Joining up health and bioinformatics: e-science meets e-health

CLEF (Co-operative Clinical e-Science Framework) is an MRC sponsored project in the e-Science programme that aims to establish methodologies and a technical infrastructure forthe next generation of integrated clinical and bioscience research. It is developing methodsfor managing and using pseudonymised repositories of the long-term patient histories whichcan be linked to genetic, genomic information or used to support patient care. CLEF concentrateson removing key barriers to managing such repositories ? ethical issues, informationcapture, integration of disparate sources into coherent ?chronicles? of events, userorientedmechanisms for querying and displaying the information, and compiling the requiredknowledge resources. This paper describes the overall information flow and technicalapproach designed to meet these aims within a Grid framework

Low-frequency QPO from the 11 Hz accreting pulsar in Terzan 5: not frame dragging

We report on 6 RXTE observations taken during the 2010 outburst of the 11 Hz accreting pulsar IGR J17480-2446 located in the globular cluster Terzan 5. During these observations we find power spectra which resemble those seen in Z-type high-luminosity neutron star low-mass X-ray binaries, with a quasi-periodic oscillation (QPO) in the 35-50 Hz range simultaneous with a kHz QPO and broad band noise. Using well known frequency-frequency correlations, we identify the 35-50 Hz QPOs as the horizontal branch oscillations (HBO), which were previously suggested to be due to Lense-Thirring precession. As IGR J17480-2446 spins more than an order of magnitude more slowly than any of the other neutron stars where these QPOs were found, this QPO can not be explained by frame dragging. By extension, this casts doubt on the Lense-Thirring precession model for other low-frequency QPOs in neutron-star and perhaps even black-hole systems.Comment: 6 pages, 5 figures, Accepted for publication in ApJ

Dynamic mooring simulation with Code_Aster with application to a floating wind turbine

This is the final version of the article. Available from Elsevier via the DOI in this record.The design of reliable station-keeping systems for permanent floating structures such as offshore renewable energy devices is vital to their lifelong integrity. In highly dynamic and/or deep-water applications, including hydrodynamics and structural dynamics in the mooring analysis is paramount for the accurate prediction of the loading on the lines and hence their dimensioning. This article presents a new workflow based on EDF R&D's open-source, finite-element analysis tool Code_Aster, enabling the dynamic analysis of catenary mooring systems, with application to a floating wind turbine concept. The University of Maine DeepCwind-OC4 basin test campaign is used for validation, showing that Code_Aster can satisfactorily predict the fairlead tensions in both regular and irregular waves. In the latter case, all of the three main spectral components of tension observed in the experiments are found numerically. Also, the dynamic line tension is systematically compared with that provided by the classic quasi-static approach, thereby confirming its limitations. Robust dynamic simulation of catenary moorings is shown to be possible using this generalist finite-element software, provided that the inputs be organised consistently with the physics of offshore hydromechanics.IDCORE is funded by the ETI and the RCUK Energy programme, grant number EP/J500847/1. The authors are grateful for the funding provided by these institutions, and to EDF R&D for hosting and supervising the industrial doctorate which expressed the present work

Tracking Cyber Adversaries with Adaptive Indicators of Compromise

A forensics investigation after a breach often uncovers network and host indicators of compromise (IOCs) that can be deployed to sensors to allow early detection of the adversary in the future. Over time, the adversary will change tactics, techniques, and procedures (TTPs), which will also change the data generated. If the IOCs are not kept up-to-date with the adversary's new TTPs, the adversary will no longer be detected once all of the IOCs become invalid. Tracking the Known (TTK) is the problem of keeping IOCs, in this case regular expressions (regexes), up-to-date with a dynamic adversary. Our framework solves the TTK problem in an automated, cyclic fashion to bracket a previously discovered adversary. This tracking is accomplished through a data-driven approach of self-adapting a given model based on its own detection capabilities. In our initial experiments, we found that the true positive rate (TPR) of the adaptive solution degrades much less significantly over time than the naive solution, suggesting that self-updating the model allows the continued detection of positives (i.e., adversaries). The cost for this performance is in the false positive rate (FPR), which increases over time for the adaptive solution, but remains constant for the naive solution. However, the difference in overall detection performance, as measured by the area under the curve (AUC), between the two methods is negligible. This result suggests that self-updating the model over time should be done in practice to continue to detect known, evolving adversaries.Comment: This was presented at the 4th Annual Conf. on Computational Science & Computational Intelligence (CSCI'17) held Dec 14-16, 2017 in Las Vegas, Nevada, US

