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Showing papers by "University of Antwerp published in 2018"


Journal ArticleDOI
Clotilde Théry1, Kenneth W. Witwer2, Elena Aikawa3, María José Alcaraz4  +414 moreInstitutions (209)
TL;DR: The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities, and a checklist is provided with summaries of key points.
Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

5,988 citations


Journal ArticleDOI
Gregory A. Roth1, Gregory A. Roth2, Degu Abate3, Kalkidan Hassen Abate4  +1025 moreInstitutions (333)
TL;DR: Non-communicable diseases comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2).

5,211 citations


Journal ArticleDOI
Jeffrey D. Stanaway1, Ashkan Afshin1, Emmanuela Gakidou1, Stephen S Lim1  +1050 moreInstitutions (346)
TL;DR: This study estimated levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs) by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017 and explored the relationship between development and risk exposure.

2,910 citations


Journal ArticleDOI
TL;DR: It is found that the antibiotic consumption rate in low- and middle- income countries (LMICs) has been converging to (and in some countries surpassing) levels typically observed in high-income countries, and projected total global antibiotic consumption through 2030 was up to 200% higher than the 42 billion DDDs estimated in 2015.
Abstract: Tracking antibiotic consumption patterns over time and across countries could inform policies to optimize antibiotic prescribing and minimize antibiotic resistance, such as setting and enforcing per capita consumption targets or aiding investments in alternatives to antibiotics. In this study, we analyzed the trends and drivers of antibiotic consumption from 2000 to 2015 in 76 countries and projected total global antibiotic consumption through 2030. Between 2000 and 2015, antibiotic consumption, expressed in defined daily doses (DDD), increased 65% (21.1–34.8 billion DDDs), and the antibiotic consumption rate increased 39% (11.3–15.7 DDDs per 1,000 inhabitants per day). The increase was driven by low- and middle-income countries (LMICs), where rising consumption was correlated with gross domestic product per capita (GDPPC) growth (P = 0.004). In high-income countries (HICs), although overall consumption increased modestly, DDDs per 1,000 inhabitants per day fell 4%, and there was no correlation with GDPPC. Of particular concern was the rapid increase in the use of last-resort compounds, both in HICs and LMICs, such as glycylcyclines, oxazolidinones, carbapenems, and polymyxins. Projections of global antibiotic consumption in 2030, assuming no policy changes, were up to 200% higher than the 42 billion DDDs estimated in 2015. Although antibiotic consumption rates in most LMICs remain lower than in HICs despite higher bacterial disease burden, consumption in LMICs is rapidly converging to rates similar to HICs. Reducing global consumption is critical for reducing the threat of antibiotic resistance, but reduction efforts must balance access limitations in LMICs and take account of local and global resistance patterns.

1,745 citations


Journal ArticleDOI
22 Jun 2018-Science
TL;DR: It is demonstrated that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine, and it is shown that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures.
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

1,357 citations


Journal ArticleDOI
TL;DR: NanoPack, a set of tools developed for visualization and processing of long‐read sequencing data from Oxford Nanopore Technologies and Pacific Biosciences, is described.
Abstract: Summary Here we describe NanoPack, a set of tools developed for visualization and processing of long-read sequencing data from Oxford Nanopore Technologies and Pacific Biosciences. Availability and implementation The NanoPack tools are written in Python3 and released under the GNU GPL3.0 License. The source code can be found at https://github.com/wdecoster/nanopack, together with links to separate scripts and their documentation. The scripts are compatible with Linux, Mac OS and the MS Windows 10 subsystem for Linux and are available as a graphical user interface, a web service at http://nanoplot.bioinf.be and command line tools. Supplementary information Supplementary data are available at Bioinformatics online.

1,296 citations


Journal ArticleDOI
TL;DR: The present review is devoted to summarizing the recent advances (2015–2017) in the field of metal-catalysed group-directed C–H functionalisation.
Abstract: The present review is devoted to summarizing the recent advances (2015-2017) in the field of metal-catalysed group-directed C-H functionalisation In order to clearly showcase the molecular diversity that can now be accessed by means of directed C-H functionalisation, the whole is organized following the directing groups installed on a substrate Its aim is to be a comprehensive reference work, where a specific directing group can be easily found, together with the transformations which have been carried out with it Hence, the primary format of this review is schemes accompanied with a concise explanatory text, in which the directing groups are ordered in sections according to their chemical structure The schemes feature typical substrates used, the products obtained as well as the required reaction conditions Importantly, each example is commented on with respect to the most important positive features and drawbacks, on aspects such as selectivity, substrate scope, reaction conditions, directing group removal, and greenness The targeted readership are both experts in the field of C-H functionalisation chemistry (to provide a comprehensive overview of the progress made in the last years) and, even more so, all organic chemists who want to introduce the C-H functionalisation way of thinking for a design of straightforward, efficient and step-economic synthetic routes towards molecules of interest to them Accordingly, this review should be of particular interest also for scientists from industrial R&D sector Hence, the overall goal of this review is to promote the application of C-H functionalisation reactions outside the research groups dedicated to method development and establishing it as a valuable reaction archetype in contemporary R&D, comparable to the role cross-coupling reactions play to date

