen: Fragenerstellung, -revision, -übersetzung; Prüfungszusammenstellung und Materialherstellung; Kandidatenvorbereitung; Prüfungsdurchführung und -auswertung. Die Qualitätssicherungsmassnahmen bestehen aus Richtlinienkohärenz bei der Fragenerstellung und Prüfungsdurchführung, Revisionsprozessen, Prüfungszusammenstellung auf Basis des nationalen Blueprints, mehrstufiger Überprüfung der Übersetzungen und des Prüfungsmaterials sowie der statistischen Auswertung der Prüfung und der Kandidatenkommentare. Bewährt hat sich dabei die enge Zusammenarbeit insbesondere von Vertretern aller beteiligten Fakultäten sowie einer zentralen Koordinationsstelle, die sämtliche Schritte methodisch begleitet und sich um die Auswertung der Prüfung kümmert. Die Endergebnisse der Qualitätssicherungsmassnahmen sind erfolgreiche Prüfungsdurchführungen und reliable Ergebnisse in den bisher elf so durchgeführten Prüfungen. Wichtige Erkenntnisse der vergangenen Jahre sind die Bedeutung der Wertschätzung der Arbeit der Beteiligten und die zentrale Organisation der Prüfungserstellung, um den Prozess langfristig erfolgreich durchzuführen. Schlussfolgerung: Um eine solche

Item does not contain fulltext, BACKGROUND: GSK2849330, an anti-HER3 monoclonal antibody that blocks HER3/Neuregulin 1 (NRG1) signaling in cancer cells, is engineered for enhanced antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. This phase I, first-in-human, open-label study assessed the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary activity of GSK2849330 in patients with HER3-expressing advanced solid tumors. PATIENTS AND METHODS: Patients with various tumor types were prospectively selected for HER3 expression by immunohistochemistry; a subset was also screened for NRG1 mRNA expression. In the dose-escalation phase, patients received GSK2849330 1.4-30 mg/kg every 2 weeks, or 3 mg/kg or 30 mg/kg weekly, intravenously (IV). In the dose-expansion phase, patients received 30 mg/kg GSK2849330 IV weekly. RESULTS: Twenty-nine patients with HER3-expressing cancers, of whom two expressed NRG1, received GSK2849330 (dose escalation: n = 18, dose expansion: n = 11). GSK2849330 was well tolerated. No dose-limiting toxicities were observed. The highest dose, of 30 mg/kg weekly, expected to provide full target engagement, was selected for dose expansion. Treatment-emergent adverse events (AEs) were mostly grade 1 or 2. The most common AEs were diarrhea (66%), fatigue (62%), and decreased appetite (31%). Dose-proportional plasma exposures were achieved, with evidence of HER3 inhibition in paired tissue biopsies. Of 29 patients, only 1 confirmed partial response, lasting 19 months, was noted in a patient with CD74-NRG1-rearranged non-small cell lung cancer (NSCLC). CONCLUSION: GSK2849330 demonstrated a favorable safety profile, dose-proportional PK, and evidence of target engagement, but limited antitumor activity in HER3-expressing cancers. The exceptional response seen in a patient with CD74-NRG1-rearranged NSCLC suggests further exploration in NRG1-fusion-positive cancers. IMPLICATIONS FOR PRACTICE: This first-in-human study confirms that GSK2849330 is well to

