scispace - formally typeset
Search or ask a question

Showing papers by "University College Dublin published in 2017"


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Fausto Acernese3  +1195 moreInstitutions (139)
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


Journal ArticleDOI
Bin Zhou1, James Bentham1, Mariachiara Di Cesare2, Honor Bixby1  +787 moreInstitutions (231)
TL;DR: The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries, and the contributions of changes in prevalence versus population growth and ageing to the increase.

1,573 citations


Journal ArticleDOI
TL;DR: The first unambiguous coincident observation of gravitational waves and electromagnetic radiation from a single astrophysical source and marks the start of gravitational-wave multi-messenger astronomy was reported in this article.
Abstract: On 2017 August 17 at 12:41:06 UTC the Fermi Gamma-ray Burst Monitor (GBM) detected and triggered on the short gamma-ray burst (GRB) 170817A. Approximately 1.7 s prior to this GRB, the Laser Interferometer Gravitational-wave Observatory triggered on a binary compact merger candidate associated with the GRB. This is the first unambiguous coincident observation of gravitational waves and electromagnetic radiation from a single astrophysical source and marks the start of gravitational-wave multi-messenger astronomy. We report the GBM observations and analysis of this ordinary short GRB, which extraordinarily confirms that at least some short GRBs are produced by binary compact mergers.

1,195 citations


Journal ArticleDOI
15 Apr 2017-Geoderma
TL;DR: In this paper, the authors surveyed the soil organic carbon (SOC) stock estimates and sequestration potentials from 20 regions in the world (New Zealand, Chile, South Africa, Australia, Tanzania, Indonesia, Kenya, Nigeria, India, China Taiwan, South Korea, China Mainland, United States of America, France, Canada, Belgium, England & Wales, Ireland, Scotland, and Russia).

1,171 citations


Journal ArticleDOI
TL;DR: In this paper, the authors present the rationale for the inclusive valuation of nature's contributions to people (NCP) in decision making, as well as broad methodological steps for doing so, and argue that transformative practices aiming at sustainable futures would benefit from embracing such diversity, which require recognizing and addressing power relationships across stakeholder groups that hold different values on human nature-relations and NCP.

985 citations


Journal ArticleDOI
TL;DR: The Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients, and makes recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD.
Abstract: Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of >90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD.

822 citations


Journal ArticleDOI
Albert M. Sirunyan, Armen Tumasyan, Wolfgang Adam1, Ece Aşılar1  +2212 moreInstitutions (157)
TL;DR: A fully-fledged particle-flow reconstruction algorithm tuned to the CMS detector was developed and has been consistently used in physics analyses for the first time at a hadron collider as mentioned in this paper.
Abstract: The CMS apparatus was identified, a few years before the start of the LHC operation at CERN, to feature properties well suited to particle-flow (PF) reconstruction: a highly-segmented tracker, a fine-grained electromagnetic calorimeter, a hermetic hadron calorimeter, a strong magnetic field, and an excellent muon spectrometer. A fully-fledged PF reconstruction algorithm tuned to the CMS detector was therefore developed and has been consistently used in physics analyses for the first time at a hadron collider. For each collision, the comprehensive list of final-state particles identified and reconstructed by the algorithm provides a global event description that leads to unprecedented CMS performance for jet and hadronic τ decay reconstruction, missing transverse momentum determination, and electron and muon identification. This approach also allows particles from pileup interactions to be identified and enables efficient pileup mitigation methods. The data collected by CMS at a centre-of-mass energy of 8\TeV show excellent agreement with the simulation and confirm the superior PF performance at least up to an average of 20 pileup interactions.

