Moytirra:Discovery of the first known deep-sea hydrothermal vent field on the slow-spreading Mid-Atlantic Ridge north of the Azores

Geological, biological, morphological, and hydrochemical data are presented for the newly discovered Moytirra vent field at 45^oN. This is the only high temperature hydrothermal vent known between the Azores and Iceland, in the North Atlantic and is located on a slow to ultraslow-spreading mid-ocean ridge uniquely situated on the 300 m high fault scarp of the eastern axial wall, 3.5 km from the axial volcanic ridge crest. Furthermore, the Moytirra vent field is, unusually for tectonically controlled hydrothermal vents systems, basalt hosted and perched midway up on the median valley wall and presumably heated by an off-axis magma chamber. The Moytirra vent field consists of an alignment of four sites of venting, three actively emitting "black smoke," producing a complex of chimneys and beehive diffusers. The largest chimney is 18 m tall and vigorously venting. The vent fauna described here are the only ones documented for the North Atlantic (Azores to Reykjanes Ridge) and significantly expands our knowledge of North Atlantic biodiversity. The surfaces of the vent chimneys are occupied by aggregations of gastropods (Peltospira sp.) and populations of alvinocaridid shrimp (Mirocaris sp. with Rimicaris sp. also present). Other fauna present include bythograeid crabs (Segonzacia sp.) and zoarcid fish (Pachycara sp.), but bathymodiolin mussels and actinostolid anemones were not observed in the vent field. The discovery of the Moytirra vent field therefore expands the known latitudinal distributions of several vent-endemic genera in the north Atlantic, and reveals faunal affinities with vents south of the Azores rather than north of Iceland. © 2013. American Geophysical Union. All Rights Reserved.

All the World's a Stage: Facilitating Discovery Science and Improved Cancer Care through the Global Alliance for Genomics and Health

The recent explosion of genetic and clinical data generated from tumor genome analysis presents an unparalleled opportunity to enhance our understanding of cancer, but this opportunity is compromised by the reluctance of many in the scientific community to share datasets and the lack of interoperability between different data platforms. The Global Alliance for Genomics and Health is addressing these barriers and challenges through a cooperative framework that encourages "team science" and responsible data sharing, complemented by the development of a series of application program interfaces that link different data platforms, thus breaking down traditional silos and liberating the data to enable new discoveries and ultimately benefit patients.

A primer for use of genetic tools in selecting and testing the suitability of set-aside sites protected from deep-sea seafloor massive sulfide mining activities

Seafloor massive sulfide (SMS) mining will likely occur at hydrothermal systems in the near future. Alongside their mineral wealth, SMS deposits also have considerable biological value. Active SMS deposits host endemic hydrothermal vent communities, whilst inactive deposits support communities of deep water corals and other suspension feeders. Mining activities are expected to remove all large organisms and suitable habitat in the immediate area, making vent endemic organisms particularly at risk from habitat loss and localised extinction. As part of environmental management strategies designed to mitigate the effects of mining, areas of seabed need to be protected to preserve biodiversity that is lost at the mine site and to preserve communities that support connectivity among populations of vent animals in the surrounding region. These "set-aside" areas need to be biologically similar to the mine site and be suitably connected, mostly by transport of larvae, to neighbouring sites to ensure exchange of genetic material among remaining populations. Establishing suitable set-asides can be a formidable task for environmental managers, however the application of genetic approaches can aid set-aside identification, suitability assessment and monitoring. There are many genetic tools available, including analysis of mitochondrial DNA (mtDNA) sequences (e.g. COI or other suitable mtDNA genes) and appropriate nuclear DNA markers (e.g. microsatellites, single nucleotide polymorphisms), environmental DNA (eDNA) techniques and microbial metagenomics. When used in concert with traditional biological survey techniques, these tools can help to identify species, assess the genetic connectivity among populations and assess the diversity of communities. How these techniques can be applied to set-aside decision making is discussed and recommendations are made for the genetic characteristics of set-aside sites. A checklist for environmental regulators forms a guide to aid decision making on the suitability of set-aside design and assessment using genetic tools. This non-technical primer document represents the views of participants in the VentBase 2014 workshop.

