Particle-in-cell Simulations of Ion Dynamics in a Pinched-beam Diode

article-in-cell simulations of a 1.6 MV, 800 kA, and 50 ns pinched-beam diode have been completed with emphasis placed on the quality of the ion beams produced. Simulations show the formation of multiple regions in the electron beam flow characterized by locally high charge and current density (“hot spots”). As ions flow through the electron-space-charge cloud, these hot spots electrostatically attract ions to produce a non-uniform ion current distribution. The length of the cavity extending beyond the anode-to-cathode gap (i.e., behind the cathode tip) influences both the number and amplitude of hot spots. A longer cavity length increases the number of hot spots yet significantly reduces the amplitude producing a smoother, more uniform ion beam than for shorter cavities. The net current and the ion bending angles are also significantly smaller with long cavities

Not all parents are equal for MO-CMA-ES

International audienceThe Steady State variants of the Multi-Objective Covariance Matrix Adaptation Evolution Strategy (SS-MO-CMA-ES) generate one offspring from a uniformly selected parent. Some other parental selection operators for SS-MO-CMA-ES are investigated in this paper. These operators involve the definition of multi-objective rewards, estimating the expectation of the offspring survival and its Hypervolume contribution. Two selection modes, respectively using tournament, and inspired from the Multi-Armed Bandit framework, are used on top of these rewards. Extensive experimental validation comparatively demonstrates the merits of these new selection operators on unimodal MO problems

Combined In Silico, In Vivo, and In Vitro Studies Shed Insights into the Acute Inflammatory Response in Middle-Aged Mice

We combined in silico, in vivo, and in vitro studies to gain insights into age-dependent changes in acute inflammation in response to bacterial endotoxin (LPS). Time-course cytokine, chemokine, and NO2-/NO3- data from "middle-aged" (6-8 months old) C57BL/6 mice were used to re-parameterize a mechanistic mathematical model of acute inflammation originally calibrated for "young" (2-3 months old) mice. These studies suggested that macrophages from middle-aged mice are more susceptible to cell death, as well as producing higher levels of pro-inflammatory cytokines, vs. macrophages from young mice. In support of the in silico-derived hypotheses, resident peritoneal cells from endotoxemic middle-aged mice exhibited reduced viability and produced elevated levels of TNF-α, IL-6, IL-10, and KC/CXCL1 as compared to cells from young mice. Our studies demonstrate the utility of a combined in silico, in vivo, and in vitro approach to the study of acute inflammation in shock states, and suggest hypotheses with regard to the changes in the cytokine milieu that accompany aging. © 2013 Namas et al

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

Killer whale genomes reveal a complex history of recurrent admixture and vicariance

Reconstruction of the demographic and evolutionary history of populations assuming a consensus tree‐like relationship can mask more complex scenarios, which are prevalent in nature. An emerging genomic toolset, which has been most comprehensively harnessed in the reconstruction of human evolutionary history, enables molecular ecologists to elucidate complex population histories. Killer whales have limited extrinsic barriers to dispersal and have radiated globally, and are therefore a good candidate model for the application of such tools. Here, we analyse a global data set of killer whale genomes in a rare attempt to elucidate global population structure in a nonhuman species. We identify a pattern of genetic homogenisation at lower latitudes and the greatest differentiation at high latitudes, even between currently sympatric lineages. The processes underlying the major axis of structure include high drift at the edge of species' range, likely associated with founder effects and allelic surfing during postglacial range expansion. Divergence between Antarctic and non‐Antarctic lineages is further driven by ancestry segments with up to fourfold older coalescence time than the genome‐wide average; relicts of a previous vicariance during an earlier glacial cycle. Our study further underpins that episodic gene flow is ubiquitous in natural populations, and can occur across great distances and after substantial periods of isolation between populations. Thus, understanding the evolutionary history of a species requires comprehensive geographic sampling and genome‐wide data to sample the variation in ancestry within individuals

The relationship between doses of mindfulness-based programs and depression, anxiety, stress, and mindfulness: a dose-response meta-regression of randomized controlled trials

Abstract Objectives: Research with mindfulness-based programs (MBPs) has found participating in an MBP to predict beneficial outcomes, however, there is currently mixed research regarding the most helpful dose. This review aimed to determine whether different doses related to MBPs significantly predict outcomes. Methods: Systematic literature searches of electronic databases and trial registration sites for all randomized controlled trials of MBPs identified 203 studies (N=15,971). Depression was the primary outcome at post-program and follow-up, with secondary outcomes being mindfulness, anxiety and stress. Doses examined related to session numbers, duration and length, facilitator contact and practice. Dose-response relationships were analyzed using meta-regression in R with separate analyses for inactive and active controls. Results: Initial meta-analyses found significant between-group differences favoring MBPs for all outcomes. Meta-regression results suggested significant dose-response relationships for the mindfulness outcome for doses relating to face-to-face contact (d=0.211; C.I.[0.064,0.358]), program intensity (d=0.895; C.I.[0.315,1.474]) and actual program use (d=0.013; C.I.[0.001,0.024]). The majority of results for psychological outcomes, including depression, were not significant. Conclusions: This meta-regression examines dose-response relationships for different types and doses relating to MBPs. Considered together, MBPs appeared helpful compared to controls, supporting previous research. Based on meta-regression results, there was no evidence that larger doses are more helpful than smaller doses for predicting psychological outcomes; a finding consistent with some previous research particularly with non-clinical populations. Additionally, greater contact, intensity and actual use of MBPs predicting increased mindfulness corresponds with previous research and theory. Potential limitations and recommendations for future research are explored

