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Objective: Methadone is a vital treatment for women with opioid use disorder in pregnancy. Previous reports suggested an association between methadone exposure and Pierre Robin sequence (PRS), a rare craniofacial anomaly. We assessed the association between gestational methadone exposure and PRS.Design/setting: This case-malformed control study used European Surveillance of Congenital Anomalies population-based registries in Ireland, the Netherlands, Italy, Switzerland, Croatia, Malta, Portugal, Germany, Wales, Norway and Spain, 1995-2011.Patients: Cases included PRS based on International Classification of Disease (ICD), Ninth Edition-British Paediatric Association (BPA) code 75 603 or ICD, Tenth Edition-BPA code Q8708. Malformed controls were all non-PRS anomalies, excluding genetic conditions, among live births, fetal deaths from 20 weeks' gestation and terminations of pregnancy for fetal anomalies. An exploratory analysis assessed the association between methadone exposure and other congenital anomalies (CAs) excluding PRS. Methadone exposure was ascertained from medical records and maternal interview.Results: Among 87 979 CA registrations, there were 127 methadone-exposed pregnancies and 336 PRS cases. There was an association between methadone exposure and PRS (OR adjusted for registry 12.3, 95% CI 5.7 to 26.8). In absolute terms, this association reflects a risk increase from approximately 1-12 cases per 10 000 births. A raised OR was found for cleft palate (adjusted OR 5.0, 95% CI 2.7 to 9.2).Conclusions: These findings suggest that gestational methadone exposure is associated with PRS. The association may be explained by unmeasured confounding factors. The small increased risk of PRS in itself does not alter the risk-benefit balance for gestational methadone use. The association with cleft palate, a more common CA, should be assessed with independent data. [ABSTRACT FROM AUTHOR]

Background: Heterozygous germline TP53 gene mutations result in Li-Fraumeni Syndrome (LFS). Breast cancer (BC) is the most frequent tumor in young women with LFS. An important issue related to BC in the Mexican population is the average age at diagnosis, which is approximately 11 years younger than that of patients in the United States (U.S.) and Europe. The aim of this study was to determine the prevalence of germline mutations in TP53 among young Mexican BC patients.Methods: We searched for germline mutations in the TP53 gene using targeted next-generation sequencing (NGS) in 78 BC patients younger than 45 years old (yo) who tested negative for BRCA1/2 mutations. A group of 509 Mexican women aged 45yo or older without personal or family BC history (parents/grandparents) was used as a control.Results: We identified five patients with pathogenic variants in the TP53 gene, equivalent to 6.4% (5/78). Among patients diagnosed at age 36 or younger, 9.4% (5/55) had pathogenic TP53 mutations. Three of these variants were missense mutations (c.844C > T, c.517G > A, and c.604C > T), and the other two mutations were frameshifts (c.291delC and c.273dupC) and had not been reported previously. We also identified a variant of uncertain clinical significance (VUS), c.672G > A, which causes a putative splice donor site mutation. All patients with TP53 mutations had high-grade and HER2-positive tumors. None of the 509 patients in the healthy control group had mutations in TP53.Conclusions: Among Mexican BC patients diagnosed at a young age, we identified a high proportion with germline mutations in the TP53 gene. All patients with the TP53 mutations had a family history suggestive of LFS. To establish the clinical significance of the VUS found, additional studies are needed. Pathogenic variants of TP53 may explain a substantial fraction of BC in young women in the Mexican population. Importantly, none of these mutations or other pathological variants in TP53 were found in the healthy control group. [ABSTRACT FROM AUTHOR]

Beer is one of the most popular beverages in the world and its complex flavor is widely appreciated. Beer flavor profiling is important for brewers to optimize beer production and to guarantee odor quality and taste stability of the final products. This is especially the case for pale lager beers that represent the beer type with the largest worldwide production volume. In this study, the combination of stir bar sorptive extraction (SBSE) with capillary gas chromatography (GC) hyphenated to time-of-flight mass spectrometry (TOFMS) was used to perform a detailed aroma profiling of lager beer samples originating from Belgium, The Netherlands, and France. A generic SBSE method was applied resulting in a very broad extraction coverage of odor solutes, while the extraction process is miniaturized, unattended and solventless, meeting green analytical chemistry requirements. Using GC-TOFMS analysis operated in untargeted mode, MS deconvolution and statistical data analysis, with principal component and hierarchical clustering analysis, it was possible to clearly differentiate brands and origins of the beer samples and to identify marker compounds for flavor profiling of these closely related beer samples. An extended database of beer aroma compounds was created. The developed method can be applied in beer quality optimization and quality control in routine laboratories., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021. Published by Elsevier B.V.)

