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Governments, businesses, and educational institutions need to collaborate and make significant investments in order to address the growing digital skills crisis. In Europe, hundreds of digital skills initiatives have been launched with different forms of government and private industry support in the last five years alone. Consequently, digital skills initiatives have come to encompass a wide array of interventions. In this context, this paper proposes a typology of digital skills initiatives that was developed based on the analysis of over 300 initiatives listed in the European Commission's repository of best digital skills initiatives. The proposed typology consists of four categories: target group, digital skills, learning format, and sponsoring organization. In terms of target group, digital skills initiatives tend to target one or more of five distinct groups: the general public, educators, adults, seniors and youth. In terms of digital skills, digital skills initiatives tend to focus on general digital skills or specialized digital skills. In terms of learning format, digital skills initiatives tend to offer training and/or a learning resource. In terms of sponsoring organization, the initiatives tend to be sponsored by organizations that are either affiliated or unaffiliated with a technology vendor. The typology is followed by a presentation of mini cases, which highlight different archetypes of the proposed typology. The paper closes with a discussion of practical implications for policy makers, administrators, and scholars interested in digital skills initiatives and the future of work.

Purpose: Since new digital micro-credential technologies emerged a decade ago, there has been a rapid rise in micro-credentials in the education landscape. Much has been promised about these educational technologies, yet there is much confusion by key stakeholders in the digital micro-credential ecosystem. This confusion has led to significant efforts globally to define micro-credentials to ensure quality learning and generate beneficial impacts to learners, employers, education providers and edtech organisations. Design/methodology/approach: This commentary reviews relevant literature on digital micro-credentials and other alternative credentials to determine how these educational technologies can meet the demands of the Fourth Industrial Revolution to nurture lifelong learning for working learners. Findings: Universities are being challenged to address the changing needs and uncertainty being introduced by the Fourth and Fifth Industrial Revolutions, particularly with implications for workforce upskilling and lifelong learning. To adapt, universities will need to rethink their roles and shift their institutional mindsets in how they may approach the challenges through mechanisms such as digital micro-credentials. Research limitations/implications: This paper focuses on the analysis of five policy statements about micro-credentials. While these policy statements represent a sample, there is a representation of Western education-related systems. Thus, they skew the findings towards Western education systems thinking. Practical implications: Understanding how micro-credentials are being positioned within education-related systems is useful for applying the educational technologies by, for example, universities, learners and employers. Social implications: Provides an overview of how these educational technologies may provide beneficial impacts for society as it plans to adapt to economic uncertainty and change. Originality/value: The commentary provides a policy context for the emerging use of micro-credential technologies to examine demands for workforce upskilling.

This article deals with understandings of change. It attempts to provide a framework for comprehending the hopes and assumptions concerning change that are implicit within global learning. The proposed framework of understanding draws on the theoretical perspectives of 'world society' (Luhmann) and "homo absconditus" (Plessner), and therefore places the proposed framework regarding an understanding of change within the context of an understanding of cultural functionality.

Although the European Roe Deer (Capreolus capreolus) is one of the most common and widespread ungulate species in Europe and inhabiting a variety of habitats, few studies have addressed its population structure at a large spatial scale using nuclear genetic data. The aims of our study were to: (i) investigate genetic diversity, level of admixture, and genetic structure across European Roe Deer populations; (ii) identify barriers to gene flow; and (iii) reveal factors that have impacted the observed pattern of population genetic structure. Using 12 microsatellite loci, we analyzed 920 European Roe Deer samples from 16 study sites from northern, southern, central, and eastern Europe. The highest genetic diversity was found in central and eastern sites, and lowest in the northern and southern sites. There were 2 main groups of genetically related populations in the study area—one inhabiting mainly Fennoscandia, and the second in the continental part of Europe. This second population was further divided into 3 to 5 spatially distributed genetic clusters. European Roe Deer belonging to the Siberian mitochondrial DNA clade, inhabiting large parts of eastern Europe, were not identified as a separate population in the analysis of microsatellite loci. No isolation by distance (IBD) was detected between roe deer from the fennoscandian and the continental study sites, but the Baltic Sea was inferred to be the main barrier to gene flow. Only weak IBD was revealed within the continental population. Three lower-level genetic barriers were detected in the western, southern, and eastern parts of the study area. The main factors inferred as shaping the observed genetic diversity and population structure of European Roe Deer were postglacial recolonization, admixture of different populations of the species originating from several Last Glacial Maximum refugial areas, and isolation of several study sites. [ABSTRACT FROM AUTHOR]

Beech is an important tree species in Europe. This study aimed to elucidate the influence of four molecular weights of phenol formaldehyde (PF) resin (266, 286, 387, and 410 g/mol) on the sorption behavior of unmodified and modified beech wood samples using a dynamic vapor sorption (DVS) apparatus. The variations in the environmental relative humidity and moisture content (MC) of the samples were recorded, and the DVS isotherms were plotted from the equipment. During the sorption process, the MC of the modified samples decreased in comparison to that of the unmodified samples, and both apparently decreased with the increasing molecular weight of the PF resin. The DVS isotherm hysteresis plot illustrated a reduction in sorption hysteresis for the modified wood with varying PF resins compared to the unmodified samples. Based on the DVS isotherm adsorption and desorption plots, the decrease in the equilibrium of the MC can be attributed to there being fewer sorption sites in the modified samples, which exhibited the lowest hygroscopicity. Overall, the moisture sorption mechanism for both types of samples was clarified, highlighting a clear correlation between the molecular weight of the applied PF resin and its influence on moisture sorption behavior. [ABSTRACT FROM AUTHOR]

Drawing on Max Scheler's political-programmatic writings produced during and after World War I, this contribution intends to examine the content and consistency of the ideal of a cultural-spiritual unity of Europe (as distinct from its political, legal, or economic unity), and to provide a basis for discussing its plausibility and fruitfulness for the present time. About 100 years ago, the philosopher thought about the future of Europe, and claimed to be able to infer concrete orientations for political action from fundamental philosophical insights. Thus, the paper proceeds from conceptual foundations to their application to concrete practical problems. The first section intends to outline the concept of cultural unity and the principle of solidarity between cultural unities; this makes it possible, in the second part, to distinguish the European cultural sphere from others; the final section gives a positive determination of the specific unity of European culture, including some educational consequences. [ABSTRACT FROM AUTHOR]

Repeated herbicide applications in agricultural fields exert strong selection on weeds such as blackgrass (Alopecurus myosuroides), which is a major threat for temperate climate cereal crops. This inadvertent selection pressure provides an opportunity for investigating the underlying genetic mechanisms and evolutionary processes of rapid adaptation, which can occur both through mutations in the direct targets of herbicides and through changes in other, often metabolic, pathways, known as non-target-site resistance. How much target-site resistance (TSR) relies on de novo mutations vs. standing variation is important for developing strategies to manage herbicide resistance. We first generated a chromosome-level reference genome for A. myosuroides for population genomic studies of herbicide resistance and genome-wide diversity across Europe in this species. Next, through empirical data in the form of highly accurate long-read amplicons of alleles encoding acetyl-CoA carboxylase (ACCase) and acetolactate synthase (ALS) variants, we showed that most populations with resistance due to TSR mutations—23 out of 27 and six out of nine populations for ACCase and ALS, respectively—contained at least two TSR haplotypes, indicating that soft sweeps are the norm. Finally, through forward-in-time simulations, we inferred that TSR is likely to mainly result from standing genetic variation, with only a minor role for de novo mutations. [ABSTRACT FROM AUTHOR]

