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Showing papers by "Trinity College, Dublin published in 2019"


Journal ArticleDOI
TL;DR: The extent and consequences of oral diseases, their social and commercial determinants, and their ongoing neglect in global health policy are described to highlight the urgent need to address oral diseases among other NCDs as a global health priority.

1,349 citations


Journal ArticleDOI
Eli A. Stahl1, Eli A. Stahl2, Gerome Breen3, Andreas J. Forstner  +339 moreInstitutions (107)
TL;DR: Genome-wide analysis identifies 30 loci associated with bipolar disorder, allowing for comparisons of shared genes and pathways with other psychiatric disorders, including schizophrenia and depression.
Abstract: Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.

1,090 citations


Journal ArticleDOI
Andrea Cossarizza1, Hyun-Dong Chang, Andreas Radbruch, Andreas Acs2  +459 moreInstitutions (160)
TL;DR: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community providing the theory and key practical aspects offlow cytometry enabling immunologists to avoid the common errors that often undermine immunological data.
Abstract: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.

698 citations


Journal ArticleDOI
TL;DR: A systematic review of the empirical literature based on the major topics that have been associated with the market for cryptocurrencies since their development as a financial asset in 2009 is presented in this article, where the authors provide a systematic analysis of the main topics that influence the perception of cryptocurrencies as a credible investment asset class and legitimate of value.

623 citations


Journal ArticleDOI
29 Apr 2019-eLife
TL;DR: The goal is to facilitate a more accurate use of the stop-signal task and provide user-friendly open-source resources intended to inform statistical-power considerations, facilitate the correct implementation of the task, and assist in proper data analysis.
Abstract: Response inhibition is essential for navigating everyday life. Its derailment is considered integral to numerous neurological and psychiatric disorders, and more generally, to a wide range of behavioral and health problems. Response-inhibition efficiency furthermore correlates with treatment outcome in some of these conditions. The stop-signal task is an essential tool to determine how quickly response inhibition is implemented. Despite its apparent simplicity, there are many features (ranging from task design to data analysis) that vary across studies in ways that can easily compromise the validity of the obtained results. Our goal is to facilitate a more accurate use of the stop-signal task. To this end, we provide 12 easy-to-implement consensus recommendations and point out the problems that can arise when they are not followed. Furthermore, we provide user-friendly open-source resources intended to inform statistical-power considerations, facilitate the correct implementation of the task, and assist in proper data analysis.

617 citations


Journal ArticleDOI
TL;DR: Highly concentrated, additive-free, aqueous and organic MXene-based inks that can be used for high-resolution extrusion and inkjet printing are reported.
Abstract: Direct printing of functional inks is critical for applications in diverse areas including electrochemical energy storage, smart electronics and healthcare. However, the available printable ink formulations are far from ideal. Either surfactants/additives are typically involved or the ink concentration is low, which add complexity to the manufacturing and compromises the printing resolution. Here, we demonstrate two types of two-dimensional titanium carbide (Ti3C2Tx) MXene inks, aqueous and organic in the absence of any additive or binary-solvent systems, for extrusion printing and inkjet printing, respectively. We show examples of all-MXene-printed structures, such as micro-supercapacitors, conductive tracks and ohmic resistors on untreated plastic and paper substrates, with high printing resolution and spatial uniformity. The volumetric capacitance and energy density of the all-MXene-printed micro-supercapacitors are orders of magnitude greater than existing inkjet/extrusion-printed active materials. The versatile direct-ink-printing technique highlights the promise of additive-free MXene inks for scalable fabrication of easy-to-integrate components of printable electronics.

611 citations


Journal ArticleDOI
TL;DR: This work advocates change towards individually tailored interventions that preserve an individual's independence, physical function, and cognition by promoting the recognition of frailty, furthering advancements in evidence-based treatment options, and identifying cost-effective care delivery strategies.

