University of Liège

Background: in 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) published a sarcopenia definition that aimed to foster advances in identifying and caring for people with sarcopenia. In early 2018, the Working Group met again (EWGSOP2) to update the original definition in order to reflect scientific and clinical evidence that has built over the last decade. This paper presents our updated findings. Objectives: to increase consistency of research design, clinical diagnoses and ultimately, care for people with sarcopenia. Recommendations: sarcopenia is a muscle disease (muscle failure) rooted in adverse muscle changes that accrue across a lifetime; sarcopenia is common among adults of older age but can also occur earlier in life. In this updated consensus paper on sarcopenia, EWGSOP2: (1) focuses on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarcopenia diagnosis, and identifies poor physical performance as indicative of severe sarcopenia; (2) updates the clinical algorithm that can be used for sarcopenia case-finding, diagnosis and confirmation, and severity determination and (3) provides clear cut-off points for measurements of variables that identify and characterise sarcopenia. Conclusions: EWGSOP2's updated recommendations aim to increase awareness of sarcopenia and its risk. With these new recommendations, EWGSOP2 calls for healthcare professionals who treat patients at risk for sarcopenia to take actions that will promote early detection and treatment. We also encourage more research in the field of sarcopenia in order to prevent or delay adverse health outcomes that incur a heavy burden for patients and healthcare systems.

The ESH/ESC Guidelines represent the views of the ESH and ESC and were arrived at after careful consideration of the available evidence at the time they were written. Health professionals are encouraged to take them fully into account when exercising their clinical judgement. The guidelines do not, however, override the individual responsibility of health professionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient, and where appropriate and necessary the patient's guardian or carer. It is also the health professional's responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription.

We have developed and implemented a selfconsistent density functional method using standard norm-conserving pseudopotentials and a flexible, numerical linear combination of atomic orbitals basis set, which includes multiple-zeta and polarization orbitals. Exchange and correlation are treated with the local spin density or generalized gradient approximations. The basis functions and the electron density are projected on a real-space grid, in order to calculate the Hartree and exchange-correlation potentials and matrix elements, with a number of operations that scales linearly with the size of the system. We use a modified energy functional, whose minimization produces orthogonal wavefunctions and the same energy and density as the Kohn-Sham energy functional, without the need for an explicit orthogonalization. Additionally, using localized Wannier-like electron wavefunctions allows the computation time and memory required to minimize the energy to also scale linearly with the size of the system. Forces and stresses are also calculated efficiently and accurately, thus allowing structural relaxation and molecular dynamics simulations.

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.

The solar chemical composition is an important ingredient in our understanding of the formation, structure, and evolution of both the Sun and our Solar System. Furthermore, it is an essential reference standard against which the elemental contents of other astronomical objects are compared. In this review, we evaluate the current understanding of the solar photospheric composition. In particular, we present a redetermination of the abundances of nearly all available elements, using a realistic new three-dimensional (3D), time-dependent hydrodynamical model of the solar atmosphere. We have carefully considered the atomic input data and selection of spectral lines, and accounted for departures from local thermodynamic equilibrium (LTE) whenever possible. The end result is a comprehensive and homogeneous compilation of the solar elemental abundances. Particularly noteworthy findings are significantly lower abundances of C, N, O, and Ne compared to the widely used values of a decade ago. The new solar chemical composition is supported by a high degree of internal consistency between available abundance indicators, and by agreement with values obtained in the Solar Neighborhood and from the most pristine meteorites. There is, however, a stark conflict with standard models of the solar interior according to helioseismology, a discrepancy that has yet to find a satisfactory resolution.