X-ray driven evaporation of exoplanet atmospheres: discovery of a uniquely suited test system

The evaporation of exoplanetary atmospheres is thought to be driven by high-energy irradiation. However, the actual mass loss rates are not well constrained. Co-I Kipping has recently discovered that the star KOI-314, an M1V dwarf at 65 pc distance, is orbited by two earth-sized planets, the inner one of them rocky and the outer one gaseous (P_orb = 14d and 23d). Other recent works have shown an abundance of small rocky planets in very close orbits around their host stars, suggesting that the stellar high-energy irradiation evaporates away gaseous envelopes. KOI-314 is the first nearby system in which earth-sized planets of both types are detected, allowing us to constrain the efficiency of planetary evaporation if the stellar X-ray irradiation is measured. We therefore propose a 10 ks Chandra ACIS-S pointing to determine the stellar X-ray luminosity and hardness ratio. The accuracy of the orbital solution decreases quickly due to Transit-Timing Variations, which is why we ask for DDT.

Phenotype-Based Discovery of 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol as a Novel Regulator of Ocular Angiogenesis

Retinal angiogenesis is tightly regulated to meet oxygenation and nutritional requirements. In diseases such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, uncontrolled angiogenesis can lead to blindness. Our goal is to better understand the molecular processes controlling retinal angiogenesis and discover novel drugs that inhibit retinal neovascularization. Phenotype-based chemical screens were performed using the ChemBridge Diverset^TM library and inhibition of hyaloid vessel angiogenesis in Tg(fli1:EGFP) zebrafish. 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol, (quininib) robustly inhibits developmental angiogenesis at 4–10 μM in zebrafish and significantly inhibits angiogenic tubule formation in HMEC-1 cells, angiogenic sprouting in aortic ring explants, and retinal revascularization in oxygen-induced retinopathy mice. Quininib is well tolerated in zebrafish, human cell lines, and murine eyes. Profiling screens of 153 angiogenic and inflammatory targets revealed that quininib does not directly target VEGF receptors but antagonizes cysteinyl leukotriene receptors 1 and 2 (CysLT_1–2) at micromolar IC₅₀ values. In summary, quininib is a novel anti-angiogenic small-molecule CysLT receptor antagonist. Quininib inhibits angiogenesis in a range of cell and tissue systems, revealing novel physiological roles for CysLT signaling. Quininib has potential as a novel therapeutic agent to treat ocular neovascular pathologies and may complement current anti-VEGF biological agents.

Real-space grids and the Octopus code as tools for the development of new simulation approaches for electronic systems

Real-space grids are a powerful alternative for the simulation of electronic systems. One of the main advantages of the approach is the flexibility and simplicity of working directly in real space where the different fields are discretized on a grid, combined with competitive numerical performance and great potential for parallelization. These properties constitute a great advantage at the time of implementing and testing new physical models. Based on our experience with the Octopus code, in this article we discuss how the real-space approach has allowed for the recent development of new ideas for the simulation of electronic systems. Among these applications are approaches to calculate response properties, modeling of photoemission, optimal control of quantum systems, simulation of plasmonic systems, and the exact solution of the Schrödinger equation for low-dimensionality systems.

Manufacturing System Simulation & Human Robot Interaction in VR:Manufacturing system simulation: Methodologies, software tools, case study in transportation design

Virtual Reality techniques are relatively new, having experienced significant development only during the last few years, in accordance with the progress achieved by computer science and hardware and software technologies. The study of such advanced design systems has led to the realization of an immersive environment in which new procedures for the evaluation of product prototypes, ergonomics and manufacturing operations have been simulated. The application of the environment realized to robotics, ergonomics, plant simulations and maintainability verifications has allowed us to highlight the advantages offered by a design methodology: the possibility of working on the industrial product in the first phase of conception; of placing the designer in front of the virtual reproduction of the product in a realistic way; and of interacting with the same concept. The aim of this book is to present an updated vision of VM through different aspects. We will describe the trends and results achieved in the automotive, aerospace and railway fields, in terms of the Digital Product Creation Process to design the product and the manufacturing process.

