European Union

Table of Contents Introduction Principles New aspects Epidemiological aspects Relationship of blood pressure to cardiovascular and renal damage Definition and classification of hypertension Prevalence of hypertension Hypertension and total cardiovascular risk Assessment of total cardiovascular risk Limitations Summary of recommendations on total cardiovascular risk assessment Diagnostic evaluation Bood pressure measurement Office or clinic blood pressure Out-of-office blood pressure White-coat (or isolated office) hypertension and masked (or isolated ambulatory) hypertension Clinical indications for out-of-office blood pressure Blood pressure during exercise and laboratory stress Central blood pressure Medical history Physical examination Summary of recommendations on blood pressure measurement, history, and physical examination Laboratory investigations Genetics Searching for asymptomatic organ damage Heart Blood vessels Kidney Fundoscopy Brain Clinical value and limitations Summary of recommendations on the search for asymptomatic organ damage, cardiovascular disease, and chronic kidney disease Searching for secondary forms of hypertension Treatment approach Evidence favouring therapeutic reduction of high blood pressure When to initiate antihypertensive drug treatment Recommendations of previous Guidelines Grade 2 and 3 hypertension and high-risk grade 1 hypertension Low-to-moderate risk, grade 1 hypertension Isolated systolic hypertension in youth Grade 1 hypertension in the elderly High normal blood pressure Summary of recommendations on initiation of antihypertensive drug treatment Blood pressure treatment targets Recommendations of previous Guidelines Low-to-moderate risk hypertensive patients Hypertension in the elderly High-risk patients The ‘lower the better’ vs. the J-shaped curve hypothesis Evidence on target blood pressure from organ damage studies Clinic vs. home and ambulatory blood pressure targets Summary of recommendations on blood pressure targets in hypertensive patients Treatment strategies Lifestyle changes Salt restriction Moderation of alcohol consumption Other dietary changes Weight reduction Regular physical exercise Smoking cessation Summary of recommendations on adoption of lifestyle changes Pharmacological therapy Choice of antihypertensive drugs Monotherapy and combination therapy Summary of recommendations on treatment strategies and choice of drugs Treatment strategies in special conditions White-coat hypertension Masked hypertension Summary of recommendations on treatment strategies in white-coat and masked hypertension Elderly Summary of recommendations on antihypertensive treatment strategies in the elderly Young adults Women Oral contraceptives Hormone replacement therapy Pregnancy Long-term cardiovascular consequences in gestational hypertension Summary of recommendations on treatment strategies in hypertensive women Diabetes mellitus Summary of recommendations on treatment strategies in patients with diabetes Metabolic syndrome Summary of recommendations on treatment strategies in hypertensive patients with metabolic syndrome Obstructive sleep apnoea Diabetic and non-diabetic nephropathy Summary of recommendations on therapeutic strategies in hypertensive patients with nephropathy Chronic kidney disease stage 5D Cerebrovascular disease Acute stroke Previous stroke or transient ischaemic attack Cognitive dysfunction and white matter lesions Summary of recommendations on therapeutic strategies in hypertensive patients with cerebrovascular disease Heart disease Coronary heart disease Heart failure Atrial fibrillation Left ventricular hypertrophy Summary of recommendations on therapeutic strategies in hypertensive patients with heart disease Atherosclerosis, arteriosclerosis, and peripheral artery disease Carotid atherosclerosis Increased arterial stiffness Peripheral artery disease Summary of recommendations on therapeutic strategies in hypertensive patients with atherosclerosis, arteriosclerosis, and peripheral artery disease Sexual dysfunction Resistant hypertension Carotid baroreceptor stimulation Renal denervation Other invasive approaches Follow-up in resistant hypertension Summary of recommendations on therapeutic strategies in patients with resistant hypertension Malignant hypertension Hypertensive emergencies and urgencies Perioperative management of hypertension Renovascular hypertension Primary aldosteronism Treatment of associated risk factors Lipid-lowering agents Antiplatelet therapy Treatment of hyperglycaemia Summary of recommendations on treatment of risk factors associated with hypertension Follow-up Follow-up of hypertensive patients Follow-up of subjects with high normal blood pressure and white-coat hypertension Elevated blood pressure at control visits Continued search for asymptomatic organ damage Can antihypertensive medications be reduced or stopped? Improvement of blood pressure control in hypertension Hypertension disease management Team approach in disease management Mode of care delivery The role of information and communication technologies 53 Gaps in evidence and need for future trials Appendix 1 Appendix 2 Acknowledgments References 1. INTRODUCTION 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) follow the guidelines jointly issued by the two societies in 2003 and 2007 [1,2]. Publication of a new document 6 years after the previous one was felt to be timely because, over this period, important studies have been conducted and many new results have been published on both the diagnosis and treatment of individuals with an elevated blood pressure (BP), making refinements, modifications and expansion of the previous recommendations necessary. The 2013 ESH/ESC guidelines continue to adhere to some fundamental principles that