Context. We present the second Gaia data release, Gaia DR2, consisting of astrometry, photometry, radial velocities, and information on astrophysical parameters and variability, for sources brighter than magnitude 21. In addition epoch astrometry and photometry are provided for a modest sample of minor planets in the solar system. Aims. A summary of the contents of Gaia DR2 is presented, accompanied by a discussion on the differences with respect to Gaia DR1 and an overview of the main limitations which are still present in the survey. Recommendations are made on the responsible use of Gaia DR2 results. Methods. The raw data collected with the Gaia instruments during the first 22 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into this second data release, which represents a major advance with respect to Gaia DR1 in terms of completeness, performance, and richness of the data products. Results. Gaia DR2 contains celestial positions and the apparent brightness in G for approximately 1.7 billion sources. For 1.3 billion of those sources, parallaxes and proper motions are in addition available. The sample of sources for which variability information is provided is expanded to 0.5 million stars. This data release contains four new elements: broad-band colour information in the form of the apparent brightness in the G BP (330–680 nm) and G RP (630–1050 nm) bands is available for 1.4 billion sources; median radial velocities for some 7 million sources are presented; for between 77 and 161 million sources estimates are provided of the stellar effective temperature, extinction, reddening, and radius and luminosity; and for a pre-selected list of 14 000 minor planets in the solar system epoch astrometry and photometry are presented. Finally, Gaia DR2 also represents a new materialisation of the celestial reference frame in the optical, the Gaia -CRF2, which is the first optical reference frame based solely on extragalactic sources. There are notable changes in the photometric system and the catalogue source list with respect to Gaia DR1, and we stress the need to consider the two data releases as independent. Conclusions. Gaia DR2 represents a major achievement for the Gaia mission, delivering on the long standing promise to provide parallaxes and proper motions for over 1 billion stars, and representing a first step in the availability of complementary radial velocity and source astrophysical information for a sample of stars in the Gaia survey which covers a very substantial fraction of the volume of our galaxy.

Abstract Gmsh is an open‐source 3‐D finite element grid generator with a build‐in CAD engine and post‐processor. Its design goal is to provide a fast, light and user‐friendly meshing tool with parametric input and advanced visualization capabilities. This paper presents the overall philosophy, the main design choices and some of the original algorithms implemented in Gmsh. Copyright © 2009 John Wiley & Sons, Ltd.

Gaia is a cornerstone mission in the science programme of the EuropeanSpace Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative, particularly in early stage tumors. It can prolong survival in patients with inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment.

The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their dating.

2014 ESC/EACTS Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI)

Context. We present the early installment of the third Gaia data release, Gaia EDR3, consisting of astrometry and photometry for 1.8 billion sources brighter than magnitude 21, complemented with the list of radial velocities from Gaia DR2. Aims. A summary of the contents of Gaia EDR3 is presented, accompanied by a discussion on the differences with respect to Gaia DR2 and an overview of the main limitations which are present in the survey. Recommendations are made on the responsible use of Gaia EDR3 results. Methods. The raw data collected with the Gaia instruments during the first 34 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium and turned into this early third data release, which represents a major advance with respect to Gaia DR2 in terms of astrometric and photometric precision, accuracy, and homogeneity. Results. Gaia EDR3 contains celestial positions and the apparent brightness in G for approximately 1.8 billion sources. For 1.5 billion of those sources, parallaxes, proper motions, and the ( G BP − G RP ) colour are also available. The passbands for G , G BP , and G RP are provided as part of the release. For ease of use, the 7 million radial velocities from Gaia DR2 are included in this release, after the removal of a small number of spurious values. New radial velocities will appear as part of Gaia DR3. Finally, Gaia EDR3 represents an updated materialisation of the celestial reference frame (CRF) in the optical, the Gaia -CRF3, which is based solely on extragalactic sources. The creation of the source list for Gaia EDR3 includes enhancements that make it more robust with respect to high proper motion stars, and the disturbing effects of spurious and partially resolved sources. The source list is largely the same as that for Gaia DR2, but it does feature new sources and there are some notable changes. The source list will not change for Gaia DR3. Conclusions. Gaia EDR3 represents a significant advance over Gaia DR2, with parallax precisions increased by 30 per cent, proper motion precisions increased by a factor of 2, and the systematic errors in the astrometry suppressed by 30–40% for the parallaxes and by a factor ~2.5 for the proper motions. The photometry also features increased precision, but above all much better homogeneity across colour, magnitude, and celestial position. A single passband for G , G BP , and G RP is valid over the entire magnitude and colour range, with no systematics above the 1% level

The current estimate of the prevalence of atrial fibrillation (AF) in the developed world is approximately 1.5–2% of the general population, with the average age of patients with this condition steadily rising, such that it now averages between 75 and 85 years. The arrhythmia is associated with a five-fold risk of stroke and a three-fold incidence of congestive heart failure, and higher mortality. Hospitalization of patients with AF is also very common. This arrhythmia is a major cardiovascular challenge in modern society and its medical, social and economic aspects are all set to worsen over the coming decades. Fortunately a number of valuable treatments have been devised in recent years that may offer some solution to this problem.

