Scrape-off layer turbulence in TCV: Evidence in support of stochastic modelling.

Manuscript. Published version available in Plasma Physics and Controlled Fusion, vol. 58, no. 4Intermittent fluctuations in the TCV scrape-off layer have been investigated by analysing long Langmuir probe data time series under stationary conditions, allowing calculation of fluctuation statistics with high accuracy. The ion saturation current signal is dominated by the frequent occurrence of large-amplitude bursts attributed to filament structures moving through the scrape-off layer. The average burst shape is well described by a double-exponential wave-form with constant duration, while the waiting times and peak amplitudes of the bursts both have an exponential distribution. Associated with bursts in the ion saturation current is a dipole-shaped floating potential structure and radially outwards directed electric drift velocity and particle flux, with average peak values increasing with the saturation current burst amplitude. The floating potential fluctuations have a normal probability density function while the distributions for the ion saturation current and estimated radial velocity have exponential tails for large fluctuations. These findings are discussed in the light of prevailing theories for filament motion and a stochastic model for intermittent scrape-off layer plasma fluctuations

Structure-Integrated Thin-Film Supercapacitor as a Sensor

Today, aircraft composite structures are generally over-dimensioned to avoid catastrophic failure by unseen damages. This leads to a higher system weight and therefore an unwanted increase in greenhouse gas emissions. To reduce this parasitic mass, load monitoring can play an important role in damage detection. Additionally, the weight and volume of future aircraft structures can also be reduced by energy storing and load carrying structures: so-called power composites. In this study a novel method of combining both approaches for maximum weight reduction is shown. This is achieved by using power composites as load monitoring sensors and energy suppliers. Therefore, supercapacitors are integrated into fiber reinforced polymers and are then used to investigate the mechanical load influence. By using four-point bending experiments and in situ electrochemical impedance spectroscopy, a strong relation between the mechanical load and the electrochemical system is found and analyzed using a model. For the first time, it is possible to detect small strain values down to 0.2% with a power composite. This strain is considerably lower than the conventional system load. The developed model and the impedance data indicate the possibility of using the composite as an energy storage as well as a strain sensor

final results of a noninterventional study

Background Data are limited regarding routine use of everolimus after initial vascular endothelial growth factor (VEGF)–targeted therapy. The aim of this prospective, noninterventional, observational study was to assess efficacy and safety of everolimus after initial VEGF-targeted treatment in patients with metastatic renal cell carcinoma (mRCC) in routine clinical settings. Methods Everolimus was administered per routine clinical practice. Patients with mRCC of any histology from 116 active sites in Germany were included. The main objective was to determine everolimus efficacy in time to progression (TTP). Progression-free survival (PFS), treatment duration, tumor response, adherence to everolimus regimen, treatment after everolimus, and safety were also assessed. Results In the total population (N = 334), median follow-up was 5.2 months (range, 0–32 months). Median treatment duration (safety population, n = 318) was 6.5 months (95% confidence interval [CI], 5–8 months). Median TTP and median PFS were similar in populations investigated. In patients who received everolimus as second-line treatment (n = 211), median (95% CI) TTP was 7.1 months (5–9 months) and median PFS was 6.9 months (5–9 months). Commonly reported adverse events (safety population, n = 318) were dyspnea (17%), anemia (15%), and fatigue (12%). Limitations of the noninterventional design should be considered. Conclusions This study reflects routine clinical use of everolimus in a large sample of patients with mRCC. Favorable efficacy and safety were seen for everolimus after previous therapy with one VEGF-targeted agent. Results of this study confirm everolimus as one of the standard options in second-line therapy for patients with mRCC. Novartis study code, CRAD001LD27: VFA registry for noninterventional studies (http://www.vfa.de/de/forschung/nisdb/ webcite)

Everolimus in metastatic renal cell carcinoma after failure of initial anti-VEGF therapy: final results of a noninterventional study

