Climate, irrigation, and land cover change explain streamflow trends in countries bordering the northeast Atlantic

Attribution of trends in streamflow is complex, but essential, in identifying optimal management options for water resources. Disagreement remains on the relative role of climate change and human factors, including water abstractions and land cover change, in driving change in annual streamflow. We construct a very dense network of gauging stations (n = 1,874) from Ireland, the United Kingdom, France, Spain, and Portugal for the period of 1961–2012 to detect and then attribute changes in annual streamflow. Using regression‐based techniques, we show that climate (precipitation and atmospheric evaporative demand) explains many of the observed trends in northwest Europe, while for southwest Europe human disturbances better explain both temporal and spatial trends. For the latter, large increases in irrigated areas, agricultural intensification, and natural revegetation of marginal lands are inferred to be the dominant drivers of decreases in streamflow

Development, characterization and sterilisation of Nanocellulose-alginate-(hyaluronic acid)- bioinks and 3D bioprinted scaffolds for tissue engineering

3D-bioprinting is an emerging technology of high potential in tissue engineering (TE), since it shows effective control over scaffold fabrication and cell distribution. Biopolymers such as alginate (Alg), nanofibrillated cellulose (NC) and hyaluronic acid (HA) offer excellent characteristics for use as bioinks due to their excellent biocompatibility and rheological properties. Cell incorporation into the bioink requires sterilisation assurance, and autoclave, β-radiation and γ-radiation are widely used sterilisation techniques in biomedicine; however, their use in 3D-bioprinting for bioinks sterilisation is still in their early stages. In this study, different sterilisation procedures were applied on NC-Alg and NC-Alg-HA bioinks and their effect on several parameters was evaluated. Results demonstrated that NC-Alg and NC-Alg-HA bioinks suffered relevant rheological and physicochemical modifications after sterilisation; yet, it can be concluded that the short cycle autoclave is the best option to sterilise both NC-Alg based cell-free bioinks, and that the incorporation of HA to the NC-Alg bioink improves its characteristics. Additionally, 3D scaffolds were bioprinted and specifically characterized as well as the D1 mesenchymal stromal cells (D1-MSCs) embedded for cell viability analysis. Notably, the addition of HA demonstrates better scaffold properties, together with higher biocompatibility and cell viability in comparison with the NC-Alg scaffolds. Thus, the use of MSCs containing NC-Alg based scaffolds may become a feasible tissue engineering approach for regenerative medicine.Author thanks the Basque Government for granted fellowship to S. Ruiz-Alonso (PRE_2020_2_0143). This study was financially supported by the Basque Country Government (IT907-16), the Ministerio de Economía, Industria y Competitividad (FEDER funds, project RTC-2016- 5451-1), Fundación Mutua Madrileña (project FMM-AP17196-2019), the Instituto de Salud Carlos III, ERDF funds (DTS19/00145) and by the Consejería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía (project no. PY18-2470 and SOMM17/6109/UGR, FEDER Funds). Authors also wish to thank the intellectual and technical assistance from the ICTS “NANBIOSIS”, more specifically by the Drug Formulation Unit (U10) of the CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN) at the University of Basque Country (UPV/ EHU

A microphysiological model designed for the research of angiogenic sprouting in an extracellular matrix

Angiogenesis is an important biological process for vascular development, as well as being involved in different health problems such as cancer, inflammatory processes, infections, and some autoimmune diseases, among others. In recent years, microphysiological devices have been proposed to study angiogenesis due to their ability to accurately recreate in vivo microenvironmental conditions. This study presents a platform to study the early stages of angiogenesis together with an in-silico model, presenting an innovative approach that allows us to better analyze the dynamics of angiogenesis. The presented platform allows the formation of an angiogenic gradient through a porous hydrogel, thus provoking the angiogenic response of endothelial cells and therefore studying the process under the desired conditions. In addition, the use of the two-photon polymerization technique has allowed us to print 3D hydrogels with the desired structure within microfluidic devices. Our results show that this microphysiological device, together with the developed mathematical model, is a valuable tool for studying the complex process of angiogenesis.We gratefully acknowledge the financial support from the Spanish Ministry of Science and Innovation (MICINN) and the Spanish State Research Agency (AEI) through grants RTI2018-097038-B-C22, PID2021-124575OB-I00 and PDC2022-133918-C22, and the the financial support from the European Union’s Horizon Europe research & innovation program (EIC-2021-PATHFINDER-OPEN- 01-01-101047099 4DBR). Finally, we also appreciate the support of Research Foundation Flanders (FWO) (1SH3W24N)

Increased Vegetation in Mountainous Headwaters Amplifies Water Stress During Dry Periods