QUADrATiC: scalable gene expression connectivity mapping for repurposing FDA-approved therapeutics

Background: Gene expression connectivity mapping has proven to be a powerful and flexible tool for research. Its application has been shown in a broad range of research topics, most commonly as a means of identifying potential small molecule compounds, which may be further investigated as candidates for repurposing to treat diseases. The public release of voluminous data from the Library of Integrated Cellular Signatures (LINCS) programme further enhanced the utilities and potentials of gene expression connectivity mapping in biomedicine. Results: We describe QUADrATiC (http://go.qub.ac.uk/QUADrATiC), a user-friendly tool for the exploration of gene expression connectivity on the subset of the LINCS data set corresponding to FDA-approved small molecule compounds. It enables the identification of compounds for repurposing therapeutic potentials. The software is designed to cope with the increased volume of data over existing tools, by taking advantage of multicore computing architectures to provide a scalable solution, which may be installed and operated on a range of computers, from laptops to servers. This scalability is provided by the use of the modern concurrent programming paradigm provided by the Akka framework. The QUADrATiC Graphical User Interface (GUI) has been developed using advanced Javascript frameworks, providing novel visualization capabilities for further analysis of connections. There is also a web services interface, allowing integration with other programs or scripts.Conclusions: QUADrATiC has been shown to provide an improvement over existing connectivity map software, in terms of scope (based on the LINCS data set), applicability (using FDA-approved compounds), usability and speed. It offers potential to biological researchers to analyze transcriptional data and generate potential therapeutics for focussed study in the lab. QUADrATiC represents a step change in the process of investigating gene expression connectivity and provides more biologically-relevant results than previous alternative solutions.

Investigating Tools used to Analyse the Impact of a Wave Farm on the surrounding Wave Field

For wave energy to become commercially viable, it is predicted that wave energy converters (WECs) will need to be installed in large wave farms. This will required an extensive environmental impact study. Assessments of impacts of these sites requires prior numerical modelling however the available tools have not been fully validated.
This project investigates the area surrounding an array of five scaled WEC models using experimental techniques. It then assesses the suitability of numerical tools to be validated with this experimental data. Validated numerical tools could then be used to predict parameters relating to the models such as reflection and transmission coefficients.
The physical aspect of this project was conducted in the Portaferry wave basin owned by Queen’s University Belfast. The device studied was a bottom hinged oscillating wave surge converter (OWSC) which penetrates the surface (similar to the Oyster device). The models were tested at 40th scale.

Embracing an integromic approach to tissue biomarker research in cancer: Perspectives and lessons learned

Modern approaches to biomedical research and diagnostics targeted towards precision medicine are generating ‘big data’ across a range of high-throughput experimental and analytical platforms. Integrative analysis of this rich clinical, pathological, molecular and imaging data represents one of the greatest bottlenecks in biomarker discovery research in cancer and other diseases. Following on from the publication of our successful framework for multimodal data amalgamation and integrative analysis, Pathology Integromics in Cancer (PICan), this article will explore the essential elements of assembling an integromics framework from a more detailed perspective. PICan, built around a relational database storing curated multimodal data, is the research tool sitting at the heart of our interdisciplinary efforts to streamline biomarker discovery and validation. While recognizing that every institution has a unique set of priorities and challenges, we will use our experiences with PICan as a case study and starting point, rationalizing the design choices we made within the context of our local infrastructure and specific needs, but also highlighting alternative approaches that may better suit other programmes of research and discovery. Along the way, we stress that integromics is not just a set of tools, but rather a cohesive paradigm for how modern bioinformatics can be enhanced. Successful implementation of an integromics framework is a collaborative team effort that is built with an eye to the future and greatly accelerates the processes of biomarker discovery, validation and translation into clinical practice.

