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The ENVASSO project (Environmental assessment of soil for monitoring) aims to harmonise the European soil monitoring networks. As part of this project, we made a review, the most exhaustive to date, on the sampling strategies used in the different networks. Soil monitoring networks exist in all the 27 European countries, most of them being members of the European Union. Nevertheless, their strategies are very heterogeneous (selection of monitoring sites, site area, number of sub-samples, time step, soil sampling). Therefore, harmonisation of the strategies remains a difficult issue: indeed most of the changes would make the comparison with the results of the previous campaigns quite impossible. Yet, harmonisation is necessary in order to compare the different European monitoring networks, and from this perspective, some recommendations have been made in that way. We estimate that more than 4000 additional sites should be selected in order to reach an acceptable level of cover age for the European soils. The areas of the sites should preferably be comprised between 100 m2 and 1 ha. The minimal number of sub-samples should be 4, and should be adapted with regards to the within-site variability. A time step of ca 10 yr is recommended. Advices are also formulated for the vertical sampling strategy, the bulk density determination, samples preparation and archiving. However, this harmonisation would require considerable efforts and some countries may not be able to achieve all of these recommendations. Nevertheless, the framework provided in the ENVASSO project can be used to reach a common acceptable level of soil monitoring in Europe.

The ENVASSO project (Environmental assessment of soil for monitoring) aims to harmonise the European soil monitoring networks. As part of this project, we made a review, the most exhaustive to date, on the sampling strategies used in the different networks. Soil monitoring networks exist in all the 27 European countries, most of them being members of the European Union. Nevertheless, their strategies are very heterogeneous (selection of monitoring sites, site area, number of sub-samples, time step, soil sampling). Therefore, harmonisation of the strategies remains a difficult issue: indeed most of the changes would make the comparison with the results of the previous campaigns quite impossible. Yet, harmonisation is necessary in order to compare the different European monitoring networks, and from this perspective, some recommendations have been made in that way. We estimate that more than 4000 additional sites should be selected in order to reach an acceptable level of cover age for the European soils. The areas of the sites should preferably be comprised between 100 m2 and 1 ha. The minimal number of sub-samples should be 4, and should be adapted with regards to the within-site variability. A time step of ca 10 yr is recommended. Advices are also formulated for the vertical sampling strategy, the bulk density determination, samples preparation and archiving. However, this harmonisation would require considerable efforts and some countries may not be able to achieve all of these recommendations. Nevertheless, the framework provided in the ENVASSO project can be used to reach a common acceptable level of soil monitoring in Europe.

We present a detailed response to the critique of "State of the Science of Endocrine Disrupting Chemicals 2012" (UNEP/WHO, 2013) by financial stakeholders, authored by Lamb et al. (2014). Lamb et al.'s claim that UNEP/WHO (2013) does not provide a balanced perspective on endocrine disruption is based on incomplete and misleading quoting of the report through omission of qualifying statements and inaccurate description of study objectives, results and conclusions. Lamb et al. define extremely narrow standards for synthesizing evidence which are then used to dismiss the UNEP/WHO 2013 report as flawed. We show that Lamb et al. misuse conceptual frameworks for assessing causality, especially the Bradford-Hill criteria, by ignoring the fundamental problems that exist with inferring causality from empirical observations. We conclude that Lamb et al.'s attempt of deconstructing the UNEP/WHO (2013) report is not particularly erudite and that their critique is not intended to be convincing to the scientific community, but to confuse the scientific data. Consequently, it promotes misinterpretation of the UNEP/WHO (2013) report by non-specialists, bureaucrats, politicians and other decision makers not intimately familiar with the topic of endocrine disruption and therefore susceptible to false generalizations of bias and subjectivity.