inspired the 2003 and 2007 guidelines, namely (i) to base recommendations on properly conducted studies identified from an extensive review of the literature, (ii) to consider, as the highest priority, data from randomized, controlled trials (RCTs) and their meta-analyses, but not to disregard—particularly when dealing with diagnostic aspects—the results of observational and other studies of appropriate scientific calibre, and (iii) to grade the level of scientific evidence and the strength of recommendations on major diagnostic and treatment issues as in European guidelines on other diseases, according to ESC recommendations (Tables 1 and 2). While it was not done in the 2003 and 2007 guidelines, providing the recommendation class and the level of evidence is now regarded as important for providing interested readers with a standard approach, by which to compare the state of knowledge across different fields of medicine. was that this on recommendations that on the of the on is not in because, for a of is and recommendations from and both of which be When this guidelines as and the of studies and evidence is in with is to a of and a of recommendations that be and by in their of of European of the in of the 2013 guidelines on hypertension have been by the and on their and of major of of forms be on the ESC and was a which was by and by two one by and by The was over during which the and with one the document was by European by and by be that the recommendations issued by the 2013 ESH/ESC guidelines on hypertension the state of the on as by and in for and the have been by and New aspects of new evidence on diagnostic and therapeutic aspects of the guidelines in many from the previous of the important Epidemiological data on hypertension and control in of the value of home blood pressure and of role for diagnosis and management of to ambulatory blood pressure of the of white-coat hypertension and masked on of cardiovascular risk asymptomatic organ damage and for total risk of the of asymptomatic blood and of the risk of and target in Hypertension in of antihypertensive and drug treatment of high normal for and target systolic blood pressure in both and risk approach to for New therapeutic for target on therapeutic strategies in special recommendations on treatment of hypertension in the treatment of to resistant hypertension and new treatment Increased to New approaches to chronic management of hypertensive Relationship of blood pressure to cardiovascular and renal damage The and and renal been in a of observational studies The in in the 2003 and 2007 ESH/ESC guidelines be as Office an with the of heart failure and peripheral artery disease as as of renal disease is at and in The with from high to of for and for to be a of after the of years and in elderly individuals pressure and been to have a role is by the high risk by patients with an elevated and a normal or systolic hypertension with is by out-of-office as by and The and and is by the of other risk Metabolic risk factors when is high when it is Definition and classification of hypertension The and and renal the and hypertension when on is because, in the and have a both to the diagnostic approach and to the The classification is from the 2003 and 2007 ESH/ESC guidelines Hypertension is as on the evidence from that in patients with and The classification is in and elderly different on in and for data from trials not on classification in and according to their and be in the on the evaluation and treatment of high in and and classification of blood pressure Prevalence of hypertension data on the of hypertension and the of in different European the of hypertension to be of the with a with to be in the across with changes in the to the of results and the of a of hypertension been is a hypertension is by the important of this of hypertension and for stroke been The and of stroke in have been by of European a in to European which a in from stroke Hypertension and total cardiovascular risk a hypertension guidelines on as the or the need the the and European Society recommendations on of heart disease in and that of be to of total (or approach is now and been the 2003 and 2007 ESH/ESC guidelines for the management of arterial hypertension [1,2]. 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physical laboratory investigations and diagnostic of the investigations in in Bood pressure measurement Office or clinic blood pressure be a in not or be according to and their be in a laboratory of at the is and and be to the the of a and which been to an risk the with the be is by one a with measurement, it be to elderly patients and in other conditions in which be or it is that be 1 and 3 after of the as a reduction in of or in of 3 of been to a for and of in the with the in an isolated providing information be as a to and to by or be associated with measurement of heart heart or in hypertension for in Table Office blood pressure Out-of-office blood pressure The major of out-of-office is that it a of from the which a assessment of Out-of-office is by or by principles and for the two of in to recommendations for measurement The be to the with and in of appropriate of the results that the of out-of-office is for and but for the and for and and different information on the and risk and 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BACKGROUND: Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. METHODS: ). For school-aged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). FINDINGS: From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. INTERPRETATION: The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity. FUNDING: UK Medical Research Council, UK Research and Innovation (Research England), UK Research and Innovation (Innovate UK), and European Union.

