Dynamics of ions in the selectivity filter of the KcsA channel

The statistical and dynamical properties of ions in the selectivity filter of the KcsA ion channel are considered on the basis of molecular dynamics (MD) simulations of the KcsA protein embedded in a lipid membrane surrounded by an ionic solution. A new approach to the derivation of a Brownian dynamics (BD) model of ion permeation through the filter is discussed, based on unbiased MD simulations. It is shown that depending on additional assumptions, ion’s dynamics can be described either by under-damped Langevin equation with constant damping and white noise or by Langevin equation with a fractional memory kernel. A comparison of the potential of the mean force derived from unbiased MD simulations with the potential produced by the umbrella sampling method demonstrates significant differences in these potentials. The origin of these differences is an open question that requires further clarifications

Anthropogenic Space Weather

Anthropogenic effects on the space environment started in the late 19th century and reached their peak in the 1960s when high-altitude nuclear explosions were carried out by the USA and the Soviet Union. These explosions created artificial radiation belts near Earth that resulted in major damages to several satellites. Another, unexpected impact of the high-altitude nuclear tests was the electromagnetic pulse (EMP) that can have devastating effects over a large geographic area (as large as the continental United States). Other anthropogenic impacts on the space environment include chemical release ex- periments, high-frequency wave heating of the ionosphere and the interaction of VLF waves with the radiation belts. This paper reviews the fundamental physical process behind these phenomena and discusses the observations of their impacts.Comment: 71 pages, 35 figure

The nocturnal intermediate layer over South Georgia : solar and magnetic influence on occurrence

Ionograms from South Georgia (54°S, 37°W; L = 1.9) are used to investigate the influence of magnetic and solar activity upon the occurrence of the nocturnal intermediate layer. The diurnal variation in occurrence of this layer exhibits a peak at about 2000 LT and a subsidiary peak after midnight. It is shown that magnetic activity has no significant influence on the behaviour before midnight, but is positively correlated with the size of the post-midnight peak. The effect of varying solar activity is to introduce a local time shift (42 min for a change in mean solar activity from 80 to 130× 10−22 Wm−2Hz−1)inthediurnal variation without otherwise changing the overall morphology of the layer significantly. Most of the features of the intermediate layer before midnight can be explained by a wind shear mechanism associated with the solar semi-diurnal tide. Some possible causes for the post-midnight observations are considered, but no firm conclusions can be made

The nocturnal intermediate layer over South Georgia

Detailed analyses of ionograms from South Georgia (54°S, 37°W; L = 1.9) show that a nocturnal intermediate layer is frequently seen between the E- and F-regions in the height range 130–180 km. The occurrence of the intermediate layer is almost totally restricted to the winter months and between the local hours of 1930 and 2300. The intermediate layer event is characterized by a prior downward movement of the F-layer, followed by the formation of the intermediate layer and its subsequent drift downwards to about 140 km. Initially, the layer is thick (~ 10–20 km), but gradually thins as it evolves. The occurrence of the intermediate layer appears to be independent of the level of magnetic activity. Observations of intermediate layers from other localities, which are briefly reviewed, are compared with those made at South Georgia. Some similarities and differences are identified. Mechanisms which account for the formation of the intermediate layer at South Georgia are considered, It is shown that the main features of the diurnal and seasonal variations of occurrence can be adequately explained by the theory of convergence of ionization driven by the solar semi-diurnal tidal winds. Some limitations of this theory are discussed, as it cannot account for all the features seen at this southern midlatitude observatory

Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-dimer concentration: a meta-analysis

INTRODUCTION The Wells clinical decision rule (CDR) and D-dimer tests can be used to exclude pulmonary embolism (PE). We performed a meta-analysis to determine the negative predictive value (NPV) of an "unlikely" CDR (The pathogenesis, clinical presentation and therapy of arterial and venous vascular disorder

Predictors of functional status at service entry and discharge among young people with first episode psychosis.

Most patients with first episode psychosis (FEP) are neither studying nor employed (have a poor functional status) when first accessing care. Knowledge of the characteristics of patients with poor functioning and the features influencing functional status over time may pave the way to better treatment. A medical file audit was used to collect data on premorbid, entry, treatment and 18-month outcome characteristics on 661 FEP patients who consecutively attended the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia, between 1998 and 2000. Functional status was ascertained using the modified vocational status index and was rated at baseline (poor or good) and according to its evolution over the treatment period (stable good, stable poor, deteriorating or improved functional status). 52.0% of patients had a poor functional status at service entry. They were more likely to be male with a non-affective psychosis. They also had lower levels of premorbid global functioning and education, and were more likely to have self-reported histories of learning disability, forensic issues, traumatic experiences and substance use. At service entry, they had more severe symptoms and poorer global functioning. 37% of these patients maintained a poor functional status at discharge, and 18% of those with a good functional status at service entry experienced a decline. Although psychosocial interventions might assist a young person with FEP with working towards functional goals, for some, the impact of factors such as ongoing substance use and forensic issues on functional status needs to be addressed

Onset of labor and use of analgesia in women using thromboprophylaxis with 2 doses of low-molecular-weight heparin: insights from the Highlow study.

BACKGROUND: Peripartum management of women using low-molecular-weight heparin (LMWH) varies widely. Minimum time intervals are required between LMWH injection and neuraxial procedure, and they differ by dose. OBJECTIVES: The objective of this study was to describe the onset of labor and use of analgesia in women using LMWH and to compare practices between intermediate-dose and low-dose LMWH. METHODS: In the Highlow study (NCT01828697), 1110 women were randomized to intermediate-dose or low-dose LMWH and were instructed to discontinue LMWH when labor commenced unplanned or 24 hours prior to planned delivery. The required time interval since last injection to receive a neuraxial procedure was ≥24 hours for intermediate-dose LMWH or ≥12 hours for low-dose LMWH. RESULTS: In total, 1018 women had an ongoing pregnancy for ≥24 weeks. Onset of labor was spontaneous in 198 of 509 (39%) women on intermediate-dose LMWH and in 246 of 509 (49%) on low-dose LMWH. With unplanned onset, a neuraxial procedure was performed in 37% on intermediate-dose and in 48% on low-dose LMWH (risk difference -11%, 95% CI -20% to -2%). Based on time interval, 61% on intermediate-dose and 82% on low-dose LMWH were eligible for a neuraxial procedure. With planned onset, 68% on intermediate-dose and 66% on low-dose LMWH received a neuraxial procedure, whereas 81% and 93%, respectively, were eligible for a neuraxial procedure (risk difference -13%, 95% CI -18% to -8%). CONCLUSION: With spontaneous onset of labor, neuraxial procedures were performed less often in women using intermediate-dose LMWH. Irrespective of onset, fewer women on intermediate-dose LMWH than those on low-dose LMWH were eligible for neuraxial procedures based on required time intervals since the last LMWH injection