Accuracy of five algorithms to diagnose gambiense human African trypanosomiasis.

Algorithms to diagnose gambiense human African trypanosomiasis (HAT, sleeping sickness) are often complex due to the unsatisfactory sensitivity and/or specificity of available tests, and typically include a screening (serological), confirmation (parasitological) and staging component. There is insufficient evidence on the relative accuracy of these algorithms. This paper presents estimates of the accuracy of five algorithms used by past Médecins Sans Frontières programmes in the Republic of Congo, Southern Sudan and Uganda

Gravito-electromagnetic analogies

We reexamine and further develop different gravito-electromagnetic (GEM) analogies found in the literature, and clarify the connection between them. Special emphasis is placed in two exact physical analogies: the analogy based on inertial fields from the so-called "1+3 formalism", and the analogy based on tidal tensors. Both are reformulated, extended and generalized. We write in both formalisms the Maxwell and the full exact Einstein field equations with sources, plus the algebraic Bianchi identities, which are cast as the source-free equations for the gravitational field. New results within each approach are unveiled. The well known analogy between linearized gravity and electromagnetism in Lorentz frames is obtained as a limiting case of the exact ones. The formal analogies between the Maxwell and Weyl tensors are also discussed, and, together with insight from the other approaches, used to physically interpret gravitational radiation. The precise conditions under which a similarity between gravity and electromagnetism occurs are discussed, and we conclude by summarizing the main outcome of each approach.Comment: 60 pages, 2 figures. Improved version (compared to v2) with some re-write, notation improvements and a new figure that match the published version; expanded compared to the published version to include Secs. 2.3 and

The dependence of dijet production on photon virtuality in ep collisions at HERA

The dependence of dijet production on the virtuality of the exchanged photon, Q^2, has been studied by measuring dijet cross sections in the range 0 < Q^2 < 2000 GeV^2 with the ZEUS detector at HERA using an integrated luminosity of 38.6 pb^-1. Dijet cross sections were measured for jets with transverse energy E_T^jet > 7.5 and 6.5 GeV and pseudorapidities in the photon-proton centre-of-mass frame in the range -3 < eta^jet <0. The variable xg^obs, a measure of the photon momentum entering the hard process, was used to enhance the sensitivity of the measurement to the photon structure. The Q^2 dependence of the ratio of low- to high-xg^obs events was measured. Next-to-leading-order QCD predictions were found to generally underestimate the low-xg^obs contribution relative to that at high xg^obs. Monte Carlo models based on leading-logarithmic parton-showers, using a partonic structure for the photon which falls smoothly with increasing Q^2, provide a qualitative description of the data.Comment: 35 pages, 6 eps figures, submitted to Eur.Phys.J.

Development and Validity of the Rating-of-Fatigue Scale

Objective: The purpose of these experiments was to develop a rating-of-fatigue (ROF) scale capable of tracking the intensity of perceived fatigue in a variety of contexts. Methods: Four experiments were carried out. The first provided the evidential basis for the construction of the ROF scale. The second tested the face validity of the ROF, and the third tested the convergent and divergent validity of the ROF scale during ramped cycling to exhaustion and 30 min of resting recovery. The final experiment tested the convergent validity of the ROF scale with time of day and physical activity (accelerometer counts) across a whole week. Results: Modal selections of descriptions and diagrams at different levels of exertion and recovery were found during Experiment 1 upon which the ROF scale was constructed and finalised. In Experiment 2, a high level of face validity was indicated, in that ROF was reported to represent fatigue rather than exertion. Descriptor and diagrammatic elements of ROF reportedly added to the coherence and ease of use of the scale. In Experiment 3, high convergence between ROF and various physiological measures were found during exercise and recovery (heart rate, blood lactate concentration, oxygen uptake, carbon dioxide production, respiratory exchange ratio and ventilation rate were all P < 0.001). During ramped cycling to exhaustion ROF and RPE did correspond (P < 0.0001) but not during recovery, demonstrating discriminant validity. Experiment 4 found ROF to correspond with waking time during each day (Mon–Sun all P < 0.0001) and with physical activity (accelerometer count) (Mon–Sun all P < 0.001). Conclusions: The ROF scale has good face validity and high levels of convergent validity during ramped cycling to exhaustion, resting recovery and daily living activities. The ROF scale has both theoretical and applied potential in understanding changes in fatigue in a variety of contexts

