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HERC2 gene encodes an E3 ubiquitin ligase involved in several cellular processes by regulating the ubiquitylation of different protein substrates. Biallelic pathogenic sequence variants in the HERC2 gene are associated with HERC2 Angelman-like syndrome. In pathogenic HERC2 variants, complete absence or marked reduction in HERC2 protein levels are observed. The most common pathological variant, c.1781C > T (p.Pro594Leu), encodes an unstable HERC2 protein. A better understanding of how pathologic HERC2 variants affect intracellular signalling may aid definition of potential new therapies for these disorders. For this purpose, we studied patient-derived cells with the HERC2 Pro594Leu variant. We observed alteration of mitogen-activated protein kinase signalling pathways, reflected by increased levels of C-RAF protein and p38 phosphorylation. HERC2 knockdown experiments reproduced the same effects in other human and mouse cells. Moreover, we demonstrated that HERC2 and RAF proteins form molecular complexes, pull-down and proteomic experiments showed that HERC2 regulates C-RAF ubiquitylation and we found out that the p38 activation due to HERC2 depletion occurs in a RAF/MKK3-dependent manner. The displayed cellular response was that patient-derived and other human cells with HERC2 deficiency showed higher resistance to oxidative stress with an increase in the master regulator of the antioxidant response NRF2 and its target genes. This resistance was independent of p53 and abolished by RAF or p38 inhibitors. Altogether, these findings identify the activation of C-RAF/MKK3/p38 signalling pathway in HERC2 Angelman-like syndrome and highlight the inhibition of RAF activity as a potential therapeutic option for individuals affected with these rare diseases. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This study was funded by the following grants: JLR (Agencia Estatal de Investigación: PID2020-120344RB-I00/MCIN/AEI/10.13039/501100011033) and FV (PDC2021-121776-I00 and PID2020-117278 GB-I00 from MCIN/AEI/10.13039/501100011033 and FEDER “Una manera de hacer Europa” “NextGenerationEU”/PRTR. And Grant 202038-30 from “La Marató de TV3”). As well, this article is based upon work from COST Action ProteoCure CA20113, supported by COST (European Cooperation in Science and Technology). JSG and AMM received FPU Fellowships (FPU17/02413 and FPU18/06325, respectively) from the Spanish Ministry of Universities.

Protein ubiquitylation acts as a complex cell signaling mechanism since the formation of different mono- and polyubiquitin chains determines the substrate’s fate in the cell. E3 ligases define the specificity of this reaction by catalyzing the attachment of ubiquitin to the substrate protein. Thus, they represent an important regulatory component of this process. Large HERC ubiquitin ligases belong to the HECT E3 protein family and comprise HERC1 and HERC2 proteins. The physiological relevance of the Large HERCs is illustrated by their involvement in different pathologies, with a notable implication in cancer and neurological diseases. Understanding how cell signaling is altered in these different pathologies is important for uncovering novel therapeutic targets. To this end, this review summarizes the recent advances in how the Large HERCs regulate the MAPK signaling pathways. In addition, we emphasize the potential therapeutic strategies that could be followed to ameliorate the alterations in MAPK signaling caused by Large HERC deficiencies, focusing on the use of specific inhibitors and proteolysis-targeting chimeras.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): CIBERCV of cardiovascular diseases; CIBERESP. OnBehalf REGICOR investigators Background Although myocardial infarction (MI) severity trends are systematically measured with mortality rates, MI incidence trends and the precision of its estimation by linkage of anonymized electronic databases are relatively untested. We validated a linked-data method (LDM) to estimate a population MI incidence and case-fatality, and to analyse the 1990-2016 trends in North-Eastern Spain. Methods LDM consisted of linking MI hospital discharges (n = 4,533,981) and mortality registry data (n = 40,676) for 2008-2016, selecting key MI diagnostic codes. The prospective REGICOR study, including all MI cases in Girona, 1990-2009, was used as the gold standard for validation purposes. Standardized MI cumulated incidence and 28-day case fatality for population aged 35-74 years was calculated, 1990-2016 trends were analysed by linear and joinpoint regression and annual percentage change (APC). Results LDM and REGICOR MI incidence and case-fatality estimates were similar for 2008-09 (Table). LDM MI incidence and case-fatality significantly decreased: APC 1990-2016 [95% CI]) was -1.8 [-2.6;-0.9] in women, and APC 2002-2016 -2.8 [-3.8;-1.8] in men; case-fatality APC 1990-2016 was -4.7% [-5.7;-3.8] in women and APC 1995-2005 -6.5%[-8.5;-4.5] in men. Conclusions LDM in population aged 35-74 reliably estimated MI incidence and case-fatality. MI incidence and case-fatality significantly decreased after 1990. Comparative analysis of REGICOR vs LDM REGICOR 2008-2009 LDM 2008-2009 Estimate 95% CI Estimate 95% CI P-Value Cumulated incidence Men 245.4 228.3; 262.5 239.7 222.5; 256.3 0.626 Women 61.1 52.6; 69.6 58.2 49.9; 66.4 0.626 Overall 28-day case-fatality Men 23.5% 19.7; 27.2 21.3% 17.8; 24.9 0.422 Women 19.3% 6.7; 31.9 17.7% 6.3; 29.1 0.855 In-hospital case-fatality Men 6.9% 4.8; 9.0 5.7% 3.8; 7.6 0.394 Women 5.0% 1.9; 8.2 3.7% 1.0; 6.5 0.540 Pre-hospital case-fatality Men 16.5% 11.8; 21.3 15.6% 11.2; 20.1 0.791 Women 14.2 % 6.6; 21.9 14.0% 6.3; 21.7 0.961 CI Confidence Interval