567 citations


Journal ArticleDOI
A. Abada1, Marcello Abbrescia2, Marcello Abbrescia3, Shehu S. AbdusSalam4  +1491 moreInstitutions (239)
TL;DR: In this article, the authors present the second volume of the Future Circular Collider Conceptual Design Report, devoted to the electron-positron collider FCC-ee, and present the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan.
Abstract: In response to the 2013 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) study was launched, as an international collaboration hosted by CERN. This study covers a highest-luminosity high-energy lepton collider (FCC-ee) and an energy-frontier hadron collider (FCC-hh), which could, successively, be installed in the same 100 km tunnel. The scientific capabilities of the integrated FCC programme would serve the worldwide community throughout the 21st century. The FCC study also investigates an LHC energy upgrade, using FCC-hh technology. This document constitutes the second volume of the FCC Conceptual Design Report, devoted to the electron-positron collider FCC-ee. After summarizing the physics discovery opportunities, it presents the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan. FCC-ee can be built with today’s technology. Most of the FCC-ee infrastructure could be reused for FCC-hh. Combining concepts from past and present lepton colliders and adding a few novel elements, the FCC-ee design promises outstandingly high luminosity. This will make the FCC-ee a unique precision instrument to study the heaviest known particles (Z, W and H bosons and the top quark), offering great direct and indirect sensitivity to new physics.

526 citations


Journal ArticleDOI
TL;DR: In this article, a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts is described. But despite the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work.
Abstract: This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.

469 citations


Journal ArticleDOI
F. Kyle Satterstrom1, Jack A. Kosmicki1, Jiebiao Wang2, Michael S. Breen3  +150 moreInstitutions (45)
TL;DR: Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, 102 risk genes are identified at a false discovery rate of ≤ 0.1, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD.
Abstract: We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained for severe neurodevelopmental delay, while 53 show higher frequencies in individuals ascertained for ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most of the risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In human cortex single-cell gene expression data, expression of risk genes is enriched in both excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD.

461 citations


Journal ArticleDOI
TL;DR: An overview of the application of ML to optical communications and networking is provided, relevant literature is classified and surveyed, and an introductory tutorial on ML is provided for researchers and practitioners interested in this field.
Abstract: Today’s telecommunication networks have become sources of enormous amounts of widely heterogeneous data. This information can be retrieved from network traffic traces, network alarms, signal quality indicators, users’ behavioral data, etc. Advanced mathematical tools are required to extract meaningful information from these data and take decisions pertaining to the proper functioning of the networks from the network-generated data. Among these mathematical tools, machine learning (ML) is regarded as one of the most promising methodological approaches to perform network-data analysis and enable automated network self-configuration and fault management. The adoption of ML techniques in the field of optical communication networks is motivated by the unprecedented growth of network complexity faced by optical networks in the last few years. Such complexity increase is due to the introduction of a huge number of adjustable and interdependent system parameters (e.g., routing configurations, modulation format, symbol rate, coding schemes, etc.) that are enabled by the usage of coherent transmission/reception technologies, advanced digital signal processing, and compensation of nonlinear effects in optical fiber propagation. In this paper we provide an overview of the application of ML to optical communications and networking. We classify and survey relevant literature dealing with the topic, and we also provide an introductory tutorial on ML for researchers and practitioners interested in this field. Although a good number of research papers have recently appeared, the application of ML to optical networks is still in its infancy: to stimulate further work in this area, we conclude this paper proposing new possible research directions.