We present a detailed response to the critique of "State of the Science of Endocrine Disrupting Chemicals 2012" (UNEP/WHO, 2013) by financial stakeholders, authored by Lamb et al. (2014). Lamb et al.'s claim that UNEP/WHO (2013) does not provide a balanced perspective on endocrine disruption is based on incomplete and misleading quoting of the report through omission of qualifying statements and inaccurate description of study objectives, results and conclusions. Lamb et al. define extremely narrow standards for synthesizing evidence which are then used to dismiss the UNEP/WHO 2013 report as flawed. We show that Lamb et al. misuse conceptual frameworks for assessing causality, especially the Bradford-Hill criteria, by ignoring the fundamental problems that exist with inferring causality from empirical observations. We conclude that Lamb et al.'s attempt of deconstructing the UNEP/WHO (2013) report is not particularly erudite and that their critique is not intended to be convincing to the scientific community, but to confuse the scientific data. Consequently, it promotes misinterpretation of the UNEP/WHO (2013) report by non-specialists, bureaucrats, politicians and other decision makers not intimately familiar with the topic of endocrine disruption and therefore susceptible to false generalizations of bias and subjectivity.

The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU. © 2013 Bergman et al.; licensee BioMed Central Ltd.

The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU. © 2013 Bergman et al.; licensee BioMed Central Ltd.

Contains fulltext : 47468.pdf (publisher's version ) (Closed access), Collection of exhaled breath condensate (EBC) is a noninvasive method for obtaining samples from the lungs. EBC contains large number of mediators including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, nitrogen oxides, peptides and cytokines. Concentrations of these mediators are influenced by lung diseases and modulated by therapeutic interventions. Similarly EBC pH also changes in respiratory diseases. The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required. Based on the currently available evidence and the consensus of the expert panel for EBC collection, the following general recommendations were put together for oral sample collection: collect during tidal breathing using a noseclip and a saliva trap; define cooling temperature and collection time (10 min is generally sufficient to obtain 1-2 mL of sample and well tolerated by patients); use inert material for condenser; do not use resistor and do not use filter between the subject and the condenser. These are only general recommendations and certain circumstances may dictate variation from them. Important areas for future research involve: ascertaining mechanisms and site of exhaled breath condensate particle formation; determination of dilution markers; improving reproducibility; employment of EBC in longitudinal studies; and determining the utility of exhaled breath condensate measures for the management of individual patients. These studies are required before recommending this technique for use in clinical practice.

Contains fulltext : 47468.pdf (publisher's version ) (Closed access), Collection of exhaled breath condensate (EBC) is a noninvasive method for obtaining samples from the lungs. EBC contains large number of mediators including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, nitrogen oxides, peptides and cytokines. Concentrations of these mediators are influenced by lung diseases and modulated by therapeutic interventions. Similarly EBC pH also changes in respiratory diseases. The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required. Based on the currently available evidence and the consensus of the expert panel for EBC collection, the following general recommendations were put together for oral sample collection: collect during tidal breathing using a noseclip and a saliva trap; define cooling temperature and collection time (10 min is generally sufficient to obtain 1-2 mL of sample and well tolerated by patients); use inert material for condenser; do not use resistor and do not use filter between the subject and the condenser. These are only general recommendations and certain circumstances may dictate variation from them. Important areas for future research involve: ascertaining mechanisms and site of exhaled breath condensate particle formation; determination of dilution markers; improving reproducibility; employment of EBC in longitudinal studies; and determining the utility of exhaled breath condensate measures for the management of individual patients. These studies are required before recommending this technique for use in clinical practice.

Contains fulltext : 47468.pdf (publisher's version ) (Closed access), Collection of exhaled breath condensate (EBC) is a noninvasive method for obtaining samples from the lungs. EBC contains large number of mediators including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, nitrogen oxides, peptides and cytokines. Concentrations of these mediators are influenced by lung diseases and modulated by therapeutic interventions. Similarly EBC pH also changes in respiratory diseases. The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required. Based on the currently available evidence and the consensus of the expert panel for EBC collection, the following general recommendations were put together for oral sample collection: collect during tidal breathing using a noseclip and a saliva trap; define cooling temperature and collection time (10 min is generally sufficient to obtain 1-2 mL of sample and well tolerated by patients); use inert material for condenser; do not use resistor and do not use filter between the subject and the condenser. These are only general recommendations and certain circumstances may dictate variation from them. Important areas for future research involve: ascertaining mechanisms and site of exhaled breath condensate particle formation; determination of dilution markers; improving reproducibility; employment of EBC in longitudinal studies; and determining the utility of exhaled breath condensate measures for the management of individual patients. These studies are required before recommending this technique for use in clinical practice.