719 citations


Journal ArticleDOI
TL;DR: In this article, the authors reported the INTernational Gamma-ray Astrophysics Laboratory (INTEGRAL) detection of the short gamma-ray burst GRB 170817A (discovered by Fermi-GBM) with a signal-to-noise ratio of 4.6, and, for the first time, its association with the gravitational waves from binary neutron star (BNS) merging event GW170817 detected by the LIGO and Virgo observatories.
Abstract: We report the INTernational Gamma-ray Astrophysics Laboratory (INTEGRAL) detection of the short gamma-ray burst GRB 170817A (discovered by Fermi-GBM) with a signal-to-noise ratio of 4.6, and, for the first time, its association with the gravitational waves (GWs) from binary neutron star (BNS) merging event GW170817 detected by the LIGO and Virgo observatories. The significance of association between the gamma-ray burst observed by INTEGRAL and GW170817 is 3.2σ, while the association between the Fermi-GBM and INTEGRAL detections is 4.2σ. GRB 170817A was detected by the SPI-ACS instrument about 2 s after the end of the GW event. We measure a fluence of (1.4 ± 0.4 ± 0.6) × 10(−)(7) erg cm(−)(2) (75–2000 keV), where, respectively, the statistical error is given at the 1σ confidence level, and the systematic error corresponds to the uncertainty in the spectral model and instrument response. We also report on the pointed follow-up observations carried out by INTEGRAL, starting 19.5 hr after the event, and lasting for 5.4 days. We provide a stringent upper limit on any electromagnetic signal in a very broad energy range, from 3 keV to 8 MeV, constraining the soft gamma-ray afterglow flux to <7.1 × 10(−)(11) erg cm(−)(2) s(−)(1) (80–300 keV). Exploiting the unique capabilities of INTEGRAL, we constrained the gamma-ray line emission from radioactive decays that are expected to be the principal source of the energy behind a kilonova event following a BNS coalescence. Finally, we put a stringent upper limit on any delayed bursting activity, for example, from a newly formed magnetar.

698 citations


Journal ArticleDOI
Stephen J. Smartt1, Ting-Wan Chen2, Anders Jerkstrand2, Michael W. Coughlin3, Erkki Kankare1, Stuart A. Sim1, Morgan Fraser4, Cosimo Inserra5, Kate Maguire1, K. C. Chambers6, M. E. Huber6, Thomas Krühler2, Giorgos Leloudas7, M. R. Magee1, Luke J. Shingles1, K. W. Smith1, David Young1, John L. Tonry6, Rubina Kotak1, Avishay Gal-Yam8, J. D. Lyman9, D. Homan10, C. Agliozzo11, C. Agliozzo12, Joseph P. Anderson13, C. Angus5, Chris Ashall14, Cristina Barbarino15, Franz E. Bauer16, Franz E. Bauer17, Franz E. Bauer11, Marco Berton18, Marco Berton19, M. T. Botticella19, Mattia Bulla15, J. Bulger6, Giacomo Cannizzaro20, Giacomo Cannizzaro21, Zach Cano22, Régis Cartier5, Aleksandar Cikota13, P. Clark1, A. De Cia13, M. Della Valle19, Larry Denneau6, M. Dennefeld23, Luc Dessart24, Georgios Dimitriadis5, Nancy Elias-Rosa, R. E. Firth5, H. Flewelling6, A. Flörs2, A. Franckowiak, C. Frohmaier25, Lluís Galbany26, Santiago González-Gaitán27, Jochen Greiner2, Mariusz Gromadzki28, A. Nicuesa Guelbenzu, Claudia P. Gutiérrez5, A. Hamanowicz13, A. Hamanowicz28, Lorraine Hanlon4, Jussi Harmanen29, Kasper E. Heintz30, Kasper E. Heintz7, A. Heinze6, M.-S. Hernandez31, Simon Hodgkin32, Isobel Hook33, Luca Izzo22, Phil A. James14, Peter G. Jonker20, Peter G. Jonker21, Wolfgang Kerzendorf13, S. Klose, Z. Kostrzewa-Rutkowska21, Z. Kostrzewa-Rutkowska20, Marek Kowalski34, Markus Kromer35, Markus Kromer36, Hanindyo Kuncarayakti29, Andy Lawrence10, T. Lowe6, Eugene A. Magnier6, Ilan Manulis8, Antonio Martin-Carrillo4, Seppo Mattila29, O. McBrien1, André Müller2, Jakob Nordin34, D. O'Neill1, F. Onori21, F. Onori20, J. Palmerio37, Andrea Pastorello19, Ferdinando Patat13, G. Pignata11, G. Pignata12, Ph. Podsiadlowski38, Maria Letizia Pumo19, Maria Letizia Pumo39, S. J. Prentice14, Arne Rau2, A. Razza24, A. Razza13, A. Rest40, A. Rest41, T. M. Reynolds29, Rupak Roy42, Rupak Roy15, Ashley J. Ruiter43, Ashley J. Ruiter44, Krzysztof A. Rybicki28, Lána Salmon4, Patricia Schady2, A. S. B. Schultz6, T. Schweyer2, Ivo R. Seitenzahl43, Ivo R. Seitenzahl44, M. Smith5, Jesper Sollerman15, B. Stalder, Christopher W. Stubbs45, Mark Sullivan5, Helene Szegedi46, Francesco Taddia15, Stefan Taubenberger2, Giacomo Terreran19, Giacomo Terreran47, B. van Soelen46, J. Vos31, Richard J. Wainscoat6, Nicholas A. Walton32, Christopher Waters6, H. Weiland6, Mark Willman6, P. Wiseman2, Darryl Wright48, Łukasz Wyrzykowski28, O. Yaron8 
02 Nov 2017-Nature
TL;DR: Observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817, indicate that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.
Abstract: Gravitational waves were discovered with the detection of binary black-hole mergers and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova. The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate. Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short γ-ray burst. The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 ± 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 ± 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 ± 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.

