The Compact Linear Collider (CLIC) - 2018 Summary Report

The Compact Linear Collider (CLIC) is a TeV-scale high-luminosity linear $e^+e^-$ collider under development at CERN. Following the CLIC conceptual design published in 2012, this report provides an overview of the CLIC project, its current status, and future developments. It presents the CLIC physics potential and reports on design, technology, and implementation aspects of the accelerator and the detector. CLIC is foreseen to be built and operated in stages, at centre-of-mass energies of 380 GeV, 1.5 TeV and 3 TeV, respectively. CLIC uses a two-beam acceleration scheme, in which 12 GHz accelerating structures are powered via a high-current drive beam. For the first stage, an alternative with X-band klystron powering is also considered. CLIC accelerator optimisation, technical developments and system tests have resulted in an increased energy efficiency (power around 170 MW) for the 380 GeV stage, together with a reduced cost estimate at the level of 6 billion CHF. The detector concept has been refined using improved software tools. Significant progress has been made on detector technology developments for the tracking and calorimetry systems. A wide range of CLIC physics studies has been conducted, both through full detector simulations and parametric studies, together providing a broad overview of the CLIC physics potential. Each of the three energy stages adds cornerstones of the full CLIC physics programme, such as Higgs width and couplings, top-quark properties, Higgs self-coupling, direct searches, and many precision electroweak measurements. The interpretation of the combined results gives crucial and accurate insight into new physics, largely complementary to LHC and HL-LHC. The construction of the first CLIC energy stage could start by 2026. First beams would be available by 2035, marking the beginning of a broad CLIC physics programme spanning 25-30 years

Evaluation of the SafeHeal Colovac+ anastomosis protection device : a preclinical study

Background The protective ostomy is the current standard of care to protect a low colorectal anastomosis from leakage, but exposes patients to complications requiring an alternative strategy. The Colovac+ is a vacuum-based intraluminal bypass device designed to shield the anastomosis from fecal content, preventing the clinical outcomes of anastomotic leakage. The objective of this study was to evaluate the preliminary efficacy, safety, and technical feasibility of the Colovac+ in a porcine model. Methods: Twelve pigs received a colorectal anastomosis with Colovac+ implantation. The device was left in situ for 10 days and then retrieved endoscopically. Six pigs were to be sacrificed immediately after device retrieval and the other 6 were to be sacrificed on day 38. Clinical, endoscopic, and histopathological examinations were performed to evaluate the following endpoints: prevention of contact between the anastomosis and fecal content, device migration, feasibility of the implantation and retrieval procedure, collateral damage to the colonic wall, colon healing after device retrieval, and systemic toxicity related to the device. Results: Eleven pigs completed the study. One pig died prematurely due to a surgical complication unrelated to the device (bladder damage with uroperitoneum). There was no evidence of contact between the anastomosis and fecal content, none of the pigs developed symptomatic anastomotic leakage, there were no significant device migrations, and there was no evidence of systemic toxicity. Colovac+ implantation was easily performed in all cases except 1 (due to an inappropriate lubricant). Colovac+ retrieval was achieved successfully in all cases. Postretrieval examinations on day 10 revealed ulcerations at the anchoring site in 4 cases indicating mechanical damage caused by the stent. However, in the recovery group, no ulcerations were observed on day 38, and the colonic wall had properly healed in all animals. Conclusions: The Colovac+ is a technically feasible, safe, and efficient device for the protection of a colorectal anastomosis in a porcine model. The device holds promise for clinical use and warrants further research

Butyrate acts through HDAC inhibition to enhance aryl hydrocarbon receptor activation by gut microbiota-derived ligands

Aryl hydrocarbon receptor (AhR) is a critical player in the crosstalk between the gut microbiota and its host. However, factors regulating AhR within the gut, which is a complex metabolomic environment, are poorly understood. This study investigates the effect of a combination of metabolites on the activation mechanism of AhR. AhR activity was evaluated using both a luciferase reporter system and mRNA levels of AhR target genes on human cell lines and human colonic explants. AhR activation was studied by radioligand-binding assay, nuclear translocation of AhR by immuofluorescence and protein co-immunoprecipitation of AhR with ARNT. Indirect activation of AhR was evaluated using several tests and inhibitors. The promoter of the target gene CYP1A1 was studied both by chromatin immunoprecipitation and by using an histone deacetylase HDAC inhibitor (iHDAC). Short-chain fatty acids, and butyrate in particular, enhance AhR activity mediated by endogenous tryptophan metabolites without binding to the receptor. This effect was confirmed in human intestinal explants and did not rely on activation of receptors targeted by SCFAs, inhibition of AhR degradation or clearance of its ligands. Butyrate acted directly on AhR target gene promoter to reshape chromatin through iHDAC activity. Our findings revealed that butyrate is not an AhR ligand but acts as iHDAC leading to an increase recruitment of AhR to the target gene promoter in the presence of tryptophan-derived AhR agonists. These data contribute to a novel understanding of the complex regulation of AhR activation by gut microbiota-derived metabolites

Re: Re: ``Adult appendicitis: Clinical practice guidelines from the French Society of Digestive Surgery (SFCD) and the Society of Abdominal and Digestive Imaging (SIAD)

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