International Federation of Clinical Neurophysiology (IFCN) – EEG research workgroup: Recommendations on frequency and topographic analysis of resting state EEG rhythms. Part 1: Applications in clinical research studies

In 1999, the International Federation of Clinical Neurophysiology (IFCN) published “IFCN Guidelines for topographic and frequency analysis of EEGs and EPs” (Nuwer et al., 1999). Here a Workgroup of IFCN experts presents unanimous recommendations on the following procedures relevant for the topographic and frequency analysis of resting state EEGs (rsEEGs) in clinical research defined as neurophysiological experimental studies carried out in neurological and psychiatric patients: (1) recording of rsEEGs (environmental conditions and instructions to participants; montage of the EEG electrodes; recording settings); (2) digital storage of rsEEG and control data; (3) computerized visualization of rsEEGs and control data (identification of artifacts and neuropathological rsEEG waveforms); (4) extraction of “synchronization” features based on frequency analysis (band-pass filtering and computation of rsEEG amplitude/power density spectrum); (5) extraction of “connectivity” features based on frequency analysis (linear and nonlinear measures); (6) extraction of “topographic” features (topographic mapping; cortical source mapping; estimation of scalp current density and dura surface potential; cortical connectivity mapping), and (7) statistical analysis and neurophysiological interpretation of those rsEEG features. As core outcomes, the IFCN Workgroup endorsed the use of the most promising “synchronization” and “connectivity” features for clinical research, carefully considering the limitations discussed in this paper. The Workgroup also encourages more experimental (i.e. simulation studies) and clinical research within international initiatives (i.e., shared software platforms and databases) facing the open controversies about electrode montages and linear vs. nonlinear and electrode vs. source levels of those analyses

Malaria and other febrile diseases among travellers: the experience of a reference centre located outside the Brazilian Amazon Region

Abstract\ud \ud Background\ud Malaria is endemic in countries located in tropical and sub-tropical regions. The increasing flow of domestic and international travellers has made malaria a relevant health problem even in non-endemic regions. Malaria has been described as the main diagnosis among travellers presenting febrile diseases after returning from tropical countries. In Brazil, malaria transmission occurs mainly in the Amazon region. Outside this area, malaria transmission is of low magnitude.\ud \ud \ud Methods\ud This cross-sectional study aimed to describe the experience in the diagnosis of malaria in a reference centre located outside the Brazilian Amazon Region, emphasizing the differences in clinical and laboratory markers between cases of malaria and those of other febrile diseases (OFD). Medical charts from adult patients (≥18 years) who underwent a thick smear test (TST) for malaria, between January 2001 and December 2014, were retrospectively reviewed.\ud \ud \ud Results\ud A total of 458 cases referred to perform the TST were included. Malaria was diagnosed in 193 (42 %) episodes. The remaining 265 episodes (58 %) were grouped as OFD. The majority of malaria episodes were acquired in the Brazilian Amazon Region. The median time between the onset of symptoms and the TST was 7 days. Only 53 (11.5 %) episodes were tested within the first 48 h after symptom onset. Comparing malaria with OFD, jaundice, nausea, vomiting, and reports of fever were more prevalent in the malaria group. Low platelet count and elevated bilirubin levels were also related to the diagnosis of malaria.\ud \ud \ud Conclusions\ud The results indicate that outside the endemic area travellers presenting febrile disease suspected of being malaria underwent diagnostic test after considerable delay. The reporting of fever combined with a recent visit to an endemic area should promptly evoke the hypothesis of malaria. In these cases, specific diagnostic tests for malaria should be a priority. For cases that jump this step, the presence of elevated bilirubin or thrombocytopaenia should also indicate a diagnosis of malaria.This work was supported by the Grant # 2014/05337-6, São Paulo Research Foundation (FAPESP)

SPIDER VII - Revealing the Stellar Population Content of Massive Early-type Galaxies out to 8Re

Radial trends of stellar populations in galaxies provide a valuable tool to understand the mechanisms of galaxy growth. In this paper, we present the first comprehensive analysis of optical-optical and optical-NIR colours, as a function of galaxy mass, out to the halo region (8Re) of early-type galaxies (ETGs). We select a sample of 674 massive ETGs (M*>3x10^10MSun) from the SDSS-based SPIDER survey. By comparing with a large range of population synthesis models, we derive robust constraints on the radial trends in age and metallicity. Metallicity is unambiguously found to decrease outwards, with a measurable steepening of the slope in the outer regions (Re<R<8Re). The gradients in stellar age are found to be more sensitive to the models used, but in general, the outer regions of ETGs feature older populations compared to the cores. This trend is strongest for the most massive galaxies in our sample (M*>10^11MSun). Furthermore, when segregating with respect to large scale environment, the age gradient is more significant in ETGs residing in higher density regions. These results shed light on the processes leading from the formation of the central core to the growth of the stellar envelope of massive galaxies. The fact that the populations in the outer regions are older and more metal-poor than in the core suggests a process whereby the envelope of massive galaxies is made up of accreted small satellites (i.e. minor mergers) whose stars were born during the first stages of galaxy formation.Comment: 20 pages, 13 figures, 10 tables. Accepted for publication in MNRA

Identification of new susceptibility loci for osteoarthritis (arcOGEN):a genome-wide association study