Background: Nintedanib is a triple angiokinase inhibitor approved with docetaxel for adenocarcinoma non-small cell lung cancer after first-line chemotherapy (FLT). In the phase III LUME-Lung 1 study, overall survival (OS) was significantly longer with nintedanib/docetaxel than with placebo/docetaxel in all adenocarcinoma patients and those with time from start of FLT (TSFLT) <9 months.Objective: This study sought to extend analyses from the LUME-Lung 1 study, specifically for adenocarcinoma patients, to explore the impact of clinically relevant characteristics on outcomes such as time to progression after FLT.Patients and Methods: Exploratory analyses were conducted of the overall and European LUME-Lung 1 adenocarcinoma population according to age, prior therapy, and tumor dynamics. Analyses also used TSFLT and time from end of FLT (TEFLT).Results: Treatment with nintedanib/docetaxel significantly improved OS in European patients independently of age or prior therapy. Analyses of several patient subgroups showed improvements in median OS: TSFLT <6 months, 9.5 versus 7.5 months (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.55-0.98); chemorefractory to FLT, 9.1 versus 6.9 months (HR 0.72, 95% CI 0.52-0.99); progressive disease (PD) as best response to FLT, 9.8 versus 6.3 months (HR 0.62, 95% CI 0.41-0.94); TEFLT ≤6 months, 11.3 versus 8.2 months (HR 0.75, 95% CI 0.61-0.92); and TEFLT <3 months, 11.0 versus 8.0 months (HR 0.74, 95% CI 0.58-0.94).Conclusions: Nintedanib/docetaxel demonstrated significant OS benefits in adenocarcinoma patients, which were more pronounced in patients with shorter TSFLT or TEFLT, or with PD as best response to FLT. This study was registered at ClinicalTrials.gov: NCT00805194. [ABSTRACT FROM AUTHOR]

Background: Antibodies to citrullinated proteins (ACPA) occur years before RA diagnosis. Porphyromonas gingivalis expresses its own peptidylarginine deiminase (PPAD), and is a proposed aetiological factor for the ACPA response. Smoking is a risk factor for both ACPA-positive RA and periodontitis. We aimed to study the relation of these factors to the risk of RA in a prospective cohort.Methods: We performed a nested case-control study by identifying pre-RA cases in four populations from the European Prospective Investigation into Cancer and nutrition, matched with three controls. Data on smoking and other covariates were obtained from baseline questionnaires. Antibodies to CCP2 and citrullinated peptides from α-enolase, fibrinogen, vimentin and PPAD were measured. Antibodies to arginine gingipain (RgpB) were used as a marker for P.gingivalis infection and validated in a separate cohort of healthy controls and subjects with periodontitis.Results: We studied 103 pre-RA cases. RA development was associated with several ACPA specificities, but not with antibodies to citrullinated PPAD peptides. Antibody levels to RgpB and PPAD peptides were higher in smokers but were not associated with risk of RA or with pre-RA autoimmunity. Former but not current smoking was associated with antibodies to α-enolase (OR 4.06; 95 % CI 1.02, 16.2 versus 0.54; 0.09-3.73) and fibrinogen peptides (OR 4.24; 95 % CI 1.2-14.96 versus 0.58; 0.13-2.70), and later development of RA (OR 2.48; 95 % CI 1.27-4.84 versus 1.57; 0.85-2.93), independent of smoking intensity.Conclusions: Smoking remains a risk factor for RA well before the clinical onset of disease. In this cohort, P.gingivalis is not associated with pre-RA autoimmunity or risk of RA in an early phase before disease-onset. Antibodies to PPAD peptides are not an early feature of ACPA ontogeny. [ABSTRACT FROM AUTHOR]

This special issue of the Financial History Review contributes to the vast literature on the political economy of monetary unions. Inspired by the recent events in Europe, it reaches back in history to consider an earlier experiment in forming a monetary (as well as economic and political) union. In this historical case the pivotal event was the ratification of the United States Constitution in 1788, two centuries before the Maastricht Treaty. Between formal independence in 1781 and the implementation of the Constitution reforms in 1789, the fledgling country was organised politically into a loose confederation of thirteen, virtually sovereign states. Despite the nominal powers granted to the national government under the Articles of Confederation, it lacked the direct means to collect taxes and to enforce its policies. Consequently, during this brief period, state governments could and did pursue their own economic and monetary policies. [ABSTRACT FROM AUTHOR]

Describes the appropriate ways of recreating the required data for the common currency zone when historical exchange rates varied substantially. Considerations for reconstructing aggregate Euro zone data; Impact of variable exchange rates on the aggregation procedure; Comparison of the constructed data with published data; Conclusion.

Objectives: This study was performed to assess the contraceptive efficacy of the drospirenone (DRSP)-only pill and to provide information regarding its safety and cycle-control profile.Study Design: This prospective, multicenter, noncomparative study was conducted at 41 European sites in healthy women at risk of pregnancy, aged 18 to 45 years. The study medication was DRSP 4.0mg daily for 24 days followed by a placebo for 4 days (DRSP 4 mg 24/4, Exeltis, Spain) for thirteen 28-day treatment cycles. The primary efficacy endpoint was the overall Pearl Index (PI). Bleeding patterns, changes in vital signs and changes in laboratory values were also analyzed.Results: A total of 713 participants with 7638 DRSP treatment cycles were analyzed. The overall PI was 0.51 (95% confidence interval, 0.1053-1.4922). The proportion of participants with any bleeding decreased from 72.7% in Cycle 1 to 40% in Cycle 6 and 32.1% in Cycle 13. Unscheduled bleeding decreased from 49.1% in Cycle 1 to 27.8% in Cycle 6 and to 22.8% in Cycle 13. Prolonged bleeding was reported by 6.5% during Cycles 2 to 4 decreasing to 4.2% during Cycles 11 to 13. There were no reports of deep vein thrombosis, pulmonary embolism or hyperkalemia. No relevant changes were observed for laboratory parameters, body weight, body mass index, blood pressure or heart rate. Study drug acceptability was considered as "excellent/good" by over 82% of subjects.Conclusion: This new DRSP-only oral contraceptive provides clinical contraceptive efficacy similar to that of the currently marketed Combination estrogen plus progestin Oral Contraceptive, with a good safety profile, and favorable cycle control.Implications: A novel 4-mg DRSP-only pill taken daily for 24 days followed by a placebo for 4 days demonstrated contraceptive efficacy similar to that of currently marketed Combination estrogen plus progestin Oral Contraceptive, with a good safety profile, and favorable cycle control. [ABSTRACT FROM AUTHOR]

Responds to an article written by Michael Pammer, entitled `Proxy-data and Income Estimates,' which focused on economic forecasting in Europe. Reference to the regression model; Indepth look at the effectiveness of the proxy-approach; Availability of statistical data.

