The road to success: drawing parallels between 'road' and 'research data' infrastructures to foster understanding between service providers, funders and policymakers [version 1; peer review: 2 approved]

Background: The work of data research infrastructure operators is poorly understood, yet the services they provide are used by millions of scientists across the planet. Policy and implications: As the data services and the underlying infrastructure are typically funded through the public purse, it is essential that policymakers, research funders, experts reviewing funding proposals, and possibly even end-users are equipped with a good understanding of the daily tasks of service providers. Recommendations: We suggest drawing parallels between research data infrastructure and road infrastructure. To trigger the imagination and foster understanding, this policy brief contains a table of corresponding aspects of the two classes of infrastructure. Conclusions: Just as economists and specialist evaluators are typically brought in to inform policies and funding decisions for road infrastructure, we encourage this to also be done for research infrastructure

The road to success: drawing parallels between 'road' and 'research data' infrastructures to foster understanding between service providers, funders and policymakers [version 2; peer review: 2 approved]

Background: The work of data research infrastructure operators is poorly understood, yet the services they provide are used by millions of scientists across the planet. Policy and implications: As the data services and the underlying infrastructure are typically funded through the public purse, it is essential that policymakers, research funders, experts reviewing funding proposals, and possibly even end-users are equipped with a good understanding of the daily tasks of service providers. Recommendations: We suggest drawing parallels between research data infrastructure and road infrastructure. To trigger the imagination and foster understanding, this policy brief contains a table of corresponding aspects of the two classes of infrastructure, and a table of policy implications. Conclusions: Just as economists and specialist evaluators are typically brought in to inform policies and funding decisions for road infrastructure, we encourage this to also be done for research infrastructure

Current practices in children with severe acute asthma across European PICUs: an ESPNIC survey

Most pediatric asthma guidelines offer evidence-based or best practice approaches to the management of asthma exacerbations but struggle with evidence-based approaches for severe acute asthma (SAA). We aimed to investigate current practices in children with SAA admitted to European pediatric intensive care units (PICUs), in particular, adjunct therapies, use of an asthma severity score, and availability of a SAA guideline. We designed a cross-sectional electronic survey across European PICUs. Thirty-seven PICUs from 11 European countries responded. In 8 PICUs (22%), a guideline for SAA management was unavailable. Inhaled beta-agonists and anticholinergics, combined with systemic steroids and IV MgSO4 was central in SAA treatment. Seven PICUs (30%) used a loading dose of a short-acting beta-agonist. Eighteen PICUs (49%) used an asthma severity score, with 8 different scores applied. Seventeen PICUs (46%) observed an increasing trend in SAA admissions. Conclusion: Variations in the treatment of children with SAA mainly existed in the use of adjunct therapies and asthma severity scores. Importantl

A four-month gatifloxacin-containing regimen for treating tuberculosis.

BACKGROUND: Shortening the course of treatment for tuberculosis would be a major improvement for case management and disease control. This phase 3 trial assessed the efficacy and safety of a 4-month gatifloxacin-containing regimen for treating rifampin-sensitive pulmonary tuberculosis. METHODS: We conducted a noninferiority, randomized, open-label, controlled trial involving patients 18 to 65 years of age with smear-positive, rifampin-sensitive, newly diagnosed pulmonary tuberculosis in five sub-Saharan African countries. A standard 6-month regimen that included ethambutol during the 2-month intensive phase was compared with a 4-month regimen in which gatifloxacin (400 mg per day) was substituted for ethambutol during the intensive phase and was continued, along with rifampin and isoniazid, during the continuation phase. The primary efficacy end point was an unfavorable outcome (treatment failure, recurrence, or death or study dropout during treatment) measured 24 months after the end of treatment, with a noninferiority margin of 6 percentage points, adjusted for country. RESULTS: A total of 1836 patients were assigned to the 4-month regimen (experimental group) or the standard regimen (control group). Baseline characteristics were well balanced between the groups. At 24 months after the end of treatment, the adjusted difference in the risk of an unfavorable outcome (experimental group [21.0%] minus control group [17.2%]) in the modified intention-to-treat population (1356 patients) was 3.5 percentage points (95% confidence interval, -0.7 to 7.7). There was heterogeneity across countries (P=0.02 for interaction, with differences in the rate of an unfavorable outcome ranging from -5.4 percentage points in Guinea to 12.3 percentage points in Senegal) and in baseline cavitary status (P=0.04 for interaction) and body-mass index (P=0.10 for interaction). The standard regimen, as compared with the 4-month regimen, was associated with a higher dropout rate during treatment (5.0% vs. 2.7%) and more treatment failures (2.4% vs. 1.7%) but fewer recurrences (7.1% vs. 14.6%). There was no evidence of increased risks of prolongation of the QT interval or dysglycemia with the 4-month regimen. CONCLUSIONS: Noninferiority of the 4-month regimen to the standard regimen with respect to the primary efficacy end point was not shown. (Funded by the Special Program for Research and Training in Tropical Diseases and others; ClinicalTrials.gov number, NCT00216385.)