El presente trabajo es una continuación del monitoreo permanente que se viene realizando desde 2009 en el Parc Natural de la Serra de Collserola, y se centra en la actividad de las familias de Diptera e Hymenoptera muestreadas en un bosque mixto mediterráneo Pinus- Quercus. De abril a octubre de 2012 se realizaron muestreos en el dosel y sotobosque, con un total de 7789 especímenes muestreados y resultando Diptera (1393; 17,9%) e Hymenoptera (1039; 13,3%) entre los grupos dominantes en el área. Se encontró una clara estratificación de la fauna, donde el dosel se mostró no solo como el estrato donde se desarrolla el mayor volumen de la actividad de los artrópodos, sino también como el estrato más biodiverso. Estos resultados contrastan con estudios realizados anteriormente en la misma área, donde el sotobosque jugaba un papel dominante sobre el dosel. Las diferencias entre los resultados del primer estudio y los obtenidos en este trabajo evidencian la necesidad de focalizar la atención hacia los diversos factores que marcan la actividad de los artrópodos entre estratos con exposición solar total y parcial., This work is part of permanent monitoring that has been conducted since 2009 in the Serra de Collserola Natural Park, and focuses on the activities of families of Diptera and Hymenoptera sampled in a Mediterranean mixed forest of Pinus-Quercus. From April to October of 2012, samples were taken in the canopy and understory, with a total of 7789 specimens with Diptera (1393; 17.9 %) and Hymenoptera (1039; 13.3 %) among the dominant groups. We found a clear stratification of arthropods, where the canopy showed not only as the layer where the bulk of the activity takes place, but also as the most biodiverse stratum. These results contrast with previous studies in the same area where the understory played a dominant role compared to the canopy. The differences between the results of the first study and those obtained in this study show the need to focus attention on the various factors that influence the activity of arthropods between strata with full and partial sun exposure.

© 2020 by the authors., HERC proteins are ubiquitin E3 ligases of the HECT family. The HERC subfamily is composed of six members classified by size into large (HERC1 and HERC2) and small (HERC3–HERC6). HERC family ubiquitin ligases regulate important cellular processes, such as neurodevelopment, DNA damage response, cell proliferation, cell migration, and immune responses. Accumulating evidence also shows that this family plays critical roles in cancer. In this review, we provide an integrated view of the role of these ligases in cancer, highlighting their bivalent functions as either oncogenes or tumor suppressors, depending on the tumor type. We include a discussion of both the molecular mechanisms involved and the potential therapeutic strategies., J.L.R. is supported by the Spanish Ministry of Science and Innovation (BFU2016-80295-R, SAF2017-90900-REDT, and UBIRed). X.R.B. is supported by grants from the Castilla-León Government (CSI252P18, CLC-2017-01), the Spanish Ministry of Science and Innovation (SAF2015-64556-R, RTI2018-096481-B-100) and the Spanish Association against Cancer (GC16173472GARC). X.R.B.’s institution is supported by the Programa de Apoyo a Planes Estratégicos de Investigación de Estructuras de Investigación de Excelencia of the Castilla-León autonomous government (CLC-2017-01). Both Spanish and Castilla-León government-associated funding is partially supported by the European Regional Development Fund. J.S.-G. and A.M.-M. received FPU Fellowships (FPU17/02413 and FPU18/06325, respectively) from the Spanish Ministry of Science, Innovation and Universities.

8 pages, 4 figures, 2 figures, supplementary figures https://doi.org/10.1016/j.scitotenv.2021.151443., COVID-19 has led to global population lockdowns that have had indirect effects on terrestrial and marine fauna, yet little is known on their effects on marine planktonic communities. We analysed the effect of the spring 2020 lockdown in a marine coastal area in Blanes Bay, NW Mediterranean. We compared a set of 23 oceanographic, microbial and biogeochemical variables sampled right after the strict lockdown in Spain, with data from the previous 15 years after correcting for long-term trends. Our analysis shows a series of changes in the microbial communities which may have been induced by the combination of the decreased nitrogen atmospheric load, the lower wastewater flux and the reduced fishing activity in the area, among other factors. In particular, we detected a slight decrease beyond the long-term trend in chlorophyll a, in the abundance of several microbial groups (phototrophic nanoflagellates and total prokaryotes) and in prokaryotic activity (heterotrophic prokaryotic production and β-glucosidase activity) which, as a whole, resulted in a moderate increase of oligotrophy in Blanes Bay after the lockdown., Data from the specific sampling in 2020 were supported by the MIAU project of the Spanish Ministerio de Ciencia e Innovación, MICINN (RTI2018-101025-B-I00), while previous years were supported by many Spanish and EU projects. Other projects of the MICINN also supported this research: DOGMA (PID2020-112653GB-I00), DIVAS (PID2019-108457RB-I00), and HICCUP (RTI2018-095083-B-I00). We thank Amanda Con and Juan Rodríguez for providing data of the Blanes WWTP. We sincerely thank Irene Forn, Carolina Antequera, Arturo Lucas, Elisabet Laia Sà and Vanessa Balagué for their invaluable laboratory work. The work of the authors was supported by Generalitat de Catalunya Grups de Recerca Consolidats 2017SGR1568 and 2017SGR1011. This study acknowledges institutional support from the “Severo Ochoa Centre of Excellence” accreditation (CEX2019-000928-S).

Resumen Introduccion y objetivos Estudiar la validez de la funcion SCORE original de bajo riesgo sin y con colesterol unido a lipoproteinas de alta densidad y SCORE calibrada en poblacion espanola. Metodos Analisis agrupado con datos individuales de 12 estudios de cohorte de base poblacional. Se incluyo a 30.919 participantes de 40-64 anos sin enfermedades cardiovasculares en el momento del reclutamiento, que se siguieron durante 10 anos para la mortalidad cardiovascular contemplada en el proyecto SCORE. La validez de las funciones se analizo mediante el area bajo la curva ROC (discriminacion) y el test de Hosmer-Lemeshow (calibracion), respectivamente. Resultados Se dispuso de 286.105 personas/ano. La mortalidad a 10 anos por causas cardiovasculares fue del 0,6%. La razon de casos esperados/observados fue de 9,1, 6,5 y 9,1 en varones y de 3,3, 1,3 y 1,9 en mujeres con las funciones SCORE original de bajo riesgo sin y con colesterol unido a lipoproteinas de alta densidad y SCORE calibrada, respectivamente; diferencias estadisticamente significativas con el test de calibracion de Hosmer-Lemeshow entre la mortalidad predicha con SCORE y la observada (p Conclusiones Todas las versiones de las funciones SCORE disponibles en Espana sobreestiman significativamente la mortalidad cardiovascular observada en la poblacion espanola. A pesar de la aceptable capacidad de discriminacion, la prediccion del numero de acontecimientos cardiovasculares mortales (calibracion) fue significativamente imprecisa.