1,057 citations


Journal ArticleDOI
31 May 2018
TL;DR: The success of MRSA is a consequence of the extensive arsenal of virulence factors produced by S. aureus combined with β-lactam resistance and, for most clones, resistance to other antibiotic classes as discussed by the authors.
Abstract: Since the 1960s, methicillin-resistant Staphylococcus aureus (MRSA) has emerged, disseminated globally and become a leading cause of bacterial infections in both health-care and community settings. However, there is marked geographical variation in MRSA burden owing to several factors, including differences in local infection control practices and pathogen-specific characteristics of the circulating clones. Different MRSA clones have resulted from the independent acquisition of staphylococcal cassette chromosome mec (SCCmec), which contains genes encoding proteins that render the bacterium resistant to most β-lactam antibiotics (such as methicillin), by several S. aureus clones. The success of MRSA is a consequence of the extensive arsenal of virulence factors produced by S. aureus combined with β-lactam resistance and, for most clones, resistance to other antibiotic classes. Clinical manifestations of MRSA range from asymptomatic colonization of the nasal mucosa to mild skin and soft tissue infections to fulminant invasive disease with high mortality. Although treatment options for MRSA are limited, several new antimicrobials are under development. An understanding of colonization dynamics, routes of transmission, risk factors for progression to infection and conditions that promote the emergence of resistance will enable optimization of strategies to effectively control MRSA. Vaccine candidates are also under development and could become an effective prevention measure.

650 citations


Journal ArticleDOI
TL;DR: Simulations show that the ability to tune the average oxidation state of copper enables control over CO adsorption and dimerization, and makes it possible to implement a preference for the electrosynthesis of C2 products.
Abstract: The electrochemical reduction of CO2 to multi-carbon products has attracted much attention because it provides an avenue to the synthesis of value-added carbon-based fuels and feedstocks using renewable electricity Unfortunately, the efficiency of CO2 conversion to C2 products remains below that necessary for its implementation at scale Modifying the local electronic structure of copper with positive valence sites has been predicted to boost conversion to C2 products Here, we use boron to tune the ratio of Cuδ+ to Cu0 active sites and improve both stability and C2-product generation Simulations show that the ability to tune the average oxidation state of copper enables control over CO adsorption and dimerization, and makes it possible to implement a preference for the electrosynthesis of C2 products We report experimentally a C2 Faradaic efficiency of 79 ± 2% on boron-doped copper catalysts and further show that boron doping leads to catalysts that are stable for in excess of ~40 hours while electrochemically reducing CO2 to multi-carbon hydrocarbons

632 citations


Journal ArticleDOI
Federica Spoto1, Federica Spoto2, Paolo Tanga1, Francois Mignard1  +498 moreInstitutions (86)
TL;DR: In this paper, the authors describe the processing of the Gaia DR2 data, and describe the criteria used to select the sample published in Gaia DR 2, and explore the data set to assess its quality.
Abstract: Context. The Gaia spacecraft of the European Space Agency (ESA) has been securing observations of solar system objects (SSOs) since the beginning of its operations. Data Release 2 (DR2) contains the observations of a selected sample of 14,099 SSOs. These asteroids have been already identified and have been numbered by the Minor Planet Center repository. Positions are provided for each Gaia observation at CCD level. As additional information, complementary to astrometry, the apparent brightness of SSOs in the unfiltered G band is also provided for selected observations.Aims. We explain the processing of SSO data, and describe the criteria we used to select the sample published in Gaia DR2. We then explore the data set to assess its quality.Methods. To exploit the main data product for the solar system in Gaia DR2, which is the epoch astrometry of asteroids, it is necessary to take into account the unusual properties of the uncertainty, as the position information is nearly one-dimensional. When this aspect is handled appropriately, an orbit fit can be obtained with post-fit residuals that are overall consistent with the a-priori error model that was used to define individual values of the astrometric uncertainty. The role of both random and systematic errors is described. The distribution of residuals allowed us to identify possible contaminants in the data set (such as stars). Photometry in the G band was compared to computed values from reference asteroid shapes and to the flux registered at the corresponding epochs by the red and blue photometers (RP and BP).Results. The overall astrometric performance is close to the expectations, with an optimal range of brightness G ~ 12 − 17. In this range, the typical transit-level accuracy is well below 1 mas. For fainter asteroids, the growing photon noise deteriorates the performance. Asteroids brighter than G ~ 12 are affected by a lower performance of the processing of their signals. The dramatic improvement brought by Gaia DR2 astrometry of SSOs is demonstrated by comparisons to the archive data and by preliminary tests on the detection of subtle non-gravitational effects.

