Efficacy, safety, and tolerance of piperacillin/tazobactam compared to co-amoxiclav plus an aminoglycoside in the treatment of severe pneumonia

An open, randomized, multicenter study was conducted to compare the efficacy and safety of piperacillin/tazobactam and co-amoxiclav plus aminoglycoside in the treatment of hospitalized patients with severe community-acquired or nosocomial pneumonia. Of the 89 patients who entered the study, 84 (94%) were clinically evaluable. A favorable clinical response was observed in 90% of the piperacillin/ tazobactam group and in 84% of the co-amoxiclav/aminoglycoside group (not significant). The bacteriological efficacy was comparable in both groups (96% vs. 92%; not significant). There was only one fatal outcome in the piperacillin/tazobactam group compared to six in the co-amoxiclav/aminoglycoside group regimenP=0.058). The adverse event rate was non-significantly lower in the piperacillin/ tazobactam group compared to the co-amoxiclav/aminoglycoside group (2% vs. 7%;P=0.32). Piperacillin/tazobactam is safe and highly efficacious in the treatment of serious pneumonia in hospitalized patients. It compares favorably with the combination of co-amoxiclav/aminoglycosid

Calibration of <i>Herschel</i> SPIRE FTS observations at different spectral resolutions

The SPIRE Fourier Transform Spectrometer on-board the Herschel Space Observatory had two standard spectral resolution modes for science observations: high resolution (HR) and low resolution (LR), which could also be performed in sequence (H+LR). A comparison of the HR and LR resolution spectra taken in this sequential mode revealed a systematic discrepancy in the continuum level. Analysing the data at different stages during standard pipeline processing demonstrates that the telescope and instrument emission affect HR and H+LR observations in a systematically different way. The origin of this difference is found to lie in the variation of both the telescope and instrument response functions, while it is triggered by fast variation of the instrument temperatures. As it is not possible to trace the evolution of the response functions using housekeeping data from the instrument subsystems, the calibration cannot be corrected analytically. Therefore, an empirical correction for LR spectra has been developed, which removes the systematic noise introduced by the variation of the response functions

Edge Label Placement in Layered Graph Drawing

Many visual languages based on node-link diagrams use edge labels. We describe different strategies of placing edge labels in the context of the layered approach to graph drawing and investigate ways of encoding edge direction in labels. We evaluate the label placement strategies based on both common aesthetic criteria and a controlled experiment. We find that placing labels on their edge can lead to more compact diagrams. Also, placing labels with additional arrows indicating edge direction can help users navigate in large diagrams and is generally preferred by participants of our experiment, outperforming other ways of indicating edge direction

Reward-Sensitive Basal Ganglia Stabilize the Maintenance of Goal-Relevant Neural Patterns in Adolescents

Maturation of basal ganglia (BG) and frontoparietal circuitry parallels developmental gains in working memory (WM). Neurobiological models posit that adult WM performance is enhanced by communication between reward-sensitive BG and frontoparietal regions, via increased stability in the maintenance of goal-relevant neural patterns. It is not known whether this reward-driven pattern stability mechanism may have a role in WM development. In 34 young adolescents (12.16–14.72 years old) undergoing fMRI, reward-sensitive BG regions were localized using an incentive processing task. WM-sensitive regions were localized using a delayed-response WM task. Functional connectivity analyses were used to examine the stability of goal-relevant functional connectivity patterns during WM delay periods between and within reward-sensitive BG and WM-sensitive frontoparietal regions. Analyses revealed that more stable goal-relevant connectivity patterns between reward-sensitive BG and WM-sensitive frontoparietal regions were associated with both greater adolescent age and WM ability. Computational lesion models also revealed that functional connections to WM-sensitive frontoparietal regions from reward-sensitive BG uniquely increased the stability of goal-relevant functional connectivity patterns within frontoparietal regions. Findings suggested (1) the extent to which goal-relevant communication patterns within reward-frontoparietal circuitry are maintained increases with adolescent development and WM ability and (2) communication from reward-sensitive BG to frontoparietal regions enhances the maintenance of goal-relevant neural patterns in adolescents’ WM. The maturation of reward-driven stability of goal-relevant neural patterns may provide a putative mechanism for understanding the developmental enhancement of WM