Journal ArticleDOI
Matteo Dainese1, Emily A. Martin1, Marcelo A. Aizen2, Matthias Albrecht, Ignasi Bartomeus3, Riccardo Bommarco4, Luísa G. Carvalheiro5, Luísa G. Carvalheiro6, Rebecca Chaplin-Kramer7, Vesna Gagic8, Lucas Alejandro Garibaldi9, Jaboury Ghazoul10, Heather Grab11, Mattias Jonsson4, Daniel S. Karp12, Christina M. Kennedy13, David Kleijn14, Claire Kremen15, Douglas A. Landis16, Deborah K. Letourneau17, Lorenzo Marini18, Katja Poveda11, Romina Rader19, Henrik G. Smith20, Teja Tscharntke21, Georg K.S. Andersson20, Isabelle Badenhausser22, Isabelle Badenhausser23, Svenja Baensch21, Antonio Diego M. Bezerra24, Felix J.J.A. Bianchi14, Virginie Boreux10, Virginie Boreux25, Vincent Bretagnolle23, Berta Caballero-López, Pablo Cavigliasso26, Aleksandar Ćetković27, Natacha P. Chacoff28, Alice Classen1, Sarah Cusser29, Felipe D. da Silva e Silva30, G. Arjen de Groot14, Jan H. Dudenhöffer31, Johan Ekroos20, Thijs P.M. Fijen14, Pierre Franck22, Breno Magalhães Freitas24, Michael P.D. Garratt32, Claudio Gratton33, Juliana Hipólito34, Juliana Hipólito9, Andrea Holzschuh1, Lauren Hunt35, Aaron L. Iverson11, Shalene Jha36, Tamar Keasar37, Tania N. Kim38, Miriam Kishinevsky37, Björn K. Klatt21, Björn K. Klatt20, Alexandra-Maria Klein25, Kristin M. Krewenka39, Smitha Krishnan40, Smitha Krishnan10, Ashley E. Larsen41, Claire Lavigne22, Heidi Liere42, Bea Maas43, Rachel E. Mallinger44, Eliana Martinez Pachon, Alejandra Martínez-Salinas45, Timothy D. Meehan46, Matthew G. E. Mitchell15, Gonzalo Alberto Roman Molina47, Maike Nesper10, Lovisa Nilsson20, Megan E. O'Rourke48, Marcell K. Peters1, Milan Plećaš27, Simon G. Potts33, Davi de L. Ramos, Jay A. Rosenheim12, Maj Rundlöf20, Adrien Rusch49, Agustín Sáez2, Jeroen Scheper14, Matthias Schleuning, Julia Schmack50, Amber R. Sciligo51, Colleen L. Seymour, Dara A. Stanley52, Rebecca Stewart20, Jane C. Stout53, Louis Sutter, Mayura B. Takada54, Hisatomo Taki, Giovanni Tamburini25, Matthias Tschumi, Blandina Felipe Viana55, Catrin Westphal21, Bryony K. Willcox19, Stephen D. Wratten56, Akira Yoshioka57, Carlos Zaragoza-Trello3, Wei Zhang58, Yi Zou59, Ingolf Steffan-Dewenter1 
University of Würzburg1, National University of Comahue2, Spanish National Research Council3, Swedish University of Agricultural Sciences4, Universidade Federal de Goiás5, University of Lisbon6, Stanford University7, Commonwealth Scientific and Industrial Research Organisation8, National University of Río Negro9, ETH Zurich10, Cornell University11, University of California, Davis12, The Nature Conservancy13, Wageningen University and Research Centre14, University of British Columbia15, Great Lakes Bioenergy Research Center16, University of California, Santa Cruz17, University of Padua18, University of New England (Australia)19, Lund University20, University of Göttingen21, Institut national de la recherche agronomique22, University of La Rochelle23, Federal University of Ceará24, University of Freiburg25, Concordia University Wisconsin26, University of Belgrade27, National University of Tucumán28, Michigan State University29, University of Brasília30, University of Greenwich31, University of Reading32, University of Wisconsin-Madison33, National Institute of Amazonian Research34, Boise State University35, University of Texas at Austin36, University of Haifa37, Kansas State University38, University of Hamburg39, Bioversity International40, University of California, Santa Barbara41, Seattle University42, University of Vienna43, University of Florida44, Centro Agronómico Tropical de Investigación y Enseñanza45, National Audubon Society46, University of Buenos Aires47, Virginia Tech48, University of Bordeaux49, University of Auckland50, University of California, Berkeley51, University College Dublin52, Trinity College, Dublin53, University of Tokyo54, Federal University of Bahia55, Lincoln University (New Zealand)56, National Institute for Environmental Studies57, International Food Policy Research Institute58, Xi'an Jiaotong-Liverpool University59
TL;DR: Using a global database from 89 studies (with 1475 locations), the relative importance of species richness, abundance, and dominance for pollination; biological pest control; and final yields in the context of ongoing land-use change is partitioned.
Abstract: Human land use threatens global biodiversity and compromises multiple ecosystem functions critical to food production. Whether crop yield-related ecosystem services can be maintained by a few dominant species or rely on high richness remains unclear. Using a global database from 89 studies (with 1475 locations), we partition the relative importance of species richness, abundance, and dominance for pollination; biological pest control; and final yields in the context of ongoing land-use change. Pollinator and enemy richness directly supported ecosystem services in addition to and independent of abundance and dominance. Up to 50% of the negative effects of landscape simplification on ecosystem services was due to richness losses of service-providing organisms, with negative consequences for crop yields. Maintaining the biodiversity of ecosystem service providers is therefore vital to sustain the flow of key agroecosystem benefits to society.

