The influence of towers and conductor sag on transmission-line shielding

This paper is the third of a sequence of papers intended to present data which may be used in determining the degree of protection from lightning obtainable by shielding transmission lines and structures with grounded overhead wires and masts. The first two papers of the sequence are: “Shielding of Transmission Lines,” and “Shielding of Substations.

The influence of towers and conductor sag on transmission-line shielding

This paper is the third of a sequence of papers intended to present data which may be used in determining the degree of protection from lightning obtainable by shielding transmission lines and structures with grounded overhead wires and masts. The first two papers of the sequence are: “Shielding of Transmission Lines,” and “Shielding of Substations.

Solid-state NMR evidence for inequivalent GvpA subunits in gas vesicles

Gas vesicles are organelles that provide buoyancy to the aquatic microorganisms that harbor them. The gas vesicle shell consists almost exclusively of the hydrophobic 70-residue gas vesicle protein A, arranged in an ordered array. Solid-state NMR spectra of intact collapsed gas vesicles from the cyanobacterium Anabaena flos-aquae show duplication of certain gas vesicle protein A resonances, indicating that specific sites experience at least two different local environments. Interpretation of these results in terms of an asymmetric dimer repeat unit can reconcile otherwise conflicting features of the primary, secondary, tertiary, and quaternary structures of the gas vesicle protein. In particular, the asymmetric dimer can explain how the hydrogen bonds in the β-sheet portion of the molecule can be oriented optimally for strength while promoting stabilizing aromatic and electrostatic side-chain interactions among highly conserved residues and creating a large hydrophobic surface suitable for preventing water condensation inside the vesicle.National Institutes of Health (U.S.) (Grant EB002175)National Institutes of Health (U.S.) (Grant EB003151)National Institutes of Health (U.S.) (Grant EB002026

A clinical and economic evaluation of Control of Hyperglycaemia in Paediatric intensive care (CHiP): a randomised controlled trial.