Summary: Trees are known to be atmospheric methane (CH4) emitters. Little is known about seasonal dynamics of tree CH4 fluxes and relationships to environmental conditions. That prevents the correct estimation of net annual tree and forest CH4 exchange.We aimed to explore the contribution of stem emissions to forest CH4 exchange. We determined seasonal CH4 fluxes of mature European beech (Fagus sylvatica) stems and adjacent soil in a typical temperate beech forest of the White Carpathians with high spatial heterogeneity in soil moisture.The beech stems were net annual CH4 sources, whereas the soil was a net CH4 sink. High CH4 emitters showed clear seasonality in their stem CH4 emissions that followed stem CO2 efflux. Elevated CH4 fluxes were detected during the vegetation season. Observed high spatial variability in stem CH4 emissions was neither explicably by soil CH4 exchange nor by CH4 concentrations, water content, or temperature studied in soil profiles near each measured tree. The stem CH4 emissions offset the soil CH4 uptake by up to 46.5% and on average by 13% on stand level.In Central Europe, widely grown beech contributes markedly to seasonal dynamics of ecosystem CH4 exchange. Its contribution should be included into forest greenhouse gas flux inventories. [ABSTRACT FROM AUTHOR]

Adequate pain management is essential for ethical and scientific reasons in animal experiments and should completely cover the period of expected pain without the need for frequent re-application. However, current depot formulations of Buprenorphine are only available in the USA and have limited duration of action. Recently, a new microparticulate Buprenorphine formulation (BUP-Depot) for sustained release has been developed as a potential future alternative to standard formulations available in Europe. Pharmacokinetics indicate a possible effectiveness for about 72 h. Here, we investigated whether the administration of the BUP-Depot ensures continuous and sufficient analgesia in two mouse fracture models (femoral osteotomy) and could, therefore, serve as a potent alternative to the application of Tramadol via the drinking water. Both protocols were examined for analgesic effectiveness, side effects on experimental readout, and effects on fracture healing outcomes in male and female C57BL/6N mice. The BUP-Depot provided effective analgesia for 72 h, comparable to the effectiveness of Tramadol in the drinking water. Fracture healing outcome was not different between analgesic regimes. The availability of a Buprenorphine depot formulation for rodents in Europe would be a beneficial addition for extended pain relief in mice, thereby increasing animal welfare. [ABSTRACT FROM AUTHOR]

European forests are an important source for timber production, human welfare, income, protection and biodiversity. During the last two decades, Europe has experienced a number of droughts which have been exceptional within the last 500 years, both in terms of duration and intensity. These droughts seem to leave remarkable imprints on the mortality dynamics of European forests. However, systematic observations on tree decline, with emphasis on a single species, has been scarce so far so that our understanding of mortality dynamics and drought occurrence is still limited at a continental scale.Here, we make use of the ICP Forest crown defoliation dataset, permitting us to retrospectively monitor tree mortality for all major conifers, major broadleaves, as well as a pooled dataset of minor tree species in Europe. In total, we analysed more than three million observations gathered during the last 25 years and employed a high‐resolution drought index which can assess soil moisture anomaly based on a hydrological water‐balance and runoff model.We found overall and species‐specific increasing trends in mortality rates, accompanied by decreasing soil moisture. A generalized linear mixed model identified a previous‐year soil moisture anomaly as the most important driver of mortality patterns in conifers, but the response was not uniform across the numerous analysed plots.We conclude that mortality patterns in European forests are currently reaching a concerning upward trend which could be further accelerated by global change‐type droughts in the near future. [ABSTRACT FROM AUTHOR]

Background: Between-country differences have been described in antibiotic prescribing for respiratory tract infection (RTI) in primary care, but not yet for diagnostic testing procedures and prescribing confidence. Aim: To describe between-country differences in RTI management, particularly diagnostic testing and antibiotic prescribing, and investigate which factors relate to antibiotic prescribing and GPs' prescribing confidence. Design & setting: Prospective audit in 18 European countries. Method: An audit of GP-registered patient, clinical, and management characteristics for patients presenting with sore throat and/or lower RTI (n = 4982), and GPs' confidence in their antibiotic prescribing decision. Factors related to antibiotic prescribing and confidence were analysed using multi-level logistic regression. Results: Antibiotic prescribing proportions varied considerably: <20% in four countries, and >40% in six countries. There was also considerable variation in point-of-care (POC) testing (0% in Croatia, Moldova, and Romania, and >65% in Denmark and Norway, mainly for C-reactive protein [CRP] and group A streptococcal [strep A] infection), and in laboratory or hospital-based testing (<3% in Hungary, the Netherlands, and Spain, and >30% in Croatia, Georgia, Greece, and Moldova, mainly chest X-ray and white blood cell counting). Antibiotic prescribing was related to illness severity, comorbidity, age, fever, and country, but not to having performed a POC test. In nearly 90% of consultations, GPs were confident in their antibiotic prescribing decision. Conclusion: Despite high confidence in decisions about antibiotic prescribing, there is considerable variation in the primary care of RTI in European countries, with GPs prescribing antibiotics overall more often than is considered appropriate. POC testing may enhance the quality of antibiotic prescribing decisions if it can safely reverse decisions confidently made on clinical grounds alone to prescribe antibiotics. [ABSTRACT FROM AUTHOR]

Simple Summary: Nerve fibers in the microenvironment have shown notable prognostic potential in various malignancies; however, its role in hepatocellular carcinoma remains to be elucidated. Therefore, the impact of nerve fibers on oncological survival was investigated in a large European cohort of patients with hepatocellular carcinoma who underwent curative-intent liver resection. By means of univariate and multivariate statistics as well as group comparisons of patients with and without nerve fibers, the presence of nerve fibers itself, as well as the corresponding density, was not shown to be associated with survival or the risk of tumor recurrence. Despite being of major prognostic value in various cancer types, nerve fibers in the microenvironment of hepatocellular carcinoma could not be used as a prognostic biomarker in these patients. It has been shown that the presence and density of nerve fibers (NFs; NFD) in the tumor microenvironment (TME) may play an important prognostic role in predicting long-term oncological outcomes in various malignancies. However, the role of NFD in the prognosis of hepatocellular carcinoma (HCC) is yet to be explored. To this end, we aimed to investigate the impact of NFs on oncological outcomes in a large European single-center cohort of HCC patients. In total, 153 HCC patients who underwent partial hepatectomy in a curative-intent setting between 2010 and 2021 at our university hospital were included in this study. Group comparisons between patients with and without NFs were conducted and the association of recurrence-free survival (RFS) and overall survival (OS) with the presence of NFs and other clinico-pathological variables were determined by univariate and multivariable Cox regression models. Patients with NFs in the TME presented with a median OS of 66 months (95% CI: 30–102) compared to 42 months (95% CI: 20–63) for patients without NFs (p = 0.804 log-rank). Further, RFS was 26 months (95% CI: 12–40) for patients with NFs compared to 18 months (95% CI: 9–27) for patients without NFs (p = 0.666 log-rank). In a subgroup analysis, patients with NFD ≤ 5 showed a median OS of 54 months (95% CI: 11–97) compared to 48 months (95% CI: 0–106) for the group of patients with NFD > 5 (p = 0.787 log-rank). Correspondingly, the RFS was 26 months (95% CI: 10–42) in patients with NFD ≤ 5 and 29 months (95% CI: 14–44) for the subcohort with NFD > 5 (p = 0.421 log-rank). Further, group comparisons showed no clinico-pathological differences between patients with NFs (n = 76) and without NFs (n = 77) and NFs were not associated with OS (p = 0.806) and RFS (p = 0.322) in our Cox regression models. In contrast to observations in various malignancies, NFs in the TME and NFD are not associated with long-term oncological outcomes in HCC patients undergoing surgery. [ABSTRACT FROM AUTHOR]