Investigates the role of banking in the industrialization in Europe during the 19th-century. Factors which contributed to the conditioning of institutional structures.

The authors have used an online community approach, and tools that were readily available via the Internet, to discover genealogically and therefore phylogenetically relevant Y-chromosome polymorphisms within core haplogroup R1b1a2-L11/ S127 (rs9786076). Presented here is the analysis of 135 unrelated L11 derived samples from the 1000 Genomes Project. We were able to discover new variants and build a much more complex phylogenetic relationship for L11 sub-clades. Many of the variants were further validated using PCR amplification and Sanger sequencing. The identification of these new variants will help further the understanding of population history including patrilineal migrations in Western and Central Europe where R1b1a2 is the most frequent haplogroup. The fine-grained phylogenetic tree we present here will also help to refine historical genetic dating studies. Our findings demonstrate the power of citizen science for analysis of whole genome sequence data. [ABSTRACT FROM AUTHOR]

David Kelsey's is read in the context of the traditions of Christian theology, especially in Europe and North America, and of Kelsey's Yale colleagues. Its theocentric, scriptural and thoughtfully experimental contribution to theological anthropology from the perspectives of creation, consummation and reconciliation is analysed, appreciated and assessed. Implications of Kelsey's identification of three distinct plotlines in the Bible are explored. Questions are raised about the range of his Christian conversations, the limitations of his reliance on narrative, his neglect of significant parts of the Bible and Christian tradition, and his focus on the interaction with secular rather than religious dimensions of the contemporary world. [ABSTRACT FROM AUTHOR]

In North America, Eurasia, and Australia, salvage logging is increasingly being used to mitigate economic losses due to fire, although the effects of this type of intervention are still essentially unknown. In a field experiment in a large recent boreal forest fire in central Quebec, we used 24 paired salvaged and non-salvaged stands to test the effect of salvage on the recruitment of two conifer species possessing an aerial seed bank (Pinus banksiana and Picea mariana). The seedbeds following salvage were, on average, more hospitable to germination, but, incongruously, engendered far lower regeneration densities. The poor recruitment on salvaged sites was due primarily to the loss of seeds following the immediate post-fire salvage, when cone-bearing branches were removed along with the trunks. By contrast, the density of the asexually-recruited Populus tremuloides was relatively unaffected. We suggest simple ways to modify current salvage procedures that would retard this transition from conifer to Populus forest, as well as leaving more wood in situ. [ABSTRACT FROM AUTHOR]

The article introduces the symposium issue of the "New York Law School Law Review" which brings together a small group of prominent defamation law practitioners and scholars from Europe, Australia and the U.S. to explore developments in defamation, free speech and privacy law both inside and outside of the U.S. It presents an overview of several articles which focus on developments related to the U.S. Supreme Court decision in the case New York Times Co. v. Sullivan in other countries. The articles reveal how freedom of speech in each society is rooted in history and subject to evolving legal and social norms.

Comments on the psychological impact of the September 11, 2001, terrorist attacks on the national psyche of Europeans. Psychic trauma caused by the terrorist attack; Analysis of pertinent topics and relevant issues; Implications on trauma studies.

Presents a discourse analysis of "The Community Action Programme on Health Promotion, Information, Education and Training 1996-2000" in European countries. Use of religious discourse analysis to construct the programme; Military discourse analysis; Shift in blame in health promotion policy.

The article discusses a study of cross-cultural conceptualizations of successful aging (SA) in younger Europeans aged 18 to 35 from countries including Romania, Belgium, and Germany. A table ranking the items that were considered by participants as being important to SA, including longevity, remaining free of chronic disease, and being able to care for oneself until close to time of death, is presented.

The article presents an insightful analysis of professor Pierre Pestieau's views on social protection and private insurance. The fundamental problem that Pierre identifies with social insurance programs is the pressure of international competition and, presumably, migration in an increasingly open Europe. As far as the actual problem of insurance is concerned (that is, the efficiency and not the redistributive function), there are other possible lessons to be drawn from the developments Pestieau describes. Also, Pestieau notes the problem created by the tendency (potential) for the winners later in life to flee the responsibilities of caring for the losers.

Focuses on the Hospitaller Order of St. John of Jerusalem, a 12th century foundation favored by Pope Benedict XIV. The Order's involvement in Colonial ventures beyond Europe and the Mediterranean between 1530 to 1798; Evangelical vigor during Pope Benedict XIV's term; Plurality of the religious atmosphere in the mid-18th century.

