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Showing papers by "University of Florence published in 2019"


Journal ArticleDOI
Phil Lee, Verneri Anttila, Hyejung Won1, Yen-Chen Anne Feng1  +603 moreInstitutions (10)
12 Dec 2019-Cell
TL;DR: Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes.

781 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: In this article, the authors investigated the drug retention rate of interleukin (IL)-1 inhibitors on systemic JIA (sJIA) patients and evaluated predictive factors of drug survival based on data from a real-world setting concerning sJIA.
Abstract: Background and Objectives: Few studies have reported the drug retention rate (DRR) of biologic drugs in juvenile idiopathic arthritis (JIA), and none of them has specifically investigated the DRR of interleukin (IL)-1 inhibitors on systemic JIA (sJIA). This study aims to describe IL-1 inhibitors DRR and evaluate predictive factors of drug survival based on data from a real-world setting concerning sJIA. Methods: Medical records from sJIA patients treated with anakinra (ANA) and canakinumab (CAN) were retrospectively analyzed from 15 Italian tertiary referral centers. Results: Seventy seven patients were enrolled for a total of 86 treatment courses. The cumulative retention rate of the IL-1 inhibitors at 12-, 24-, 48-, and 60-months of follow-up was 79.9, 59.5, 53.5, and 53.5%, respectively, without any statistically significant differences between ANA and CAN (p = 0.056), and between patients treated in monotherapy compared to the subgroup co-administered with conventional immunosuppressors (p = 0.058). On the contrary, significant differences were found between biologic-naive patients and those previously treated with biologic drugs (p = 0.038) and when distinguishing according to adverse events (AEs) occurrence (p = 0.04). In regression analysis, patients pre-treated with other biologics (HR = 3.357 [CI: 1.341-8.406], p = 0.01) and those experiencing AEs (HR = 2.970 [CI: 1.186-7.435], p = 0.020) were associated with a higher hazard ratio of IL-1 inhibitors withdrawal. The mean treatment delay was significantly higher among patients discontinuing IL-1 inhibitors (p = 0.0002). Conclusions: Our findings suggest an excellent overall DRR for both ANA and CAN that might be further augmented by paying attention to AEs and employing these agents as first-line biologics in an early disease phase.

615 citations


Journal ArticleDOI
TL;DR: This review will highlight a number of emerging NMR techniques and technologies that are being used to strengthen its utility and overcome its inherent limitations in metabolomic applications.
Abstract: Over the past two decades, nuclear magnetic resonance (NMR) has emerged as one of the three principal analytical techniques used in metabolomics (the other two being gas chromatography coupled to mass spectrometry (GC-MS) and liquid chromatography coupled with single-stage mass spectrometry (LC-MS)). The relative ease of sample preparation, the ability to quantify metabolite levels, the high level of experimental reproducibility, and the inherently nondestructive nature of NMR spectroscopy have made it the preferred platform for long-term or large-scale clinical metabolomic studies. These advantages, however, are often outweighed by the fact that most other analytical techniques, including both LC-MS and GC-MS, are inherently more sensitive than NMR, with lower limits of detection typically being 10 to 100 times better. This review is intended to introduce readers to the field of NMR-based metabolomics and to highlight both the advantages and disadvantages of NMR spectroscopy for metabolomic studies. It will also explore some of the unique strengths of NMR-based metabolomics, particularly with regard to isotope selection/detection, mixture deconvolution via 2D spectroscopy, automation, and the ability to noninvasively analyze native tissue specimens. Finally, this review will highlight a number of emerging NMR techniques and technologies that are being used to strengthen its utility and overcome its inherent limitations in metabolomic applications.

539 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
Hunna J. Watson1, Hunna J. Watson2, Hunna J. Watson3, Zeynep Yilmaz3  +255 moreInstitutions (99)
TL;DR: The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index.
Abstract: Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.

