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As part of an International Agency for Research on Cancer (IARC) international epidemiological study of workers in the pulp and paper industry, previously unpublished exposure measurements were assembled in a database. This article summarizes the results of 3,873 measurements carried out in the production departments of paper and paperboard mills and recycling plants in 12 countries. In the paper and paperboard mills, most of the agents were measured in the pulping and refining departments and in on-machine coating and winding of paper/paperboard. Exposures to asbestos, carbon monoxide, formaldehyde, fungal spores, bacteria, nitrogen dioxide, minerals dusts, paper dust, sulphuric acid and different solvents sometimes exceeded exposure limit values. In the re-pulping and de-inking departments of recycling plants high exposures to formaldehyde, fungal spores, bacteria and paper dust were observed. High exposures to asbestos, bioaerosols, carbon monoxide and paper dust were found in many departments; ammonia, formaldehyde, mineral and paper dust and solvents were found in coating machines; and diphenyl and polychlorobiphenyls (PCBs) were found in some special circumstances. Measurements in the newsprint and uncoated paper machine departments revealed only a few elevated exposures. In nearly all departments, measurements of epichlorohydrin, PCBs, sulphur dioxide, hydrogen sulphide and mercaptans tended to be low, often even below their detection limits. In spite of some uncertainties in the measurement data, the study provides new insights into the level and variation of occupational exposures of production workers in the paper and paperboard industry.

Purpose: The Cervical Spine Research Society Europe (CSRS-E) actively promotes scientific activities, the annual meeting being the most evident of them. The publication rate of oral and poster presentations at the annual meeting could be a measure for the success of the promotional activities. The publication rates of abstracts presented at the annual European meetings of the CSRS are unknown. The quality of the abstracts presented at a conference is reflected by the publication rate. A high publication rate is usually interpreted as representative of high scientific value of the conference., Methods: Poster and podium presentations from the 2007 to 2012 annual meetings were identified. Pubmed was used to search for the abstract title and/or the combination of authors to verify whether the data were published in a peer-reviewed journal. Abstracts were considered published if the data presented at the meeting were identical to that in the publication. The journals in which the data were published were identified, as well as the origin of the research centre., Results: From 2007 to 2012 826 abstracts were featured at the CSRS Europe annual meetings. There were 236 podium presentations and 590 poster presentations. 42 % of the podium presentations resulted in a publication, and 28 % of the poster presentations led to a publication. Overall, 32 % of accepted abstracts effectuated a publication in a peer-reviewed scientific journal. Abstracts from European research groups had a publication rate of 29 % compared to 34 % for abstracts from non-European research groups. Spine, European Spine Journal, Journal of Spinal Disorders and Techniques and J Neurosurgery Spine were the most common publication journals for the abstracts. The mean impact factor of the journals in which was published was 2.2., Conclusion: 42 % of the abstracts that were accepted for podium presentation at the CSRS Europe resulted in a publication in peer-reviewed MEDLINE indexed journals. Publication rates are at the high end of the publication rate spectrum of abstracts accepted for European scientific meetings.

The European paper wasp, Polistes dominulus Christ, is an abundant wasp species in South and Central Europe which dispersed to the north in recent times. Polistes dominulus exhibits an energy-extensive mode of life, spending much time resting at the nest, which should be reflected in adaptations regarding gas exchange and standard metabolism. We analysed the resting metabolism (CO2 emission) of Polistes dominulus workers in the ambient temperature range an individual may be exposed to during a breeding season (T a = 2.4-40.6 °C) via flow through respirometry. Behaviour and endothermic activity were assessed by infrared thermography. With rising T a, CO2 release followed an exponential increase from 27 to 149 and 802 nl g(-1) min(-1) at T a = 3, 20 and 35 °C, respectively. Measurements of the thermal regime at the nest showed that resting P. dominulus are most of the time in the lower range of their standard metabolic curve. A comparison with a "highly energetic" wasp like Vespula sp. revealed that Polistes dominulus not only optimises behaviour but also reduces metabolism to save energy. The CO2 emission patterns changed with ambient temperature, from discontinuous (≤ 25 °C) to cyclic (25-36 °C) and continuous gas exchange at higher temperatures. A pronounced break appeared in the data progression regarding cycle frequency and CO2 emission per gas exchange cycle between 15 and 10 °C. This striking change in gas exchange features indicates a physiological adaptation to special respiratory requirements at low temperatures.

Glaucoma, a chronic progressive neuropathy and the most frequent cause of irreversible blindness worldwide, is commonly treated by medication or surgery aimed at lowering intraocular pressure. In view of the limited therapeutic options, the European Glaucoma Society (EGS) sponsored two Think Tank Meetings with the goal of assessing the current status and the overall perspectives for neuroprotective treatment strategies in glaucoma. The results of the meetings are summarized in this EGS White Paper.

Based on current data and experience, the joint working group of the European Society of Minimally Invasive Neurological Therapy (ESMINT) and the European Society of Neuroradiology (ESNR) make suggestions on trial design and conduct aimed to investigate therapeutic effects of mechanical thrombectomy (MT). We anticipate that this roadmap will facilitate the setting up and conduct of successful trials in close collaboration with our neighbouring disciplines.

A new era of stroke treatment may have begun with mechanical thrombectomy (MT) by fully deployed closed-cell self-expanding stents (stent-triever). Multiple case series and the first randomised controlled trials (RCTs) have now been published. More studies are under way involving large numbers of patients, which in turn has resulted in less strict "pragmatic" study protocols. Problems with current trials include a lack of standardisation in the conduct of the recanalisation procedure, the definition of primary endpoints such as the grade of arterial recanalisation and tissue reperfusion, and the post-surgical care provided. In Part 1 of this two part series, we outline the current situation and the major research questions.

The development of new molecular and neurobiological methods, computer-assisted quantification techniques and neurobiological investigation methods which can be applied to the human brain, all have evoked an increased demand for post-mortem tissue in research. Psychiatric disorders are considered to be of neurobiological origin. Thus far, however, the etiology and pathophysiology of schizophrenia, depression and dementias are not well understood at the cellular and molecular level. The following will outline the consensus of the working group for neuropsychiatric brain banking organized in the Brainnet Europe II, on ethical guidelines for brain banking, clinical diagnostic criteria, the minimal clinical data set of retrospectively analyzed cases as well as neuropathological standard investigations to perform stageing for neurodegenerative disorders in brain tissue. We will list regions of interest for assessments in psychiatric disorder, propose a dissection scheme and describe preservation and storage conditions of tissue. These guidelines may be of value for future implementations of additional neuropsychiatric brain banks world-wide.