695 citations


Journal ArticleDOI
TL;DR: A formal Delphi consensus process was used to help develop a definition of ACP and provide recommendations for its application, and it is believed that these recommendations can provide guidance for clinical practice, ACP policy, and research.
Abstract: Advance care planning (ACP) is increasingly implemented in oncology and beyond, but a definition of ACP and recommendations concerning its use are lacking. We used a formal Delphi consensus process to help develop a definition of ACP and provide recommendations for its application. Of the 109 experts (82 from Europe, 16 from North America, and 11 from Australia) who rated the ACP definitions and its 41 recommendations, agreement for each definition or recommendation was between 68-100%. ACP was defined as the ability to enable individuals to define goals and preferences for future medical treatment and care, to discuss these goals and preferences with family and health-care providers, and to record and review these preferences if appropriate. Recommendations included the adaptation of ACP based on the readiness of the individual; targeting ACP content as the individual's health condition worsens; and, using trained non-physician facilitators to support the ACP process. We present a list of outcome measures to enable the pooling and comparison of results of ACP studies. We believe that our recommendations can provide guidance for clinical practice, ACP policy, and research.

692 citations


Journal ArticleDOI
TL;DR: In this article, a high-accuracy global digital elevation model (DEM) was proposed by eliminating major error components from existing DEMs, such as absolute bias, stripe noise, speckle noise, and tree height bias.
Abstract: Spaceborne digital elevation models (DEMs) are a fundamental input for many geoscience studies, but they still include nonnegligible height errors Here we introduce a high-accuracy global DEM at 3″ resolution (~90 m at the equator) by eliminating major error components from existing DEMs We separated absolute bias, stripe noise, speckle noise, and tree height bias using multiple satellite data sets and filtering techniques After the error removal, land areas mapped with ±2 m or better vertical accuracy were increased from 39% to 58% Significant improvements were found in flat regions where height errors larger than topography variability, and landscapes such as river networks and hill-valley structures, became clearly represented We found the topography slope of previous DEMs was largely distorted in most of world major floodplains (eg, Ganges, Nile, Niger, and Mekong) and swamp forests (eg, Amazon, Congo, and Vasyugan) The newly developed DEM will enhance many geoscience applications which are terrain dependent


