Comparative Developmental Neurotoxicity of Organophosphate Insecticides: Effects on Brain Development Are Separable from Systemic Toxicity

A comparative approach to the differences between systemic toxicity and developmental neurotoxicity of organophosphates is critical to determine the degree to which multiple mechanisms of toxicity carry across different members of this class of insecticides. We contrasted neuritic outgrowth and cholinergic synaptic development in neonatal rats given different organophosphates (chlorpyrifos, diazinon, parathion) at doses spanning the threshold for impaired growth and viability. Animals were treated daily on postnatal days 1–4 by subcutaneous injection so as to bypass differences in first-pass activation to the oxon or catabolism to inactive products. Evaluations occurred on day 5. Parathion (maximum tolerated dose, 0.1 mg/kg) was far more systemically toxic than was chlorpyrifos or diazinon (maximum tolerated dose, 1–5 mg/kg). Below the maximum tolerated dose, diazinon impaired neuritic outgrowth in the forebrain and brainstem, evidenced by a deficit in the ratio of membrane protein to total protein. Diazinon also decreased choline acetyltransferase activity, a cholinergic neuronal marker, whereas it did not affect hemicholinium-3 binding to the presynaptic choline transporter, an index of cholinergic neuronal activity. There was no m(2)-muscarinic acetylcholine receptor down-regulation, as would have occurred with chronic cholinergic hyper-stimulation. The same pattern was found previously for chlorpyrifos. In contrast, parathion did not elicit any of these changes at its maximum tolerated dose. These results indicate a complete dichotomy between the systemic toxicity of organophosphates and their propensity to elicit developmental neurotoxicity. For parathion, the threshold for lethality lies below that necessary for adverse effects on brain development, whereas the opposite is true for chlorpyrifos and diazinon

Genetics of height and risk of atrial fibrillation: A Mendelian randomization study.

BACKGROUND: Observational studies have identified height as a strong risk factor for atrial fibrillation, but this finding may be limited by residual confounding. We aimed to examine genetic variation in height within the Mendelian randomization (MR) framework to determine whether height has a causal effect on risk of atrial fibrillation. METHODS AND FINDINGS: In summary-level analyses, MR was performed using summary statistics from genome-wide association studies of height (GIANT/UK Biobank; 693,529 individuals) and atrial fibrillation (AFGen; 65,446 cases and 522,744 controls), finding that each 1-SD increase in genetically predicted height increased the odds of atrial fibrillation (odds ratio [OR] 1.34; 95% CI 1.29 to 1.40; p = 5 × 10-42). This result remained consistent in sensitivity analyses with MR methods that make different assumptions about the presence of pleiotropy, and when accounting for the effects of traditional cardiovascular risk factors on atrial fibrillation. Individual-level phenome-wide association studies of height and a height genetic risk score were performed among 6,567 European-ancestry participants of the Penn Medicine Biobank (median age at enrollment 63 years, interquartile range 55-72; 38% female; recruitment 2008-2015), confirming prior observational associations between height and atrial fibrillation. Individual-level MR confirmed that each 1-SD increase in height increased the odds of atrial fibrillation, including adjustment for clinical and echocardiographic confounders (OR 1.89; 95% CI 1.50 to 2.40; p = 0.007). The main limitations of this study include potential bias from pleiotropic effects of genetic variants, and lack of generalizability of individual-level findings to non-European populations. CONCLUSIONS: In this study, we observed evidence that height is likely a positive causal risk factor for atrial fibrillation. Further study is needed to determine whether risk prediction tools including height or anthropometric risk factors can be used to improve screening and primary prevention of atrial fibrillation, and whether biological pathways involved in height may offer new targets for treatment of atrial fibrillation

Central Exclusive Production in QCD

We investigate the theoretical description of the central exclusive production process, h1+h2 -> h1+X+h2. Taking Higgs production as an example, we sum logarithmically enhanced corrections appearing in the perturbation series to all orders in the strong coupling. Our results agree with those originally presented by Khoze, Martin and Ryskin except that the scale appearing in the Sudakov factor, mu=0.62 \sqrt{\hat{s}}, should be replaced with mu=\sqrt{\hat{s}}, where \sqrt{\hat{s}} is the invariant mass of the centrally produced system. We confirm this result using a fixed-order calculation and show that the replacement leads to approximately a factor 2 suppression in the cross-section for central system masses in the range 100-500 GeV.Comment: 41 pages, 19 figures; minor typos fixed; version published in JHE

Radiocarbon dating of methane and carbon dioxide evaded from a temperate peatland stream

