Hazardous alcohol consumption is associated with increased levels of B-type natriuretic peptide: evidence from two population-based studies

Russia has very high mortality from cardiovascular disease (CVD), with evidence that heavy drinking may play a role. To throw further light on this association we have studied the association of alcohol with predictors of CVD risk including B-type natriuretic peptide (BNP). Levels of BNP increase primarily in response to abnormal cardiac chamber wall stretch which can occur both as a result of atherosclerosis as well as due to other types of damage to the myocardium. No previous population-based studies have investigated the association with alcohol. We analysed cross-sectional data on drinking behaviour in 993 men aged 25-60 years from the Izhevsk Family Study 2 (IFS2), conducted in the Russian city of Izhevsk in 2008-2009. Relative to non-drinkers, men who drank hazardously had an odds ratio (OR) of being in the top 20 % of the BNP distribution of 4.66 (95 % CI 2.13, 10.19) adjusted for age, obesity, waist-hip ratio, and smoking. Further adjustment for class of hypertension resulted in only slight attenuation of the effect, suggesting that this effect was not secondary to the influence of alcohol on blood pressure. In contrast hazardous drinking was associated with markedly raised ApoA1 and HDL cholesterol levels, but had little impact on levels of ApoB and LDL cholesterol. Similar but less pronounced associations were found in the Belfast (UK) component of the PRIME study conducted in 1991. These findings suggest that the association of heavy drinking with increased risk of cardiovascular disease may be partly due to alcohol-induced non-atherosclerotic damage to the myocardium.

Intermittent chemotherapy plus either intermittent or continuous cetuximab for first-line treatment of patients with KRAS wild-type advanced colorectal cancer (COIN-B): a randomised phase 2 trial

Background: Advanced colorectal cancer is treated with a combination of cytotoxic drugs and targeted treatments. However, how best to minimise the time spent taking cytotoxic drugs and whether molecular selection can refine this further is unknown. The primary aim of this study was to establish how cetuximab might be safely and effectively added to intermittent chemotherapy.

Methods: COIN-B was an open-label, multicentre, randomised, exploratory phase 2 trial done at 30 hospitals in the UK and one in Cyprus. We enrolled patients with advanced colorectal cancer who had received no previous chemotherapy for metastases. Randomisation was done centrally (by telephone) by the Medical Research Council Clinical Trials Unit using minimisation with a random element. Treatment allocation was not masked. Patients were assigned (1:1) to intermittent chemotherapy plus intermittent cetuximab or to intermittent chemotherapy plus continuous cetuximab. Chemotherapy was FOLFOX (folinic acid and oxaliplatin followed by bolus and infused fluorouracil). Patients in both groups received FOLFOX and weekly cetuximab for 12 weeks, then either had a planned interruption (those taking intermittent cetuximab) or planned maintenance by continuing on weekly cetuximab (continuous cetuximab). On RECIST progression, FOLFOX plus cetuximab or FOLFOX was recommenced for 12 weeks followed by further interruption or maintenance cetuximab, respectively. The primary outcome was failure-free survival at 10 months. The primary analysis population consisted of patients who completed 12 weeks of treatment without progression, death, or leaving the trial. We tested BRAF and NRAS status retrospectively. The trial was registered, ISRCTN38375681.

Findings: We registered 401 patients, 226 of whom were enrolled. Results for 169 with KRAS wild-type are reported here, 78 (46%) assigned to intermittent cetuximab and 91 (54%) to continuous cetuximab. 64 patients assigned to intermittent cetuximab and 66 of those assigned to continuous cetuximab were included in the primary analysis. 10-month failure-free survival was 50% (lower bound of 95% CI 39) in the intermittent group versus 52% (lower bound of 95% CI 41) in the continuous group; median failure-free survival was 12·2 months (95% CI 8·8–15·6) and 14·3 months (10·7–20·4), respectively. The most common grade 3–4 adverse events were skin rash (21 [27%] of 77 patients vs 20 [22%] of 92 patients), neutropenia (22 [29%] vs 30 [33%]), diarrhoea (14 [18%] vs 23 [25%]), and lethargy (20 [26%] vs 19 [21%]).

Interpretation: Cetuximab was safely incorporated in two first-line intermittent chemotherapy strategies. Maintenance of biological monotherapy, with less cytotoxic chemotherapy within the first 6 months, in molecularly selected patients is promising and should be validated in phase 3 trials.