The European continent has one of the longest life expectancies in the world, but still faces a significant challenge to meet the health targets set by the Sustainable Development Goals of the United Nations for 2030. To improve the understanding of the rationale that guides health outcomes in Europe, this study assesses the direction and magnitude effects of the drivers that contribute to explain life expectancy at birth across 30 European countries for the period 2008-2018 at macro-level. For this purpose, an aggregated health production function is used allowing for spatial effects. The results indicate that an increase in the income level, health expenditure, trade openness, education attainment, or urbanisation might lead to an increase in life expectancy at birth, whereas calories intake or quantity of air pollutants have a negative impact on this health indicator. This implies that health policies should look beyond economic factors and focus also on social and environmental drivers. The results also indicate the existence of significant spillover effects, highlighting the need for coordinated European policies that account for the synergies between countries. Finally, a foresight analysis is conducted to obtain projections for 2030 under different socioeconomic pathways. Results reveal significant differences on longevity projections depending on the adoption, or not, of a more sustainable model of human development and provides valuable insight on the need for anticipatory planning measures to make longer life-spans compatible with the maintenance of the welfare state., (© 2022. The Author(s).)

From both the methodological point of view and standardization of methodology, little attention has been paid to the estimation of direct costs in evaluation of healthcare technologies. The objective is to revise the recommendations on direct costs provided in European economic evaluation guidelines and to identify the commonalities and divergences among them. To achieve this, a comprehensive search through several online databases was performed resulting in 41 documents from 26 European countries, be they economic evaluation guidelines or costing guidelines. The results show a large disparity in methodologies used in estimation of direct costs to be included in economic evaluations of health technologies recommended by European countries. A lack of standardization of cost estimation methodologies influences arbitrariness in selecting costs of resources included in economic evaluations of medicinal products or any other technologies and, therefore, in decision making process necessary to introduce new technology. In addition, this heterogeneity poses a major challenge for identifying factors that could affect the variability of unit costs across countries., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Therapeutical monoclonal antibodies are structurally and functionally complex, whereas the innovator's manufacturing processes are proprietary. With respect to the similarity assessment, a proposed biosimilar product needs to demonstrate a side-by-side comparison between the reference product (RP) and candidate product in terms of physicochemical properties and biological activities, as well as nonclinical and clinical outcomes. Here, a comprehensive analytical similarity assessment was performed for in-depth comparison of HLX04, China-sourced Avastin ® (CN-Avastin ® ), and Europe-sourced Avastin ® (EU-Avastin ® ) following a tier-based quality attribute (QA) evaluation. A series of orthogonal and state-of-the-art analytical techniques were developed for the assessment. Ten lots of HLX04 were compared with 29 lots bevacizumab RP. Referred to the characterization results, HLX04 is highly similar to the RPs with respect to physicochemical properties and biological functions. In addition, HLX04 was found with similar stability and degradation behaviors upon multiple stressed conditions to bevacizumab. Minor differences were observed in glycosylation, aggregates, FcγRIIIa(F), and FcγRIIIa(V) binding activities; nevertheless, they were evaluated and demonstrated not to impact clinical outcomes. According to the reported clinical results, the totality of evidence, including the pharmacokinetic, efficacy, safety, and immunogenicity, further shows that HLX04 is similar to CN-/EU-Avastin ® ., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The aim of this article was to examine the relationship between precarious employment (PE), welfare states (WS) and mental health in Europe from a gender perspective., Methods: Data were derived from the European Working Conditions Survey 2015. PE was measured through the Employment Precariousness Scale for Europe (EPRES-E), validated for comparative research in 22 European countries, and categorized into quartiles. Countries were classified into Continental, Anglo-Saxon, Scandinavian, Southern and Central-Eastern WS. Mental health was assessed through the WHO-5 Well-Being Index and dichotomized into poor and good mental health. In a sample of 22,555 formal employees, we performed gender-stratified multi-level logistic regression models., Results: Results showed greater prevalences of PE and poor mental health among women. However, the association between them was stronger among men. Cross-country differences were observed in multi-level regressions, but the interaction effect of WS was only significant among women. More precisely, Central-Eastern WS enhanced the likelihood of poor mental health among women in high precarious employment situations (quartiles 3 and 4)., Conclusions: These findings suggest the interaction between contextual and individual factors in the production of mental health inequalities, both within and across countries. They also call for the incorporation of gender-sensitive welfare policies if equitable and healthy labor markets are to be achieved in Europe., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The International Abstract(s) of Surgery (IAS) was a monthly supplement to Surgery, Gynecology & Obstetrics (SG&O, later Journal of the American College of Surgeons) from 1913-1994, approximately equal in size to the journal itself. It followed the example of the Zentralblatt für Chirurgie (ZblCh), which had been compiling abstracts of the current world surgical literature since 1874 (but in the German language). This article seeks to review the relationships of these surgical abstract journals in historical context., Methods: Citations in the IAS were systematically sampled for 1913-1990, and in the ZblCh and other American and German surgical publications for 1905-1940. Changes in the proportions of citations by language category were tabulated over time and related to concurrent international events and the publication histories of the sampled journals., Results: German-language citations were most frequent until the First World War, even in America. They subsequently became less frequent in America, but remained dominant in Germany. Articles in French or other languages were occasionally cited by Americans, but in German publications, they were cited as frequently as those in English. Contemporary observations from this time confirm that the American literature was being disregarded by most German surgeons. Since the Second World War, surgical publications have become predominantly English-language, even in Germany, and printed abstract compilations have become irrelevant., Conclusions: The history of the IAS and ZblCh reflects world events of the early twentieth century, the isolation and decline of German scientific leadership, the rise of American surgery, and the transition from a multilingual print-based era to one where scientific communication is primarily electronic and in English., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The history of women in neurosurgery worldwide has been characterized by adversity and hardships in a male-dominated field, where resilient, tenacious, and ingenious women have nevertheless left their mark. The first women in neurosurgery appeared in Europe at the end of the 1920s, and since then have emerged in all continents in the world. Women neurosurgeons all over the globe have advanced the field in numerous directions, introducing neurosurgical subspecialties to their countries, making scientific and technical advances, and dedicating themselves to humanitarian causes, to name a few. The past 30 years, in particular, have been a period of increasing involvement and responsibility for women in neurosurgery. We must now focus on continual system improvements that will promote a diverse and talented workforce, building a welcoming environment for all aspiring neurosurgeons, in order to advance the specialty in the service of neurosurgical patients., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The objective of this paper was to investigate the existence of a trade-off between health system resilience and the economic efficiency of the health system, using data for 173 regions in the European Union and the European Free Trade Association countries. Data Envelopment Analysis was used to measure the efficiency of regional health systems before the COVID-19 pandemic. Then, a spatial econometrics model was used to estimate whether this measure of efficiency, adjusted for several covariates, has a significant impact on regional health system resilience during the COVID-19 pandemic, measured by the number of COVID-19 deaths per hundred thousand inhabitants. The results show that COVID-19 death rates were significantly higher in regions with higher population density, higher share of employment in industry, and higher share of women in the population. Results also show that regions with higher values of the health system efficiency index in 2017 had significantly higher rates of COVID-19 deaths in 2020 and 2021, suggesting the existence of a trade-off between health system efficiency and health system resilience during the COVID-19 pandemic., (© 2023. The Author(s).)