A Role for the Vacuolating Cytotoxin, VacA, in Colonization and Helicobacter pylori-Induced Metaplasia in the Stomach

Carriage of Helicobacter pylori strains producing more active (s1/i1) forms of VacA is strongly associated with gas-tric adenocarcinoma. To our knowledge, we are the first to determine effects of different polymorphic forms of VacA on inflammation and metaplasia in the mouse stomach. Bacteria producing the less active s2/i2 form of VacA colonized mice more efficiently than mutants null for VacA or producing more active forms of it, providing the first evidence of a positive role for the minimally active s2/i2 toxin. Strains producing more active toxin forms induced more severe and extensive metaplasia and in flammation in the mouse stomach than strains producing weakly active (s2/i2) toxin. We also examined the association in humans, controlling for cag PAI status. In human gastric biopsy specimens, the vacA i1 allele was strongly associated with precancerous intestinal metaplasia, with almost complete absence of intestinal metaplasia in subjects infected with i2-type strains, even in a vacA s1, cagA+ background

A NICER Discovery of a Low-Frequency Quasi-Periodic Oscillation in the Soft-Intermediate State of MAXI J1535-571

We present the discovery of a low-frequency $\approx 5.7$ Hz quasi-periodic oscillation (QPO) feature in observations of the black hole X-ray binary MAXI J1535-571 in its soft-intermediate state, obtained in September-October 2017 by the Neutron Star Interior Composition Explorer (NICER). The feature is relatively broad (compared to other low-frequency QPOs; quality factor $Q\approx 2$) and weak (1.9% rms in 3-10 keV), and is accompanied by a weak harmonic and low-amplitude broadband noise. These characteristics identify it as a weak Type A/B QPO, similar to ones previously identified in the soft-intermediate state of the transient black hole X-ray binary XTE J1550-564. The lag-energy spectrum of the QPO shows increasing soft lags towards lower energies, approaching 50 ms at 1 keV (with respect to a 3-10 keV continuum). This large phase shift has similar amplitude but opposite sign to that seen in Rossi X-ray Timing Explorer data for a Type B QPO from the transient black hole X-ray binary GX 339-4. Previous phase-resolved spectroscopy analysis of the Type B QPO in GX 339-4 pointed towards a precessing jet-like corona illuminating the accretion disk as the origin of the QPO signal. We suggest that this QPO in MAXI J1535-571 may have the same origin, with the different lag sign depending on the scale height of the emitting region and the observer inclination angle.Comment: Accepted for publication in ApJ Letter

The impact of hunting on tropical mammal and bird populations

Hunting is a major driver of biodiversity loss, but a systematic large-scale estimate of hunting-induced defaunation is lacking. We synthesized 176 studies to quantify hunting-induced declines of mammal and bird populations across the tropics. Bird and mammal abundances declined by 58% (25 to 76%) and by 83% (72 to 90%) in hunted compared with unhunted areas. Bird and mammal populations were depleted within 7 and 40 kilometers from hunters’ access points (roads and settlements). Additionally, hunting pressure was higher in areas with better accessibility to major towns where wild meat could be traded. Mammal population densities were lower outside protected areas, particularly because of commercial hunting. Strategies to sustainably manage wild meat hunting in both protected and unprotected tropical ecosystems are urgently needed to avoid further defaunation

Some distorted thoughts about ketamine as a psychedelic and a novel hypothesis based on NMDA receptor-mediated synaptic plasticity.

Ketamine, a channel blocking NMDA receptor antagonist, is used off-label for its psychedelic effects, which may arise from a combination of several inter-related actions. Firstly, reductions of the contribution of NMDA receptors to afferent information from external and internal sensory inputs may distort sensations and their processing in higher brain centres. Secondly, reductions of NMDA receptor-mediated excitation of GABAergic interneurons can result in glutamatergic overactivity. Thirdly, limbic cortical disinhibition may indirectly enhance dopaminergic and serotonergic activity. Fourthly, inhibition of NMDA receptor mediated synaptic plasticity, such as short-term potentiation (STP) and long-term potentiation (LTP), could lead to distorted memories. Here, for the first time, we compared quantitatively the effects of ketamine on STP and LTP. We report that ketamine inhibits STP in a double sigmoidal fashion with low (40 nM) and high (5.6 μM) IC50 values. In contrast, ketamine inhibits LTP in a single sigmoidal manner (IC50 value ∼ 15 μM). A GluN2D-subunit preferring NMDA receptor antagonist, UBP145, has a similar pharmacological profile. We propose that the psychedelic effects of ketamine may involve the inhibition of STP and, potentially, associated forms of working memory. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'