Resumen Introduccion y objetivos La fibrilacion auricular (FA) es la arritmia mas frecuente en la practica clinica. Nuestro objetivo es determinar la asociacion entre la duracion de la onda P y el bloqueo interauricular (BIA) avanzado y la FA. Metodos Estudio de casos y controles anidado en una cohorte (REGICOR: REgistre GIroni del COR) emparejada por edad y sexo. Entre 1999 y 2005 se realizaron 2 estudios transversales en los que participaron 9.380 individuos; entre 2009 y 2013 se invito a todos los participantes a un segundo examen. Se selecciono a los participantes de 25-79 anos que participaron en el segundo examen. Dos observadores determinaron la duracion y la morfologia de la onda P para determinar la presencia de BIA (ausencia, parcial o avanzado). Resultados La mediana de seguimiento fue 7,12 anos. Se incluyo a 80 participantes que sufrieron FA y 160 controles. La duracion de la onda P y la presencia de BIA se asociaron con la FA. Al considerar simultaneamente las 2 variables, solo la duracion de la onda P (≥ 110 ms) se asocio con la aparicion de FA. Las odds ratio de FA para la duracion de la onda P entre 110-119, 120-129 y ≥ 130 ms frente a Conclusiones La duracion de la onda P ≥ 110 ms aumenta el riesgo de FA. No parece que el BIA avanzado aporte un riesgo adicional al de la duracion de la onda P.

The p53 tumor suppressor protein is a transcription factor that plays a prominent role in protecting cells from malignant transformation. Protein levels of p53 and its transcriptional activity are tightly regulated by the ubiquitin E3 ligase MDM2, the gene expression of which is transcriptionally regulated by p53 in a negative feedback loop. The p53 protein is transcriptionally active as a tetramer, and this oligomerization state is modulated by a complex formed by NEURL4 and the ubiquitin E3 ligase HERC2. Here, we report that MDM2 forms a complex with oligomeric p53, HERC2, and NEURL4. HERC2 knockdown results in a decline in MDM2 protein levels without affecting its protein stability, as it reduces its mRNA expression by inhibition of its promoter activation. DNA damage induced by bleomycin dissociates MDM2 from the p53/HERC2/NEURL4 complex and increases the phosphorylation and acetylation of oligomeric p53 bound to HERC2 and NEURL4. Moreover, the MDM2 promoter, which contains p53‐response elements, competes with HERC2 for binding of oligomeric, phosphorylated and acetylated p53. We integrate these findings in a model showing the pivotal role of HERC2 in p53‐MDM2 loop regulation. Altogether, these new insights in p53 pathway regulation are of great interest in cancer and may provide new therapeutic targets., The ubiquitin ligase MDM2 regulates protein levels of the p53 tumor suppressor protein. p53 is a transcription factor that regulates MDM2 expression. This study reports the formation of a NEURL4/HERC2/oligomeric p53/MDM2 complex and how it participates in the stability of p53 and MDM2 proteins and in the transcriptional activation of p53 in response to DNA damage.

Homologous to the E6AP carboxyl terminus (HECT) and regulator of chromosome condensation 1 (RCC1)-like domain-containing proteins (HERCs) belong to the superfamily of ubiquitin ligases. HERC proteins are divided into two subfamilies, Large and Small HERCs. Despite their similarities in terms of both structure and domains, these subfamilies are evolutionarily very distant and result from a convergence phenomenon rather than from a common origin. Large HERC genes, HERC1 and HERC2, are present in most metazoan taxa. They encode very large proteins (approximately 5,000 amino acid residues in a single polypeptide chain) that contain more than one RCC1-like domain as a structural characteristic. Accumulating evidences show that these unusually large proteins play key roles in a wide range of cellular functions which include neurodevelopment, DNA damage repair, and cell proliferation. To better understand the origin, evolution, and function of the Large HERC family, this minireview provides with an integrated overview of their structure and function and details their physiological implications. This study also highlights and discusses how dysregulation of these proteins is associated with severe human diseases such as neurological disorders and cancer.

10 pages, 4 figures, 4 tables, The analysis of fish spillover from marine protected areas (MPA) is often based on data collected after the implementation of protection. In the present study we used a methodology based on the combination of Vessel Monitoring System (VMS) and landings data before and after the establishment of protection for spillover analysis. We defined areas of similar size to the protected zone in order to compare them over time. In addition to the no-take zone effectiveness, using this methodology, we were also able to analyze the spatiotemporal behavior of the hake population. Our results on the hake distribution were consistent with those of previous studies. The juveniles were concentrated on the continental shelf (0 - 200 m), whereas the adults were found over the shelf and the slope (300 - 500 m). We found evidence suggesting a positive spillover effect for the juveniles on the continental shelf, enhancing its fishing yields. The analysis of longer time series on the performance of the protected area combined with field sampling inside the no-take zone would lead us to confirm effective spillover effect contributing to fisheries’ long-term sustainability in this zone, This study was supported by the Government of Catalonia through FEMP (European Maritime and Fisheries Fund): ARP005/17/00174, With the funding support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S), of the Spanish Research Agency (AEI)

Foreshore Assessment using Space Technology [1] (FAST, 2014-2018, EU-FP7 607131) has created a platform for EU Earth Observation (EO) Programme Copernicus services, to support cost-effective, nature-based shoreline protection. Called “MI-SAFE”, it is developed with Open Source (OS) Intelligent Geographical Information System (IGIS) components from the OpenEarth [2] stack, and interoperable OGC standards. Processing large volumes of EO data for global coastal vegetation and elevation products is done using the cloud native Google Earth Engine platform. These are intelligently combined with other layers to form the inputs to XBeach [3], an OS hydrodynamic model developed by Deltares, UNESCO-IHE and TU Delft. Access to data is via a web-based user interface with different resolutions and complexity (Educational and Expert modes), and a Catalogue Service for the Web (CSW). MI-SAFE is intended to be a sustainable contribution to coastal Nature-based Solutions, increasing both awareness and facilitating advanced modelling, within the engineering community.

