Alcoholic liver cirrhosis, more than a simple hepatic disease – A brief review of the risk factors associated with alcohol abuse

Liver cirrhosis is a significant public health problem, being an important cause of mortality and morbidity, responsible for approximately 1.8% of the total number of deaths in Europe. Chronic alcohol consumption is the most common cause of liver cirrhosis in developed countries. Europe has the highest level of alcohol consumption among all the global World Health Organisation (WHO) regions. In this paper, we briefly review major factors leading to excessive alcohol consumption in order to draw attention to the fact that alcoholic liver cirrhosis is more than a simple liver disease, and if those risk/causal factors can be prevented, the incidence of this disease could be reduced greatly. Although excessive alcohol consumption is regarded as the cause of alcoholic liver cirrhosis, the etiology is complex, involving multiple factors that act in synchrony, and which, if prevented, could greatly reduce the incidence of this disease. Children of addicts are likely to develop an alcohol-related mental disorder; however, there is no “gene for alcoholism”

Testing the Higgs Mechanism in the Lepton Sector with multi-TeV e+e- Collisions

Multi-TeV e+e- collisions provide with a large enough sample of Higgs bosons to enable measurements of its suppressed decays. Results of a detailed study of the determination of the muon Yukawa coupling at 3 TeV, based on full detector simulation and event reconstruction, are presented. The muon Yukawa coupling can be determined with a relative accuracy of 0.04 to 0.08 for Higgs bosons masses from 120 GeV to 150 GeV, with an integrated luminosity of 5 inverse-ab. The result is not affected by overlapping two-photon background.Comment: 6 pages, 2 figures, submitted to J Phys G.: Nucl. Phy

Pion and proton showers in the CALICE scintillator-steel analogue hadron calorimeter

Showers produced by positive hadrons in the highly granular CALICE scintillator-steel analogue hadron calorimeter were studied. The experimental data were collected at CERN and FNAL for single particles with initial momenta from 10 to 80 GeV/c. The calorimeter response and resolution and spatial characteristics of shower development for proton- and pion-induced showers for test beam data and simulations using Geant4 version 9.6 are compared.Comment: 26 pages, 16 figures, JINST style, changes in the author list, typos corrected, new section added, figures regrouped. Accepted for publication in JINS

Infrastructure for Detector Research and Development towards the International Linear Collider

The EUDET-project was launched to create an infrastructure for developing and testing new and advanced detector technologies to be used at a future linear collider. The aim was to make possible experimentation and analysis of data for institutes, which otherwise could not be realized due to lack of resources. The infrastructure comprised an analysis and software network, and instrumentation infrastructures for tracking detectors as well as for calorimetry.Comment: 54 pages, 48 picture

Status of the commissioning of the X-band injector prototype for AWAKE Run 2c

The status of commissioning of the electron injector intended for the next phase of the proton driven wakefield experiment, Advanced Wakefield Experiment (AWAKE), is presented, showing first results from operating the brazingfree electron gun. To provide a high-quality electron beam, the UV laser was centered on the copper cathode, and a novel beam-based alignment of the focusing solenoid was performed. Measurements of the beam parameters and working points are addressed. The electron gun is shown to provide a high quality, stable and reproducible beam

A compact water window X-ray source based on inverse Compton scattering

X-rays in the water window (2.33 nm to 4.40 nm wavelength) can be used to provide high quality images of wet biological samples. Given the limited availability of current generation light sources in this energy range, table-top water window X-ray sources have been proposed as alternatives. We present start-to-end simulations in RF-Track of a water window X-ray source based on inverse Compton scattering. A brazing-free electron gun with a maximum beam energy of 7 MeV is considered, providing photon energies covering the full water window range. Performance estimates for the gun operating with copper and cesium telluride cathodes are presented. The cesium telluride cathode, combined with a burst mode Fabry-Perot cavity, allows for an increase in flux by orders of magnitude compared to single bunch copper cathode operation. A beamline of 1 m was determined to be sufficient to produce a high photon flux

Dissimilar responses of fungal and bacterial communities to soil transplantation simulating abrupt climate changes.

