Personalized antiplatelet therapy with P2Y12 receptor inhibitors: benefits and pitfalls.

Antiplatelet therapy with P2Y12 receptor inhibitors has become the cornerstone of medical treatment in patients with acute coronary syndrome, after percutaneous coronary intervention and in secondary prevention of atherothrombotic events. Clopidogrel used to be the most broadly prescribed P2Y12 receptor inhibitor with undisputable benefits especially in combination with aspirin, but a considerable number of clopidogrel-treated patients experience adverse thrombotic events in whom insufficient P2Y12-inhibition and a consequential high on-treatment platelet reactivity is a common finding. This clinically relevant limitation of clopidogrel has driven the increased use of new antiplatelet agents. Prasugrel (a third generation thienopyridine) and ticagrelor (a cyclopentyl-triazolo-pyrimidine) feature more potent and predictable P2Y12-inhibition compared to clopidogrel, which translates into improved ischemic outcomes. However, excessive platelet inhibition and consequential low on-treatment platelet reactivity comes at the price of increased risk of major bleeding. The majority of randomized clinical trials failed to demonstrate improved clinical outcomes with platelet function testing and tailored antiplatelet therapy, but results of all recent trials of potent antiplatelets and prolonged antiplatelet durations point towards a need for individualized antiplatelet approach in order to decrease thrombotic events without increasing bleeding. This review focuses on potential strategies for personalizing antiplatelet treatment

JExTRA – Jet Noise Experiments at AT-TRA

This report by Max Nussbaumer is the result of his summer internship from 1. July 2015 to 11. September 2015 at DLR engine acoustics in Berlin. Under the supervision of Henri Siller, he performed acoustic measurements with a microphone array in the JExTRA jet facility. The jet facility was provided by Robert Meyer, the anechoic set-up of the microphone array has been conceived and constructed by Alessandro Bassetti with the support of Wolfram Hage and Larisa Hritsevskyy, who together with Stefan Funke supported the experiments. Stefan Funke also consulted Max Nussbaumer during the data reduction. Karsten Liesner supported the operation of the jet facility and adapted the control software

The hussites and the catholics (1414 – 1434). To the language creating the image of an enemy

Die Verbrennung des böhmischen Gelehrten und Reformators Jan Hus als Häretiker am 6. Juli 1415 am Konzil zu Konstanz führte ab den 20er Jahren des 15. Jahrhunderts zu enormen kriegerischen Auseinandersetzungen zwischen Hussiten und Katholiken, die ganz Zentraleuropa erfassten. Jan Hus und seine Nachfolger wurden am Konzil und in der Folge zu absoluten Feindfiguren der Christenheit stilisiert. Dem Krieg der Waffen ging ein „Krieg der Wörter“ (Wertheimer 2003) voraus. Sprachlich stand dabei eine gewisse Metapher im Mittelpunkt, die mit dem Namen tschechisch Hus = deutsch ‚Gans‘ spielte: Der Feuertod des Jan Hus wurde sarkastisch als „Braten der Gans“, die kriegerische Verfolgung der Hussiten als „Rupfen“ und „Braten der Gänslein“ dargestellt. Durch die Animalisierung der Gegner wurden die Grausamkeiten gegen sie verharmlost und zynisch gerechtfertigt. Die in Konstanz agitierenden und an Kriegshandlungen beteiligten Dichter Muskatblüt, Konrad Attinger und Oswald von Wolkenstein hatten wesentlichen Anteil an der Konstituierung der Feindbilder und der publizistischen Hetze, wobei vor allem bei Oswald der Verdacht naheliegt, dass seine poetisch-agitatorische Tätigkeit nicht frei von Eigennutz war. Als Diener des Königs Sigismund kam ihm möglicherweise einige Bedeutung zu, als Hus unter Missachtung des königlichen Geleits seinem Schicksal überlassen wurde.Burning at the stake of the Czech reformer and scholar Jan Hus for heresy at the Council of Constance on 6th July 1415 was the cause of numerous military conflicts between the Hussites and the Catholics which affected the whole Central Europe from the 1420s. At the council and also after that, Jan Hus and his followers were called principal enemies of Christianity. The “war of words” (Wertheimer 2003) preceded the war of weapons. From the linguistic point of view, a certain metaphor alluding to the meaning of the Czech name Hus =”husa”, which means “goose”, was at the forefront. Burning Master Jan Hus was sarcastically called “roasting a goose”; military persecutions of the Hussites was called “plucking” and “roasting goslings”. The animalization of adversaries served as the justification and cynical trivialization of the atrocities committed against them. Poets Muskatblüt, Konrad Attinger and Oswald von Wolkenstein agitating in Constance and participating in military campaigns had fundamental influence on the creation of the image of enemies and journalistic propaganda. In the case of Oswald, especially, there are suspicions that his poetic-canvassing activities were affected by his own interests. As a servant of King Sigismund, he possibly gained more influence after Hus was left to the mercy of fate, despite his royal safe-conduct