An account is presented of a series of investigations and collaborative studies, initiated by BCR, on current methods of metal speciation by extraction of soils and sediments with chemical reagents. It was established by extensive consultation with European experts that the diverse procedures used could be harmonized into agreed methods. These methods, including both single extractant and sequential extraction procedures were subjected to collaborative, interlaboratory trials and the results, presented briefly here, showed that it was both possible and desirable that reference soils and sediments, characterised by certified values for extractable contents, be prepared. As a consequence of these studies two soils have been prepared and will shortly be the subject of interlaboratory analysis with a view to certification of their EDTA and acetic acid extractable contents of some heavy metals. Following this workshop a feasibility study of the agreed sequential extraction procedure will, it is believed, shortly lead to certification of sediments for contents extractable by a defined sequential extraction procedure.

Assessing Biodiversity Declines Understanding human impact on biodiversity depends on sound quantitative projection. Pereira et al. (p. 1496 , published online 26 October) review quantitative scenarios that have been developed for four main areas of concern: species extinctions, species abundances and community structure, habitat loss and degradation, and shifts in the distribution of species and biomes. Declines in biodiversity are projected for the whole of the 21st century in all scenarios, but with a wide range of variation. Hoffmann et al. (p. 1503 , published online 26 October) draw on the results of five decades' worth of data collection, managed by the International Union for Conservation of Nature Species Survival Commission. A comprehensive synthesis of the conservation status of the world's vertebrates, based on an analysis of 25,780 species (approximately half of total vertebrate diversity), is presented: Approximately 20% of all vertebrate species are at risk of extinction in the wild, and 11% of threatened birds and 17% of threatened mammals have moved closer to extinction over time. Despite these trends, overall declines would have been significantly worse in the absence of conservation actions.

Abstract not Available.

Staphylococcal food poisoning (SFP) is one of the most common food-borne diseases and results from the ingestion of staphylococcal enterotoxins (SEs) preformed in food by enterotoxigenic strains of Staphylococcus aureus. To date, more than 20 SEs have been described: SEA to SElV. All of them have superantigenic activity whereas half of them have been proved to be emetic, representing a potential hazard for consumers. This review, divided into four parts, will focus on the following: (1) the worldwide story of SFP outbreaks, (2) the characteristics and behaviour of S. aureus in food environment, (3) the toxinogenic conditions and characteristics of SEs, and (4) SFP outbreaks including symptomatology, occurrence in the European Union and currently available methods used to characterize staphylococcal outbreaks.