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Osteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insufficient sample sizes and phenotype heterogeneity. We undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11,009 unrelated controls from the UK. We replicated the most promising signals in an independent set of up to 7473 cases and 42,938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent. We identified five genome-wide significant loci (binomial test p≤5·0×10(-8)) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1·12 [95% CI 1·08-1·16]; p=7·24×10(-11)), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a missense polymorphism within the nucleostemin-encoding gene GNL3. Levels of nucleostemin were raised in chondrocytes from patients with osteoarthritis in functional studies. Other significant loci were on chromosome 9 close to ASTN2, chromosome 6 between FILIP1 and SENP6, chromosome 12 close to KLHDC5 and PTHLH, and in another region of chromosome 12 close to CHST11. One of the signals close to genome-wide significance was within the FTO gene, which is involved in regulation of bodyweight-a strong risk factor for osteoarthritis. All risk variants were common in frequency and exerted small effects. Our findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention.Arthritis Research UK 1803

Steroid receptor coactivator-1 modulates the function of Pomc neurons and energy homeostasis

Hypothalamic neurons expressing the anorectic peptide Pro-opiomelanocortin (Pomc) regulate food intake and body weight. Here, we show that Steroid Receptor Coactivator-1 (SRC-1) interacts with a target of leptin receptor activation, phosphorylated STAT3, to potentiate Pomc transcription. Deletion of SRC-1 in Pomc neurons in mice attenuates their depolarization by leptin, decreases Pomc expression and increases food intake leading to high-fat diet-induced obesity. In humans, fifteen rare heterozygous variants in SRC-1 found in severely obese individuals impair leptin-mediated Pomc reporter activity in cells, whilst four variants found in non-obese controls do not. In a knock-in mouse model of a loss of function human variant (SRC-1L1376P), leptin-induced depolarization of Pomc neurons and Pomc expression are significantly reduced, and food intake and body weight are increased. In summary, we demonstrate that SRC-1 modulates the function of hypothalamic Pomc neurons, and suggest that targeting SRC-1 may represent a useful therapeutic strategy for weight loss.Peer reviewe

Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants

Measurement of the bb̄ dijet cross section in pp collisions at √s = 7 TeV with the ATLAS detector

The dijet production cross section for jets containing a b-hadron (b-jets) has been measured in proton–proton collisions with a centre-of-mass energy of √s = 7 TeV, using the ATLAS detector at the LHC. The data used correspond to an integrated luminosity of 4.2fb −¹. The cross section is measured for events with two identified b-jets with a transverse momentum pT>20 GeV and a minimum separation in the η–ϕ plane of ΔR=0.4. At least one of the jets in the event is required to have pT>270 GeV. The cross section is measured differentially as a function of dijet invariant mass, dijet transverse momentum, boost of the dijet system, and the rapidity difference, azimuthal angle and angular distance between the b-jets. The results are compared to different predictions of leading order and next-to-leading order perturbative quantum chromodynamics matrix elements supplemented with models for parton-showers and hadronization

Study of the rare decays of B 0 s Bs0 and B 0 B0 into muon pairs from data collected during the LHC Run 1 with the ATLAS detector

A study of the decays B 0 s →μ + μ − Bs0→μ+μ− and B 0 →μ + μ − B0→μ+μ− has been performed using data corresponding to an integrated luminosity of 25 fb −1 −1 of 7 and 8 TeV proton–proton collisions collected with the ATLAS detector during the LHC Run 1. For the B 0 B0 dimuon decay, an upper limit on the branching fraction is set at B(B 0 →μ + μ − )<4.2×10 −10 B(B0→μ+μ−)<4.2×10−10 at 95 % confidence level. For B 0 s Bs0, the branching fraction B(B 0 s →μ + μ − )=(0.9 +1.1 −0.8 )×10 −9 B(Bs0→μ+μ−)=(0.9−0.8+1.1)×10−9 is measured. The results are consistent with the Standard Model expectation with a p value of 4.8 %, corresponding to 2.0 standard deviations

Search for lepton-flavour-violating decays of the Higgs and Z bosons with the ATLAS detector

Direct searches for lepton flavour violation in decays of the Higgs and Z bosons with the ATLAS detector at the LHC are presented. The following three decays are considered: H→eτ, H→μτ, and Z→μτ. The searches are based on the data sample of proton–proton collisions collected by the ATLAS detector corresponding to an integrated luminosity of 20.3 fb−1 at a centre-of-mass energy of s√=8 TeV. No significant excess is observed, and upper limits on the lepton-flavour-violating branching ratios are set at the 95 % confidence level: Br (H→eτ)<1.04%, Br (H→μτ)<1.43%, and Br (Z→μτ)<1.69×10−5

Test of CP Invariance in vector-boson fusion production of the Higgs boson using the Optimal Observable method in the ditau decay channel with the ATLAS detector

A test of CP invariance in Higgs boson production via vector-boson fusion using the method of the Optimal Observable is presented. The analysis exploits the decay mode of the Higgs boson into a pair of τ leptons and is based on 20.3 fb −1 of proton-proton collision data at s √ = 8 TeV collected by the ATLAS experiment at the LHC. Contributions from CP-violating interactions between the Higgs boson and electroweak gauge bosons are described in an effective field theory framework, in which the strength of CP violation is governed by a single parameter d ~ . The mean values and distributions of CP-odd observables agree with the expectation in the Standard Model and show no sign of CP violation. The CP-mixing parameter d ~ is constrained to the interval [-0.11,0.05] at 68% confidence level, consistent with the Standard Model expectation of d ~ =0