584 citations


Journal ArticleDOI
Amina Helmi1, F. van Leeuwen2, Paul J. McMillan3, Davide Massari1  +481 moreInstitutions (82)
TL;DR: In this paper, the second data release of the Gaia mission and its power for constraining many different aspects of the dynamics of the satellites of the Milky Way is demonstrated. But the accuracy of the errors, statistical and systematic, are relatively well understood.
Abstract: Context. Aims: The goal of this paper is to demonstrate the outstanding quality of the second data release of the Gaia mission and its power for constraining many different aspects of the dynamics of the satellites of the Milky Way. We focus here on determining the proper motions of 75 Galactic globular clusters, nine dwarf spheroidal galaxies, one ultra-faint system, and the Large and Small Magellanic Clouds. Methods: Using data extracted from the Gaia archive, we derived the proper motions and parallaxes for these systems, as well as their uncertainties. We demonstrate that the errors, statistical and systematic, are relatively well understood. We integrated the orbits of these objects in three different Galactic potentials, and characterised their properties. We present the derived proper motions, space velocities, and characteristic orbital parameters in various tables to facilitate their use by the astronomical community. Results: Our limited and straightforward analyses have allowed us for example to (i) determine absolute and very precise proper motions for globular clusters; (ii) detect clear rotation signatures in the proper motions of at least five globular clusters; (iii) show that the satellites of the Milky Way are all on high-inclination orbits, but that they do not share a single plane of motion; (iv) derive a lower limit for the mass of the Milky Way of 9.1-2.6+6.2 × 1011 M⊙ based on the assumption that the Leo I dwarf spheroidal is bound; (v) derive a rotation curve for the Large Magellanic Cloud based solely on proper motions that is competitive with line-of-sight velocity curves, now using many orders of magnitude more sources; and (vi) unveil the dynamical effect of the bar on the motions of stars in the Large Magellanic Cloud. Conclusions: All these results highlight the incredible power of the Gaia astrometric mission, and in particular of its second data release.

Journal ArticleDOI
Douglas M. Ruderfer1, Stephan Ripke2, Stephan Ripke3, Stephan Ripke4  +628 moreInstitutions (156)
14 Jun 2018-Cell
TL;DR: For the first time, specific loci that distinguish between BD and SCZ are discovered and polygenic components underlying multiple symptom dimensions are identified that point to the utility of genetics to inform symptomology and potential treatment.

Journal ArticleDOI
13 Sep 2018-Nature
TL;DR: A global modelling approach shows that in response to rises in global sea level, gains of up to 60% in coastal wetland areas are possible, if appropriate coastal management solutions are developed to help support wetland resilience.
Abstract: The response of coastal wetlands to sea-level rise during the twenty-first century remains uncertain Global-scale projections suggest that between 20 and 90 per cent (for low and high sea-level rise scenarios, respectively) of the present-day coastal wetland area will be lost, which will in turn result in the loss of biodiversity and highly valued ecosystem services1-3 These projections do not necessarily take into account all essential geomorphological4-7 and socio-economic system feedbacks8 Here we present an integrated global modelling approach that considers both the ability of coastal wetlands to build up vertically by sediment accretion, and the accommodation space, namely, the vertical and lateral space available for fine sediments to accumulate and be colonized by wetland vegetation We use this approach to assess global-scale changes in coastal wetland area in response to global sea-level rise and anthropogenic coastal occupation during the twenty-first century On the basis of our simulations, we find that, globally, rather than losses, wetland gains of up to 60 per cent of the current area are possible, if more than 37 per cent (our upper estimate for current accommodation space) of coastal wetlands have sufficient accommodation space, and sediment supply remains at present levels In contrast to previous studies1-3, we project that until 2100, the loss of global coastal wetland area will range between 0 and 30 per cent, assuming no further accommodation space in addition to current levels Our simulations suggest that the resilience of global wetlands is primarily driven by the availability of accommodation space, which is strongly influenced by the building of anthropogenic infrastructure in the coastal zone and such infrastructure is expected to change over the twenty-first century Rather than being an inevitable consequence of global sea-level rise, our findings indicate that large-scale loss of coastal wetlands might be avoidable, if sufficient additional accommodation space can be created through careful nature-based adaptation solutions to coastal management

Journal ArticleDOI
TL;DR: PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC, and showed an acceptable safety profile and clinical activity in a subset of patients with MBC.
Abstract: Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2–50 weeks and followed for 6–15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1− tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.