Systematic review of tools to measure outcomes for young children with autism spectrum disorder

BACKGROUND: The needs of children with autism spectrum disorder (ASD) are complex and this is reflected in the number and diversity of outcomes assessed and measurement tools used to collect evidence about children's progress. Relevant outcomes include improvement in core ASD impairments, such as communication, social awareness, sensory sensitivities and repetitiveness; skills such as social functioning and play; participation outcomes such as social inclusion; and parent and family impact.

OBJECTIVES: To examine the measurement properties of tools used to measure progress and outcomes in children with ASD up to the age of 6 years. To identify outcome areas regarded as important by people with ASD and parents.

METHODS: The MeASURe (Measurement in Autism Spectrum disorder Under Review) research collaboration included ASD experts and review methodologists. We undertook systematic review of tools used in ASD early intervention and observational studies from 1992 to 2013; systematic review, using the COSMIN checklist (Consensus-based Standards for the selection of health Measurement Instruments) of papers addressing the measurement properties of identified tools in children with ASD; and synthesis of evidence and gaps. The review design and process was informed throughout by consultation with stakeholders including parents, young people with ASD, clinicians and researchers.

RESULTS: The conceptual framework developed for the review was drawn from the International Classification of Functioning, Disability and Health, including the domains 'Impairments', 'Activity Level Indicators', 'Participation', and 'Family Measures'. In review 1, 10,154 papers were sifted - 3091 by full text - and data extracted from 184; in total, 131 tools were identified, excluding observational coding, study-specific measures and those not in English. In review 2, 2665 papers were sifted and data concerning measurement properties of 57 (43%) tools were extracted from 128 papers. Evidence for the measurement properties of the reviewed tools was combined with information about their accessibility and presentation. Twelve tools were identified as having the strongest supporting evidence, the majority measuring autism characteristics and problem behaviour. The patchy evidence and limited scope of outcomes measured mean these tools do not constitute a 'recommended battery' for use. In particular, there is little evidence that the identified tools would be good at detecting change in intervention studies. The obvious gaps in available outcome measurement include well-being and participation outcomes for children, and family quality-of-life outcomes, domains particularly valued by our informants (young people with ASD and parents).

CONCLUSIONS: This is the first systematic review of the quality and appropriateness of tools designed to monitor progress and outcomes of young children with ASD. Although it was not possible to recommend fully robust tools at this stage, the review consolidates what is known about the field and will act as a benchmark for future developments. With input from parents and other stakeholders, recommendations are made about priority targets for research.

FUTURE WORK: Priorities include development of a tool to measure child quality of life in ASD, and validation of a potential primary outcome tool for trials of early social communication intervention.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002223.

FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Systematic Review of the Measurement Properties of Tools Used to Measure Behaviour Problems in Young Children with Autism

Background
Behaviour problems are common in young children with autism spectrum disorder (ASD). There are many different tools used to measure behavior problems but little is known about their validity for the population.

Objectives
To evaluate the measurement properties of behaviour problems tools used in evaluation of intervention or observational research studies with children with ASD up to the age of six years.

Methods
Behaviour measurement tools were identified as part of a larger, two stage, systematic review. First, sixteen major electronic databases, as well as grey literature and research registers were searched, and tools used listed and categorized. Second, using methodological filters, we searched for articles examining the measurement properties of the tools in use with young children with ASD in ERIC, MEDLINE, EMBASE, CINAHL, and PsycINFO. The quality of these papers was then evaluated using the COSMIN checklist.

Results
We identified twelve tools which had been used to measure behaviour problems in young children with ASD, and fifteen studies which investigated the measurement properties of six of these tools. There was no evidence available for the remaining six tools. Two questionnaires were found to be the most robust in their measurement properties, the Child Behavior Checklist and the Home Situations Questionnaire—Pervasive Developmental Disorders version.

Conclusions
We found patchy evidence on reliability and validity, for only a few of the tools used to measure behaviour problems in young children with ASD. More systematic research is required on measurement properties of tools for use in this population, in particular to establish responsiveness to change which is essential in measurement of outcomes of intervention.

PROSPERO Registration Number

CRD42012002223