The European research project DIFFERENCE (“Dioxins in Food and Feed – Reference methods and New Certified Reference Materials”) was focussed on the development of an alternative methods for analysis of polychlorinated dibenzodioxins (PCDDs), dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dl-PCBs) using comprehensive multi-dimensional gas chromatography (GC×GC), gas chromatography combined with low resolution ion-trap mass spectrometry (GCLRMS/ MS), the CALUX bioassay and an Ah-PCR technique. GC combined with high resolution mass spectrometry (HRMS) was used as a reference method in all comparisons.

From an environmental point of view, an increasing important group of organohalogen compounds are the brominated flame retardants (BFRs), which are widely used in polymers and textiles and applied in construction materials, furniture, and electronic equipment. BFRs with the highest production volume are the polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A (TBBP-A), and hexabromocyclododecane (HBCD). Because of their persistence and low biodegradation profile, several of the PBDE congeners accumulate in biota and are widely found in the aquatic food chain. Their levels in the environment and in humans have increased during the last decades, in contrast to compounds such as polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT), for example. Humans may be exposed to PBDEs mainly through consumption of fatty food of animal origin (e.g., fish), but exposure through skin contact with textiles protected with flame retardants or through inhalation of BFRs volatilized from electronic and electric equipment may also occur. The levels of PBDEs in Swedish human milk showed a doubling in concentration every five years over the period 1972 to 1997 (2,2',4,4'-tetraBDE being the predominant congener). The levels of penta- and hexa-BDEs increased at the same rate in ringed seals collected in the Canadian Arctic from 1981 to 2000. PBDEs exhibit a great variety of biological effects, depending on the bromine substitution pattern. PBDEs are potential endocrine disrupters, based on shared toxicity with the structurally related PCBs, polychlorinated dibenzofurans (PCDFs), and polychlorinated dibenzo-p-dioxins (PCDDs) (partial aryl hydrocarbon- [Ah-] receptor agonist and antagonist activity in vitro, thyroid toxicity, and immune effects), including developmental toxicity. The potency of TBBP-A to interact with thyroid hormone homeostasis is indicated from in vitro studies in which the compound competes with thyroxin (T4) for binding to transthyretin (TTR)

The potential of Human Biomonitoring (HBM) in exposure characterisation and risk assessment is well established in the scientific HBM community and regulatory arena by many publications. The European Environment and Health Strategy as well as the Environment and Health Action Plan 2004-2010 of the European Commission recognised the value of HBM and the relevance and importance of coordination of HBM programmes in Europe. Based on existing and planned HBM projects and programmes of work and capabilities in Europe the Seventh Framework Programme (FP 7) funded COPHES (COnsortium to Perform Human Biomonitoring on a European Scale) to advance and improve comparability of HBM data across Europe. The pilot study protocol was tested in 17 European countries in the DEMOCOPHES feasibility study (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale) cofunded (50%) under the LIFE+ programme of the European Commission. The potential of HBM in supporting and evaluating policy making (including e.g. REACH) and in awareness raising on environmental health, should significantly advance the process towards a fully operational, continuous, sustainable and scientifically based EU HBM programme. From a number of stakeholder activities during the past 10 years and the national engagement, a framework for sustainable HBM structure in Europe is recommended involving national institutions within environment, health and food as well as European institutions such as ECHA, EEA, and EFSA. An economic frame with shared cost implications for national and European institutions is suggested benefitting from the capacity building set up by COPHES/DEMOCOPHES.

Animal and a few human studies suggest that polybrominated diphenyl ethers (PBDEs) may affect male reproductive function. The aim of the present study was to evaluate if male reproductive function was associated with serum level of PBDEs. We evaluated, in a cross-sectional study, the effects of environmental exposure to BDE-47 and BDE-153 on reproductive hormones and semen quality, including markers of DNA damage and apoptosis, in 299 spouses of pregnant women from Greenland, Poland and Ukraine. Adjusted linear regression models indicated no strong associations between BDE-47 or BDE-153 exposure and markers of male semen quality or reproductive hormones. In the largest study to date we demonstrate that BDE-47 and BDE-153 exposure was not associated with altered semen characteristics or reproductive hormones, indicating that male reproductive function is not affected by the exposure level of these compounds in fertile European or Arctic populations.