Journal ArticleDOI
Albert M. Sirunyan, Armen Tumasyan, Wolfgang Adam1, Federico Ambrogi1  +2238 moreInstitutions (159)
TL;DR: In this paper, the discriminating variables and the algorithms used for heavy-flavour jet identification during the first years of operation of the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, are presented.
Abstract: Many measurements and searches for physics beyond the standard model at the LHC rely on the efficient identification of heavy-flavour jets, i.e. jets originating from bottom or charm quarks. In this paper, the discriminating variables and the algorithms used for heavy-flavour jet identification during the first years of operation of the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, are presented. Heavy-flavour jet identification algorithms have been improved compared to those used previously at centre-of-mass energies of 7 and 8 TeV. For jets with transverse momenta in the range expected in simulated events, these new developments result in an efficiency of 68% for the correct identification of a b jet for a probability of 1% of misidentifying a light-flavour jet. The improvement in relative efficiency at this misidentification probability is about 15%, compared to previous CMS algorithms. In addition, for the first time algorithms have been developed to identify jets containing two b hadrons in Lorentz-boosted event topologies, as well as to tag c jets. The large data sample recorded in 2016 at a centre-of-mass energy of 13 TeV has also allowed the development of new methods to measure the efficiency and misidentification probability of heavy-flavour jet identification algorithms. The b jet identification efficiency is measured with a precision of a few per cent at moderate jet transverse momenta (between 30 and 300 GeV) and about 5% at the highest jet transverse momenta (between 500 and 1000 GeV).

Journal ArticleDOI
Patrycja Nowak-Sliwinska1, Kari Alitalo2, Elizabeth Allen3, Andrey Anisimov2, Alfred C. Aplin4, Robert Auerbach5, Hellmut G. Augustin6, Hellmut G. Augustin7, David O. Bates8, Judy R. van Beijnum9, R. Hugh F. Bender10, Gabriele Bergers3, Gabriele Bergers11, Andreas Bikfalvi12, Joyce Bischoff13, Barbara C. Böck6, Barbara C. Böck7, Peter C. Brooks14, Federico Bussolino15, Bertan Cakir13, Peter Carmeliet3, Daniel Castranova16, Anca Maria Cimpean, Ondine Cleaver17, George Coukos18, George E. Davis19, Michele De Palma20, Anna Dimberg21, Ruud P.M. Dings22, Valentin Djonov23, Andrew C. Dudley24, Neil Dufton25, Sarah-Maria Fendt3, Napoleone Ferrara26, Marcus Fruttiger27, Dai Fukumura13, Bart Ghesquière28, Bart Ghesquière3, Yan Gong13, Robert J. Griffin22, Adrian L. Harris29, Christopher C.W. Hughes10, Nan W. Hultgren10, M. Luisa Iruela-Arispe30, Melita Irving18, Rakesh K. Jain13, Raghu Kalluri31, Joanna Kalucka3, Robert S. Kerbel32, Jan Kitajewski33, Ingeborg Klaassen34, Hynda K. Kleinmann35, Pieter Koolwijk18, Elisabeth Kuczynski32, Brenda R. Kwak1, Koen Marien, Juan M. Melero-Martin13, Lance L. Munn13, Roberto F. Nicosia4, Agnès Noël36, Jussi Nurro37, Anna-Karin Olsson21, Tatiana V. Petrova38, Kristian Pietras, Roberto Pili39, Jeffrey W. Pollard40, Mark J. Post41, Paul H.A. Quax42, Gabriel A. Rabinovich43, Marius Raica, Anna M. Randi25, Domenico Ribatti44, Curzio Rüegg45, Reinier O. Schlingemann18, Reinier O. Schlingemann34, Stefan Schulte-Merker, Lois E.H. Smith13, Jonathan W. Song46, Steven A. Stacker47, Jimmy Stalin, Amber N. Stratman16, Maureen Van de Velde36, Victor W.M. van Hinsbergh18, Peter B. Vermeulen48, Johannes Waltenberger49, Brant M. Weinstein16, Hong Xin26, Bahar Yetkin-Arik34, Seppo Ylä-Herttuala37, Mervin C. Yoder39, Arjan W. Griffioen9 
University of Geneva1, University of Helsinki2, Katholieke Universiteit Leuven3, University of Washington4, University of Wisconsin-Madison5, Heidelberg University6, German Cancer Research Center7, University of Nottingham8, VU University Amsterdam9, University of California, Irvine10, University of California, San Francisco11, French Institute of Health and Medical Research12, Harvard University13, Maine Medical Center14, University of Turin15, National Institutes of Health16, University of Texas Southwestern Medical Center17, University of Lausanne18, University of Missouri19, École Polytechnique Fédérale de Lausanne20, Uppsala University21, University of Arkansas for Medical Sciences22, University of Bern23, University of Virginia24, Imperial College London25, University of California, San Diego26, University College London27, Flanders Institute for Biotechnology28, University of Oxford29, University of California, Los Angeles30, University of Texas MD Anderson Cancer Center31, University of Toronto32, University of Illinois at Chicago33, University of Amsterdam34, George Washington University35, University of Liège36, University of Eastern Finland37, Ludwig Institute for Cancer Research38, Indiana University39, University of Edinburgh40, Maastricht University41, Loyola University Medical Center42, National Scientific and Technical Research Council43, University of Bari44, University of Fribourg45, Ohio State University46, University of Melbourne47, University of Antwerp48, University of Münster49
TL;DR: In vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis are described and critical aspects that are relevant for their execution and proper interpretation are highlighted.
Abstract: The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.