This paper proposes a new approach in polarimetric synthetic aperture radar (SAR) speckle filtering. The new approach emphasizes preserving polarimetric properties and statistical correlation between channels, not introducing crosstalk, and not degrading the image quality. In the last decade, speckle reduction of polarimetric SAR imagery has been studied using several different approaches. All of these approaches exploited the degree of statistical independence between linear polarization channels. The preservation of polarimetric properties and statistical characteristics such as correlation between channels were not carefully addressed. To avoid crosstalk, each element of the covariance matrix must be filtered independently. This rules out current methods of polarimetric SAR filtering. To preserve the polarimetric signature, each element of the covariance matrix should be filtered in a way similar to multilook processing by averaging the covariance matrix of neighboring pixels. However, this must be done without the deficiency of smearing the edges, which degrades image quality and corrupts polarimetric properties. The proposed polarimetric SAR filter uses edge-aligned nonsquare windows and applies the local statistics filter. The impact of using this polarimetric speckle filtering on terrain classification is quite dramatic in boosting classification performance. Airborne polarimetric radar images are used for illustration.

Allergic rhinoconjunctivitis (AR) is an allergic disorder of the nose and eyes affecting about a fifth of the general population. Symptoms of AR can be controlled with allergen avoidance measures and pharmacotherapy. However, many patients continue to have ongoing symptoms and an impaired quality of life; pharmacotherapy may also induce some side-effects. Allergen immunotherapy (AIT) represents the only currently available treatment that targets the underlying pathophysiology, and it may have a disease-modifying effect. Either the subcutaneous (SCIT) or sublingual (SLIT) routes may be used. This Guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on AIT for AR and is part of the EAACI presidential project "EAACI Guidelines on Allergen Immunotherapy." It aims to provide evidence-based clinical recommendations and has been informed by a formal systematic review and meta-analysis. Its generation has followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included involvement of the full range of stakeholders. In general, broad evidence for the clinical efficacy of AIT for AR exists but a product-specific evaluation of evidence is recommended. In general, SCIT and SLIT are recommended for both seasonal and perennial AR for its short-term benefit. The strongest evidence for long-term benefit is documented for grass AIT (especially for the grass tablets) where long-term benefit is seen. To achieve long-term efficacy, it is recommended that a minimum of 3 years of therapy is used. Many gaps in the evidence base exist, particularly around long-term benefit and use in children.

Abstract: This article argues that current widespread characterisations of EU governance as multi‐level and networked overlook the emergent architecture of the EU's public rule making. In this architecture, framework goals (such as full employment, social inclusion, ‘good water status’, a unified energy grid) and measures for gauging their achievement are established by joint action of the Member States and EU institutions. Lower‐level units (such as national ministries or regulatory authorities and the actors with whom they collaborate) are given the freedom to advance these ends as they see fit. But in return for this autonomy, they must report regularly on their performance and participate in a peer review in which their results are compared with those pursuing other means to the same general ends. Finally, the framework goals, performance measures, and decision‐making procedures themselves are periodically revised by the actors, including new participants whose views come to be seen as indispensable to full and fair deliberation. Although this architecture cannot be read off from either Treaty provisions or textbook accounts of the formal competences of EU institutions, the article traces its emergence and diffusion across a wide range of policy domains, including telecommunications, energy, drug authorisation, occupational health and safety, employment promotion, social inclusion, pensions, health care, environmental protection, food safety, maritime safety, financial services, competition policy, state aid, anti‐discrimination policy and fundamental rights.