The European collaborative study of HIV-infected pregnant women in Europe now indicates a 13% risk of fetal HIV infection (originally thought to be about 30%, and possibly higher in some countries)- Several reports suggest transplacental passage. However, the detailed mechanisms associated with such vertical transmission have not yet been clarified. We have examined the possibility that HIV enters placental tissue from maternal blood via binding to CD4 and Fc receptors (FcR) at the trophoblast level, allowing intraplacental infection. Here we report the detection of several FcR with distinct localization in the placental villus as well as CD4 surface expression on human trophoblast cells. In addition, we show that trophoblastic cells interact specifically with the gp120/gp160 viral envelope protein. By their tissue localization, these receptors could be responsible or the entry of HIV into the fetal placental cells. Furthermore, purified placental cells can be directly infected by HIV in vitro, and the infection is inhibited by soluble CD4. This suggests a crucial role of the CD4 receptor but an additional way of entry cannot be excluded. Such an in vitro model may be suitable for further studies concerning placental HIV transmission and its prevention. [ABSTRACT FROM AUTHOR]

The transition from the Middle Paleolithic (MP) to Upper Paleolithic (UP) is marked by the replacement of late Neandertals by modern humans in Europe between 50,000 and 40,000 y ago. Châtelperronian (CP) artifact assemblages found in central France and northern Spain date to this time period. So far, it is the only such assemblage type that has yielded Neandertal remains directly associated with UP style artifacts. CP assemblages also include body ornaments, otherwise virtually unknown in the Neandertal world. However, it has been argued that instead of the CP being manufactured by Neandertals, site formation processes and layer admixture resulted in the chance association of Neanderthal remains, CP assemblages, and body ornaments. Here, we report a series of accelerator mass spectrometry radiocarbon dates on ultrafiltered bone collagen extracted from 40 well-preserved bone fragments from the late Mousterian, CP, and Protoaurignacian layers at the Grotte du Renne site (at Arcy-sur-Cure, France). Our radiocarbon results are inconsistent with the admixture hypothesis. Further, we report a direct date on the Neandertal CP skeleton from Saint-Césaire (France). This date corroborates the assignment of CP assemblages to the latest Neandertals of western Europe. Importantly, our results establish that the production of body ornaments in the CP postdates the arrival of modern humans in neighboring regions of Europe. This new behavior could therefore have been the result of cultural diffusion from modern to Neandertal groups.

Cultural differences between countries are customarily calculated by comparing mean scores on multiple dimensions, which ignores heterogeneity within societies. This article proposes a fundamentally new way of measuring cultural differences by evaluating the functioning of the emotional brain—that is, by comparing how people think, rather than what they think. Deep learning as a supervised machine learning technique is used to mathematically represent the emotional brain of the Volksgeist ("folk spirit") with a complex system of nonlinear combinations of value priorities, opinions, and other factors with subjective feelings of well-being. Cross-validating how well one Volksgeist's artificial brain fits another country provides a novel measure for emotional cultural differences, which also considers heterogeneity within a society. This measure is conceptually and statistically unrelated to the Kogut–Singh index calculated from mean scores on cultural dimensions. However, it shows good face validity and supports international marketing and business theory as a negative and highly significant predictor for bilateral trade flows within Europe, using a classic gravity model. [ABSTRACT FROM AUTHOR]

This article reports on the first meeting of the Research Planning Group on International Tourism and Urban Restructuring. The Research Planning Group on International Tourism and Urban Restructuring held its first meeting on April 16-18, 1998, at the University of Amsterdam, at Amsterdam, Netherlands. Funded by a grant from the Ford Foundation through the Council for European Studies, the group brought together participants from North America, West and East Central Europe, to examine the impact of tourism on cities and regions. Although tourism has become one of the largest and fastest growing sectors of the world economy and a central component of the economic and cultural revitalization of cities and regions in the 1990s, it remains understudied in its urban and regional effects. The tourism industry generates volumes of data directed at marketing, but this has not given rise to theoretically grounded investigations. To the extent that tourism has been studied, it has been unevenly studied with less attention to the phenomenon in the United States than in western Europe, and with few comparative analyses.

Millennial-scale climate variations during the last glacial period, such as Dansgaard–Oeschger (DO) cycles and Heinrich events, have been extensively studied using ice core and marine proxy records. However, there is a limited understanding of the magnitude of these temperature fluctuations in continental regions, and questions remain about the seasonal signal of these climate events. This study presents a 60 000-year-long temperature reconstruction based on branched glycerol dialkyl glycerol tetraethers (brGDGTs) extracted from lake sediments from the Eifel Volcanic Field, Germany. brGDGTs are bacterial membrane-spanning lipids that are known to have a strong relationship with temperature, making them suitable for temperature reconstructions. We test several temperature calibration models on modern samples taken from soils and multiple maar lakes. We find a negative bias in brGDGT-based temperature estimates associated with water depth and anoxic conditions that can be corrected for by accounting for a brGDGT isomer that is only produced in anoxic conditions. The corrected temperature reconstruction correlates with proxy and climate model estimates of temperature spanning the same time period, validating the calibration approach we selected. However, millennial-scale variability is significantly dampened in the brGDGT record, and in contrast to other Northern Hemisphere climate records, during several Heinrich stadials, temperatures actually increase. We demonstrate that these apparent discrepancies can be explained by the unique seasonal response of the brGDGT paleothermometer to temperatures of months above freezing (TMAF). Our data support the view that warm-season temperatures in Europe varied minimally during the last glacial period and that abrupt millennial-scale events were defined by colder, longer winters. Our continuous high-resolution temperature reconstruction provides important information about the magnitude of seasonal climate variability during the last glacial period that can be used to test climate models and inform studies of paleoecological change. [ABSTRACT FROM AUTHOR]