Journal ArticleDOI
A. Abada1, Marcello Abbrescia2, Marcello Abbrescia3, Shehu S. AbdusSalam4  +1496 moreInstitutions (238)
TL;DR: In this paper, the authors describe the detailed design and preparation of a construction project for a post-LHC circular energy frontier collider in collaboration with national institutes, laboratories and universities worldwide, and enhanced by a strong participation of industrial partners.
Abstract: Particle physics has arrived at an important moment of its history. The discovery of the Higgs boson, with a mass of 125 GeV, completes the matrix of particles and interactions that has constituted the “Standard Model” for several decades. This model is a consistent and predictive theory, which has so far proven successful at describing all phenomena accessible to collider experiments. However, several experimental facts do require the extension of the Standard Model and explanations are needed for observations such as the abundance of matter over antimatter, the striking evidence for dark matter and the non-zero neutrino masses. Theoretical issues such as the hierarchy problem, and, more in general, the dynamical origin of the Higgs mechanism, do likewise point to the existence of physics beyond the Standard Model. This report contains the description of a novel research infrastructure based on a highest-energy hadron collider with a centre-of-mass collision energy of 100 TeV and an integrated luminosity of at least a factor of 5 larger than the HL-LHC. It will extend the current energy frontier by almost an order of magnitude. The mass reach for direct discovery will reach several tens of TeV, and allow, for example, to produce new particles whose existence could be indirectly exposed by precision measurements during the earlier preceding e+e– collider phase. This collider will also precisely measure the Higgs self-coupling and thoroughly explore the dynamics of electroweak symmetry breaking at the TeV scale, to elucidate the nature of the electroweak phase transition. WIMPs as thermal dark matter candidates will be discovered, or ruled out. As a single project, this particle collider infrastructure will serve the world-wide physics community for about 25 years and, in combination with a lepton collider (see FCC conceptual design report volume 2), will provide a research tool until the end of the 21st century. Collision energies beyond 100 TeV can be considered when using high-temperature superconductors. The European Strategy for Particle Physics (ESPP) update 2013 stated “To stay at the forefront of particle physics, Europe needs to be in a position to propose an ambitious post-LHC accelerator project at CERN by the time of the next Strategy update”. The FCC study has implemented the ESPP recommendation by developing a long-term vision for an “accelerator project in a global context”. This document describes the detailed design and preparation of a construction project for a post-LHC circular energy frontier collider “in collaboration with national institutes, laboratories and universities worldwide”, and enhanced by a strong participation of industrial partners. Now, a coordinated preparation effort can be based on a core of an ever-growing consortium of already more than 135 institutes worldwide. The technology for constructing a high-energy circular hadron collider can be brought to the technology readiness level required for constructing within the coming ten years through a focused R&D programme. The FCC-hh concept comprises in the baseline scenario a power-saving, low-temperature superconducting magnet system based on an evolution of the Nb3Sn technology pioneered at the HL-LHC, an energy-efficient cryogenic refrigeration infrastructure based on a neon-helium (Nelium) light gas mixture, a high-reliability and low loss cryogen distribution infrastructure based on Invar, high-power distributed beam transfer using superconducting elements and local magnet energy recovery and re-use technologies that are already gradually introduced at other CERN accelerators. On a longer timescale, high-temperature superconductors can be developed together with industrial partners to achieve an even more energy efficient particle collider or to reach even higher collision energies.The re-use of the LHC and its injector chain, which also serve for a concurrently running physics programme, is an essential lever to come to an overall sustainable research infrastructure at the energy frontier. Strategic R&D for FCC-hh aims at minimising construction cost and energy consumption, while maximising the socio-economic impact. It will mitigate technology-related risks and ensure that industry can benefit from an acceptable utility. Concerning the implementation, a preparatory phase of about eight years is both necessary and adequate to establish the project governance and organisation structures, to build the international machine and experiment consortia, to develop a territorial implantation plan in agreement with the host-states’ requirements, to optimise the disposal of land and underground volumes, and to prepare the civil engineering project. Such a large-scale, international fundamental research infrastructure, tightly involving industrial partners and providing training at all education levels, will be a strong motor of economic and societal development in all participating nations. The FCC study has implemented a set of actions towards a coherent vision for the world-wide high-energy and particle physics community, providing a collaborative framework for topically complementary and geographically well-balanced contributions. This conceptual design report lays the foundation for a subsequent infrastructure preparatory and technical design phase.