Recently, due to the corona virus outbreak, pandemics and their effects have been at the forefront of the research agenda. However, estimates of the perceived value of early warning systems (EWSs) for identifying, containing, and mitigating outbreaks remain scarce. This paper aims to show how potential health gains due to an international EWS might be valued. This paper reports on a study into willingness to pay (WTP) in six European countries for health gains due to an EWS. The context in which health is gained, those affected, and the reduction in risk of contracting the disease generated by the EWS are varied across seven scenarios. Using linear regression, we analyse this 'augmented' willingness to pay for a QALY (WTP-Q) for each of the scenarios, where 'augmented' refers to the possible inclusion of context specific elements of value, such as feelings of safety. An initial WTP-Q estimate for the basic scenario is €17,400. This can be interpreted as a threshold for investment per QALY into an EWS. Overall, WTP estimates move in the expected directions (e.g. higher risk reduction leads to higher WTP). However, changes in respondents' WTP for reductions in risk were not proportional to the magnitude of the change in risk reduction. This study provided estimates of the monetary value of health gains in the context of a pandemic under seven scenarios which differ in terms of outcome, risk reduction and those affected. It also highlights the importance of future research into optimal ways of eliciting thresholds for investments in public health interventions., (© 2022. The Author(s).)

When healthcare interventions prolong life, people consume medical and non-medical goods during the years of life they gain. It has been argued that the costs for medical consumption should be included in cost-effectiveness analyses from both a healthcare and societal perspective, and the costs for non-medical consumption should additionally be included when a societal perspective is applied. Standardized estimates of these so-called future costs are available in only a few countries and the impact of inclusion of these costs is likely to differ between countries. In this paper we present and compare future costs for five European countries and estimate the impact of including these costs on the cost-effectiveness of life-prolonging interventions. As countries differ in the availability of data, we illustrate how both individual- and aggregate-level data sources can be used to construct standardized estimates of future costs. Results show a large variation in costs between countries. The medical costs for the Netherlands, Germany, and the United Kingdom are large compared to Spain and Greece. Non-medical costs are higher in Germany, Spain, and the United Kingdom than in Greece. The impact of including future costs on the ICER similarly varied between countries, ranging from €1000 to €35,000 per QALY gained. The variation between countries in impact on the ICER is largest when considering medical costs and indicate differences in both structure and level of healthcare financing in these countries. Case study analyses were performed in which we highlight the large impact of including future costs on ICER relative to willingness-to-pay thresholds., (© 2022. The Author(s).)

Bonelli's eagle (Aquila fasciata) is an endangered raptor species in Europe, and trichomonosis is one of the menaces affecting chicks at nest. In this paper, we attempt to describe the oral microbiome of Bonelli's eagle nestlings and evaluate the influence of several factors, such as captivity breeding, Trichomonas gallinae infection, and the presence of lesions at the oropharynx. The core oral microbiome of Bonelli's eagle is composed of Firmicutes, Bacteroidota, Fusobacteria and Proteobacteria as the most abundant phyla, and Megamonas and Bacteroides as the most abundant genera. None of the factors analysed showed a significant influence on alfa diversity, but beta diversity was affected for some of them. Captivity breeding exerted a high influence on the composition of the oral microbiome, with significant differences in the four most abundant phyla, with a relative increase of Proteobacteria and a decrease of the other three phyla in comparison with chicks bred at nest. Some genera were more abundant in captivity bred chicks, such as Escherichia-Shigella, Enterococcus, Lactobacillus, Corynebacterium, Clostridium and Staphylococcus, while Bacteroides, Oceanivirga, Peptostreptococcus, Gemella, Veillonella, Mycoplasma, Suttonella, Alloscardovia, Varibaculum and Campylobacter were more abundant in nest raised chicks. T. gallinae infection slightly influenced the composition of the microbiome, but chicks displaying trichomonosis lesions had a higher relative abundance of Bacteroides and Gemella, being the last one an opportunistic pathogen of abscess complications in humans. Raptor's microbiomes are scarcely studied. This is the first study on the factors that influence the oral microbiome of Bonelli's eagle., (© 2022. The Author(s).)

