Charles University

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 European Working Group on Sarcopenia in Older People (EWGSOP) developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia. EWGSOP included representatives from four participant organisations, i.e. the European Geriatric Medicine Society, the European Society for Clinical Nutrition and Metabolism, the International Association of Gerontology and Geriatrics-European Region and the International Association of Nutrition and Aging. These organisations endorsed the findings in the final document. The group met and addressed the following questions, using the medical literature to build evidence-based answers: (i) What is sarcopenia? (ii) What parameters define sarcopenia? (iii) What variables reflect these parameters, and what measurement tools and cut-off points can be used? (iv) How does sarcopenia relate to cachexia, frailty and sarcopenic obesity? For the diagnosis of sarcopenia, EWGSOP recommends using the presence of both low muscle mass + low muscle function (strength or performance). EWGSOP variously applies these characteristics to further define conceptual stages as 'presarcopenia', 'sarcopenia' and 'severe sarcopenia'. EWGSOP reviewed a wide range of tools that can be used to measure the specific variables of muscle mass, muscle strength and physical performance. Our paper summarises currently available data defining sarcopenia cut-off points by age and gender; suggests an algorithm for sarcopenia case finding in older individuals based on measurements of gait speed, grip strength and muscle mass; and presents a list of suggested primary and secondary outcome domains for research. Once an operational definition of sarcopenia is adopted and included in the mainstream of comprehensive geriatric assessment, the next steps are to define the natural course of sarcopenia and to develop and define effective treatment.

A search for the Standard Model Higgs boson in proton-proton collisions with the ATLAS detector at the LHC is presented. The datasets used correspond to integrated luminosities of approximately 4.8 fb^-1 collected at sqrt(s) = 7 TeV in 2011 and 5.8 fb^-1 at sqrt(s) = 8 TeV in 2012. Individual searches in the channels H->ZZ^(*)->llll, H->gamma gamma and H->WW->e nu mu nu in the 8 TeV data are combined with previously published results of searches for H->ZZ^(*), WW^(*), bbbar and tau^+tau^- in the 7 TeV data and results from improved analyses of the H->ZZ^(*)->llll and H->gamma gamma channels in the 7 TeV data. Clear evidence for the production of a neutral boson with a measured mass of 126.0 +/- 0.4(stat) +/- 0.4(sys) GeV is presented. This observation, which has a significance of 5.9 standard deviations, corresponding to a background fluctuation probability of 1.7x10^-9, is compatible with the production and decay of the Standard Model Higgs boson.

New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.

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.

BACKGROUND: In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes. METHODS: In this phase 3, placebo-controlled trial, we randomly assigned 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either dapagliflozin (at a dose of 10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death. RESULTS: Over a median of 18.2 months, the primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). A first worsening heart failure event occurred in 237 patients (10.0%) in the dapagliflozin group and in 326 patients (13.7%) in the placebo group (hazard ratio, 0.70; 95% CI, 0.59 to 0.83). Death from cardiovascular causes occurred in 227 patients (9.6%) in the dapagliflozin group and in 273 patients (11.5%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.69 to 0.98); 276 patients (11.6%) and 329 patients (13.9%), respectively, died from any cause (hazard ratio, 0.83; 95% CI, 0.71 to 0.97). Findings in patients with diabetes were similar to those in patients without diabetes. The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ between treatment groups. CONCLUSIONS: Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes. (Funded by AstraZeneca; DAPA-HF ClinicalTrials.gov number, NCT03036124.).