Journal ArticleDOI
A. Abada1, Marcello Abbrescia2, Marcello Abbrescia3, Shehu S. AbdusSalam4  +1501 moreInstitutions (239)
TL;DR: In this article, the physics opportunities of the Future Circular Collider (FC) were reviewed, covering its e+e-, pp, ep and heavy ion programs, and the measurement capabilities of each FCC component, addressing the study of electroweak, Higgs and strong interactions.
Abstract: We review the physics opportunities of the Future Circular Collider, covering its e+e-, pp, ep and heavy ion programmes. We describe the measurement capabilities of each FCC component, addressing the study of electroweak, Higgs and strong interactions, the top quark and flavour, as well as phenomena beyond the Standard Model. We highlight the synergy and complementarity of the different colliders, which will contribute to a uniquely coherent and ambitious research programme, providing an unmatchable combination of precision and sensitivity to new physics.

Journal ArticleDOI
TL;DR: In this article, a new definition of a weak and strong safe-haven within a bivariate cross-quantilogram approach was proposed, which considers the lowest tails of both the safe-avenance asset and the stock index.

Journal ArticleDOI
TL;DR: The need to reduce sugar consumption is focused on and how this can be achieved through the adoption of a range of upstream policies designed to combat the corporate strategies used by the global sugar industry to promote sugar consumption and profits is described.

Journal ArticleDOI
TL;DR: In this article, a comprehensive analysis of transparent conductive electrodes (TCEs) is provided, covering detailed thin film fabrication methods, evaluation metrics, performance limitations as well as approaches to beat these limitations.

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TL;DR: All of these studies point towards itaconate being a critical immunometabolite that could have far-reaching consequences for immunity, host defence and tumorigenesis.
Abstract: Itaconate is one of the best examples of the consequences of metabolic reprogramming during immunity. It is made by diverting aconitate away from the tricarboxylic acid cycle during inflammatory macrophage activation. The main reason macrophages exhibit this response currently appears to be for an anti-inflammatory effect, with itaconate connecting cell metabolism, oxidative and electrophilic stress responses and immune responses. A role for itaconate in the regulation of type I interferons during viral infection has also been described, as well as in M2 macrophage function under defined circumstances. Finally, macrophage-specific itaconate production has also been shown to have a pro-tumour effect. All of these studies point towards itaconate being a critical immunometabolite that could have far-reaching consequences for immunity, host defence and tumorigenesis.

Journal ArticleDOI
TL;DR: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989–2013, suggesting a doubling in incidence rate within approximately 20 years in Europe.
Abstract: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years. Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989–2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends. Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004–2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4 year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012. Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20 years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4 year periodicity, no plausible explanation for this can be given.

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TL;DR: This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated, to increase awareness and knowledge of adult ADHD in and outside Europe.

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TL;DR: The classification criteria for SLE is outlined, current treatment strategies and medications, the evidence supporting their use, and the potential future therapies are explored are explored.

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TL;DR: In this paper, the authors present prevailing concepts and state of the science in neutrophil extracellular traps (NET) related research and elaborate on open questions and areas of dispute.
Abstract: Since the discovery and definition of neutrophil extracellular traps (NETs) 14 years ago, numerous characteristics and physiological functions of NETs have been uncovered. Nowadays, the field continues to expand and novel mechanisms that orchestrate formation of NETs, their previously unknown properties, and novel implications in disease continue to emerge. The abundance of available data has also led to some confusion in the NET research community due to contradictory results and divergent scientific concepts, such as pro- and anti-inflammatory roles in pathologic conditions, demarcation from other forms of cell death, or the origin of the DNA that forms the NET scaffold. Here, we present prevailing concepts and state of the science in NET-related research and elaborate on open questions and areas of dispute.

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TL;DR: Advancing knowledge of the cutaneous microbiome and its function in modulating the course of skin disorders, such as AD, might result in novel therapeutic strategies, and crosstalk between commensals and the immune system is now recognized.
Abstract: As an interface with the environment, the skin is a complex ecosystem colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome inhibits colonization with pathogens, such as Staphylococcus aureus, and is a crucial component for function of the epidermal barrier. Moreover, crosstalk between commensals and the immune system is now recognized because microorganisms can modulate both innate and adaptive immune responses. Host-commensal interactions also have an effect on the developing immune system in infants and, subsequently, the occurrence of diseases, such as asthma and atopic dermatitis (AD). Later in life, the cutaneous microbiome contributes to the development and course of skin disease. Accordingly, in patients with AD, a decrease in microbiome diversity correlates with disease severity and increased colonization with pathogenic bacteria, such as S aureus. Early clinical studies suggest that topical application of commensal organisms (eg, Staphylococcus hominis or Roseomonas mucosa) reduces AD severity, which supports an important role for commensals in decreasing S aureus colonization in patients with AD. Advancing knowledge of the cutaneous microbiome and its function in modulating the course of skin disorders, such as AD, might result in novel therapeutic strategies.