Non-pharmaceutical interventions aimed at reducing the spread of COVID-19 rely largely on voluntary compliance among the target population to be effective, since such measures, which are aimed at the entire population, are very hard to enforce. In this paper, we focus on the impact of different work ethics on the spread of COVID-19. There are indeed reasons to believe that populations with different attitudes toward work will react differently to stay-at-home orders and other policies that forbid people from working. By means of a quantitative analysis, using hybrid model estimators, we test the impact of different work ethics on COVID-19 diffusion in a sample of 30 European countries. Results show that the more a population holds certain beliefs about work-namely, that it is humiliating to receive money without working, that people who do not work become lazy, and that work always comes first-the higher contagion rates of COVID-19 are, ceteris paribus. On the other hand, the more a population perceives work as a social duty, the lower contagion rates are. All this suggests that different work ethics matter in the containment of COVID-19., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Often presented as a global pandemic spreading all over the world, COVID-19, however, hit not only countries but also regions differently. The objective of this paper is to focus on the spatial heterogeneity in the spread of the COVID-19 pandemic and to contribute to an understanding of the channels by which it spread, focusing on the regional socioeconomic dimension. For this, we use a dataset covering 125 European regions in 12 countries. Considering that the impact of the COVID-19 crisis differed sharply not only across countries but also across regions within the same country, the empirical strategy is based, on the one hand, on an exploratory analysis of spatial autocorrelations, which makes it possible to identify regional clusters of the disease. On the other hand, we use spatial regression models to capture the diffusion effect and the role of different families of regional factors in this process. We find that the share of older people in the population, GDP per capita, distance from achieving EU objectives, and the unemployment rate are correlated with high COVID-19 death rates. In contrast, the number of medical practitioners and hospital beds and the level of social trust are correlated with low COVID-19 death rates.

This paper explores the association between health measures and long-term care (LTC) use in the 70+ old population. We examine how different measures of health-subjective versus objective-predict LTC use, provided either formally or informally. We consider an absolute measure of subjective health, the grade given by the individual to his/her health status, and additionally construct a relative measure capturing the difference between this grade and the average grade given to health by individuals sharing the same characteristics. Conceptually, this difference comes from the perception of the individual, corresponding to both the private health information and the reporting behavior affecting self-rated health. We use the baseline data from the SPRINTT study, an ongoing randomized control trial on 1519 subjects facing physical frailty and sarcopenia (PF&S) in 11 European countries. Our sample population is older than 70 (mean: 79 years) and comprises a majority (71%) of women. Results show that self-rated health indicators correlate to formal care even when objective health measures are included, while it is not the case for informal care. Formal care consumption thus appears to be more sensitive to the individual's perception of health than informal care.

In the last decade, adverse outcome pathways have been introduced in the fields of toxicology and risk assessment of chemicals as pragmatic tools with broad application potential. While their use in the pharmaceutical and cosmetics sectors has been well documented, their application in the food area remains largely unexplored. In this respect, an expert group of the International Life Sciences Institute Europe has recently explored the use of adverse outcome pathways in the safety evaluation of food additives. A key activity was the organization of a workshop, gathering delegates from the regulatory, industrial and academic areas, to discuss the potentials and challenges related to the application of adverse outcome pathways in the safety assessment of food additives. The present paper describes the outcome of this workshop followed by a number of critical considerations and perspectives defined by the International Life Sciences Institute Europe expert group.

Contrast-enhanced ultrasound (CEUS) and diffusion-weighted imaging (DWI) are safe, repeatable imaging techniques. The aim of this paper is to discuss the advantages, technical factors and possible clinical applications of these imaging tools in focal renal lesions in children.

Cyanobacteria are photoautotrophic organisms which occur in aquatic and terrestrial environments. They have the potential to produce toxins which pose a threat to human and animal health. This review covers the global distribution of the common cyanotoxins and related poisoning cases. A total of 468 selected articles on toxic cyanobacteria, dating from the earliest records until 2018, were reviewed. Most of the articles were published after 2000 (72%; 337 out of 468), which is consistent with the recent growth in interest in the analysis, toxinology and ecotoxicology of cyanotoxins. Animal and/or human poisoning cases were described in more than a third of the overall publications (38%; 177 out of 468). The reviewed publications showed that there were 1118 recorded identifications of major cyanotoxins in 869 freshwater ecosystems from 66 countries throughout the world. Microcystins were the most often recorded cyanotoxins worldwide (63%; 699 out of 1118), followed by cylindrospermopsin (10%; 107 out of 1118), anatoxins (9%; 100 out of 1118), and saxitoxins (8%; 93 out of 1118). Nodularins were the most rarely recorded cyanotoxins (2%; 19 out of 1118); however, there were also reports where cyanotoxins were not analysed or specified (9%; 100 out of 1118). The most commonly found toxic cyanobacterial genera were Microcystis spp. (669 reports), Anabaena spp. (397 reports), Aphanizomenon spp. (100 reports), Planktothrix spp. (98 reports), and Oscillatoria spp. (75 reports). Furthermore, there were 183 recorded cyanotoxin poisonings of humans and/or animals. Out of all toxic cyanobacterial blooms reviewed in this paper, the highest percentage of associated poisonings was found in North and Central America (39%; 69 cases out of 179), then Europe (20%; 35 out of 179), Australia including New Zealand (15%; 27 out of 179), and Africa (11%; 20 out of 179), while the lowest percentage was related to Asia (8%; 14 cases out of 179) and South America (8%; 14 cases out of 179). Events where only animals were known to have been affected were 63% (114 out of 182), whereas 32% (58 out of 182) of the investigated events involved only humans. A historical overview of human and animal poisoning episodes associated with cyanobacterial blooms is presented. Further, geographical data on the occurrence of cyanotoxins and related poisonings based on the available literature are shown. Some countries (mainly European) have done very intensive research on the occurrence of toxic cyanobacteria and cyanotoxins, and reported related ecotoxicological observations, while in some countries the lack of data is apparent. The true global extent of cyanotoxins and associated poisonings is likely to be greater than found in the available literature, and it can be assumed that ecotoxicological and hygienic problems caused by toxic cyanobacteria may occur in more environments.

This paper analyses whether government ideology and other political- and electoral-related factors influence country-level public healthcare expenditures, focussing on the impact of the Great Recession on that relationship. We test this hypothesis for the OECD countries in 1970-2016. Our results reveal the presence of a partisan effect, left-wing governments being more likely to raise public expenditures in the health sector. We also find that coalitions increase these expenditures, whilst minority governments and those with a high presence in the lower house decrease them. Meanwhile, the opportunistic behaviour of incumbents related to the timing of elections is not supported by our results. The percentage of public expenditures over total health expenditures is also examined, obtaining similar results regarding the partisan effect. However, the onset of the Great Recession has altered these relationships, neutralizing the impact of political factors.