Optimized intermolecular potential for nitriles based on Anisotropic United Atoms model

An extension of the Anisotropic United Atoms intermolecular potential model is proposed for nitriles. The electrostatic part of the intermolecular potential is calculated using atomic charges obtained by a simple Mulliken population analysis. The repulsion-dispersion interaction parameters for methyl and methylene groups are taken from transferable AUA4 literature parameters [Ungerer et al., J. Chem. Phys., 2000, 112, 5499]. Non-bonding Lennard-Jones intermolecular potential parameters are regressed for the carbon and nitrogen atoms of the nitrile group (–C≡N) from experimental vapor-liquid equilibrium data of acetonitrile. Gibbs Ensemble Monte Carlo simulations and experimental data agreement is very good for acetonitrile, and better than previous molecular potential proposed by Hloucha et al. [J. Chem. Phys., 2000, 113, 5401]. The transferability of the resulting potential is then successfully tested, without any further readjustment, to predict vapor-liquid phase equilibrium of propionitrile and n-butyronitrile

Allelic Variation in the Toll-Like Receptor Adaptor Protein

Host genetic variation is known to contribute to differential pathogenesis following infection. Mouse models allow direct assessment of host genetic factors responsible for susceptibility to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV). Based on an assessment of early stage lines from the Collaborative Cross mouse multi-parent population, we identified two lines showing highly divergent susceptibilities to SARS-CoV: the resistant CC003/Unc and the susceptible CC053/Unc. We generated 264 F2 mice between these strains, and infected them with SARS-CoV. Weight loss, pulmonary hemorrhage, and viral load were all highly correlated disease phenotypes. We identified a quantitative trait locus of major effect on chromosome 18 (27.1-58.6 Mb) which affected weight loss, viral titer and hemorrhage. Additionally, each of these three phenotypes had distinct quantitative trait loci [Chr 9 (weight loss), Chrs 7 and 12 (virus titer), and Chr 15 (hemorrhage)]. We identified Ticam2 , an adaptor protein in the TLR signaling pathways, as a candidate driving differential disease at the Chr 18 locus. Ticam2 -/- mice were highly susceptible to SARS-CoV infection, exhibiting increased weight loss and more pulmonary hemorrhage than control mice. These results indicate a critical role for Ticam2 in SARS-CoV disease, and highlight the importance of host genetic variation in disease responses

The Use of Single-Sided NMR to Study Moisture Behaviour in an Activated Carbon Fibre/Phenolic Composite

Nuclear Magnetic Resonance (NMR) has been shown to be a useful technique to study the form and content of water in polymer composites. Composites using activated carbon fibres with phenolic resin have complex water absorption behaviour which would benefit from such investigation; however, the presence of the conductive fibres can make NMR problematic. In this study, single-sided NMR has been successfully used on such material by developing a method for sample-to-sample compensation for the effect of conductivity. Transverse relaxation curves showed water to be primarily in two states in the resin, corresponding to "bound" and "mobile" molecules. In addition, two much less bound states were identified in the composite, associated firstly with water adsorbed on to the fibre surface and secondly with clusters of water molecules moving more freely within the fibre pores