Background: Predicting pathological complete response (pCR) in patients affected by locally advanced rectal cancer (LARC) who undergo neoadjuvant chemoradiotherapy (nCRT) is a challenging field of investigation, but many of the published models are burdened by a lack of reliable external validation. Aim of this study was to evaluate the applicability of a magnetic resonance imaging (MRI) radiomic-based pCR model developed and validated in Europe, to a different cohort of patients from an intercontinental cancer center.Methods: The original model was based on two clinical and two radiomics features extracted from T2-weighted 1.5 T MRI of 161 LARC patients acquired before nCRT, considered as training set. Such model is here validated using the T2-w 1.5 and 3 T staging MRI of 59 LARC patients with different clinical characteristics consecutively treated in mainland Chinese cancer center from March 2017 to January 2018. Model performance were evaluated in terms of area under the receiver operator characteristics curve (AUC) and relative parameters, such as accuracy, specificity, negative and positive predictive value (NPV and PPV).Results: An AUC of 0.83 (CI 95%, 0.71-0.96) was achieved for the intercontinental cohort versus a value of 0.75 (CI 95%, 0.61-0.88) at the external validation step reported in the original experience. Considering the best cut-off threshold identified in the first experience (0.26), the following predictive performance were obtained: 0.65 as accuracy, 0.64 as specificity, 0.70 as sensitivity, 0.91 as NPV and 0.28 as PPV.Conclusions: Despite the introduction of significant different factors, the proposed model appeared to be replicable on a real-world data extra-European patients' cohort, achieving a TRIPOD 4 level. [ABSTRACT FROM AUTHOR]

European flood frequency and intensity change on a multidecadal scale. Floods were more frequent in the 19th (central Europe) and early 20th century (western Europe) than during the mid-20th century and again more frequent since the 1970s. The causes of this variability are not well understood and the relation to climate change is unclear. Palaeoclimate studies from the northern Alps suggest that past flood-rich periods coincided with cold periods. In contrast, some studies suggest that more floods might occur in a future, warming world. Here we address the contribution of atmospheric circulation and of warming to multidecadal flood variability. For this, we use long series of annual peak streamflow, daily weather data, reanalyses, and reconstructions. We show that both changes in atmospheric circulation and moisture content affected multidecadal changes of annual peak streamflow in central and western Europe over the past two centuries. We find that during the 19th and early 20th century, atmospheric circulation changes led to high peak values of moisture flux convergence. The circulation was more conducive to strong and long-lasting precipitation events than in the mid-20th century. These changes are also partly reflected in the seasonal mean circulation and reproduced in atmospheric model simulations, pointing to a possible role of oceanic variability. For the period after 1980, increasing moisture content in a warming atmosphere led to extremely high moisture flux convergence. Thus, the main atmospheric driver of flood variability changed from atmospheric circulation variability to water vapour increase. [ABSTRACT FROM AUTHOR]

In the European Union, all bat species are strictly protected and member states must ensure their conservation. However, if populations are genetically structured, conservation units that correspond to whole countries may be too large, putting small populations with specific conservation requirements at risk. Geoffroy's bat (Myotis emarginatus) has undergone well-documented declines at its north-western European range edge between the 1960 and 1990s and is considered to be negatively affected by habitat fragmentation. Here we analysed the species' genetic population structure and diversity to identify subpopulations with reduced genetic diversity and to scientifically inform conservation management. We generated 811 microsatellite-based genetic profiles obtained from 42 European nursery colonies and analysed a total of 932 sequences of the hypervariable region II of the mitochondrial control region sampled from across Europe. While two geographically widespread genetic populations were inferred to be present in north-western Europe, both nuclear and mitochondrial genetic diversity were lowest in the areas that had experienced a decline during the last century. A microsatellite-based analysis of demographic history did not permit, however, to unequivocally link that reduced genetic diversity to the population contraction event. Given the large geographic extent of the genetic populations, preserving the connectivity of mating sites requires concerted conservation efforts across multiple political jurisdictions. Genetic monitoring ought to be done on a regular basis to ensure that large-scale connectivity is maintained and further loss of genetic diversity is prevented. [ABSTRACT FROM AUTHOR]

Satellite-based remote sensing might provide a potential way for monitoring the global flight activities and their environment impacts, while the remote sensing community pays less attention on it. In this study, we presented a flying aircraft detection algorithm which effectively handles the noise on Landsat 8 OLI cirrus band caused by energetic particles in the South Atlantic Anomaly region, and a new framework based on cloud infrastructure was proposed to map global flying aircraft activities from 2013 to 2020 using Landsat 8 Operational Land Imager (OLI) data. Validation was performed for 254 scenes recorded for various cloudy and surface conditions and vapor contents. The overall percentages of false alarms and omissions for these validation images were 5.37% and 7.80%, respectively. Limited to the resolution of Landsat data, cloud, the size and flight altitude of the aircraft, 42.99% flying aircraft were undetected compared with the FlightRadar24. Instead of using the Google Earth Engine, we employed more flexible cloud computing techniques, Google Cloud Storage and Google Calculation Engine, to construct our framework for the larger volume data. A total of 1.94 million Landsat images were analyzed to obtain the activities maps, and the results showed that globally flying aircraft increased by 25.85% from 2014 to 2019 (the year 2013 was excluded for the low coverage of Landsat scenes), with an annual rate of 4.31%. In 2020, flying aircraft were reduced by 40% compared with 2019 due to the influence of COVID-19 and traveling restrictions, and Europe was the most severely affected by COVID-19, with an 84.59% decline of flying aircraft in April 2020. This study provides a unique long-term supplement to monitor aviation activities and their climate impact. [ABSTRACT FROM AUTHOR]

Background: Tremendous progress in acute stroke therapy has improved short-term outcome but part of this achievement may be lost in the long run. Concepts for a better long-term management of stroke survivors are needed to address their unmet needs and to reduce the burden of post-stroke complications, residual deficits, and recurrent vascular events. Aims: This review summarizes current knowledge on post-hospital care and the scientific evidence supporting individual programs. Summary of review: A systematic search of electronic databases according to PRISMA guidelines identified 10,374 articles, 77 of which met the inclusion criteria. One large randomised controlled trial on a multifaceted care program delivered by the multidisciplinary stroke team reduced recurrent vascular events and improved quality of life and functional outcome one year after the event, while a number of studies offer solutions for individual components of post-hospital disease management like patient education, counselling, and self-management or the management of poststroke complications and residual deficits. A majority of studies, however, was small in size and limited by a short followup. Most initiatives with a narrow focus on risk factor control failed to lower the risk of recurrent events. The caregivers' central role in post-stroke patient management is broadly neglected in research. Conclusions: Over the past years, first knowledge on how to best organize post-hospital care of stroke patients has emerged. Comprehensive and pragmatic programs operated by the multidisciplinary stroke team hold promise to reduce the long-term health burden of stroke. There is a clear need for further high-quality studies with both clinical endpoints and patient-reported outcomes to establish sustainable solutions in different settings and regions to improve life after stroke, a key priority of the Stroke Action Plan for Europe 2018-2030. [ABSTRACT FROM AUTHOR]

We evaluated whether protected European butterflies can potentially be at risk if transgenic maize is extensively grown in Central Europe. We explored potential consequences of both insect resistant (IR) and herbicide resistant (HR) transgenic maize. IR maize can produce pollen that is toxic to lepidopteran larvae, and this puts butterfly species at possible risk if the presence of young larvae coincides with maize flowering, during which large quantities of maize pollen can be deposited on vegetation. By considering the timing of maize flowering in Europe and the phenology of the protected Lepidoptera species, we found that 31 species had at least one generation where 50% of the larval stage overlapped with maize flowering, and 69 species for which first instar larvae were present during maize pollen shedding. HR maize allows high concentration herbicide treatments on fields without seasonal limitation, which can drastically reduce weed densities. In cases where such weed species are host plants for protected butterflies, reduced host plant/food availability can result, causing population decreases. By using published information, we first identified the important weed species in major maize‐growing European countries. Subsequently, we checked whether the host plants of protected Lepidoptera included species that are common maize weeds. We identified 140 protected species having food plants that are common weeds in one or more of the major European maize‐growing countries. If HR maize is grown in Europe, there is a potential hazard that their food plants will seriously decline, causing a subsequent decline of these protected species. [ABSTRACT FROM AUTHOR]