Journal ArticleDOI
TL;DR: The multiplex PCR protocol should be particularly interesting in settings or laboratories with limited resources for performing genetic analysis as it provides information on the mechanism of colistin resistance without requiring genome sequencing.
Abstract: Background and aimPlasmid-mediated colistin resistance mechanisms have been identified worldwide in the past years. A multiplex polymerase chain reaction (PCR) protocol for detection of all currently known transferable colistin resistance genes (mcr-1 to mcr-5, and variants) in Enterobacteriaceae was developed for surveillance or research purposes. Methods: We designed four new primer pairs to amplify mcr-1, mcr-2, mcr-3 and mcr-4 gene products and used the originally described primers for mcr-5 to obtain a stepwise separation of ca 200 bp between amplicons. The primer pairs and amplification conditions allow for single or multiple detection of all currently described mcr genes and their variants present in Enterobacteriaceae. The protocol was validated testing 49 European Escherichia coli and Salmonella isolates of animal origin. Results: Multiplex PCR results in bovine and porcine isolates from Spain, Germany, France and Italy showed full concordance with whole genome sequence data. The method was able to detect mcr-1, mcr-3 and mcr-4 as singletons or in different combinations as they were present in the test isolates. One new mcr-4 variant, mcr-4.3, was also identified. Conclusions: This method allows rapid identification of mcr-positive bacteria and overcomes the challenges of phenotypic detection of colistin resistance. The multiplex PCR should be particularly interesting in settings or laboratories with limited resources for performing genetic analysis as it provides information on the mechanism of colistin resistance without requiring genome sequencing.

Journal ArticleDOI
TL;DR: Current knowledge on SCAD is set-out for the benefit of practicing clinicians caring for patients with this condition and the consensus on contemporary management and areas of controversy and uncertainty are presented.
Abstract: Spontaneous coronary artery dissection (SCAD) has long been recognized as a cause of acute coronary syndromes (ACS). Initially considered very rare and associated primarily with pregnancy and the peripartum period, the use of higher sensitivity Troponin assays and early angiography in ACS, coupled with greater awareness of the condition, has led to increased diagnosis, and it is now understood that SCAD represents a significant cause of ACS in predominantly young to middle-aged women, with most cases occurring outside the context of recent pregnancy.1,2 Although there are no randomized controlled trials in SCAD, knowledge has further advanced in the last 5-years as a result of an international research effort primarily focused on building and studying national SCAD registries.3–19 These studies have demonstrated, not only that SCAD is a distinct pathophysiological entity, but that there are key differences in management and outcomes compared to ACS of atherosclerotic aetiology. This position paper aims to set-out current knowledge on SCAD for the benefit of practicing clinicians caring for patients with this condition. It presents the consensus on contemporary management and areas of controversy and uncertainty, which remain a focus of ongoing research. The information is provided to support clinical care providers but is not intended to replace individualized decision-making by clinicians and other health care professionals.

Journal ArticleDOI
Ann Versporten1, Peter Zarb2, Isabelle Caniaux3, Marie Francoise Gros3, Nico Drapier1, Mark Miller3, Vincent Jarlier4, Dilip Nathwani5, Herman Goossens1, Andi Koraqi6, Iris Hoxha, Silva Tafaj, Denada Lacej, Martin Hojman, Rodolfo Ernesto Quiros, Lilit Ghazaryan, Kelly A. Cairns, Allen C. Cheng, Kylie Horne, Fiona F. Doukas, Thomas Gottlieb, Jameela Alsalman, Koen Magerman, Gounongbe Yt Marielle, Amela Dedeic Ljubovic, André Afonso Machado Coelho, Ana Cristina Gales, Emma Keuleyan, Deana Sabuda, Jennifer Lee Boswell, John M. Conly, Alvaro Rojas, Camila Carvajal, Jaime Labarca, Antonio Solano, Carlos Ramírez Valverde, Juan M. Villalobos-Vindas, Irina Pristaš, Vanda Plecko, Niki Paphitou, Erjona Shaqiri, Maija Liisa Rummukainen, Karaman Pagava, Irma Korinteli, Tobias Brandt, Sabine Messler, Anthony Enimil, Elias Iosifidis, Emmanuel Roilides, Mamadou Saliou Sow, Sharmila Sengupta, Joby V. George, Aruna Poojary, Priyanka Patil, Jafar Soltani, Zahra Jafarpour, Hadi Ameen, David Fitzgerald, Yasmin Maor, Michal Chowers, Elizabeth Temkin, Susanna Esposito, Luca Arnoldo, Silvio Brusaferro, Yoshiaki Gu, Feras Darwish El-Hajji, Nam Joong Kim, Baktygul Kambaralieva, Jana Pavare, Lelde Zarakauska, Vytautas Usonis, Sigita Burokiene, Inga Ivaskeviciene, Gordana Mijovic, Natasa Duborija-Kovacevic, Kristen Bondesio, Kenneth Iregbu, OO Oduyebo, Denis Raka, Lul Raka, Svetlana Rachina, Mushira Enani, Mohamed Al Shehri, Biljana Carevic, Gorana Dragovac, Dusanka Obradovic, Aleksandra Stojadinovic, Lili Radulovic, Jia En Wu, Gladys Wei Teng Chung, Hui Hiong Chen, Paul A. Tambyah, David C. Lye, Sock Hoon Tan, Tat Ming Ng, Hui Lin Tay, Moi Lin Ling, Maciej Piotr Chlebicki, Andrea L. Kwa, Winnie Lee, Bojana Beović, Angela Dramowski, Heather Finlayson, Jantjie Taljaard, Guillermo Ojeda-Burgos, Pilar Retamar, Johan Lucas, Wolter Pot, Cees Verduin, Jan Kluytmans, Michael G. Scott, Mamoon A. Aldeyab, Bernadette McCullagh, Cairine Gormley, David Sharpe, Mark Gilchrist, Laura Whitney, Matthew Laundy, Debbie Lockwood, Simon B. Drysdale, Jennifer Boudreaux, Edward J. Septimus, Nickie Greer, Gerard Gawrys, Edgar Rios, Suzanne May 
TL;DR: Detailed data about antimicrobial prescribing and resistance from hospitals worldwide will help to improve the quality of antibiotic prescribing through education and practice changes, particularly in low-income and middle-income countries that have no tools to monitor antibiotic prescribing in hospitals.

