An alternative approach to estimate any subdaily extreme of rainfall and wind from usually available records

A wide variety of engineering applications requires the use of maximum values of rainfall intensity and wind speed related to short recording intervals, which can often only be estimated from available less exhaustive records. Given that many locations lack exhaustive climatic records that would allow accurate empirical correlations between different recording intervals to be identified, generic equations are often used to estimate these extreme values. The accuracy of these generic estimates is especially important in fields such as the study of wind-driven rain, in which both climatic variables are combined to characterise the phenomenon. This work assesses the reliability and functionality of some of these most widespread generic equations, analysing climatic datasets gathered since 2008 in 109 weather stations in Spain and the Netherlands. Considering multiple recording intervals at each location, it is verified that most of these generic estimations, used especially in the study of wind-driven rain, have functional limitations and can cause significant errors when characterising both variables for subdaily intervals and extreme conditions. Finally, an alternative approach is proposed to accurately extrapolate extreme values of both variables related to any subdaily recording interval in a functional manner and from any available records. © 2021, The Author(s)

Air temperature measurements using autonomous self-recording dataloggers in mountainous and snow covered areas

High mountain areas are poorly represented by official weather observatories. It implies that new instruments must be evaluated over snow-covered and strongly insolated environments (i.e. mid-latitude mountain areas). We analyzed uncertainty sources over snow covered areas including: 1) temperature logger accuracy and bias of two widely used temperature sensors (Tinytag and iButton); 2) radiation shield performance under various radiation, snow, and wind conditions; 3) appropriate measurement height over snow covered ground; and 4) differences in air temperature measured among nearby devices over a horizontal band. The major results showed the following. 1) Tinytag performance device (mean absolute error: MAE≈ 0.1–0.2°C in relation to the reference thermistor) was superior to the iButton (MAE≈ 0.7°C), which was subject to operating errors. 2) Multi-plate radiation shield showed the best performance under all conditions (> 90% samples has bias between ±0.5°C). The tube shield required wind (> 2.5ms⁠−1) for adequate performance, while the funnel shield required limited radiation (< 400Wm⁠−2). Snow cover causes certain overheating. 3) Air temperatures were found to stabilize at 75–100cm above the snow surface. Air temperature profile was more constant at night, showing a considerable cooling on near surface at midday. 4) Horizontal air temperature differences were larger at midday (0.5°C). These findings indicate that to minimize errors air temperature measurements over snow surfaces should be carried out using multi-plate radiation shields with high-end thermistors such as Tinytags, and be made at a minimum height above the snow covered ground.This study was funded by the research projects “El papel de la nieve en la hidrología de la peninsula ibérica y su respuesta a procesos de cambio global-HIDROIBERNIEVE-CGL2017-82216-R” and CLIMPY “Characterization of the evolution of climate and provision of information for adaptation in the Pyrenees” (FEDER-POCTEFA)

Clinical impact of acute kidney injury on short- and long-term outcomes after transcatheter aortic valve implantation with the CoreValve prosthesis

AbstractBackgroundAcute kidney injury (AKI) after cardiac surgery is associated with increased mortality, but few data exist on the occurrence and clinical impact of AKI associated with transcatheter aortic valve implantation (TAVI). The objective of this study was to determine the incidence and prognosis of AKI after percutaneous implantation of the CoreValve® (Medtronic, Minneapolis, MN, USA) prosthesis.MethodsA total of 357 patients with severe aortic stenosis and 9 patients with pure native aortic regurgitation were treated with the CoreValve prosthesis. AKI was defined according to Valve Academic Research Consortium criteria as the absolute increase in serum creatinine ≥0.3mg/dl at 72h post percutaneous procedure.ResultsAKI was identified in 58 patients (15.8%), none of whom required renal replacement therapy. In patients with AKI, the mortality at 30 days was 13.5% compared with 1.6% of patients without AKI, [odds ratio (OR)=12.2 (95% CI 3.53–41.9); p<0.001] and total mortality after a mean of 26.2±17 months was 29.3% vs. 14.9% [OR=2.36 (95% CI 1.23–4.51), p=0.008]. In the multivariate analysis, AKI was an independent predictor of cumulative total mortality [hazard ratio=2.151, (95% CI from 1.169 to 3.957), p=0.014].ConclusionsThe deterioration of renal function in patients undergoing TAVI with the CoreValve prosthesis is a serious and frequent complication. The occurrence of AKI was associated with increased early mortality and was also a predictor of worse outcomes in follow-up