Climate change derived in changing weather patterns making risks very difficult to predict and one very representative example is flood events. Flooding due to overflow from water bodies can be analyzed through change detection techniques with satellite imagery from the Synthetic Aperture Radar (SAR) sensors such as the one on board the ESA Sentinel-1. This analysis will help us have a better understanding of the floodable areas and therefore provide better support and response to these events. The presented open-source Quantum GIS (QGIS) plugin for flood mapping provides this analysis to a growing earth observation user community as described in the following abstract. The flood mapping QGIS plugin has been developed in the context of a FP7 EU funded earth observation project named RASOR (Rapid Analysis and Spatialisation Of Risk), a multi-hazard risk analysis and assessment to support the full cycle of disaster management. The plugin available through QGIS repository enables any user to execute the processing of flood maps based on S1 data in their local work environments. Moreover, results can be uploaded to the RASOR platform in order to be shared with the community. The RASOR Floodmap plugin takes as input two Sentinel-1 SAR images, one taken as reference and another just after the flood event. In parallel, the Area Of Interest (AOI) can be established with one or more polygons in a Shapefile format. The algorithm calibrates and co-registers both images to obtain a change detection RGB GeoTiff file. A K-Means filtering is performed in order to smooth the results and in preparation for the last classification step. Classification is performed by the plugin in which one or more classes are identified as flooded area and therefore polygonise of the extent is conducted, the user can make use of the QGIS workspace in order to supervise results and perform the necessary refinements, for instance by comparing them with different optical images or land cover information. The algorithm is run with the assistance of a Graphical User Interface (GUI) developed in PyQT for the QGIS open-source software suite. The underlying components for this algorithm are well-known open-source earth observation tools and libraries such as SNAP (Sentinel Application Platform), Orfeo toolbox and GDAL/Osgeo. The work presented illustrates how open source software provides valuable tools to exploit Earth Observation data, by enabling the creation of new interfaces for the geoscientist community. Moreover, it contributes to the study of flood events based on S1, and the use of flood map information for the planning of emergency actions, the improvement of flood forecasts and its use in water resource management by international groups.

Background Current evidence shows that single-stage treatment of concomitant choledocholithiasis and cholelithiasis is as effective and safe as two-stage treatment. However, several studies suggest that single-stage approach requires shorter hospitalization time and is more cost-effective than the two-stage approach, even though it requires considerable training. This study aimed to evaluate the implementation of a protocol for managing concomitant choledocholithiasis and cholelithiasis using single-stage treatment. Methods A prospective cohort study of patients diagnosed with cholelithiasis and choledocholithiasis who were treated with the single-stage treatment – transcystic instrumentation, choledocotomy or intraoperative endoscopic retrograde cholangiopancreatography (ERCP) – between September 2010 and June 2017 was assessed. The primary outcomes were complications, hospital stay, operative time and recurrence rate. Results 164 patients were enrolled. 141 (86%) were operated laparoscopically. Preoperatively diagnosed stones were not found by intraoperative imaging or disappeared after “flushing” in 38 patients (23.2%). Surgical approach was transcystic in 45 patients (27.41%), choledochotomy in 74 (45.1%), intraoperative ERCP in 4 (2.4%), and bilioenteric derivation in 3 (1.8%). Mean hospitalization stay was 4.4 days. Mean operative time was 166 min 27 patients (16.5%) had complications and 1 patient was exitus (0.6%). Recurrence rate was 1.2%. Conclusions Single-stage approach is a safe and effective management option for concomitant cholelithiasis and choledocolithiasis. Furthermore, a significant number of common bile duct stones pass spontaneously to duodenum or can benefit from a transcystic approach, with presumable low morbidity and cost-efficiency.

Information systems are widely used to enable access to scientific data by different user communities. MyOcean information system is a good example of such applications in Europe. The present work describes a specific distributed information system for Ocean Numerical Model (ONM) data in the scope of the INDESO project, a project focused on Infrastructure Development of Space Oceanography in Indonesia. INDESO, as part of the Blue Revolution policy conducted by the Indonesian government for the sustainable development of fisheries and aquaculture, presents challenging service requirements in terms of services performance, reliability, security and overall usability. Following state-of-the-art technologies on scientific data networks, this robust information system provides a high level of interoperability of services to discover, view and access INDESO dynamic ONM scientific data. The entire system is automatically updated four times a day, including dataset metadata, taking into account every new file available in the data repositories. The INDESO system architecture has been designed in great part around the extension and integration of open-source flexible and mature technologies. It involves three separate modules: web portal, dissemination gateway, and user administration. Supporting different gridded and non-gridded data, the INDESO information system features search-based data discovery, data access by temporal and spatial subset extraction, direct download and ftp, and multiple-layer visualization of datasets. A complex authorization system has been designed and applied throughout all components, in order to enable services authorization at dataset level, according to the different user profiles stated in the data policy. Finally, a web portal has been developed as the single entry point and standardized interface to all data services (discover, view, and access). Apache SOLR has been implemented as the search server, allowing faceted browsing among ocean data products and the connection to an external catalogue of metadata records. ncWMS and Godiva2 have been the basis of the viewing server and client technologies developed, MOTU has been used for data subsetting and intelligent management of data queues, and has allowed the deployment of a centralised download interface applicable to all ONM products. Unidata’s Thredds server has been employed to provide file metadata and remote access to ONM data. CAS has been used as the single sign-on protocol for all data services. The user management application developed has been based on GOSA2. Joomla and Bootstrap have been the technologies used for the web portal, compatible with mobile phone and tablet devices. The INDESO information system comes up as an information system that is scalable, extremely easy to use, operate and maintain. This will facilitate the extensive use of ocean numerical model data by the scientific community in Indonesia. Constituted mostly of open-source solutions, the system is able to meet strict operational requirements, and carry out complex functions. It is feasible to adapt this architecture to different static and dynamic oceanographic data sources and large data volumes, in an accessible, fast, and comprehensive manner.

An online application has been developed for the visualization and analysis of space-based hydrology information. In particular, the application, built on state-of-the-art technologies, provides a user friendly and fast-performing analysis of the evolution of continental water bodies over time and space. Altimetry measurements of water levels, digital elevation models (DEM), synthetic aperture radar images (SAR), and their combination with additional complementary in situ data can be also displayed by the graphical interface.