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Rhinosinusitis is a significant and increasing health problem which results in a large financial burden on society. This evidence based position paper describes what is known about rhinosinusitis and nasal polyps, offers evidence based recommendations on diagnosis and treatment, and considers how we can make progress with research in this area. Rhinitis and sinusitis usually coexist and are concurrent in most individuals; thus, the correct terminology is now rhinosinusitis. Rhinosinusitis (including nasal polyps) is defined as inflammation of the nose and the paranasal sinuses characterised by two or more symptoms, one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip), +/- facial pain/pressure, +/- reduction or loss of smell; and either endoscopic signs of polyps and/or mucopurulent discharge primarily from middle meatus and/or; oedema/mucosal obstruction primarily in middle meatus, and/or CT changes showing mucosal changes within the ostiomeatal complex and/or sinuses. The paper gives different definitions for epidemiology, first line and second line treatment and for research. Furthermore the paper describes the anatomy and (patho)physiology, epidemiology and predisposing factors, inflammatory mechanisms, evidence based diagnosis, medical and surgical treatment in acute and chronic rhinosinusitis and nasal polyposis in adults and children. Evidence based schemes for diagnosis and treatment are given for the first and second line clinicians. Moreover attention is given to complications and socio-economic cost of chronic rhinosinusitis and nasal polyps. Last but not least the relation to the lower airways is discussed.

Our previous study demonstrated increased expression of Heat shock protein (Hsp) 90 in the skin of patients with systemic sclerosis (SSc). We aimed to evaluate plasma Hsp90 in SSc and characterize its association with SSc-related features. Ninety-two SSc patients and 92 age-/sex-matched healthy controls were recruited for the cross-sectional analysis. The longitudinal analysis comprised 30 patients with SSc associated interstitial lung disease (ILD) routinely treated with cyclophosphamide. Hsp90 was increased in SSc compared to healthy controls. Hsp90 correlated positively with C-reactive protein and negatively with pulmonary function tests: forced vital capacity and diffusing capacity for carbon monoxide (DLCO). In patients with diffuse cutaneous (dc) SSc, Hsp90 positively correlated with the modified Rodnan skin score. In SSc-ILD patients treated with cyclophosphamide, no differences in Hsp90 were found between baseline and after 1, 6, or 12 months of therapy. However, baseline Hsp90 predicts the 12-month change in DLCO. This study shows that Hsp90 plasma levels are increased in SSc patients compared to age-/sex-matched healthy controls. Elevated Hsp90 in SSc is associated with increased inflammatory activity, worse lung functions, and in dcSSc, with the extent of skin involvement. Baseline plasma Hsp90 predicts the 12-month change in DLCO in SSc-ILD patients treated with cyclophosphamide.

We describe an open-source toolkit for statistical machine translation whose novel contributions are (a) support for linguistically motivated factors, (b) confusion network decoding, and (c) efficient data formats for translation models and language models. In addition to the SMT decoder, the toolkit also includes a wide variety of tools for training, tuning and applying the system to many translation tasks.

Author(s): Collaboration, The ATLAS; Aad, G; Abat, E; Abdallah, J; Abdelalim, AA; Abdesselam, A; Abdinov, O; Abi, BA; Abolins, M; Abramowicz, H; Acerbi, E; Acharya, BS; Achenbach, R; Ackers, M; Adams, DL; Adamyan, F; Addy, TN; Aderholz, M; Adorisio, C; Adragna, P; Aharrouche, M; Ahlen, SP; Ahles, F; Ahmad, A; Ahmed, H; Aielli, G; Åkesson, PF; Åkesson, TPA; Akimov, AV; Alam, SM; Albert, J; Albrand, S; Aleksa, M; Aleksandrov, IN; Aleppo, M; Alessandria, F; Alexa, C; Alexander, G; Alexopoulos, T; Alimonti, G; Aliyev, M; Allport, PP; Allwood-Spiers, SE; Aloisio, A; Alonso, J; Alves, R; Alviggi, MG; Amako, K; Amaral, P; Amaral, SP; Ambrosini, G; Ambrosio, G; Amelung, C; Ammosov, VV; Amorim, A; Amram, N; Anastopoulos, C; Anderson, B; Anderson, KJ; Anderssen, EC; Andreazza, A; Andrei, V; Andricek, L; Andrieux, M-L; Anduaga, XS; Anghinolfi, F; Antonaki, A; Antonelli, M; Antonelli, S; Apsimon, R; Arabidze, G; Aracena, I; Arai, Y; Arce, ATH; Archambault, JP; Arguin, J-F; Arik, E; Arik, M; Arms, KE; Armstrong, SR; Arnaud, M; Arnault, C; Artamonov, A; Asai, S; Ask, S

Includes foreword to the 1947 ed.