517 citations


Journal ArticleDOI
TL;DR: The manuscript addresses frequently encountered challenges, such as evaluation of congestion and clinical euvolaemia, assessment of diuretic response/resistance in the treatment of acute heart failure, and an approach towards stepped pharmacologic diUREtic strategies, based upon diuretics response.
Abstract: The vast majority of acute heart failure episodes are characterized by increasing symptoms and signs of congestion with volume overload. The goal of therapy in those patients is the relief of congestion through achieving a state of euvolaemia, mainly through the use of diuretic therapy. The appropriate use of diuretics however remains challenging, especially when worsening renal function, diuretic resistance and electrolyte disturbances occur. This position paper focuses on the use of diuretics in heart failure with congestion. The manuscript addresses frequently encountered challenges, such as (i) evaluation of congestion and clinical euvolaemia, (ii) assessment of diuretic response/resistance in the treatment of acute heart failure, (iii) an approach towards stepped pharmacologic diuretic strategies, based upon diuretic response, and (iv) management of common electrolyte disturbances. Recommendations are made in line with available guidelines, evidence and expert opinion.

498 citations


Journal ArticleDOI
TL;DR: This document is for the purpose of private study or non-commercial research, and users may not further distribute the material nor use it for the purposes of commercial gain.
Abstract: • Users may freely distribute the URL that is used to identify this publication. • Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. • User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?) • Users may not further distribute the material nor use it for the purposes of commercial gain.

461 citations


Journal ArticleDOI
Albert M. Sirunyan, Armen Tumasyan, Wolfgang Adam1, Federico Ambrogi1  +2265 moreInstitutions (153)
TL;DR: Combined measurements of the production and decay rates of the Higgs boson, as well as its couplings to vector bosons and fermions, are presented and constraints are placed on various two Higgs doublet models.
Abstract: Combined measurements of the production and decay rates of the Higgs boson, as well as its couplings to vector bosons and fermions, are presented. The analysis uses the LHC proton–proton collision data set recorded with the CMS detector in 2016 at $\sqrt{s}=13\,\text {Te}\text {V} $ , corresponding to an integrated luminosity of 35.9 ${\,\text {fb}^{-1}} $ . The combination is based on analyses targeting the five main Higgs boson production mechanisms (gluon fusion, vector boson fusion, and associated production with a $\mathrm {W}$ or $\mathrm {Z}$ boson, or a top quark-antiquark pair) and the following decay modes: $\mathrm {H} \rightarrow \gamma \gamma $ , $\mathrm {Z}\mathrm {Z}$ , $\mathrm {W}\mathrm {W}$ , $\mathrm {\tau }\mathrm {\tau }$ , $\mathrm {b} \mathrm {b} $ , and $\mathrm {\mu }\mathrm {\mu }$ . Searches for invisible Higgs boson decays are also considered. The best-fit ratio of the signal yield to the standard model expectation is measured to be $\mu =1.17\pm 0.10$ , assuming a Higgs boson mass of $125.09\,\text {Ge}\text {V} $ . Additional results are given for various assumptions on the scaling behavior of the production and decay modes, including generic parametrizations based on ratios of cross sections and branching fractions or couplings. The results are compatible with the standard model predictions in all parametrizations considered. In addition, constraints are placed on various two Higgs doublet models.

451 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Fausto Acernese3  +1237 moreInstitutions (131)
TL;DR: In this paper, the authors place constraints on the dipole radiation and possible deviations from GR in the post-Newtonian coefficients that govern the inspiral regime of a binary neutron star inspiral.
Abstract: The recent discovery by Advanced LIGO and Advanced Virgo of a gravitational wave signal from a binary neutron star inspiral has enabled tests of general relativity (GR) with this new type of source. This source, for the first time, permits tests of strong-field dynamics of compact binaries in the presence of matter. In this Letter, we place constraints on the dipole radiation and possible deviations from GR in the post-Newtonian coefficients that govern the inspiral regime. Bounds on modified dispersion of gravitational waves are obtained; in combination with information from the observed electromagnetic counterpart we can also constrain effects due to large extra dimensions. Finally, the polarization content of the gravitational wave signal is studied. The results of all tests performed here show good agreement with GR.

