SPHERES, J\"ulich's High-Flux Neutron Backscattering Spectrometer at FRM II

SPHERES (SPectrometer with High Energy RESolution) is a third-generation neutron backscattering spectrometer, located at the 20 MW German neutron source FRM II and operated by the Juelich Centre for Neutron Science. It offers an energy resolution (fwhm) better than 0.65 micro-eV, a dynamic range of +-31 micro-eV, and a signal-to-noise ratio of up to 1750:1.Comment: 12 pages, 7 figures, 2 tables. Supplemental material consists of 3 pages, 2 figures, 2 table

NM-300 Silver Characterisation, Stability, Homogeneity

This report describes the characteriation of NM-300, a nano-silver reference material used in the context of risk and exposure assessment studies. The material was produced in the context of the JRC IHCP activity on nano-materials. A representative set test items was handed over to the JRC IES analytical laboratory for further characterisation. First, inorganic chemical characterisation of the total silver content and the homogeneity of the Ag-distribution was done using ICP-AES. To this end, a dedicated method was developed and validated according to the requirements laid down in ISO 17025. This works were completed by different types of microscopy analyses (Scanning Electron Microscope, Transmission Electron Microscope and Nanoparticle Tracking Analysis) performed in close collaboration with the German Institute of Energy and Environmental Technology e.V. (IUTA), the Swiss Federal Laboratories for Materials Science and Technology (EMPA) and Belgium Veterinary and Agrochemical Research Centre (VAR). This report summarises all technical details and discusses the assessments made.JRC.DG.I.5-Nanobioscience

Apolipoprotein E-dependent load of white matter hyperintensities in Alzheimer’s disease: a voxel-based lesion mapping study

Introduction: White matter (WM) magnetic resonance imaging (MRI) hyperintensities are common in Alzheimer’s disease (AD), but their pathophysiological relevance and relationship to genetic factors are unclear. In the present study, we investigated potential apolipoprotein E (APOE)-dependent effects on the extent and cognitive impact of WM hyperintensities in patients with AD. Methods: WM hyperintensity volume on fluid-attenuated inversion recovery images of 201 patients with AD (128 carriers and 73 non-carriers of the APOE ε4 risk allele) was determined globally as well as regionally with voxel-based lesion mapping. Clinical, neuropsychological and MRI data were collected from prospective multicenter trials conducted by the German Dementia Competence Network. Results: WM hyperintensity volume was significantly greater in non-carriers of the APOE ε4 allele. Lesion distribution was similar among ε4 carriers and non-carriers. Only ε4 non-carriers showed a correlation between lesion volume and cognitive performance. Conclusion: The current findings indicate an increased prevalence of WM hyperintensities in non-carriers compared with carriers of the APOE ε4 allele among patients with AD. This is consistent with a possibly more pronounced contribution of heterogeneous vascular risk factors to WM damage and cognitive impairment in patients with AD without APOE ε4-mediated risk

Impaired Ca2+-handling in HIF-1α+/− mice as a consequence of pressure overload

The hypoxia-inducible factor (HIF)-1 is critically involved in the cellular adaptation to a decrease in oxygen availability. The influence of HIF-1α for the development of cardiac hypertrophy and cardiac function that occurs in response to sustained pressure overload has been mainly attributed to a challenged cardiac angiogenesis and cardiac hypertrophy up to now. Hif-1α+/+ and Hif-1α+/− mice were studied regarding left ventricular hypertrophy and cardiac function after being subjected to transverse aortic constriction (TAC). After TAC, both Hif-1α+/+ and Hif-1α+/− mice developed left ventricular hypertrophy with increased posterior wall thickness, septum thickness and increased left ventricular weight to a similar extent. No significant difference in cardiac vessel density was observed between Hif-1α+/+ and Hif-1α+/− mice. However, only the Hif-1α+/− mice developed severe heart failure as revealed by a significantly reduced fractional shortening mostly due to increased end-systolic left ventricular diameter. On the single cell level this correlated with reduced myocyte shortenings, decreased intracellular Ca2+-transients and SR-Ca2+ content in myocytes of Hif-1a+/− mice. Thus, HIF-1α can be critically involved in the preservation of cardiac function after chronic pressure overload without affecting cardiac hypertrophy. This effect is mediated via HIF-dependent modulation of cardiac calcium handling and contractility