All transretinoic acid (ATRA) followed by daunorubicin (DNR)-AraC chemotherapy (CT) has improved the outcome of acute promyelocytic leukemia (APL) by comparison to CT alone. In a randomized trial, (1) we compared 2 induction schedules (ATRA followed by CT [ATRA-->CT] and ATRA plus CT [ATRA+CT, with CT added on day 3 of ATRA treatment]) and (2) we assessed the role of maintenance treatment. Four hundred thirteen patients </=75 years of age and with newly diagnosed APL were included. Induction treatment was stratified on white blood cell (WBC) count and age: patients </=65 years of age and with an initial WBC count of </=5,000/microL (n = 208) were randomized between ATRA-->CT and ATRA+CT (initially randomized patients); patients with a WBC count greater than (high WBC count group, n = 163) and patients 66 to 75 years of age with a WBC count greater than 5,000/microL (elderly group, n = 42) were not initially randomized and received ATRA+CT from day 1 and ATRA -->CT, respectively. All patients achieving CR received 2 additional DNR-AraC courses (only 1 in patients 66 to 75 years of age) and were then randomized for maintenance between no treatment, intermittent ATRA (15 days every 3 months) for 2 years, continuous low-dose CT (6 mercaptopurine + methotrexate) for 2 years, or both, using a 2-by-2 factorial design. Overall, 381 (92%) of the patients achieved complete remission (CR), 31 (7%) suffered an early death, and only 1 patient had leukemic resistance. ATRA syndrome occurred in 64 patients (15%) and was fatal in 5 cases. The CR rate was similar in all induction treatment groups. Event-free survival (EFS) was significantly lower in the high WBC group (P =.0002) and close to significance in the elderly group (P =.086) as compared with initially randomized patients. Relapse at 2 years was estimated at 6% in the ATRA+CT group, versus 16% in the ATRA-->CT group (P =.04, relative risk [RR] =.41). EFS at 2 years was estimated at 84% in the ATRA+CT group, versus 77% in the ATRA-->CT group (P =.1, RR =.62). Two hundred eighty-nine patients were randomized for maintenance. The 2-year relapse rate was 11% in patients randomized to continuous maintenance CT and 27% in patients randomized to no CT (P =.0002) and 13% in patients randomized to intermittent ATRA and 25% in patients randomized to no ATRA (P =.02). An additive effect of continuous maintenance CT and intermittent ATRA was seen, and only 6 of the 74 patients who received both maintenance treatments had relapsed. Overall survival was improved in patients who received maintenance CT (P =.01), and there was a trend for better survival in patients who received maintenance ATRA (P =.22). Our findings strongly suggest that early addition of chemotherapy to ATRA and maintenance therapy combining continuous CT and intermittent ATRA can reduce the incidence of relapse in APL. This effect already translates into significantly better survival for maintenance treatment with continuous CT.

PURPOSE: To compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) and anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. PATIENTS AND METHODS: Patients (n = 451) with advanced breast cancer were randomized to receive fulvestrant 250 mg as a once-monthly (one x 5 mL) intramuscular injection or an oral dose of anastrozole 1 mg in this open, parallel-group, multicenter trial. The primary end point was time to progression (TTP). Secondary end points included objective response (OR) rates, defined as complete response (CR) or partial response (PR), duration of response (DOR), and tolerability. RESULTS: Patients were followed for a median period of 14.4 months. In terms of TTP, fulvestrant was as effective as anastrozole (hazard ratio, 0.98; confidence interval [CI], 0.80 to 1.21; P =.84). Median TTP was 5.5 months for fulvestrant and 5.1 months for anastrozole. OR rates showed a numerical advantage for fulvestrant (20.7%) over anastrozole (15.7%) (odds ratio, 1.38; CI, 0.84 to 2.29; P =.20). Clinical benefit rates (CR + PR + stable disease > or = 24 weeks) were 44.6% for fulvestrant and 45.0% for anastrozole. Median DOR was 14.3 months for fulvestrant and 14.0 months for anastrozole. Both treatments were well tolerated, with 3.2% and 1.3% of fulvestrant- and anastrozole-treated patients, respectively, withdrawn from treatment because of an adverse event. CONCLUSION: Fulvestrant was as effective as anastrozole. These data confirm that fulvestrant is an additional, effective, and well-tolerated treatment for advanced breast cancer in postmenopausal women whose disease progressed on prior endocrine therapy.

Abstract International organizations are widely believed to undermine domestic democracy. Our analysis challenges this conventional wisdom, arguing that multilateral institutions can enhance the quality of national democratic processes, even in well-functioning democracies, in a number of important ways: by restricting the power of special interest factions, protecting individual rights, and improving the quality of democratic deliberation, while also increasing capacities to achieve important public purposes. The article discusses conflicts and complementarities between multilateralism and democracy, outlines a working conception of constitutional democracy, elaborates theoretically the ways in which multilateral institutions can enhance constitutional democracy, and discusses the empirical conditions under which multilateralism is most likely to have net democratic benefits, using contemporary examples to illustrate the analysis. The overall aim is to articulate a set of critical democratic standards appropriate for evaluating and helping to guide the reform of international institutions.