BACKGROUND: Early research in adults admitted to intensive care suggested that tight control of blood glucose during acute illness can be associated with reductions in mortality, length of hospital stay and complications such as infection and renal failure. Prior to our study, it was unclear whether or not children could also benefit from tight control of blood glucose during critical illness. OBJECTIVES: This study aimed to determine if controlling blood glucose using insulin in paediatric intensive care units (PICUs) reduces mortality and morbidity and is cost-effective, whether or not admission follows cardiac surgery. DESIGN: Randomised open two-arm parallel group superiority design with central randomisation with minimisation. Analysis was on an intention-to-treat basis. Following random allocation, care givers and outcome assessors were no longer blind to allocation. SETTING: The setting was 13 English PICUs. PARTICIPANTS: Patients who met the following criteria were eligible for inclusion: ≥ 36 weeks corrected gestational age; ≤ 16 years; in the PICU following injury, following major surgery or with critical illness; anticipated treatment > 12 hours; arterial line; mechanical ventilation; and vasoactive drugs. Exclusion criteria were as follows: diabetes mellitus; inborn error of metabolism; treatment withdrawal considered; in the PICU > 5 consecutive days; and already in CHiP (Control of Hyperglycaemia in Paediatric intensive care). INTERVENTION: The intervention was tight glycaemic control (TGC): insulin by intravenous infusion titrated to maintain blood glucose between 4.0 and 7.0 mmol/l. CONVENTIONAL MANAGEMENT (CM): This consisted of insulin by intravenous infusion only if blood glucose exceeded 12.0 mmol/l on two samples at least 30 minutes apart; insulin was stopped when blood glucose fell below 10.0 mmol/l. MAIN OUTCOME MEASURES: The primary outcome was the number of days alive and free from mechanical ventilation within 30 days of trial entry (VFD-30). The secondary outcomes comprised clinical and economic outcomes at 30 days and 12 months and lifetime cost-effectiveness, which included costs per quality-adjusted life-year. RESULTS: CHiP recruited from May 2008 to September 2011. In total, 19,924 children were screened and 1369 eligible patients were randomised (TGC, 694; CM, 675), 60% of whom were in the cardiac surgery stratum. The randomised groups were comparable at trial entry. More children in the TGC than in the CM arm received insulin (66% vs. 16%). The mean VFD-30 was 23 [mean difference 0.36; 95% confidence interval (CI) -0.42 to 1.14]. The effect did not differ among prespecified subgroups. Hypoglycaemia occurred significantly more often in the TGC than in the CM arm (moderate, 12.5% vs. 3.1%; severe, 7.3% vs. 1.5%). Mean 30-day costs were similar between arms, but mean 12-month costs were lower in the TGC than in CM arm (incremental costs -£3620, 95% CI -£7743 to £502). For the non-cardiac surgery stratum, mean costs were lower in the TGC than in the CM arm (incremental cost -£9865, 95% CI -£18,558 to -£1172), but, in the cardiac surgery stratum, the costs were similar between the arms (incremental cost £133, 95% CI -£3568 to £3833). Lifetime incremental net benefits were positive overall (£3346, 95% CI -£11,203 to £17,894), but close to zero for the cardiac surgery stratum (-£919, 95% CI -£16,661 to £14,823). For the non-cardiac surgery stratum, the incremental net benefits were high (£11,322, 95% CI -£15,791 to £38,615). The probability that TGC is cost-effective is relatively high for the non-cardiac surgery stratum, but, for the cardiac surgery subgroup, the probability that TGC is cost-effective is around 0.5. Sensitivity analyses showed that the results were robust to a range of alternative assumptions. CONCLUSIONS: CHiP found no differences in the clinical or cost-effectiveness of TGC compared with CM overall, or for prespecified subgroups. A higher proportion of the TGC arm had hypoglycaemia. This study did not provide any evidence to suggest that PICUs should stop providing CM for children admitted to PICUs following cardiac surgery. For the subgroup not admitted for cardiac surgery, TGC reduced average costs at 12 months and is likely to be cost-effective. Further research is required to refine the TGC protocol to minimise the risk of hypoglycaemic episodes and assess the long-term health benefits of TGC. TRIAL REGISTRATION: Current Controlled Trials ISRCTN61735247. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 26. See the NIHR Journals Library website for further project information

Research Exploring Physical Activity in Care Homes (REACH): study protocol for a randomised controlled trial

Background: As life expectancy increases and the number of older people, particularly those aged 85 years and over, expands there is an increase in demand for long-term care. A large proportion of people in a care home setting spend most of their time sedentary, and this is one of the leading preventable causes of death. Encouraging residents to engage in more physical activity could deliver benefits in terms of physical and psychological health, and quality of life. This study is the final stage of a programme of research to develop and preliminarily test an evidence-based intervention designed to enhance opportunities for movement amongst care home residents, thereby increasing levels of physical activity. Methods/design: This is a cluster randomised feasibility trial, aiming to recruit at least 8–12 residents at each of 12 residential care homes across Yorkshire, UK. Care homes will be randomly allocated on a 1:1 basis to receive either the intervention alongside usual care, or to continue to provide usual care alone. Assessment will be undertaken with participating residents at baseline (prior to care home randomisation) and at 3, 6, and 9 months post-randomisation. Data relating to changes in physical activity, physical function, level of cognitive impairment, mood, perceived health and wellbeing, and quality of life will be collected. Data at the level of the home will also be collected and will include staff experience of care, and changes in the numbers and types of adverse events residents experience (for example, hospital admissions, falls). Details of National Health Service (NHS) usage will be collected to inform the economic analysis. An embedded process evaluation will obtain information to test out the theory of change underpinning the intervention and its acceptability to staff and residents. Discussion: This feasibility trial with embedded process evaluation and collection of health economic data will allow us to undertake detailed feasibility work to inform a future large-scale trial. It will provide valuable information to inform research procedures in this important but challenging area