Journal ArticleDOI
Roel Aaij1, Bernardo Adeva2, Marco Adinolfi3, Ziad Ajaltouni4  +818 moreInstitutions (68)
TL;DR: In this article, a test of lepton universality is performed by measuring the ratio of the branching fractions of the B$0$ → K$*0}$ e$+}$ π$−}$ decays, and the ratio is measured in two regions of the dilepton invariant mass squared.
Abstract: A test of lepton universality, performed by measuring the ratio of the branching fractions of the B$^{0}$ → K$^{*0}$ μ$^{+}$ μ$^{−}$ and B$^{0}$ → K$^{*0}$ e$^{+}$ e$^{−}$ decays, $ {R}_{K^{*0}} $ , is presented. The K$^{*0}$ meson is reconstructed in the final state K$^{+}$ π$^{−}$, which is required to have an invariant mass within 100 MeV/c$^{2}$ of the known K$^{*}$(892)$^{0}$ mass. The analysis is performed using proton-proton collision data, corresponding to an integrated luminosity of about 3 fb$^{−1}$, collected by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. The ratio is measured in two regions of the dilepton invariant mass squared, q$^{2}$, to be $ {R}_{K^{*0}}=\left\{\begin{array}{l}{0.66_{-}^{+}}_{0.07}^{0.11}\left(\mathrm{stat}\right)\pm 0.03\left(\mathrm{syst}\right)\kern1em \mathrm{f}\mathrm{o}\mathrm{r}\kern1em 0.045<{q}^2<1.1\kern0.5em {\mathrm{GeV}}^2/{c}^4,\hfill \\ {}{0.69_{-}^{+}}_{0.07}^{0.11}\left(\mathrm{stat}\right)\pm 0.05\left(\mathrm{syst}\right)\kern1em \mathrm{f}\mathrm{o}\mathrm{r}\kern1em 1.1<{q}^2<6.0\kern0.5em {\mathrm{GeV}}^2/{c}^4.\hfill \end{array}\right. $

Journal ArticleDOI
TL;DR: In this paper, the authors examined published literature on neighbourhood air quality modifications by green interventions and provided a better understanding of the interactions between vegetation and surrounding built-up environments and ascertain means of reducing local air pollution exposure using green infrastructure.

Journal ArticleDOI
TL;DR: In this paper, the trigger system consists of two levels designed to select events of potential physics interest from a GHz (MHz) interaction rate of proton-proton (heavy ion) collisions.
Abstract: This paper describes the CMS trigger system and its performance during Run 1 of the LHC. The trigger system consists of two levels designed to select events of potential physics interest from a GHz (MHz) interaction rate of proton-proton (heavy ion) collisions. The first level of the trigger is implemented in hardware, and selects events containing detector signals consistent with an electron, photon, muon, tau lepton, jet, or missing transverse energy. A programmable menu of up to 128 object-based algorithms is used to select events for subsequent processing. The trigger thresholds are adjusted to the LHC instantaneous luminosity during data taking in order to restrict the output rate to 100 kHz, the upper limit imposed by the CMS readout electronics. The second level, implemented in software, further refines the purity of the output stream, selecting an average rate of 400 Hz for offline event storage. The objectives, strategy and performance of the trigger system during the LHC Run 1 are described.

Journal ArticleDOI
TL;DR: The present article summarizes the most important co-morbidities of obesity and their prevalence and describes classification and grading systems that can be used to assess the individual and combined impact of co-Morbid conditions on mortality risk.
Abstract: Obesity and its repercussions constitute an important source of morbidity, impaired quality of life and its complications can have a major bearing on life expectancy. The present article summarizes the most important co-morbidities of obesity and their prevalence. Furthermore, it describes classification and grading systems that can be used to assess the individual and combined impact of co-morbid conditions on mortality risk. The literature was screened for assessment tools that can be deployed in the quantification of morbidity and mortality risk in individual patients. Thirteen specific domains have been identified that account for morbidity and mortality in obesity. Cardiovascular disease (CVD) and cancer account for the greatest mortality risk associated with obesity. The King’s Criteria and Edmonton Obesity Staging System (EOSS) were identified as useful tools for the detection and monitoring of individual patient mortality risk in obesity care. The stark facts on the complications of obesity should be capitalized on to improve patient management and knowledge and referred to in the wider dissemination of public health messages aimed at improving primary prevention.