Bacillus subtilis is the best-characterized member of the Gram-positive bacteria. Its genome of 4,214,810 base pairs comprises 4,100 protein-coding genes. Of these protein-coding genes, 53% are represented once, while a quarter of the genome corresponds to several gene families that have been greatly expanded by gene duplication, the largest family containing 77 putative ATP-binding transport proteins. In addition, a large proportion of the genetic capacity is devoted to the utilization of a variety of carbon sources, including many plant-derived molecules. The identification of five signal peptidase genes, as well as several genes for components of the secretion apparatus, is important given the capacity of Bacillus strains to secrete large amounts of industrially important enzymes. Many of the genes are involved in the synthesis of secondary metabolites, including antibiotics, that are more typically associated with Streptomyces species. The genome contains at least ten prophages or remnants of prophages, indicating that bacteriophage infection has played an important evolutionary role in horizontal gene transfer, in particular in the propagation of bacterial pathogenesis.

The ESC/EACTS Guidelines represent the views of the ESC and the EACTS and were arrived at after careful consideration of the available evidence at the time they were written. Health professionals are encouraged to take them fully into account when exercising their clinical judgement. The guidelines do not, however, override the individual responsibility of health professionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient and, where appropriate and necessary, the patient's guardian or carer. It is also the health professional's responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription.

Oxygen is fundamental to life. Not only is it essential for the survival of individual animals, but it regulates global cycles of major nutrients and carbon. The oxygen content of the open ocean and coastal waters has been declining for at least the past half-century, largely because of human activities that have increased global temperatures and nutrients discharged to coastal waters. These changes have accelerated consumption of oxygen by microbial respiration, reduced solubility of oxygen in water, and reduced the rate of oxygen resupply from the atmosphere to the ocean interior, with a wide range of biological and ecological consequences. Further research is needed to understand and predict long-term, global- and regional-scale oxygen changes and their effects on marine and estuarine fisheries and ecosystems.

Guidance is provided in a European setting on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis. INTRODUCTION: The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2013. This manuscript updates these in a European setting. METHODS: Systematic reviews were updated. RESULTS: The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of osteoporosis; monitoring of treatment; assessment of fracture risk; case-finding strategies; investigation of patients; health economics of treatment. The update includes new information on the evaluation of bone microstructure evaluation in facture risk assessment, the role of FRAX® and Fracture Liaison Services in secondary fracture prevention, long-term effects on fracture risk of dietary intakes, and increased fracture risk on stopping drug treatment. CONCLUSIONS: A platform is provided on which specific guidelines can be developed for national use.

A plant biostimulant is any substance or microorganism applied to plants with the aim to enhance nutrition efficiency, abiotic stress tolerance and/or crop quality traits, regardless of its nutrients content. By extension, plant biostimulants also designate commercial products containing mixtures of such substances and/or microorganisms. The definition proposed by this article is supported by arguments related to the scientific knowledge about the nature, modes of action and types of effects of biostimulants on crop and horticultural plants. Furthermore, the proposed definition aims at contributing to the acceptance of biostimulants by future regulations, especially in the EU, drawing the lines between biostimulants and fertilisers, pesticides or biocontrol agents. Many biostimulants improve nutrition and they do so regardless of their nutrients contents. Biofertilisers, which we propose as a subcategory of biostimulants, increase nutrient use efficiency and open new routes of nutrients acquisition by plants. In this sense, microbial biostimulants include mycorrhizal and non-mycorrhizal fungi, bacterial endosymbionts (like Rhizobium) and Plant Growth-Promoting Rhizobacteria. Thus, microorganisms applied to plants can have a dual function of biocontrol agent and of biostimulant, and the claimed agricultural effect will be instrumental in their regulatory categorization. The present review gives an overview of the definition and concept of plant biostimulants, as well as the main categories. This paper will also briefly describe the legal and regulatory status of biostimulants, with a focus on the EU and the US, and outlines the drivers, opportunities and challenges of their market development.

Over the last few decades, researchers have developed a number of empirical and theoretical models for the correlation and prediction of the thermophysical properties of pure fluids and mixtures treated as pseudo-pure fluids. In this paper, a survey of all the state-of-the-art formulations of thermophysical properties is presented. The most-accurate thermodynamic properties are obtained from multiparameter Helmholtz-energy-explicit-type formulations. For the transport properties, a wider range of methods has been employed, including the extended corresponding states method. All of the thermophysical property correlations described here have been implemented into CoolProp, an open-source thermophysical property library. This library is written in C++, with wrappers available for the majority of programming languages and platforms of technical interest. As of publication, 110 pure and pseudo-pure fluids are included in the library, as well as properties of 40 incompressible fluids and humid air. The source code for the CoolProp library is included as an electronic annex.