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

Abstract We herein present an overview of the upcoming 5 th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4 th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5 th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.

BACKGROUND: Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. METHODS: We used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. FINDINGS: The number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. INTERPRETATION: Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings. FUNDING: WHO.

Abstract We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the solar system, exploring the transient optical sky, and mapping the Milky Way. LSST will be a large, wide-field ground-based system designed to obtain repeated images covering the sky visible from Cerro Pachón in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg 2 field of view, a 3.2-gigapixel camera, and six filters ( ugrizy ) covering the wavelength range 320–1050 nm. The project is in the construction phase and will begin regular survey operations by 2022. About 90% of the observing time will be devoted to a deep-wide-fast survey mode that will uniformly observe a 18,000 deg 2 region about 800 times (summed over all six bands) during the anticipated 10 yr of operations and will yield a co-added map to r ∼ 27.5. These data will result in databases including about 32 trillion observations of 20 billion galaxies and a similar number of stars, and they will serve the majority of the primary science programs. The remaining 10% of the observing time will be allocated to special projects such as Very Deep and Very Fast time domain surveys, whose details are currently under discussion. We illustrate how the LSST science drivers led to these choices of system parameters, and we describe the expected data products and their characteristics.

In this position statement of the ESC Working Group on Myocardial and Pericardial Diseases an expert consensus group reviews the current knowledge on clinical presentation, diagnosis and treatment of myocarditis, and proposes new diagnostic criteria for clinically suspected myocarditis and its distinct biopsy-proven pathogenetic forms. The aims are to bridge the gap between clinical and tissue-based diagnosis, to improve management and provide a common reference point for future registries and multicentre randomised controlled trials of aetiology-driven treatment in inflammatory heart muscle disease.

Obesity is a chronic metabolic disease characterised by an increase of body fat stores. It is a gateway to ill health, and it has become one of the leading causes of disability and death, affecting not only adults but also children and adolescents worldwide. In clinical practice, the body fatness is estimated by BMI, and the accumulation of intra-abdominal fat (marker for higher metabolic and cardiovascular disease risk) can be assessed by waist circumference. Complex interactions between biological, behavioural, social and environmental factors are involved in regulation of energy balance and fat stores. A comprehensive history, physical examination and laboratory assessment relevant to the patient's obesity should be obtained. Appropriate goals of weight management emphasise realistic weight loss to achieve a reduction in health risks and should include promotion of weight loss, maintenance and prevention of weight regain. Management of co-morbidities and improving quality of life of obese patients are also included in treatment aims. Balanced hypocaloric diets result in clinically meaningful weight loss regardless of which macronutrients they emphasise. Aerobic training is the optimal mode of exercise for reducing fat mass while a programme including resistance training is needed for increasing lean mass in middle-aged and overweight/obese individuals. Cognitive behavioural therapy directly addresses behaviours that require change for successful weight loss and weight loss maintenance. Pharmacotherapy can help patients to maintain compliance and ameliorate obesity-related health risks. Surgery is the most effective treatment for morbid obesity in terms of long-term weight loss. A comprehensive obesity management can only be accomplished by a multidisciplinary obesity management team. We conclude that physicians have a responsibility to recognise obesity as a disease and help obese patients with appropriate prevention and treatment. Treatment should be based on good clinical care, and evidence-based interventions; should focus on realistic goals and lifelong multidisciplinary management.

doi: 10.1093/ageing/afy169 In the original version of the above paper there was an error in Table 3, which shows the recommended cut-off points for ASM/height2 in women. The cut-off point was given as <6.0 kg/m2, but the correct value is <5.5 kg/m2. This has now been corrected online. The authors wish to apologise for this error.

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