Cost-effectiveness of paediatric central venous catheters in the UK:A secondary publication from the CATCH clinical trial

Background: Antibiotic-impregnated central venous catheters (CVCs) reduce the risk of bloodstream infections (BSIs) in patients treated in pediatric intensive care units (PICUs). However, it is unclear if they are cost-effective from the perspective of the National Health Service (NHS) in the UK.Methods: Economic evaluation alongside the CATCH trial (ISRCTN34884569) to estimate the incremental cost effectiveness ratio (ICER) of antibiotic-impregnated (rifampicin and minocycline), heparin-bonded and standard polyurethane CVCs. The 6-month costs of CVCs and hospital admissions and visits were determined from administrative hospital data and case report forms.Results: BSIs were detected in 3.59% (18/502) of patients randomized to standard, 1.44% (7/486) to antibiotic and 3.42% (17/497) to heparin CVCs. Lengths of hospital stay did not differ between intervention groups. Total mean costs (95% confidence interval) were: £45,663 (£41,647–£50,009) for antibiotic, £42,065 (£38,322–£46,110) for heparin, and £44,503 (£40,619–£48,666) for standard CVCs. As heparin CVCs were not clinically effective at reducing BSI rate compared to standard CVCs, they were considered not to be cost-effective. The ICER for antibiotic vs. standard CVCs, of £54,057 per BSI avoided, was sensitive to the analytical time horizon.Conclusions: Substituting standard CVCs for antibiotic CVCs in PICUs will result in reduced occurrence of BSI but there is uncertainty as to whether this would be a cost-effective strategy for the NHS

Thinking like a man? The cultures of science

Culture includes science and science includes culture, but conflicts between the two traditions persist, often seen as clashes between interpretation and knowledge. One way of highlighting this false polarity has been to explore the gendered symbolism of science. Feminism has contributed to science studies and the critical interrogation of knowledge, aware that practical knowledge and scientific understanding have never been synonymous. Persisting notions of an underlying unity to scientific endeavour have often impeded rather than fostered the useful application of knowledge. This has been particularly evident in the recent rise of molecular biology, with its delusory dream of the total conquest of disease. It is equally prominent in evolutionary psychology, with its renewed attempts to depict the fundamental basis of sex differences. Wars over science have continued to intensify over the last decade, even as our knowledge of the political, economic and ideological significance of science funding and research has become ever more apparent

Thermal susceptibility of the Planck-LFI receivers

This paper is part of the Prelaunch status LFI papers published on JINST: http://www.iop.org/EJ/journal/-page=extra.proc5/jinst . This paper describes the impact of the Planck Low Frequency Instrument front end physical temperature fluctuations on the output signal. The origin of thermal instabilities in the instrument are discussed, and an analytical model of their propagation and impact on the receivers signal is described. The experimental test setup dedicated to evaluate these effects during the instrument ground calibration is reported together with data analysis methods. Finally, main results obtained are discussed and compared to the requirements.Comment: This is an author-created, un-copyedited version of an article accepted for publication in Journal of Instrumentation. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The definitive publisher authenticated version is available online at 10.1088/1748-0221/4/12/T1201

Dynamic Blood-Brain Barrier Regulation in Mild Traumatic Brain Injury

Whereas the diagnosis of moderate and severe traumatic brain injury (TBI) is readily visible on current medical imaging paradigms (magnetic resonance imaging [MRI] and computed tomography [CT] scanning), a far greater challenge is associated with the diagnosis and subsequent management of mild TBI (mTBI), especially concussion which, by definition, is characterized by a normal CT. To investigate whether the integrity of the blood-brain barrier (BBB) is altered in a high-risk population for concussions, we studied professional mixed martial arts (MMA) fighters and adolescent rugby players. Additionally, we performed the linear regression between the BBB disruption defined by increased gadolinium contrast extravasation on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) on MRI and multiple biomechanical parameters indicating the severity of impacts recorded using instrumented mouthguards in professional MMA fighters. MMA fighters were examined pre-fight for a baseline and again within 120 h post-competitive fight, whereas rugby players were examined pre-season and again post-season or post-match in a subset of cases. DCE-MRI, serological analysis of BBB biomarkers, and an analysis of instrumented mouthguard data, was performed. Here, we provide pilot data that demonstrate disruption of the BBB in both professional MMA fighters and rugby players, dependent on the level of exposure. Our data suggest that biomechanical forces in professional MMA and adolescent rugby can lead to BBB disruption. These changes on imaging may serve as a biomarker of exposure of the brain to repetitive subconcussive forces and mTBI

Planck pre-launch status: calibration of the Low Frequency Instrument flight model radiometers

