Showing papers by "Cardiff University published in 2017"
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TL;DR: The association of GRB 170817A, detected by Fermi-GBM 1.7 s after the coalescence, corroborates the hypothesis of a neutron star merger and provides the first direct evidence of a link between these mergers and short γ-ray bursts.
Abstract: On August 17, 2017 at 12∶41:04 UTC the Advanced LIGO and Advanced Virgo gravitational-wave detectors made their first observation of a binary neutron star inspiral. The signal, GW170817, was detected with a combined signal-to-noise ratio of 32.4 and a false-alarm-rate estimate of less than one per 8.0×10^{4} years. We infer the component masses of the binary to be between 0.86 and 2.26 M_{⊙}, in agreement with masses of known neutron stars. Restricting the component spins to the range inferred in binary neutron stars, we find the component masses to be in the range 1.17-1.60 M_{⊙}, with the total mass of the system 2.74_{-0.01}^{+0.04}M_{⊙}. The source was localized within a sky region of 28 deg^{2} (90% probability) and had a luminosity distance of 40_{-14}^{+8} Mpc, the closest and most precisely localized gravitational-wave signal yet. The association with the γ-ray burst GRB 170817A, detected by Fermi-GBM 1.7 s after the coalescence, corroborates the hypothesis of a neutron star merger and provides the first direct evidence of a link between these mergers and short γ-ray bursts. Subsequent identification of transient counterparts across the electromagnetic spectrum in the same location further supports the interpretation of this event as a neutron star merger. This unprecedented joint gravitational and electromagnetic observation provides insight into astrophysics, dense matter, gravitation, and cosmology.
7,327 citations
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Harvard University1, University of Sheffield2, University of Warwick3, Vita-Salute San Raffaele University4, University of Bern5, St James's University Hospital6, Katholieke Universiteit Leuven7, Aberdeen Royal Infirmary8, University of Aberdeen9, Cardiff University10, Netherlands Cancer Institute11, Erasmus University Rotterdam12
TL;DR: The 2016 EAU-STRO-IOG Prostate Cancer (PCa) Guidelines present updated information on the diagnosis, and treatment of clinically localised prostate cancer and reflect the multidisciplinary nature of PCa management.
2,767 citations
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TL;DR: In this paper, the authors used the observed time delay of $(+1.74\pm 0.05)\,{\rm{s}}$ between GRB 170817A and GW170817 to constrain the difference between the speed of gravity and speed of light to be between $-3
Abstract: On 2017 August 17, the gravitational-wave event GW170817 was observed by the Advanced LIGO and Virgo detectors, and the gamma-ray burst (GRB) GRB 170817A was observed independently by the Fermi Gamma-ray Burst Monitor, and the Anti-Coincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory. The probability of the near-simultaneous temporal and spatial observation of GRB 170817A and GW170817 occurring by chance is $5.0\times {10}^{-8}$. We therefore confirm binary neutron star mergers as a progenitor of short GRBs. The association of GW170817 and GRB 170817A provides new insight into fundamental physics and the origin of short GRBs. We use the observed time delay of $(+1.74\pm 0.05)\,{\rm{s}}$ between GRB 170817A and GW170817 to: (i) constrain the difference between the speed of gravity and the speed of light to be between $-3\times {10}^{-15}$ and $+7\times {10}^{-16}$ times the speed of light, (ii) place new bounds on the violation of Lorentz invariance, (iii) present a new test of the equivalence principle by constraining the Shapiro delay between gravitational and electromagnetic radiation. We also use the time delay to constrain the size and bulk Lorentz factor of the region emitting the gamma-rays. GRB 170817A is the closest short GRB with a known distance, but is between 2 and 6 orders of magnitude less energetic than other bursts with measured redshift. A new generation of gamma-ray detectors, and subthreshold searches in existing detectors, will be essential to detect similar short bursts at greater distances. Finally, we predict a joint detection rate for the Fermi Gamma-ray Burst Monitor and the Advanced LIGO and Virgo detectors of 0.1–1.4 per year during the 2018–2019 observing run and 0.3–1.7 per year at design sensitivity.