The GM content in a food or feed product produced from or containing genetically modified organisms (GMO) has to be expressed in Europe in the form of a GM mass fraction. However, the most widely used quantification methods, based on PCR, are basically counting PCR-amplifiable DNA fragments in a sample extract. This paper outlines the requirements for obtaining comparable measurement results which are fit for regulatory decision-making. It introduces the concept of a reference measurement system which enables GMO analysis laboratories to relate their results to a universally accessible reference, thus establishing metrological traceability to a unique reference point. The conversion factors required for transforming data from one measurement unit into the other have to carry a minimum uncertainty and are anchored to specified certified reference materials. The establishment of such conversion factors and related calibration approaches to achieve comparable GM quantification results are sketched. Graphical abstract ᅟ.

This paper examines inequality and polarization in self-assessed health, contributing towards the limited research existing on health economics. We use data from the European Health Interview Survey (EHIS) to investigate the relationship between health inequality and polarization across 27 European countries in two periods: 2006-2009 and 2013-2015. As our key variable is of an ordinal nature, we employ median based measures. Our empirical results suggest that Greece is the country with the highest level of health polarization in both periods, whereas Ireland has the lowest one when we consider countries where the median category is "very good", coinciding with the findings obtained in the inequality index. Estonia, Hungary and Lithuania have the highest degree of health polarization in both periods while Malta, The Netherlands and Spain are the countries with the lowest when we focus on those countries whose median category is "good" health.

This paper analyses the effects of health on wages in sixteen European countries using production frontier methodology. It is assumed that workers have a potential income/productivity which basically depends on their human capital, but due to several health problems, situations could exist where workers fail to reach their potential income frontier. The estimation of a true-random-effects model allows us to conclude that the potential hourly wage of workers is significantly influenced by their level of education and their job experience. However, health problems, especially those strongly influencing work activities, contribute towards an individual not attaining the potential income which would otherwise be guaranteed by their human capital endowment. Suffering a strong limitation reduces gross wage per hour by 6.1%. This wage reduction is also observed in the case of a weak limitation, but here the wage difference with respect to workers without any limitation is 2.6%. Additionally, other factors, such as being a woman, the economic cycle or having a temporary contract, appear to distance an individual from their wage frontier.

The first commercialization of seedlings inoculated with truffle fungi occurred in 1973. Over the last 40 years, considerable progress has been made relative to quality control for inoculated seedlings. A recently published paper by Andrés-Alpuente and colleagues (Mycorrhiza 24:29-37, 2014) reviewed and tested the different methods of mycorrhization assessment currently used in Europe. The aim of this paper is to augment their findings by adding information to the discussion about the most important steps in seedling quality control. Additionally, the history of seedlings inoculated with truffles, procedures currently used in France for seedling control quality, and a reflection on future research aimed at increasing truffle production will be presented.

This paper describes how cooperation among international organizations, as modeled in Europe, can work to improve imaging safety and standards for children throughout the world. This is demonstrated in the mechanisms employed in a large-scale multi-national study on CT imaging safety practices described elsewhere in this issue of Pediatric Radiology. Here we learn approaches through which CT safety standards have been achieved and the international resources available to help in standardizing safety practices in medical imaging. There are unique strengths of the approach in Europe, which has mandatory requirements on member states to facilitate strengthening of radiation protection. Most countries have national regulatory mechanisms for radiation protection in medicine. International organizations play a significant role in supporting projects in lower-resource countries such that a large proportion of radiologic professionals in low-resource countries are trained through assistance by these organizations. Many of these international organizations make it possible for professionals worldwide to download free training material. Collaboration among international organizations and the Image Gently campaign toward consensus with regard to radiation protection can go further than individual opinions in promoting a higher standard of radiation protection around the world.

The first biosimilar monoclonal antibody (infliximab, CT-P13) was registered by the European Medicines Agency in 2013 for the treatment of several inflammatory conditions including rheumatoid arthritis (RA). Biosimilar infliximab is first being marketed in the Central and Eastern European countries. This paper presents the estimated budget impact of the introduction of biosimilar infliximab in RA over a 3-year time period in six selected countries, namely Bulgaria, the Czech Republic, Hungary, Poland, Romania and Slovakia. A prevalence-based model was constructed for budget impact analysis. Two scenarios were compared to the reference scenario (RSc) where no biosimilar infliximab is available: biosimilar scenario 1 (BSc1), where interchanging the originator infliximab with biosimilar infliximab is disallowed, and only patients who start new biological therapy are allowed to use biosimilar infliximab; as well as biosimilar scenario 2 (BSc2), where interchanging the originator infliximab with biosimilar infliximab is allowed, and 80% of patients treated with originator infliximab are interchanged to biosimilar infliximab. Compared to the RSc, the net savings are estimated to be €15.3 or €20.8 M in BSc1 and BSc2, respectively, over the 3 years. If budget savings were spent on reimbursement of additional biosimilar infliximab treatment, approximately 1,200 or 1,800 more patients could be treated in the six countries within 3 years in the two biosimilar scenarios, respectively. The actual saving is most sensitive to the assumption of the acquisition cost of the biosimilar drug and to the initial number of patients treated with biological therapy. The study focused on one indication (RA) and demonstrated that the introduction of biosimilar infliximab can lead to substantial budget savings in health care budgets. Further savings are expected for other indications where biosimilar medicines are implemented.

When the patent of a brand-name, marketed drug expires, new, generic products are usually offered. Small-molecule generic and originator drug products are expected to be chemically identical. Their pharmaceutical similarity can be typically assessed by simple regulatory criteria such as the expectation that the 90% confidence interval for the ratio of geometric means of some pharmacokinetic parameters be between 0.80 and 1.25. When such criteria are satisfied, the drug products are generally considered to exhibit therapeutic equivalence. They are then usually interchanged freely within individual patients. Biological drugs are complex proteins, for instance, because of their large size, intricate structure, sensitivity to environmental conditions, difficult manufacturing procedures, and the possibility of immunogenicity. Generic and brand-name biologic products can be expected to show only similarity but not identity in their various features and clinical effects. Consequently, the determination of biosimilarity is also a complicated process which involves assessment of the totality of the evidence for the close similarity of the two products. Moreover, even when biosimilarity has been established, it may not be assumed that the two biosimilar products can be automatically substituted by pharmacists. This generally requires additional, careful considerations. Without declaring interchangeability, a new product could be prescribed, i.e. it is prescribable. However, two products can be automatically substituted only if they are interchangeable. Interchangeability is a statistical term and it means that products can be used in any order in the same patient without considering the treatment history. The concepts of interchangeability and prescribability have been widely discussed in the past but only in relation to small molecule generics. In this paper we apply these concepts to biosimilars and we discuss: definitions of prescribability and interchangeability and their statistical implementation; the relation between bioequivalence and interchangeability for small-molecule drug products; regulatory requirements and expectations of biosimilar products in various jurisdictions; possible statistical approaches to establish the similarity and interchangeability of biologic drug products; definition of other technical terms such as switchability and automatic substitution. The paper will be concluded with a discussion of the anticipated future use of interchangeability of biological drug products.