Aims: Liquid chromatography‐mass spectrometry (LC‐MS/MS) is an objective new technique to assess non‐adherence to medications. We used this method to study the prevalence, predictors and outcomes of non‐adherence in patients with heart failure with reduced left ventricular ejection fraction (HFrEF). Methods and results: This study included 1296 patients with HFrEF from BIOSTAT‐CHF, a study that aimed to optimise guideline‐recommended therapies. Angiotensin‐converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists, β‐blockers and loop diuretics were measured in a single spot urine sample at 9 months using LC‐MS/MS. The relationship between medication non‐adherence and the composite endpoint of all‐cause death or heart failure hospitalisation, over a median follow‐up of 21 months, was evaluated. Non‐adherence to at least one prescribed medication was observed in 45.9% of patients. The strongest predictor of non‐adherence was non‐adherence to any of the other medication classes (P < 0.0005). Regional differences within Europe were observed. On multivariable analyses, non‐adherence to ACEi/ARBs and β‐blockers was associated with an increased risk of the composite endpoint [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.09–1.95, P = 0.008 and HR 1.48, 95% CI 1.12–1.96, P = 0.006, respectively). Non‐adherence to β‐blockers was also associated with an increased risk of death (HR 2.48, 95% CI 1.67–3.68, P < 0.0005). Patients who were non‐adherent to loop diuretics were healthier and had a decreased risk of the composite endpoint (HR 0.69, 95% CI 0.51–0.93, P = 0.014). Non‐adherence to mineralocorticoid receptor antagonists was not related to any clinical outcome. Conclusion: Non‐adherence to medications, assessed by a single urine test, is common and predicts clinical outcomes in patients with HFrEF. [ABSTRACT FROM AUTHOR]

Gastrointestinal fistulation has been widely reported as an adverse effect of nicorandil therapy in Europe. People who have underlying diverticular disease are most at risk of this side effect. In Western countries, diverticular disease is highly prevalent and can be clinically silent. This study aimed to identify diverticular disease genetic risk scores (GRSs) associated with early nicorandil stoppage, a surrogate marker for drug intolerance. A case‐control study was carried out on 1,077 patients from the Genetics of Diabetes Audit and Research Tayside Scotland (GoDARTS) database. Cases were defined as having < 9 nicorandil prescriptions with no identifiable reason for stopping (n = 230). Controls had either ≥ 9 prescriptions, treatment continuation to death/study end or stoppage post‐myocardial infarction. Two diverticular GRSs were created and used in logistic regression models. Isosorbide mononitrate was used as a control analysis. Patients with a raised diverticular GRS, based on 23 replicable loci, had increased risk of stopping nicorandil therapy early (univariate (odds ratio (OR) 2.26; P = 0.04], multivariate (OR 3.96; P = 0.01)). Similar trends were noted when using the full 42 variant diverticular score but statistical significance was not reached. The isosorbide control analysis did not reach statistical significance. Our analysis demonstrates a novel positive association between a raised diverticular GRS and early stoppage of nicorandil therapy. [ABSTRACT FROM AUTHOR]

The 2018 drought was one of the worst European droughts of the twenty-first century in terms of its severity, extent and duration. The effects of the drought could be seen in a reduction in harvest yields in parts of Europe, as well as an unprecedented browning of vegetation in summer. Here, we quantify the effect of the drought on net ecosystem exchange (NEE) using five independent regional atmospheric inversion frameworks. Using a network of atmospheric CO2 mole fraction observations, we estimate NEE with at least monthly and 0.5° × 0.5° resolution for 2009–2018. We find that the annual NEE in 2018 was likely more positive (less CO2 uptake) in the temperate region of Europe by 0.09 ± 0.06 Pg C yr−1 (mean ± s.d.) compared to the mean of the last 10 years of −0.08 ± 0.17 Pg C yr−1, making the region close to carbon neutral in 2018. Similarly, we find a positive annual NEE anomaly for the northern region of Europe of 0.02 ± 0.02 Pg C yr−1 compared the 10-year mean of −0.04 ± 0.05 Pg C yr−1. In both regions, this was largely owing to a reduction in the summer CO2 uptake. The positive NEE anomalies coincided spatially and temporally with negative anomalies in soil water. These anomalies were exceptional for the 10-year period of our study. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'. [ABSTRACT FROM AUTHOR]

Atmospheric inversions have been used for the past two decades to derive large-scale constraints on the sources and sinks of CO2 into the atmosphere. The development of dense in situ surface observation networks, such as ICOS in Europe, enables in theory inversions at a resolution close to the country scale in Europe. This has led to the development of many regional inversion systems capable of assimilating these high-resolution data, in Europe and elsewhere. The EUROCOM (European atmospheric transport inversion comparison) project is a collaboration between seven European research institutes, which aims at producing a collective assessment of the net carbon flux between the terrestrial ecosystems and the atmosphere in Europe for the period 2006–2015. It aims in particular at investigating the capacity of the inversions to deliver consistent flux estimates from the country scale up to the continental scale. The project participants were provided with a common database of in situ-observed CO2 concentrations (including the observation sites that are now part of the ICOS network) and were tasked with providing their best estimate of the net terrestrial carbon flux for that period, and for a large domain covering the entire European Union. The inversion systems differ by the transport model, the inversion approach, and the choice of observation and prior constraints, enabling us to widely explore the space of uncertainties. This paper describes the intercomparison protocol and the participating systems, and it presents the first results from a reference set of inversions, at the continental scale and in four large regions. At the continental scale, the regional inversions support the assumption that European ecosystems are a relatively small sink (-0.21±0.2 Pg C yr -1). We find that the convergence of the regional inversions at this scale is not better than that obtained in state-of-the-art global inversions. However, more robust results are obtained for sub-regions within Europe, and in these areas with dense observational coverage, the objective of delivering robust country-scale flux estimates appears achievable in the near future. [ABSTRACT FROM AUTHOR]

Employment in the municipal workforce is a key area in which cities shape the inclusion of their population of immigrant origin. While many European cities have developed policies aiming to foster the employment of staff of immigrant origin, little is known about the drivers and barriers of their implementation. Based on a comparative case study of local administrations in one German regional state and drawing on organizational theory, this article explores the role of organizational factors. It shows how the interplay of mainly two factors matters: support from the administrative leadership and the pragmatic recruitment rationalities of the human resources practitioners. Additionally, the findings suggest that the local identity as municipality more or less shaped by immigration also informs practices. The article argues that to understand the implementation of policies promoting workforce diversity organizational structures and rationalities must be considered. [ABSTRACT FROM AUTHOR]

Objectives Research suggests that cognitive functioning is associated with technology use in late life, but longitudinal research in this domain is still sparse. This study explored the reciprocal association between Internet use and cognitive functioning over a 2-year period. Method We analyzed representative data across 14 countries from the Survey of Health, Ageing and Retirement in Europe (SHARE). The sample included 29,576 participants between 50 and 100 years of age. We used data from 2013 (Wave 5) and a 2-year follow-up in 2015 (Wave 6). Participants provided information on cognitive functioning measures and Internet use at both time points. Results Cross-lagged panel analysis indicated reciprocal effects between cognitive functioning and Internet use. Internet use had a greater impact on cognitive functioning than vice versa. Discussion This study sheds light on the direction of the association between cognitive functioning and Internet use. Findings indicate that using the Internet positively affects cognitive functioning in late life. [ABSTRACT FROM AUTHOR]

Europe is witnessing a new wave of collective self-organized forms of housing provision. We refer to the wide variety of these forms under the umbrella term "Collaborative Housing". Alongside growing grassroots activity, the number and breadth of academic publications is rapidly growing. Nevertheless, the field remains thematically fragmented, with literature spread across disciplines. This article aims to establish a basis for greater conceptual clarity by exploring the domain of collaborative housing research over the period of 1990–2017. We carry out a thematic mapping and assessment covering 195 relevant peer-reviewed journal articles in English, German and French. These are inductively synthesized and categorized into five main thematic areas: socio-demographic, collaboration, motivation, effects and context. We conclude that the systematic and inductive approach of our review unravels new perspectives and makes the case for the conceptualization of collaborative housing as an independent research field, providing a basis for further theory development. [ABSTRACT FROM AUTHOR]

The vast majority of firms in Europe are micro firms. Still, we know little about their financing patterns. Our paper aims to close this gap. Based on a large European firm-level data set, we find that micro firms differ in their financing patterns from larger SMEs. Our empirical results show that micro firms are more likely to use internal financing instruments, whereas they are less likely to use state subsidies, trade credit or asset-based financing instruments. Furthermore, micro firms differ from larger SMEs by using more short-term debt financing instruments such as credit card overdrafts, credit lines and bank overdrafts. The implications of these findings for micro firms and policy makers are discussed. [ABSTRACT FROM AUTHOR]