CD13 as a new tumor target for antibody-drug conjugates: validation with the conjugate MI130110

BACKGROUND: In the search for novel antibody-drug conjugates (ADCs) with therapeutic potential, it is imperative to identify novel targets to direct the antibody moiety. CD13 seems an attractive ADC target as it shows a differential pattern of expression in a variety of tumors and cell lines and it is internalized upon engagement with a suitable monoclonal antibody. PM050489 is a marine cytotoxic compound tightly binding tubulin and impairing microtubule dynamics which is currently undergoing clinical trials for solid tumors. METHODS: Anti-CD13 monoclonal antibody (mAb) TEA1/8 has been used to prepare a novel ADC, MI130110, by conjugation to the marine compound PM050489. In vitro and in vivo experiments have been carried out to demonstrate the activity and specificity of MI130110. RESULTS: CD13 is readily internalized upon TEA1/8 mAb binding, and the conjugation with PM050489 did not have any effect on the binding or the internalization of the antibody. MI130110 showed remarkable activity and selectivity in vitro on CD13-expressing tumor cells causing the same effects than those described for PM050489, including cell cycle arrest at G2, mitosis with disarrayed and often multipolar spindles consistent with an arrest at metaphase, and induction of cell death. In contrast, none of these toxic effects were observed in CD13-null cell lines incubated with MI130110. Furthermore, in vivo studies showed that MI130110 exhibited excellent antitumor activity in a CD13-positive fibrosarcoma xenograft murine model, with total remissions in a significant number of the treated animals. Mitotic catastrophes, typical of the payload mechanism of action, were also observed in the tumor cells isolated from mice treated with MI130110. In contrast, MI130110 failed to show any activity in a xenograft mouse model of myeloma cells not expressing CD13, thereby corroborating the selectivity of the ADC to its target and its stability in circulation. CONCLUSION: Our results show that MI130110 ADC combines the antitumor potential of the PM050489 payload with the selectivity of the TEA1/8 monoclonal anti-CD13 antibody and confirm the correct intracellular processing of the ADC. These results demonstrate the suitability of CD13 as a novel ADC target and the effectiveness of MI130110 as a promising antitumor therapeutic agent.This work was partially supported by grant IPT-2012-0198-090000 (“MARINMAB” project) from Ministerio de Economía y Competitividad (MINECO) and European Regional Development’s funds (ERDF) and by CSIC grant 2019AEP146.S

Diseño del instrumento de ayuda para la toma de decisiones: “alternativas de tratamiento para el cáncer de mama: ¿qué opción prefiero?”