Biological drugs revolutionized the treatment of inflammatory rheumatic diseases. Access to treatment presents substantial variability across Europe. The economic level of a particular country as well as administrative restrictions have been proved as determining factors of biological drug uptake. The objective of this paper was to provide an overview of biological treatment in six selected Central and Eastern European (CEE) countries, namely in the Bulgaria, Czech Republic, Hungary, Poland, Romania and Slovakia. The literature is summarized with regard to the epidemiology, disease burden and use of biological agents in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Moreover, an estimate is provided on the prevalence and number of patients with biological treatment based on international and local sources. In view of the limited availability of information and uncertainty in data, there is an urgent need for development of systematic and comprehensive data collection in inflammatory rheumatic diseases in CEE countries.

The European Society of Paediatric Radiology Uroradiology Task Force and the ESUR Paediatric Work Group jointly publish guidelines for paediatric urogenital imaging. Two yet unaddressed topics involving patient safety and imaging load are addressed in this paper: renal biopsy in childhood and imaging of the neonatal genital tract, particularly in girls. Based on our thorough review of literature and variable practice in multiple centers, procedural recommendations are proposed on how to perform renal biopsy in children and how to approach the genital tract in (female) neonates. These are statements by consensus due to lack of sufficient evidence-based data. The procedural recommendation on renal biopsy in childhood aims at improving patient safety and reducing the number of unsuccessful passes and/or biopsy-related complications. The recommendation for an imaging algorithm in the assessment of the neonatal genital tract focuses on the potential of ultrasonography to reduce the need for more invasive or radiating imaging, however, with additional fluoroscopy or MRI to be used in selected cases. Adherence to these recommendations will allow comparable data and evidence to be generated for future adaptation of imaging strategies in paediatric uroradiology.

Background: Multifocal papillary thyroid carcinoma (MPTC) has been reported in literature in 18-87 % of cases. This paper aims to review controversies in the molecular pathogenesis, prognosis, and management of MPTC., Methods: A review of English-language literature focusing on MPTC was carried out, and analyzed in an evidence-based perspective. Results were discussed at the 2013 Workshop of the European Society of Endocrine Surgeons devoted to surgery of thyroid carcinoma., Results: Literature reports no prospective randomized studies; thus, a relatively low level of evidence may be achieved., Conclusions: MPTC could be the result of either true multicentricity or intrathyroidal metastasis from a single malignant focus. Radiation and familial nonmedullary thyroid carcinoma are conditions at risk of MPTC development. The prognostic importance of multifocal tumor growth in PTC remains controversial. Prognosis might be impaired in clinical MPTC but less or none in MPTC <1 cm. MPTC can be diagnosed preoperatively by FNAB and US, with low sensitivity for MPTC <1 cm. Total or near-total thyroidectomy is indicated to reduce the risk of local recurrence. Prophylactic central node dissection should be considered in patients with total tumor diameter >1 cm, or in cases with high number of cancer foci. Completion thyroidectomy might be necessary when MPTC is diagnosed after less than near-total thyroidectomy. Radioactive iodine ablation should be considered in selected patients with MPTC at increased risk of recurrence or metastatic spread.

In the second half of the nineteenth century venereal diseases attained more attention and explosiveness in public discourse than ever before. Collective fear of the so-called French disease culminated in the emergence of melancholic syphilophobia a previously unknown form of hypochondriac suffering. This paper addresses the question of how this development occurred and focuses more specifically on the epistemological implications of the pathological fear of syphilis and highlights the systematic significance of etiological interpretation and nosological conceptualization of venereal disease.

Standardized and transparent priority setting in medicine, desirable as it is, will generally exacerbate inter-temporal equity problems arising from changes in treatment priorities: when can it be fair that the treatment of already waiting patients who would have had priority under an established system should be postponed (withheld) for an extended period of time to advance the treatment of others under a reformed system? The reform of the Eurotransplant system of priority setting in kidney allocation (ETKAS), which is in many respects ideal, is a case in point. To give due weight to new medical knowledge, waiting time after the onset of end state renal failure should change from a priority-enhancing to a priority-reducing factor. Since those who have gained in priority by waiting under the present system would be set back under the new, severe problems of transitional justice must be overcome when responding to advances in medical knowledge. The paper explores conceptually some possible ways of rule change and indicates their general relevance from an ethical and a practical point of view for future problems of medical resource allocation under transparent, standardized priority-setting rules.

Bioaccumulation of PFAS in aquatic organisms is an environmental problem of growing concern around the world. This problem has been tackled by regulatory bodies by proposing EQS for biota in EU water bodies and tolerable daily intake for food. The introduction of regulatory limits requires the availability of harmonised and validated analytical methods of sufficient sensitivity. This paper reviews recent advances in analytical methods for analysis of PFAS in aquatic organisms. The methods available for biota analysis are mostly based on three extraction procedures: ion-pair extraction, solvent liquid extraction, and alkaline digestion. The resulting extracts are then subjected to different clean-up or enrichment steps on solid adsorbents, for example graphitized carbon black, C(18), and WAX phases. All methods reviewed in this work give reliable results but are partially validated only, because of the lack of certified reference materials and regular interlaboratory exercises. The few interlaboratory exercises performed on real unspiked samples did not afford satisfactory results for PFAS other than PFOS, especially for matrices with high lipid content, for example mussels. The reasons for those partially negative results have been identified, and can mainly be attributed to calibration procedures and availability and purity of standards. The urgent need for certified reference materials for this type of analysis is emphasized.

