Proteomic analysis at the sites of clinical infection with invasive Streptococcus pyogenes

Invasive Streptococcus pyogenes infections are rare, with often-unexplained severity. Prompt diagnosis is desirable, as deaths can occur rapidly following onset and there is an increased, but preventable, risk to contacts. Here, proteomic analyses of clinical samples from invasive human S. pyogenes infections were undertaken to determine if novel diagnostic targets could be detected, and to augment our understanding of disease pathogenesis. Fluid samples from 17 patients with confirmed invasive S. pyogenes infection (empyema, septic arthritis, necrotising fasciitis) were analysed by proteomics for streptococcal and human proteins; 16/17 samples had detectable S. pyogenes DNA. Nineteen unique S. pyogenes proteins were identified in just 6/17 samples, and 15 of these were found in a single pleural fluid sample including streptococcal inhibitor of complement, trigger factor, and phosphoglycerate kinase. In contrast, 469 human proteins were detected in patient fluids, 177 (38%) of which could be identified as neutrophil proteins, including alpha enolase and lactotransferrin which, together, were found in all 17 samples. Our data suggest that streptococcal proteins are difficult to detect in infected fluid samples. A vast array of human proteins associated with leukocyte activity are, however, present in samples that deserve further evaluation as potential biomarkers of infection

Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: analysis of individual data from 94,638 patients treated in 55 breast cancer centers

Neoadjuvant chemotherapy (NACT) is frequently used in patients with early breast cancer. Randomized controlled trials have demonstrated similar survival after NACT or adjuvant chemotherapy (ACT). However, certain subtypes may benefit more when NACT contains regimes leading to high rates of pathologic complete response (pCR) rates. In this study we analyzed data using the OncoBox research from 94,638 patients treated in 55 breast cancer centers to describe the current clinical practice of and outcomes after NACT under routine conditions. These data were compared to patients treated with ACT. 40% of all patients received chemotherapy. The use of NACT increased over time from 5% in 2007 up to 17.3% in 2016. The proportion of patients receiving NACT varied by subtype. It was low in patients with HR-positive/HER2-negative breast cancer (5.8%). However, 31.8% of patients with triple-negative, 31.9% with HR-negative/HER2-positive, and 26.5% with HR-positive/HER2-positive breast cancer received NACT. The rates of pCR were higher in patients with HR-positive/HER2-positive, HR negative/HER2-positive and triple-negative tumors (36, 53 and 38%) compared to HR-positive/HER2-negative tumors (12%). PCR was achieved more often in HER2-positive and triple-negative tumors over time. This is the largest study on use and effects of NACT in German breast cancer centers. It demonstrates the increased use of NACT based on recommendations in current clinical guidelines. An improvement of pCR was shown in particular in HER2-positive and triple-negative breast cancer, which is consistent with data from randomized controlled trails

LOW SPEED WIND TUNNEL TEST OF A MORPHING LEADING EDGE

Because of the large potential of drag reduction natural laminar flow is one of the challenging aims of the current international aerospace research. For the achievement of the absolutely essential surface quality new concepts for the high lift system at the leading edge are required. Five years ago DLR started a new morphing activity aiming at a smart leading edge device [1]. The concept incorporates a flexible glass fibre structure of the leading edge which is actuated by conventional actuators and kinematic stations. The glass fibre structure is especially tailored to achieve a desired aerodynamic target shape and fully closed so that there are not steps and gaps for a high quality surface. In a first step a functional demonstrator was realized and tested in a ground test which is able to continuously alter the shape of a leading wing edge under wing bending loads. As a second step a European consortium of leading research groups and European aeronautic industry started the common project SADE in 2008 which aims to demonstrate the functionality of smart high lift devices in low speed wind tunnel tests. A functional full-scale demonstrator of 5m span and 3m chord is planned in the project. The paper gives a survey on the concept of the smart leading edge, the design of the wind tunnel demonstrator and on the recent results from the wind tunnel tests. The paper will focus on the validation of finite element calculations with the comparison of stress/strain data and the predicted deformations under aerodynamic loading