Frequency of exercise-induced ST-T-segment deviations and cardiac arrhythmias in recreational endurance athletes during a marathon race: results of the prospective observational Berlin Beat of Running study

OBJECTIVES: While regular physical exercise has many health benefits, strenuous physical exercise may have a negative impact on cardiac function. The 'Berlin Beat of Running' study focused on feasibility and diagnostic value of continuous ECG monitoring in recreational endurance athletes during a marathon race. We hypothesised that cardiac arrhythmias and especially atrial fibrillation are frequently found in a cohort of recreational endurance athletes. The main secondary hypothesis was that pathological laboratory findings in these athletes are (in part) associated with cardiac arrhythmias. DESIGN: Prospective observational cohort study including healthy volunteers. SETTING AND PARTICIPANTS: One hundred and nine experienced marathon runners wore a portable ECG recorder during a marathon race in Berlin, Germany. Athletes underwent blood tests 2-3 days prior, directly after and 1-2 days after the race. RESULTS: Overall, 108 athletes (median 48 years (IQR 45-53), 24% women) completed the marathon in 249±43 min. Blinded ECG analysis revealed abnormal findings during the marathon in 18 (16.8%) athletes. Ten (9.3%) athletes had at least one episode of non-sustained ventricular tachycardia, one of whom had atrial fibrillation; eight (7.5%) individuals showed transient ST-T-segment deviations. Abnormal ECG findings were associated with advanced age (OR 1.11 per year, 95% CI 1.01 to 1.23), while sex and cardiovascular risk profile had no impact. Directly after the race, high-sensitive troponin T was elevated in 18 (16.7%) athletes and associated with ST-T-segment deviation (OR 9.9, 95% CI 1.9 to 51.5), while age, sex and cardiovascular risk profile had no impact. CONCLUSIONS: ECG monitoring during a marathon is feasible. Abnormal ECG findings were present in every sixth athlete. Exercise-induced transient ST-T-segment deviations were associated with elevated high-sensitive troponin T (hsTnT) values. TRIAL REGISTRATION: ClinicalTrials.gov NCT01428778; Results

Septischer Schock - Molekulare Pathophysiologie und therapeutische Ansaetze. Offene, orientierende klinische Pruefung zum Einfluss der Kombination von Iloprost (Prostazyklin-Analog) und Rolipram (Inhibitor des Phosphodiesterase-Isoenzymes 4) auf das extravaskulaere Lungenwasser bei Patienten mit akutem Atemnotsyndrom (ARDS) und weitere begleitende experimentelle Untersuchungen Schlussbericht

State of the art: Noncardiogenic pulmonary edema is an important and life threatening complication in patients with sepsis. The global goal of the study was to test the innovative therapeutic concept that vascular barrier dysfunction in ARDS-patients can be reversed by simultaneous stimulation of adenylylcyclase and inhibition of phosphodiesterase (PDE)-isoenzyme 4. Key parameters determined were reduction of pulmonary edema (methods: quantification of extravascular lung water and intrathoracic blood volume via a double-indicator-dilution method) and increase in pulmonary oxygenation function. Results: The project supported was a phase-2 clinical trial in ARDS-patients; it was completed successfully, i.e., the study goals were reached. Additional accompanying experimental studies were performed which tried to identify useful approaches to maintain or improve vascular barrier function. In these studies the PDE isoenzyme pattern was determined in different pulmonary cells; moreover the usefulness of 'guanylyl-cyclase stimulation/PDE2-inhibition' was examined and the stimulus-independency of endothelial barrier stabilization by cyclic nucleotides was established (see attached reprints). Conclusions: The successful phase-2 trail should form the basis for a phase-3 trial to be initiated. (orig.)SIGLEAvailable from TIB Hannover: DtF QN1(79,60) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman

Miniaturisierter Thermocycler Wissenschaftlicher Abschlussbericht

In the context of genome projects, efficient and automizable systems are needed for a high sample throughput, particularly to perform the polymerase chain reaction (PCR). Currently available devices for PCR are not suited to achieve the requested specifications regarding number of samples and total speed to the reaction. Through miniaturization of the PCR devices it should be possible to accelerate the reactions. A promising start to achieve this goal is the application of microsystems technique for miniaturization and automation. The aim of this project was the development of miniaturized items for automated PCR. By consistent application of microsystems technique, a significant reduction of sample volumes and raise of heating and cooling rates should be achievable. Based on thermal simulations for the modelling of different thermocycler elements, silicon chips with up to 90 reaction chambers were realized. Heating and cooling rates of 18 K/s or 9 K/s respectively could be achieved. The feasibility of parallel reactions could be demonstrated with a prototype device. Procedures for liquid handling were evaluated and the materials were optimised regarding their biocompatibility. Based on the results of this project it should be possible to realize an integrated miniaturized thermocycler using the methods of microsystems technique. (orig.)SIGLEAvailable from TIB Hannover: DtF QN1(71,17) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Psychosoziale Unterstuetzung in einer Radiologischen Klinik Abschlussbericht

SIGLEAvailable from TIB Hannover: F96B982+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Targeting Drug Resistance in EGFR with Covalent Inhibitors: A Structure-Based Design Approach

Receptor tyrosine kinases represent one of the prime targets in cancer therapy, as the dysregulation of these elementary transducers of extracellular signals, like the epidermal growth factor receptor (EGFR), contributes to the onset of cancer, such as non-small cell lung cancer (NSCLC). Strong efforts were directed to the development of irreversible inhibitors and led to compound CO-1686, which takes advantage of increased residence time at EGFR by alkylating Cys797 and thereby preventing toxic effects. Here, we present a structure-based approach, rationalized by subsequent computational analysis of conformational ligand ensembles in solution, to design novel and irreversible EGFR inhibitors based on a screening hit that was identified in a phenotype screen of 80 NSCLC cell lines against approximately 1500 compounds. Using protein X-ray crystallography, we deciphered the binding mode in engineered cSrc (T338M/S345C), a validated model system for EGFR-T790M, which constituted the basis for further rational design approaches. Chemical synthesis led to further compound collections that revealed increased biochemical potency and, in part, selectivity toward mutated (L858R and L858R/T790M) vs nonmutated EGFR. Further cell-based and kinetic studies were performed to substantiate our initial findings. Utilizing proteolytic digestion and nano-LC-MS/MS analysis, we confirmed the alkylation of Cys797

Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone

BACKGROUND: The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. METHODS: In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, ≥12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of life-threatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone-salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. RESULTS: Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone-salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthma-related event in the fluticasone-salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P=0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthma-related intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone-salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone-salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P<0.001). CONCLUSIONS: Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone-salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group

Encyclopédie des historiographies : Afriques, Amériques, Asies

Quels rapports les sociétés humaines entretiennent-elles avec leur passé et quels récits font-elles du temps révolu ? Pour ce premier volume de l’Encyclopédie des historiographies. Afriques, Amériques, Asies, 157 spécialistes représentant 88 institutions académiques en France et dans le monde explorent l’univers des productions humaines qui constituent des sources pour l’historien et déchiffrent les nombreuses modalités (« scientifiques », littéraires, artistiques, monumentales…) de l’écriture du passé. Évoquant tour à tour l’Afrique, l’Amérique latine, l’Asie, l’Océanie, les 216 notices de l’ouvrage présentent des matériaux historiques de toute nature, issus de toutes les époques, souvent méconnus, ainsi que l’histoire de leurs usages. L’entreprise collective qu’est l’Encyclopédie se veut novatrice : il s’agit de susciter une réflexion historiographique résolument non-occidentalo-centrée qui complète utilement les démarches épistémologiques traditionnelles. Nouvel outil de connaissance historique forgé à l’heure de la mondialisation, l’Encyclopédie des historiographies est aussi une véritable invitation au voyage.What are the different types of relations that non-Western societies upkeep with their past and how are narratives about the past produced by them? In this first volume of the Encyclopaedia of Historiography: Africa, America, Asia, 157 specialists from 88 international academic institutions explore the wealth of evidence that constitutes source material for historians. They also examine the immensely diverse modes or genres of narrated history: “scientific”, literary, artistic, architectural, etc. 216 entries dealing with Africa, Latin America, Oceania, and Asia, cover a large variety of sources, including many which are unfamiliar to the Western or non-Western reader, along with the history of how they have been exploited. By bringing together for the first time such an abundance of material the reader is offered the possibility of exploring continents and building meaningful connections across space and time. In addition to being a new tool for historical enquiry in an era of globalization, this encyclopaedia is also an invitation to travel the world