New Multiphase CP and DP 1000 MPa strength level grades for improved performance after hot forming

Pure martensitic steels have after hot forming limited performance in terms of rest ductility which limits the application in crash relevant parts. New steel grades were designed in the EU project HOTFORM including the corresponding process routes. These steel grades have ferritic-martensitic dual phase (DP) and martensitic-bainitic complex phase (CP) microstructures after hot forming process. The laboratory tests show an improved formability after hot forming. The basic concepts of the new alloys are explained. Furthermore, for validation of upscaling purposes a semi-industrial test is carried out and the results are discussed. The main application is for vehicle safety. This is evaluated by comparing the crash performance of these hot formed grades with cold rolled DP1000 and CP1000 for crash cans in a drop tower test.The research leading to these results was carried out in the framework of HOTFORM project with a financial grant of the Research Programme RFCS (Research Funds for Coal and Steel) under grant agreement (RFSR-CT-2015-00017)

Uptake of Leishmania major by dendritic cells is mediated by Fcγ receptors and facilitates acquisition of protective immunity

Uptake of Leishmania major by dendritic cells (DCs) results in activation and interleukin (IL)-12 release. Infected DCs efficiently stimulate CD4− and CD8− T cells and vaccinate against leishmaniasis. In contrast, complement receptor 3–dependent phagocytosis of L. major by macrophages (MΦ) leads exclusively to MHC class II–restricted antigen presentation to primed, but not naive, T cells, and no IL-12 production. Herein, we demonstrate that uptake of L. major by DCs required parasite-reactive immunoglobulin (Ig)G and involved FcγRI and FcγRIII. In vivo, DC infiltration of L. major–infected skin lesions coincided with the appearance of antibodies in sera. Skin of infected B cell–deficient mice and Fcγ−/− mice contained fewer parasite-infected DCs in vivo. Infected B cell–deficient mice as well as Fcγ−/− mice (all on the C57BL/6 background) showed similarly increased disease susceptibility as assessed by lesion volumes and parasite burdens. The B cell–deficient mice displayed impaired T cell priming and dramatically reduced IFN-γ production, and these deficits were normalized by infection with IgG-opsonized parasites. These data demonstrate that DC and MΦ use different receptors to recognize and ingest L. major with different outcomes, and indicate that B cell–derived, parasite-reactive IgG and DC FcγRI and FcγRIII are essential for optimal development of protective immunity

The registry of the German Network for Systemic Scleroderma: frequency of disease subsets and patterns of organ involvement

Objective. Systemic sclerosis (SSc) is a rare, heterogeneous disease, which affects different organs and therefore requires interdisciplinary diagnostic and therapeutic management. To improve the detection and follow-up of patients presenting with different disease manifestations, an interdisciplinary registry was founded with contributions from different subspecialties involved in the care of patients with SSc

Versorgungsrealität der stationären vasoaktiven Therapie mit Prostazyklinderivaten bei Patienten mit akralen Durchblutungsstörungen bei systemischer Sklerose in Deutschland

Zusammenfassung Hintergrund Das Raynaud-Phänomen und die damit häufig einhergehenden digitalen Ulzerationen stellen für Patienten mit systemischer Sklerose (Sklerodermie [SSc]) ein frühes und sehr belastendes Symptom mit bedeutenden Einschränkungen der Arbeitsfähigkeit und Lebensqualität dar. Der Einsatz vasoaktiver Medikamente (insbesondere intravenöser Prostazyklinderivate) soll helfen, das Risiko hypoxischer Gewebeschäden bis hin zum Verlust der Finger zu reduzieren. Methoden Um Aufschluss über die aktuelle Versorgung von Patienten mit Prostazyklinderivaten im klinischen Alltag in Deutschland zu erhalten, führten wir eine Umfrage unter den im Deutschen Netzwerk für systemische Sklerodermie (DNSS) zusammengeschlossenen Kliniken durch. Zusätzlich erfolgte eine separate Patientenbefragung über die Sklerodermie Selbsthilfe e. V., die sich nur auf die Symptome „Raynaud-Phänomen“ und „Digitale Ulzera“ und den Einsatz intravenöser Prostazyklinderivate bezog. Ergebnisse Von den befragten 433 Patienten gaben 56 % an, dass sie bereits aufgrund ihrer Erkrankung und Symptome mit Prostazyklinderivaten behandelt wurden. Insgesamt 61 % erhielten die Therapie aufgrund starker Raynaud-Symptomatik und 39 % aufgrund digitaler Ulzerationen. Die meisten Befragten erfuhren durch die Therapie nicht nur eine Verbesserung des Raynaud-Phänomens und der digitalen Ulzera, sondern auch eine wesentliche Verbesserung von Einschränkungen im Alltag. Sie gaben zudem an, wesentlich weniger fremde Hilfe in Anspruch genommen sowie wesentlich weniger Fehlzeiten bei der Arbeit gehabt zu haben. Schlussfolgerung Die Patienten empfanden durchweg einen positiven Effekt der Therapie mit Prostazyklinderivaten auf das Raynaud-Phänomen, ihre digitalen Ulzerationen, Schmerzen und Alltagseinschränkung und fühlten sich durch die stationäre Therapie gut und sicher betreut. Diese positiven Effekte in der Patientenwahrnehmung sind eine eindrückliche Stütze und bestätigen nachdrücklich die auf europäischer und internationaler Ebene erarbeiteten Therapieempfehlungen

Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p<0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice