A model for the assessment of bluetongue virus serotype 1 persistence in Spain

Bluetongue virus (BTV) is an arbovirus of ruminants that has been circulating in Europe continuously for more than two decades and has become endemic in some countries such as Spain. Spain is ideal for BTV epidemiological studies since BTV outbreaks from different sources and serotypes have occurred continuously there since 2000; BTV-1 has been reported there from 2007 to 2017. Here we develop a model for BTV-1 endemic scenario to estimate the risk of an area becoming endemic, as well as to identify the most influential factors for BTV-1 persistence. We created abundance maps at 1-km2 spatial resolution for the main vectors in Spain, Culicoides imicola and Obsoletus and Pulicaris complexes, by combining environmental satellite data with occurrence models and a random forest machine learning algorithm. The endemic model included vector abundance and host-related variables (farm density). The three most relevant variables in the endemic model were the abundance of C. imicola and Obsoletus complex and density of goat farms (AUC 0.86); this model suggests that BTV-1 is more likely to become endemic in central and southwestern regions of Spain. It only requires host- and vector-related variables to identify areas at greater risk of becoming endemic for bluetongue. Our results highlight the importance of suitable Culicoides spp. prediction maps for bluetongue epidemiological studies and decision-making about control and eradication measures

Identifying spanish areas at more risk of monthly BTV transmission with a basic reproduction number approach

Bluetongue virus (BTV) causes a disease that is endemic in Spain and its two major biological vector species, C. imicola and the Obsoletus complex species, differ greatly in their ecology and distribution. Understanding the seasonality of BTV transmission in risk areas is key to improving surveillance and control programs, as well as to better understand the pathogen transmission networks between wildlife and livestock. Here, monthly risk transmission maps were generated using risk categories based on well-known BTV R0 equations and predicted abundances of the two most relevant vectors in Spain. Previously, Culicoides spp. predicted abundances in mainland Spain and the Balearic Islands were obtained using remote sensing data and random forest machine learning algorithm. Risk transmission maps were externally assessed with the estimated date of infection of BTV-1 and BTV-4 historical outbreaks. Our results highlight the differences in risk transmission during April-October, June-August being the period with higher R0 values. Likewise, a natural barrier has been identified between northern and central-southern areas at risk that may hamper BTV spread between them. Our results can be relevant to implement risk-based interventions for the prevention, control and surveillance of BTV and other diseases shared between livestock and wildlife host populations

CFD investigation of a complete floating offshore wind turbine

This chapter presents numerical computations for floating offshore wind turbines for a machine of 10-MW rated power. The rotors were computed using the Helicopter Multi-Block flow solver of the University of Glasgow that solves the Navier-Stokes equations in integral form using the arbitrary Lagrangian-Eulerian formulation for time-dependent domains with moving boundaries. Hydrodynamic loads on the support platform were computed using the Smoothed Particle Hydrodynamics method. This method is mesh-free, and represents the fluid by a set of discrete particles. The motion of the floating offshore wind turbine is computed using a Multi-Body Dynamic Model of rigid bodies and frictionless joints. Mooring cables are modelled as a set of springs and dampers. All solvers were validated separately before coupling, and the loosely coupled algorithm used is described in detail alongside the obtained results

Implementation and validation of an economic module for the epidemiological model Be-FAST to predict the costs generated by livestock diseases epidemics. Application to the Classical Swine Fever case in Spain.

Classical Swine Fever (CSF) is one of the most harmful livestock di-seases for the economy of the swine sector worldwide. Specifically in Spain, the costs in the two last CSF outbreaks (1997 and 2001) have been estimated above 108 million euros. In this work, we aim to evaluate the economic impact of important livestock disease epidemics, and particularly the CSF in Spain. This study starts with a preliminary classification of the costs associated with CSF epidemics. In order to estimate the expected costs of a given epidemic in a considered area, a new economic module has been integrated into the epidemiological model Be-FAST, a time-spatial stochastic spread mathematical model for studying the transmission of diseases within and between farms. The input data for economic parameters have been obtained from entities related with the swine industry in Spain. The new Be-FAST module is tested by comparing the results obtained with historical data from CSF epidemics in Spain. The outcomes show that severe CSF epidemics also have a strong economic impact with around 80% of the costs related to animal culling, while costs associated with control measures are directly associated with the number of infected farms and the duration of the epidemic. The results presented in this work are expected to provide valuable information to decision makers, including animal health officials and insurance companies, and can be extended to other livestock diseases or used to predict the economic impact of future outbreaks

