DNA methylation profiles at birth and child ADHD symptoms

Attention deficit/hyperactivity disorder (ADHD) is a common and highly heritable psychiatric disorder. In addition, early life environmental factors contribute to the occurrence of ADHD. Recently, DNA methylation has emerged as a mechanism potentially mediating genetic and environmental effects.Here, we investigated whether newborn DNA methylation patterns of selected candidate genes involved in psychiatric disorders or fetal growth are associated with ADHD symptoms in childhood. Participants were 426 children from a large population based cohort of Dutch national origin. Behavio

Quantum dynamics and thermalization for out-of-equilibrium phi^4-theory

The quantum time evolution of \phi^4-field theory for a spatially homogeneous system in 2+1 space-time dimensions is investigated numerically for out-of-equilibrium initial conditions on the basis of the Kadanoff-Baym equations including the tadpole and sunset self-energies. Whereas the tadpole self-energy yields a dynamical mass, the sunset self-energy is responsible for dissipation and an equilibration of the system. In particular we address the dynamics of the spectral (`off-shell') distributions of the excited quantum modes and the different phases in the approach to equilibrium described by Kubo-Martin-Schwinger relations for thermal equilibrium states. The investigation explicitly demonstrates that the only translation invariant solutions representing the stationary fixed points of the coupled equation of motions are those of full thermal equilibrium. They agree with those extracted from the time integration of the Kadanoff-Baym equations in the long time limit. Furthermore, a detailed comparison of the full quantum dynamics to more approximate and simple schemes like that of a standard kinetic (on-shell) Boltzmann equation is performed. Our analysis shows that the consistent inclusion of the dynamical spectral function has a significant impact on relaxation phenomena. The different time scales, that are involved in the dynamical quantum evolution towards a complete thermalized state, are discussed in detail. We find that far off-shell 1 3 processes are responsible for chemical equilibration, which is missed in the Boltzmann limit. Finally, we address briefly the case of (bare) massless fields. For sufficiently large couplings $\lambda$ we observe the onset of Bose condensation, where our scheme within symmetric \phi^4-theory breaks down.Comment: 77 pages, 26 figure

Exome-wide meta-analysis identifies rare 3'-UTR variant in ERCC1/CD3EAP associated with symptoms of sleep apnea

Obstructive sleep apnea (OSA) is a common sleep breathing disorder associated with an increased risk of cardiovascular and cerebrovascular diseases and mortality. Although OSA is fairly heritable (~40%), there have been only few studies looking into the genetics of OSA. In the present study, we aimed to identify genetic variants associated with symptoms of sleep apnea by performing a whole-exome sequence meta-analysis of symptoms of sleep apnea in 1,475 individuals of European descent. We identified 17 rare genetic variants with at least suggestive evidence of significance. Replication in an independent dataset confirmed the association of a rare genetic variant (rs2229918; minor allele frequency = 0.3%) with symptoms of sleep apnea (p-valuemeta = 6.98 × 10-9, ßmeta = 0.99). Rs2229918 overlaps with the 3' untranslated regions of ERCC1 and CD3EAP genes on chromosome 19q13. Both genes are expressed in tissues in the neck area, such as the tongue, muscles, cartilage and the trachea. Further, CD3EAP is localized in the nucleus and mitochondria and involved in the tumor necrosis factor-alpha/nuclear factor kappa B signaling pathway. Our results and biological functions of CD3EAP/ERCC1 genes suggest that the 19q13 locus is interesting for further OSA research

Astroparticle Physics with a Customized Low-Background Broad Energy Germanium Detector

The MAJORANA Collaboration is building the MAJORANA DEMONSTRATOR, a 60 kg array of high purity germanium detectors housed in an ultra-low background shield at the Sanford Underground Laboratory in Lead, SD. The MAJORANA DEMONSTRATOR will search for neutrinoless double-beta decay of 76Ge while demonstrating the feasibility of a tonne-scale experiment. It may also carry out a dark matter search in the 1-10 GeV/c^2 mass range. We have found that customized Broad Energy Germanium (BEGe) detectors produced by Canberra have several desirable features for a neutrinoless double-beta decay experiment, including low electronic noise, excellent pulse shape analysis capabilities, and simple fabrication. We have deployed a customized BEGe, the MAJORANA Low-Background BEGe at Kimballton (MALBEK), in a low-background cryostat and shield at the Kimballton Underground Research Facility in Virginia. This paper will focus on the detector characteristics and measurements that can be performed with such a radiation detector in a low-background environment.Comment: Submitted to NIMA Proceedings, SORMA XII. 9 pages, 4 figure

