Alcohol-related adverse consequences: cross-cultural variations in attribution process among young adults

Background: Social norms around what is culturally accepted in terms of alcohol consumption and drunken comportment appear important regarding the acceptance of alcohol-related adverse consequences; however, investigations often neglect to consider differences in terms of attribution. This study aims at assessing cross-cultural differences in the reporting of alcohol-related adverse consequences. It also considers differences across consequences that might explain which type of consequences (mainly acute or mainly chronic) are most affected by an attribution process. Methods: Conditional regression models were estimated based on data from eight European countries participating in the Gender, Alcohol and Culture—An International Study (GENACIS) project. Cases were matched to controls based on usual drinking patterns in order to control for average volume of alcohol and frequency of ‘risky single occasion drinking' (RSOD). Results: Differences among the patterns of associations between countries and consequences were evident. The distinction between Nordic and other European countries was persistent. A higher variability of associations was observed for some consequences, namely the mainly acute instances. Finally, the Isle of Man and Switzerland showed specific trends with associations across consequences. Conclusion: Reporting of alcohol-related adverse consequences seemed strongly affected by cultural norms. The latter may be exemplified by viewing drinking as ‘time-out' behaviour. Respondents in countries with a stereotypical history of being ‘dry' or with a stereotyped ‘binge' drinking culture were more likely to attribute consequences to their alcohol consumption than people in ‘wet' countries. This was particularly true for consequences that related to episodic ‘time-out' heavy drinkin

Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism : a pooled analysis of the EINSTEIN-DVT and PE randomized studies

Background: Standard treatment for venous thromboembolism (VTE) consists of a heparin combined with vitamin K antagonists. Direct oral anticoagulants have been investigated for acute and extended treatment of symptomatic VTE; their use could avoid parenteral treatment and/or laboratory monitoring of anticoagulant effects. Methods: A prespecified pooled analysis of the EINSTEIN-DVT and EINSTEIN-PE studies compared the efficacy and safety of rivaroxaban (15 mg twice-daily for 21 days, followed by 20 mg once-daily) with standard-therapy (enoxaparin 1.0 mg/kg twice-daily and warfarin or acenocoumarol). Patients were treated for 3, 6, or 12 months and followed for suspected recurrent VTE and bleeding. The prespecified noninferiority margin was 1.75. Results: 8282 patients were enrolled. 4151 received rivaroxaban and 4131 received standard-therapy. The primary efficacy outcome occurred in 86 rivaroxaban-treated patients (2.1%) compared with 95 (2.3%) standard-therapy-treated patients (hazard ratio, 0.89; 95% confidence interval [CI], 0.66-1.19; pnoninferiority<0.001). Major bleeding was observed in 40 (1.0%) and 72 (1.7%) patients in the rivaroxaban and standard-therapy groups, respectively (hazard ratio, 0.54; 95% CI, 0.37-0.79; p=0.002). In key subgroups, including fragile patients, cancer patients, patients presenting with large clots and those with a history of recurrent VTE, the efficacy and safety of rivaroxaban was similar compared with standard-therapy. Conclusion: The single-drug approach with rivaroxaban resulted in similar efficacy to standard-therapy and was associated with a significantly lower rate of major bleeding. Efficacy and safety results were consistent among key patient subgroups

Electroluminescence of hot electrons in AlGaN/GaN high-electron-mobility transistors under radio frequency operation

Hot electrons in AlGaN/GaN high electron mobility transistors are studied during radio frequency (RF) and DC operation by means of electroluminescence (EL) microscopy and spectroscopy. The measured EL intensity is decreased under RF operation compared to DC at the same average current, indicating a lower hot electron density. This is explained by averaging the DC EL intensity over the measured load line used in RF measurements, giving reasonable agreement. In addition, the hot electron temperature is lower by up to 15% under RF compared to DC, again at least partially explainable by the weighted averaging along the specific load line. However, peak electron temperature under RF occurs at high VDS and low IDS where EL is insignificant suggesting that any wear-out differences between RF and DC stress of the devices will depend on the balance between hot-carrier and field driven degradation mechanisms