Desarrollo de simulador de negocios en la industria de sensores: estrategia y toma de decisiones

En el presente trabajo se exponen las decisiones tomadas en el simulador de negocios Capstone en el que se trabajó en una compañía de la industria de sensores. Se presenta el marco teórico en el que se define el concepto de estrategia y se revisan teorías de distintos autores. Se hace un análisis general de la industria de sensores y se establecen las estrategias que se implementarán en la compañía

Implementation and validation of an economic module for the epidemiological model Be-FAST to predict the costs generated by livestock diseases epidemics. Application to the Classical Swine Fever case in Spain

Abstract Classical Swine Fever (CSF) is one of the most harmful livestock diseases for the economy of the swine sector worldwide. Specifically in Spain, the costs in the two last CSF outbreaks (1997 and 2001) have been estimated above 108 million euros. In this work, we aim to evaluate the economic impact of important livestock disease epidemics, and particularly the CSF in Spain. This study starts with a preliminary classification of the costs associated with CSF epidemics. In order to estimate the expected costs of a given epidemic in a considered area, a new economic module has been integrated into the epidemiological model Be-FAST, a time-spatial stochastic spread mathematical model for studying the transmission of diseases within and between farms. The input data for economic parameters have been obtained from entities related with the swine industry in Spain. The new Be-FAST module is tested by comparing the results obtained with historical data from CSF epidemics in Spain. The outcomes show that severe CSF epidemics also have a strong economic impact with around 80% of the costs related to animal culling, while costs associated with control measures are directly associated with the number of infected farms and the duration of the epidemic. The results presented in this work * Corresponding author: [email protected] 1 are expected to provide valuable information to decision makers, including animal health officials and insurance companies, and can be extended to other livestock diseases or used to predict the economic impact of future outbreaks

Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma.

Background Glioblastoma (GBM) is one of the most aggressive and vascularized brain tumors in adults, with a median survival of 20.9 months. In newly diagnosed and recurrent GBM, bevacizumab demonstrated an increase in progression-free survival, but not in overall survival. Methods We conducted an in silico analysis of VEGF expression, in a cohort of 1082 glioma patients. Then, to determine whether appropriate bevacizumab dose adjustment could increase the anti-angiogenic response, we used in vitro and in vivo GBM models. Additionally, we analyzed VEGFA expression in tissue, serum, and plasma in a cohort of GBM patients before and during bevacizumab treatment. Results We identified that 20% of primary GBM did not express VEGFA suggesting that these patients would probably not respond to bevacizumab therapy as we proved in vitro and in vivo. We found that a specific dose of bevacizumab calculated based on VEGFA expression levels increases the response to treatment in cell culture and serum samples from mice bearing GBM tumors. Additionally, in a cohort of GBM patients, we observed a correlation of VEGFA levels in serum, but not in plasma, with bevacizumab treatment performance. Conclusions Our data suggest that bevacizumab dose adjustment could improve clinical outcomes in Glioblastoma treatment.post-print1360 K

Effectiveness and safety of sofosbuvir‐based regimens plus an NS5A inhibitor for patients with HCV genotype 3 infection and cirrhosis: results of a multicenter real‐life cohort

