Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial

BACKGROUND Postoperative hemithoracic radiotherapy has been used to treat malignant pleural mesothelioma, but it has not been assessed in a randomised trial. We assessed high-dose hemithoracic radiotherapy after neoadjuvant chemotherapy and extrapleural pneumonectomy in patients with malignant pleural mesothelioma. METHODS We did this phase 2 trial in two parts at 14 hospitals in Switzerland, Belgium, and Germany. We enrolled patients with pathologically confirmed malignant pleural mesothelioma; resectable TNM stages T1-3 N0-2, M0; WHO performance status 0-1; age 18-70 years. In part 1, patients were given three cycles of neoadjuvant chemotherapy (cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 given every 3 weeks) and extrapleural pneumonectomy; the primary endpoint was complete macroscopic resection (R0-1). In part 2, participants with complete macroscopic resection were randomly assigned (1:1) to receive high-dose radiotherapy or not. The target volume for radiotherapy encompassed the entire hemithorax, the thoracotomy channel, and mediastinal nodal stations if affected by the disease or violated surgically. A boost was given to areas at high risk for locoregional relapse. The allocation was stratified by centre, histology (sarcomatoid vs epithelioid or mixed), mediastinal lymph node involvement (N0-1 vs N2), and T stage (T1-2 vs T3). The primary endpoint of part 1 was the proportion of patients achieving complete macroscopic resection (R0 and R1). The primary endpoint in part 2 was locoregional relapse-free survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00334594. FINDINGS We enrolled patients between Dec 7, 2005, and Oct 17, 2012. Overall, we analysed 151 patients receiving neoadjuvant chemotherapy, of whom 113 (75%) had extrapleural pneumonectomy. Median follow-up was 54·2 months (IQR 32-66). 52 (34%) of 151 patients achieved an objective response. The most common grade 3 or 4 toxic effects were neutropenia (21 [14%] of 151 patients), anaemia (11 [7%]), and nausea or vomiting (eight [5%]). 113 patients had extrapleural pneumonectomy, with complete macroscopic resection achieved in 96 (64%) of 151 patients. We enrolled 54 patients in part 2; 27 in each group. The main reasons for exclusion were patient refusal (n=20) and ineligibility (n=10). 25 of 27 patients completed radiotherapy. Median total radiotherapy dose was 55·9 Gy (IQR 46·8-56·0). Median locoregional relapse-free survival from surgery, was 7·6 months (95% CI 4·5-10·7) in the no radiotherapy group and 9·4 months (6·5-11·9) in the radiotherapy group. The most common grade 3 or higher toxic effects related to radiotherapy were nausea or vomiting (three [11%] of 27 patients), oesophagitis (two [7%]), and pneumonitis (two [7%]). One patient died of pneumonitis. We recorded no toxic effects data for the control group. INTERPRETATION Our findings do not support the routine use of hemithoracic radiotherapy for malignant pleural mesothelioma after neoadjuvant chemotherapy and extrapleural pneumonectomy. FUNDING Swiss Group for Clinical Cancer Research, Swiss State Secretariat for Education, Research and Innovation, Eli Lilly.

Computer-based summative assessment of clinical reasoning in clerkships: A mixed-method comparison of key feature problems with case-based multiple choice questions

Background: It is yet unclear if there are differences between using electronic key feature problems (KFPs) or electronic case-based multiple choice questions (cbMCQ) for the assessment of clinical decision making. Summary of Work: Fifth year medical students were exposed to clerkships which ended with a summative exam. Assessment of knowledge per exam was done by 6-9 KFPs, 9-20 cbMCQ and 9-28 MC questions. Each KFP consisted of a case vignette and three key features (KF) using “long menu” as question format. We sought students’ perceptions of the KFPs and cbMCQs in focus groups (n of students=39). Furthermore statistical data of 11 exams (n of students=377) concerning the KFPs and (cb)MCQs were compared. Summary of Results: The analysis of the focus groups resulted in four themes reflecting students’ perceptions of KFPs and their comparison with (cb)MCQ: KFPs were perceived as (i) more realistic, (ii) more difficult, (iii) more motivating for the intense study of clinical reasoning than (cb)MCQ and (iv) showed an overall good acceptance when some preconditions are taken into account. The statistical analysis revealed that there was no difference in difficulty; however KFP showed a higher discrimination and reliability (G-coefficient) even when corrected for testing times. Correlation of the different exam parts was intermediate. Conclusions: Students perceived the KFPs as more motivating for the study of clinical reasoning. Statistically KFPs showed a higher discrimination and higher reliability than cbMCQs. Take-home messages: Including KFPs with long menu questions into summative clerkship exams seems to offer positive educational effects.

Computerbasierte Prüfung von klinischem Denken in der klinischen Ausbildung: Ein Mixed-Method Vergleich von Key Feature Problemen mit fallbasierten Multiple Choice Typ A Fragen