SN 2009N: linking normal and subluminous Type II-P Sne

We present ultraviolet, optical, near-infrared photometry and spectroscopy of SN 2009N in NGC 4487. This object is a Type II-P supernova with spectra resembling those of subluminous II-P supernovae, while its bolometric luminosity is similar to that of the intermediate-luminosity SN 2008in. We created SYNOW models of the plateau phase spectra for line identification and to measure the expansion velocity. In the near-infrared spectra we find signs indicating possible weak interaction between the supernova ejecta and the pre-existing circumstellar material. These signs are also present in the previously unpublished near-infrared spectra of SN 2008in. The distance to SN 2009N is determined via the expanding photosphere method and the standard candle method as D = 21.6 ± 1.1 Mpc. The produced nickel-mass is estimated to be ∼0.020 ± 0.004 M⊙. We infer the physical properties of the progenitor at the explosion through hydrodynamical modelling of the observables. We find the values of the total energy as ∼0.48 × 1051 erg, the ejected mass as ∼11.5 M⊙, and the initial radius as ∼287 R⊙.

A statistical analysis of circumstellar material in Type Ia supernovae

A key tracer of the elusive progenitor systems of Type Ia supernovae (SNe Ia) is the detection of narrow blueshifted time-varying Na I D absorption lines, interpreted as evidence of circumstellar material surrounding the progenitor system. The origin of this material is controversial, but the simplest explanation is that it results from previous mass-loss in a system containing a white dwarf and a non-degenerate companion star. We present new single-epoch intermediate-resolution spectra of 17 low-redshift SNe Ia taken with XShooter on the European Southern Observatory Very Large Telescope. Combining this sample with events from the literature, we confirm an excess (∼20 per cent) of SNe Ia displaying blueshifted narrow Na I D absorption features compared to redshifted Na I D features. The host galaxies of SNe Ia displaying blueshifted absorption profiles are skewed towards later-type galaxies, compared to SNe Ia that show no Na I D absorption and SNe Ia displaying blueshifted narrow Na I D absorption features have broader light curves. The strength of the Na I D absorption is stronger in SNe Ia displaying blueshifted Na I D absorption features than those without blueshifted features, and the strength of the blueshifted Na I D is correlated with the B − V colour of the SN at maximum light. This strongly suggests the absorbing material is local to the SN. In the context of the progenitor systems of SNe Ia, we discuss the significance of these findings and other recent observational evidence on the nature of SN Ia progenitors. We present a summary that suggests that there are at least two distinct populations of normal, cosmologically useful SNe Ia.

The effect of the spectral distribution of wave energy on the performance of a bottom hinged flap type wave energy converter

The power output from a wave energy converter is typically predicted using experimental and/or numerical modelling techniques. In order to yield meaningful results the relevant characteristics of the device, together with those of the wave climate must be modelled with sufficient accuracy.

The wave climate is commonly described using a scatter table of sea states defined according to parameters related to wave height and period. These sea states are traditionally modelled with the spectral distribution of energy defined according to some empirical formulation. Since the response of most wave energy converters vary at different frequencies of excitation, their performance in a particular sea state may be expected to depend on the choice of spectral shape employed rather than simply the spectral parameters. Estimates of energy production may therefore be affected if the spectral distribution of wave energy at the deployment site is not well modelled. Furthermore, validation of the model may be affected by differences between the observed full scale spectral energy distribution and the spectrum used to model it.

This paper investigates the sensitivity of the performance of a bottom hinged flap type wave energy converter to the spectral energy distribution of the incident waves. This is investigated experimentally using a 1:20 scale model of Aquamarine Power’s Oyster wave energy converter, a bottom hinged flap type device situated at the European Marine Energy Centre (EMEC) in approximately 13m water depth. The performance of the model is tested in sea states defined according to the same wave height and period parameters but adhering to different spectral energy distributions.

The results of these tests show that power capture is reduced with increasing spectral bandwidth. This result is explored with consideration of the spectral response of the device in irregular wave conditions. The implications of this result are discussed in the context of validation of the model against particular prototype data sets and estimation of annual energy production.