Highlights • The butterfly diversity is high in farmland of Romania and Spain, and less in Sweden. • The coefficient of variance of transect-specific species richness declined beyond 800 m transect length. • The required sample size to record a 10% loss of species was less than 30 transects per region. • The time to be invested in field work differed between countries. • The final effort to document a change of a certain magnitude was similar between countries. Abstract In agro-ecosystems, environmental monitoring is fundamental to detect and survey changes related to land use change and management practices. Butterflies and moths have often been suggested as suitable indicators for monitoring environmental effects on biodiversity in farmlands. Here, we estimated the required sample size and monitoring effort necessary to run a Lepidoptera survey in European farmland, assessing in particular if monitoring investment would differ between representative bio-geographical regions. We operated linear 1-km long transect routes in farmland of Romania, Spain and Sweden from 2013 to 2015, and recorded butterflies and burnet moths (Papilionoidea, Zygaenidae). The transects were walked back and forth four times a season, and replicated yearly. The lepidopteran diversity was high in farmlands of Romania and Spain, but comparatively low in Sweden. The coefficient of variation (CV) of recorded species number differed between countries being lowest in Sweden and highest in Spain. In general, the CV dropped above a transect length of 400–800 m, thus indicating an increase in statistical power. Assuming a non-parametric test for matched samples, power calculations were conducted with the raw count data and with log-transformed count data for comparison. When using log-transformed data, the required sample size to detect an effect was less than 10 transects per country or region (in order to detect a 10% loss of species or a decrease of 30% in total abundance). Specific subgroups of species, e.g. protected species or specific indicator groups, showed a higher variance, thus requiring a higher sample size to detect effects ranging from 12 to 16 transects (equivalent to 21–29 working days per country and year). When using original, untransformed count data a considerably larger sample size would be needed. Actual time to be invested in field work differed between countries due to contrasting regional constraints and conditions. Nevertheless, the final monitoring effort in working days was similar between countries as the factors involved balanced out each other, in particular due to the differing year-to-year variations. Our study demonstrated the feasibility of an environmental monitoring programme in arable land using farmland butterflies across Europe. We present a suitable approach and guidelines as well as the necessary effort to be invested in future Europe-wide monitoring programmes of butterflies in agro-ecosystems, based on predictions of statistical power. [ABSTRACT FROM AUTHOR]

Purpose: Recombinant granulocyte colony-stimulating factors (rG-CSFs), such as filgrastim, are administered to prevent complications in patients receiving chemotherapy. In Europe, a biosimilar to filgrastim, tevagrastim/ratiograstim/biograstim, was approved in 2008. In the USA, the same product was approved as tbo-filgrastim under a 351(a) biologic license application in 2012 with the brand name Granix®. Postmarket surveillance remains a priority for monitoring the safety of biologics and biosimilars to identify rare and immunogenicity-related events. We report the global and US pharmacovigilance data for tevagrastim/ratiograstim/biograstim and tbo-filgrastim, respectively.Methods: Cumulative exposure and adverse event data from initial approval in Europe to December 31, 2016, were collected globally from spontaneous reports submitted by healthcare professionals and consumers, scientific literature, competent authorities, and solicited case reports from non-interventional studies. A separate search was conducted on the global data set to identify reports originating from the USA and Puerto Rico to describe the US experience.Results: Overall, the global safety profile of tevagrastim/ratiograstim/biograstim in the postmarket, real-world setting was comparable to clinical trial experience. Postmarket safety experience of tbo-filgrastim in the USA was consistent with global data. The most common SAEs were febrile neutropenia and decreased white blood cell count. The most common non-serious event was bone pain. There was no evidence of immunogenicity.Conclusions: This pharmacovigilance analysis indicates that postmarket experience of tevagrastim/ratiograstim/biograstim and tbo-filgrastim is consistent with clinical trials. Adverse reactions associated with the originator rG-CSF (capillary leak syndrome and glomerulonephritis) have not been observed with tevagrastim/ratiograstim/biograstim or tbo-filgrastim during the postmarket period. [ABSTRACT FROM AUTHOR]

Background and Aims: To describe the biology of alveolar bone regeneration. Material and Methods: Four comprehensive reviews were performed on (a) mesenchymal cells and differentiation factors leading to bone formation; (b) the critical interplay between bone resorbing and formative cells; (c) the role of osteoimmunology in the formation and maintenance of alveolar bone; and (d) the self‐regenerative capacity following bone injury or tooth extraction were prepared prior to the workshop. Results and Conclusions: This summary information adds to the fuller understanding of the alveolar bone regenerative response with implications to reconstructive procedures for patient oral rehabilitation. The group collectively formulated and addressed critical questions based on each of the reviews in this consensus report to advance the field. The report concludes with identified areas of future research. [ABSTRACT FROM AUTHOR]

Abstract The terrestrial margins of the Middle Pleistocene ice sheets in northern central Europe were characterised by the formation of extensive ice-dammed lakes, which were controlled by the blockage of spillways by the ice margin. The largest ice-dammed lake had a volume of ∼224 km³ and formed in a late stage of the first Saalian ice advance (MIS 6) in central Germany. The failure of the ice dam in the bedrock-outlet channel triggered a major glacial lake-outburst flood. Flood-related erosional and depositional features include large-scale scours, trench-like channels, streamlined hills, giant bars and run-up deposits, indicating a wide spreading of the outburst flood in an early stage and the incision of trench-like valleys in a later stage. The incision of large valleys in the proximal flood pathway strongly impacted the regional drainage system by providing an efficient drainage network. The trench-like channels initiated by the lake-outburst flood became a crucial part of the ice-marginal drainage and subsequent fluvial system. The reconstructed outlet hydrographs imply peak discharges of 465,000–673,000 m³s−1. The numerical simulation indicates flow depths of up to 87 m, flow velocities of up to 7 ms−1, peaks of the bed-shear stress of 2500 Nm−2 and the inundation of large parts of northwestern Germany and the northern Netherlands. The numerical simulation of the outburst flood was conducted on both the modern digital elevation model and on palaeotopographic models, representing the palaeotopography prior to the outburst flood and during maximum flood-related incision, respectively. Distally, the outburst flood probably followed an east-west trending route through northwestern Germany and the central Netherlands into the ice-dammed lake in the southern North Sea Basin. The added water volume might have led to the overspill and drainage of the proglacial lakes in the central Netherlands and the North Sea Lake in a chain reaction, eventually opening an east-west trending meltwater-drainage pathway along the southwestern margin of the decaying ice sheet. Highlights • Reconstruction of Middle Pleistocene (Saalian) lake-drainage events. • Integration of geomorphologic and sedimentologic evidence with numerical simulation. • Reconstruction of pre-flood and syn-flood palaeotopography. • Flood-related features became a crucial part of the meltwater-drainage system. [ABSTRACT FROM AUTHOR]

Background: The 6-minute walk test (6MWT) is a simple and inexpensive way of measuring exercise capacity in patients with heart failure (HF) that predicts morbidity and mortality. However, there are few reports from large multicentre cohorts assessing the predictive value of baseline and changing walk distance.Methods and Results: In BIOSTAT-CHF, a 6MWT was performed at baseline (n = 1714) and 9 months (n = 1520). Cox proportional hazards models were used to assess the associations between 6MWT distance and the composite of HF hospitalization and/or death. Median follow-up was 21 months. The median (pct25-75 ) of the 6MWT distance at baseline was 300 m (200-388 m). Independent predictors of a shorter 6MWT distance included older age, female sex, higher heart rate, New York Heart Association class III/IV, orthopnoea, ischaemic heart disease, a previous stroke, current malignancy, and higher N-terminal pro-B-type natriuretic peptide (all P < 0.05). Patients in the lowest baseline 6MWT tertile (≤ 240 m) were less likely to receive guideline-recommended doses of disease-modifying therapies (P < 0.05). Compared to patients in the highest baseline 6MWT tertile (> 360 m), those in the lowest and middle tertiles had a worse prognosis [adjusted hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.38-2.18]. Patients with a decrease in the distance walked had a worse prognosis (adjusted HR for each 50 m decrease 1.09, 95% CI 1.06-1.12). 6MWT distance was not modified by treatment up-titration nor the 6MWT improved the BIOSTAT-CHF prognostic models.Conclusions: The 6-minute walk test distance at baseline and a decline in walking distance were both associated with worse prognosis but did not improve the prognostic models. 6MWT distance was not modified by treatment up-titration and its use for assessing the benefits of pharmacologic treatment up-titration may be limited. [ABSTRACT FROM AUTHOR]