Journal ArticleDOI
TL;DR: In this paper, the performance of continuous carbon, Kevlar and glass fibre reinforced composites manufactured using the fused deposition modelling (FDM) additive manufacturing technique was evaluated both in tension and flexure.
Abstract: This study evaluates the performance of continuous carbon, Kevlar and glass fibre reinforced composites manufactured using the fused deposition modelling (FDM) additive manufacturing technique. The fibre reinforced nylon composites were fabricated using a Markforged Mark One 3D printing system. The mechanical performance of the composites was evaluated both in tension and flexure. The influence of fibre orientation, fibre type and volume fraction on mechanical properties were also investigated. The results were compared with that of both non-reinforced nylon control specimens, and known material property values from literature. It was demonstrated that of the fibres investigated, those fabricated using carbon fibre yielded the largest increase in mechanical strength per fibre volume. Its tensile strength values were up to 6.3 times higher than those obtained with the non-reinforced nylon polymer. As the carbon and glass fibre volume fraction increased so too did the level of air inclusion in the composite matrix, which impacted on mechanical performance. As a result, a maximum efficiency in tensile strength was observed in glass specimen as fibre content approached 22.5%, with higher fibre contents (up to 33%), yielding only minor increases in strength.

Journal ArticleDOI
Khachatryan1, Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam  +2285 moreInstitutions (147)
TL;DR: In this paper, an improved jet energy scale corrections, based on a data sample corresponding to an integrated luminosity of 19.7 fb^(-1) collected by the CMS experiment in proton-proton collisions at a center-of-mass energy of 8 TeV, are presented.
Abstract: Improved jet energy scale corrections, based on a data sample corresponding to an integrated luminosity of 19.7 fb^(-1) collected by the CMS experiment in proton-proton collisions at a center-of-mass energy of 8 TeV, are presented. The corrections as a function of pseudorapidity η and transverse momentum p_T are extracted from data and simulated events combining several channels and methods. They account successively for the effects of pileup, uniformity of the detector response, and residual data-simulation jet energy scale differences. Further corrections, depending on the jet flavor and distance parameter (jet size) R, are also presented. The jet energy resolution is measured in data and simulated events and is studied as a function of pileup, jet size, and jet flavor. Typical jet energy resolutions at the central rapidities are 15–20% at 30 GeV, about 10% at 100 GeV, and 5% at 1 TeV. The studies exploit events with dijet topology, as well as photon+jet, Z+jet and multijet events. Several new techniques are used to account for the various sources of jet energy scale corrections, and a full set of uncertainties, and their correlations, are provided. The final uncertainties on the jet energy scale are below 3% across the phase space considered by most analyses (p_T > 30 GeV and 0|η| 30 GeV is reached, when excluding the jet flavor uncertainties, which are provided separately for different jet flavors. A new benchmark for jet energy scale determination at hadron colliders is achieved with 0.32% uncertainty for jets with p_T of the order of 165–330 GeV, and |η| < 0.8.

Journal ArticleDOI
TL;DR: It is proposed that relationships between soil food web structure and carbon cycling in soils need to be reconsidered and the efficiency of nutrient cycling and carbon uptake can increase by a shift in fungal composition and/or fungal activity during nature restoration.
Abstract: Soil organisms have an important role in aboveground community dynamics and ecosystem functioning in terrestrial ecosystems. However, most studies have considered soil biota as a black box or focussed on specific groups, whereas little is known about entire soil networks. Here we show that during the course of nature restoration on abandoned arable land a compositional shift in soil biota, preceded by tightening of the belowground networks, corresponds with enhanced efficiency of carbon uptake. In mid- and long-term abandoned field soil, carbon uptake by fungi increases without an increase in fungal biomass or shift in bacterial-to-fungal ratio. The implication of our findings is that during nature restoration the efficiency of nutrient cycling and carbon uptake can increase by a shift in fungal composition and/or fungal activity. Therefore, we propose that relationships between soil food web structure and carbon cycling in soils need to be reconsidered.