430 citations


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
TL;DR: Combined analysis of the genetic and geographic distances between isolates with different β-lactam resistance determinants suggests that the propensity of K. pneumoniae to spread in hospital environments correlates with the degree of resistance and that carbapenemase-positive isolates have the highest transmissibility.
Abstract: Public health interventions to control the current epidemic of carbapenem-resistant Klebsiella pneumoniae rely on a comprehensive understanding of its emergence and spread over a wide range of geographical scales. We analysed the genome sequences and epidemiological data of >1,700 K. pneumoniae samples isolated from patients in 244 hospitals in 32 countries during the European Survey of Carbapenemase-Producing Enterobacteriaceae. We demonstrate that carbapenemase acquisition is the main cause of carbapenem resistance and that it occurred across diverse phylogenetic backgrounds. However, 477 of 682 (69.9%) carbapenemase-positive isolates are concentrated in four clonal lineages, sequence types 11, 15, 101, 258/512 and their derivatives. Combined analysis of the genetic and geographic distances between isolates with different β-lactam resistance determinants suggests that the propensity of K. pneumoniae to spread in hospital environments correlates with the degree of resistance and that carbapenemase-positive isolates have the highest transmissibility. Indeed, we found that over half of the hospitals that contributed carbapenemase-positive isolates probably experienced within-hospital transmission, and interhospital spread is far more frequent within, rather than between, countries. Finally, we propose a value of 21 for the number of single nucleotide polymorphisms that optimizes the discrimination of hospital clusters and detail the international spread of the successful epidemic lineage, ST258/512.

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
20 Sep 2019-Science
TL;DR: The climate change–impact literature is reviewed, expanding on the recent report of the Intergovernmental Panel on Climate Change, and it is argued that impacts accelerating as a function of distance from the optimal temperature for an organism or an ecosystem process is a consequence of impacts accelerating.
Abstract: Increased concentrations of atmospheric greenhouse gases have led to a global mean surface temperature 1.0°C higher than during the pre-industrial period. We expand on the recent IPCC Special Report on global warming of 1.5°C and review the additional risks associated with higher levels of warming, each having major implications for multiple geographies, climates, and ecosystems. Limiting warming to 1.5°C rather than 2.0°C would be required to maintain substantial proportions of ecosystems and would have clear benefits for human health and economies. These conclusions are relevant for people everywhere, particularly in low- and middle-income countries, where the escalation of climate-related risks may prevent the achievement of the United Nations Sustainable Development Goals.

Journal ArticleDOI
TL;DR: This review is thus organized to critically assess the significant role of nanotechnology for encapsulation of AIs for pesticides and the future trends of pesticide nanoformulations including nanomaterials as AIs and nanoemulsions of biopesticides are explored.

Journal ArticleDOI
TL;DR: Quantum cryptography is arguably the fastest growing area in quantum information science as mentioned in this paper, and many quantum key distribution protocols have been proposed, both theoretically and experimentally, over the last few decades.
Abstract: Quantum cryptography is arguably the fastest growing area in quantum information science. Novel theoretical protocols are designed on a regular basis, security proofs are constantly improving, and experiments are gradually moving from proof-of-principle lab demonstrations to in-field implementations and technological prototypes. In this review, we provide both a general introduction and a state of the art description of the recent advances in the field, both theoretically and experimentally. We start by reviewing protocols of quantum key distribution based on discrete variable systems. Next we consider aspects of device independence, satellite challenges, and high rate protocols based on continuous variable systems. We will then discuss the ultimate limits of point-to-point private communications and how quantum repeaters and networks may overcome these restrictions. Finally, we will discuss some aspects of quantum cryptography beyond standard quantum key distribution, including quantum data locking and quantum digital signatures.

Journal ArticleDOI
Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam, Federico Ambrogi  +2298 moreInstitutions (160)
TL;DR: In this article, a search for invisible decays of a Higgs boson via vector boson fusion is performed using proton-proton collision data collected with the CMS detector at the LHC in 2016 at a center-of-mass energy root s = 13 TeV, corresponding to an integrated luminosity of 35.9fb(-1).

Journal ArticleDOI
TL;DR: This paper surveys the different approaches to automatic detection of fake news and rumours proposed in the recent literature and provides a comprehensive analysis on the various techniques used to perform rumour and fake news detection.

Journal ArticleDOI
TL;DR: In a combined experimental and theoretical analysis, this work determines the parameter regime for the formation of coherent stripes, whose lifetime of a few tens of milliseconds is limited by the eventual destruction of the stripe pattern due to three-body losses.
Abstract: The competition of dipole-dipole and contact interactions leads to exciting new physics in dipolar gases, well illustrated by the recent observation of quantum droplets and rotons in dipolar condensates. We show that the combination of the roton instability and quantum stabilization leads under proper conditions to a novel regime that presents supersolid properties due to the coexistence of stripe modulation and phase coherence. In a combined experimental and theoretical analysis, we determine the parameter regime for the formation of coherent stripes, whose lifetime of a few tens of milliseconds is limited by the eventual destruction of the stripe pattern due to three-body losses. Our results open intriguing prospects for the development of long-lived dipolar supersolids.