Background: Data are limited regarding routine use of everolimus after initial vascular endothelial growth factor (VEGF)-targeted therapy. The aim of this prospective, noninterventional, observational study was to assess efficacy and safety of everolimus after initial VEGF-targeted treatment in patients with metastatic renal cell carcinoma (mRCC) in routine clinical settings. Methods: Everolimus was administered per routine clinical practice. Patients with mRCC of any histology from 116 active sites in Germany were included. The main objective was to determine everolimus efficacy in time to progression (TTP). Progression-free survival (PFS), treatment duration, tumor response, adherence to everolimus regimen, treatment after everolimus, and safety were also assessed. Results: In the total population (N = 334),median follow-up was 5.2 months (range, 0-32 months). Median treatment duration (safety population, n = 318) was 6.5 months (95% confidence interval [CI], 5-8 months). Median TTP and median PFS were similar in populations investigated. In patients who received everolimus as second-line treatment (n = 211),median (95% CI) TTP was 7.1 months (5-9 months) and median PFS was 6.9 months (5-9 months). Commonly reported adverse events (safety population, n = 318) were dyspnea (17%),anemia (15%), and fatigue (12%). Limitations of the noninterventional design should be considered. Conclusions: This study reflects routine clinical use of everolimus in a large sample of patients with mRCC. Favorable efficacy and safety were seen for everolimus after previous therapy with one VEGF-targeted agent. Results of this study confirm everolimus as one of the standard options in second-line therapy for patients with mRCC

Everolimus in Metastatic Renal Cell Carcinoma after Failure of Initial Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor (VEGFr-TKI) Therapy: Results of an Interim Analysis of a Non-Interventional Study

Background: Everolimus is approved for treatment of anti-vascularendothelial growth factor (VEGF)-refractory patients with metastaticrenal cell carcinoma (mRCC). Clinical trials rarely mirror treatmentreality. Thus, a broader evaluation of everolimus is valuable forroutine use. Patients and Methods: A German multicenternon-interventional study documented mRCC patients starting everolimusafter failure of initial VEGF-targeted therapy. Primary endpoint waseffectiveness, defined as time to progression (TIP) according toinvestigator assessment (time from first dose to progression). Results:Of 382 documented patients, 196 were included in this interim analysis

Rapid diagnostic tests as a source of DNA for Plasmodium species-specific real-time PCR

<p>Abstract</p> <p>Background</p> <p>This study describes the use of malaria rapid diagnostic tests (RDTs) as a source of DNA for <it>Plasmodium </it>species-specific real-time PCR.</p> <p>Methods</p> <p>First, the best method to recover DNA from RDTs was investigated and then the applicability of this DNA extraction method was assessed on 12 different RDT brands. Finally, two RDT brands (OptiMAL Rapid Malaria Test and SDFK60 malaria Ag <it>Plasmodium falciparum</it>/Pan test) were comprehensively evaluated on a panel of clinical samples submitted for routine malaria diagnosis at ITM. DNA amplification was done with the 18S rRNA real-time PCR targeting the four <it>Plasmodium </it>species. Results of PCR on RDT were compared to those obtained by PCR on whole blood samples.</p> <p>Results</p> <p>Best results were obtained by isolating DNA from the proximal part of the nitrocellulose component of the RDT strip with a simple DNA elution method. The PCR on RDT showed a detection limit of 0.02 asexual parasites/μl, which was identical to the same PCR on whole blood. For all 12 RDT brands tested, DNA was detected except for one brand when a low parasite density sample was applied. In RDTs with a plastic seal covering the nitrocellulose strip, DNA extraction was hampered. PCR analysis on clinical RDT samples demonstrated correct identification for single species infections for all RDT samples with asexual parasites of <it>P. falciparum </it>(n = 60), <it>Plasmodium vivax </it>(n = 10), <it>Plasmodium ovale </it>(n = 10) and <it>Plasmodium malariae </it>(n = 10). Samples with only gametocytes were detected in all OptiMAL and in 10 of the 11 SDFK60 tests. None of the negative samples (n = 20) gave a signal by PCR on RDT. With PCR on RDT, higher Ct-values were observed than with PCR on whole blood, with a mean difference of 2.68 for OptiMAL and 3.53 for SDFK60. Mixed infections were correctly identified with PCR on RDT in 4/5 OptiMAL tests and 2/5 SDFK60 tests.</p> <p>Conclusions</p> <p>RDTs are a reliable source of DNA for <it>Plasmodium </it>real-time PCR. This study demonstrates the best method of RDT fragment sampling for a wide range of RDT brands in combination with a simple and low cost extraction method, allowing RDT quality control.</p

GEO-6 assessment for the pan-European region

Through this assessment, the authors and the United Nations Environment Programme (UNEP) secretariat are providing an objective evaluation and analysis of the pan-European environment designed to support environmental decision-making at multiple scales. In this assessment, the judgement of experts is applied to existing knowledge to provide scientifically credible answers to policy-relevant questions. These questions include, but are not limited to the following:• What is happening to the environment in the pan-European region and why?• What are the consequences for the environment and the human population in the pan-European region?• What is being done and how effective is it?• What are the prospects for the environment in the future?• What actions could be taken to achieve a more sustainable future?<br/

Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma

Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing