State of palliative care development in European Countries with and without legally regulated physician-assisted dying.

A

Radio Afterglows of Gamma-Ray Bursts and Hypernovae at High Redshift, and their Potential for 21-cm Absorption Studies

We investigate the radio afterglows of gamma-ray bursts (GRBs) and hypernovae (HNe) at high redshifts and quantify their detectability, as well as their potential usefulness for 21 cm absorption line studies of the intergalactic medium (IGM) and intervening structures. We examine several sets of source and environment model parameters that are physically plausible at high redshifts. The radio afterglows of GRBs would be detectable out to z ~ 30, while the energetic HNe could be detectable out to z ~ 20 even by the current Very Large Array (VLA). We find that the 21 cm absorption line due to the diffuse neutral IGM is difficult to detect even by the proposed Square Kilometer Array (SKA), except for highly energetic sources. We also find that the 21 cm line due to collapsed gas clouds with high optical depth may be detected on rare occasions.Comment: 36 pages, 12 figures, 1 table, accepted for publication in Ap

Follow-up of CRT-D patients downgraded to CRT-P at the time of generator exchange

Background: Some patients with cardiac resynchronisation therapy (CRT) experience super-response (LVEF improvements to ≥50%). At generator exchange (GE), downgrading (DG) from CRT-defibrillator (CRT-D) to CRT-pacemaker (CRT-P) could be an option for these patients on primary prevention ICD indication and no required ICD therapies. Long-term data on arrhythmic events in super-responders is scarce. Methods: CRT-D patients with LVEF improvement to ≥50% at GE were identified in four large centres for retrospective analysis. Mortality, significant ventricular tachyarrhythmia and appropriate ICD-therapy were determined, and patient analysis was split into two groups (downgraded to CRT-P or not). Results: Sixty-six patients (53% male, 26% coronary artery disease) on primary prevention were followed for a median of 129 months [IQR: 101–155] after implantation. 27 (41%) patients were downgraded to CRT-P at GE after a median of 68 [IQR: 58–98] months (LVEF 54% ± 4%). The other 39 (59%) continued with CRT-D therapy (LVEF 52% ± 6%). No cardiac death or significant arrhythmia occurred in the CRT-P group (median follow-up (FU) 38 months [IQR: 29–53]). Three appropriate ICD-therapies occurred in the CRT-D group [median FU 70 months (IQR: 39–97)]. Annualized event-rates after DG/GE were 1.5%/year and 1.0%/year in the CRT-D group and the whole cohort, respectively. Conclusions: No significant tachyarrhythmia were detected in the patients downgraded to CRT-P during follow-up. However, three events were observed in the CRT-D group. Whilst downgrading CRT-D patients is an option, a small residual risk for arrhythmic events remains and decisions regarding downgrade should be made on a case-by-case basis.</p

The Cluster-EAGLE project: global properties of simulated clusters with resolved galaxies

We introduce the Cluster-EAGLE (C-EAGLE) simulation project, a set of cosmological hydrodynamical zoom simulations of the formation of 30 galaxy clusters in the mass range of 1014 < M200/M⊙ < 1015.4 that incorporates the Hydrangea sample of Bahé et al. (2017). The simulations adopt the state-of-the-art EAGLE galaxy formation model, with a gas particle mass of 1.8 × 106 M⊙ and physical softening length of 0.7 kpc. In this paper, we introduce the sample and present the low-redshift global properties of the clusters. We calculate the X-ray properties in a manner consistent with observational techniques, demonstrating the bias and scatter introduced by using estimated masses. We find the total stellar content and black hole masses of the clusters to be in good agreement with the observed relations. However, the clusters are too gas rich, suggesting that the active galactic nucleus (AGN) feedback model is not efficient enough at expelling gas from the high-redshift progenitors of the clusters. The X-ray properties, such as the spectroscopic temperature and the soft-band luminosity, and the Sunyaev–Zel'dovich properties are in reasonable agreement with the observed relations. However, the clusters have too high central temperatures and larger-than-observed entropy cores, which is likely driven by the AGN feedback after the cluster core has formed. The total metal content and its distribution throughout the intracluster medium are a good match to the observations

On the Use of Ly-alpha Emitters as Probes of Reionization

We use numerical simulations to study the effects of the patchiness of a partly reionized intergalactic medium (IGM) on the observability of Ly-alpha emitters (LAEs) at high redshifts (z ~ 6). We present a new model that divides the Ly-alpha radiative transfer into a (circum-)galactic and an extragalactic (IGM) part, and investigate how the choice of intrinsic line model affects the IGM transmission results. We use our model to study the impact of neutral hydrogen on statistical observables such as the Ly-alpha restframe equivalent width (REW) distribution, the LAE luminosity function and the two-point correlation function. We find that if the observed changes in LAE luminosity functions and equivalent width distributions between z ~ 6 and z ~ 7 are to be explained by an increased IGM neutral fraction alone, we require an extremely late and rapid reionization scenario, where the Universe was ~ 40 % ionized at z = 7, ~ 50 % ionized at z = 6.5 and ~ 100 % ionized at z = 6. This is in conflict with other observations, suggesting that intrinsic LAE evolution at z > 6 cannot be completely neglected. We show how the two-point correlation function can provide more robust constraints once future observations obtain larger LAE samples, and provide predictions for the sample sizes needed to tell different reionization scenarios apart.Comment: Accepted for publication in MNRA

Sunyaev-Zel'dovich clusters in millennium gas simulations

Large surveys using the Sunyaev–Zel’dovich (SZ) effect to find clusters of galaxies are now starting to yield large numbers of systems out to high redshift, many of which are new dis- coveries. In order to provide theoretical interpretation for the release of the full SZ cluster samples over the next few years, we have exploited the large-volume Millennium gas cosmo- logical N-body hydrodynamics simulations to study the SZ cluster population at low and high redshift, for three models with varying gas physics. We confirm previous results using smaller samplesthattheintrinsic(spherical)Y500–M500relationhasverylittlescatter(σlog10Y ≃0.04), is insensitive to cluster gas physics and evolves to redshift 1 in accordance with self-similar expectations. Our preheating and feedback models predict scaling relations that are in excel- lent agreement with the recent analysis from combined Planck and XMM–Newton data by the Planck Collaboration. This agreement is largely preserved when r500 and M500 are derived using thehydrostaticmassproxy,YX,500,albeitwithsignificantlyreducedscatter(σlog10Y ≃0.02),a result that is due to the tight correlation between Y500 and YX,500. Interestingly, this assumption also hides any bias in the relation due to dynamical activity. We also assess the importance of projection effects from large-scale structure along the line of sight, by extracting cluster Y500 values from 50 simulated 5 × 5-deg2 sky maps. Once the (model-dependent) mean signal is subtracted from the maps we find that the integrated SZ signal is unbiased with respect to the underlying clusters, although the scatter in the (cylindrical) Y500–M500 relation increases in the preheating case, where a significant amount of energy was injected into the intergalactic medium at high redshift. Finally, we study the hot gas pressure profiles to investigate the origin of the SZ signal and find that the largest contribution comes from radii close to r500 in all cases. The profiles themselves are well described by generalized Navarro, Frenk & White profiles but there is significant cluster-to-cluster scatter. In conclusion, our results support the notion that Y500 is a robust mass proxy for use in cosmological analyses with clusters

Linkage and association studies identify a novel locus for Alzheimer disease at 7q36 in a Dutch population-based sample

We obtained conclusive linkage of Alzheimer disease (AD) with a candidate region of 19.7 cM at 7q36 in an extended multiplex family, family 1270, ascertained in a population-based study of early-onset AD in the northern Netherlands. Single-nucleotide polymorphism and haplotype association analyses of a Dutch patient-control sample further supported the linkage at 7q36. In addition, we identified a shared haplotype at 7q36 between family 1270 and three of six multiplex AD-affected families from the same geographical region, which is indicative of a founder effect and defines a priority region of 9.3 cM. Mutation analysis of coding exons of 29 candidate genes identified one linked synonymous mutation, g.38030G-->C in exon 10, that affected codon 626 of the PAX transactivation domain interacting protein gene (PAXIP1). It remains to be determined whether PAXIP1 has a functional role in the expression of AD in family 1270 or whether another mutation at this locus explains the observed linkage and sharing. Together, our linkage data from the informative family 1270 and the association data in the population-based early-onset AD patient-control sample strongly support the identification of a novel AD locus at 7q36 and re-emphasize the genetic heterogeneity of AD

On the APM power spectrum and the CMB anisotropy: Evidence for a phase transition during inflation?

Adams et al. (1997b) have noted that according to our current understanding of the unification of fundamental interactions, there should have been phase transitions associated with spontaneous symmetry breaking {\em during} the inflationary era. This may have resulted in the breaking of scale-invariance of the primordial density perturbation for brief periods. A possible such feature was identified in the power spectrum of galaxy clustering in the APM survey at the scale $k \sim 0.1 h$ Mpc^{-1} and it was shown that the secondary acoustic peaks in the power spectrum of the CMB anisotropy should consequently be suppressed. We demonstrate that this prediction is confirmed by the recent Boomerang and Maxima observations, which favour a step-like spectral feature in the range $k \sim (0.06-0.6)h$ Mpc^{-1}, independently of the similar previous indication from the APM data. Such a spectral break enables an excellent fit to both APM and CMB data with a baryon density consistent with the BBN value. It also allows the possibility of a matter-dominated universe with zero cosmological constant, which we show can now account for even the evolution of the abundance of rich clusters.Comment: 11 pages (LaTeX, mn.sty) incl. 9 eps figs; small changes to match version accepted for publication in MNRA

The learning curve associated with the introduction of the subcutaneous implantable defibrillator

Aims: The subcutaneous implantable cardioverter defibrillator (S-ICD) was introduced to overcome complications related to transvenous leads. Adoption of the S-ICD requires implanters to learn a new implantation technique. The aim of this study was to assess the learning curve for S-ICD implanters with respect to implant-related complications, procedure time, and inappropriate shocks (IASs). Methods and results: In a pooled cohort from two clinical S-ICD databases, the IDE Trial and the EFFORTLESS Registry, complications, IASs at 180 days follow-up and implant procedure duration were assessed. Patients were grouped in quartiles based on experience of the implanter and Kaplan-Meier estimates of complication and IAS rates were calculated. A total of 882 patients implanted in 61 centres by 107 implanters with a median of 4 implants (IQR 1,8) were analysed. There were a total of 59 patients with complications and 48 patients with IAS. The complication rate decreased significantly from 9.8% in Quartile 1 (least experience) to 5.4% in Quartile 4 (most experience) (P = 0.02) and non-significantly for IAS from 7.9 to 4.8% (P = 0.10). Multivariable analysis demonstrated a hazard ratio of 0.78 (P = 0.045) for complications and 1.01 (P = 0.958) for IAS. Dual-zone programming increased with experience of the individual implanter (P 13 implants). Conclusion: There is a short and significant learning curve associated with physicians adopting the S-ICD. Performance stab

Dutch Outcome in Implantable Cardioverter-Defibrillator Therapy:Implantable Cardioverter-Defibrillator-Related Complications in a Contemporary Primary Prevention Cohort

Background One third of primary prevention implantable cardioverter-defibrillator patients receive appropriate therapy, but all remain at risk of defibrillator complications. Information on these complications in contemporary cohorts is limited. This study assessed complications and their risk factors after defibrillator implantation in a Dutch nationwide prospective registry cohort and forecasts the potential reduction in complications under distinct scenarios of updated indication criteria. Methods and Results Complications in a prospective multicenter registry cohort of 1442 primary implantable cardioverter-defibrillator implant patients were classified as major or minor. The potential for reducing complications was derived from a newly developed prediction model of appropriate therapy to identify patients with a low probability of benefitting from the implantable cardioverter-defibrillator. During a follow-up of 2.2 years (interquartile range, 2.0-2.6 years), 228 complications occurred in 195 patients (13.6%), with 113 patients (7.8%) experiencing at least one major complication. Most common ones were lead related (n=93) and infection (n=18). Minor complications occurred in 6.8% of patients, with lead-related (n=47) and pocket-related (n=40) complications as the most prevailing ones. A surgical reintervention or additional hospitalization was required in 53% or 61% of complications, respectively. Complications were strongly associated with device type. Application of stricter implant indication results in a comparable proportional reduction of (major) complications. Conclusions One in 13 patients experiences at least one major implantable cardioverter-defibrillator-related complication, and many patients undergo a surgical reintervention. Complications are related to defibrillator implantations, and these should be discussed with the patient. Stricter implant indication criteria and careful selection of device type implanted may have significant clinical and financial benefits