Demonstrating public value to funders and other stakeholders—the journey of ELIXIR, a virtual and distributed research infrastructure for life science data

Open Science is a founding principle of ELIXIR, a pan-European research infrastructure for life science data, with 21 Member countries plus the European Molecular Biology Laboratory. The mission of ELIXIR is to coordinate bioinformatics resources so that they form a single, integrated and pan-European infrastructure, which can be used freely by academic and private-sector researchers across the globe. As a recipient of public and charitable funding, ELIXIR must demonstrate its value, and the need to produce evidence in support of this is intensifying. Our practice-led journey towards demonstrating public value is articulated around five main challenges and, for each, we present our pragmatic approach for tackling it. We begin by showing how we are working towards demystifying what research infrastructures do. We then shed light on the sort of evidence our funders and other stakeholders are asking us for, how this evidence varies in nature and scope, and our tactics to satisfy them. We follow-on by providing our thoughts on possible barriers and solutions to embedding impact evaluation in our activities. Finally, we provide lessons learned, which we believe are sufficiently transferable and will be inspirational to other research infrastructures as they embark on their own journeys to demonstrate public value.publishedVersio

Seagrass meadows (Posidonia oceanica) distribution and trajectories of change.

Posidonia oceanica meadows are declining at alarming rates due to climate change and human activities. Although P. oceanica is considered the most important and well-studied seagrass species of the Mediterranean Sea, to date there has been a limited effort to combine all the spatial information available and provide a complete distribution of meadows across the basin. The aim of this work is to provide a fine-scale assessment of (i) the current and historical known distribution of P. oceanica, (ii) the total area of meadows and (iii) the magnitude of regressive phenomena in the last decades. The outcomes showed the current spatial distribution of P. oceanica, covering a known area of 1,224,707 ha, and highlighted the lack of relevant data in part of the basin (21,471 linear km of coastline). The estimated regression of meadows amounted to 34% in the last 50 years, showing that this generalised phenomenon had to be mainly ascribed to cumulative effects of multiple local stressors. Our results highlighted the importance of enforcing surveys to assess the status and prioritize areas where cost-effective schemes for threats reduction, capable of reversing present patterns of change and ensuring P. oceanica persistence at Mediterranean scale, could be implemented.This study was supported and financed by the Commission of the European Union (DG MARE) within the MAREA Framework contract (Call for tenders MARE/2009/05_Lot1) through the Specific Project MEDISEH (SI2.600741): Mediterranean Sensitive Habitats, that received 568.996 euro. The opinions expressed are those of the authors of the study only and do not represent the Commission’s official position. The European Commission is thankfully acknowledged.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/srep1250

Primary tumor–derived systemic nANGPTL4 inhibits metastasis

Primary tumors and distant site metastases form a bidirectionally communicating system. Yet, the molecular mechanisms of this crosstalk are poorly understood. Here, we identified the proteolytically cleaved fragments of angiopoietin-like 4 (ANGPTL4) as contextually active protumorigenic and antitumorigenic contributors in this communication ecosystem. Preclinical studies in multiple tumor models revealed that the C-terminal fragment (cANGPTL4) promoted tumor growth and metastasis. In contrast, the N-terminal fragment of ANGPTL4 (nANGPTL4) inhibited metastasis and enhanced overall survival in a postsurgical metastasis model by inhibiting WNT signaling and reducing vascularity at the metastatic site. Tracing ANGPTL4 and its fragments in tumor patients detected full-length ANGPTL4 primarily in tumor tissues, whereas nANGPTL4 predominated in systemic circulation and correlated inversely with disease progression. The study highlights the spatial context of the proteolytic cleavage-dependent pro- and antitumorigenic functions of ANGPTL4 and identifies and validates nANGPTL4 as a novel biomarker of tumor progression and antimetastatic therapeutic agent