2,633 citations
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TL;DR: The magnitude of modifications to the gravitational-wave dispersion relation is constrain, the graviton mass is bound to m_{g}≤7.7×10^{-23} eV/c^{2} and null tests of general relativity are performed, finding that GW170104 is consistent with general relativity.
Abstract: We describe the observation of GW170104, a gravitational-wave signal produced by the coalescence of a pair of stellar-mass black holes. The signal was measured on January 4, 2017 at 10∶11:58.6 UTC by the twin advanced detectors of the Laser Interferometer Gravitational-Wave Observatory during their second observing run, with a network signal-to-noise ratio of 13 and a false alarm rate less than 1 in 70 000 years. The inferred component black hole masses are 31.2^(8.4) _(−6.0)M_⊙ and 19.4^(5.3)_( −5.9)M_⊙ (at the 90% credible level). The black hole spins are best constrained through measurement of the effective inspiral spin parameter, a mass-weighted combination of the spin components perpendicular to the orbital plane, χ_(eff) = −0.12^(0.21)_( −0.30). This result implies that spin configurations with both component spins positively aligned with the orbital angular momentum are disfavored. The source luminosity distance is 880^(450)_(−390) Mpc corresponding to a redshift of z = 0.18^(0.08)_( −0.07) . We constrain the magnitude of modifications to the gravitational-wave dispersion relation and perform null tests of general relativity. Assuming that gravitons are dispersed in vacuum like massive particles, we bound the graviton mass to m_g ≤ 7.7 × 10^(−23) eV/c^2. In all cases, we find that GW170104 is consistent with general relativity.
2,569 citations
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21 Jul 2017
TL;DR: A unified implementation of the Faster R-CNN, R-FCN and SSD systems is presented and the speed/accuracy trade-off curve created by using alternative feature extractors and varying other critical parameters such as image size within each of these meta-architectures is traced out.
Abstract: The goal of this paper is to serve as a guide for selecting a detection architecture that achieves the right speed/memory/accuracy balance for a given application and platform. To this end, we investigate various ways to trade accuracy for speed and memory usage in modern convolutional object detection systems. A number of successful systems have been proposed in recent years, but apples-toapples comparisons are difficult due to different base feature extractors (e.g., VGG, Residual Networks), different default image resolutions, as well as different hardware and software platforms. We present a unified implementation of the Faster R-CNN [30], R-FCN [6] and SSD [25] systems, which we view as meta-architectures and trace out the speed/accuracy trade-off curve created by using alternative feature extractors and varying other critical parameters such as image size within each of these meta-architectures. On one extreme end of this spectrum where speed and memory are critical, we present a detector that achieves real time speeds and can be deployed on a mobile device. On the opposite end in which accuracy is critical, we present a detector that achieves state-of-the-art performance measured on the COCO detection task.
2,484 citations
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TL;DR: For the first time, the nature of gravitational-wave polarizations from the antenna response of the LIGO-Virgo network is tested, thus enabling a new class of phenomenological tests of gravity.
Abstract: On August 14, 2017 at 10∶30:43 UTC, the Advanced Virgo detector and the two Advanced LIGO detectors coherently observed a transient gravitational-wave signal produced by the coalescence of two stellar mass black holes, with a false-alarm rate of ≲1 in 27 000 years. The signal was observed with a three-detector network matched-filter signal-to-noise ratio of 18. The inferred masses of the initial black holes are 30.5-3.0+5.7M⊙ and 25.3-4.2+2.8M⊙ (at the 90% credible level). The luminosity distance of the source is 540-210+130 Mpc, corresponding to a redshift of z=0.11-0.04+0.03. A network of three detectors improves the sky localization of the source, reducing the area of the 90% credible region from 1160 deg2 using only the two LIGO detectors to 60 deg2 using all three detectors. For the first time, we can test the nature of gravitational-wave polarizations from the antenna response of the LIGO-Virgo network, thus enabling a new class of phenomenological tests of gravity.
1,979 citations
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TL;DR: This work argues for the adoption of measures to optimize key elements of the scientific process: methods, reporting and dissemination, reproducibility, evaluation and incentives, in the hope that this will facilitate action toward improving the transparency, reproducible and efficiency of scientific research.