A Novel fry1 Allele Reveals the Existence of a Mutant Phenotype Unrelated to 5′->3′ Exoribonuclease (XRN) Activities in Arabidopsis thaliana Roots

BACKGROUND Mutations in the FRY1/SAL1 Arabidopsis locus are highly pleiotropic, affecting drought tolerance, leaf shape and root growth. FRY1 encodes a nucleotide phosphatase that in vitro has inositol polyphosphate 1-phosphatase and 3',(2'),5'-bisphosphate nucleotide phosphatase activities. It is not clear which activity mediates each of the diverse biological functions of FRY1 in planta. PRINCIPAL FINDINGS A fry1 mutant was identified in a genetic screen for Arabidopsis mutants deregulated in the expression of Pi High affinity Transporter 1;4 (PHT1;4). Histological analysis revealed that, in roots, FRY1 expression was restricted to the stele and meristems. The fry1 mutant displayed an altered root architecture phenotype and an increased drought tolerance. All of the phenotypes analyzed were complemented with the AHL gene encoding a protein that converts 3'-polyadenosine 5'-phosphate (PAP) into AMP and Pi. PAP is known to inhibit exoribonucleases (XRN) in vitro. Accordingly, an xrn triple mutant with mutations in all three XRNs shared the fry1 drought tolerance and root architecture phenotypes. Interestingly these two traits were also complemented by grafting, revealing that drought tolerance was primarily conferred by the rosette and that the root architecture can be complemented by long-distance regulation derived from leaves. By contrast, PHT1 expression was not altered in xrn mutants or in grafting experiments. Thus, PHT1 up-regulation probably resulted from a local depletion of Pi in the fry1 stele. This hypothesis is supported by the identification of other genes modulated by Pi deficiency in the stele, which are found induced in a fry1 background. CONCLUSIONS/SIGNIFICANCE Our results indicate that the 3',(2'),5'-bisphosphate nucleotide phosphatase activity of FRY1 is involved in long-distance as well as local regulatory activities in roots. The local up-regulation of PHT1 genes transcription in roots likely results from local depletion of Pi and is independent of the XRNs.This work was supported by an ANR-GENOPLANT grant (RIBOROOT-ANR06 GPLA 011) and the CEA agency. Array hybridizations have been partly supported by RNG (Réseau National des Génopoles, Evry, France). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study

Field-Induced Magnetization Steps in Intermetallic Compounds and Manganese Oxides: The Martensitic Scenario

Field-induced magnetization jumps with similar characteristics are observed at low temperature for the intermetallic germanide Gd5Ge4and the mixed-valent manganite Pr0.6Ca0.4Mn0.96Ga0.04O3. We report that the field location -and even the existence- of these jumps depends critically on the magnetic field sweep rate used to record the data. It is proposed that, for both compounds, the martensitic character of their antiferromagnetic-to-ferromagnetic transitions is at the origin of the magnetization steps.Comment: 4 pages,4 figure

Darwin -— an experimental astronomy mission to search for extrasolar planets

As a response to ESA call for mission concepts for its Cosmic Vision 2015–2025 plan, we propose a mission called Darwin. Its primary goal is the study of terrestrial extrasolar planets and the search for life on them. In this paper, we describe different characteristics of the instrument

Mutation in human CLPX elevates levels of δ-aminolevulinate synthase and protoporphyrin IX to promote erythropoietic protoporphyria