Animal and a few human studies suggest that polybrominated diphenyl ethers (PBDEs) may affect male reproductive function. The aim of the present study was to evaluate if male reproductive function was associated with serum level of PBDEs. We evaluated, in a cross-sectional study, the effects of environmental exposure to BDE-47 and BDE-153 on reproductive hormones and semen quality, including markers of DNA damage and apoptosis, in 299 spouses of pregnant women from Greenland, Poland and Ukraine. Adjusted linear regression models indicated no strong associations between BDE-47 or BDE-153 exposure and markers of male semen quality or reproductive hormones. In the largest study to date we demonstrate that BDE-47 and BDE-153 exposure was not associated with altered semen characteristics or reproductive hormones, indicating that male reproductive function is not affected by the exposure level of these compounds in fertile European or Arctic populations.

Udgivelsesdato: 2010-May-12, Brominated flame retardants (BFRs), in particular the polybrominated diphenyl ethers (PBDEs), have been used in consumer products for many years to increase fire resistance. Recently, developmental neurotoxicity at very low levels has increased the concern about these compounds. The major objectives of this study were to investigate the maternal and fetal exposure to PBDEs on the basis of maternal and umbilical cord plasma samples and to study the extent of placental transfer for different PBDE congeners. The findings were also compared with previously observed PBDE levels and patterns determined in placental tissue from the same individuals, and the relationship with the external exposure from house dust from the participants' homes was explored. Samples of maternal and umbilical cord plasma from a cohort of 51 pregnant women from the Copenhagen area were collected. Paired maternal and umbilical cord plasma were analysed for BDE-28, 37, 47, 85, 99, 100, 119, 138, 153, 154, 183, 209 and the brominated biphenyl BB-153 using automated SPE extraction and GC-HRMS for the tri- to hepta-BDEs and GC-LRMS (ECNI) for BDE-209. PBDEs were detected in all maternal and umbilical cord plasma samples. The sum of tri- to hexa-BDEs (SigmaPBDE) in maternal plasma varied between 640 and 51,946pg/g lipid weight (lw) with a median level of 1765pg/g lw. In the umbilical cord samples SigmaPBDE varied between 213 and 54,346pg/g lw with a median of 958pg/g lw. The levels observed in fetal and maternal plasma were highly correlated, but the placental transport of PBDE congeners was found to decrease with increasing diphenyl ether bromination. Maternal concentrations were significantly correlated (p<0.05) for most congeners with the previously determined concentrations in placental tissue from the same individuals. Furthermore, positive correlations (p<0.05) were found for BDE-28, 47, 100, 209 and SigmaPBDE in maternal plasma and house dust as well as for SigmaPBDE in umbilical cord pla

Udgivelsesdato: 2010-May-12, Brominated flame retardants (BFRs), in particular the polybrominated diphenyl ethers (PBDEs), have been used in consumer products for many years to increase fire resistance. Recently, developmental neurotoxicity at very low levels has increased the concern about these compounds. The major objectives of this study were to investigate the maternal and fetal exposure to PBDEs on the basis of maternal and umbilical cord plasma samples and to study the extent of placental transfer for different PBDE congeners. The findings were also compared with previously observed PBDE levels and patterns determined in placental tissue from the same individuals, and the relationship with the external exposure from house dust from the participants' homes was explored. Samples of maternal and umbilical cord plasma from a cohort of 51 pregnant women from the Copenhagen area were collected. Paired maternal and umbilical cord plasma were analysed for BDE-28, 37, 47, 85, 99, 100, 119, 138, 153, 154, 183, 209 and the brominated biphenyl BB-153 using automated SPE extraction and GC-HRMS for the tri- to hepta-BDEs and GC-LRMS (ECNI) for BDE-209. PBDEs were detected in all maternal and umbilical cord plasma samples. The sum of tri- to hexa-BDEs (SigmaPBDE) in maternal plasma varied between 640 and 51,946pg/g lipid weight (lw) with a median level of 1765pg/g lw. In the umbilical cord samples SigmaPBDE varied between 213 and 54,346pg/g lw with a median of 958pg/g lw. The levels observed in fetal and maternal plasma were highly correlated, but the placental transport of PBDE congeners was found to decrease with increasing diphenyl ether bromination. Maternal concentrations were significantly correlated (p<0.05) for most congeners with the previously determined concentrations in placental tissue from the same individuals. Furthermore, positive correlations (p<0.05) were found for BDE-28, 47, 100, 209 and SigmaPBDE in maternal plasma and house dust as well as for SigmaPBDE in umbilical cord pla