The dynamics of blue and green water partitioning under vegetation and climate change, as well as their different interactions during wet and dry periods, are poorly understood in the literature. We analyzed the impact of vegetation changes on blue water generation in a central Spanish Pyrenees basin undergoing intense afforestation. We found that vegetation change is a key driver of large decreases in blue water availability. The effect of vegetation increase is amplified during dry years, and mainly during the dry season, with streamflow reductions of more than 50%. This pattern can be attributed primarily to increased plant water consumption. Our findings highlight the importance of vegetation changes in reinforcing the decrease in water resource availability. With aridity expected to rise in southern Europe over the next few decades, interactions between climate and land management practices appear to be amplifying future hydrological drought risk in the region.This work was supported by projects CGL2017-82216-R, PCI2019-103631, and PID2019-108589RA-I00 financed by the Spanish Commission of Science and Technology and FEDER; CROSSDRO project financed by AXIS (Assess-ment of Cross(X)-sectoral climate Impacts and pathways for Sustainable transformation), JPI-Climate co-funded call of the European Commission and INDECIS which is part of ERA4CS, an ERA-NET initiated by JPI Climate, and funded by FORMAS (SE), DLR (DE), BMWFW (AT), IFD (DK), MINECO (ES), ANR (FR) with co-funding by the European Union (Grant 690462). Dhais Peña-Angulo received a “Juan de la Cierva” postdoctoral contract (FJCI-2017-33652 Spanish Ministry of Economy and Competitiveness, MEC). Miquel Tomas-Burguera received a “Juan de la Cierva” postdoctoral contract (FJCI-2019-039261-I Spanish Ministry of Science and Innovation). C. Azorin-Molina and S. Grainger. acknowledge funding from the Irish Environmental Protection Agency grant 2019-CCRP-MS.60. C. Juez acknowl-edges funding from the H2020-MSCA-IF-2018 programme (Marie Sklodows-ka-Curie Actions) of the European Union under REA grant agreement, number 834329-SEDILAND

SANTANDER (Puerto). Cartas náuticas. 1874 (1840). 1:21000

Fecha de publicación más antigua de las que aparecen en el documento :"1843"Escalas gráficas de 2 millas marinas [= 17,4] y 2220 varas de Burgos [= 8,6 cm]. Coordenadas de la dársena referidas al parecer al meridiano de San Fernando (E 2°23'33'' / N 43°27'52''). Orientado con lis en gráfico de declinación magnéticaOrografía por normales y puntos acotados expresados en piesIndica sondas batimetrícas en brazas de seis pies de Burgos, veriles, bancos de arena, fondeaderos, derrotas y faros destacados en rojo y amarilloNota relativa a la amplitud de las mareasClave hidrográfica para determinar la calidad del fondoNota referente a las caracteristicas del puertoDestacan caminos, núcleos de población y río