The return of war to Europe with the Russo-Ukrainian conflict generated mental health effects even in countries not directly involved in the war. The present study describes the Italian adaptation and validation of the Fear of War Scale (FOWARS), i.e., a 13-item Likert scale built by a Romanian research team and exploring the fear of war. For the Italian adaptation, a sample of 150 young Italian adults (aged 18–30, M = 21.7; SD = 2.2) has been collected. Exploratory Factor Analysis conducted with PCA confirmed the bifactorial structure of the scale and detected two dimensions, i.e., the "Physiological dimension of fear" and the "Experiential dimension of fear". The results of the Confirmatory Factor Analysis show adequate goodness of fit and the last version of the scale, consisting of 12 items, shows good internal consistency and convergent and discriminant validity. Positive significant correlations with the Worry Domains Questionnaire (WDQ) and the Depression Anxiety and Stress Scale (DASS-21) were also found. Moreover, results from ANOVA display significant differences between men and women, with the latter showing higher values of fear of war. Finally, t-test analyses highlight the impact of the fear of war on Italian young adults' mental health and worry. The Italian adaptation of FOWARS has good overall psychometric properties and can be used to explore the fear of war in the Italian young adult population to highlight the psychological impact of war and its relationship with mental health. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, most workers had to work from home due to the successive lockdowns across European countries. This constraint posed significant challenges to many workers and companies regarding working conditions and work–life balance. Framed by the job demands–resources model (JD–R), the goal of this paper is to examine the association of perceived organizational support (POS) and individual resilience (IR) with work–life balance (WLB) during the COVID-19 pandemic across European countries. This goal is complemented by assessing the role of work-from-home (WFH) as a mediator. Based on a quantitative approach, data were extracted from the second round of the survey "Living, Working, and COVID-19" from Eurofound. A series of regressions using SEM-PLS tested the hypothesis. Findings reveal that WFH negatively influences WLB. POS positively influences WFH and negatively influences WLB when mediated by WFH. IR negatively influences WFH and positively influences WLB when mediated by WFH. These results have essential theoretical implications related to the relations between individual and organizational resources and WLB and practical implications for the management of WFH, namely, the importance of providing adequate organizational resources and promoting the development of individual resources. [ABSTRACT FROM AUTHOR]

The categories of "amateur" and "professional" remain central in studies on the sociology of nineteenth-century science. This article joins a growing body of literature that points out the complicated and intersecting connections between these two groups and how blurred the boundaries could be. This study focuses on pyrotechny, the art of fireworks, a field of far more obvious importance in the nineteenth century than it is today. Firework displays were mounted by artisan firework makers, who by the end of the century had become industrialists, and by military specialists, usually artillerymen. They had also become a common amateur pursuit. Across the nineteenth century, the art was transformed by the introduction of new materials, and the key discoveries were the work of enthusiasts who did not seek to profit financially from their discoveries. In this sense, they too were amateurs, although some had a scientific education. This article asks how they were able to make such major contributions to the field, and it situates them within networks that often crossed the boundaries between those who made fireworks for a living, or who studied them in military contexts, and those who were simple enthusiasts. [ABSTRACT FROM AUTHOR]

We present a timeseries of flood and slumping phases in central Europe for the past 65,000 years from event layers in sediment cores from infilled Eifel maar basins (Germany). Palynological, petrographic and organic carbon (chlorins) records are used to understand the precise timing of these events. Periods of increased flood activity seem to coincide with Heinrich stadials in marine sediment records, which are associated with cold and more arid climate conditions, indicating a vegetation response within the maars' catchment areas. This multi-proxy correlation reveals prominent slumps at different maar sites during Greenland Stadial (GS) 12. The stratigraphy is based on sediment records from the Auel infilled maar and we thus call this event Auel Cold Event (ACE). Frozen and fractured sediment packages within the slump suggest deep frost or permafrost conditions for the region during the stadial. The results agree well with sediment archives and archeological sites across Europe that report severely cold and arid conditions for the stadial. This supports the assumption that GS12 was indeed one of the coldest periods of the last glacial cycle rather than the Heinrich stadials. Based on our age model, the ACE occurred at 43,500 yr b2k (years before the year 2000), which coincides with the initial weakening of Earth's magnetic field strength prior to the Laschamp geomagnetic excursion. [ABSTRACT FROM AUTHOR]

This study addresses the incompatibility question between the corporate organization of industry and a system based on the general recognition of economic rights and freedoms in continental western Europe. A dissociation/identification model based on a comparative analysis verifies the consistency of the premise that makes the emergence of economic rights possible only after suppressing the corporations of trades. The model stems coherently from the ideas of eighteenth-century political economists and crystallizes in reform policies aimed at eliminating corporate elements contrary to economic freedoms. The results directly link the intellectual model and the actual expressions of economic rights within the declarations written at the end of the old regime. While dissociation creates an opportunity for corporate continuity within a framework of recognized economic freedoms, the French identification model implies the suppression of corporations. [ABSTRACT FROM AUTHOR]

Radiocarbon dating is the most widely applied dating method in archaeology, especially in human evolution studies, where it is used to determine the chronology of key events, such as the replacement of Neanderthals by modern humans in Europe. However, the method does not always provide precise and accurate enough ages to understand the important processes of human evolution. Here we review the newest method developments in radiocarbon dating ('Radiocarbon 3.0'), which can lead us to much better chronologies and understanding of the major events in recent human evolution. As an example, we apply these new methods to discuss the dating of the important Palaeolithic site of Bacho Kiro (Bulgaria). [ABSTRACT FROM AUTHOR]