In a study comprising 50 subjects, we investigated the relationship between acrylamide (AA) intake from food using food frequency questionnaires and the concentration of hemoglobin (Hb) adducts of AA and its genotoxic metabolite glycidamide (GA) as a measure of the internal exposure. A method using solid-phase extraction and liquid chromatography with negative electrospray tandem mass spectrometric (MS/MS) detection for the determination of the Hb adducts as phenylthiohydantoin derivatives in human blood was developed. The limit of quantification for AA- and GA-Hb adducts were 2 and 6 pmol/g globin, respectively, and the between-assay precision was below 25%. The estimated dietary intake of AA was (median and range) 13.5 mu g/day (4.1-72.6) in nonsmokers and 18.3 mu g/day (7.8-32.0) in smokers. In nonsmokers, males had a higher intake than females, 16.6 mu g/ day (18.6-72.6) and 12.8 mu g/day (4.1-30.2), respectively. Non-smokers had a median AA and GA adduct concentration of 36.8 (range 17.9-65.5) and 18.2 (range 6.7-45.6) pmol/g globin, respectively. In smokers, the values were 165.8 (98.8-211) and 83.2 (29.1-99.0) pmol/g globin, respectively. Using multiple linear regression analysis, a significant positive correlation was found between the AA-Hb adduct concentration and the intake of chips/snacks and crisp bread. GA-Hb adduct did not correlate with consumption of any of the main food groups. Neither AA-Hb nor GA-Hb adduct concentration correlated with total dietary intake of AA as calculated from the reported food intake. Adduct concentrations did not correlate with 24 h urinary excretion of mercapturic acid metabolites of AA and GA in the same subjects reported previously.

In a study comprising 50 subjects, we investigated the relationship between acrylamide (AA) intake from food using food frequency questionnaires and the concentration of hemoglobin (Hb) adducts of AA and its genotoxic metabolite glycidamide (GA) as a measure of the internal exposure. A method using solid-phase extraction and liquid chromatography with negative electrospray tandem mass spectrometric (MS/MS) detection for the determination of the Hb adducts as phenylthiohydantoin derivatives in human blood was developed. The limit of quantification for AA- and GA-Hb adducts were 2 and 6 pmol/g globin, respectively, and the between-assay precision was below 25%. The estimated dietary intake of AA was (median and range) 13.5 mu g/day (4.1-72.6) in nonsmokers and 18.3 mu g/day (7.8-32.0) in smokers. In nonsmokers, males had a higher intake than females, 16.6 mu g/ day (18.6-72.6) and 12.8 mu g/day (4.1-30.2), respectively. Non-smokers had a median AA and GA adduct concentration of 36.8 (range 17.9-65.5) and 18.2 (range 6.7-45.6) pmol/g globin, respectively. In smokers, the values were 165.8 (98.8-211) and 83.2 (29.1-99.0) pmol/g globin, respectively. Using multiple linear regression analysis, a significant positive correlation was found between the AA-Hb adduct concentration and the intake of chips/snacks and crisp bread. GA-Hb adduct did not correlate with consumption of any of the main food groups. Neither AA-Hb nor GA-Hb adduct concentration correlated with total dietary intake of AA as calculated from the reported food intake. Adduct concentrations did not correlate with 24 h urinary excretion of mercapturic acid metabolites of AA and GA in the same subjects reported previously.