The Low Frequency Instrument (LFI) on-board the ESA Planck satellite carries eleven radiometer subsystems, called Radiometer Chain Assemblies (RCAs), each composed of a pair of pseudo-correlation receivers. We describe the on-ground calibration campaign performed to qualify the flight model RCAs and to measure their pre-launch performances. Each RCA was calibrated in a dedicated flight-like cryogenic environment with the radiometer front-end cooled to 20K and the back-end at 300K, and with an external input load cooled to 4K. A matched load simulating a blackbody at different temperatures was placed in front of the sky horn to derive basic radiometer properties such as noise temperature, gain, and noise performance, e.g. 1/f noise. The spectral response of each detector was measured as was their susceptibility to thermal variation. All eleven LFI RCAs were calibrated. Instrumental parameters measured in these tests, such as noise temperature, bandwidth, radiometer isolation, and linearity, provide essential inputs to the Planck-LFI data analysis.Comment: 15 pages, 18 figures. Accepted for publication in Astronomy and Astrophysic

Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient

VERITAS Observations of the gamma-Ray Binary LS I +61 303

LS I +61 303 is one of only a few high-mass X-ray binaries currently detected at high significance in very high energy gamma-rays. The system was observed over several orbital cycles (between September 2006 and February 2007) with the VERITAS array of imaging air-Cherenkov telescopes. A signal of gamma-rays with energies above 300 GeV is found with a statistical significance of 8.4 standard deviations. The detected flux is measured to be strongly variable; the maximum flux is found during most orbital cycles at apastron. The energy spectrum for the period of maximum emission can be characterized by a power law with a photon index of Gamma=2.40+-0.16_stat+-0.2_sys and a flux above 300 GeV corresponding to 15-20% of the flux from the Crab Nebula.Comment: accepted for publication in The Astrophysical Journa

Long-term multi-wavelength variability and correlation study of Markarian 421 from 2007 to 2009

We study the multi-band variability and correlations of the TeV blazar Mrk 421 on year time scales, which can bring additional insight on the processes responsible for its broadband emission. We observed Mrk 421 in the very high energy (VHE) gamma-ray range with the Cherenkov telescope MAGIC-I from March 2007 to June 2009 for a total of 96 hours of effective time after quality cuts. The VHE flux variability is quantified with several methods, including the Bayesian Block algorithm, which is applied to data from Cherenkov telescopes for the first time. The 2.3 year long MAGIC light curve is complemented with data from the Swift/BAT and RXTE/ASM satellites and the KVA, GASP-WEBT, OVRO, and Mets\"ahovi telescopes from February 2007 to July 2009, allowing for an excellent characterisation of the multi-band variability and correlations over year time scales. Mrk 421 was found in different gamma-ray emission states during the 2.3 year long observation period. Flares and different levels of variability in the gamma-ray light curve could be identified with the Bayesian Block algorithm. The same behaviour of a quiet and active emission was found in the X-ray light curves measured by Swift/BAT and the RXTE/ASM, with a direct correlation in time. The behaviour of the optical light curve of GASP-WEBT and the radio light curves by OVRO and Mets\"ahovi are different as they show no coincident features with the higher energetic light curves and a less variable emission. The fractional variability is overall increasing with energy. The comparable variability in the X-ray and VHE bands and their direct correlation during both high- and low-activity periods spanning many months show that the electron populations radiating the X-ray and gamma-ray photons are either the same, as expected in the Synchrotron-Self-Compton mechanism, or at least strongly correlated, as expected in electromagnetic cascades.Comment: Corresponding authors: Ann-Kristin Overkemping ([email protected]), Marina Manganaro ([email protected]), Diego Tescaro ([email protected]), To be published in Astronomy&Astrophysics (A&A), 12 pages, 9 figure

Detection of very high energy gamma-ray emission from the gravitationally-lensed blazar QSO B0218+357 with the MAGIC telescopes

Context. QSO B0218+357 is a gravitationally lensed blazar located at a redshift of 0.944. The gravitational lensing splits the emitted radiation into two components, spatially indistinguishable by gamma-ray instruments, but separated by a 10-12 day delay. In July 2014, QSO B0218+357 experienced a violent flare observed by the Fermi-LAT and followed by the MAGIC telescopes. Aims. The spectral energy distribution of QSO B0218+357 can give information on the energetics of z ~ 1 very high energy gamma- ray sources. Moreover the gamma-ray emission can also be used as a probe of the extragalactic background light at z ~ 1. Methods. MAGIC performed observations of QSO B0218+357 during the expected arrival time of the delayed component of the emission. The MAGIC and Fermi-LAT observations were accompanied by quasi-simultaneous optical data from the KVA telescope and X-ray observations by Swift-XRT. We construct a multiwavelength spectral energy distribution of QSO B0218+357 and use it to model the source. The GeV and sub-TeV data, obtained by Fermi-LAT and MAGIC, are used to set constraints on the extragalactic background light. Results. Very high energy gamma-ray emission was detected from the direction of QSO B0218+357 by the MAGIC telescopes during the expected time of arrival of the trailing component of the flare, making it the farthest very high energy gamma-ray sources detected to date. The observed emission spans the energy range from 65 to 175 GeV. The combined MAGIC and Fermi-LAT spectral energy distribution of QSO B0218+357 is consistent with current extragalactic background light models. The broad band emission can be modeled in the framework of a two zone external Compton scenario, where the GeV emission comes from an emission region in the jet, located outside the broad line region.Comment: 11 pages, 6 figures, accepted for publication in A&