This paper presents an attempt at establishing an association between crime levels and prison populations across European countries. We observe that the situation in Central and Eastern European countries differs distinctly from the rest of Europe. Building on this, we offer justification that is methodologically based on correlations and regressions of country incarceration rates on crime rates, with reference to governance indicators. Our cross-sectional analysis uses data on crime and prisoner rates by offence from Eurostat and SPACE for the year 2018. The paper's empirical analysis is preceded by a discussion of the challenges faced when attempting to compare crime between countries in Europe. A review of research focused on relationships between incarceration and crime follows, with the emphasis on the deterrence effect and the prison paradox. Typically, this stream of research uses microdata covering a single country or limited to a smaller geographic area. International comparisons are rare, and are usually based on time series and trend analyses. The quantitative approach applied here is based on recognizing two clusters of countries: the Central and Eastern European (CEE) cluster and the Western European (WE) cluster. We show that the observation of higher prisoner rates and lower crime rates for CEE countries is confirmed with regression analysis. Our study encompasses four types of offences: assault, rape, robbery, and theft. The final section of the paper presents an attempt to incorporate Worldwide Governance Indicators into the analysis of the association between incarceration and crime rates. The results confirm that crime rates in WE countries are distinctly higher than in CEE countries, while incarceration rates in WE are significantly lower than in CEE countries. We think this is due to a higher percentage of crimes being reported and the greater accuracy of police statistics in WE countries. The prison population in each country is largely determined by its criminal and penal policies, which differ substantially between CEE and WE countries (e.g., in terms of frequency of imposing prison sentences and the length of imprisonment). These tendencies result in higher incarceration rates in CEE countries, despite lower crime rates when compared to WE countries. [ABSTRACT FROM AUTHOR]

Civil society organizations (CSOs) are a cornerstone of democracy in Europe. Nonetheless, "civil society" and "political society" should not be equated as membership-based organizations are not necessarily politically engaged. This paper theorizes and empirically examines which membership-based CSOs engage in interest representation through sustained advocacy activity. We propose an incentive-theoretical framework on CSO investments in advocacy activities—a collective, non-exclusive incentive from which also non-members can profit—by organizations fundamentally dependent on member support. Theorizing how CSOs' own structural characteristics, resource dependencies, and government demand for CSO input affect how CSOs reconcile selective and collective incentive provision, we test our hypotheses using new data from four recent surveys conducted in four European democracies. In line with our framework, CSOs organizing individual citizens rather than corporate actors and those pursuing member interests are less likely to engage in advocacy, while CSO professionalization and state funding access enhance CSOs' propensities to do so. Furthermore, the analysis shows that the former structural CSO characteristics are similarly relevant for CSO advocacy across distinct country settings, while the role of resource variables is mediated by institutional context revealing an important source of inequality in democratic interest representation. [ABSTRACT FROM AUTHOR]

The concept of dual quality of products provided by the same manufacturers is not a novel one, however, the awareness of its existence and implications has only recently been noticed in Europe by the general public. The response of the media was immediate and massive. The reality of what dual quality represents for consumers was largely exaggerated and companies applying such strategies were criticised by public opinions. However, there is a lack of knowledge of how this phenomenon affects changes in buyers' behaviour and therefore, companies are unable to develop their strategies in accordance with current and believable data. This paper provides information on the relationship between the dual quality of goods and changes in buyers' behaviour, resulting in developed guidelines and recommendations for international producers on the issue of dual quality and how to incorporate it into their marketing strategies in order to gain competitive advantage. The findings based on research conducted in Slovak Republic include a detailed structure of customer segments and their response to dual quality. [ABSTRACT FROM AUTHOR]

Purpose: To determine the diagnostic accuracy of judging optic disc photographs for glaucoma by ophthalmologists. Design: Evaluation of diagnostic test and technology. Participants: A total of 243 of 875 invited ophthalmologists in 11 European countries. Methods: We determined how well each participant classified 40 healthy eyes and 48 glaucomatous eyes with varying severity of the disease on stereoscopic slides. Duplicate slides were provided for determining intraobserver agreement. All eyes were also imaged with the GDx with variable corneal compensation (GDx-VCC) (Carl Zeiss Meditec AG, Jena, Germany) and the Heidelberg Retina Tomograph (HRT) I (Heidelberg Engineering GmbH, Heidelberg, Germany). Diagnostic accuracies of clinicians were compared with those of the best machine classifiers. Main Outcome Measures: Accuracy of classification, expressed as sensitivity, specificity, and overall accuracy. Intraobserver agreement (κ). Results: The overall diagnostic accuracy of ophthalmologists was 80.5% (standard deviation [SD], 6.8; range, 61.4%–94.3%). The machine classifiers outperformed most observers in diagnostic accuracy; the GDx-VCC nerve fiber indicator and the HRT''s best classifier correctly classified 93.2% and 89.8% of eyes, respectively. The intraobserver agreement (κ) varied between −0.13 and 1.0 and was on average good (0.7). Conclusions: In general, ophthalmologists classify optic disc photographs moderately well for detecting glaucoma. There is, however, large variability in diagnostic accuracy among and agreement within clinicians. Common imaging devices outperform most clinicians in classifying optic discs. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Many cases of wildlife poisoning in Europe have been reported causing population declines, especially in raptors. Toxicovigilance and risk assessment studies are essential to reinforce the knowledge of the number of illegal poisoning cases and the substances involved in these crimes. Many researchers and projects in different institutions have suggested the creation of a network to improve communication and share information between European countries. This article presents the results of the Short-Term Scientific Mission titled "Developing a Network of Analytical Labs and Government Institutions" supported by the COST Action European Raptor Biomonitoring Facility (CA16224), which aims to initiate a network of veterinary forensic toxicology laboratories, in order to improve communication among laboratories to prevent wildlife poisoning, especially in raptors. For this purpose, a questionnaire was designed and sent by email to 119 laboratories in Europe. It contained 39 questions on different topics (e.g. laboratory activities, analytical information). A total of 29 responses were received. Most participant laboratories work on veterinary forensic toxicology research and external cases at the same time, which provides a robust overview of the actual situation in the field. Analytical techniques and data collection methods should be harmonised, and communication between laboratories is encouraged to create a more effective network. The present study established contact between laboratories as an initial step to create a European network and compiled basic data to identify strengths and weaknesses that will help harmonise methodologies across Europe and increase pan-European capacities. [ABSTRACT FROM AUTHOR]