The tactile inspection of the bladder had a long tradition in urology. Examination results and their interpretation depended heavily on the individual tactile skills of the urologist. Because this examination method (if correctly applied) proved the artistic skills and experience of a doctor, urologists did not see any need to replace tactile examinations with a competing method.Nevertheless, urology as well as many other medical disciplines was receptive to techniques aiming at the visualization of pathology. Visualizations served the purposes of science-oriented medicine to be objective and to document examination results. However, it needed the development of specific technologies to create objective images. One major problem in urology was the question of how to light body cavities. After extracorporeal light sources had proven to be ineffective, attempts were made at bringing light sources into the interior of the body. It needed heated tungsten filaments and later mignon bulbs at the tip of endoscopes to illuminate the bladder to such an extent that images from the interior of the bladder could be produced. The paper examines the status of these images as self-evident and objective. It is argued that the images produced were not self-evident. It is shown how combinations of texts and images were needed to develop an endoscopic viewing technique in order to read endoscopic images properly and to recognize those aspects of endoscopic documentations which were necessary for correct interpretations of the images.

Recently, several checklists systematically assessed factors that affect the transferability of cost-effectiveness (CE) studies between jurisdictions. The role of the threshold value for a QALY has been given little consideration in these checklists, even though the importance of a factor as a cause of between country differences in CE depends on this threshold. In this paper, we study the impact of the willingness-to-pay (WTP) per QALY on the importance of transferability factors in the case of smoking cessation support (SCS). We investigated, for several values of the WTP, how differences between six countries affect the incremental net monetary benefit (INMB) of SCS. The investigated factors were demography, smoking prevalence, mortality, epidemiology and costs of smoking-related diseases, resource use and unit costs of SCS, utility weights and discount rates. We found that when the WTP decreased, factors that mainly affect health outcomes became less important and factors that mainly effect costs became more important. With a WTP below 1,000, the factors most responsible for between country differences in INMB were resource use and unit costs of SCS and the costs of smoking-related diseases. Utility values had little impact. At a threshold above 10,000, between country differences were primarily due to different discount rates, utility weights and epidemiology of smoking-related diseases. Costs of smoking-related diseases had little impact. At all thresholds, demography had little impact. We concluded that, when judging the transferability of a CE study, we should consider the between country differences in WTP threshold values.

Recently, the state of California enacted a law requiring radiologists to record the radiation dose that each patient receives for a CT scan. Failure to do so is penalized by law. This law becomes effective in July 2012. By July 2013, every facility that performs CT scans must become accredited by one of three professional groups. This report discusses the role that legislation is playing in the practice of medicine in regard to CT practice. Inherent in this discussion is the assumption that pediatric radiologists know the right dose that a child should receive for a specific clinical indication. But do we really know the answer to this? Compared to the European radiology community, the United States radiology community lags in this regard. This paper defines diagnostic reference levels (DRL) and reviews the history of DRL in the United States compared to that in the European community and the progress by the American College of Radiology's National Radiology Data Registry (NRDR) to establish national registries. The establishment of the first pediatric Quality Improvement Registry in CT Scans in Children (QuIRCC) and its progress to date will be discussed.

Background: The goal of the present study was to evaluate the publication rate of abstracts presented during the German Anesthesia Congress (Deutscher Anästhesiecongress, DAC) and the meeting of the European Society of Anesthesiologists (ESA) in the years 2000 and 2005 in Medline listed journals (http://www.ncbi.nlm.nih.gov/pubmed). In addition, the respective impact factors of the journals in which the articles were published were evaluated (http://www.isiknowledge.com)., Methods: All abstracts of free papers and posters presented at the DAC and ESA from the years 2000 and 2005 were included into the study. The presence of authors and the topics of abstracts in the literature were analyzed by a Medline based inquiry over a time period of 5 years. The search was based on the last name and initials of authors and when these could not be identified in Medline the search was extended by keywords of relevant topics of the abstract. Umlauts "ä/ö/ü" were replaced by "ae/oe/ue" and "ß" was replaced by "ss". Only original papers were included in this analysis. Once an original paper was found the impact factor of the journal in that year was identified., Results: A total of 465 abstracts from the DAC 2000, 378 abstracts from the DAC 2005, 644 abstracts from the ESA 2000 and 720 abstracts from the ESA 2005 were included. Of the abstracts from the DAC 2000, 183 (39%) were published in Medline listed journals, 179 (47%) from DAC 2005, 218 (34%) from ESA 2000 and 233 (32%) from ESA 2005. The ESA abstracts were published in English more often than the DAC abstracts (ESA 2000: 95%; ESA 2005: 95%; DAC 2000: 78%; DAC 2005: 86%). While the publication rate after the ESA remained nearly unchanged between 2000 and 2005, the publication rate after the DAC increased by about 7%. The average impact factors of the publications were 1.777 (DAC 2000), 2.836 (DAC 2005), 1.825 (ESA 2000) and 2.36 (ESA 2005). Independent of the congress (DAC or ESA) where the abstract was presented, most articles were published in the journal Anesthesia & Analgesia., Conclusion: In the year 2005 more abstracts of the DAC were published in Medline listed papers than in 2000. When comparing the number of abstracts published in Medline listed journals, more abstracts of the DAC were published compared to abstracts of the ESA. The increase in papers written in English after abstract presentation on the DAC is mostly due to the wider readership which can be reached with manuscripts in the English language. Besides a larger readership, English journals often also have a higher ranked impact factor. This analysis does not claim to be a complete registration of all published abstracts due to the limitation on Medline listed journals and publications in other journals were not rated. Medline was selected because of the widespread and international use of this database.

This paper analyses the effect of absolute deductibles on the cost of insurance for outpatient services. Moreover, cost savings on retained losses are estimated. Sharing risks between the insured and the insurer reduces total expenditure for outpatient benefits by up to 35%. In particular, optimal deductibles are determined in their utilitarian sense: the maximum possible savings on medical expenses are computed from the ground up. As part of the study, the effect of age and gender on these savings is analysed. The analysis is based on data taken from the private medical insurance industry in Germany. Similarities and discrepancies with respect to results obtained in the RAND Health Insurance Experiment conducted in the United States from 1971 to 1982 are highlighted.