Flood impacts, such as damage and casualties are increasingly important in flood risk management. Estimation of flood impacts enables policy makers to decide on the type of measures to reduce flood risk, and how much investment is warranted. A flexible, generic tool (Delft-FIAT) has been developed using Python, NumPy and GDAL to enable the quick set up a flood impact model in conjunction with the OGC WMS to visualize the results in maps. Delft-FIAT uses the unit loss method, which requires a combination of different data layers: (i) Flood hazard variables; (ii) land-use or objects information (location, type and maximum damage); and (iii) impact functions (usually relating some hazard variable e.g. water depth to an impact or damage fraction). The main advantage of this open-source tool is that it is flexible, as it can take up many different types of impact categories and these can be easily adjusted by the user. Moreover, it is efficient because the calculation engine can handle very large and high resolution input maps thanks to block division techniques in the input/output rasters and vector files. The presented tool is a good example of how open source geospatial software can contribute to environmental monitoring and in particular to flood risk simulations. The tool has already been applied in more than 10 flood risk studies around the world on different spatial scales. These studies show that Delft-FIAT enables researchers to focus on the data and impact knowledge rather than the calculation technology.

Marine Information systems like the operational Copernicus Marine Service (CMEMS) are widely used to enable access to sea data by a significant worldwide user community of nearly 5000 registered users from intergovernmental bodies, European agencies, regional and national service provides and the private sector. The central information system (CIS) beneath this service is the result of more than 6 years of intensive research and improvements carried out in the course of the MyOcean projects (2009-2013) under FP7 and H2020. The Central Information System covers all the service needs from data discovery, download with authentication, viewing and catalogue management. This abstract focuses on the evolutions being performed on the new version of the distributed software component named MOTU for data dissemination, present in all the oceanographic data production units spread through Europe. The MOTU open-source servlet provides REST (Representational State Transfer) services to the registered users willing to download data with or without subset through a queue system and with authentication relaying on a Central Authentication System (CAS). MOTU 2.0 presented strong limitations for the management of NetCDF4 data and intensive memory usage. In the scope of CMEMS, MOTU 3.0 will include several new features, being the compatibility with compressed NetCDF4 data the most attractive one for fast download and increased disk management efficiency. Other improvements such as the OGC protocol WCS 2.0 and better log management to gather download service statistics will be also conducted and included in this upgraded version here presented. For the design of the MOTU 3.0 subset service, TDS (Thredds Data Server) has been considered due to its overall performance and full compatibility with NetCDF4. However, TDS alone may present operational limitations, particularly in the handling of large volumes and number of concurrent users. Hence, MOTU 3.0 will be based on the new NetCDF subset service (NCSS) in conjunction with the latest NetCDF Java library in order to provide geographic, temporal and depth subset of the NetCDF files. Moreover, the use of the MOTU servlet as a proxy of the subset service will add robustness and performance through the queue management system and solve the around the world subset and the depth selection limitations of the NCSS implementation. In conclusion, the upgraded MOTU software envisaged under the Copernicus Marine Service in 2016 will allow users to benefit from the compression of the files and the new OGC standard WCS with a system that will increase in robustness and performance.

MyOcean (http://www.myocean.eu) is providing a pre-operational service, for forecasts, analysis and expertise on ocean currents, temperature, salinity, sea level, primary ecosystems and ice coverage. Since 2009, three successive projects (MyOcean-I, MyOcean-II and MyOcean-Follow-on) have been designed to prepare and to lead the demonstration phases of the future Copernicus Marine Environment Monitoring Service. The main goal of these projects was to build a system of systems offering the users a unique access point to European oceanographic data. Reaching this goal at European level with 59 partners from 28 different countries was a real challenge: initially, each local system had its own human processes and methodology, its own interfaces for production and dissemination. At the end of MyOcean Follow-on, any user can connect to one web portal, browse an interactive catalogue of products and services, use one login to access all data disseminated through harmonized interfaces in a common format and contact a unique centralized service desk. In this organization the central information system plays a key role. The production of observation and forecasting data is done by 48 Production Units (PU). Product download and visualisation are hosted by 26 Dissemination Units (DU). All these products and associated services are gathered in a single system hiding the intricate distributed organization of PUs and DUs. This central system will be presented in detail, including notably the technical choices in architecture and technologies which have been made and why, and the lessons learned during these years of real life of the system, taking into account internal and external feedbacks. Then, perspectives will be presented to sketch the future of such system in the next Marine Copernicus Service which is meant to be fully operational from 2015 onwards.

New visualization trends bring new light to the way environmental monitoring data is exploited today. The presented application is an enhancement of the user experience for the visualization and analysis of the Argos service for animal tracking. Argos is a satellite-based system that collects data from Platform Terminal Transmitters, and distributes sensor and location data in order to understand the distribution of wildlife in a given territory. Virtual globes constitute a visualization platform of geospatial information projected onto the Earth Digital Elevation Model (DEM) in three dimensions, users interactively rotate, zoom and pan the available data, usually projected on a given background that provides a geographic context. The 3D platform allows access to animal tracking data. It also permits the extraction of specific information, path animation and data download from a dedicated and secure platform, with the objective of facilitating the extensive use of this source of information. The animal tracking 3D desktop application has been built with the World Wind SDK, an open source virtual globe built in Java/OpenGL and developed by the National Aeronautics and Space Administration (NASA). The user can combine tracking data with layers from any public server implementing the WMS (Web Mapping Service) protocol of the OGC (Open Geospatial Consortium) through a tab menu able to handle the layers and opacity. Animal tracks can be animated individually alongside the elevation profile of the trajectory with the error ellipsoids of each position of the animal. As for the input/output capabilities of the tool, the CSV format is used as default in order to be compatible with existing operational services. KML is also available to enhance interoperability within GIS communities. The application allows the possibility to query directly from the WebServices that hold the animal data through a REST API using SOAP (Simple Object Access Protocol) with authentication. The new 3D approach to the way data is visualized and the possibility to overlay a wide range of data from open WMS servers, allows users of the service to have a more realistic and integrated vision of their animal positioning data.&nbsp

The objective of the FAST project is to develop Copernicus downstream services. The role of work package 5 (WP5) is to develop the MI-SAFE package, as well as developing the business case and the interaction with end users. The project has implemented several products and services, including an online viewer ‘MI-SAFE’, a wealth of downloadable data layers, Open Software modelling and more Advanced services (training and consultancy). Together, we call this the ‘MI-SAFE package’, which is available online via this link: http://fast.openearth.eu/index.htm. In this deliverable we focus on the validation and uncertainty in the Earth Observation (EO) and field data used as input into the XBeach modelling calculations as well as on the quality of the outputs from the model.

