Civil helicopter wire strike assessment study. Volume 1: Findings and recommendations

Approximately 208 civil helicopter wire strike accidents for a ten year period 1970 to 1979 are analyzed. It is found that 83% of the wire strikes occurred during bright clear weather. Analysis of the accidents is organized under pilot, environment, and machine factors. Methods to reduce the wire strike accident rate are discussed, including detection/warning devices, identification of wire locations prior to flight, wire cutting devices, and implementation of training programs. The benefits to be gained by implementing accident avoidance methods are estimated to be fully justified by reduction in injury and death and reduction of aircraft damage and loss

Conceptual design of a floating support structure for an offshore vertical axis wind turbine : the lessons learnt

The design of floating support structures for wind turbines located offshore is a relatively new field. In contrast, the offshore oil and gas industry has been developing its technologies since the mid 1950s. However, the significantly and subtly different requirements of the offshore wind industry call for new methodologies. An Energy Technologies Institute (ETI) funded project called NOVA (for Novel Vertical Axis wind turbine) examined the feasibility of a large offshore vertical axis wind turbine in the 10-20 MW power range. The development of a case study for the NOVA project required a methodology to be developed to select the best configuration, based on the system dynamics. The design space has been investigated, ranking the possible options using a multi-criteria decision making (MCDM) method called TOPSIS. The best 'class' or design solution (based on water plane area stability) has been selected for a more detailed analysis. Two configurations are considered: a barge and a semi-submersible. The iterations to optimise and compare these two options are presented here, taking their dynamics and costs into account. The barge concept evolved to the 'triple doughnut-Miyagawa' concept, consisting of an annular cylindrical shape with an inner (to control the damping) and outer (to control added mass) bottom flat plates. The semi-submersible was optimised to obtain the best trade-off between dynamic behaviour and amount of material needed. The main conclusion is that the driving requirement is an acceptable response to wave action, not the ability to float or the ability to counteract the wind turbine overturning moment. A simple cost comparison is presented

KA-Search, a method for rapid and exhaustive sequence identity search of known antibodies

Antibodies with similar amino acid sequences, especially across their complementarity-determining regions, often share properties. Finding that an antibody of interest has a similar sequence to naturally expressed antibodies in healthy or diseased repertoires is a powerful approach for the prediction of antibody properties, such as immunogenicity or antigen specificity. However, as the number of available antibody sequences is now in the billions and continuing to grow, repertoire mining for similar sequences has become increasingly computationally expensive. Existing approaches are limited by either being low-throughput, non-exhaustive, not antibody specific, or only searching against entire chain sequences. Therefore, there is a need for a specialized tool, optimized for a rapid and exhaustive search of any antibody region against all known antibodies, to better utilize the full breadth of available repertoire sequences. We introduce Known Antibody Search (KA-Search), a tool that allows for the rapid search of billions of antibody variable domains by amino acid sequence identity across either the variable domain, the complementarity-determining regions, or a user defined antibody region. We show KA-Search in operation on the ∼2.4 billion antibody sequences available in the OAS database. KA-Search can be used to find the most similar sequences from OAS within 30 minutes and a representative subset of 10 million sequences in less than 9 seconds. We give examples of how KA-Search can be used to obtain new insights about an antibody of interest. KA-Search is freely available at https://github.com/oxpig/kasearch

Clinical importance of cystic fibrosis-related diabetes

AbstractThe prevalence of cystic fibrosis-related diabetes (CFRD) and glucose intolerance (IGT) has risen dramatically over the past 20 years as survival has increased for people with cystic fibrosis (CF). Diabetes is primarily caused by pancreatic damage, which reduces insulin secretion, but glucose tolerance is also modified by factors that alter insulin resistance, such as intercurrent illness and infection. CFRD not only causes the symptoms and micro and macrovascular complications seen in type 1 and type 2 diabetes in the general population, but also is associated with accelerated pulmonary decline and increased mortality. Pulmonary effects are seen some years before the diagnosis of CFRD, implying that impaired glucose tolerance may be detrimental.Current practice is to screen for changes in glucose tolerance by regular measurement of fasting blood glucose, by oral glucose tolerance test or a combination of these approaches with symptom review and measurement of HbA1C. Treatment is clearly indicated for those with CFRD and fasting hyperglycaemia to control symptoms and reduce complications. As nutrition is critical in people with CF to maintain body mass and lung function, blood glucose should be controlled in CFRD by adjusting insulin doses to the requirements of adequate food intake and not by calorie restriction. It is less clear whether blood glucose control will have clinical benefits in the management of patients with CFRD without fasting hyperglycaemia or with impaired glucose tolerance and further studies are required to establish the best treatment for this patient group