Abstract Recent work on the European Union (EU) indicates an emerging consensus that the boundaries between the ‘domestic’ and the ‘international’ spheres, as well as between the ‘state’ and ‘society’, have to be crossed when conceptualizing the EU. This article starts with reviewing the controversy between neofunctionalism and intergovernmentalism, arguing that it lacks some categories necessary to capture distinctive features of the EU. It then presents a framework combining insights from work on transnational politics by international relations scholars, on policy networks and Politikveflechtung (interlocking politics) by comparative policy analysis, and by historical institutionalism. Propositions are generated on the institutional and structural conditions under which network analysis is better suited than intergovernmentalism to capture the EU policy‐making process. Finally, the article argues that social constructivism has to be taken more seriously in the study of the EU and that network analysis should move beyond rational choice models and incorporate theories of communicative action. More work is needed on the role of ideas and principled beliefs in the EU integration process.

We make distributed stochastic gradient descent faster by exchanging sparse updates instead of dense updates. Gradient updates are positively skewed as most updates are near zero, so we map the 99% smallest updates (by absolute value) to zero then exchange sparse matrices. This method can be combined with quantization to further improve the compression. We explore different configurations and apply them to neural machine translation and MNIST image classification tasks. Most configurations work on MNIST, whereas different configurations reduce convergence rate on the more complex translation task. Our experiments show that we can achieve up to 49% speed up on MNIST and 22% on NMT without damaging the final accuracy or BLEU.

The decision to trust a medical trainee with the critical responsibility to care for a patient is fundamental to clinical training. When carefully and deliberately made, such decisions can serve as significant stimuli for learning and also shape the assessment of trainees. Holding back entrustment decisions too much may hamper the trainee's development toward unsupervised practice. When carelessly made, however, they jeopardize patient safety. Entrustment decision-making processes, therefore, deserve careful analysis.Members (including the authors) of the International Competency-Based Medical Education Collaborative conducted a content analysis of the entrustment decision-making process in health care training during a two-day summit in September 2013 and subsequently reviewed the pertinent literature to arrive at a description of the critical features of this process, which informs this article.The authors discuss theoretical backgrounds and terminology of trust and entrustment in the clinical workplace. The competency-based movement and the introduction of entrustable professional activities force educators to rethink the grounds for assessment in the workplace. Anticipating a decision to grant autonomy at a designated level of supervision appears to align better with health care practice than do most current assessment practices. The authors distinguish different modes of trust and entrustment decisions and elaborate five categories, each with related factors, that determine when decisions to trust trainees are made: the trainee, supervisor, situation, task, and the relationship between trainee and supervisor. The authors' aim in this article is to lay a theoretical foundation for a new approach to workplace training and assessment.

The FAIR principles have been widely cited, endorsed and adopted by a broad range of stakeholders since their publication in 2016. By intention, the 15 FAIR guiding principles do not dictate specific technological implementations, but provide guidance for improving Findability, Accessibility, Interoperability and Reusability of digital resources. This has likely contributed to the broad adoption of the FAIR principles, because individual stakeholder communities can implement their own FAIR solutions. However, it has also resulted in inconsistent interpretations that carry the risk of leading to incompatible implementations. Thus, while the FAIR principles are formulated on a high level and may be interpreted and implemented in different ways, for true interoperability we need to support convergence in implementation choices that are widely accessible and (re)-usable. We introduce the concept of FAIR implementation considerations to assist accelerated global participation and convergence towards accessible, robust, widespread and consistent FAIR implementations. Any self-identified stakeholder community may either choose to reuse solutions from existing implementations, or when they spot a gap, accept the challenge to create the needed solution, which, ideally, can be used again by other communities in the future. Here, we provide interpretations and implementation considerations (choices and challenges) for each FAIR principle.