Many academic papers have looked at the economic effects of the EU cohesion policy, which still remain an open empirical issue. The focus of the most recent literature has been on the heterogeneous effects of the policy and the identification of regional conditioning factors. However, most of the existing studies generally assume slope homogeneity for different cross‐sectional units (i.e., regions) and they estimate the average effects of the policy for all the European regions and/or selected groups of regions. Past works also employ data covering few programming periods. This paper has two main goals. First, we study the heterogeneous consequences of EU cohesion policy on regional economic growth in Europe over the past three decades, by applying a heterogeneous coefficient approach to new panel‐time series data. We calculate the region‐specific effects of the policy in terms of long‐run gross domestic product growth. Second, we study regional differences in terms of policy effects depending on the level of assistance received by the regions. We make a distinction among cases of effective, ineffective, trigger and marginal policy. We also document that the effectiveness of EU cohesion policy in the long run can be explained by some of the key factors used in the literature. Finally, we discuss the need for ineffective cases to learn from effective and trigger ones. [ABSTRACT FROM AUTHOR]

Quadruple and Quintuple Helix Innovation Systems aim to optimize the design and operation of modern, democratic societies and economies in a smart, sustainable, inclusive, resilient and efficacious manner via the cyber-physical ecosystems that align with Industry 5.0 and Society 5.0 precepts. In this context, the Quintuple Innovation Helix Framework (which is part of the Quadruple/Quintuple Innovation Helix or Q2IH) represents the most comprehensive, meaningful and valuable construct and modality as it encompasses the five key core dimensions of modern, sustainable and democratic knowledge economies and societies. These are the Environment, the Civil Society as well as the Government, University and Industry dimensions. We strongly feel that it is appropriate and even critical, given current events in Europe that starkly highlight the conflict and struggle between democracies and autocracies, to enable, facilitate and even accelerate the further development of an Emerging Unified Theory of Helical Architectures (EUTOHA). The objective would be to bring clarity, coherence and consistency to the process of leveraging the helical architectures to advance and enhance the design of solutions for the digital transformation of modern knowledge economies and societies towards more democratic and sustainable (green) ones. [ABSTRACT FROM AUTHOR]

This review explores recent historiography on the international and imperial dimensions of nineteenth-century British politics. In particular, it charts historians' attempts to assess how British engagement with politics overseas – in Europe, the empire, and the 'rest of the world' – helped to shape domestic political structures, cultures, and ideologies. While concentrating mainly on studies produced during the last twenty years, the review also affirms the continued relevance of work from before the turn of the century, and suggests that some of the most compelling approaches to connecting 'domestic' and 'international' politics may lie in older historiography. It proposes also that political historians might engage more closely with relevant scholarship by intellectual historians and historians of political thought. [ABSTRACT FROM AUTHOR]

Much of the recent debate on immigration to Europe has focused on how many refugees should be allowed to enter and how refugees should be distributed among EU member states, but there has been less academic focus on under what conditions, if any, human smuggling is morally permissible. How should we morally assess those who make a business out of helping migrants reach their desired destination and those who pay smugglers to reach their destination? We argue that human smuggling is morally permissible under some conditions even if it is illegal. Human trafficking, by contrast, is immoral and should be illegal. The moral conditions for permissible human smuggling are sometimes being met on the route from Africa to Europe (but are all too often grossly violated). We consider and rebut objections based on the arguments that a legal prohibition on human smuggling must translate into a moral one, and that human smuggling violates the rights of individuals to freedom of association in receiving countries. We conclude with policy implications. [ABSTRACT FROM AUTHOR]

The launch of the European New Green Deal represents a strategic plan developed in Europe to favor the transition to more sustainable business models. One of the main initiative is represented by the revision of the Directive 95/2014/EU. This revision came in response to several criticisms of the directive's application to European Public Interest Entities, including the low degree of comparability that characterize the resulting nonfinancial declarations. This research paper analyzes how 70 Italian PIEs adhere to the comparability principle when preparing their nonfinancial declarations. Furthermore, a difference‐in‐differences analysis has been performed to assess the impacts of Directive 95/2014/EU on nonfinancial declarations' comparability. Our results highlight how the comparability of nonfinancial reports is an objective not yet achieved. In this regard, the revision of Directive 95/2014/EU will represent an opportunity for policymakers to address this critical issue. [ABSTRACT FROM AUTHOR]

Cocaine is still one of the most commonly used illicit substances worldwide, with an estimated 4 million users in Europe in the last year. Hair samples have been widely used for the determination of episodic or repeated consumption of this substance, but the use of miniaturized techniques for hair sample clean-up has been challenging due to the sample complexity. Despite hair's complex matrix, MEPS provides a method that is fast, reduces the volume of extraction solvents used, and offers low-cost options (since extraction beds may be reused several times). Microextraction by packed sorbent using a mixed-mode sorbent was optimized for hair sample clean-up in order to determine cocaine, benzoylecgonine, ecgonine methyl ester, norcocaine, cocaethylene and anhydroecgonine methyl ester by gas chromatography coupled to tandem mass spectrometry. The method was fully validated according to internationally accepted criteria, presenting good linearity between the limits of quantification (0.01–0.15) and 5 ng/mg. Precision and accuracy resulted in coefficients of variation typically lower than 15%, with mean relative errors within ±15% for all compounds, except for the limit of quantification (±20%). The present work describes the first application of microextraction by packed sorbent for the concentration of cocaine and metabolites extracted from hair samples. [ABSTRACT FROM AUTHOR]