Purpose: To design a Decision-making Aid within the ‘Breast cancer’ healthcare process modelling of the Andalusian Public Health System (SSPA) for the therapeutic approach of early-stage disease. Methods: The Decision Aid design was conducted in four phases: 1) Explore the receptiveness of users and professionals in the mainstream of the SSPA Decision Aid “Breast Cancer” process. 2) Select a Decision Aid from international experiences. 3) Transcultural adaptation of above selected Decision Aid. 4) Decision Aid Validation in the SSPA. Results: The Decision Aid “Alternative treatment for breast cancer: What option do I prefer?” designed for the SSPA includes innovative contents compared to other reviewed experiences. The results of the validation of Decision Aid have shown that the design is attractive for the patient, ideal size and suitable language, and that the clinical information it contains is of quality. The Decision Aid answers your questions (95%) and summarizes the essential information to make the decision (90%). The Decision Aid offers relevant information that help the patient in the decision making process (lack of decisional confl ict: 85.31), facilitates the work in the practice and doctor-patient communication. Conclusion: Patients and professionals agree to recommend the use of Decision Aid and to encourage participation in decisionmaking while recognizing that the time factor is the main obstacle to incorporate its use in the SSPA.Objetivo: Diseñar un Instrumento de Ayuda para la Toma de Decisiones (IATD) en el Proceso Asistencial Integrado ‘Cáncer de mama’ del Sistema Sanitario Público de Andalucía (SSPA) para el abordaje terapéutico de esta enfermedad en estadio inicial. Método: El diseño del IATD se realizó en cuatro fases: 1) Explorar la receptividad de las usuarias y los profesionales del SSPA sobre la incorporación de IATD en el proceso “Cáncer de mama”. 2). Seleccionar un IATD entre las experiencias internacionales.; 3) Adaptar transculturalmente del IATD seleccionado al entorno del SSPA. 4) Validar el IATD en el SSPA. Resultado: El IATD “Alternativas de tratamiento para el cáncer de mama: ¿Qué opción prefiero?” diseñado para el SSPA incluye contenidos innovadores frente a otras experiencias revisadas. Los resultados de la validación del IATD han mostrado que su diseño es atractivo para la paciente, su extensión y lenguaje idóneos, y la información clínica que contiene es de calidad. El Instrumento resuelve sus dudas (95%) y resume la información esencial para tomar la decisión (90%). El IATD ofrece información relevante que prepara a la paciente para la toma de decisiones (ausencia de conflicto decisional: 85,31), facilita la labor en consulta y la comunicación médico-paciente. Conclusiones: Pacientes y profesionales coinciden en recomendar la utilización del IATD y fomentar la participación en la toma de decisiones aunque reconocen que el factor tiempo es el principal obstáculo para incorporar su uso en el SSPA

Upgrade of a climate service tailored to water reservoirs management

We present the upgrade of a web tool designed to help in the decision making process for water reservoirs management in Spain. The tool, called S-ClimWaRe (Seasonal Climate predictions in support of Water Reservoirs management), covers the extended winter season (from November to March), when the North Atlantic Oscillation (NAO) pattern strongly influences the hydrological interannual variability in South-Western Europe. This climate service is fully user driven, and aims at meeting their requirements incorporating recent scientific progress.The research leading to these results has received funding from the MEDSCOPE project co-funded by the European Commission as part of ERA4CS, an ERA-NET initiated by JPI Climate, grant agreement 690462

Elaboración de recursos docentes para la enseñanza presencial y semipresencial en el área de la Ingeniería Química empleando Jupyter Notebook

El objetivo principal de este proyecto es la elaboración de recursos docentes, para estudiantes y profesores, dentro del área de la Ingeniería Química, utilizando el software libre Jupyter Notebook, empleado bajo el lenguaje de programación Python

The Absence of Caspase-8 in the Dopaminergic System Leads to Mild Autism-like Behavior

In the last decade, new non-apoptotic roles have been ascribed to apoptotic caspases. This family of proteins plays an important role in the sculpting of the brain in the early stages of development by eliminating excessive and nonfunctional synapses and extra cells. Consequently, impairments in this process can underlie many neurological and mental illnesses. This view is particularly relevant to dopamine because it plays a pleiotropic role in motor control, motivation, and reward processing. In this study, we analyze the effects of the elimination of caspase-8 (CASP8) on the development of catecholaminergic neurons using neurochemical, ultrastructural, and behavioral tests. To do this, we selectively delete the CASP8 gene in cells that express tyrosine hydroxylase with the help of recombination through the Cre-loxP system. Our results show that the number of dopaminergic neurons increases in the substantia nigra. In the striatum, the basal extracellular level of dopamine and potassium-evoked dopamine release decreased significantly in mice lacking CASP8, clearly showing the low dopamine functioning in tissues innervated by this neurotransmitter. This view is supported by electron microscopy analysis of striatal synapses. Interestingly, behavioral analysis demonstrates that mice lacking CASP8 show changes reminiscent of autism spectrum disorders (ASD). Our research reactivates the possible role of dopamine transmission in the pathogenesis of ASD and provides a mild model of autism.Ministerio de Economía y Competitividad RTI2018-098645-B-I00, PID2019-109569GB-I00, RTI2018-099778-B-I00Junta de Andalucía P18-RT-1372, US-1264806, PI-0080-2017, PI-0009-2017, PI-0134-2018, PEMP-0008-2020, P20_00958, CTS-510Instituto de Salud Carlos III PI18/01691Instituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz-INiBICA LI19/06IN-CO22, IN-C09European Union 95568