Improving inpatient pharmacoterapeutic process by Lean Six Sigma methodology

[EN] Background Lean Six Sigma methodology has been used to improve care processes, eliminate waste, reduce costs, and increase patient satisfaction. Objective To analyse the results obtained with Lean Six Sigma methodology in the diagnosis and improvement of the inpatient pharmacotherapy process during structural and organisational changes in a tertiary hospital. Material and methods Scope: 1.000 beds tertiary hospital. Design prospective observational study. The define, measure, analyse, improve and control (DMAIC), were deployed from March to September 2011. An Initial Project Charter was updated as results were obtained. Population and sample: 131 patients with treatments prescribed within 24 h after admission and with 4 drugs. Variables: safety indicators (medication errors), and efficiency indicators (complaints and time delays). Results Proportion of patients with a medication error was reduced from 61.0% (25/41 patients) to 55.7% (39/70 patients) in four months. Percentage of errors (regarding the opportunities for error) decreased in the different phases of the process: Prescription: from 5.1% (19/372 opportunities) to 3.3% (19/572 opportunities); Preparation: from 2.7% (14/525 opportunities) to 1.3% (11/847 opportunities); and administration: from 4.9% (16/329 opportunities) to 3.0% (13/433 opportunities). Nursing complaints decreased from 10.0% (2119/21038 patients) to 5.7% (1779/31097 patients). The estimated economic impact was 76,800 euros saved. Conclusions An improvement in the pharmacotherapeutic process and a positive economic impact was observed, as well as enhancing patient safety and efficiency of the organization. Standardisation and professional training are future Lean Six Sigma candidate projects.[ES] Introducción La metodología Lean Seis Sigma se utilizó para mejorar procesos, eliminar desperdicios, reducir costes y aumentar la satisfacción de clientes. Objetivo Analizar los resultados obtenidos con la metodología Lean Seis Sigma en el diagnóstico y la mejora del proceso farmacoterapéutico del paciente hospitalizado durante el cambio estructural y organizativo de un hospital terciario. Material y métodos Ámbito: hospital general terciario con 1.000 camas. Diseño del estudio: observacional y prospectivo. Se desplegaron las etapas definir, medir, analizar, mejorar y controlar (DMAIC) entre marzo y septiembre de 2011, actualizando el Project Charter inicial según resultados. Población y muestra: 131 pacientes hospitalizados con tratamientos prescritos en las 24 h siguientes al ingreso y con 4 medicamentos. Variables: indicadores de seguridad (errores de medicación) y de eficiencia (tiempos de demora y reclamaciones). Resultados La proporción de pacientes con algún error de medicación se redujo del 61,0 (25/41 pacientes) al 55,7% (39/70 pacientes) en 4 meses. Los porcentajes de errores, con respecto a las oportunidades de error, en distintas fases del proceso disminuyeron: prescripción 5,1 (19/372) a 3,3% (19/572); preparación 2,7 (14/525) a 1,3% (11/847 oportunidades); y administración: 4,9 (16/329) a 3,0% (13/433). Las reclamaciones se redujeron del 10,0 (2.119/21.038 pacientes) a 5,7% (1.779/31.097 pacientes). El impacto económico se estimó en 76.800 euros evitados. Conclusiones Se observó una mejora del proceso farmacoterapéutico y un impacto financiero positivo que ha repercutido en la seguridad del paciente y la eficiencia de la organización. La normalización y la formación de profesionales podrían ser proyectos futuros de Lean Seis Sigma.Font Noguera, I.; Fernández Megía, M.; Ferrer, A.; Balasch Parisi, S.; Edo Solsona, M.; Poveda Andres, J. (2013). Mejora del proceso farmacoterapéutico del paciente hospitalizado mediante la metodología Lean Seis Sigma. Revista de Calidad Asistencial. 28(6):370-380. doi:10.1016/j.cali.2013.04.003S37038028

Transcriptome characterization by RNA sequencing identifies a major molecular and clinical subdivision in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) has heterogeneous clinical and biological behavior. Whole-genome and -exome sequencing has contributed to the characterization of the mutational spectrum of the disease, but the underlying transcriptional profile is still poorly understood. We have performed deep RNA sequencing in different subpopulations of normal B-lymphocytes and CLL cells from a cohort of 98 patients, and characterized the CLL transcriptional landscape with unprecedented resolution. We detected thousands of transcriptional elements differentially expressed between the CLL and normal B cells, including protein-coding genes, noncoding RNAs, and pseudogenes. Transposable elements are globally derepressed in CLL cells. In addition, two thousand genes-most of which are not differentially expressed-exhibit CLL-specific splicing patterns. Genes involved in metabolic pathways showed higher expression in CLL, while genes related to spliceosome, proteasome, and ribosome were among the most down-regulated in CLL. Clustering of the CLL samples according to RNA-seq derived gene expression levels unveiled two robust molecular subgroups, C1 and C2. C1/C2 subgroups and the mutational status of the immunoglobulin heavy variable (IGHV) region were the only independent variables in predicting time to treatment in a multivariate analysis with main clinico-biological features. This subdivision was validated in an independent cohort of patients monitored through DNA microarrays. Further analysis shows that B-cell receptor (BCR) activation in the microenvironment of the lymph node may be at the origin of the C1/C2 differences

The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease

Background\ud In order to identify novel loci associated with Alzheimer's disease (AD), we conducted a genome-wide association study (GWAS) in the Spanish population.\ud \ud Methods\ud We genotyped 1,128 individuals using the Affymetrix Nsp I 250K chip. A sample of 327 sporadic AD patients and 801 controls with unknown cognitive status from the Spanish general population were included in our initial study. To increase the power of the study, we combined our results with those of four other public GWAS datasets by applying identical quality control filters and the same imputation methods, which were then analyzed with a global meta-GWAS. A replication sample with 2,200 sporadic AD patients and 2,301 controls was genotyped to confirm our GWAS findings.\ud \ud Results\ud Meta-analysis of our data and independent replication datasets allowed us to confirm a novel genome-wide significant association of AD with the membrane-spanning 4-domains subfamily A (MS4A) gene cluster (rs1562990, P = 4.40E-11, odds ratio = 0.88, 95% confidence interval 0.85 to 0.91, n = 10,181 cases and 14,341 controls).\ud \ud Conclusions\ud Our results underscore the importance of international efforts combining GWAS datasets to isolate genetic loci for complex diseases

Adaptive Radiation within Marine Anisakid Nematodes: A Zoogeographical Modeling of Cosmopolitan, Zoonotic Parasites