Systematic characterisation of the Herschel SPIRE Fourier Transform Spectrometer

A systematic programme of calibration observations was carried out to monitor the performance of the SPIRE FTS instrument on board the Herschel Space Observatory. Observations of planets (including the prime point-source calibrator, Uranus), asteroids, line sources, dark sky, and cross-calibration sources were made in order to monitor repeatability and sensitivity, and to improve FTS calibration. We present a complete analysis of the full set of calibration observations and use them to assess the performance of the FTS. Particular care is taken to understand and separate out the effect of pointing uncertainties, including the position of the internal beam steering mirror for sparse observations in the early part of the mission. The repeatability of spectral line centre positions is <5km/s, for lines with signal-to-noise ratios >40, corresponding to <0.5-2.0% of a resolution element. For spectral line flux, the repeatability is better than 6%, which improves to 1-2% for spectra corrected for pointing offsets. The continuum repeatability is 4.4% for the SLW band and 13.6% for the SSW band, which reduces to ~1% once the data have been corrected for pointing offsets. Observations of dark sky were used to assess the sensitivity and the systematic offset in the continuum, both of which were found to be consistent across the FTS detector arrays. The average point-source calibrated sensitivity for the centre detectors is 0.20 and 0.21 Jy [1 sigma; 1 hour], for SLW and SSW. The average continuum offset is 0.40 Jy for the SLW band and 0.28 Jy for the SSW band.Comment: 41 pages, 37 figures, 32 tables. Accepted for publication in MNRA

LSD1 controls metastasis of androgen-independent prostate cancer cells through PXN and LPAR6

Lysine-specific demethylase 1 (LSD1) was shown to control gene expression and cell proliferation of androgen-dependent prostate cancer (PCa) cells, whereas the role of LSD1 in androgen-independent metastatic prostate cancer remains elusive. Here, we show that depletion of LSD1 leads to increased migration and invasion of androgen-independent PCa cells. Transcriptome and cistrome analyses reveal that LSD1 regulates expression of lysophosphatidic acid receptor 6 (LPAR6) and cytoskeletal genes including the focal adhesion adaptor protein paxillin (PXN). Enhanced LPAR6 signalling upon LSD1 depletion promotes migration with concomitant phosphorylation of PXN. In mice LPAR6 overexpression enhances, whereas knockdown of LPAR6 abolishes metastasis of androgen-independent PCa cells. Taken together, we uncover a novel mechanism of how LSD1 controls metastasis and identify LPAR6 as a promising therapeutic target to treat metastatic prostate cancer

An all-sky search algorithm for continuous gravitational waves from spinning neutron stars in binary systems

Rapidly spinning neutron stars with non-axisymmetric mass distributions are expected to generate quasi-monochromatic continuous gravitational waves. While many searches for unknown, isolated spinning neutron stars have been carried out, there have been no previous searches for unknown sources in binary systems. Since current search methods for unknown, isolated neutron stars are already computationally limited, expanding the parameter space searched to include binary systems is a formidable challenge. We present a new hierarchical binary search method called TwoSpect, which exploits the periodic orbital modulations of the continuous waves by searching for patterns in doubly Fourier-transformed data. We will describe the TwoSpect search pipeline, including its mitigation of detector noise variations and corrections for Doppler frequency modulation caused by changing detector velocity. Tests on Gaussian noise and on a set of simulated signals will be presented.Comment: 22 pages, 10 figures, 1 table, Submitted to Classical and Quantum Gravit

Identification and quantification of microplastics in wastewater using focal plane array-based reflectance micro-FT-IR imaging

Microplastics (<5 mm) have been documented in environmental samples on a global scale. While these pollutants may enter aquatic environments via wastewater treatment facilities, the abundance of microplastics in these matrices has not been investigated. Although efficient methods for the analysis of microplastics in sediment samples and marine organisms have been published, no methods have been developed for detecting these pollutants within organic-rich wastewater samples. In addition, there is no standardized method for analyzing microplastics isolated from environmental samples. In many cases, part of the identification protocol relies on visual selection before analysis, which is open to bias. In order to address this, a new method for the analysis of microplastics in wastewater was developed. A pretreatment step using 30% hydrogen peroxide (H2O2) was employed to remove biogenic material, and focal plane array (FPA)-based reflectance micro-Fourier-transform (FT-IR) imaging was shown to successfully image and identify different microplastic types (polyethylene, polypropylene, nylon-6, polyvinyl chloride, polystyrene). Microplastic-spiked wastewater samples were used to validate the methodology, resulting in a robust protocol which was nonselective and reproducible (the overall success identification rate was 98.33%). The use of FPA-based micro-FT-IR spectroscopy also provides a considerable reduction in analysis time compared with previous methods, since samples that could take several days to be mapped using a single-element detector can now be imaged in less than 9 h (circular filter with a diameter of 47 mm). This method for identifying and quantifying microplastics in wastewater is likely to provide an essential tool for further research into the pathways by which microplastics enter the environment.This work is funded by a NERC (Natural Environment Research Council) CASE studentship (NE/K007521/1) with contribution from industrial partner Fera Science Ltd., United Kingdom. The authors would like to thank Peter Vale, from Severn Trent Water Ltd, for providing access to and additionally Ashley Howkins (Brunel University London) for providing travel and assistance with the sampling of the Severn Trent wastewater treatment plant in Derbyshire, UK. We are grateful to Emma Bradley and Chris Sinclair for providing helpful suggestions for our research