Journal ArticleDOI
TL;DR: The role of mitochondrial oxidative stress in the aging process is reviewed, with a specific focus on neurodegenerative diseases, to help to identify new strategies for improving the health and extending lifespan.
Abstract: Age is the main risk factor for a number of human diseases, including neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, which increasing numbers of elderly individuals suffer. These pathological conditions are characterized by progressive loss of neuron cells, compromised motor or cognitive functions, and accumulation of abnormally aggregated proteins. Mitochondrial dysfunction is one of the main features of the aging process, particularly in organs requiring a high-energy source such as the heart, muscles, brain, or liver. Neurons rely almost exclusively on the mitochondria, which produce the energy required for most of the cellular processes, including synaptic plasticity and neurotransmitter synthesis. The brain is particularly vulnerable to oxidative stress and damage, because of its high oxygen consumption, low antioxidant defenses, and high content of polyunsaturated fats very prone to be oxidized. Thus, it is not surprising the importance of protecting systems, including antioxidant defenses, to maintain neuronal integrity and survival. Here, we review the role of mitochondrial oxidative stress in the aging process, with a specific focus on neurodegenerative diseases. Understanding the molecular mechanisms involving mitochondria and oxidative stress in the aging and neurodegeneration may help to identify new strategies for improving the health and extending lifespan.

Journal ArticleDOI
TL;DR: A 32-multi-model ensemble is tested and applied to simulate global wheat yield and quality in a changing climate to potential benefits of elevated atmospheric CO2 concentration by 2050, likely to be negated by impacts from rising temperature and changes in rainfall, but with considerable disparities between regions.
Abstract: Wheat grain protein concentration is an important determinant of wheat quality for human nutrition that is often overlooked in efforts to improve crop production. We tested and applied a 32‐multi‐model ensemble to simulate global wheat yield and quality in a changing climate. Potential benefits of elevated atmospheric CO2 concentration by 2050 on global wheat grain and protein yield are likely to be negated by impacts from rising temperature and changes in rainfall, but with considerable disparities between regions. Grain and protein yields are expected to be lower and more variable in most low‐rainfall regions, with nitrogen availability limiting growth stimulus from elevated CO2. Introducing genotypes adapted to warmer temperatures (and also considering changes in CO2 and rainfall) could boost global wheat yield by 7% and protein yield by 2%, but grain protein concentration would be reduced by −1.1 percentage points, representing a relative change of −8.6%. Climate change adaptations that benefit grain yield are not always positive for grain quality, putting additional pressure on global wheat production.

Journal ArticleDOI
TL;DR: A comprehensive overview of the most updated recommendations for practicing cardiologists and sport physicians managing athletes with cardiomyopathies and myo-pericarditis is offered and pragmatic advice for safe participation in competitive sport at professional and amateur level, as well as in a variety of recreational physical activities is provided.
Abstract: Myocardial diseases are associated with an increased risk of potentially fatal cardiac arrhythmias and sudden cardiac death/cardiac arrest during exercise, including hypertrophic cardiomyopathy, dilated cardiomyopathy, left ventricular non-compaction, arrhythmogenic cardiomyopathy, and myo-pericarditis. Practicing cardiologists and sport physicians are required to identify high-risk individuals harbouring these cardiac diseases in a timely fashion in the setting of preparticipation screening or medical consultation and provide appropriate advice regarding the participation in competitive sport activities and/or regular exercise programmes. Many asymptomatic (or mildly symptomatic) patients with cardiomyopathies aspire to participate in leisure-time and amateur sport activities to take advantage of the multiple benefits of a physically active lifestyle. In 2005, The European Society of Cardiology (ESC) published recommendations for participation in competitive sport in athletes with cardiomyopathies and myo-pericarditis. One decade on, these recommendations are partly obsolete given the evolving knowledge of the diagnosis, management and treatment of cardiomyopathies and myo-pericarditis. The present document, therefore, aims to offer a comprehensive overview of the most updated recommendations for practicing cardiologists and sport physicians managing athletes with cardiomyopathies and myo-pericarditis and provides pragmatic advice for safe participation in competitive sport at professional and amateur level, as well as in a variety of recreational physical activities.