Streams draining peatlands export large quantities of carbon in different chemical forms and are an important part of the carbon cycle. Radiocarbon (14C) analysis/dating provides unique information on the source and rate that carbon is cycled through ecosystems, as has recently been demonstrated at the air-water interface through analysis of carbon dioxide (CO2) lost from peatland streams by evasion (degassing). Peatland streams also have the potential to release large amounts of methane (CH4) and, though 14C analysis of CH4 emitted by ebullition (bubbling) has been previously reported, diffusive emissions have not. We describe methods that enable the 14C analysis of CH4 evaded from peatland streams. Using these methods, we investigated the 14C age and stable carbon isotope composition of both CH4 and CO2 evaded from a small peatland stream draining a temperate raised mire. Methane was aged between 1617-1987 years BP, and was much older than CO2 which had an age range of 303-521 years BP. Isotope mass balance modelling of the results indicated that the CO2 and CH4 evaded from the stream were derived from different source areas, with most evaded CO2 originating from younger layers located nearer the peat surface compared to CH4. The study demonstrates the insight that can be gained into peatland carbon cycling from a methodological development which enables dual isotope (14C and 13C) analysis of both CH4 and CO2 collected at the same time and in the same way

Structures and waves in a nonlinear heat-conducting medium

The paper is an overview of the main contributions of a Bulgarian team of researchers to the problem of finding the possible structures and waves in the open nonlinear heat conducting medium, described by a reaction-diffusion equation. Being posed and actively worked out by the Russian school of A. A. Samarskii and S.P. Kurdyumov since the seventies of the last century, this problem still contains open and challenging questions.Comment: 23 pages, 13 figures, the final publication will appear in Springer Proceedings in Mathematics and Statistics, Numerical Methods for PDEs: Theory, Algorithms and their Application

Genetically Predicted Blood Pressure and Risk of Atrial Fibrillation.

Observational studies have shown an association between hypertension and atrial fibrillation (AF). Aggressive blood pressure management in patients with known AF reduces overall arrhythmia burden, but it remains unclear whether hypertension is causative for AF. To address this question, this study explored the relationship between genetic predictors of blood pressure and risk of AF. We secondarily explored the relationship between genetically proxied use of antihypertensive drugs and risk of AF. Two-sample Mendelian randomization was performed using an inverse-variance weighted meta-analysis with weighted median Mendelian randomization and Egger intercept tests performed as sensitivity analyses. Summary statistics for systolic blood pressure, diastolic blood pressure, and pulse pressure were obtained from the International Consortium of Blood Pressure and the UK Biobank discovery analysis and AF from the 2018 Atrial Fibrillation Genetics Consortium multiethnic genome-wide association studies. Increases in genetically proxied systolic blood pressure, diastolic blood pressure, or pulse pressure by 10 mm Hg were associated with increased odds of AF (systolic blood pressure: odds ratio [OR], 1.17 [95% CI, 1.11-1.22]; P=1×10-11; diastolic blood pressure: OR, 1.25 [95% CI, 1.16-1.35]; P=3×10-8; pulse pressure: OR, 1.1 [95% CI, 1.0-1.2]; P=0.05). Decreases in systolic blood pressure by 10 mm Hg estimated by genetic proxies of antihypertensive medications showed calcium channel blockers (OR, 0.66 [95% CI, 0.57-0.76]; P=8×10-9) and β-blockers (OR, 0.61 [95% CI, 0.46-0.81]; P=6×10-4) decreased the risk of AF. Blood pressure-increasing genetic variants were associated with increased risk of AF, consistent with a causal relationship between blood pressure and AF. These data support the concept that blood pressure reduction with calcium channel blockade or β-blockade could reduce the risk of AF

Heavy Flavour Production at Tevatron and Parton Shower Effects

We present hadron-level predictions from the Monte Carlo generator Cascade and numerical calculations of charm and beauty production at the Fermilab Tevatron within the framework of the $k_T$-factorization QCD approach. Our consideration is based on the CCFM-evolved unintegrated gluon densities in a proton. The performed analysis covers the total and differential cross sections of open charm and beauty quarks, $B$ and $D$ mesons (or rather muons from their semileptonic decays) and the total and differential cross sections of $b \bar b$ di-jet hadroproduction. We study the theoretical uncertainties of our calculations and investigate the effects coming from parton showers in initial and final states. Our predictions are compared with the recent experimental data taken by the D0 and CDF collaborations. Special attention is put on the specific angular correlations between the final-state particles. We demonstrate that the final state parton shower plays a crucial role in the description of such observables. The decorrelated part of angular separations can be fully described, if the process $gg^*\rightarrow gg$ is included.Comment: Fig 8,9 10 replaced, small corrections in text A discussion of the delta phi results is adde

Gravitational waves from single neutron stars: an advanced detector era survey

With the doors beginning to swing open on the new gravitational wave astronomy, this review provides an up-to-date survey of the most important physical mechanisms that could lead to emission of potentially detectable gravitational radiation from isolated and accreting neutron stars. In particular we discuss the gravitational wave-driven instability and asteroseismology formalism of the f- and r-modes, the different ways that a neutron star could form and sustain a non-axisymmetric quadrupolar "mountain" deformation, the excitation of oscillations during magnetar flares and the possible gravitational wave signature of pulsar glitches. We focus on progress made in the recent years in each topic, make a fresh assessment of the gravitational wave detectability of each mechanism and, finally, highlight key problems and desiderata for future work.Comment: 39 pages, 12 figures, 2 tables. Chapter of the book "Physics and Astrophysics of Neutron Stars", NewCompStar COST Action 1304. Minor corrections to match published versio