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TL;DR: A strain-driven 90° lattice rotation is found in the magnetic VSSe monolayer with an extremely high reversal strain, indicating an intrinsic ferroelasticity and the combination of piezoelectricity and valley polarization make magnetic 2D Janus VSSe a tantalizing material for potential applications in nanoelectronics, optoelectronic, and valleytronics.
Abstract: Inspired by recent experiments on the successful fabrication of monolayer Janus transition-metal dichalcogenides [Lu, A.-Y.; Nat. Nanotechnol. 2017, 12, (8), 744 and ferromagnetic VSe2 [Bonilla, M.; Nat. Nanotechnol. 2018, 13, (4), 289], we predict a highly stable room-temperature ferromagnetic Janus monolayer (VSSe) by density functional theory methods and further confirmed the stability by a global minimum search with the particle-swarm optimization method. The VSSe monolayer exhibits a large valley polarization due to the broken space- and time-reversal symmetry. Moreover, its low symmetry C3v point group results in giant in-plane piezoelectric polarization. Most interestingly, a strain-driven 90° lattice rotation is found in the magnetic VSSe monolayer with an extremely high reversal strain (73%), indicating an intrinsic ferroelasticity. The combination of piezoelectricity and valley polarization make magnetic 2D Janus VSSe a tantalizing material for potential applications in nanoelectronics, optoelec...

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TL;DR: The electrochemical performance of electrodes fabricated using assembled V2 CTx flakes surpasses Ti3 C2 Tx in various aqueous electrolytes and opens a new venue for future development of high-performance supercapacitor electrodes using a variety of 2D materials as building blocks.
Abstract: Electrochemical capacitors (ECs) that store charge based on the pseudocapacitive mechanism combine high energy densities with high power densities and rate capabilities. 2D transition metal carbides (MXenes) have been recently introduced as high-rate pseudocapacitive materials with ultrahigh areal and volumetric capacitances. So far, 20 different MXene compositions have been synthesized and many more are theoretically predicted. However, since most MXenes are chemically unstable in their 2D forms, to date only one MXene composition, Ti3 C2 Tx , has shown stable pseudocapacitive charge storage. Here, a cation-driven assembly process is demonstrated to fabricate highly stable and flexible multilayered films of V2 CTx and Ti2 CTx MXenes from their chemically unstable delaminated single-layer flakes. The electrochemical performance of electrodes fabricated using assembled V2 CTx flakes surpasses Ti3 C2 Tx in various aqueous electrolytes. These electrodes show specific capacitances as high as 1315 F cm-3 and retain ≈77% of their initial capacitance after one million charge/discharge cycles, an unprecedented performance for pseudocapacitive materials. This work opens a new venue for future development of high-performance supercapacitor electrodes using a variety of 2D materials as building blocks.

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TL;DR: The role of claudin-5 and its regulation in homeostatic and pathological conditions is focused on, with therapeutic strategies to restore integrity of cerebral vessels by targeting tight junction protein complexes summarised.
Abstract: Tight junction proteins of the blood–brain barrier are vital for maintaining integrity of endothelial cells lining brain blood vessels. The presence of these protein complexes in the space between endothelial cells creates a dynamic, highly regulated and restrictive microenvironment that is vital for neural homeostasis. By limiting paracellular diffusion of material between blood and brain, tight junction proteins provide a protective barrier preventing the passage of unwanted and potentially damaging material. Simultaneously, this protective barrier hinders the therapeutic effectiveness of central nervous system acting drugs with over 95% of small molecule therapeutics unable to bypass the blood–brain barrier. At the blood–brain barrier, claudin-5 is the most enriched tight junction protein and its dysfunction has been implicated in neurodegenerative disorders such as Alzheimer’s disease, neuroinflammatory disorders such as multiple sclerosis as well as psychiatric disorders including depression and schizophrenia. By regulating levels of claudin-5, it is possible to abrogate disease symptoms in many of these disorders. This review will give an overview of the blood–brain barrier and the role of tight junction complexes in maintaining blood–brain barrier integrity before focusing on the role of claudin-5 and its regulation in homeostatic and pathological conditions. We will also summarise therapeutic strategies to restore integrity of cerebral vessels by targeting tight junction protein complexes.