Lack of Detectable HIV-1 Molecular Evolution during Suppressive Antiretroviral Therapy

A better understanding of changes in HIV-1 population genetics with combination antiretroviral therapy (cART) is critical for designing eradication strategies. We therefore analyzed HIV-1 genetic variation and divergence in patients' plasma before cART, during suppression on cART, and after viral rebound. Single-genome sequences of plasma HIV-1 RNA were obtained from HIV-1 infected patients prior to cART (N = 14), during suppression on cART (N = 14) and/or after viral rebound following interruption of cART (N = 5). Intra-patient population diversity was measured by average pairwise difference (APD). Population structure was assessed by phylogenetic analyses and a test for panmixia. Measurements of intra-population diversity revealed no significant loss of overall genetic variation in patients treated for up to 15 years with cART. A test for panmixia, however, showed significant changes in population structure in 2/10 patients after short-term cART (<1 year) and in 7/10 patients after long-term cART (1-15 years). The changes consisted of diverse sets of viral variants prior to cART shifting to populations containing one or more genetically uniform subpopulations during cART. Despite these significant changes in population structure, rebound virus after long-term cART had little divergence from pretherapy virus, implicating long-lived cells infected before cART as the source for rebound virus. The appearance of genetically uniform virus populations and the lack of divergence after prolonged cART and cART interruption provide strong evidence that HIV-1 persists in long-lived cells infected before cART was initiated, that some of these infected cells may be capable of proliferation, and that on-going cycles of viral replication are not evident

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Spatio-Temporal Variation in Length-Weight Relationships and Condition of the Ribbonfish Trichiurus lepturus (Linnaeus, 1758): Implications for Fisheries Management

Knowledge of length-weight relationships for commercially exploited fish is an important tool for assessing and managing of fish stocks. However, analyses of length-weight relationship fisheries data typically do not consider the inherent differences in length-weight relationships for fish caught from different habitats, seasons, or years, and this can affect the utility of these data for developing condition indices or calculating fisheries biomass. Here, we investigated length-weight relationships for ribbonfish Trichiurus lepturus in the waters of the Arabian Sea off Oman collected during three periods (2001-02, 2007-08, and 2014-15) and showed that a multivariate modelling approach that considers the areas and seasons in which ribbonfish were caught improved estimation of length-weight relationships. We used the outputs of these models to explore spatio-temporal variations in condition indices and relative weights among ribbonfish, revealing fish of 85-125 cm were in the best overall condition. We also found that condition differed according to where and when fish were caught, with condition lowest during spring and pre-south-west monsoon periods and highest during and after the south-west monsoons. We interpret these differences to be a consequence of variability in temperature and food availability. Based on our findings, we suggest fishing during seasons that have the lowest impact on fish condition and which are commercially most viable; such fishery management would enhance fisheries conservation and economic revenue in the region

Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications.

Methylation of cytosine deoxynucleotides generates 5-methylcytosine (m(5)dC), a well-established epigenetic mark. However, in higher eukaryotes much less is known about modifications affecting other deoxynucleotides. Here, we report the detection of N(6)-methyldeoxyadenosine (m(6)dA) in vertebrate DNA, specifically in Xenopus laevis but also in other species including mouse and human. Our methylome analysis reveals that m(6)dA is widely distributed across the eukaryotic genome and is present in different cell types but is commonly depleted from gene exons. Thus, direct DNA modifications might be more widespread than previously thought.M.J.K. was supported by the Long-Term Human Frontiers Fellowship (LT000149/2010-L), the Medical Research Council grant (G1001690), and by the Isaac Newton Trust Fellowship (R G76588). The work was sponsored by the Biotechnology and Biological Sciences Research Council grant BB/M022994/1 (J.B.G. and M.J.K.). The Gurdon laboratory is funded by the grant 101050/Z/13/Z (J.B.G.) from the Wellcome Trust, and is supported by the Gurdon Institute core grants, namely by the Wellcome Trust Core Grant (092096/Z/10/Z) and by the Cancer Research UK Grant (C6946/A14492). C.R.B. and G.E.A. are funded by the Wellcome Trust Core Grant. We are grateful to D. Simpson and R. Jones-Green for preparing X. laevis eggs and oocytes, F. Miller for providing us with M. musculus tissue, T. Dyl for X. laevis eggs and D. rerio samples, and to Gurdon laboratory members for their critical comments. We thank U. Ruether for providing us with M. musculus kidney DNA (Entwicklungs- und Molekularbiologie der Tiere, Heinrich Heine Universitaet Duesseldorf, Germany). We also thank J. Ahringer, S. Jackson, A. Bannister and T. Kouzarides for critical input and advice, M. Sciacovelli and E. Gaude for suggestions.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nsmb.314