Abstract: Improving the reliability and efficiency of scientific research will increase the credibility of the published scientific literature and accelerate discovery. Here we argue for the adoption of measures to optimize key elements of the scientific process: methods, reporting and dissemination, reproducibility, evaluation and incentives. There is some evidence from both simulations and empirical studies supporting the likely effectiveness of these measures, but their broad adoption by researchers, institutions, funders and journals will require iterative evaluation and improvement. We discuss the goals of these measures, and how they can be implemented, in the hope that this will facilitate action toward improving the transparency, reproducibility and efficiency of scientific research.
1,951 citations
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University College London1, London Research Institute2, University of Leicester3, Francis Crick Institute4, University of Manchester5, University of Birmingham6, Glenfield Hospital7, Middlesex University8, Princess Alexandra Hospital NHS Trust9, Cardiff University10, University of Oxford11, Max Delbrück Center for Molecular Medicine12, Katholieke Universiteit Leuven13
TL;DR: Intratumor heterogeneity mediated through chromosome instability was associated with an increased risk of recurrence or death, a finding that supports the potential value of chromosome instability as a prognostic predictor.
Abstract: BackgroundAmong patients with non–small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC. MethodsIn this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy. We sequenced and analyzed 327 tumor regions to define evolutionary histories, obtain a census of clonal and subclonal events, and assess the relationship between intratumor heterogeneity and recurrence-free survival. ResultsWe observed widespread intratumor heterogeneity for both somatic copy-number alterations and mutations. Driver mutations in EGFR, MET, BRAF, and TP53 were almost always clonal. However, heterogeneous driver alterations that occurred later in evolution w...
1,679 citations
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Royal Liverpool University Hospital1, University of Liverpool2, Clatterbridge Cancer Centre NHS Foundation Trust3, University of Manchester4, Manchester Royal Infirmary5, The Royal Marsden NHS Foundation Trust6, Weston Park Hospital7, Royal Free Hospital8, St James's University Hospital9, Karolinska Institutet10, Uppsala University11, University of Hamburg12, Royal Surrey County Hospital13, Guy's Hospital14, Hammersmith Hospital15, Beatson West of Scotland Cancer Centre16, Cardiff University17, Queen Elizabeth Hospital Birmingham18, Churchill Hospital19, Derriford Hospital20, University Hospital Coventry21, Heidelberg University22
TL;DR: The adjuvant combination of gem citabine and capecitabine should be the new standard of care following resection for pancreatic ductal adenocarcinoma.
1,378 citations
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TL;DR: The 2016 EAU-ESTRO-SIOG Guidelines on PCa summarise the most recent findings and advice for use in clinical practice and reflect the multidisciplinary nature of PCa management.
1,271 citations
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TL;DR: In this article, a GW signal from the merger of two stellar-mass black holes was observed by the two Advanced Laser Interferometer Gravitational-Wave Observatory detectors with a network signal-to-noise ratio of 13.5%.
Abstract: On 2017 June 8 at 02:01:16.49 UTC, a gravitational-wave (GW) signal from the merger of two stellar-mass black holes was observed by the two Advanced Laser Interferometer Gravitational-Wave Observatory detectors with a network signal-to-noise ratio of 13. This system is the lightest black hole binary so far observed, with component masses of ${12}_{-2}^{+7}\,{M}_{\odot }$ and ${7}_{-2}^{+2}\,{M}_{\odot }$ (90% credible intervals). These lie in the range of measured black hole masses in low-mass X-ray binaries, thus allowing us to compare black holes detected through GWs with electromagnetic observations. The source's luminosity distance is ${340}_{-140}^{+140}\,\mathrm{Mpc}$, corresponding to redshift ${0.07}_{-0.03}^{+0.03}$. We verify that the signal waveform is consistent with the predictions of general relativity.
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University College London1, Francis Crick Institute2, Natera3, University of Leicester4, Harvard University5, Brigham and Women's Hospital6, Institute of Cancer Research7, The Royal Marsden NHS Foundation Trust8, University of Manchester9, University of Birmingham10, University of Aberdeen11, Glenfield Hospital12, Middlesex University13, Royal Free Hospital14, Princess Alexandra Hospital15, Royal Surrey County Hospital16, Ashford University17, Cardiff University18, University Hospital of Wales19, Whittington Hospital20, Boston Children's Hospital21, Technical University of Denmark22, Semmelweis University23, Max Delbrück Center for Molecular Medicine24, Katholieke Universiteit Leuven25
TL;DR: It is shown that phylogenetic ct DNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.