Journal ArticleDOI
TL;DR: Withaferin A (WA) is identified as a natural ferroptosis-inducing agent in neuroblastoma, which acts through a novel double-edged mechanism that might explain the superior efficacy of WA as compared with etoposide or cisplatin in killing a heterogeneous panel of high-risk Neuroblastoma cells, and in suppressing the growth and relapse rate of neuroblastomas xenografts.
Abstract: High-risk neuroblastoma is a devastating malignancy with very limited therapeutic options. Here, we identify withaferin A (WA) as a natural ferroptosis-inducing agent in neuroblastoma, which acts through a novel double-edged mechanism. WA dose-dependently either activates the nuclear factor-like 2 pathway through targeting of Kelch-like ECH-associated protein 1 (noncanonical ferroptosis induction) or inactivates glutathione peroxidase 4 (canonical ferroptosis induction). Noncanonical ferroptosis induction is characterized by an increase in intracellular labile Fe(II) upon excessive activation of heme oxygenase-1, which is sufficient to induce ferroptosis. This double-edged mechanism might explain the superior efficacy of WA as compared with etoposide or cisplatin in killing a heterogeneous panel of high-risk neuroblastoma cells, and in suppressing the growth and relapse rate of neuroblastoma xenografts. Nano-targeting of WA allows systemic application and suppressed tumor growth due to an enhanced accumulation at the tumor site. Collectively, our data propose a novel therapeutic strategy to efficiently kill cancer cells by ferroptosis.

Journal ArticleDOI
TL;DR: In this article, the most common types of plasma reactors with their characteristic features are presented, illustrating why some plasma types exhibit better energy efficiency than others, and highlighting current research in the fields of CO2 conversion (including the combined conversion of CO 2 with CH4, H2O, or H2) as well as N2 fixation (for NH3 or NOx synthesis).
Abstract: Plasma technology is gaining increasing interest for gas conversion applications, such as CO2 conversion into value-added chemicals or renewable fuels, and N2 fixation from the air, to be used for the production of small building blocks for, e.g., mineral fertilizers. Plasma is generated by electric power and can easily be switched on/off, making it, in principle, suitable for using intermittent renewable electricity. In this Perspective article, we explain why plasma might be promising for this application. We briefly present the most common types of plasma reactors with their characteristic features, illustrating why some plasma types exhibit better energy efficiency than others. We also highlight current research in the fields of CO2 conversion (including the combined conversion of CO2 with CH4, H2O, or H2) as well as N2 fixation (for NH3 or NOx synthesis). Finally, we discuss the major limitations and steps to be taken for further improvement.

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TL;DR: The finding that VSMC senescence can promote Atherosclerosis further illustrates that normal, adequate VSMC function is crucial in protecting the vessel wall against atherosclerosis.
Abstract: In the present review, we describe the causes and consequences of loss of vascular smooth muscle cells (VSMCs) or their function in advanced atherosclerotic plaques and discuss possible mechanisms such as cell death or senescence, and induction of autophagy to promote cell survival. We also highlight the potential use of pharmacological modulators of these processes to limit plaque progression and/or improve plaque stability. VSMCs play a pivotal role in atherogenesis. Loss of VSMCs via initiation of cell death leads to fibrous cap thinning and promotes necrotic core formation and calcification. VSMC apoptosis is induced by pro-inflammatory cytokines, oxidized low density lipoprotein, high levels of nitric oxide and mechanical injury. Apoptotic VSMCs are characterized by a thickened basal lamina surrounding the cytoplasmic remnants of the VSMC. Inefficient clearance of apoptotic VSMCs results in secondary necrosis and subsequent inflammation. A critical determinant in the VSMC stress response and phenotypic switching is autophagy, which is activated by various stimuli, including reactive oxygen and lipid species, cytokines, growth factors and metabolic stress. Successful autophagy stimulates VSMC survival, whereas reduced autophagy promotes age-related changes in the vasculature. Recently, an interesting link between autophagy and VSMC senescence has been uncovered. Defective VSMC autophagy accelerates not only the development of stress-induced premature senescence but also atherogenesis, albeit without worsening plaque stability. VSMC senescence in atherosclerosis is likely a result of replicative senescence and/or stress-induced premature senescence in response to DNA damaging and/or oxidative stress-inducing stimuli. The finding that VSMC senescence can promote atherosclerosis further illustrates that normal, adequate VSMC function is crucial in protecting the vessel wall against atherosclerosis.