Introduction: Patients with symptomatic heart failure (HF) require additive therapies and have a poor prognosis. However, patient characteristics and clinical outcome between HF patients treated in the outpatient setting vs. those who are hospitalized remain scarce.Methods and Results: The BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) included 2516 patients with symptoms and/or signs of HF: 1694 as inpatients and 822 as outpatients. Compared to ambulatory HF patients, inpatients had higher heart rate, urea, N-terminal pro-brain natriuretic peptide, lower blood pressure, lower estimated glomerular filtration rate, sodium, potassium, high-density lipoprotein cholesterol, had more often peripheral oedema, diabetes, anaemia, and were less often treated with beta-blockers and angiotensin-converting enzyme inhibitors (ACEi). Outpatients had a more frequent history of HF hospitalization and received more frequently beta-blockers and/or ACEi/angiotensin receptor blockers up-titrated to target doses (P < 0.001). Inpatients had higher rates of the primary outcome of death or HF hospitalization: incidence rate per 100 person-years of 33.4 [95% confidence interval (CI) 31.1-35.9] for inpatients vs. 18.5 (95% CI 16.4-21.0) for outpatients; adjusted hazard ratio 1.24 (95% CI 1.07-1.43). Subdividing patients into low, intermediate and high-risk categories, the primary outcome event rates were 14.3 (95% CI 12.3-16.7), 36.6 (95% CI 32.2-41.5), and 71.3 (95% CI 64.4-79.0) for inpatients vs. 8.4 (95% CI 6.6-10.6), 29.8 (95% CI 24.5-36.2), and 43.3 (95% CI 34.7-54.0) for outpatients, respectively. These findings were externally replicated.Conclusions: Marked differences were observed between inpatients and outpatients with HF. Overall, inpatients were sicker and had higher event rates. However, a substantial proportion of outpatients had similar or higher event rates compared to inpatients. These findings suggest that HF outpatients also have poor prognosis and may be the focus of future trials. [ABSTRACT FROM AUTHOR]

Background: In hepatocellular carcinoma (HCC), the third leading cause of cancer-related mortality worldwide, the Child-Turcotte-Pugh score (CTP) is one of the most established tools to assess hepatic reserve and determine survival. Serum levels of insulin-like growth factor-1 (IGF-1) are decreased in patients with chronic liver disease or HCC. A modified score combining circulating IGF-1 with the CTP score (IGF-CTP) was recently proposed.Methods: IGF-CTP scoring was evaluated in 216 patients diagnosed with HCC between 2007 and 2017 to assess the predictive value of serum IGF-1 levels for patient risk stratification and overall survival (OS).Results: Liver cirrhosis was identified in 80.1% of the study cohort, and alcohol-induced liver disease was the most frequent underlying cause of HCC (44.4%). Serum IGF-1 levels were significantly lower in patients with HCC in cirrhosis compared with non-cirrhotic HCC (p < 0.01). A lower serum level of IGF-1 was associated with more advanced stages of liver cirrhosis (p < 0.05) and cancer stages (p < 0.001). Median OS in the cohort was 11.4 months (range 0.5-118.2 months). OS was significantly higher (10.9 vs. 7.9 months; p < 0.05) in patients with a serum IGF-1 level above the median of 43.4 ng/mL. Patient reassignment using IGF-CTP scoring reclassified 35.6% of patients. Through reassignment, stratification regarding OS was comparable to CTP.Conclusions: This study is the first to investigate IGF-1 and the IGF-CTP classification in a European cohort of HCC patients. Serum IGF-1 correlates with OS in patients with HCC. However, the IGF-CTP classification was not superior compared to CTP score regarding OS. [ABSTRACT FROM AUTHOR]

Objectives: Coronary angiography is regularly performed in patients with worsening signs and/or symptoms of heart failure (HF). However, little is known on the determinants, findings and associated clinical outcomes of coronary angiography performed in patients with worsening HF.Methods: The BIOSTAT-CHF (a systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure) programme enrolled 2516 patients with worsening symptoms and/or signs of HF, either hospitalised or in the outpatient setting. All patients were included in the present analysis.Results: Of the 2516 patients included, 315 (12.5%) underwent coronary angiography within the 30 days after the onset of worsening symptoms and/or signs of HF. Subjects who underwent angiography were more often observed as inpatients, had more often an overt acute coronary syndrome, had higher troponin I levels, were younger and had better renal function (all p≤0.01). Patients who underwent coronary angiography had a lower risk of the primary outcome of death and/or HF hospitalisation (adjusted HR=0.71, 95% CI 0.57 to 0.89, p=0.003) and death (adjusted HR=0.59, 95% CI 0.43 to 0.80, p=0.001). Among the patients who underwent coronary angiography, those with a coronary stenosis (39%) had a worse prognosis than those without stenosis (adjusted HR for the primary outcome=1.71, 95% CI 1.10 to 2.64, p=0.016).Conclusions: Coronary angiography was performed in <13% of patients with symptoms and/or signs of worsening HF. These patients were remarkably different from those who did not undergo coronary angiography and had a lower risk of subsequent events. The presence of coronary stenosis on coronary angiography was associated with a worse prognosis. [ABSTRACT FROM AUTHOR]

Periods of ongoing growth in the economy and demographics have come to a halt for many European regions for various reasons, challenging their economic development prospects. Despite the heterogeneous nature of stagnation, decline, peripheralization or even stigmatization to be found there, these configurations ‘beyond growth’ have in common that short-term ‘fire-fighting’ policy approaches aiming to foster regional economic growth face some important limitations. We argue that this has to do, among other things, with the overall direction of established and orthodox planning approaches that are predominantly based on growth-oriented paradigms and implicitly or explicitly work with dichotomous categories such as core–periphery and metropolitan versus non-metropolitan spaces; these do, however, not capture local realities in these cases. Using the notion of non-core regions, we plead for conceptualizing non-core regions and their regional economic development trajectories in different ways: thinking ‘beyond growth’. Such alternative ideas should be informed by alternative understandings of growth, development and sustainability in order to influence theories and concepts, but also to support new approaches to planning practice. To this aim, we discuss non-core regions from a social constructivist perspective, elaborating some points of departure for conceptualizing and practising regional planning ‘beyond growth’. [ABSTRACT FROM PUBLISHER]

Objective:The aim of this study was to analyze long-term trends in prostate cancer (PCa) incidence, mortality and survival in Estonia, with specific focus on age and stage. Materials and methods:Data on PCa incident cases and deaths in 1995–2014 were obtained from the Estonian Cancer Registry and the Causes of Death Registry, respectively. Joinpoint regression was used to estimate the annual percentage change for incidence and mortality trends. Relative survival ratios (RSRs) were calculated for four 5 year periods. Incidence and survival were analyzed by age and stage. Results: The average annual number of new PCa cases in Estonia increased more than three-fold from 1995–1999 to 2010–2014. The age-standardized overall incidence and the incidence of localized cancer increased steeply until 2011, then leveled off. The incidence of locally/regionally spread or distant PCa remained stable. A significant increase in PCa mortality was seen only in men aged 65 years and older. The overall 5 year RSR increased from 58% to 90% over the study period. Survival increased considerably for all stages. Conclusions:The dramatic rise in the incidence of PCa in Estonia since the late 1990s was limited to localized cancers. This, together with rapid increases in survival, is probably due predominantly to extensive opportunistic prostate-specific antigen testing of middle-aged and elderly men. The ongoing increase in PCa mortality among older men warrants validation of causes of death to avoid possible overestimation. Evaluation of diagnostic and treatment strategies could identify possibilities for improving outcomes of non-localized PCa. [ABSTRACT FROM AUTHOR]