Abstract: The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.
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TL;DR: The Human Gene Mutation Database constitutes de facto the central unified gene/disease-oriented repository of heritable mutations causing human genetic disease used worldwide by researchers, clinicians, diagnostic laboratories and genetic counsellors, and is an essential tool for the annotation of next-generation sequencing data.
Abstract: The Human Gene Mutation Database (HGMD®) constitutes a comprehensive collection of published germline mutations in nuclear genes that underlie, or are closely associated with human inherited disease. At the time of writing (March 2017), the database contained in excess of 203,000 different gene lesions identified in over 8000 genes manually curated from over 2600 journals. With new mutation entries currently accumulating at a rate exceeding 17,000 per annum, HGMD represents de facto the central unified gene/disease-oriented repository of heritable mutations causing human genetic disease used worldwide by researchers, clinicians, diagnostic laboratories and genetic counsellors, and is an essential tool for the annotation of next-generation sequencing data. The public version of HGMD (http://www.hgmd.org) is freely available to registered users from academic institutions and non-profit organisations whilst the subscription version (HGMD Professional) is available to academic, clinical and commercial users under license via QIAGEN Inc.
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TL;DR: A measurement of the Hubble constant is reported that combines the distance to the source inferred purely from the gravitational-wave signal with the recession velocity inferred from measurements of the redshift using the electromagnetic data.
Abstract: On 17 August 2017, the Advanced LIGO1 and Virgo2 detectors observed the gravitational-wave event GW170817—a strong signal from the merger of a binary neutron-star system3. Less than two seconds after the merger, a γ-ray burst (GRB 170817A) was detected within a region of the sky consistent with the LIGO–Virgo-derived location of the gravitational-wave source4, 5, 6. This sky region was subsequently observed by optical astronomy facilities7, resulting in the identification8, 9, 10, 11, 12, 13 of an optical transient signal within about ten arcseconds of the galaxy NGC 4993. This detection of GW170817 in both gravitational waves and electromagnetic waves represents the first ‘multi-messenger’ astronomical observation. Such observations enable GW170817 to be used as a ‘standard siren’14, 15, 16, 17, 18 (meaning that the absolute distance to the source can be determined directly from the gravitational-wave measurements) to measure the Hubble constant. This quantity represents the local expansion rate of the Universe, sets the overall scale of the Universe and is of fundamental importance to cosmology. Here we report a measurement of the Hubble constant that combines the distance to the source inferred purely from the gravitational-wave signal with the recession velocity inferred from measurements of the redshift using the electromagnetic data. In contrast to previous measurements, ours does not require the use of a cosmic ‘distance ladder’19: the gravitational-wave analysis can be used to estimate the luminosity distance out to cosmological scales directly, without the use of intermediate astronomical distance measurements. We determine the Hubble constant to be about 70 kilometres per second per megaparsec. This value is consistent with existing measurements20, 21, while being completely independent of them. Additional standard siren measurements from future gravitational-wave sources will enable the Hubble constant to be constrained to high precision.
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Abstract: The second-generation of gravitational-wave detectors are just starting operation, and have already yielding their first detections. Research is now concentrated on how to maximize the scientific potential of gravitational-wave astronomy. To support this effort, we present here design targets for a new generation of detectors, which will be capable of observing compact binary sources with high signal-to-noise ratio throughout the Universe.
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TL;DR: It is highlighted that there is not a single “right” way to process resting state data that reveals the “true” nature of the brain, and different processing approaches likely reveal complementary insights about the brain's functional organisation.
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Christian R. Marshall, Daniel P. Howrigan1, Daniel P. Howrigan2, Daniele Merico +326 more•Institutions (98)
TL;DR: In this article, a centralized analysis pipeline was applied to a SCZ cohort of 21,094 cases and 20,227 controls, and a global enrichment of copy number variants (CNVs) was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10-15), which persisted after excluding loci implicated in previous studies.