Background: Previous gene-environment interaction studies of breast cancer risk have provided sparse evidence of interactions. Using the largest available dataset to date, we performed a comprehensive assessment of potential effect modification of 205 common susceptibility variants by 13 established breast cancer risk factors, including replication of previously reported interactions.Methods: Analyses were performed using 28 176 cases and 32 209 controls genotyped with iCOGS array and 44 109 cases and 48 145 controls genotyped using OncoArray from the Breast Cancer Association Consortium (BCAC). Gene-environment interactions were assessed using unconditional logistic regression and likelihood ratio tests for breast cancer risk overall and by estrogen-receptor (ER) status. Bayesian false discovery probability was used to assess the noteworthiness of the meta-analysed array-specific interactions.Results: Noteworthy evidence of interaction at ≤1% prior probability was observed for three single nucleotide polymorphism (SNP)-risk factor pairs. SNP rs4442975 was associated with a greater reduction of risk of ER-positive breast cancer [odds ratio (OR)int = 0.85 (0.78-0.93), Pint = 2.8 x 10-4] and overall breast cancer [ORint = 0.85 (0.78-0.92), Pint = 7.4 x 10-5) in current users of estrogen-progesterone therapy compared with non-users. This finding was supported by replication using OncoArray data of the previously reported interaction between rs13387042 (r2 = 0.93 with rs4442975) and current estrogen-progesterone therapy for overall disease (Pint = 0.004). The two other interactions suggested stronger associations between SNP rs6596100 and ER-negative breast cancer with increasing parity and younger age at first birth.Conclusions: Overall, our study does not suggest strong effect modification of common breast cancer susceptibility variants by established risk factors. [ABSTRACT FROM AUTHOR]

Objectives: To describe the epidemiology and geographical differences in prevalence of congenital cerebral anomalies in Europe.Design and Setting: Congenital cerebral anomalies (International Classification of Diseases, 10th Revision code Q04) recorded in 29 population-based EUROCAT registries conducting surveillance of 1.7 million births per annum (29% of all European births).Participants: All birth outcomes (live births, fetal deaths from 20 weeks gestation and terminations of pregnancy after prenatal diagnosis of a fetal anomaly (TOPFA)) from 2005 to 2014.Main Outcome Measures: Prevalence, proportion of associated non-cerebral anomalies, prenatal detection rate.Results: 4927 cases with congenital cerebral anomalies were identified; a prevalence (adjusted for under-reporting) of 9.8 (95% CI: 8.5 to 11.2) per 10 000 births. There was a sixfold difference in prevalence across the registries. Registries with higher proportions of prenatal diagnoses had higher prevalence. Overall, 55% of all cases were liveborn, 3% were fetal deaths and 41% resulted in TOPFA. Forty-eight per cent of all cases were an isolated cerebral anomaly, 25% had associated non-cerebral anomalies and 27% were chromosomal or part of a syndrome (genetic or teratogenic). The prevalence excluding genetic or chromosomal conditions increased by 2.4% per annum (95% CI: 1.3% to 3.5%), with the increases occurring only for congenital malformations of the corpus callosum (3.0% per annum) and 'other reduction deformities of the brain' (2.8% per annum).Conclusions: Only half of the cases were isolated cerebral anomalies. Improved prenatal and postnatal diagnosis may account for the increase in prevalence of congenital cerebral anomalies from 2005 to 2014. However, major differences in prevalence remain between regions. [ABSTRACT FROM AUTHOR]

Little is known about the interface between separate marketing units and sales units. This article develops a multidimensional model of the marketing and sales interface. The model integrates a broad range of conceptual domains, including information sharing, structural linkages, power, orientations, and knowledge of marketing and sales. The authors empirically explore the conceptual model through a cross-industry study of 337 European Unionbased companies. They identify five empirical archetypes of the marketing and sales interface. The taxonomy shows that the role and characteristics of marketing and sales vary a great deal. This finding challenges existing stereotypes about marketing and sales. Finally, the article explores organizational outcomes of the five configurations. The findings suggest that the most successful configurations are characterized by strong structural linkages between marketing and sales and a high extent of market knowledge in marketing. [ABSTRACT FROM AUTHOR]

Formulating a strategy to compete effectively in international markets is one of the major challenges a firm faces. The authors provide insight into how automobile firms devise strategies that respond to the conflicting pressures for local responsiveness and integration in the context of Western Europe, where Japanese automobile firms compete with European-based manufacturers. The authors develop a conceptual framework to test integration-responsiveness in terms of marketing-mix responses and market conditions, using data that cover four major European markets (73% of Western European sales) and a critical period in European integration. The findings indicate that Japanese firms are successfully pursuing standardization strategies rather than fully combining integration and responsiveness. These firms competitively adapt to limited differences between markets, and this strategy appears to be quite successful compared with the European firms' strategies of combining integration and responsiveness. The European strategy appears to undermine the ability to respond to Japanese firms' targeted competitive moves, despite the presence of significant barriers to Japanese exports. Whereas Japanese firms were able to maintain market share, European firms' market shares decreased over the three-year period examined. [ABSTRACT FROM AUTHOR]