Fragestellung/Einleitung: Es ist unklar inwiefern Unterschiede bestehen im Einsatz von Key Feature Problemen (KFP) mit Long Menu Fragen und fallbasierten Typ A Fragen (FTA) für die Überprüfung des klinischen Denkens (Clinical Reasoning) in der klinischen Ausbildung von Medizinstudierenden. Methoden: Medizinstudierende des fünften Studienjahres nahmen an ihrer klinischen Pädiatrie-Rotation teil, die mit einer summativen Prüfung endete. Die Überprüfung des Wissen wurde pro Prüfung elektronisch mit 6-9 KFP [1], [3], 9-20 FTA und 9-28 nichtfallbasierten Multiple Choice Fragen (NFTA) durchgeführt. Jedes KFP bestand aus einer Fallvignette und drei Key Features und nutzen ein sog. Long Menu [4] als Antwortformat. Wir untersuchten die Perzeption der KFP und FTA in Focus Gruppen [2] (n of students=39). Weiterhin wurden die statistischen Kennwerte der KFP und FTA von 11 Prüfungen (n of students=377) verglichen. Ergebnisse: Die Analyse der Fokusgruppen resultierte in vier Themen, die die Perzeption der KFP und deren Vergleich mit FTA darstellten: KFP wurden als 1. realistischer, 2. schwerer, und 3. motivierender für das intensive Selbststudium des klinischen Denkens als FTA aufgenommen und zeigten 4. insgesamt eine gute Akzeptanz sofern gewisse Voraussetzungen berücksichtigt werden. Die statistische Auswertung zeigte keinen Unterschied im Schwierigkeitsgrad; jedoch zeigten die KFP eine höhere Diskrimination und Reliabilität (G-coefficient) selbst wenn für die Prüfungszeit korrigiert wurde. Die Korrelation der verschiedenen Prüfungsteile war mittel. Diskussion/Schlussfolgerung: Die Studierenden erfuhren die KFP als motivierenden für das Selbststudium des klinischen Denkens. Statistisch zeigten die KFP eine grössere Diskrimination und höhere Relibilität als die FTA. Der Einbezug von KFP mit Long Menu in Prüfungen des klinischen Studienabschnitts erscheint vielversprechend und einen „educational effect“ zu haben.

Na 1 Nachlass Max Horkheimer, 695 - "The Collapse of German Democracy and the Expansion of National Socialism", "Cultural Aspects of National Socialism" u.a. (p. IX 169.1a - IX 170.1-4)

"The Collapse of German Democracy and the Expansion of National Socialism" (1940):; 1. Darstellung des Forschungsprojekts (15.9.1940), b. Typoskript mit handschriftlichen Korrekturen, 78 Blatt; 2. "Research work on recent trends in the history of ideas (parts of the Research project on the Collapse of German Democracy would be included)". Als Memorandum zur Eröffnung zur Eröffnung einer Zweigstelle des Instituts in Los Angeles (12.12.1940): a) Typoskript, 2 Blatt, b) Teilstück, Typoskript mit handschriftlichen Korrekturen, 1 Blatt, c) Teilstück, Typoskript mit handschriftlichen Korrekturen, 1 Blatt, d) Teilstück, Typoskript, 1 Blatt, e) Teilstück, Typoskript, 1 Blatt, f) Entwurf, Typoskript mit handschriftlichen Korrekturen und Manuskript, 3 Blatt; 3. University of California, Los Angeles: 2 Briefe (Abschrift) von Max Horkheimer, o.O., 1940, 2 Briefe (Abschrift) an Max Horkheimer, 1940, 2 Blatt; A.R.L. Gurland: "Survey of Structural Changes in the German Economy, 1933 to 1939. Technological Bases and Organizational Forms of the National Socialist Economic System". Typoskript mit handschriftlichen Korrekturen unter anderem von Theodor W. Adorno, 48 Blatt (formal nicht identisch mit "Technological Trends and Economic Structure under National Socialism", Studies in Philosophy and Social Science, Bd. IX, 1941, S. 226ff.); "Cultural Aspects of National Socialism. A Research Project" (1941):; 1. Institute of Social Research: Mitteilung über das Forschungsprojekt und das 'Supplementary Statement', Typoskript, englisch, 4 Blatt; 2. Supplementary Statement to the Research Project, a) Typoskript, 14.4.1941, 63 Blatt, b) Typoskript, 12.4.1941, mit handschriftlichen Korrekturen, 35 Blatt; 3. "Cultural Aspects of National Socialism. A Research Project" (24.2.1941), a) als Typoskript vervielfältigt, 54 Blatt, b) Typoskript mit handschriftlichen Korrekturen, 34 Blatt, c) Fassung Januar 1941, Typoskript mit handschriftlichen Korrekturen, 40 Blatt; 4. Inhaltsverzeichnisse, mit handschriftlichen Korrekturen, 3 Blatt;

Geochemistry of the oceanic crust from ocean drilling samples

This book presents new data on chemical and mineral compositions and on density of altered and fresh igneous rocks from key DSDP and ODP holes drilled on the following main tectonomagmatic structures of the ocean floor: 1. Mid-ocean ridges and abyssal plains and basins (DSDP Legs 37, 61, 63, 64, 65, 69, 70, 83, and 91 and ODP Legs 106, 111, 123, 129, 137, 139, 140, 148, and 169); 2. Seamounts and guyots (DSDP Legs 19, 55, and 62 and ODP Legs 143 and 144); 3. Intraplate rises (DSDP Legs 26, 33, 51, 52, 53, 72, and 74 and ODP Legs 104, 115, 120, 121, and 183); and 4. Marginal seas (DSDP Legs 19, 59, and 60 and ODP Legs 124, 125, 126, 127, 128, and 135). Study results of altered gabbro from the Southwest Indian Ridge (ODP Leg 118) and serpentinized ultramafic rocks from the Galicia margin (ODP Leg 103) are also presented. Samples were collected by the authors from the DSDP/ODP repositories, as well as during some Glomar Challenger and JOIDES Resolution legs. The book also includes descriptions of thin sections, geochemical diagrams, data on secondary mineral assemblages, and recalculated results of chemical analyses with corrections for rock density. Atomic content of each element can be quantified in grams per standard volume (g/1000 cm**3). The suite of results can be used to estimate mass balance, but parts of the data need additional work, which depends on locating fresh analogs of altered rocks studied here. Results of quantitative estimation of element mobility in recovered sections of the upper oceanic crust as a whole are shown for certain cases: Hole 504B (Costa Rica Rift) and Holes 856H, 857C, and 857D (Middle Valley, Juan de Fuca Ridge).