CRISTOPH – A cluster-randomised intervention study to optimise the treatment of patients with hypertension in General Practice

<p>Abstract</p> <p>Background</p> <p>Recent guidelines for the management of hypertension focus on treating patients according to their global cardiovascular risk (CVR), rather than strictly keeping blood pressure, or other risk factors, below set limit values. The objective of this study is to compare the effect of a simple versus a complex educational intervention implementing this new concept among General Practitioners (GPs).</p> <p>Methods/design</p> <p>A prospective longitudinal cluster-randomised intervention trial with 94 German GPs consecutively enroling 40 patients each with known hypertension. All GPs then received a written manual specifically developed to transfer the global concept of CVR into daily General Practice. After cluster-randomisation, half of the GPs additionally received a clinical outreach visit, with a trained peer discussing with them the concept of global CVR referring to example study patients from the respective GP. Main outcome measure is the improvement of calculated CVR six months after intervention in the subgroup of patients with high CVR (but no history of cardiovascular disease), defined as 10-year-mortality ≥ 5% employing the European SCORE formula. Secondary outcome measures include the intervention's effect on single risk factors, and on prescription rates of drugs targeting CVR. All outcome measures are separately studied in the three subgroups of patients with 1. high CVR (defined as above), 2. low CVR (SCORE < 5%), and 3. a history of cardiovascular disease. The influence of age, sex, social status, and the perceived quality of the respective doctor-patient-relation on the effects will be examined.</p> <p>Discussion</p> <p>To our knowledge, no other published intervention study has yet evaluated the impact of educating GPs with the goal to treat patients with hypertension according to their global cardiovascular risk.</p> <p>Trial registration</p> <p>ISRCTN44478543</p

Light, the universe and everything – 12 Herculean tasks for quantum cowboys and black diamond skiers

The Winter Colloquium on the Physics of Quantum Electronics (PQE) has been a seminal force in quantum optics and related areas since 1971. It is rather mind-boggling to recognize how the concepts presented at these conferences have transformed scientific understanding and human society. In January 2017, the participants of PQE were asked to consider the equally important prospects for the future, and to formulate a set of questions representing some of the greatest aspirations in this broad field. The result is this multi-authored paper, in which many of the world’s leading experts address the following fundamental questions: (1) What is the future of gravitational wave astronomy? (2) Are there new quantum phases of matter away from equilibrium that can be found and exploited – such as the time crystal? (3) Quantum theory in uncharted territory: What can we learn? (4) What are the ultimate limits for laser photon energies? (5) What are the ultimate limits to temporal, spatial and optical resolution? (6) What novel roles will atoms play in technology? (7) What applications lie ahead for nitrogen-vacancy centres in diamond? (8) What is the future of quantum coherence, squeezing and entanglement for enhanced super-resolution and sensing? (9) How can we solve (some of) humanity’s biggest problems through new quantum technologies? (10) What new understanding of materials and biological molecules will result from their dynamical characterization with free-electron lasers? (11) What new technologies and fundamental discoveries might quantum optics achieve by the end of this century? (12) What novel topological structures can be created and employed in quantum optics

Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage

Vos et al. compare the prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage based on the IWG-1, IWG-2 and NIA-AA criteria. All three aid identification of early Alzheimer's disease, but combining amyloid and neuronal injury markers according to the NIA-AA criteria offers the most accurate prognosi

Association of candidate pharmacogenetic markers with platinum-induced ototoxicity:PanCareLIFE dataset

Genetic association studies suggest a genetic predisposi- tion for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase ( TPMT ) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross- sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnos- tic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patients were assigned to three phenotype categories: no, minor, and clinically relevant hearing loss. Fourteen variants in eleven candidate genes ( ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1, and ACYP2 ) were genotyped. The genotype and phenotype data represent a resource for conducting meta- analyses to derive a more precise pooled estimate of the ef- fects of genes on the risk of hearing loss due to platinum treatment