Do (and say) as I say: Linguistic adaptation in human-computer dialogs

© Theodora Koulouri, Stanislao Lauria, and Robert D. Macredie. This article has been made available through the Brunel Open Access Publishing Fund.There is strong research evidence showing that people naturally align to each other’s vocabulary, sentence structure, and acoustic features in dialog, yet little is known about how the alignment mechanism operates in the interaction between users and computer systems let alone how it may be exploited to improve the efficiency of the interaction. This article provides an account of lexical alignment in human–computer dialogs, based on empirical data collected in a simulated human–computer interaction scenario. The results indicate that alignment is present, resulting in the gradual reduction and stabilization of the vocabulary-in-use, and that it is also reciprocal. Further, the results suggest that when system and user errors occur, the development of alignment is temporarily disrupted and users tend to introduce novel words to the dialog. The results also indicate that alignment in human–computer interaction may have a strong strategic component and is used as a resource to compensate for less optimal (visually impoverished) interaction conditions. Moreover, lower alignment is associated with less successful interaction, as measured by user perceptions. The article distills the results of the study into design recommendations for human–computer dialog systems and uses them to outline a model of dialog management that supports and exploits alignment through mechanisms for in-use adaptation of the system’s grammar and lexicon

Assessing the Potential Return on Investment of the Proposed UK NHS Diabetes Prevention Programme in Different Population Subgroups: An Economic Evaluation

Objectives: To evaluate potential return on investment of the NHS Diabetes Prevention Programme (DPP) in England, and estimate which population subgroups are likely to benefit most in terms of cost-effectiveness, cost-savings and health benefits. Design: Economic Analysis using the School for Public Health Research Diabetes Prevention Model Setting: England 2015-16 Population: Adults aged 16 or over with high risk of type 2 diabetes (HbA1c 6-6.4%). Population subgroups defined by age, sex, ethnicity, socioeconomic deprivation, baseline BMI, baseline HbA1c and working status. Interventions: The proposed NHS DPP: An intensive lifestyle intervention focussing on dietary advice, physical activity and weight loss. Comparator: No diabetes prevention intervention. Main outcome measures: Incremental costs, savings and return on investment, quality adjusted life years (QALYs), diabetes cases, cardiovascular cases and net monetary benefit from an NHS perspective. Results: Intervention costs will be recouped through NHS savings within 12 years, with net NHS saving of £1.28 over 20 years for each £1 invested. Per 100,000 DPP interventions given, 3,552 QALYs are gained. The DPP is most cost-effective and cost-saving in obese individuals, those with baseline HbA1c 6.2-6.4% and those aged 40-74. QALY gains are lower in minority ethnic and low socioeconomic status subgroups. Probabilistic sensitivity analysis suggests that there is 97% probability that the DPP will be cost-effective within 20 years. NHS savings are highly sensitive to intervention cost, effectiveness and duration of effect. Conclusions: The DPP is likely to be cost-effective and cost-saving under current assumptions. Prioritising obese individuals could create the most value for money and obtain the greatest health benefits per individual targeted. Low socioeconomic status or ethnic minority groups may gain fewer QALYs per intervention, so targeting strategies should ensure the DPP does not contribute to widening health inequalities. Further evidence is needed around the differential responsiveness of population subgroups to the DPP.

Simvastatin inhibits TLR8 signaling in primary human monocytes and spontaneous TNF production from rheumatoid synovial membrane cultures

Simvastatin has been shown to have anti-inflammatory effects that are independent of its serum cholesterol lowering action, but the mechanisms by which these anti-inflammatory effects are mediated have not been elucidated. To explore the mechanism involved, the effect of simvastatin on Toll-like receptor (TLR) signalling in primary human monocytes was investigated. A short pre-treatment with simvastatin dose-dependently inhibited the production of tumor necrosis factor-α (TNF) in response to TLR8 (but not TLRs 2, 4, or 5) activation. Statins are known inhibitors of the cholesterol biosynthetic pathway, but intriguingly TLR8 inhibition could not be reversed by addition of mevalonate or geranylgeranyl pyrophosphate; downstream products of cholesterol biosynthesis. TLR8 signalling was examined in HEK 293 cells stably expressing TLR8, where simvastatin inhibited IKKα/β phosphorylation and subsequent NF-κB activation without affecting the pathway to AP-1. Since simvastatin has been reported to have anti-inflammatory effects in RA patients and TLR8 signalling contributes to TNF production in human RA synovial tissue in culture, simvastatin was tested in these cultures. Simvastatin significantly inhibited the spontaneous release of TNF in this model which was not reversed by mevalonate. Together, these results demonstrate a hitherto unrecognized mechanism of simvastatin inhibition of TLR8 signalling that may in part explain its beneficial anti-inflammatory effects

drawProteins: a Bioconductor/R package for reproducible and programmatic generation of protein schematics

Protein schematics are valuable for research, teaching and knowledge communication. However, the tools used to automate the process are challenging. The purpose of the drawProteins package is to enable the generation of schematics of proteins in an automated fashion that can integrate with the Bioconductor/R suite of tools for bioinformatics and statistical analysis. Using UniProt accession numbers, the package uses the UniProt API to get the features of the protein from the UniProt database. The features are assembled into a data frame and visualized using adaptations of the ggplot2 package. Visualizations can be customised in many ways including adding additional protein features information from other data frames, altering colors and protein names and adding extra layers using other ggplot2 functions. This can be completed within a script that makes the workflow reproducible and sharable

Creating massive entanglement of Bose condensed atoms

We propose a direct, coherent coupling scheme that can create massively entangled states of Bose-Einstein condensed atoms. Our idea is based on an effective interaction between two atoms from coherent Raman processes through a (two atom) molecular intermediate state. We compare our scheme with other recent proposals for generation of massive entanglement of Bose condensed atoms.Comment: 5 pages, 3 figures; Updated figure 3(a), original was "noisy