Why Are Clinicians Not Embracing the Results from Pivotal Clinical Trials in Severe Sepsis? A Bayesian Analysis

BACKGROUND: Five pivotal clinical trials (Intensive Insulin Therapy; Recombinant Human Activated Protein C [rhAPC]; Low-Tidal Volume; Low-Dose Steroid; Early Goal-Directed Therapy [EGDT]) demonstrated mortality reduction in patients with severe sepsis and expert guidelines have recommended them to clinical practice. Yet, the adoption of these therapies remains low among clinicians. OBJECTIVES: We selected these five trials and asked: Question 1--What is the current probability that the new therapy is not better than the standard of care in my patient with severe sepsis? Question 2--What is the current probability of reducing the relative risk of death (RRR) of my patient with severe sepsis by meaningful clinical thresholds (RRR >15%; >20%; >25%)? METHODS: Bayesian methodologies were applied to this study. Odds ratio (OR) was considered for Question 1, and RRR was used for Question 2. We constructed prior distributions (enthusiastic; mild, moderate, and severe skeptic) based on various effective sample sizes of other relevant clinical trials (unfavorable evidence). Posterior distributions were calculated by combining the prior distributions and the data from pivotal trials (favorable evidence). MAIN FINDINGS: Answer 1--The analysis based on mild skeptic prior shows beneficial results with the Intensive Insulin, rhAPC, and Low-Tidal Volume trials, but not with the Low-Dose Steroid and EGDT trials. All trials' results become unacceptable by the analyses using moderate or severe skeptic priors. Answer 2--If we aim for a RRR>15%, the mild skeptic analysis shows that the current probability of reducing death by this clinical threshold is 88% for the Intensive Insulin, 62-65% for the Low-Tidal Volume, rhAPC, EGDT trials, and 17% for the Low-Dose Steroid trial. The moderate and severe skeptic analyses show no clinically meaningful reduction in the risk of death for all trials. If we aim for a RRR >20% or >25%, all probabilities of benefits become lower independent of the degree of skepticism. CONCLUSIONS: Our clinical threshold analysis offers a new bedside tool to be directly applied to the care of patients with severe sepsis. Our results demonstrate that the strength of evidence (statistical and clinical) is weak for all trials, particularly for the Low-Dose Steroid and EGDT trials. It is essential to replicate the results of each of these five clinical trials in confirmatory studies if we want to provide patient care based on scientifically sound evidence

The First Post-Kepler Brightness Dips of KIC 8462852

We present a photometric detection of the first brightness dips of the unique variable star KIC 8462852 since the end of the Kepler space mission in 2013 May. Our regular photometric surveillance started in October 2015, and a sequence of dipping began in 2017 May continuing on through the end of 2017, when the star was no longer visible from Earth. We distinguish four main 1-2.5% dips, named "Elsie," "Celeste," "Skara Brae," and "Angkor", which persist on timescales from several days to weeks. Our main results so far are: (i) there are no apparent changes of the stellar spectrum or polarization during the dips; (ii) the multiband photometry of the dips shows differential reddening favoring non-grey extinction. Therefore, our data are inconsistent with dip models that invoke optically thick material, but rather they are in-line with predictions for an occulter consisting primarily of ordinary dust, where much of the material must be optically thin with a size scale <<1um, and may also be consistent with models invoking variations intrinsic to the stellar photosphere. Notably, our data do not place constraints on the color of the longer-term "secular" dimming, which may be caused by independent processes, or probe different regimes of a single process

Should all adjunctive corticosteroid therapy be avoided in the management of hemodynamically stabile Staphylococcus aureus bacteremia?

The purpose of this study was to examine the prognostic impact of corticosteroids in hemodynamically stabile Staphylococcus aureus bacteremia (SAB). There were 361 hemodynamically stabile methicillin-sensitive SAB patients with prospective follow-up and grouping according to time-point, dose and indication for corticosteroid therapy. To enable analyses without external interfering corticosteroid therapy all patients with corticosteroid therapy equivalent to prednisone > 10 mg/day for >= 1 month prior to positive blood culture results were excluded. Twenty-five percent (92) of patients received corticosteroid therapy of which 11 % (40) had therapy initiated within 1 week (early initiation) and 9 % (31) had therapy initiated 2-4 weeks after (delayed initiation) positive blood culture. Twenty-one patients (6 %) had corticosteroid initiated after 4 weeks and were not included in the analyses. A total of 55 % (51/92) received a weekly prednisone dose > 100 mg. Patients with early initiated corticosteroid therapy had higher mortality compared to patients treated without corticosteroid therapy at 28 days (20 % vs. 7 %) (OR, 3.11; 95% CI, 1.27-7.65; p = 100 mg/week the negative prognostic impact on 28-day mortality was accentuated (HR 4.8, p = 0.001). Corticosteroid therapy initiation after 1 week of positive blood cultures had no independent prognostic impact. Early initiation of corticosteroid therapy may be associate to increased mortality in hemodynamically stabile SAB.Peer reviewe