EL CVn-type binaries - Discovery of 17 helium white dwarf precursors in bright eclipsing binary star systems

The star 1SWASP J024743.37-251549.2 was recently discovered to be a binary star in which an A-type dwarf star eclipses the remnant of a disrupted red giant star (WASP 0247-25 B). The remnant is in a rarely observed state evolving to higher effective temperatures at nearly constant luminosity prior to becoming a very low mass white dwarf composed almost entirely of helium, i.e. it is a pre-helium white dwarf (pre-He-WD). We have used the photometric database from theWide Angle Search for Planets (WASP) to find 17 eclipsing binary stars with orbital periods P = 0.7-2.2 d with similar light curves to 1SWASP J024743.37-251549.2. The only star in this group previously identified as a variable star is the brightest one, EL CVn, which we adopt as the prototype for this class of eclipsing binary star. The characteristic light curves of EL CVn-type stars show a total eclipse by an A-type dwarf star of a smaller, hotter star and a secondary eclipse of comparable depth to the primary eclipse. We have used new spectroscopic observations for six of these systems to confirm that the companions to the A-type stars in these binaries have very low masses (≈0.2M⊙). This includes the companion to EL CVn which was not previously known to be a pre-He-WD. EL CVn-type binary star systems will enable us to study the formation of very low mass white dwarfs in great detail, particularly in those cases where the pre-He-WD star shows non-radial pulsations similar to those recently discovered in WASP0247-25 B. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

Quantum state storage and processing for polarization qubits in an inhomogeneously broadened Λ-type three-level medium

We address the propagation of a single photon pulse with two polarization components, i.e., a polarization qubit, in an inhomogeneously broadened "phaseonium" \Lambda-type three-level medium. We combine some of the non-trivial propagation effects characteristic for this kind of coherently prepared systems and the controlled reversible inhomogeneous broadening technique to propose several quantum information processing applications, such as a protocol for polarization qubit filtering and sieving as well as a tunable polarization beam splitter. Moreover, we show that, by imposing a spatial variation of the atomic coherence phase, an effcient quantum memory for the incident polarization qubit can be also implemented in \Lambda-type three-level systems.

Optical quantum memory for polarization qubits with V-type three-level atoms

We investigate an optical quantum memory scheme with V-type three-level atoms based on the controlled reversible inhomogeneous broadening (CRIB) technique. We theoretically show the possibility to store and retrieve a weak light pulse interacting with the two optical transitions of the system. This scheme implements a quantum memory for a polarization qubit - a single photon in an arbitrary polarization state - without the need of two spatially separated two-level media, thus offering the advantage of experimental compactness overcoming the limitations due to mismatching and unequal efficiencies that can arise in spatially separated memories. The effects of a relative phase change between the atomic levels, as well as of phase noise due to, for example, the presence of spurious electric and magnetic fields are analyzed.

Shame, intimacy and self-definition: An assessment of the emotional foundation and intimate relationship consequences of an introjective personality orientation.

The current study sought to elaborate and test a theoretical proposition that introjective personality functioning, which has been implicated in various psychological difficulties (e.g., self-critical depression, obsessive-compulsive disorder), has an emotional foundation in the self-conscious emotion of shame and is supported by dissociation. Moreover, introjective functioning was predicted to be associated with reduced interpersonal intimacy. To test the model, a Web-based survey design using path analysis was used. Three hundred and fifteen university students were assessed with measures of self-conscious emotions (i.e., shame, guilt, and embarrassment), introjective (self-definition) and anaclitic (relational) personality style, pathological dissociation, and interpersonal intimacy. Introjective personality was found to be associated with increased shame and reduced interpersonal intimacy. However, the path between pathological dissociation and introjective functioning was not significant. The results are discussed with reference to the moderating influence of introjective functioning between shame and reduced interpersonal intimacy.

Treatment of choroidal neovascularisation secondary to membranoproliferative glomerulonephritis type II with intravitreal ranibizumab

Membranoproliferative glomerulonephritis type II (MPGN II) is characterised by electron-dense deposits of complement components in the glomerular basement membrane and retinal pigment epithelium. Approximately, 10% of affected individuals develop serious ocular complications similar to age-related macular degeneration such as choroidal neovascularisation (CNV), which has been managed with photocoagulation or photodynamic therapy; however, these treatments can impact visual acuity. We report the case of a 42-year-old woman with MPGN II presenting with decreased visual acuity and paracentral scotoma in her left eye due to an extrafoveal choroidal neovascular membrane (growth of new vessels under the retina). The patient was successfully treated with intravitreal ranibizumab (Lucentis) with restoration of visual function. This case highlights the successful management of CNV secondary to MPGN II with the antivascular endothelial growth factor agent ranibizumab and emphasises the importance of early referral of patients with MPGN II who are reporting of visual 'distortion'.