Journal ArticleDOI
TL;DR: It is shown that two-dimensional titanium carbide or carbonitride nanosheets, known as MXenes, can be used as a conductive binder for silicon electrodes produced by a simple and scalable slurry-casting technique without the need of any other additives.
Abstract: The ever-increasing demands for advanced lithium-ion batteries have greatly stimulated the quest for robust electrodes with a high areal capacity. Producing thick electrodes from a high-performance active material would maximize this parameter. However, above a critical thickness, solution-processed films typically encounter electrical/mechanical problems, limiting the achievable areal capacity and rate performance as a result. Herein, we show that two-dimensional titanium carbide or carbonitride nanosheets, known as MXenes, can be used as a conductive binder for silicon electrodes produced by a simple and scalable slurry-casting technique without the need of any other additives. The nanosheets form a continuous metallic network, enable fast charge transport and provide good mechanical reinforcement for the thick electrode (up to 450 µm). Consequently, very high areal capacity anodes (up to 23.3 mAh cm−2) have been demonstrated.

Posted ContentDOI
Matteo Dainese1, Emily A. Martin1, Marcelo A. Aizen2, Matthias Albrecht, Ignasi Bartomeus3, Riccardo Bommarco4, Luísa G. Carvalheiro5, Luísa G. Carvalheiro6, Rebecca Chaplin-Kramer7, Vesna Gagic8, Lucas Alejandro Garibaldi9, Jaboury Ghazoul10, Heather Grab11, Mattias Jonsson4, Daniel S. Karp12, Christina M. Kennedy13, David Kleijn14, Claire Kremen15, Douglas A. Landis16, Deborah K. Letourneau17, Lorenzo Marini18, Katja Poveda11, Romina Rader19, Henrik G. Smith20, Teja Tscharntke21, Georg K.S. Andersson20, Isabelle Badenhausser22, Isabelle Badenhausser23, Svenja Baensch21, Antonio Diego M. Bezerra24, Felix J.J.A. Bianchi14, Virginie Boreux10, Vincent Bretagnolle23, Berta Caballero-López, Pablo Cavigliasso25, Aleksandar Ćetković26, Natacha P. Chacoff27, Alice Classen1, Sarah Cusser28, Felipe D. da Silva e Silva29, G. Arjen de Groot14, Jan H. Dudenhöffer30, Johan Ekroos20, Thijs P.M. Fijen14, Pierre Franck22, Breno Magalhães Freitas24, Michael P.D. Garratt31, Claudio Gratton32, Juliana Hipólito9, Andrea Holzschuh1, Lauren Hunt33, Aaron L. Iverson11, Shalene Jha34, Tamar Keasar35, Tania N. Kim36, Miriam Kishinevsky35, Björn K. Klatt21, Björn K. Klatt20, Alexandra-Maria Klein37, Kristin M. Krewenka38, Smitha Krishnan10, Ashley E. Larsen39, Claire Lavigne22, Heidi Liere40, Bea Maas41, Rachel E. Mallinger42, Eliana Martinez Pachon, Alejandra Martínez-Salinas43, Timothy D. Meehan44, Matthew G. E. Mitchell15, Gonzalo Alberto Roman Molina45, Maike Nesper10, Lovisa Nilsson20, Megan E. O'Rourke46, Marcell K. Peters1, Milan Plećaš26, Simon G. Potts31, Davi de L. Ramos29, Jay A. Rosenheim17, Maj Rundlöf20, Adrien Rusch47, Agustín Sáez2, Jeroen Scheper14, Matthias Schleuning, Julia Schmack48, Amber R. Sciligo17, Colleen L. Seymour, Dara A. Stanley49, Rebecca Stewart20, Jane C. Stout50, Louis Sutter, Mayura B. Takada51, Hisatomo Taki, Giovanni Tamburini4, Matthias Tschumi, Blandina Felipe Viana52, Catrin Westphal21, Bryony K. Willcox19, Stephen D. Wratten53, Akira Yoshioka54, Carlos Zaragoza-Trello3, Wei Zhang55, Yi Zou56, Ingolf Steffan-Dewenter1 
University of Würzburg1, National University of Comahue2, Spanish National Research Council3, Swedish University of Agricultural Sciences4, University of Lisbon5, Universidade Federal de Goiás6, Stanford University7, Commonwealth Scientific and Industrial Research Organisation8, National University of Río Negro9, ETH Zurich10, Cornell University11, University of California, Davis12, The Nature Conservancy13, Wageningen University and Research Centre14, University of British Columbia15, Great Lakes Bioenergy Research Center16, University of California, Berkeley17, University of Padua18, University of New England (United States)19, Lund University20, University of Göttingen21, Institut national de la recherche agronomique22, University of La Rochelle23, Federal University of Ceará24, Concordia University Wisconsin25, University of Belgrade26, National University of Tucumán27, Michigan State University28, University of Brasília29, University of Greenwich30, University of Reading31, University of Wisconsin-Madison32, Boise State University33, University of Texas at Austin34, University of Haifa35, Kansas State University36, University of Freiburg37, University of Hamburg38, University of California, Santa Barbara39, Seattle University40, University of Vienna41, University of Florida42, Centro Agronómico Tropical de Investigación y Enseñanza43, National Audubon Society44, University of Buenos Aires45, Virginia Tech46, University of Bordeaux47, University of Auckland48, University College Dublin49, Trinity College, Dublin50, University of Tokyo51, Federal University of Bahia52, Lincoln University (Pennsylvania)53, National Institute for Environmental Studies54, International Food Policy Research Institute55, Xi'an Jiaotong-Liverpool University56
20 Feb 2019-bioRxiv
TL;DR: Using a global database from 89 crop systems, the relative importance of abundance and species richness for pollination, biological pest control and final yields in the context of on-going land-use change is partitioned.
Abstract: Human land use threatens global biodiversity and compromises multiple ecosystem functions critical to food production. Whether crop yield-related ecosystem services can be maintained by few abundant species or rely on high richness remains unclear. Using a global database from 89 crop systems, we partition the relative importance of abundance and species richness for pollination, biological pest control and final yields in the context of on-going land-use change. Pollinator and enemy richness directly supported ecosystem services independent of abundance. Up to 50% of the negative effects of landscape simplification on ecosystem services was due to richness losses of service-providing organisms, with negative consequences for crop yields. Maintaining the biodiversity of ecosystem service providers is therefore vital to sustain the flow of key agroecosystem benefits to society.