Leishmania-Induced Inactivation of the Macrophage Transcription Factor AP-1 Is Mediated by the Parasite Metalloprotease GP63

Leishmania parasites have evolved sophisticated mechanisms to subvert macrophage immune responses by altering the host cell signal transduction machinery, including inhibition of JAK/STAT signalling and other transcription factors such as AP-1, CREB and NF-κB. AP-1 regulates pro-inflammatory cytokines, chemokines and nitric oxide production. Herein we show that upon Leishmania infection, AP-1 activity within host cells is abolished and correlates with lower expression of 5 of the 7 AP-1 subunits. Of interest, c-Jun, the central component of AP-1, is cleaved by Leishmania. Furthermore, the cleavage of c-Jun is dependent on the expression and activity of the major Leishmania surface protease GP63. Immunoprecipitation of c-Jun from nuclear extracts showed that GP63 interacts, and cleaves c-Jun at the perinuclear area shortly after infection. Phagocytosis inhibition by cytochalasin D did not block c-Jun down-regulation, suggesting that internalization of the parasite might not be necessary to deliver GP63 molecules inside the host cell. This observation was corroborated by the maintenance of c-Jun cleavage upon incubation with L. mexicana culture supernatant, suggesting that secreted, soluble GP63 could use a phagocytosis-independent mechanism to enter the host cell. In support of this, disruption of macrophage lipid raft microdomains by Methyl β-Cyclodextrin (MβCD) partially inhibits the degradation of full length c-Jun. Together our results indicate a novel role of the surface protease GP63 in the Leishmania-mediated subversion of host AP-1 activity

Protein adsorption on preadsorbed polyampholytic monolayers

The adsorption behaviour of five different globular proteins on pure silicon substrates and on preadsorbed polyampholytic monolayers has been investigated as a function of protein concentration. The prelayers were prepared by adsorption of the ampholytic diblock copolymer poly(methacrylic acid)-block-poly ((dimethylamino)ethyl methacrylate) (PMAA-b-PDMAEMA). This polyampholyte adsorbs in densely packed micelles directly from aqueous solution. Ellipsometry was used to determine the amount of adsorbed polyampholyte and protein. While ATR-IR spectroscopy gives information about the adsorption and desorption behaviour of the preadsorbed polyampholytic layer, the lateral structures of the dried films were investigated by scanning force microscopy (SFM). The amount of protein adsorbed was found to be strongly influenced by the preadsorbed polyampholyte compared to the adsorption on the pure silicon substrates. No displacement of the polyampholyte by the proteins was detected. In most cases the protein adsorption was reduced by the preadsorbed polyampholytic layer. The observed trends are explained by the change in electrostatic and hydrophilic characteristics of the substrates. Furthermore, the entropy of adsorption has to be taken into account.Peer reviewe

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Search for a singly produced third-generation scalar leptoquark decaying to a tau lepton and a bottom quark in proton-proton collisions at root s=13 TeV

A search is presented for a singly produced third-generation scalar leptoquark decaying to a tau lepton and a bottom quark. Associated production of a leptoquark and a tau lepton is considered, leading to a final state with a bottom quark and two tau leptons. The search uses proton-proton collision data at a center-of-mass energy of 13 TeV recorded with the CMS detector, corresponding to an integrated luminosity of 35.9 fb(-1). Upper limits are set at 95% confidence level on the production cross section of the third-generation scalar leptoquarks as a function of their mass. From a comparison of the results with the theoretical predictions, a third-generation scalar leptoquark decaying to a tau lepton and a bottom quark, assuming unit Yukawa coupling (lambda), is excluded for masses below 740 GeV. Limits are also set on lambda of the hypothesized leptoquark as a function of its mass. Above lambda = 1.4, this result provides the best upper limit on the mass of a third-generation scalar leptoquark decaying to a tau lepton and a bottom quark.Peer reviewe