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TL;DR: The prevalence of sexting has increased in recent years and increases as youth age, and further research focusing on nonconsensual sexts is necessary to appropriately target and inform intervention, education, and policy efforts.
Abstract: Importance The existing literature on sexting among youth shows that sexting is a predictor of sexual behavior and may be associated with other health outcomes and risky behaviors. However, there remains a lack of consensus on the prevalence of sexting, which is needed to inform future research, intervention, and policy development. Objective To provide a meta-analytic synthesis of studies examining the prevalence of multiple forms of sexting behavior, analyzed by age, sex, geography, and method of sexting. Data Sources In an academic setting, electronic searches in MEDLINE, PsycINFO, EMBASE, and Web of Science were conducted for the period January 1990 to June 2016, yielding 1147 nonduplicate records. Study Selection Studies were included if participants were younger than 18 years and the prevalence of sexting explicit images, videos, or messages was reported. Data Extraction and Synthesis Literature review and data extraction followed established PRISMA guidelines. Two independent reviewers extracted all relevant data. Random-effects meta-analyses were used to derive the mean prevalence rates. Thirty-nine studies met final inclusion criteria. Main Outcomes and Measures Meta-analyses of the prevalence of sending, receiving, and forwarding without consent, as well as having one’s sext forwarded without consent. Results Among 39 included studies, there were 110 380 participants; the mean age was 15.16 years (age range, 11.9-17.0 years), and on average 47.2% were male. Studies were available for sending (n = 34), receiving (n = 20), forwarding without consent (n = 5), and having a sext forwarded without consent (n = 4). The mean prevalences for sending and receiving sexts were 14.8% (95% CI, 12.8%-16.8%) and 27.4% (95% CI, 23.1%-31.7%), respectively. Moderator analyses revealed that effect sizes varied as a function of child age (prevalence increased with age), year of data collection (prevalence increased over time), and sexting method (higher prevalence on mobile devices compared with computers). The prevalence of forwarding a sext without consent was 12.0% (95% CI, 8.4%-15.6%), and the prevalence of having a sext forwarded without consent was 8.4% (95% CI, 4.7%-12.0%). Conclusions and Relevance The prevalence of sexting has increased in recent years and increases as youth age. Further research focusing on nonconsensual sexting is necessary to appropriately target and inform intervention, education, and policy efforts.

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TL;DR: In this paper, the performance of the modified system is studied using proton-proton collision data at center-of-mass energy √s=13 TeV, collected at the LHC in 2015 and 2016.
Abstract: The CMS muon detector system, muon reconstruction software, and high-level trigger underwent significant changes in 2013–2014 in preparation for running at higher LHC collision energy and instantaneous luminosity. The performance of the modified system is studied using proton-proton collision data at center-of-mass energy √s=13 TeV, collected at the LHC in 2015 and 2016. The measured performance parameters, including spatial resolution, efficiency, and timing, are found to meet all design specifications and are well reproduced by simulation. Despite the more challenging running conditions, the modified muon system is found to perform as well as, and in many aspects better than, previously. We dedicate this paper to the memory of Prof. Alberto Benvenuti, whose work was fundamental for the CMS muon detector.

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TL;DR: A global tree mortality map is updated and a roadmap to a more holistic understanding of forest mortality across scales is presented to achieve scientific understanding for realistic predictions of drought-induced tree mortality.
Abstract: Accumulating evidence highlights increased mortality risks for trees during severe drought, particularly under warmer temperatures and increasing vapour pressure deficit (VPD). Resulting forest die-off events have severe consequences for ecosystem services, biophysical and biogeochemical land–atmosphere processes. Despite advances in monitoring, modelling and experimental studies of the causes and consequences of tree death from individual tree to ecosystem and global scale, a general mechanistic understanding and realistic predictions of drought mortality under future climate conditions are still lacking. We update a global tree mortality map and present a roadmap to a more holistic understanding of forest mortality across scales. We highlight priority research frontiers that promote: (1) new avenues for research on key tree ecophysiological responses to drought; (2) scaling from the tree/plot level to the ecosystem and region; (3) improvements of mortality risk predictions based on both empirical and mechanistic insights; and (4) a global monitoring network of forest mortality. In light of recent and anticipated large forest die-off events such a research agenda is timely and needed to achieve scientific understanding for realistic predictions of drought-induced tree mortality. The implementation of a sustainable network will require support by stakeholders and political authorities at the international level.

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TL;DR: This work estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods and used the cohort-component method of population projection, with inputs of fertility, mortality, population, and migration data.

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TL;DR: A plasma is a partially ionized gas, consisting of electrons, ions, molecules, radicals, photons, and excited species, which are all active species for catalyst preparation and treatment.
Abstract: Catalyst preparation with plasmas is increasingly attracting interest A plasma is a partially ionized gas, consisting of electrons, ions, molecules, radicals, photons, and excited species, which are all active species for catalyst preparation and treatment Under the influence of plasma, nucleation and crystal growth in catalyst preparation can be very different from those in the conventional thermal approach Some thermodynamically unfavorable reactions can easily take place with plasmas Compounds such as sulfides, nitrides, and phosphides that are produced under harsh conditions can be synthesized by plasma under mild conditions Plasmas can produce catalysts with smaller particle sizes and controllable structure Plasma is also a facile tool for reduction, oxidation, doping, etching, coating, alloy formation, surface treatment, and surface cleaning in a simple and direct way A rapid and convenient plasma template removal has thus been established for zeolite synthesis It can operate at room tempera

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TL;DR: This work implements cutting-edge Reinforcement Learning techniques and shows that their performance is comparable to optimal control methods in the task of finding short, high-fidelity driving protocol from an initial to a target state in non-integrable many-body quantum systems of interacting qubits.
Abstract: New experiments show that reinforcement learning algorithms, a cutting-edge technique for machine learning, can quickly and accurately learn to prepare a desired quantum state despite no knowledge of quantum mechanics.

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TL;DR: Women in the USA and western Europe have higher prepregnancy BMI and higher rates of gestational weight gain outside 2009 IOM guidelines than women in east Asia, however, when using regional BMI categories inEast Asia, rates of GWG above guidelines are similar across the three continents.
Abstract: The association between Institute of Medicine (IOM) guidelines and pregnancy outcomes across ethnicities is uncertain. We evaluated the associations of gestational weight gain (GWG) outside 2009 IOM guidelines, with maternal and infant outcomes across the USA, western Europe and east Asia, with subgroup analyses in Asia. The aim was to explore ethnic differences in maternal prepregnancy body mass index (BMI), GWG and health outcomes across these regions. Systematic review, meta-analysis and meta-regression of observational studies were used for the study. MEDLINE, MEDLINE In-Process, Embase and all Evidence-Based Medicine (EBM) Reviews were searched from 1999 to 2017. Studies were stratified by prepregnancy BMI category and total pregnancy GWG. Odds ratio (ORs) 95% confidence intervals (CI) applied recommended GWG within each BMI category as the reference. Primary outcomes were small for gestational age (SGA), preterm birth and large for gestational age (LGA). Secondary outcomes were macrosomia, caesarean section and gestational diabetes. Overall, 5874 studies were identified and 23 were included (n = 1,309,136). Prepregnancy overweight/obesity in the USA, Europe and Asia was measured at 42%, 30% and 10% respectively, with underweight 5%, 3% and 17%. GWG below guidelines in the USA, Europe and Asia was 21%, 18% and 31%, and above was 51%, 51% and 37% respectively. Applying regional BMI categories in Asia showed GWG above guidelines (51%) was similar to that in the USA and Europe. GWG below guidelines was associated with a higher risk of SGA (USA/Europe [OR 1.51; CI 1.39, 1.63]; Asia [1.63; 1.45, 1.82]) and preterm birth (USA/Europe [1.35; 1.17, 1.56]; Asia [1.06; 0.78, 1.44]) than GWG within guidelines. GWG above guidelines was associated with a higher risk of LGA (USA/Europe [1.93; 1.81, 2.06]; Asia [1.68; 1.51 , 1.87]), macrosomia (USA/Europe [1.87; 1.70, 2.06]; Asia [2.18; 1.91, 2.49]) and caesarean (USA/Europe [1.26; 1.21, 1.33]; Asia [1.37; 1.30, 1.45]). Risks remained elevated when regional BMI categories were applied for GWG recommendations. More women in Asia were categorised as having GWG below guidelines using World Health Organization (WHO) (60%) compared to regional BMI categories (16%), yet WHO BMI was not accompanied by increased risks of adverse outcomes. Women in the USA and western Europe have higher prepregnancy BMI and higher rates of GWG above guidelines than women in east Asia. However, when using regional BMI categories in east Asia, rates of GWG above guidelines are similar across the three continents. GWG outside guidelines is associated with adverse outcomes across all regions. If regional BMI categories are used in east Asia, IOM guidelines are applicable in the USA, western Europe and east Asia.

Journal ArticleDOI
Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam, Federico Ambrogi  +2240 moreInstitutions (157)
TL;DR: In this article, a measurement of the H→ττ signal strength is performed using events recorded in proton-proton collisions by the CMS experiment at the LHC in 2016 at a center-of-mass energy of 13TeV.