Aims: Mineralocorticoid receptor antagonists (MRAs) are recommended (unless contraindicated) to all patients with heart failure with reduced ejection fraction (HFrEF). However, MRAs are still largely underused in routine clinical practice. This study aims to describe the determinants and pattern of use of MRAs in HFrEF.Methods and Results: BIOSTAT-CHF is a European multicentre, prospective study which enrolled patients suboptimally treated with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) and/or beta-blockers, with the aim of optimizing guideline-based use of these agents. From the original 2516 subjects, this retrospective post hoc analysis included the 1325 patients with an indication for MRA therapy (i.e. left ventricular ejection fraction ≤35%, estimated glomerular filtration rate ≥30 mL/min/1.73 m2 , K+ ≤5.0 mmol/L). The mean age was 66.1 ± 12.2 years. At baseline an MRA was prescribed to 741 (56%) patients. Patients who were prescribed MRAs at baseline were younger, more often male, had higher body mass index, lower sodium, higher proportion of hypertension history and ACEi/ARB prescription (all P < 0.05). Of the 1049 patients who completed the baseline plus the 9 month visit, 585 (56%) had an MRA prescribed at baseline and 662 (63%) had an MRA prescribed at 9 months. Among the 585 patients with MRA at baseline, 91 (16%) had discontinued therapy and among the 461 (44%) patients without MRA at baseline 168 (36%) had initiated therapy subsequently. MRA discontinuation was more likely in subjects with higher left ventricular ejection fraction and NYHA class III/IV (P < 0.05 for both). MRA prescription both at baseline and 9 months was not associated with the outcome of death or heart failure hospitalization (adjusted hazard ratio 1.02, 95% confidence interval 0.66-1.58; P = 0.93).Conclusions: In this prospective observational study across Europe, MRAs were largely under-prescribed and frequently discontinued. Owing to these dynamic changes, outcome inferences are inconclusive. [ABSTRACT FROM AUTHOR]

The article discusses the proposed directive that was adopted by European Commission that strengthen the powers of European Union Member States national competition authorities and the effect to fundamental rights of the companies. Topics mentioned include the Article three of the directive entitled "Safeguards," the Recital 12 of the directive that mentions the rights of defence and good administration, and the relationship between judicial review and administrative stage.

The paper depicts the emergence of metropolitan region policies in Europe as being linked to the globalization debate and demonstrates how the idea of supporting metropolitan regions as national growth engines appeared to become not only an element of European regional policy but has appeared more and more in national urban policies as well. We propose to regard the diffusion of the underlying spatial development ideas as being linked to Europeanization processes as a form of transnational socialization and learning. We demonstrate how the urban dimension has been more and more strengthened in EU regional policies since the early 1990s and how influential some national level policies might have been for the European level. Some new member states show recent shifts towards more neoliberal development models arguing for more competitiveness through metropolization. We propose that this interrelates to a general shift towards the paradigm of a regional policy based on growth potentials and competitiveness across the EU. While the cohesion objective is nevertheless maintained, there seems to be a widespread consensus among policy-makers in Europe that to a certain extent the metropolitan paradigm is a logical and unavoidable result of economic transformation and globalization and is needed to achieve overall competitiveness. [ABSTRACT FROM PUBLISHER]

Objective: To investigate whether knowledge of fetal outcome influences retrospective interpretation of cardiotocographic tracings and subsequent management recommendations.Design: Prospective online study.Setting: Seven university hospitals in five European countries.Population: Forty-two intrapartum tracings from women with singleton pregnancies and uneventful antepartum courses.Methods: Using an online questionnaire, 123 healthcare professionals interpreted 42 tracings without any knowledge of fetal outcome and provided management recommendations according to the National Institute of Clinical Excellence guidelines (intrapartum care). Two months later, 93 of the 123 participants re-interpreted the same re-ordered tracings, this time with information on the newborn's umbilical artery pH.Outcome Measures: Comparison of the evaluation of tracing features, overall tracing classification, and management recommendations between the initial analysis and re-interpretation.Results: In newborns with umbilical artery pH ≤ 7.05, knowledge of the pH value led to significant changes in the evaluation of all basic tracing features. In this group, classification of tracings as 'normal' decreased 76% (8.8-2.1%, P < 0.001), whereas classification as 'pathologic' increased 51% (44.7-67.5%, P < 0.001). In newborns with pH 7.06-7.19, classification of tracings as 'normal' decreased 36% (22.4-14.4%, P < 0.001), and in those with pH ≥ 7.20, classification of tracings as 'pathologic' decreased 40% (23.4-14.1%, P < 0.001). In the group of newborns with umbilical artery pH ≤ 7.05, the recommendations 'no attention needed' decreased 75% (10.2-2.6%, P < 0.001), and the number of recommendations 'rapid reversal of hypoxic cause or immediate delivery' increased 70.3% (42.1-71.7%, P < 0.001).Conclusions: When provided with information on adverse fetal outcome, healthcare professionals provide a more pessimistic evaluation of basic tracing features, overall classification, and clinical management recommendations.Tweetable Abstract: Knowledge of adverse fetal outcome leads to more pessimistic CTG evaluation and management recommendations. [ABSTRACT FROM AUTHOR]

Aims: Despite major improvements in pharmacological and device treatments, heart failure remains a syndrome with high morbidity and mortality, poor quality of life, and high health-care costs. Given the extensive heterogeneity among patients with heart failure, substantial differences in the response to therapy can be expected. We hypothesize that individualized therapy is an essential next step to improve outcomes in patients with heart failure.Methods: The BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) included 2516 patients with worsening signs and/or symptoms of heart failure from 11 European countries, who were considered to be on suboptimal medical treatment. Another 1738 patients from Scotland were included in a validation cohort. Overall, both patient cohorts were well matched. The majority of patients were hospitalized for acute heart failure, and the remainder presented with worsening signs and/or symptoms of heart failure at outpatient clinics. Approximately half of the patients were in New York Heart Association class III, and 7% vs 34% of patients of the index vs validation cohort had heart failure with preserved ejection fraction. According to study design, all patients used diuretics, but owing to the inclusion criteria of both cohorts, patients were not on optimal, evidence-based medical therapy. In the follow-up phase, uptitration to guideline-recommended doses was encouraged.Conclusion: By using a novel systems biology approach, incorporating demographics, biomarkers, genome-wide analysis, and proteomics, a model that predicts response to therapy will be developed, which should be instrumental in developing alternative therapies for patients with suboptimal response to currently recommended therapies and thus further improve care for patients with heart failure. [ABSTRACT FROM AUTHOR]

This is the first paper to test the ability of conventional asset pricing models to explain the excess returns of European infrastructure stocks. Specifically, we firstly run the well-known Fama and French three-factor model, including three common stock market factors (market risk, size risk and value risk), and subsequently augment the model with two common bond risk factors (term and default risk), as infrastructure firms should be closely related to bond markets. The times-series regressions span the period from July 1992 to June 2014 and are conducted using an individually created infrastructure equity data-set. With the help of an intensive screening process, we only include those infrastructure stocks that in fact own and/or operate physical infrastructure. The results reveal that the three-factor model is unable to capture most of the variation in infrastructure returns. Therefore, bond risk factors should be included in asset pricing models in order increase the goodness of fit, as infrastructure stocks prove to be sensitive to interest rate changes. Nevertheless, even the augmented asset pricing model leaves a substantial part of the variance unexplained, thus indicating that infrastructure firms exhibit a high level of idiosyncratic risk. In addition, the results suggest that there may be further risk factors which should be investigated in future studies. [ABSTRACT FROM AUTHOR]

