Daily precipitation statistics in a EURO-CORDEX RCM ensemble: added value of raw and bias-corrected high-resolution simulations

Daily precipitation statistics as simulated by the ERA-Interim-driven EURO-CORDEX regional climate model (RCM) ensemble are evaluated over two distinct regions of the European continent, namely the European Alps and Spain. The potential added value of the high-resolution 12 km experiments with respect to their 50 km resolution counterparts is investigated. The statistics considered consist of wet-day intensity and precipitation frequency as a measure of mean precipitation, and three precipitation-derived indicators (90th percentile on wet days?90pWET, contribution of the very wet days to total precipitation?R95pTOT and number of consecutive dry days?CDD). As reference for model evaluation high resolution gridded observational data over continental Spain (Spain011/044) and the Alpine region (EURO4M-APGD) are used. The assessment and comparison of the two resolutions is accomplished not only on their original horizontal grids (approximately 12 and 50 km), but the high-resolution RCMs are additionally regridded onto the coarse 50 km grid by grid cell aggregation for the direct comparison with the low resolution simulations. The direct application of RCMs e.g. in many impact modelling studies is hampered by model biases. Therefore bias correction (BC) techniques are needed at both resolutions to ensure a better agreement between models and observations. In this work, the added value of the high resolution (before and after the bias correction) is assessed and the suitability of these BC methods is also discussed. Three basic BC methods are applied to isolate the effect of biases in mean precipitation, wet-day intensity and wet-day frequency on the derived indicators. Daily precipitation percentiles are strongly affected by biases in the wet-day intensity, whereas the dry spells are better represented when the simulated precipitation frequency is adjusted to the observed one. This confirms that there is no single optimal way to correct for RCM biases, since correcting some distributional features typically leads to an improvement of some aspects but to a deterioration of others. Regarding mean seasonal biases before the BC, we find only limited evidence for an added value of the higher resolution in the precipitation intensity and frequency or in the derived indicators. Thereby, evaluation results considerably depend on the RCM, season and indicator considered. High resolution simulations better reproduce the indicators? spatial patterns, especially in terms of spatial correlation. However, this improvement is not statistically significant after applying specific BC methods.The authors are grateful to Prof. C. Schär for his helpful comments and E. van Meijgaard for making available the RACMO model data. We acknowledge the observational data providers. Calculations for WRF311F were made using the TGCC super computers under the GENCI time allocation GEN6877. The WRF331A from CRP-GL (now LIST) was funded by the Luxembourg National Research Fund (FNR) through grant FNR C09/SR/16 (CLIMPACT). The KNMI-RACMO2 simulations were supported by the Dutch Ministry of Infrastructure and the Environment. The CCLM and REMO simulations were supported by the Federal Ministry of Education and Research (BMBF) and performed under the Konsortial share at the German Climate Computing Centre (DKRZ). The CCLM simulations were furthermore supported by the Swiss National Supercomputing Centre (CSCS) under project ID s78. Part of the SMHI contribution was carried out in the Swedish Mistra-SWECIA programme founded by Mistra (the Foundation for Strategic Environmental Research). This work is supported by CORWES (CGL2010-22158-C02) and EXTREMBLES (CGL2010-21869) projects funded by the Spanish R&D programme and the European COST ACTION VALUE (ES1102). A. C. thanks the Spanish Ministry of Economy and Competitiveness for the funding provided within the FPI programme (BES-2011-047612 and EEBB-I-13-06354). We also thank two anonymous referees for their useful comments that helped to improve the original manuscript

HTLV-1 infection in solid organ transplant donors and recipients in Spain

HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3–5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes. © 2021, The Author(s), under exclusive licence to Springer Nature Limited

Bioinspired gelatin/bioceramic composites loaded with bone morphogenetic protein-2 (BMP-2) promote osteoporotic bone repair