Dark Energy Survey Year 1 Results: A Precise H0 Measurement from DES Y1, BAO, and D/H Data

We combine Dark Energy Survey Year 1 clustering and weak lensing data with baryon acoustic oscillations and Big Bang nucleosynthesis experiments to constrain the Hubble constant. Assuming a flat ΛCDM model with minimal neutrino mass (Σm υ = 0.06 eV), we find H 0 = 67.4 -1.2+1.1 km s -1 Mpc -1 (68 per cent CL). This result is completely independent of Hubble constant measurements based on the distance ladder, cosmic microwave background anisotropies (both temperature and polarization), and strong lensing constraints. There are now five data sets that: (a) have no shared observational systematics; and (b) each constrains the Hubble constant with fractional uncertainty at the few percent level. We compare these five independent estimates, and find that, as a set, the differences between them are significant at the 2.5σ level (χ 2 /dof = 24/11, probability to exceed = 1.1 per cent). Having set the threshold for consistency at 3σ, we combine all five data sets to arrive at H 0 = 69.3 -0.6+0.4 km s -1 Mpc -

Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns

Folate is vital for fetal development. Periconceptional folic acid supplementation and food fortification are recommended to prevent neural tube defects. Mechanisms whereby periconceptional folate influences normal development and disease are poorly understood: epigenetics may be involved. We examine the association between maternal plasma folate during pregnancy and epigenome-wide DNA methylation using Illumina" s HumanMethyl450 Beadchip in 1,988 newborns from two European cohorts. Here we report the combined covariate-adjusted results using meta-analysis and employ pathway and gene expression analyses. Four-hundred forty-three CpGs (320 genes) are significantly associated with maternal plasma folate levels during pregnancy (false discovery rate 5%); 48 are significant after Bonferroni correction. Most genes are not known for folate biology, including APC2, GRM8, SLC16A12, OPCML, PRPH, LHX1, KLK4 and PRSS21. Some relate to birth defects other than neural tube defects, neurological functions or varied aspects of embryonic development. These findings may inform how maternal folate impacts the developing epigenome and health outcomes in offspring

Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Association of heat shock proteins with all-cause mortality

Experimental mild heat shock is widely known as an intervention that results in extended longevity in various models along the evolutionary lineage. Heat shock proteins (HSPs) are highly upregulated immediately after a heat shock. The elevation in HSP levels was shown to inhibit stress-mediated cell death, and recent experiments indicate a highly versatile role for these proteins as inhibitors of programmed cell death. In this study, we examined common genetic variations in 31 genes encoding all members of the HSP70, small HSP, and heat shock factor (HSF) families for their association with all-cause mortality. Our discovery cohort was the Rotterdam study (RS1) containing 5,974 participants aged 55 years and older (3,174 deaths). We assessed 4,430 single nucleotide polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina. After adjusting for multiple testing by permutation analysis, three SNPs showed evidence for association with all-cause mortality in RS1. These findings were followed in eight independent population-based cohorts, leading to a total of 25,007 participants (8,444 deaths). In the replication phase, only HSF2 (rs1416733) remained significantly associated with all-causemortality. Rs1416733 is a known ciseQTL for HSF2. Our findings suggest a role of HSF2 in all-cause mortality

An Eccentric Massive Jupiter Orbiting a Subgiant on a 9.5-day Period Discovered in the Transiting Exoplanet Survey Satellite Full Frame Images

We report the discovery of TOI-172 b from the Transiting Exoplanet Survey Satellite (TESS) mission, a massive hot Jupiter transiting a slightly evolved G star with a 9.48-day orbital period. This is the first planet to be confirmed from analysis of only the TESS full frame images, because the host star was not chosen as a two-minute cadence target. From a global analysis of the TESS photometry and follow-up observations carried out by the TESS Follow-up Observing Program Working Group, TOI-172 (TIC 29857954) is a slightly evolved star with an effective temperature of T eff = 5645 ± 50 K, a mass of M ∗ = 1.128-0.061 +0.065 M o, radius of R ∗ = 1.777-0.044 +0.047 R o, a surface gravity of log g ∗ = 3.993-0.028 +0.027, and an age of 7.4-1.5 +1.6. Its planetary companion (TOI-172 b) has a radius of R P = 0.965-0.029 +0.032 R J, a mass of M P = 5.42-0.20 +0.22 M J, and is on an eccentric orbit (e = 0.3806-0.0090 +0.0093 ). TOI-172 b is one of the few known massive giant planets on a highly eccentric short-period orbit. Future study of the atmosphere of this planet and its system architecture offer opportunities to understand the formation and evolution of similar systems