National and international carbon reporting systems require information on carbon stocks of forests. For this purpose, terrestrial assessment systems such as forest inventory data in combination with carbon estimation methods are often used. In this study we analyze and compare terrestrial carbon estimation methods from 12 European countries. The country-specific methods are applied to five European tree species ( Fagus sylvatica L. , Quercus robur L. , Betula pendula Roth, Picea abies (L.) Karst. and Pinus sylvestris L.), using a standardized theoretically-generated tree dataset. We avoid any bias due to data collection and/or sample design by using this approach. We are then able to demonstrate the conceptual differences in the resulting carbon estimates with regard to the applied country-specific method. In our study we analyze (i) allometric biomass functions, (ii) biomass expansion factors in combination with volume functions and (iii) a combination of both. The results of the analysis show discrepancies in the resulting estimates for total tree carbon and for single tree compartments across the countries analyzed of up to 140 t carbon/ha. After grouping the country-specific approaches by European Forest regions, the deviation within the results in each region is smaller but still remains. This indicates that part of the observed differences can be attributed to varying growing conditions and tree properties throughout Europe. However, the large remaining error is caused by differences in the conceptual approach, different tree allometry, the sample material used for developing the biomass estimation models and the definition of the tree compartments. These issues are currently not addressed and require consideration for reliable and consistent carbon estimates throughout Europe. [ABSTRACT FROM AUTHOR]

Graduate students' mobility has increased within Europe. Yet, empirical evidence on the validity of standardized admission tests in Europe is still scarce. The aim of the present study was therefore to investigate the incremental validity of the GRE® revised general test above undergraduate grade point average ( U- GPA) by focusing on a multinational sample of master students ( N = 282) enrolled at a Dutch university. Results indicated that the Analytical Writing part of the GRE predicts graduate grade point average above and beyond U- GPA. Furthermore, the results suggest that the relationship is independent of students' socioeconomic status as indexed by parental education. Implications for graduate student selection in a European context are discussed. [ABSTRACT FROM AUTHOR]

In most European countries, the proportion of adult students among both full-time and part-time workers has increased significantly over recent decades. Undertaking paid work is also increasingly common among traditional students. The opportunities to work while studying depend largely on the role of employers in promoting learning. However, both theoretical frameworks and empirical studies typically focus on the behaviour of firms in providing training. The support of employers for formal adult education has remained a marginal topic. The aim of this article is to analyse the contributions of employers to the acquisition of higher education from the perspective of the adult learners; we investigated how employers support their staff in higher education studies. We also tried to identify which kinds of learners have a better chance of receiving various benefits. We used two different data-sets: quantitative data from a study of adult students in higher education and qualitative data from interviews with managers of small- and medium-sized enterprises and at least one employed participant in formal adult education, collected in the framework of the international research project Towards a Lifelong Learning Society in Europe: The Contribution of the Education System supported by the EU Sixth Framework Programme. [ABSTRACT FROM PUBLISHER]

Rationale, aims and objectives Differences in the performance of medical care may be due to variation in the introduction and diffusion of medical innovations. The objective of this paper is to compare seven European countries ( United Kingdom, the Netherlands, West Germany, France, Spain, Estonia and Sweden) with regard to the year of introduction of six specific pharmaceutical innovations (antiretroviral drugs, cimetidine, tamoxifen, cisplatin, oxalaplatin and cyclosporin) that may have had important population health impacts. Methods We collected information on introduction and further diffusion of drugs using searches in the national and international literature, and questionnaires to national informants. We combined various sources of information, both official years of registration and other indicators of introduction (clinical trials, guidelines, evaluation reports, sales statistics). Results and conclusions The total length of the period between first and last introduction varied between 8 years for antiretroviral drugs and 22 years for cisplatin. Introduction in Estonia was generally delayed until the 1990s. The average time lags were smallest in France (2.2 years), United Kingdom (2.8 years) and the Netherlands (3.5 years). Similar rank orders were seen for year of registration suggesting that introduction lags are not only explained by differences in the process of registration. We discuss possible reasons for these between-country differences and implications for the evaluation of medical care. [ABSTRACT FROM AUTHOR]

Aim To provide a narrative review of the current literature elaborating on fundamental principles of periodontal plastic surgical procedures. Methods Based on a presumptive outline of the narrative review, MESH terms have been used to search the relevant literature electronically in the PubMed and Cochrane Collaboration databases. If possible, systematic reviews were included. The review is divided into three phases associated with periodontal plastic surgery: a) pre-operative phase, b) surgical procedures and c) post-surgical care. The surgical procedures were discussed in the light of a) flap design and preparation, b) flap mobilization and c) flap adaptation and stabilization. Results Pre-operative paradigms include the optimal plaque control and smoking counselling. Fundamental principles in surgical procedures address basic knowledge in anatomy and vascularity, leading to novel appropriate flap designs with papilla preservation. Flap mobilization based on releasing incisions can be performed up to 5 mm. Flap adaptation and stabilization depend on appropriate wound bed characteristics, undisturbed blood clot formation, revascularization and wound stability through adequate suturing. Conclusion Delicate tissue handling and tension free wound closure represent prerequisites for optimal healing outcomes. [ABSTRACT FROM AUTHOR]

Background The scope was to review the three main clinical indications in periodontal plastic surgical procedures. Aims To review the fundamental principles in periodontal plastic surgery, the main surgical designs in flap surgery applied to the treatment of recessions, peri-implant soft tissue deficiencies and soft tissue ridge augmentation, as well as the surgical principles of using autologous connective tissue grafts and soft tissue substitutes. Fundamental Principles in Plastic Surgery In the pre-operative phase, the key elements are the control of prognostic factors affecting the patient, namely oral hygiene, tobacco smoking cessation and systemic disease control. In the operative phase, the principles of flap design, mobilization, advancement, adaptation and stabilization. In the post-operative phase infection control, including effective oral hygiene measures, antiseptic treatment and other medications. Critical Elements in Flap Design and Surgical Execution In single recession defects, the most widely used flap technique is the coronally advanced flap and in specific clinical situations the laterally positioned flap. In multiple recession defects, the number of defects and their location and depth guide the surgical design, being one design with and the other without vertical releasing incisions. When flaps are used in combination with grafts the tunnel flap is also used extensively. Critical Elements in the Use of Soft Tissue Replacement Grafts The key elements are the donor site selection and harvesting technique, its tissue integration and volume stability. Clinical Recommendations Given the current evidence, various clinical recommendations on the use of flaps and grafts are provided. [ABSTRACT FROM AUTHOR]

Introduction Implant dentistry is a treatment modality which has mainstream clinical practice of comprehensive care, which however is not adequately represented in the undergraduate dental curricula. A consensus workshop organised by ADEE in 2008, set the benchmarks for the knowledge and competences a modern dental practitioner must possess with regard to implant dentistry, as well as defined undergraduate and postgraduate pathways for the acquisition of these competences. Today, 5 years later, there exist several challenges for the implementation of these benchmarks in both undergraduate curricula but also post-graduation educational pathways. Methods A consensus workshop was organised by ADEE, bringing together 48 opinion leaders, including academic teachers of all disciplines related to implant dentistry, specialists, representatives of relevant scientific and professional associations, as well as industry delegates. The objectives of the workshop were to evaluate the existing scientific literature, reported experience and best practices in order to identify potential and limitations for the implementation of implant dentistry in the undergraduate curriculum, as well produce recommendations for the optimal educational structures for postgraduate programmes and continuing professional development. Results The scientific committee conducted two European-wide questionnaire surveys to better document the current state of education in implant dentistry. Upon completion of the surveys, reviewers were appointed to produce three scientific review papers, identifying current achievements and future challenges. Finally, during the 3 days of the workshop, all the evidence was reviewed and the main conclusions and recommendations that were adopted by all participants are reported in the present Consensus Paper. Conclusions Implementation of implant dentistry in the undergraduate curriculum has improved significantly, but still lags behind the benchmarks set in 2008 and the diversity between institutions remains big. At the post-graduation level, there is currently a wide diversity of courses and pathways towards competences related to implant dentistry and there is at present a great need for quality assurance, as well as standardisation and transparency of the learning outcomes. [ABSTRACT FROM AUTHOR]