Abstract: Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10-15), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 × 10-6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 × 10-11) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 × 10-5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.
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University of Aberdeen1, University of Milan2, Technische Universität München3, Cardiff University4, Karolinska Institutet5, Copenhagen University Hospital6, Nova Southeastern University7, Hacettepe University8, Finnish Institute of Occupational Health9, Mater Misericordiae University Hospital10, Paris Descartes University11
TL;DR: These recommendations are underpinned by high-quality reviews and meta-analyses and propose research priorities clarifying who will benefit from specific interventions, their effect in combination and organisation of healthcare systems to optimise outcome.
Abstract: Objective The original European League Against Rheumatism recommendations for managing fibromyalgia assessed evidence up to 2005. The paucity of studies meant that most recommendations were ‘expert opinion’.
Methods A multidisciplinary group from 12 countries assessed evidence with a focus on systematic reviews and meta-analyses concerned with pharmacological/non-pharmacological management for fibromyalgia. A review, in May 2015, identified eligible publications and key outcomes assessed were pain, fatigue, sleep and daily functioning. The Grading of Recommendations Assessment, Development and Evaluation system was used for making recommendations.
Results 2979 titles were identified: from these 275 full papers were selected for review and 107 reviews (and/or meta-analyses) evaluated as eligible. Based on meta-analyses, the only ‘strong for’ therapy-based recommendation in the guidelines was exercise. Based on expert opinion, a graduated approach, the following four main stages are suggested underpinned by shared decision-making with patients. Initial management should involve patient education and focus on non-pharmacological therapies. In case of non-response, further therapies (all of which were evaluated as ‘weak for’ based on meta-analyses) should be tailored to the specific needs of the individual and may involve psychological therapies (for mood disorders and unhelpful coping strategies), pharmacotherapy (for severe pain or sleep disturbance) and/or a multimodal rehabilitation programme (for severe disability).
Conclusions These recommendations are underpinned by high-quality reviews and meta-analyses. The size of effect for most treatments is relatively modest. We propose research priorities clarifying who will benefit from specific interventions, their effect in combination and organisation of healthcare systems to optimise outcome.
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TL;DR: Three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease are observed, providing additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's Disease.
Abstract: We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
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VU University Medical Center1, University of Southern California2, Max Planck Society3, McMaster University4, University of Adelaide5, University of California, Irvine6, Erasmus University Rotterdam7, Delft University of Technology8, Erasmus University Medical Center9, German Center for Neurodegenerative Diseases10, Greifswald University Hospital11, University of Münster12, University of Marburg13, University of Queensland14, QIMR Berghofer Medical Research Institute15, Queensland University of Technology16, Virginia Commonwealth University17, University of Göttingen18, University Hospital Heidelberg19, University of Sydney20, Trinity College, Dublin21, Otto-von-Guericke University Magdeburg22, University of Regensburg23, University Medical Center Groningen24, Leiden University Medical Center25, University of Melbourne26, University of Texas Health Science Center at Houston27, Charité28, University of Bonn29, University of Lübeck30, University Medical Center Freiburg31, Stanford University32, University of Calgary33, Warneford Hospital34, Royal Edinburgh Hospital35, University of Edinburgh36, University of Bern37, Cardiff University38, Leibniz Institute for Neurobiology39, University of Tübingen40, Mental Health Research Institute41, Siberian State Medical University42, Tomsk State University43
TL;DR: In this article, the authors present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD.
Abstract: The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.
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TL;DR: The current understanding of the role of inflammation and cell metabolism in tissue-regenerative responses is reviewed, emerging concepts that may expand therapeutic perspectives are highlighted, and where important knowledge gaps remain are discussed.
Abstract: Tissue repair after injury is a complex, metabolically demanding process. Depending on the tissue’s regenerative capacity and the quality of the inflammatory response, the outcome is generally imperfect, with some degree of fibrosis, which is defined by aberrant accumulation of collagenous connective tissue. Inflammatory cells multitask at the wound site by facilitating wound debridement and producing chemokines, metabolites, and growth factors. If this well-orchestrated response becomes dysregulated, the wound can become chronic or progressively fibrotic, with both outcomes impairing tissue function, which can ultimately lead to organ failure and death. Here we review the current understanding of the role of inflammation and cell metabolism in tissue-regenerative responses, highlight emerging concepts that may expand therapeutic perspectives, and briefly discuss where important knowledge gaps remain.