The EU Foreshore Assessment using Space Technology (FAST) focuses on the assessment of foreshores, including vegetation and stability variables, using satellite imagery, to be used in a foreshore assessment package, named MI-SAFE. This report, Deliverable 5.12 (D5.12), describes the structures and functionalities of the MI-SAFE viewer specifically, but also discusses the added value of this product for end user and how it is applied to real cases from the field (study sites) and to all coasts of the world.

Resumen Antecedentes y objetivos La fibrilacion auricular es la arritmia cronica mas comun. El proposito de este estudio fue determinar la prevalencia de la fibrilacion auricular y su relacion con los factores de riesgo cardiovascular en Espana. Metodologia Estudio transversal a partir de un analisis agrupado de 17.291 individuos aleatorizados reclutados en 6 estudios poblacionales. Resultados La prevalencia de fibrilacion auricular fue de 1,5%. (intervalo de confianza 95%: 1,3-1,7%). Los hombres tuvieron mayor prevalencia que las mujeres (1,9 vs. 1,1%, respectivamente). La prevalencia de fibrilacion auricular se incremento progresivamente con la edad: 0,05% en los menores de 45 anos, 0,5% entre los 45-59 anos, 2,3% entre los 60-74 anos, y 6,3% en los mayores de 75 anos. El porcentaje de individuos que recibia tratamiento anticoagulante fue de 74,3%. Los factores de riesgo asociados significativamente con la arritmia fueron: edad mayor de 60 anos (odds ratio [OR]: 7,6; IC 95%: 5,1-11,2), sexo masculino (OR : 1,8; IC 95%: 1,4-2,4), hipertension arterial (OR : 1,6; IC 95%: 1,2-2,1), obesidad (OR : 1,5; IC 95%: 1,2-2,1), y antecedentes de enfermedad coronaria (OR : 1,9; IC 95%: 1,3-3,0). Conclusion La fibrilacion auricular es una enfermedad frecuente en los individuos de mayor edad mientras que su prevalencia es baja en individuos menores de 60 anos. La mayoria de los individuos con fibrilacion auricular estaban bajo tratamiento anticoagulante. Los factores de riesgo para padecer esta arritmia fueron la edad, el sexo masculino, la hipertension, la obesidad y los antecedentes de enfermedad coronaria.

Background and objectives Atrial fibrillation (AF) is the most common type of arrhythmia. The purpose of this study was to determine the prevalence of atrial fibrillation and its relationship with cardiovascular risk factors in Spain. Methodology Cross-sectional study based on a grouped analysis of 17,291 randomized individuals recruited in 6 population studies. Results The prevalence of atrial fibrillation was 1.5% (95% CI: 1.3–1.7%). Men had a greater prevalence of the disease than women (1.9 vs. 1.1%, respectively). The prevalence of atrial fibrillation progressively increased with age: 0.05% for patients younger than 45 years, 0.5% for those between 45 and 59 years of age, 2.3% for those between 60 and 74 years of age and 6.3% for those older than 75 years. The percentage of individuals who underwent anticoagulant treatment was 74.3%. The risk factors significantly associated with arrhythmia were ages older than 60 years (odds ratio [OR]: 7.6; 95% CI: 5.1–11.2), the male sex (OR: 1.8; 95% CI: 1.4–2.4), arterial hypertension (OR: 1.6; 95% CI: 1.2–2.1), obesity (OR: 1.5; 95% CI: 1.2–2.1) and a history of coronary artery disease (OR: 1.9; 95% CI: 1.3–3.0). Conclusion Atrial fibrillation is a common disease in elderly individuals, while its prevalence is low in individuals younger than 60 years. Most individuals with atrial fibrillation were on anticoagulant treatment. The risk factors for this type of arrhythmia are age, the male sex, hypertension, obesity and a history of coronary artery disease.

Introduction Blood pressure increases in cold periods, but its implications on prevalence of hypertension and on individual progression to hypertension remain unclear. Our aim was to develop a pre-screening test for identifying candidates to suffer hypertension only in cold months among non-hypertensive subjects. Methods We included 95,277 subjects registered on a primary care database from Girona (Catalonia, Spain), with ≥3 blood pressure measures recorded between 2003 and 2009 and distributed in both cold (October–March) and warm (April–September) periods. We defined four blood pressure patterns depending on the presence of hypertension through these periods. A Cox model determined the risk to develop vascular events associated with blood pressure patterns. A logistic regression distinguished those nonhypertensive individuals who are more prone to suffer cold-induced hypertension. Validity was assessed on the basis of calibration (using Brier score) and discrimination (using the area under the receiver operating characteristics). Results In cold months, the mean systolic blood pressure increased by 3.3±0.1 mmHg and prevalence of hypertension increased by 8.2%. Cold-induced hypertension patients were at higher vascular events risk (Hazard ratio=1.44 [95% Confidence interval 1.15–1.81]), than nonhypertensive individuals. We identified age, diabetes, body mass index and prehypertension as the major contributing factors to cold-induced hypertension onset. Discussion Hypertension follows a seasonal pattern in some individuals. We recommend screening for hypertension during the cold months, at least in those nonhypertensive individuals identified as cold-induced hypertensive by this assessment tool.

AIM To determine whether circulating antibodies against oxidized low-density lipoprotein (LDL; OLAB) levels are associated with acute myocardial infarction (AMI) in individuals without classical cardiovascular risk factors. METHODS A case-control study including 34 first AMI patients without classical risk factors (smoking, dyslipidemia, hypertension or diabetes) and 45 population-based healthy controls. RESULTS There were no differences in anthropometric variables between cases and controls. Oxidized LDL levels were similar in both groups. Total cholesterol, LDL cholesterol, apolipoprotein B and physical activity were lower in cases than in controls. OLAB levels were also lower in cases than controls (128 versus 447 U/l, P < 0.001). After adjusting for age, oxidized LDL and physical activity, participants with OLAB levels of 165 U/l or less had a higher risk of AMI (odds ratio, OR = 7.48, 95% confidence interval: 1.57-35.66). When the model was fitted with OLAB as a continuous variable, the natural logarithm (LnOLAB) levels were independently associated with AMI with an OR of 0.40 (95% confidence interval: 0.19-0.86). After adjusting the model by Framingham-risk-adapted score and oxidized LDL, the LnOLAB levels maintained their independent association (OR of 0.43, 95% confidence interval: 0.23-0.79). CONCLUSION First AMI patients without classical risk factors had lower levels of OLAB compared with healthy controls. It is likely that the immunological reaction due to oxidized LDL participates as a preventive factor in the physiopathology of atherosclerosis.