Parasites of the nematode genus Anisakis are associated with aquatic organisms. They can be found in a variety of marine hosts including whales, crustaceans, fish and cephalopods and are known to be the cause of the zoonotic disease anisakiasis, a painful inflammation of the gastro-intestinal tract caused by the accidental consumptions of infectious larvae raw or semi-raw fishery products. Since the demand on fish as dietary protein source and the export rates of seafood products in general is rapidly increasing worldwide, the knowledge about the distribution of potential foodborne human pathogens in seafood is of major significance for human health. Studies have provided evidence that a few Anisakis species can cause clinical symptoms in humans. The aim of our study was to interpolate the species range for every described Anisakis species on the basis of the existing occurrence data. We used sequence data of 373 Anisakis larvae from 30 different hosts worldwide and previously published molecular data (n = 584) from 53 field-specific publications to model the species range of Anisakis spp., using a interpolation method that combines aspects of the alpha hull interpolation algorithm as well as the conditional interpolation approach. The results of our approach strongly indicate the existence of species-specific distribution patterns of Anisakis spp. within different climate zones and oceans that are in principle congruent with those of their respective final hosts. Our results support preceding studies that propose anisakid nematodes as useful biological indicators for their final host distribution and abundance as they closely follow the trophic relationships among their successive hosts. The modeling might although be helpful for predicting the likelihood of infection in order to reduce the risk of anisakiasis cases in a given area

Expression of HMGCS2 in intestinal epithelial cells is downregulated in inflammatory bowel disease associated with endoplasmic reticulum stress.

INTRODUCTION The Unfolded Protein Response, a mechanism triggered by the cell in response to Endoplasmic reticulum stress, is linked to inflammatory responses. Our aim was to identify novel Unfolded Protein Response-mechanisms that might be involved in triggering or perpetuating the inflammatory response carried out by the Intestinal Epithelial Cells in the context of Inflammatory Bowel Disease. METHODS We analyzed the transcriptional profile of human Intestinal Epithelial Cell lines treated with an Endoplasmic Reticulum stress inducer (thapsigargin) and/or proinflammatory stimuli. Several genes were further analyzed in colonic biopsies from Ulcerative Colitis patients and healthy controls. Lastly, we generated Caco-2 cells lacking HMGCS2 by CRISPR Cas-9 and analyzed the functional implications of its absence in Intestinal Epithelial Cells. RESULTS Exposure to a TLR ligand after thapsigargin treatment resulted in a powerful synergistic modulation of gene expression, which led us to identify new genes and pathways that could be involved in inflammatory responses linked to the Unfolded Protein Response. Key differentially expressed genes in the array also exhibited transcriptional alterations in colonic biopsies from active Ulcerative Colitis patients, including NKG2D ligands and the enzyme HMGCS2. Moreover, functional studies showed altered metabolic responses and epithelial barrier integrity in HMGCS2 deficient cell lines. CONCLUSION We have identified new genes and pathways that are regulated by the Unfolded Protein Response in the context of Inflammatory Bowel Disease including HMGCS2, a gene involved in the metabolism of Short Chain Fatty Acids that may have an important role in intestinal inflammation linked to Endoplasmic Reticulum stress and the resolution of the epithelial damage.This work was supported by grants from Ministerio de Ciencia e Innovación (MCIN) from Spain [SAF2016-78711R and PID202-11794 to EM-N and FJC]; Comunidad de Madrid [B2017/BMD-3727 to EMN and FJC]; Comunidad de Madrid (REACT-UE, ANTICIPA-CM Ref. PR38/21-24) to E.M-N and HORIZON-HLTH-2022-STAYHLTH-02 under agreement No 101095679 to FJC the European Union’s Horizon 2020 research and innovation program [ERC-2016- Consolidator Grant 725091 to DS]; MCIN/AEI/10.13039/ 501100011033 [PID2019-108157RB to DS]; la Caixa Foundation (ID 100010434) [LCF/BQ/PR20/11770008 to SW]; Instituto de Salud Carlos III (ISCIII) [PI18/00348 to VE]; ISCIII [PI21/01641 to RT-R]; Spanish National Research and Development Plan, ISCIII and FEDER [PI17/02303 and PI20/01837 to SR-P]; Proyecto Desarrollo Tecnológico [DTS19/00111 to SR-P], AEI/MICIU EXPLORA Project [BIO2017-91272-EXP to SR-P]; Programa Estratégico Instituto de Biologıa y Gene ́ ́ tica Molecular (IBGM), Junta de Castilla y León (CCVC8485) [PID2019-104218RB-I00 to DB]; NIH [DK088199 to RB] and Universidad Complutense de Madrid (UCM 920631) [CT42/ 18-CT43/18 and EB15/21 to BM-A].S