Journal ArticleDOI
Richard Anney1, Richard Anney2, Stephan Ripke3, Stephan Ripke4  +211 moreInstitutions (77)
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.

Journal ArticleDOI
TL;DR: In this paper, the authors report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci.
Abstract: Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.

Journal ArticleDOI
TL;DR: A rapid search in PubMed shows that using "flow cytometry immunology" as a search term yields more than 68 000 articles, the first of which is not about lymphocytes as mentioned in this paper.
Abstract: The marriage between immunology and cytometry is one of the most stable and productive in the recent history of science. A rapid search in PubMed shows that, as of July 2017, using “flow cytometry immunology” as a search term yields more than 68 000 articles, the first of which, interestingly, is not about lymphocytes. It might be stated that, after a short engagement, the exchange of the wedding rings between immunology and cytometry officially occurred when the idea to link fluorochromes to monoclonal antibodies came about. After this, recognizing different types of cells became relatively easy and feasible not only by using a simple fluorescence microscope, but also by a complex and sometimes esoteric instrument, the flow cytometer that is able to count hundreds of cells in a single second, and can provide repetitive results in a tireless manner. Given this, the possibility to analyse immune phenotypes in a variety of clinical conditions has changed the use of the flow cytometer, which was incidentally invented in the late 1960s to measure cellular DNA by using intercalating dyes, such as ethidium bromide. The epidemics of HIV/AIDS in the 1980s then gave a dramatic impulse to the technology of counting specific cells, since it became clear that the quantification of the number of peripheral blood CD4+ T cells was crucial to follow the course of the infection, and eventually for monitoring the therapy. As a consequence, the development of flow cytometers that had to be easy-to-use in all clinical laboratories helped to widely disseminate this technology. Nowadays, it is rare to find an immunological paper or read a conference abstract in which the authors did not use flow cytometry as the main tool to dissect the immune system and identify its fine and complex functions. Of note, recent developments have created the sophisticated technology of mass cytometry, which is able to simultaneously identify dozens of molecules at the single cell level and allows us to better understand the complexity and beauty of the immune system.

Journal ArticleDOI
Carel W. le Roux1, Carel W. le Roux2, Arne Astrup3, Ken Fujioka4  +197 moreInstitutions (11)
TL;DR: Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes in this trial, with the limitation that withdrawn individuals were not followed up after discontinuation.

Journal ArticleDOI
TL;DR: A review of the state-of-the-art of biogas cleaning and upgrading technologies, including its composition, upgrading efficiency, methane recovery and loss, is presented in this paper.
Abstract: Biogas is a valuable renewable energy and also a secondary energy carrier produced from biodegradable organic materials via anaerobic digestion. It can be used as a fuel or as starting material for the production of chemicals, hydrogen and/or synthesis gas etc. The main constituents of biogas are methane (CH4) and carbon dioxide (CO2), with various quantities of contaminants, such as ammonia (NH3), water vapour (H2O), hydrogen sulfide (H2S), methyl siloxanes, nitrogen (N2), oxygen (O2), halogenated volatile organic compounds (VOCs), carbon monoxide (CO) and hydrocarbons. These contaminants presence and quantities depend largely on the biogas source, which could be anaerobic digestion of many substrates and landfill decompositions. The removal of these contaminants especially H2S and CO2 will significantly improve the quality of the biogas for its further uses. In parallel, biogas upgrading market is facing challenges in term of operating costs and energy consumption. The selection of appropriate technology depends on the specific biogas requirements, site specific, local circumstances and is case sensitive. This paper reviews the present state-of-the-art of biogas cleaning and upgrading technologies, including its composition, upgrading efficiency, methane recovery and loss. In addition, biogas production, utilization and the corresponding requirements on gas quality for grid injection and vehicle usage are investigated. Based on the results of comparisons of various technologies, recommendations are made on further research on the appropriate low cost technologies, especially using solid waste as low cost materials for biogas purification and upgrading.