Objective To derive and validate a set of functions to predict coronary heart disease (CHD) and stroke, and validate the Framingham-REGICOR function. Method Pooled analysis of 11 population-based Spanish cohorts (1992–2005) with 50,408 eligible participants. Baseline smoking, diabetes, systolic blood pressure (SBP), lipid profile, and body mass index were recorded. A ten-year follow-up included re-examinations/telephone contact and cross-linkage with mortality registries. For each sex, two models were fitted for CHD, stroke, and both end-points combined: model A was adjusted for age, smoking, and body mass index and model B for age, smoking, diabetes, SBP, total and HDL cholesterol, and for hypertension treatment by SBP, and age by smoking and by SBP interactions. Results The 9.3-year median follow-up accumulated 2973 cardiovascular events. The C-statistic improved from model A to model B for CHD (0.66 to 0.71 for men; 0.70 to 0.74 for women) and the combined CHD-stroke end-points (0.68 to 0.71; 0.72 to 0.75, respectively), but not for stroke alone. Framingham-REGICOR had similar C-statistics but overestimated CHD risk. Conclusions The new functions accurately estimate 10-year stroke and CHD risk in the adult population of a typical southern European country. The Framingham-REGICOR function provided similar CHD prediction but overestimated risk.

Background The use of validated multivariate cardiovascular predictive models in a population setting is of interest for public health policy makers. We aimed to validate the estimations of the CASSANDRA model (coronary heart disease (CHD) incidence and CHD risk distribution), considering the population changes in age, sex and CHD risk factors prevalence in a 10-year period. Methods We compared the projected CHD incidence estimated with CASSANDRA with that observed in the Girona Heart Registry (REGICOR) for 1995–2004 and 2000–2009 in the population of Girona (Spain) aged 35–74 years. We used official age and sex distributions for this population. Baseline cardiovascular risk factors prevalence and the distribution of cardiovascular risk were obtained from three cross-sectional studies performed in 1995, 2000 and 2005. To validate the future distribution of cardiovascular risk, we tested the yearly CHD risk variance over the study period. Results No significant differences between the estimated and observed annual CHD incidence per 100 000 men were found in 1995–2004 (CASSANDRA=457.8 and REGICOR=420.3, incidence rate ratio (IRR) (95% CI)=0.92 (0.89 to 0.96)) and in 2000–2009 (441.4 and 409.6, respectively, IRR=0.93 (0.90 to 0.96)). However, overpredictions of 18% and 22%, respectively, were observed in women (198.8 and 160.4, IRR=0.82 (0.77 to 0.86), and 197.1 and 152.8, IRR=0.78 (0.74 to 0.83), respectively). No significant differences were found in the CHD risk variance in the three different cross-sectional studies. Conclusions The CASSANDRA model produces valid estimates, particularly in men, of the future burden of disease and in the distribution of cardiovascular risk in individuals aged 35–74 years.

Objectives To assess 1) the association of lipid oxidation biomarkers with 10-year coronary artery disease (CAD) events and subclinical atherosclerosis, and 2) the reclassification capacity of these biomarkers over Framingham-derived CAD risk functions, in a general population. Methods Within the framework of the REGICOR study, 4782 individuals aged between 25 and 74 years were recruited in a population-based cohort study. Follow-up of the 4042 who met the eligibility criteria was carried out. Plasma, circulating oxidized low-density lipoprotein (oxLDL) and oxLDL antibodies (OLAB) were measured in a random sample of 2793 participants. End-points included fatal and non-fatal acute myocardial infarction (AMI) and angina. Carotid intima-media thickness (IMT) in the highest quintile and ankle-brachial index Results Mean age was 50.0 (13.4) years, and 52.4% were women. There were 103 CAD events (34 myocardial infarction, 43 angina, 26 coronary deaths), and 306 subclinical atherosclerosis cases. Oxidized LDL was independently associated with higher incidence of CAD events (HR = 1.70; 95% Confidence Interval: 1.02–2.84), but not with subclinical atherosclerosis. The net classification index of the Framingham-derived CAD risk function was significantly improved when ox-LDL was included (NRI = 14.67% [4.90; 24.45], P = 0.003). No associations were found between OLAB and clinical or subclinical events. The reference values for oxLDL and OLAB are also provided (percentiles). Conclusions OxLDL was independently associated with 10-year CAD events but not subclinical atherosclerosis in a general population, and improved the reclassification capacity of Framingham-derived CAD risk functions.

Resumen Introduccion y objetivos Analizar las diferencias en funcion del sexo en las caracteristicas clinicas, tratamiento y mortalidad a los 28 dias y a los 7 anos de un primer infarto de miocardio. Metodos Entre 2001 y 2003, 2.042 pacientes con un primer infarto de miocardio ingresaron consecutivamente en seis hospitales espanoles. Se recogen prospectivamente las caracteristicas clinicas, el tratamiento y la mortalidad a los 28 dias. Se dispone del estado vital a los 7 anos mediante consulta del Indice Nacional de Defunciones. Resultados Se incluyo a 449 mujeres y 1.593 varones con un primer infarto de miocardio. En comparacion con los varones, las mujeres eran mayores y tenian mayor prevalencia de hipertension y diabetes mellitus; tambien recibieron mas tratamiento con inhibidores de la enzima de conversion de la angiotensina, pero menos bloqueadores beta y trombolisis. No hubo diferencias en el uso de procedimientos invasivos. Las mujeres tuvieron mas infartos de miocardio sin elevacion del segmento ST o no clasificables (el 37,9 frente al 31,3% y el 9,8 frente al 6,1% respectivamente; p Conclusiones Hay diferencias clinicas y demograficas entre varones y mujeres que ingresan por un primer infarto de miocardio. El pronostico a corto plazo es similar en ambos sexos. La mortalidad a 7 anos de un primer infarto de miocardio es peor en varones que en mujeres. Estos resultados se observan en infartos agudos de miocardio con y sin elevacion del segmento ST.