We present a compilation and analysis of 1099 Holocene relative shore-level (RSL) indicators locatedaround the Baltic Sea including 867 relative sea-level data points and 232 data points from the Ancylus Lake and the following transitional phase. The spatial distribution covers the Baltic Sea and near-coastal areas fairly well, but some gaps remain mainly in Sweden. RSL data follow the standardized HOLSEA format and, thus, are ready for spatially comprehensive applications in, e.g. glacial isostatic adjustment (GIA) modelling. We apply a SQL database system to store the nationally provided data sets in their individual form and to map the different input into the HOLSEA format as the information content of the individual data sets from the Baltic Sea area differs. About 80% of the RSL data is related to the last marine stage in Baltic Sea history after 8.5 ka BP (thousand years before present). These samples are grouped according to their dominant RSL tendencies into three clusters: regions with negative, positive and complex (transitional) RSL tendencies. Overall, regions with isostatic uplift driven negative tendencies dominate and show regression in the Baltic Sea basin during the last marine stage. Shifts from positive to negative tendencies in RSL data from transitional regions show a mid-Holocene highstand around 7.5 - 6.5 ka BP which is consistent with the end of the final melting of the Laurentide Ice Sheet. Comparisons of RSL data with GIA predictions including global ICE-5G and ICE-6G_C ice histories show goodfit withRSL data from the regions with negative tendencies, whereas in the transitional areas in the eastern Baltic, predictions for the mid-Holocene clearly overestimate the RSL and fail to recover the mid-Holocene RSL highstand derived from the proxy reconstructions. These results motivate improvements of ice-sheet and Earth-structure models and show the potential and benefits of the new compilation forfuture studies.

We present a compilation and analysis of 1099 Holocene relative shore-level (RSL) indicators locatedaround the Baltic Sea including 867 relative sea-level data points and 232 data points from the Ancylus Lake and the following transitional phase. The spatial distribution covers the Baltic Sea and near-coastal areas fairly well, but some gaps remain mainly in Sweden. RSL data follow the standardized HOLSEA format and, thus, are ready for spatially comprehensive applications in, e.g. glacial isostatic adjustment (GIA) modelling. We apply a SQL database system to store the nationally provided data sets in their individual form and to map the different input into the HOLSEA format as the information content of the individual data sets from the Baltic Sea area differs. About 80% of the RSL data is related to the last marine stage in Baltic Sea history after 8.5 ka BP (thousand years before present). These samples are grouped according to their dominant RSL tendencies into three clusters: regions with negative, positive and complex (transitional) RSL tendencies. Overall, regions with isostatic uplift driven negative tendencies dominate and show regression in the Baltic Sea basin during the last marine stage. Shifts from positive to negative tendencies in RSL data from transitional regions show a mid-Holocene highstand around 7.5 - 6.5 ka BP which is consistent with the end of the final melting of the Laurentide Ice Sheet. Comparisons of RSL data with GIA predictions including global ICE-5G and ICE-6G_C ice histories show goodfit withRSL data from the regions with negative tendencies, whereas in the transitional areas in the eastern Baltic, predictions for the mid-Holocene clearly overestimate the RSL and fail to recover the mid-Holocene RSL highstand derived from the proxy reconstructions. These results motivate improvements of ice-sheet and Earth-structure models and show the potential and benefits of the new compilation forfuture studies.

Highlights: • A first standardized and publicly available Holocene relative sea-level database for the Baltic Sea is presented. • The database holds 1099 revised data points with an estimation of vertical and chronological uncertainties. • Negative RSL tendencies prevail over the positive and complex tendencies in the Baltic Sea Basin. • Mid-Holocene RSL highstand occurred around 7.5–6.5 ka BP being consistent with the end of the final melting of the LIS. • The contribution of ice loading in the eastern Baltic Sea Basin is likely overestimated in the ICE-5G and ICE-6G_C models. Abstract: We present a compilation and analysis of 1099 Holocene relative shore-level (RSL) indicators located around the Baltic Sea including 867 relative sea-level data points and 232 data points from the Ancylus Lake and the following transitional phase. The spatial distribution covers the Baltic Sea and near-coastal areas fairly well, but some gaps remain mainly in Sweden. RSL data follow the standardized HOLSEA format and, thus, are ready for spatially comprehensive applications in, e.g., glacial isostatic adjustment (GIA) modelling. We apply a SQL database system to store the nationally provided data sets in their individual form and to map the different input into the HOLSEA format as the information content of the individual data sets from the Baltic Sea area differs. About 80% of the RSL data is related to the last marine stage in Baltic Sea history after 8.5 ka BP (thousand years before present). These samples are grouped according to their dominant RSL tendencies into three clusters: regions with negative, positive and complex (transitional) RSL tendencies. Overall, regions with isostatic uplift driven negative tendencies dominate and show regression in the Baltic Sea basin during the last marine stage. Shifts from positive to negative tendencies in RSL data from transitional regions show a mid-Holocene highstand around 7.5–6.5 ka BP which is consistent with the end of the final me