[Abstract] Patients with HCV genotype 3 (GT3) infection and cirrhosis are currently the most difficult to cure. We report our experience with sofosbuvir+daclatasvir (SOF+DCV) or sofosbuvir/ledipasvir (SOF/LDV), with or without ribavirin (RBV) in clinical practice in this population. This was a multicenter observational study including cirrhotic patients infected by HCV GT3, treated with sofosbuvir plus an NS5A inhibitor (May 2014‐October 2015). In total, 208 patients were included: 98 (47%) treatment‐experienced, 42 (20%) decompensated and 55 (27%) MELD score >10. In 131 (63%), treatment was SOF+DCV and in 77 (37%), SOF/LDV. Overall, 86% received RBV. RBV addition and extension to 24 weeks was higher in the SOF/LDV group (95% vs 80%, P=.002 and 83% vs 72%, P=.044, respectively). A higher percentage of decompensated patients were treated with DCV than LDV (25% vs 12%, P=.013). Overall, SVR12 was 93.8% (195/208): 94% with SOF+DCV and 93.5% with SOF/LDV. SVR12 was achieved in 90.5% of decompensated patients. Eleven treatment failures: 10 relapses and one breakthrough. RBV addition did not improve SVR (RR: 1.08; P=.919). The single factor associated with failure to achieve SVR was platelet count <75×10E9/mL (RR: 3.50, P=.019). In patients with MELD <10, type of NS5A inhibitor did not impact on SVR12 (94% vs 97%; adjusted RR: 0.49). Thirteen patients (6.3%) had serious adverse events, including three deaths (1.4%) and one therapy discontinuation (0.5%), higher in decompensated patients (16.7% vs 3.6%, P<.006). In patients with GT3 infection and cirrhosis, SVR12 rates were high with both SOF+DCV and SOF/LDV, with few serious adverse events

Reconstruction of Past Environment and Climate Using Wetland Sediment Records from the Sierra Nevada

Understanding the effects of climate change and human activities on fragile mountain ecosystems is necessary to successfully managing these environments under future climate scenarios (e.g., global warming, enhanced aridity). This can be done through the study of paleoecological records, which can provide long paleoenvironmental databases containing information on how ecosystems reacted to climate change and human disturbances before the historical record. These studies can be particularly interesting when focusing on especially warm and/or dry past climatic phases. Biotic (pollen, charcoal) and abiotic (physical, geochemistry) analyses from wetland sediment records from the Sierra Nevada, southern Spain record changes in vegetation, fire history and lake sedimentation since ~11,700 years (cal yr BP). This multiproxy paleoecological study indicates that maxima in temperature and humidity occurred in the area in the Early and Middle Holocene, with a peak in precipitation between ~10,500 and 7000 cal yr BP. This is deduced by maxima in water runoff, the highest abundance of tree species and algae and high total organic carbon values recorded in the alpine wetland’s sedimentary records of the Sierra Nevada during that time period. In the last 7000 cal yr BP, and especially after a transition period between ~7000 and 5000 cal yr BP, a progressive aridification process took place, indicated by the decrease in tree species and the increase in xerophytic herbs in this region and a reduction in water runoff evidenced by the decrease in detritic input in the wetland sedimentary records. An increasing trend in Saharan dust deposition in the Sierra Nevada wetlands is also recorded through inorganic geochemical proxies, probably due to a coetaneous loss of vegetation cover in North Africa. The process of progressive aridification during the Middle and Late Holocene was interrupted by millennial-scale climatic oscillations and several periods of relative humid/droughty conditions and warm/cold periods have been identified in different temperature and/or precipitation proxies. Enhanced human impact has been observed in the Sierra Nevada in the last ~3000 cal yr BP through the increase in fires, grazing, cultivation, atmospheric pollution as well as reforestation by Pinus and the massive cultivation of Olea at lower altitudes.This study was supported by projects CGL2013-47038-R and CGL2017-85415-R funded by Ministerio de Economía y Competitividad of Spain and Fondo Europeo de Desarrollo Regional FEDER; Séneca Project 20788/PI/18; Junta de Andalucía I+D+i Junta de Andalucía 2020 Retos P-20-00059, FEDER Project B-RNM-144-UGR18, UGR-FEDER B-RNM-144-UGR18 Proyectos I + D + i del Programa Operativo FEDER 2018 and the research group RNM-190 (Junta de Andalucía). M.J.R.R. acknowledges the postdoctoral funding provided by the European Commission/H2020 (ERC-2017-ADG, project number 788616). J.C. acknowledges the postdoctoral funding provided by the Academy of Finland (project number 316702). A.G.-A. acknowledges the Ramón y Cajal fellowship RYC-2015-18966 provided by the Ministerio de Economía y Competitividad of the Spanish Government. M.R.G. acknowledges funding by the Juan de la Cierva-Incorporación program in the University of Granada (IJCI-2017-33755) from Secretaría de Estado de I+D+i, Spain. RSA acknowledges several travel grants from Northern Arizona University to support this work