There is limited prospective evidence at population scale of the impacts of lifestyle and surrogate measures of general and abdominal adiposity on the transition of a metabolically healthy (absence of a metabolic disorder) overweight/obese (MHOO) phenotype to a metabolically abnormal overweight/obese (MAOO) phenotype. Therefore, we determined the relationship between 10-year body mass index (BMI), waist circumferences (WC), waist to height ratio (WHtR), and lifestyle changes and the transition of the MHOO phenotype.We conducted a prospective population-based study of 3,052 male and female Spaniards aged 25-74 years who were followed from 2000 through 2009. Diet and leisure-time physical activity were recorded on validated questionnaires. Weight, height, WC, blood lipids, glycemia, and blood pressure were measured. All variables were obtained at baseline (BL) and follow-up (FL). Participants with a BMI ≥ 25 kg/m(2) and free from hypercholesterolemia, hypertriglyceridemia, diabetes, hypertension, and low HDL and high LDL cholesterol levels were characterized as the MHOO phenotype. A composite healthy lifestyle index (HLI) was constructed by including temporary changes in 3 lifestyle variables (diet, leisure-time physical activity, and smoking).Initially, 20.8% of subjects had the MHOO phenotype; 49.2% of these shifted to MAOO phenotype. In multivariate analysis, changes in BMI, WC, WHtR were positively associated (p = 0.004, p = 0.018, and p = 0.016, respectively) with this transition. One unit increase in the HLI was associated with a 33% lower risk (p = 0.025) to the MAOO phenotype transition after adjusting for age, sex, educational level, and baseline energy intake, BMI, WC, and WHtR.The presence of metabolic disorders in the MHOO phenotype is predicted by an increase in anthropometric surrogate measures of general and abdominal adiposity. In contrast, a healthy lifestyle protects against a transition to the MAOO phenotype.

Anal (EcoA) and rectal endosonography (EcoEAR) is a useful test in the evaluation of patients with anorectal pathology. However, there is no clear consensus on its indications. The aim of this study was to determine the opinion of clinicians regarding the current indications and usefulness of this diagnostic test in daily clinical practice. A cross-sectional observational study was conducted using a survey sent to the services of General surgery in a specific area of Spain. The clinical usefulness of the test was evaluated using an analog scale from 0 (lowest value) to 10 (maximum utility) for each pathology. Of the 47 hospitals, 23 responded to the questionnaire (48.9%). The average number of ultrasounds performed in these centers was 217 per year (standard deviation: 140.1, range 73–450) during the last 3 years. The most common indications for this test were: rectal tumor (85%), anal fistula (80%), and fecal incontinence (70%). This test was suggested more, depending on availability in the hospital itself. In conclusion, anal and rectal endosonography remains a very useful diagnostic clinical test in the opinion of clinicians in general and digestive surgery, especially in the evaluation of patients with anal fistula, fecal incontinence, or rectal tumors.

Resumen Introduccion La fistula quilosa es poco frecuente en el postoperatorio de diferentes tipos de intervenciones abdominales, especialmente del espacio retroperitoneal, como las pancreaticas. Puede desarrollarse tambien en el curso de una pancreatitis aguda grave. El tratamiento inicialmente es conservador y puede dilatarse en el tiempo, aunque puede abreviarse con el uso de somatostatina u octreotido. Pacientes y metodos Los pacientes afectos de enfermedad pancreatica que presentaron una fistula quilosa durante su ingreso (debito mayor de 100 cc/24 h, niveles de amilasa pancreatica normales y trigliceridos superiores a 110 mg/dl) fueron tratados inicialmente con dieta absoluta y nutricion parenteral total, seguido de la administracion de octreotido 0,1 mg/8 h por via subcutanea. Resultados Cuatro pacientes mujeres de entre 55 y 80 anos, presentando cirugia pancreatica o pancreatitis aguda, desarrollaron una fistula quilosa con debitos entre 100 y 2.000 ml cada 24 h. Tras la administracion de octreotido, las fistulas se solucionaron entre el quinto y el septimo dia de tratamiento, sin presentar recidiva durante un seguimiento de 2 a 4 anos. Conclusiones Dado que el tratamiento medico de la fistula quilosa en general se asocia a un curso lento, y que la administracion de somatostatina u octreotido produce una drastica resolucion del cuadro, tal como hemos constatado en nuestra observacion y como aparece descrito por otros autores, el inicio precoz de este tratamiento puede acelerar su curacion, lo que redunda en un acortamiento de la recuperacion del paciente y en una disminucion del gasto hospitalario.

Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia. P-wave duration and interatrial blocks (IAB) have been reported to be associated with AF. Our aim was to determine the individual and combined association of P-wave duration and advanced IAB morphology with AF.We designed an age-, sex-, and survey-matched case-control study nested in a population-based cohort (REGICOR: REgistre GIroní del COR). Two different surveys recruited a total of 9380 participants from 1999 to 2005; all participants were invited to a second examination between 2009 and 2013. For the present study, we selected participants aged 25 to 79 years with follow-up through the end of the study. All electrocardiograms were analyzed by 2 observers to determine P-wave duration and morphology (normal, partial, or advanced IAB).The median follow-up was 7.12 years. Eighty participants presented with AF, had a legible baseline electrocardiogram, and were included in the study, along with 160 controls. P-wave duration and the presence of partial or advanced IAB were associated with AF. When P-wave duration and morphology were considered together, only P-wave duration (≥ 110 milliseconds) showed an independent and strong association with AF. The odds ratio for AF of P-wave duration between 110-119, 120-129 and ≥ 130 milliseconds vs110 milliseconds were 5.33; 95%CI, 1.74-16.33, 5.08; 95%CI, 1.73-14.90 and 5.44; 95%CI, 1.95-15.15, respectively.A P-wave longer than 110 milliseconds increases the risk of AF. Advanced IAB morphology did not seem to provide an additional AF risk beyond that of P-wave duration.