Journal ArticleDOI
TL;DR: A significant synthesis of Agent Based Modelling and Simulation (ABMS) resources has been performed in this review that stimulates further investigation into this topic.

Journal ArticleDOI
TL;DR: In this paper, the Proto-Tethys Ocean is defined as a complex complex paleo-ocean located between the Tarim-North China and the Sibumasu/Baoshan blocks, and it was opened from the rifting of the Supercontinent Rodinia and mainly closed at the end of the Early Paleozoic.

Journal ArticleDOI
Roel Aaij1, Bernardo Adeva2, Marco Adinolfi3, Ziad Ajaltouni4  +813 moreInstitutions (52)
TL;DR: In this article, a doubly charmed baryon Ξcc++ was observed in a sample of proton-proton collision data collected by the LHCb experiment at a center-of-mass energy of 13 TeV.
Abstract: A highly significant structure is observed in the Λc+K-π+π+ mass spectrum, where the Λc+ baryon is reconstructed in the decay mode pK-π+. The structure is consistent with originating from a weakly decaying particle, identified as the doubly charmed baryon Ξcc++. The difference between the masses of the Ξcc++ and Λc+ states is measured to be 1334.94±0.72(stat.)±0.27(syst.) MeV/c2, and the Ξcc++ mass is then determined to be 3621.40±0.72(stat.)±0.27(syst.)±0.14(Λc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Λc+ mass. The state is observed in a sample of proton-proton collision data collected by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.7 fb-1, and confirmed in an additional sample of data collected at 8 TeV.

Journal ArticleDOI
TL;DR: The possibility of targeting hypoxia-sensitive pathways in immune cells for the treatment of inflammatory disease is discussed and the consequences for immunity and inflammation in different immunological niches are distinguished.
Abstract: Immunological niches are focal sites of immune activity that can have varying microenvironmental features. Hypoxia is a feature of physiological and pathological immunological niches. The impact of hypoxia on immunity and inflammation can vary depending on the microenvironment and immune processes occurring in a given niche. In physiological immunological niches, such as the bone marrow, lymphoid tissue, placenta and intestinal mucosa, physiological hypoxia controls innate and adaptive immunity by modulating immune cell proliferation, development and effector function, largely via transcriptional changes driven by hypoxia-inducible factor (HIF). By contrast, in pathological immunological niches, such as tumours and chronically inflamed, infected or ischaemic tissues, pathological hypoxia can drive tissue dysfunction and disease development through immune cell dysregulation. Here, we differentiate between the effects of physiological and pathological hypoxia on immune cells and the consequences for immunity and inflammation in different immunological niches. Furthermore, we discuss the possibility of targeting hypoxia-sensitive pathways in immune cells for the treatment of inflammatory disease.

Journal ArticleDOI
TL;DR: The efficacy of tofacitinib was superior to that of placebo at month 3 in patients with psoriatic arthritis who had previously had an inadequate response to conventional synthetic DMARDs.
Abstract: BackgroundTofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who previously had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs). MethodsIn this 12-month, double-blind, active-controlled and placebo-controlled, phase 3 trial, we randomly assigned patients in a 2:2:2:1:1 ratio to receive one of the following regimens: tofacitinib at a 5-mg dose taken orally twice daily (107 patients), tofacitinib at a 10-mg dose taken orally twice daily (104), adalimumab at a 40-mg dose administered subcutaneously once every 2 weeks (106), placebo with a blinded switch to the 5-mg tofacitinib dose at 3 months (52), or placebo with a blinded switch to the 10-mg tofacitinib dose at 3 months (53). Placebo groups were pooled for analyses up to month 3. Primary end points were the proportion of patients who had an American College of Rheumatology 20 ...

Journal ArticleDOI
TL;DR: In oestrogen receptor-positive, HER2-negative, lymph node-negative patients, multianalyte tests such as urokinase plasminogen activator (uPA)-PAI-1, Oncotype DX, MammaPrint, EndoPredict, Breast Cancer Index (BCI) and Prosigna (PAM50) may be used to predict outcome and aid adjunct therapy decision-making.