Journal ArticleDOI
TL;DR: It is recommended that the diagnosis of XLH is based on signs of rickets and/or osteomalacia in association with hypophosphataemia and renal phosphate wasting in the absence of vitamin D or calcium deficiency.
Abstract: X-linked hypophosphataemia (XLH) is the most common cause of inherited phosphate wasting and is associated with severe complications such as rickets, lower limb deformities, pain, poor mineralization of the teeth and disproportionate short stature in children as well as hyperparathyroidism, osteomalacia, enthesopathies, osteoarthritis and pseudofractures in adults. The characteristics and severity of XLH vary between patients. Because of its rarity, the diagnosis and specific treatment of XLH are frequently delayed, which has a detrimental effect on patient outcomes. In this Evidence-Based Guideline, we recommend that the diagnosis of XLH is based on signs of rickets and/or osteomalacia in association with hypophosphataemia and renal phosphate wasting in the absence of vitamin D or calcium deficiency. Whenever possible, the diagnosis should be confirmed by molecular genetic analysis or measurement of levels of fibroblast growth factor 23 (FGF23) before treatment. Owing to the multisystemic nature of the disease, patients should be seen regularly by multidisciplinary teams organized by a metabolic bone disease expert. In this article, we summarize the current evidence and provide recommendations on features of the disease, including new treatment modalities, to improve knowledge and provide guidance for diagnosis and multidisciplinary care. In this Evidence-Based Guideline on X-linked hypophosphataemia, the authors identify the criteria for diagnosis of this disease, provide guidance for medical and surgical treatment and explain the challenges of follow-up.

Journal ArticleDOI
TL;DR: In this article, the authors present measurements of the expansion rate of the universe based on a Hubble diagram of quasars, whose distances are estimated from their X-ray and ultraviolet emission.
Abstract: The concordance model (Λ cold dark matter (ΛCDM) model, where Λ is the cosmological constant) reproduces the main current cosmological observations1–4 assuming the validity of general relativity at all scales and epochs and the presence of CDM and of Λ, equivalent to dark energy with a constant density in space and time. However, the ΛCDM model is poorly tested in the redshift interval between the farthest observed type Ia supernovae5 and the cosmic microwave background. We present measurements of the expansion rate of the Universe based on a Hubble diagram of quasars. Quasars are the most luminous persistent sources in the Universe, observed up to redshifts of z ≈ 7.5 (refs. 6,7). We estimate their distances following a method developed by our group8–10, based on the X-ray and ultraviolet emission of the quasars. The distance modulus/redshift relation of quasars at z < 1.4 is in agreement with that of supernovae and with the concordance model. However, a deviation from the ΛCDM model emerges at higher redshift, with a statistical significance of ~4σ. If an evolution of the dark energy equation of state is allowed, the data suggest dark energy density increasing with time. The concordance cosmology model is poorly tested at high redshifts. Here the expansion rate of the Universe in the range 0.5 < z < 5.1 is measured based on a Hubble diagram of quasars, whose distances are estimated from their X-ray and ultraviolet emission.

Posted Content
TL;DR: A parametrization of linear feedback systems is derived that paves the way to solve important control problems using data-dependent linear matrix inequalities only and is remarkable in that no explicit system's matrices identification is required.
Abstract: In a paper by Willems and coauthors it was shown that persistently exciting data can be used to represent the input-output behavior of a linear system. Based on this fundamental result, we derive a parametrization of linear feedback systems that paves the way to solve important control problems using data-dependent Linear Matrix Inequalities only. The result is remarkable in that no explicit system's matrices identification is required. The examples of control problems we solve include the state and output feedback stabilization, and the linear quadratic regulation problem. We also discuss robustness to noise-corrupted measurements and show how the approach can be used to stabilize unstable equilibria of nonlinear systems.