Highlights: • A first standardized and publicly available Holocene relative sea-level database for the Baltic Sea is presented. • The database holds 1099 revised data points with an estimation of vertical and chronological uncertainties. • Negative RSL tendencies prevail over the positive and complex tendencies in the Baltic Sea Basin. • Mid-Holocene RSL highstand occurred around 7.5–6.5 ka BP being consistent with the end of the final melting of the LIS. • The contribution of ice loading in the eastern Baltic Sea Basin is likely overestimated in the ICE-5G and ICE-6G_C models. Abstract: We present a compilation and analysis of 1099 Holocene relative shore-level (RSL) indicators located around the Baltic Sea including 867 relative sea-level data points and 232 data points from the Ancylus Lake and the following transitional phase. The spatial distribution covers the Baltic Sea and near-coastal areas fairly well, but some gaps remain mainly in Sweden. RSL data follow the standardized HOLSEA format and, thus, are ready for spatially comprehensive applications in, e.g., glacial isostatic adjustment (GIA) modelling. We apply a SQL database system to store the nationally provided data sets in their individual form and to map the different input into the HOLSEA format as the information content of the individual data sets from the Baltic Sea area differs. About 80% of the RSL data is related to the last marine stage in Baltic Sea history after 8.5 ka BP (thousand years before present). These samples are grouped according to their dominant RSL tendencies into three clusters: regions with negative, positive and complex (transitional) RSL tendencies. Overall, regions with isostatic uplift driven negative tendencies dominate and show regression in the Baltic Sea basin during the last marine stage. Shifts from positive to negative tendencies in RSL data from transitional regions show a mid-Holocene highstand around 7.5–6.5 ka BP which is consistent with the end of the final me

Highlights: • A first standardized and publicly available Holocene relative sea-level database for the Baltic Sea is presented. • The database holds 1099 revised data points with an estimation of vertical and chronological uncertainties. • Negative RSL tendencies prevail over the positive and complex tendencies in the Baltic Sea Basin. • Mid-Holocene RSL highstand occurred around 7.5–6.5 ka BP being consistent with the end of the final melting of the LIS. • The contribution of ice loading in the eastern Baltic Sea Basin is likely overestimated in the ICE-5G and ICE-6G_C models. Abstract: We present a compilation and analysis of 1099 Holocene relative shore-level (RSL) indicators located around the Baltic Sea including 867 relative sea-level data points and 232 data points from the Ancylus Lake and the following transitional phase. The spatial distribution covers the Baltic Sea and near-coastal areas fairly well, but some gaps remain mainly in Sweden. RSL data follow the standardized HOLSEA format and, thus, are ready for spatially comprehensive applications in, e.g., glacial isostatic adjustment (GIA) modelling. We apply a SQL database system to store the nationally provided data sets in their individual form and to map the different input into the HOLSEA format as the information content of the individual data sets from the Baltic Sea area differs. About 80% of the RSL data is related to the last marine stage in Baltic Sea history after 8.5 ka BP (thousand years before present). These samples are grouped according to their dominant RSL tendencies into three clusters: regions with negative, positive and complex (transitional) RSL tendencies. Overall, regions with isostatic uplift driven negative tendencies dominate and show regression in the Baltic Sea basin during the last marine stage. Shifts from positive to negative tendencies in RSL data from transitional regions show a mid-Holocene highstand around 7.5–6.5 ka BP which is consistent with the end of the final me