There are currently several commercialized products approved by the Food and Drug Administration and the European Medicines Agency based on the use of recombinant human BMP-2 for the treatment of non-unions long fractures and spinal fusion. However, the adverse effects recorded with the use of BMPs suggest the need for drug delivery carriers that allow reducing the required doses and improve their cost-effectiveness. Herein, we have developed a new osteoconductive scaffold that reduces the required doses of BMP-2 for promoting bone regeneration in an osteoporotic defect model. The composite is, in brief, a gelatin-based 3D scaffold reinforced with either calcium sulfate or hydroxyapatite as an inorganic osteoconductive biomaterial. To this end, the organic/inorganic composite systems showed high hydration capacity and good in vitro degradability. The incorporation of 7.5% (m/v) ceramic compounds resulted in scaffolds with stiffer Young modulus (179 and 75 kPa for CaSO4_7 and HA_7, respectively) than bare gelatin hydrogels (48 kPa). Studies with human bone-marrow derived mesenchymal stem cells (hBM-MSCs) revealed that the 3D scaffolds promote cell adhesion and proliferation along with osteogenic differentiation capabilities. Specifically, downregulation of stemness (Nanog, Oct4) genes and upregulation of osteogenic markers (ALP, Col1a1, Fmod) by two fold were observed over 10 days under basal culture conditions. Promisingly, the sustained in vitro release of BMP-2 observed from the porous reinforced scaffolds allowed us to address the critical-sized osteoporotic mice calvarial defects with a relatively low growth factor doses (600 ng BMP-2/scaffold) compared to conventional doses at 2-15 micrograms. Overall, this study demonstrates the promising potential of osteoconductive gelatin/calcium bioceramics composites as osteogenic growth factors delivery carriers for bone-regeneration via ultra-low growth factor doses

Disruption of Nuclear Organization during the Initial Phase of African Swine Fever Virus Infection ▿

African swine fever virus (ASFV), the causative agent of one of the most devastating swine diseases, has been considered exclusively cytoplasmic, even though some authors have shown evidence of an early stage of nuclear replication. In the present study, an increment of lamin A/C phosphorylation was observed in ASFV-infected cells as early as 4 h postinfection, followed by the disassembling of the lamina network close to the sites where the viral genome starts its replication. At later time points, this and other nuclear envelope markers were found in the cytoplasm of the infected cells. The effect of the infection on the cell nucleus was much more severe than previously expected, since a redistribution of other nuclear proteins, such as RNA polymerase II, the splicing speckle SC-35 marker, and the B-23 nucleolar marker, was observed from 4 h postinfection. All this evidence, together with the redistribution, dephosphorylation, and subsequent degradation of RNA polymerase II after ASFV infection, suggests the existence of sophisticated mechanisms to regulate the nuclear machinery during viral infection

The NUTRAOLEOUM Study, a randomized controlled trial, for achieving nutritional added value for olive oils

Background: Virgin olive oil, a recognized healthy food, cannot be consumed in great quantities. We aim to assess in humans whether an optimized virgin olive oil with high phenolic content (OVOO, 429 mg/Kg) and a functional one (FOO), both rich in phenolic compounds (429 mg/Kg) and triterpenic acids (389 mg/kg), could provide health benefits additional to those supplied a by a standard virgin olive oil (VOO). Methods/design: A randomized, double-blind, crossover, controlled study will be conducted. Healthy volunteers (aged 20 to 50) will be randomized into one of three groups of daily raw olive oil consumption: VOO, OVOO, and FOO (30 mL/d). Olive oils will be administered over 3-week periods preceded by 2-week washout ones. The main outcomes will be markers of lipid and DNA oxidation, inflammation, and vascular damage. A bioavailability and dose-response study will be nested within this sustained- consumption one. It will be made up of 18 volunteers and be performed at two stages after a single dose of each olive oil. Endothelial function and nitric oxide will be assessed at baseline and at 4 h and 6 h after olive oil single dose ingestion. Discussion: For the first time the NUTRAOLEUM Study will provide first level evidence on the health benefits in vivo in humans of olive oil triterpenes (oleanolic and maslinic acid) in addition to their bioavailability and disposition