Journal ArticleDOI
TL;DR: The role that molecular chemistry can have in the current second quantum revolution, i.e., the use of quantum physics principles to create new quantum technologies, is highlighted by identifying the key advances recently made by the molecular chemistry community.
Abstract: Implementation of modern Quantum Technologies might benefit from the remarkable quantum properties shown by molecular spin systems. In this Perspective, we highlight the role that molecular chemistry can have in the current second quantum revolution, i.e., the use of quantum physics principles to create new quantum technologies, in this specific case by means of molecular components. Herein, we briefly review the current status of the field by identifying the key advances recently made by the molecular chemistry community, such as for example the design of molecular spin qubits with long spin coherence and the realization of multiqubit architectures for quantum gates implementation. With a critical eye to the current state-of-the-art, we also highlight the main challenges needed for the further advancement of the field toward quantum technologies development.

Journal ArticleDOI
TL;DR: The authors show that Anak Krakatau exhibited an elevated state of activity several months prior to the collapse, including precursory thermal anomalies, an increase in the island’s surface area, and a gradual seaward motion of the southwestern flank.
Abstract: Flank instability and sector collapses, which pose major threats, are common on volcanic islands. On 22 Dec 2018, a sector collapse event occurred at Anak Krakatau volcano in the Sunda Strait, triggering a deadly tsunami. Here we use multiparametric ground-based and space-borne data to show that prior to its collapse, the volcano exhibited an elevated state of activity, including precursory thermal anomalies, an increase in the island’s surface area, and a gradual seaward motion of its southwestern flank on a dipping decollement. Two minutes after a small earthquake, seismic signals characterize the collapse of the volcano’s flank at 13:55 UTC. This sector collapse decapitated the cone-shaped edifice and triggered a tsunami that caused 430 fatalities. We discuss the nature of the precursor processes underpinning the collapse that culminated in a complex hazard cascade with important implications for the early detection of potential flank instability at other volcanoes. On 22 December 2018, the western flank of Anak Krakatau collapsed into the sea of the Sunda Strait triggering a tsunami which killed approximately 430 people and displaced 33,000. Here, the authors show that Anak Krakatau exhibited an elevated state of activity several months prior to the collapse, including precursory thermal anomalies, an increase in the island’s surface area, and a gradual seaward motion of the southwestern flank.

Journal ArticleDOI
TL;DR: It is concluded that population-level shifts in GM could play a regulatory role in the gut-liver axis and, consequently, etiopathogenesis of chronic liver diseases.
Abstract: The rapid scientific interest in gut microbiota (GM) has coincided with a global increase in the prevalence of infectious and non-infectivous liver diseases. GM, which is also called “the new virtual metabolic organ”, makes axis with a number of extraintestinal organs, such as kidneys, brain, cardiovascular, and the bone system. The gut-liver axis has attracted greater attention in recent years. GM communication is bi-directional and involves endocrine and immunological mechanisms. In this way, gut-dysbiosis and composition of “ancient” microbiota could be linked to pathogenesis of numerous chronic liver diseases such as chronic hepatitis B (CHB), chronic hepatitis C (CHC), alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), development of liver cirrhosis, and hepatocellular carcinoma (HCC). In this paper, we discuss the current evidence supporting a GM role in the management of different chronic liver diseases and potential new therapeutic GM targets, like fecal transplantation, antibiotics, probiotics, prebiotics, and symbiotics. We conclude that population-level shifts in GM could play a regulatory role in the gut-liver axis and, consequently, etiopathogenesis of chronic liver diseases. This could have a positive impact on future therapeutic strategies.

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TL;DR: NIRS imaging of non-obstructive territories in patients undergoing cardiac catheterisation and possible percutaneous coronary intervention was safe and can aid in identifying patients and segments at higher risk for subsequent NC-MACE.

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TL;DR: An update on the current understanding of perineuronal net composition, formation and functional roles in brain function and disease is provided.
Abstract: Perineuronal nets (PNNs) are extracellular matrix (ECM) chondroitin sulfate proteoglycan (CSPG)-containing structures that surround the soma and dendrites of various mammalian neuronal cell types. PNNs appear during development around the time that the critical periods for developmental plasticity end and are important for both their onset and closure. A similar structure - the perinodal ECM - surrounds the axonal nodes of Ranvier and appears as myelination is completed, acting as an ion-diffusion barrier that affects axonal conduction speed. Recent work has revealed the importance of PNNs in controlling plasticity in the CNS. Digestion, blocking or removal of PNNs influences functional recovery after a variety of CNS lesions. PNNs have further been shown to be involved in the regulation of memory and have been implicated in a number of psychiatric disorders.