Loss-of-function mutations in genes for heme biosynthetic enzymes can give rise to congenital porphyrias, eight forms of which have been described. The genetic penetrance of the porphyrias is clinically variable, underscoring the role of additional causative, contributing, and modifier genes. We previously discovered that the mitochondrial AAA+ unfoldase ClpX promotes heme biosynthesis by activation of δ-aminolevulinate synthase (ALAS), which catalyzes the first step of heme synthesis. CLPX has also been reported to mediate heme-induced turnover of ALAS. Here we report a dominant mutation in the ATPase active site of human CLPX, p.Gly298Asp, that results in pathological accumulation of the heme biosynthesis intermediate protoporphyrin IX (PPIX). Amassing of PPIX in erythroid cells promotes erythropoietic protoporphyria (EPP) in the affected family. The mutation in CLPX inactivates its ATPase activity, resulting in coassembly of mutant and WT protomers to form an enzyme with reduced activity. The presence of low-activity CLPX increases the posttranslational stability of ALAS, causing increased ALAS protein and ALA levels, leading to abnormal accumulation of PPIX. Our results thus identify an additional molecular mechanism underlying the development of EPP and further our understanding of the multiple mechanisms by which CLPX controls heme metabolism. Keywords: heme biosynthesis; porphyria; ALAS; protein unfoldases; AAA+ ATPaseNational Institutes of Health (U.S.) (Grant F32 DK095726)National Institutes of Health (U.S.) (Grant R01 GM049224

Cost-effectiveness of palbociclib in early breast cancer patients with a high risk of relapse: Results from the PENELOPE-B trial

BACKGROUND Patients with hormone receptor-positive, HER2-negative breast cancer who have residual invasive disease after neoadjuvant chemotherapy (NACT) are at a high risk of relapse. PENELOPE-B was a double-blind, placebo-controlled, phase III trial that investigated adding palbociclib (PAL) for thirteen 28-day cycles to adjuvant endocrine therapy (ET) in these patients. Clinical results showed no significant improvement in invasive disease-free survival with PAL. METHODS We performed a pre-planned cost-effectiveness analysis of PAL within PENELOPE-B from the perspective of the German statutory health insurance. Health-related quality of life scores, collected in the trial using the EQ-5D-3L instrument, were converted to utilities based on the German valuation algorithm. Resource use was valued using German price weights. Outcomes were discounted at 3% and modeled with mixed-level linear models to adjust for attrition, repeated measurements, and residual baseline imbalances. Subgroup analyses were performed for key prognostic risk factors. Scenario analyses addressed data limitations and evaluated the robustness of the estimated cost-effectiveness of PAL to methodological choices. RESULTS The effects of PAL on quality-adjusted life years (QALYs) were marginal during the active treatment phase, increasing thereafter to 0.088 (95% confidence interval: -0.001; 0.177) QALYs gained over the 4 years of follow-up. The incremental costs were dominated by PAL averaging EUR 33,000 per patient; costs were higher in the PAL arm but not significantly different after the second year. At an incremental cost-effectiveness ratio of EUR 380,000 per QALY gained, PAL was not cost-effective compared to the standard-of-care ET. Analyses restricted to Germany and other subgroups were consistent with the main results. Findings were robust in the scenarios evaluated. CONCLUSIONS One year of PAL added to ET is not cost-effective in women with residual invasive disease after NACT in Germany

K0s K0s Final State in Two-Photon Collisions and Implications for Glueballs

The K0s K0s final state in two-photon collisions is studied with the L3 detector at LEP. The mass spectrum is dominated by the formation of the f_2'(1525) tensor meson in the helicity-two state with a two-photon width times the branching ratio into K Kbar of 76 +- 6 +- 11 eV. A clear signal for the formation of the f_J(1710) is observed and it is found to be dominated by the spin-two helicity-two state. No resonance is observed in the mass region around 2.2 GeV and an upper limit of 1.4 eV at 95% C.L. is derived for the two-photon width times the branching ratio into K0s K0s for the glueball candidate xi(2230)

Direct Observation of Longitudinally Polarised W Bosons

The three different helicity states of W bosons, produced in the reaction e+e- -> W+W- -> l nu q q~ are studied using leptonic and hadronic W decays at sqrt{s}=183GeV and 189GeV. The W polarisation is also measured as a function of the scattering angle between the W- and the direction of the e- beam. The analysis demonstrates that W bosons are produced with all three helicities, the longitudinal and the two transverse states. Combining the results from the two center-of-mass energies and with leptonic and hadronic W decays, the fraction of longitudinally polarised W bosons is measured to be 0.261 +/- 0.051(stat.) +/- 0.016(syst.) in agreement with the expectation from the Standard Model