Type Ia supernova bolometric light curves and ejected mass estimates from the nearby supernova factory

We present a sample of normal Type Ia supernovae (SNe Ia) from the Nearby Supernova Factory data set with spectrophotometry at sufficiently late phases to estimate the ejected mass using the bolometric light curve.Wemeasure Ni masses from the peak bolometric luminosity, then compare the luminosity in the Co-decay tail to the expected rate of radioactive energy release from ejecta of a given mass. We infer the ejected mass in a Bayesian context using a semi-analytic model of the ejecta, incorporating constraints from contemporary numerical models as priors on the density structure and distribution of Ni throughout the ejecta. We find a strong correlation between ejected mass and light-curve decline rate, and consequently Ni mass, with ejected masses in our data ranging from 0.9 to 1.4 M. Most fast-declining (SALT2 x <-1) normal SNe Ia have significantly sub-Chandrasekhar ejected masses in our fiducial analysis.

The effect of helium accretion efficiency on rates of Type Ia supernovae: Double detonations in accreting binaries

he double-detonation explosion scenario of Type Ia supernovae (SNe Ia) has gained increased support from the SN Ia community as a viable progenitor model, making it a promising candidate alongside the well-known single degenerate and double degenerate scenarios. We present delay times of double-detonation SNe, in which a sub-Chandrasekhar mass carbon–oxygen white dwarf (WD) accretes non-dynamically from a helium-rich companion. One of the main uncertainties in quantifying SN rates from double detonations is the (assumed) retention efficiency of He-rich matter. Therefore, we implement a new prescription for the treatment of accretion/accumulation of He-rich matter on WDs. In addition, we test how the results change depending on which criteria are assumed to lead to a detonation in the helium shell. In comparing the results to our standard case (Ruiter et al.), we find that regardless of the adopted He accretion prescription, the SN rates are reduced by only ∼25 per cent if low-mass He shells (≲0.05 M⊙) are sufficient to trigger the detonations. If more massive (0.1 M⊙) shells are needed, the rates decrease by 85 per cent and the delay time distribution is significantly changed in the new accretion model – only SNe with prompt (<500 Myr) delay times are produced. Since theoretical arguments favour low-mass He shells for normal double-detonation SNe, we conclude that the rates from double detonations are likely to be high, and should not critically depend on the adopted prescription for accretion of He.

'Super-Chandrasekhar' Type Ia Supernovae at nebular epochs

We present a first systematic comparison of superluminous Type Ia supernovae (SNe Ia) at late epochs, including previously unpublished photometric and spectroscopic observations of SN 2007if, SN 2009dc and SNF20080723-012. Photometrically, the objects of our sample show a diverse late-time behaviour, some of them fading quite rapidly after a light-curve break at ∼ 150-200 d. The latter is likely the result of flux redistribution into the infrared, possibly caused by dust formation, rather than a true bolometric effect. Nebular spectra of superluminous SNe Ia are characterized by weak or absent [Fe III] emission, pointing at a low ejecta ionization state as a result of high densities. To constrain the ejecta and Ni masses of superluminous SNe Ia, we compare the observed bolometric light curve of SN 2009dc with synthetic model light curves, focusing on the radioactive tail after ∼60 d. Models with enough Ni to explain the light-curve peak by radioactive decay, and at the same time sufficient mass to keep the ejecta velocities low, fail to reproduce the observed light-curve tail of SN 2009dc because of too much γ -ray trapping.We instead propose a model with ∼1M of Ni and ∼2 M of ejecta, which may be interpreted as the explosion of a Chandrasekhar-mass white dwarf (WD) enshrouded by 0.6-0.7 M of C/O-rich material, as it could result from a merger of two massive C/O WDs. This model reproduces the late light curve of SN 2009dc well. A flux deficit at peak may be compensated by light from the interaction of the ejecta with the surrounding material.