Both fungi and bacteria play essential roles in regulating soil carbon cycling. To predict future carbon stability, it is imperative to understand their responses to environmental changes, which is subject to large uncertainty. As current global warming is causing range shifts toward higher latitudes, we conducted three reciprocal soil transplantation experiments over large transects in 2005 to simulate abrupt climate changes. Six years after soil transplantation, fungal biomass of transplanted soils showed a general pattern of changes from donor sites to destination, which were more obvious in bare fallow soils than in maize cropped soils. Strikingly, fungal community compositions were clustered by sites, demonstrating that fungi of transplanted soils acclimatized to the destination environment. Several fungal taxa displayed sharp changes in relative abundance, including Podospora, Chaetomium, Mortierella and Phialemonium. In contrast, bacterial communities remained largely unchanged. Consistent with the important role of fungi in affecting soil carbon cycling, 8.1%-10.0% of fungal genes encoding carbon-decomposing enzymes were significantly (p < 0.01) increased as compared with those from bacteria (5.7%-8.4%). To explain these observations, we found that fungal occupancy across samples was mainly determined by annual average air temperature and rainfall, whereas bacterial occupancy was more closely related to soil conditions, which remained stable 6 years after soil transplantation. Together, these results demonstrate dissimilar response patterns and resource partitioning between fungi and bacteria, which may have considerable consequences for ecosystem-scale carbon cycling

Genome analysis and physiological comparison of Alicycliphilus denitrificans strains BC and K601T

The genomes of the Betaproteobacteria Alicycliphilus denitrificans strains BC and K601T have been sequenced to get insight into the physiology of the two strains. Strain BC degrades benzene with chlorate as electron acceptor. The cyclohexanol-degrading denitrifying strain K601T is not able to use chlorate as electron acceptor, while strain BC cannot degrade cyclohexanol. The 16S rRNA sequences of strains BC and K601T are identical and the fatty acid methyl ester patterns of the strains are similar. Basic Local Alignment Search Tool (BLAST) analysis of predicted open reading frames of both strains showed most hits with Acidovorax sp. JS42, a bacterium that degrades nitro-aromatics. The genomes include strain-specific plasmids (pAlide201 in strain K601T and pAlide01 and pAlide02 in strain BC). Key genes of chlorate reduction in strain BC were located on a 120 kb megaplasmid (pAlide01), which was absent in strain K601T. Genes involved in cyclohexanol degradation were only found in strain K601T. Benzene and toluene are degraded via oxygenase-mediated pathways in both strains. Genes involved in the meta-cleavage pathway of catechol are present in the genomes of both strains. Strain BC also contains all genes of the ortho-cleavage pathway. The large number of mono- and dioxygenase genes in the genomes suggests that the two strains have a broader substrate range than known thus far.This research was supported by the Technology Foundation, the Applied Science Division (STW) of the Netherlands Organization for Scientific Research (NWO), project number 08053, the graduate school WIMEK (Wageningen Institute for Environment and Climate Research, which is part of SENSE Research School for Socio-Economic and Natural Sciences of the Environment, www.wimek-new.wur.nl and www.sense.nl), SKB (Dutch Centre for Soil Quality Management and Knowledge Transfer, www.skbodem.nl) and the Consolider project CSD-2007-00055. The research was incorporated in the TRIAS (TRIpartite Approaches 469 toward Soil systems processes) program (http://www.nwo.nl/en/research-and-results/programmes/alw/trias-tripartite-approach-to-soil-system-processes/index. html). Flávia Talarico Saia was supported by a FAPESP (the State of São Paulo Research Foundation) scholarship (2006-01997/5). The work conducted by the DOE JGI is supported by the Office of Science of the United States Department of Energy under contract number DE-AC02-05CH11231. Alfons Stams acknowledges support by an ERC (European Research Counsil) advanced grant (project 323009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Alcoholic liver cirrhosis, more than a simple hepatic disease – A brief review of the risk factors associated with alcohol abuse

Liver cirrhosis is a significant public health problem, being an important cause of mortality and morbidity, responsible for approximately 1.8% of the total number of deaths in Europe. Chronic alcohol consumption is the most common cause of liver cirrhosis in developed countries. Europe has the highest level of alcohol consumption among all the global World Health Organisation (WHO) regions. In this paper, we briefly review major factors leading to excessive alcohol consumption in order to draw attention to the fact that alcoholic liver cirrhosis is more than a simple liver disease, and if those risk/causal factors can be prevented, the incidence of this disease could be reduced greatly. Although excessive alcohol consumption is regarded as the cause of alcoholic liver cirrhosis, the etiology is complex, involving multiple factors that act in synchrony, and which, if prevented, could greatly reduce the incidence of this disease. Children of addicts are likely to develop an alcohol-related mental disorder; however, there is no “gene for alcoholism”