Silver clusters of five atoms as highly selective antitumoral agents through irreversible oxidation of thiols

Low atomicity clusters present properties dependent on the size, due to the quantum confinement, with well-defined electronic structures and high stability. Here it is shown that Ag5 clusters catalyze the complete oxidation of sulfur to S+6. Ag5 catalytic activity increases with different oxidant species in the order O2 ≪ H2O2 < OH•. Selective oxidation of thiols on the cysteine residues of glutathione and thioredoxin is the primary mechanism human cells have to maintain redox homeostasis. Contingent upon oxidant concentration, Ag5 catalyzes the irreversible oxidation of glutathione and thioredoxin, triggering apoptosis. Modification of the intracellular environment to a more oxidized state to mimic conditions within cancer cells through the expression of an activated oncogene (HRASG12V) or through ARID1A mutation, sensitizes cells to Ag5 mediated apoptosis. While cancers evolve to evade treatments designed to target pathways or genetic mutations that drive them, they cannot evade a treatment that takes advantage of aberrant redox homeostasis, which is essential for tumor progression and metastasis. Ag5 has antitumor activity in mice with orthotopic lung tumors reducing primary tumor size, and the burden of affected lymphatic nodes. The findings suggest the unique intracellular redox chemistry of Ag5 may lead to new redox-based approaches to cancer therapyThis research was partially supported by 1) “la Caixa” Foundation, Ref. LCF/PR/PR12/11070003 to F.D. and M.A.L.Q.; 2) Ministerio de Ciencia, Innovación y Universidades (MAT2017-89678-R, AEI/FEDER, UE) to F.D. and A.V.; 3) the Consellería de Educación (Xunta de Galicia), Grants No. Grupos Ref. Comp. ED431C 2017/22, ED431C 2019/13 and AEMAT-ED431E2018/08 to M.A.L.Q.; and ED431C 2019/13 to A.V. This project has received funding from the European Union's Horizon 2020 Research and Innovation Programme (Bac-To-Fuel) under Grant Agreement No. 825999 (M.A.L.Q.). J.C.H. acknowledge financial support from European Union's Horizon 2020 research and innovation programme under grant agreement no. 823717-ESTEEM3, and the MICIIN (projects PID2019-107578GA-100 and PID-110018GA-100). J.M.D, L.J.G., and F.G.R. thank to the ANPCyT (PICT 2015-2285 and 2017-3944), UNLP (Project 11/X790) and the partial support by the Laboratório Nacional de Luz Síncrotron (LNLS, Brazil) under proposal SXS-20180280. G.B. acknowledges the CINECA Award N. IsC51, year 2017, under the ISCRA initiative, for the availability of high-performance computing resources and support. D.B. expresses gratitude for a postdoctoral grant from Xunta de Galicia, Spain (POS-A/2013/018). B.D. expresses gratitude for a predoctoral grant from MICINN, Spain (BES-2016-076765). F.D. and A.V. also acknowledged Xunta de Galicia (Centro singular de investigación de Galicia accreditation 2019-2022 ref ED431G 2019/02) and the European Union (European Regional Development Fund – ERDF). Work in M.P.M.'s lab was supported by the Medical Research Council UK (MC_U105663142). T.G.C. gratefully acknowledges the technical assistance of María José Otero-Fraga (FIDIS)S