Controlled density-downramp injection in a beam-driven plasma wakefield accelerator

This paper describes the utilization of beam-driven plasma wakefield acceleration to implement a high-quality plasma cathode via density-downramp injection in a short injector stage at the FLASHForward facility at DESY. Electron beams with charge of up to 105 pC and energy spread of a few percent were accelerated by a tunable effective accelerating field of up to 2.7 GV/m. The plasma cathode was operated drift-free with very high injection efficiency. Sources of jitter, the emittance and divergence of the resulting beam were investigated and modeled, as were strategies for performance improvements that would further increase the wide-ranging applications for a plasma cathode with the demonstrated operational stabilityComment: 11 pages, 9 figure

Fifth European Dirofilaria and Angiostrongylus Days (FiEDAD) 2016

Peer reviewe

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Crosstalk between different family members: IL27 recapitulates IFNγ responses in HCC cells, but is inhibited by IL6-type cytokines

Interleukin-27 (IL27) is a type-I-cytokine of the IL6/IL12 family predominantly secreted by activated macrophages and dendritic cells. In the liver, IL27 expression was observed to be upregulated in patients with hepatitis B, and sera of hepatocellular carcinoma (HCC) patients contain significantly elevated levels of IL27 compared to healthy controls or patients with hepatitis and/or liver cirrhosis. In this study, we show that IL27 induces STAT1 and STAT3 phosphorylation in 5 HCC lines and 3 different types of non-transformed liver cells. We were especially interested in the relevance of the IL27-induced STAT3 activation in liver cells. Thus, we compared the IL27 responses with those induced by IFNγ (STAT1-dominated response) or IL6-type cytokines (IL6, hyper-IL6 (hy-IL6) or OSM) (STAT3-dominated response) by microarray analysis and find that in HCC cells, IL27 induces an IFNγ-like, STAT1-dependent transcriptional response, but we do not find an effective STAT3-dependent response. Validation experiments corroborate the finding from the microarray evaluation. Interestingly, the availability of STAT1 seems critical in the shaping of the IL27 response, as the siRNA knock-down of STAT1 revealed the ability of IL27 to induce the acute-phase protein γ-fibrinogen, a typical IL6 family characteristic. Moreover, we describe a crosstalk between the signaling of IL6-type cytokines and IL27: responses to the gp130-engaging cytokine IL27 (but not those to IFNs) can be inhibited by IL6-type cytokine pre-stimulation, likely by a SOCS3-mediated mechanism. Thus, IL27 recapitulates IFNγ responses in liver cells, but differs from IFNγ by its sensitivity to SOCS3 inhibition

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Progress of beam driven plasma acceleration at FLASHForward

The FLASHForward experiment at DESY is a beam line build for beam-driven plasma-wakefield acceleration. The drive beams, supplied by the linac of the free-electron laser FLASH, have energies of up to 1.25GeV, a typical charge of 400 pC, emittance of a few mm mrad and a pulse duration down to 50fs. The extensive experimental programme consists of various experiments among which three are considered core experiments, focussing on internally (X-1) and externally (X-2) injected witness bunch acceleration as well as studies on high repetition rate and high average power operation (X-3). The latter is facilitated by the unique capability of extracting multiple electron bunches from the superconducting linac at a variable temporal spacing down to 333 ns. Here the present status of the facility and its capabilities as well as the status of current and future experiments will be detailed

Plasmas in liquids and their use for biomedical application

Plasma formation in liquids has due to the tremendous application potential been a fast developing topic in the past two decades. Here a study on sub-kV plasma formation in conducting liquids is presented. In this environment the temporal evolution from initiation of power input into the liquid can be separated into different phases. First of all, an Ohmic heating phase leads to vapour formation in the electrode proximity. This will be investigated experimentally as well as with a computer model. The present experimental studies demonstrate not only the complexity of this multi parameter system but also reveal the influence of specific parameters, such as conductivity and applied voltage. Those results have lead to incorporation and refinement of the model. Consecutively the advanced model enabled further understanding of the system and effects involved effects, e.g. superheating of the liquid before evaporation. When formed the vapour regime leads to isolation of the electrode from the liquid. Since electrode surface properties play an important role on discharge formation study of these lead to detection and information on salt as a surface contaminant after evaporation. For plasma formation those small salt crystals play a crucial role in discharge formation processes. After generation of a low density vapour environment formation of a plasma is observed within it. Regimes with stochastic discharge appearance as well as continuous discharges have been observed and ultimately lead to characterisation of the discharge type as well as determination of the electron density. Pronounced differences for positive and negative polarity are also highlighted. The rich chemistry with its reactive species in the liquid phase is then used for investigation of cancer cell treatment efficiency and compared with conventional x-ray treatment and there are indications of higher efficiency, in particular relating to range effects.EThOS - Electronic Theses Online ServiceGBUnited Kingdo