Proceedings ArticleDOI
01 Aug 2019
TL;DR: Findings about the nature of the counterfactuals that humans create are a helpful guide to maximize the effectiveness ofcounterfactual use in AI.
Abstract: Counterfactuals about what could have happened are increasingly used in an array of Artificial Intelligence (AI) applications, and especially in explainable AI (XAI). Counterfactuals can aid the provision of interpretable models to make the decisions of inscrutable systems intelligible to developers and users. However, not all counterfactuals are equally helpful in assisting human comprehension. Discoveries about the nature of the counterfactuals that humans create are a helpful guide to maximize the effectiveness of counterfactual use in AI.

Journal ArticleDOI
01 Jan 2019
TL;DR: This review summarizes the non-metabolic signalling mechanisms of succinate, fumarate, itaconate, 2-hydroxyglutarate isomers and acetyl-CoA in both immune cells and cancer cells.
Abstract: Metabolic reprogramming has become a key focus for both immunologists and cancer biologists, with exciting advances providing new insights into the mechanisms underlying disease. There is now extensive evidence that intermediates and derivatives of the mitochondrial Krebs cycle—metabolites traditionally associated with bioenergetics or biosynthesis—also possess ‘non-metabolic’ signalling functions. In this review, we summarize the non-metabolic signalling mechanisms of succinate, fumarate, itaconate, 2-hydroxyglutarate isomers (d-2-hydroxyglutarate and l-2-hydroxyglutarate) and acetyl-CoA, with a specific focus on how such signalling pathways alter immune cell and transformed cell function. We believe that the insights gained from immune and cancer cells that are summarized here will also be useful for understanding and treating a range of other diseases. Intermediate metabolites of the Krebs cycle serve bioenergetic and biosynthetic needs but have recently also been linked to signalling. The authors of this Review summarize such non-metabolic signalling functions of succinate, fumarate, itaconate, 2-hydroxyglutarate isomers and acetyl-CoA in both immune cells and cancer cells.