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University of Leicester1, University of Warwick2, University of Cambridge3, Los Alamos National Laboratory4, University of Birmingham5, Stockholm University6, University of Copenhagen7, INAF8, Space Telescope Science Institute9, Spanish National Research Council10, Liverpool John Moores University11, Instituto Politécnico Nacional12, Cardiff University13, University of St Andrews14, Nagoya University15, Max Planck Society16, University of Iceland17, Pontifical Catholic University of Chile18, Monash University19, University of Amsterdam20, ASTRON21, Weizmann Institute of Science22
TL;DR: In this article, the authors reported the discovery and monitoring of the near-infrared counterpart (AT2017gfo) of a binary neutron-star merger event detected as a gravitational wave source by Advanced Laser Interferometer Gravitational-wave Observatory (LIGO)/Virgo (GW170817) and as a short gamma-ray burst by Fermi Gamma-ray Burst Monitor (GBM) and Integral SPI-ACS (GRB 170817A).
Abstract: We report the discovery and monitoring of the near-infrared counterpart (AT2017gfo) of a binary neutron-star merger event detected as a gravitational wave source by Advanced Laser Interferometer Gravitational-wave Observatory (LIGO)/Virgo (GW170817) and as a short gamma-ray burst by Fermi Gamma-ray Burst Monitor (GBM) and Integral SPI-ACS (GRB 170817A). The evolution of the transient light is consistent with predictions for the behavior of a "kilonova/macronova" powered by the radioactive decay of massive neutron-rich nuclides created via r-process nucleosynthesis in the neutron-star ejecta. In particular, evidence for this scenario is found from broad features seen in Hubble Space Telescope infrared spectroscopy, similar to those predicted for lanthanide-dominated ejecta, and the much slower evolution in the near-infrared ${K}_{{\rm{s}}}$-band compared to the optical. This indicates that the late-time light is dominated by high-opacity lanthanide-rich ejecta, suggesting nucleosynthesis to the third r-process peak (atomic masses $A\approx 195$). This discovery confirms that neutron-star mergers produce kilo-/macronovae and that they are at least a major—if not the dominant—site of rapid neutron capture nucleosynthesis in the universe.
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TL;DR: In this article, the authors compared the performance of feed-forward back-propagation artificial neural network (ANN) with random forest (RF), an ensemble-based method gaining popularity in prediction, for predicting the hourly HVAC energy consumption of a hotel in Madrid, Spain.
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TL;DR: What lessons have been learned from working with traditional probiotics are discussed, the kinds of organisms that are likely to be used as novel microbial therapeutics are explored, the regulatory framework required is discussed, and how scientists may meet this challenge is proposed.
Abstract: The leading probiotics currently available to consumers are generally drawn from a narrow range of organisms. Knowledge of the gut microbiota and its constituent actors is changing this paradigm, particularly given the phylogenetic range and relatively unknown characteristics of the organisms under investigation as novel therapeutics. For this reason, and because their development is likely to be more amenable to a pharmaceutical than a food delivery route, these organisms are often operationally referred to as next-generation probiotics, a concept that overlaps with the emerging concept of live biotherapeutic products. The latter is a class of organisms developed exclusively for pharmaceutical application. In this Perspective, we discuss what lessons have been learned from working with traditional probiotics, explore the kinds of organisms that are likely to be used as novel microbial therapeutics, discuss the regulatory framework required, and propose how scientists may meet this challenge.
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TL;DR: The quality of intervention studies intended to increase hand hygiene compliance remains disappointing and although multifaceted campaigns with social marketing or staff involvement appear to have an effect, there is insufficient evidence to draw a firm conclusion.
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The Dartmouth Institute for Health Policy and Clinical Practice1, Radboud University Nijmegen2, Johns Hopkins University3, Palo Alto Medical Foundation4, University of Wolverhampton5, Akershus University Hospital6, Maine Medical Center7, University of Hamburg8, Cardiff University9, Tokyo University of Technology10, University of Sydney11, Laval University12, Maastricht University Medical Centre13
TL;DR: The revised three-talk model of shared decision making depicts conversational steps, initiated by providing support when introducing options, followed by strategies to compare and discuss trade-offs, before deliberation based on informed preferences.