The WHO European Office for Integrated Health Care Services in Barcelona is an integral part of the World Health Organizations' Regional Office for Europe. The main purpose of the Barcelona office is within the integration of services to encourage and facilitate changes in health care services in order to promote health and improve management and patient satisfaction by working for quality, accessibility, cost-effectiveness and participation. This position paper outlines the need for Integrated Care from a European perspective, provides a theoretical framework for the meaning of Integrated Care and its strategies and summarizes the programmes of the office that will support countries in the WHO European Region to improve health services.

In the present study we assessed the frequency and characteristics of the main causes of morbidity and mortality in SLE during a 5-year period and analyzed the prognostic significance for morbidity and mortality of the main immunologic parameters used in clinical practice. We started in 1990 a multicenter study of 1,000 patients from 7 European countries. All had medical histories documented and underwent medical interview and routine general physical examination when entered in the study, and all were followed prospectively by the same physicians during the ensuing 5 years (1990-1995). Four hundred thirteen patients (41.3%) presented 1 or more episodes of arthritis, 264 (26.4%) had malar rash, 222 (22.2%) active nephropathy, 139 (13.9%) fever, 136 (13.6%) neurologic involvement, 132 (13.2%) Raynaud phenomenon, 129 (12.9%) serositis (pleuritis and/or pericarditis), 95 (9.5%) thrombocytopenia, and 72 (7.2%) thrombosis. Two hundred seventy patients (27%) presented infections, 113 (11.3%) hypertension, 75 (7.5%) osteoporosis, and 59 (5.9%) cytopenia due to immunosuppressive agents. Sixteen patients (1.6%) developed malignancies, with the most frequent primary localizations the uterus and the breast. Several immunologic parameters (anti-dsDNA or antiphospholipid antibodies) were found to have a predictive value for the development of SLE manifestations during the period of the study. Forty-five patients (4.5%) died; the most frequent causes of death were divided similarly among active SLE (28.9%), infections (28.9%), and thromboses (26.7%). A survival probability of 95% at 5 years was found. A lower survival probability (92%) was detected in those patients who presented at the beginning of the study with nephropathy.

Abstract: The question of whether the adoption of International Financial Reporting Standards (IFRS) results in measurable economic benefits is of special interest, particularly in light of the European Union's adoption of IFRS for listed companies. In this paper, I investigate the common conjecture that internationally recognised financial reporting standards (IAS/IFRS or US‐GAAP) reduce the cost of capital for adopting firms. Building on Leuz and Verrecchia (2000) , I use a set of German firms that have adopted such standards and investigate the potential economic benefits of this reporting strategy by analysing their cost of equity capital through the use and customisation of available implied estimation methods. Evidence from the 1993–2002 period fails to document lower expected cost of equity capital for firms applying IAS/IFRS or US‐GAAP. During the transition period I analyse, the expected cost of equity capital in fact appear to have rather increased under non‐local accounting standards.

In 2012, the European Centre for Disease Prevention and Control (ECDC) launched the 'European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE)' project to gain insights into the occurrence and epidemiology of carbapenemase-producing Enterobacteriaceae (CPE), to increase the awareness of the spread of CPE, and to build and enhance the laboratory capacity for diagnosis and surveillance of CPE in Europe. Data collected through a post-EuSCAPE feedback questionnaire in May 2015 documented improvement compared with 2013 in capacity and ability to detect CPE and identify the different carbapenemases genes in the 38 participating countries, thus contributing to their awareness of and knowledge about the spread of CPE. Over the last two years, the epidemiological situation of CPE worsened, in particular with the rapid spread of carbapenem-hydrolysing oxacillinase-48 (OXA-48)- and New Delhi metallo-beta-lactamase (NDM)-producing Enterobacteriaceae. In 2015, 13/38 countries reported inter-regional spread of or an endemic situation for CPE, compared with 6/38 in 2013. Only three countries replied that they had not identified one single case of CPE. The ongoing spread of CPE represents an increasing threat to patient safety in European hospitals, and a majority of countries reacted by establishing national CPE surveillances systems and issuing guidance on control measures for health professionals. However, 14 countries still lacked specific national guidelines for prevention and control of CPE in mid-2015.