Dietrich von Pleningen: Des Senece Trostung zú Marcia : eine schwäbische Übersetzung aus dem frühen 16. Jahrhundert ; Text, Glossare, Untersuchungen

vorgelegt von: Max SillerInnsbruck, Univ., Diss., 1974(VLID)394658

Ignaz Vincenz Zingerle und die tirolische Literaturgeschichtsschreibung des Mittelalters

(VLID)174458

A human and animal model-based approach to investigating the anti-inflammatory profile and potential of the 5-HT_2B receptor antagonist AM1030

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by highly pruritic eczematous lesions that are commonly treated with topical corticosteroids and calcineurin inhibitors. Side-effects and safety concerns associated with these agents restrict their use, and new, safe treatment options are therefore needed. Recent reports suggest that serotonin, i.e. 5-hydroxytryptamine (5-HT) and the 5-HT(2) receptor family may contribute to inflammation and pruritus in the skin. The objective of this particular study was to investigate the 5HT(2B) receptor antagonist AM1030 with respect to its anti-inflammatory profile and potential. METHODS: AM1030 was tested in a set of distinct human and rodent in vitro and in vivo models, differing with respect to e.g. T cell involvement, triggering stimulus, main read-outs and route of drug administration. The in vitro systems used were staphylococcal enterotoxin A (SEA)-stimulated human peripheral blood mononuclear cells, lipopolysaccharide (LPS)-stimulated human primary monocytes, LPS-stimulated human THP-1 monocytes and LPS-stimulated mouse primary macrophages. The in vivo systems used were LPS- and SEA-induced cytokine production in the mouse, antigen-induced arthritis in the rat, glucose-6-phosphate isomerase-induced arthritis in the mouse and delayed-type hypersensitivity reaction in the mouse. In addition, different cell populations were analyzed with respect to their expression of the 5-HT(2B) receptor at the mRNA level. RESULTS: AM1030 significantly reduced both T cell-dependent and T cell-independent inflammatory responses, in vivo and in vitro. Due to the low or absent expression of the 5-HT(2B) receptor on T cell populations, the influence of AM1030 in T cell-dependent systems is suggested to be mediated via an indirect effect involving antigen-presenting cell types, such as monocytes and macrophages. CONCLUSION: Based on the wide range of model systems used in this study, differing e.g. with respect to species, T cell involvement, triggering stimuli, route of drug administration and read-outs, our results suggest a broad anti-inflammatory effect of AM1030 and identify the 5-HT(2B) receptor as a promising future target for anti-inflammatory intervention, e.g. in AD

Ein kleiner Freistrahlprüfstand für aeroakustische Messungen

Beschreibung des Aufbaus des kleinen Strahlprüfstands JExTRA für aeroakustische Experimente beim DLR Institut für Antriebstechnik, Abteilung Triebwerksakustik in Berlin

Left Main Coronary Artery Disease and Outcomes after Percutaneous Coronary Intervention for Chronic Total Occlusions

BACKGROUND Concomitant left main coronary artery (LMCA) disease in patients with chronic total occlusions (CTO) commonly results in referral for coronary artery bypass grafting, although the impact of LMCA in CTO patients remains largely unknown. Nevertheless, patient selection for percutaneous coronary intervention of CTOs (CTO-PCI) or alternative revascularization strategies should be based on precise evaluation of the coronary anatomy to anticipate those patients that most likely benefit from a procedure and not on strict adherence to perpetual clinical practice. Therefore, the aim of this study was to assess the impact of LMCA disease on long-term outcomes in patients undergoing percutaneous coronary intervention for CTO. METHODS We enrolled 3860 consecutive patients undergoing PCI for at least one CTO lesion and investigated the predictive value of concomitant LMCA disease. All-cause mortality was defined as the primary study endpoint. RESULTS We observed that LMCA disease is significantly associated with mortality. In the Cox regression analysis, we observed a crude hazard ratio (HR) 1.59 (95% confidence interval (CI) 1.23-2.04, p < 0.001) for patients with LMCA disease as compared to patients without. Results remained unchanged after bootstrap- or clinical confounder-based adjustment. CONCLUSION LMCA disease is associated with excess mortality in CTO patients. Specifically, anatomical features such as CTO of the circumflex artery represent a high risk patient population

Characteristics of divertor plasma in neutral beam heated ASDEX discharges

SIGLEDEGerman