Abstract: OBJECTIVES
To revise an existing three-talk model for learning how
to achieve shared decision making, and to consult
with relevant stakeholders to update and obtain wider
engagement.
DESIGN
Multistage consultation process.
SETTING
Key informant group, communities of interest, and
survey of clinical specialties.
PARTICIPANTS
19 key informants, 153 member responses from
multiple communities of interest, and 316 responses
to an online survey from medically qualified clinicians
from six specialties.
RESULTS
After extended consultation over three iterations, we
revised the three-talk model by making changes to
one talk category, adding the need to elicit patient
goals, providing a clear set of tasks for each talk
category, and adding suggested scripts to illustrate
each step. A new three-talk model of shared decision
making is proposed, based on “team talk,” “option
talk,” and “decision talk,” to depict a process of
collaboration and deliberation. Team talk places
emphasis on the need to provide support to patients
when they are made aware of choices, and to elicit
their goals as a means of guiding decision making
processes. Option talk refers to the task of comparing
alternatives, using risk communication principles.
Decision talk refers to the task of arriving at decisions
that reflect the informed preferences of patients,
guided by the experience and expertise of health
professionals.
CONCLUSIONS
The revised three-talk model of shared decision
making depicts conversational steps, initiated by
providing support when introducing options, followed
by strategies to compare and discuss trade-offs,
before deliberation based on informed preferences.
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TL;DR: The results suggest the likelihood of a wide dissemination of the novel mobile colistin resistance gene mCR-3 among Enterobacteriaceae and aeromonads; the latter may act as a potential reservoir for mcr-3.
Abstract: The mobile colistin resistance gene mcr-1 has attracted global attention,
as it heralds the breach of polymyxins, one of the last-resort antibiotics for
the treatment of severe clinical infections caused by multidrug-resistant Gramnegative
bacteria. To date, six slightly different variants of mcr-1, and a second
mobile colistin resistance gene, mcr-2, have been reported or annotated in the
GenBank database. Here, we characterized a third mobile colistin resistance gene,
mcr-3. The gene coexisted with 18 additional resistance determinants in the 261-kb
IncHI2-type plasmid pWJ1 from porcine Escherichia coli. mcr-3 showed 45.0% and
47.0% nucleotide sequence identity to mcr-1 and mcr-2, respectively, while the deduced
amino acid sequence of MCR-3 showed 99.8 to 100% and 75.6 to 94.8% identity
to phosphoethanolamine transferases found in other Enterobacteriaceae species
and in 10 Aeromonas species, respectively. pWJ1 was mobilized to an E. coli recipient
by conjugation and contained a plasmid backbone similar to those of other mcr-
1-carrying plasmids, such as pHNSHP45-2 from the original mcr-1-harboring E. coli
strain. Moreover, a truncated transposon element, TnAs2, which was characterized
only in Aeromonas salmonicida, was located upstream of mcr-3 in pWJ1. This
ΔTnAs2-mcr-3 element was also identified in a shotgun genome sequence of a porcine
E. coli isolate from Malaysia, a human Klebsiella pneumoniae isolate from Thailand,
and a human Salmonella enterica serovar Typhimurium isolate from the United
States. These results suggest the likelihood of a wide dissemination of the novel mobile
colistin resistance gene mcr-3 among Enterobacteriaceae and aeromonads; the
latter may act as a potential reservoir for mcr-3.
IMPORTANCE The emergence of the plasmid-mediated colistin resistance gene mcr-1
has attracted substantial attention worldwide. Here, we examined a colistin-resistant
Escherichia coli isolate that was negative for both mcr-1 and mcr-2 and discovered a
novel mobile colistin resistance gene, mcr-3. The amino acid sequence of MCR-3
aligned closely with phosphoethanolamine transferases from Enterobacteriaceae and
Aeromonas species originating from both clinical infections and environmental samples
collected in 12 countries on four continents. Due to the ubiquitous profile of
aeromonads in the environment and the potential transfer of mcr-3 between Enterobacteriaceae
and Aeromonas species, the wide spread of mcr-3 may be largely underestimated.