Chromatin loop anchors are associated with genome instability in cancer and recombination hotspots in the germline

Abstract Background Chromatin loops form a basic unit of interphase nuclear organization, with chromatin loop anchor points providing contacts between regulatory regions and promoters. However, the mutational landscape at these anchor points remains under-studied. Here, we describe the unusual patterns of somatic mutations and germline variation associated with loop anchor points and explore the underlying features influencing these patterns. Results Analyses of whole genome sequencing datasets reveal that anchor points are strongly depleted for single nucleotide variants (SNVs) in tumours. Despite low SNV rates in their genomic neighbourhood, anchor points emerge as sites of evolutionary innovation, showing enrichment for structural variant (SV) breakpoints and a peak of SNVs at focal CTCF sites within the anchor points. Both CTCF-bound and non-CTCF anchor points harbour an excess of SV breakpoints in multiple tumour types and are prone to double-strand breaks in cell lines. Common fragile sites, which are hotspots for genome instability, also show elevated numbers of intersecting loop anchor points. Recurrently disrupted anchor points are enriched for genes with functions in cell cycle transitions and regions associated with predisposition to cancer. We also discover a novel class of CTCF-bound anchor points which overlap meiotic recombination hotspots and are enriched for the core PRDM9 binding motif, suggesting that the anchor points have been foci for diversity generated during recent human evolution. Conclusions We suggest that the unusual chromatin environment at loop anchor points underlies the elevated rates of variation observed, marking them as sites of regulatory importance but also genomic fragility

FOXM1 binds directly to non-consensus sequences in the human genome.

BACKGROUND: The Forkhead (FKH) transcription factor FOXM1 is a key regulator of the cell cycle and is overexpressed in most types of cancer. FOXM1, similar to other FKH factors, binds to a canonical FKH motif in vitro. However, genome-wide mapping studies in different cell lines have shown a lack of enrichment of the FKH motif, suggesting an alternative mode of chromatin recruitment. We have investigated the role of direct versus indirect DNA binding in FOXM1 recruitment by performing ChIP-seq with wild-type and DNA binding deficient FOXM1. RESULTS: An in vitro fluorescence polarization assay identified point mutations in the DNA binding domain of FOXM1 that inhibit binding to a FKH consensus sequence. Cell lines expressing either wild-type or DNA binding deficient GFP-tagged FOXM1 were used for genome-wide mapping studies comparing the distribution of the DNA binding deficient protein to the wild-type. This shows that interaction of the FOXM1 DNA binding domain with target DNA is essential for recruitment. Moreover, analysis of the protein interactome of wild-type versus DNA binding deficient FOXM1 shows that the reduced recruitment is not due to inhibition of protein-protein interactions. CONCLUSIONS: A functional DNA binding domain is essential for FOXM1 chromatin recruitment. Even in FOXM1 mutants with almost complete loss of binding, the protein-protein interactions and pattern of phosphorylation are largely unaffected. These results strongly support a model whereby FOXM1 is specifically recruited to chromatin through co-factor interactions by binding directly to non-canonical DNA sequences.We would like to acknowledge the Genomics and bioinformatics core at the CRUK Research Institute for the Illumina sequencing and the Proteomics core for the LC/MS-MS protein analysis for the RIME experiments. We acknowledge the support from The University of Cambridge and Cancer Research UK. The Balasubramanian Laboratory is supported by core funding from Cancer Research UK (C14303/A17197). SB is a Wellcome Trust Principle Investigator.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13059-015-0696-