This analysis aims to get a step further in the understanding of the determining factors of social health inequalities, and to explore particularly the role played by parents' social status and their vital status or age at death on the social health inequalities in adulthood among European older adults. The wealth-related health inequalities are measured using the popular concentration index. We then implement the decomposition method of the indices and evaluate the contribution of the various determinants of health introduced in interval regression models. Health is measured using self-assessed health and country-specific cut-points that correct observed differences in self-report due to cross-cultural differences in reporting styles. This paper uses data for ten European countries from the first wave of the 2004 SHARE. The study highlights significantly higher wealth-related health inequalities in the Netherlands, Denmark and Germany. These social inequalities of health in Europe are explained largely by individuals' current social conditions, particularly wealth. Nevertheless, our analysis attests the existence of a long-term influence of initial conditions in childhood on health in middle-aged and beyond, independently of current social characteristics, which contribute to differences in health status across social groups. This article contributes to the identification of social determinants, which are important determinants of health and follows recommendations suggested to help 'close the gap' in various health inequities.

Health effects of exposures at low doses and/or low dose rates are recognized as requiring intensive research activity to answer several questions. To address these issues at a strategic level in Europe, with the perspective of integrating national and EC efforts (in particular those within the Euratom research programmes), a "European High Level and Expert Group (HLEG) on low dose risk research" was formed and carried out its work during 2008. The Group produced a report published by the European Commission in 2009 and available on the website http://www.hleg.de . The more important research issues identified by the HLEG were as follows: (a) the shape of dose-response for cancer; (b) the tissue sensitivities for cancer induction; (c) the individual variability in cancer risk; (d) the effects of radiation quality (type); (e) the risks from internal radiation exposure; and (f) the risks of, and dose response relationships for, non-cancer diseases. In this paper, the radiation quality issues are especially considered, since they are closely linked to health problems and related radioprotection in space and in emerging radiotherapeutic techniques (i.e., hadrontherapy). The peculiar features of low-fluence, high-LET radiation exposures can question in particular the validity of the radiation-weighting factor (w ( R )) approach. Specific strategies are therefore needed to assess such risks. A multi-scale/systems biology approach, based on mechanistic studies coordinated with molecular-epidemiological studies, is considered essential to elucidate differences and similarities between specific effects of low- and high-LET radiation.

The structure and methods to complete and derive a quality score from the European Network of Health Economic Evaluation Databases (EURONHEED) transferability information checklists for published economic evaluations were reported and discussed in a previous paper (Boulenger et al. in Eur J Health Econ 6, 334-346, 2005). Within the same paper, the use of the checklists was illustrated through their application to a sample of economic evaluations conducted in France and UK. The transferability information subchecklist, consisting of 16 items from the original 42-point checklist, and methods used to derive it, were validated among 16 health economists across Europe participating in the EURONHEED project. Recent correspondence with other researchers, however, indicates that the checklists are now being utilised in empirical work and the methodology of assessing transferability and generalisability. This supplementary paper provides full details of the guidelines that have been developed and recently updated by the authors, such that the overall and subchecklists can be more widely and consistently completed and utilised. We also briefly discuss associated issues such as weighting of items in the checklists and give further clarifications regarding what we consider the most appropriate applications of the checklists to be.

Osteoporosis is one of the 10 most important and widespread global diseases. In Germany alone the cost of osteoporosis runs into many billions of Euros. However, it should be noted that in the past 15 years great progress has been made both in diagnosis and in the development of new medications, and this has changed the general perception of and attitude to osteoporosis. It is now taken very seriously and recognised as a national and global disorder which is both preventable and treatable. In spite of this progress, in Europe and especially in Germany, osteoporosis remains an underdiagnosed and undertreated disease. In Germany, only about 10%-15% of patients with manifest osteoporosis are properly treated. However, in addition to national guidelines, there is now a new edition of the "European Position Paper for the Diagnosis and Management of Osteoporosis". This provides physicians treating osteoporosis patients with additional information and therefore more confidence.

Osteoporosis is one of the ten most important and widespread global diseases. In Germany alone the costs of osteoporosis run into billions of Euros. However, during the past 15 years great progress has been made both in diagnosis and in the development of new medications. Osteoporosis is now taken very seriously and recognized as a national and global disorder which is now both preventable and treatable. Nevertheless, at a practical level, both in Europe and especially in Germany, osteoporosis remains an underdiagnosed and undertreated disease. In Germany, only about 10-15% of patients with manifest osteoporosis are properly treated. The consequences of such inadequate care are high additional costs-not to mention the unnecessary suffering of the patients involved. However, in support of national guidelines, a new edition of the "European Position Paper for the Diagnosis and Management of Osteoporosis" provides the doctors who treat patients with osteoporosis with additional information and therefore more confidence. In this paper several aspects are emphasized: improvements in diagnostic evaluation, assessment of the efficacy of fracture-oriented medications, and cost-effectiveness of the treatment of patients with osteoporosis.

This paper is an introduction to the study "The Burden of Rheumatoid Arthritis and Patient Access to Treatment". The objective of the study is to compare patient access to new drugs in Europe, North America and a selection of other countries, and to analyse the determinants of differences between countries, as basis for a discussion on how patients' access to new and effective treatments can be improved. There were few treatments available that could affect the progression of the disease prior to the introduction of the first TNF inhibitors in the late 1990s. Since the cost per patient treated with these biological drugs is high compared to previously available treatments, reimbursement through private and public insurance is an important determinant for access to treatment.

The aim of this methodological paper is to summarize evidence on how to implement cost-benefit assessment according to the new German legislative framework (Competition Enhancement Act). Given the complexity of existing health policy frameworks within industrialised countries in adapting health economics in their respective regulatory scheme, no clear international scientific consensus on which health economic methods should be chosen for assessment can be determined. Nevertheless, a broad consensus on the internal properties of methods itself can be found. Based on these common international standards in methodology, this work provides a minimum catalogue of methods and criteria that meet legal and local German requirements with regard to specific factors of its health care system. Aside from categorising clearly defined standards (e.g., study forms, cost and benefit categories) the suggested catalogue specifies some intensively debated areas in Germany (e.g., the QALY, modelling, the perspective used in the assessment). After the proposition of certain methods the paper leads to a first recommendation of a detailed assessment-process itself specific for the German way in implementing cost-benefit ratios within regulatory decision making in Germany.