PURPOSE: The challenges of accurate dosimetry for stereotactic radiotherapy (SRT) with small unflattened radiation fields have been widely reported in the literature. In this case, suitable dosimeters would have to offer a submillimeter spatial resolution. The CyberKnife® (Accuray Inc., Sunnyvale, CA, USA) is an SRT-dedicated linear accelerator (linac), which can deliver treatments with submillimeter positional accuracy using circular fields. Beams are delivered with the desired field size using fixed cones, the InCise™ multileaf collimator or a dynamic variable-aperture Iris™ collimator. The latter, allowing for field sizes to be varied during treatment delivery, has the potential to decrease treatment time, but its reproducibility in terms of output factors (OFs) and dose profiles (DPs) needs to be verified. METHODS: A 2D monolithic silicon array detector, the "Octa", was evaluated for dosimetric quality assurance (QA) for a CyberKnife system. OFs, DPs, percentage depth-dose (PDD) and tissue maximum ratio (TMR) were investigated, and results were benchmarked against the PTW SRS diode. Cross-plane, in-plane and 2 diagonal dose profiles were measured simultaneously with high spatial resolution (0.3 mm). Monte Carlo (MC) simulations with a GEANT4 (GEometry ANd Tracking 4) tool-kit were added to the study to support the experimental characterization of the detector response. RESULTS: For fixed cones and the Iris, for all field sizes investigated in the range between 5 and 60 mm diameter, OFs, PDDs, TMRs, and DPs in terms of FWHM measured by the Octa were accurate within 3% when benchmarked against the SRS diode and MC calculations. CONCLUSIONS: The Octa was shown to be an accurate dosimeter for measurements with a 6 MV FFF beam delivered with a CyberKnife system. The detector enabled real-time dosimetric verification for the variable aperture Iris collimator, yielding OFs and DPs consistent with those obtained with alternative methods.

Zusammenfassung: Hauttuberkulosen können sich mit sehr unterschiedlichen klinischen Bildern manifestieren und damit die Diagnosestellung erschweren. Wir stellen den Fall einer 79-jährigen Patientin vor, mit einer atypischen Präsentation eines Erythema induratum Bazin (EIB) am Oberkörper und einer tuberkulösen Osteomyelitis des Olekranon links. Aus den Biopsien der EIB-Knoten konnte M.tuberculosis kulturell nachgewiesen werden. Das widerspricht der klassischen Vorstellung, dass das EIB als Folge einer Hypersensitivitätsreaktion auf Mykobakterien entsteht, und unterstützt die Hypothese, dass das EIB auch durch eine hämatogene oder lymphogene Streuung von lebenden M.tuberculosis entstehen kann

Zusammenfassung: Die Harnwegsinfektion ist die häufigste Infektion des Erwachsenen im Spital. Sie ist meistens mit dem Tragen von Harnwegskathetern assoziiert. Entscheidend sind daher die richtige Indikationsstellung für die Kathetereinlage, die frühzeitige Wiederentfernung des Katheters sowie die korrekte Diagnosestellung zur Vermeidung unnötiger antibiotischer Behandlungen. Die therapeutischen Überlegungen sollten die Komorbiditäten und potenzielle Behinderungen des Urinabflusses mit einschließen. In der Behandlung stehen Chinolone, Breitspektrumpenizilline und Cephalosporine der 3.Generation im Vordergrund. Bei den ökonomischen Überlegungen sollte v.a. der höhere Preis von i.v.-Antibiotika im Vergleich zu per os mit einfließen

pH and oxygen are usually considered as the main factors influencing the organoleptic stability of beer. Polyphenols from malt and hop contribute to several characteristics of beer flavor, but their incidence on astringency is rarely mentioned. In this work, effects of pH (3.0 and 5.0) and accelerated aging (0 or 5 days at 40 degrees C with low or high level of oxygen in the bottle) on astringency were measured by two sensory analysis methods: quantitative descriptive analysis and time-intensity analysis. In addition, the polymerization degree of polyphenols was determined for the different samples in this study. Whatever the sensory technique used, a trained panel showing high repeatability identified pH as the only factor having a significant effect on astringency. Accelerated aging, even with high level of oxygen in the bottle, does not significantly modify perception of this sensation compared with the 4 degrees C-stored beer, probably because the variation of polymerization degree of polyphenols was not sufficient to be detected by the panelists. (C) 2005 Elsevier Ltd. All rights reserved.