En este trabajo se analiza el impacto en forma de aprendizaje y transferencia tecnológica de aquellos proyectos de I+D+i financiados con fondos públicos. Analizando el nivel de aprendizaje y de transferencia tecnológica, el perfil de las empresas con un mayor o menor nivel de aprendizaje. Además se analiza la relación del aprendizaje con el efecto de adicionalidad financiera de las ayudas, es decir, se relaciona el nivel de aprendizaje con el impacto de las ayudas sobre el gasto en I+D de las empresas subvencionadas. La conclusión principal de este trabajo es que las características del comportamiento innovador de las empresas están altamente relacionadas con el nivel de aprendizaje. Resulta que las empresas con un mayor esfuerzo y orientación innovador consideran los efectos de aprendizaje mucho más importante que las empresas pocas innovadoras. Además se ha detectado un grupo de empresas pequeñas y pocas innovadoras que apenas han mejorado su capacidad tecnológica. Parece que para este tipo de empresas el proceso de aprendizaje no esta asegurada debido a la falta de experiencia y una masa crítica en un campo tan complejo y especializado como la innovación., This paper analyzes the impact in the form of learning and technology transfer of those publicly funded R & D + I proyects. Analyzing the level of learning and technology transfer, the profile of the companies with a higher or lower level of learning. It also analyzes the relationship between learning and financial additionality aid effect, it means, the level of learning related to the impact of aid on expenditure on R & D of the subsidized firms. The main conclusion of this study is that the innovative behavior characteristics of firms are highly correlated with the level of learning. It turns out that companies with a major effort and oriented to innovative learning effects are considered much more important than a few innovative companies. It has also identified a group of small enterprises and hardly few have improved the innovative technology. It seems that for these companies the learning process is not assured due to lack of expertise and critical mass in a field as complex and specialized as innovation.

En este documento de trabajo analizamos diversos instrumentos utilizados por los gobiernos regionales de los “Länder” alemanes. Los instrumentos aquí analizados han sido evaluados por responsables políticos en Alemania para comprobar su eficacia y utilidad, ésto nos permite obtener conocimientos muy detallados sobre su posible impacto –nivel de éxito o fracaso- y las razones, los problemas y soluciones prácticos de su implantación y evolución, así como la respuesta de las empresas a los incentivos. Por lo que para cada instrumento se analizan los posibles problemas y soluciones de su aplicación en el caso de España. En concreto los instrumentos analizados son los siguientes: el programa EXIST —destinado a impulsar la creación de spin-offs a partir de las universidades—, el modelo Steinbeis y los Institutos Asociados—que promueven la transferencia tecnológica entre empresas y el sector universitario o las escuelas politécnicas—, el programa INNOMAN — cuyo objeto es facilitar la transferencia tecnológica y la gestión externa de la innovación en PYMES—, “La subvención de los Costes salariales para empleados dedicados a la innovación”, así como el modelo Fraunhofer, que destaca por la doble articulación de su personal debido a sus relaciones tanto con el mundo empresarial como con el académico, así como por su peculiar sistema de financiación. ABSTRACT In this working paper we present several regional policy instruments for R&D and innovation policies used in the case of Germany. We present not only the outline and the structure of the instruments, and we also analyse its possible use in the case of the Spanish regions. We analyse their efficiency and usefulness which allows us to detect detailed information about the possible impact –level of success and failure- and its determinants, the problems and solutions during the implementation and the response of the enterprises to the incentives. And at the end of each section we offer an overview of the lessons learned for

Se analiza la tasa de cobertura, dentro del sistema productivo español, de los créditos de bajo interés para proyectos de I+D ofrecido por el estado español. Abstract: The first part of this paper presents a short introduction concerning the importance of evaluation studies concerning technology policies and a brief discussion about the problems of the selection and use of comparison groups. The empirical part of this paper analyses the diffusion and take-up rate, by Spanish firms, of the low interest credits for R&D projects offered by the Spanish government. This form of public finance of the company’s R&D activity in Spain is carried out by the Centre for the Development of Industrial Technology (CDTI) an institution which plays a fundamental role in the Spanish national and regional system of innovation. The empirical information suggests that less than 1% of all industrial firms, 7% of innovative firms in the broad sense (undertaken any kind of innovative activities) and 23% of the innovative firms in a strict sense (doing R&D) were supported once or in several occasions by the Spanish government over the period 1984-1994. The credits are meant as a general non selective instrument for the promotion of technological development which should be available to all firms that are carrying out innovative activities. But the comparison of the supported firms with other innovative firms makes clear that some firms are excluded or are excluding themselves from this public support scheme.