As colistin has been and still is widely used in veterinary medicine and
used at increasing frequencies in human medicine, the continuous monitoring of
mobile colistin resistance determinants in colistin-resistant Gram-negative bacteria is
imperative for understanding and tackling the dissemination of mcr genes in both
the agricultural and health care sectors.
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University Medical Center Groningen1, University of Freiburg2, Wellcome Trust3, European Centre for Disease Prevention and Control4, Imperial College London5, Spanish National Research Council6, Karolinska University Hospital7, Karolinska Institutet8, Université catholique de Louvain9, University of East Anglia10, Public Health England11, University of Fribourg12, University of Paris-Sud13, University of Siena14, University of Cologne15, Cardiff University16
TL;DR: The development of a consistent sampling framework and the results of the first structured survey on the occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in European hospitals are reported.
Abstract: Summary Background Gaps in the diagnostic capacity and heterogeneity of national surveillance and reporting standards in Europe make it difficult to contain carbapenemase-producing Enterobacteriaceae. We report the development of a consistent sampling framework and the results of the first structured survey on the occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in European hospitals. Methods National expert laboratories recruited hospitals with diagnostic capacities, who collected the first ten carbapenem non-susceptible clinical isolates of K pneumoniae or E coli and ten susceptible same-species comparator isolates and pertinent patient and hospital information. Isolates and data were relayed back to national expert laboratories, which made laboratory-substantiated information available for central analysis. Findings Between Nov 1, 2013, and April 30, 2014, 455 sentinel hospitals in 36 countries submitted 2703 clinical isolates (2301 [85%] K pneumoniae and 402 (15%) E coli ). 850 (37%) of 2301 K pneumoniae samples and 77 (19%) of 402 E coli samples were carbapenemase (KPC, NDM, OXA-48-like, or VIM) producers. The ratio of K pneumoniae to E coli was 11:1. 1·3 patients per 10 000 hospital admissions had positive clinical specimens. Prevalence differed greatly, with the highest rates in Mediterranean and Balkan countries. Carbapenemase-producing K pneumoniae isolates showed high resistance to last-line antibiotics. Interpretation This initiative shows an encouraging commitment by all participants, and suggests that challenges in the establishment of a continent-wide enhanced sentinel surveillance for carbapenemase-producing Enterobacteriaeceae can be overcome. Strengthening infection control efforts in hospitals is crucial for controlling spread through local and national health care networks. Funding European Centre for Disease Prevention and Control.
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TL;DR: A significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4 is identified and identified.
Abstract: Background: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the
understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried
by the true risk variants and the corresponding statistical power to observe such effects given the study design and
sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however,
these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15).
Methods: We conducted a large-scale coordinated international collaboration to combine independent genotyping
data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide
genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary
statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls).
Results: We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription
factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social
skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia
which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P=9 ×10−6). We further
combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to
identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12
novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a
‘neurodevelopmental hub’ on chromosome 8p11.23.
Conclusions: This study is an important step in the ongoing endeavour to identify the loci which underpin the common
variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia
and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4.
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TL;DR: It is demonstrated that the resulting methanol incorporated a substantial fraction of gas-phase O2, suggesting that the controlled breakdown of H2O2 activates methane, which subsequently incorporates molecular oxygen through a radical process.
Abstract: The selective oxidation of methane, the primary component of natural gas, remains an important challenge in catalysis. We used colloidal gold-palladium nanoparticles, rather than the same nanoparticles supported on titanium oxide, to oxidize methane to methanol with high selectivity (92%) in aqueous solution at mild temperatures. Then, using isotopically labeled oxygen (O2) as an oxidant in the presence of hydrogen peroxide (H2O2), we demonstrated that the resulting methanol incorporated a substantial fraction (70%) of gas-phase O2. More oxygenated products were formed than the amount of H2O2 consumed, suggesting that the controlled breakdown of H2O2 activates methane, which subsequently incorporates molecular oxygen through a radical process. If a source of methyl radicals can be established, then the selective oxidation of methane to methanol using molecular oxygen is possible.