Evolución temporal de las olas de calor en la meseta central española, entre 1961 y 2010

Ponencia presentada en: VIII Congreso de la Asociación Española de Climatología celebrado en Salamanca entre el 25 y el 28 de septiembre de 2012.[ES]Se establece el comportamiento temporal de las frecuencias anuales de olas de calor producidas entre 1961 y 2010. A partir de los datos diarios de anomalías de temperatura se determinan las series de anomalías diarias de temperaturas máxima (ATMAD) y mínima (ATMID) para el área de trabajo. Se obtienen los valores umbrales de las dichas anomalías, determinados por el percentil P90 de las series correspondientes. Se establece la existencia de ola de calor cuando se observan dos o más días consecutivos en los que ATMAD y ATMID superan, simultáneamente, los valores de los umbrales establecidos. Se identifican las olas de calor que han afectado a la Meseta Central española durante el periodo de estudio y se establecen sus frecuencias mensuales y anuales. Los resultados indican que los meses de mayor número de olas de calor entre 1961 y 2010, son Mayo (25 olas) y Junio (23 olas). El análisis de tendencia de las series de frecuencias anuales obtenidas indica que existe una tendencia creciente de las olas de calor con un nivel de confianza mayor del 99%. El modelo lineal establece que, se ha producido un aumento en la frecuencia de olas de calor en la Meseta Central española del orden de 0,6 olas cada 10 años.[EN]The temporal behavior of annual frequency of heat waves, produced between 1961 and 2010, is established. From the daily data of temperature, the maximum and the minimum temperature anomalies (ATMAD and ATMID) for the studied zone are obtained. The values of the thresholds of these anomalies, determined by the 90 percentile of the corresponding series are calculated. The existence of heat wave is established when there are two or more consecutive days in which ATMAD and ATMID exceed, at the same time, the values of the corresponding thresholds. The heat waves that have affected the Spanish Central Plateau during the study period are identified, and its annual and monthly frequencies are established. The results indicate that the months of highest number of waves of heat between 1961and 2010 are May (25 waves) and June (23 waves). Analysis of trend of the series of annual frequencies obtained indicates that there is an increasing trend of heat waves to a greater than 99% confidence level. The linear model establishes that there has been an increase in the frequency of heat waves in the Spanish Central Plateau in the order of 0.6 waves every 10 years.Este trabajo se ha realizado en el marco del proyecto de investigación CGL2009-08565 financiado por el MICINN

Tendencia de las frecuencias de las olas de frío en la meseta central española, entre 1961 y 2010

Ponencia presentada en: VIII Congreso de la Asociación Española de Climatología celebrado en Salamanca entre el 25 y el 28 de septiembre de 2012.[ES]A partir de las series de datos diarios de anomalías de temperatura máxima (ATMAD) y mínima (ATMID), se analiza el comportamiento de las olas de frío detectadas en ella durante el periodo 1961- 2010. En función de los valores umbrales de ATMAD y ATMID determinados por el percentil P10 de las series de trabajo se establecen los días extremadamente fríos. Se define una ola de frío como una sucesión de dos o más días consecutivos en los que las ATMAD y ATMID son inferiores, simultáneamente, a los umbrales establecidos. Se identifican las olas de frío en el intervalo de estudio y se determinan sus frecuencias mensuales y anuales.[EN]From the series of daily data of anomalies of maximum temperature (ATMAD) and minimum temperature (ATMID), the behavior of cold waves detected in it during the period 1961-2010 is analyzed. Extremely cold days are established based on the thresholds values for ATMAD and ATMID determined by the P10 percentile of the work series. Defines a cold wave as a succession of two or more consecutive days in which the ATMAD and ATMID are below, at the same time, to the established thresholds. The waves of cold in the interval of study are identified and their monthly and annual frequencies are determined.Este trabajo se ha realizado en el marco del proyecto de investigación CGL2009-08565 financiado por el MICINN

Iridium(I)-Catalyzed Intramolecular Cycloisomerization of Enynes: Scope and Mechanistic Course

NOTICE: This is the peer reviewed version of the following article: David F. Fernández, Catarina A. B. Rodrigues, Martín Calvelo, Moisés Gulías, José L. Mascareñas and Fernando López (2018), Iridium(I)-Catalyzed Intramolecular Cycloisomerization of Enynes: Scope and Mechanistic Course. ACS Catalysis, 2018, 8 (8), 7397–7402 [DOI: 10.1021/acscatal.8b02139]. This article may be used for non-commercial purposes in accordance with American Chemical Society Terms and Conditions for self-archivingWe report an Ir(I)-catalyzed cycloisomerization methodology that provides access to carbocyclic systems bearing exo-alkene moieties from alkynyl-equipped acyclic precursors. The method relies on the C–H activation of olefinic and (hetero)aromatic C(sp2)–H bonds, followed by an exocyclization to a tethered alkyne, and provides interesting cyclic diene products that are amenable of further elaboration. Importantly, DFT calculations suggests that, in contrast to related hydrocarbonations of alkenes in which either migratory insertions or C–C reductive eliminations have been suggested to be rate-determining, in our reactions, the energetic barrier of these steps is lower than that of the previous C–H activationThis work received financial support from the Spanish MINECO (Nos. SAF2016-76689-R, CTQ2016-77047-P, and CTQ2017-84767-P, as well as an FPI fellowship to D.F.F.), the Xunta de Galicia (Nos. ED431C 2017/19 and 2015-CP082, as well as Centro Singular de Investigación de Galicia accreditation 2016-2019 ED431G/09 and predoctoral fellowship to M.C.), the ERDF, ERC (Adv. Grant No. 340055) and the Orfeo-Cinqa network (No. CTQ2016-81797-REDC). Dr. Rebeca García-Fandiño is acknowledged for helpful suggestions on DFT studiesS

Hepatitis B surface antigen loss after discontinuing nucleos(t)ide analogue for treatment of chronic hepatitis B patients is persistent in White patients

[Objective]: The objective of this study was to determine the long-term clinical outcome and persistence of hepatitis B surface antigen (HBsAg) loss after discontinuation of treatment. [Background]: The prognosis of patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs) who discontinue treatment after loss of HBsAg remains largely unknown, particularly in White patients. [Patients and methods]: We analysed a cohort of patients with CHB who discontinued NA treatment after loss of HBsAg. A total of 69 patients with hepatitis-B-e antigen-positive or hepatitis-B-e antigen-negative CHB with undetectable HBsAg during NA treatment were included after discontinuation of treatment, and followed up for a median period of 37.8 months (interquartile range: 23.8–54.6 months). [Results]: At the end of follow-up, none of the patients showed spontaneous reappearance of HBsAg and only one patient had detectable hepatitis B virus DNA (22 IU/ml). Another patient negative for HBsAg and anti-HBs developed hepatitis B virus reactivation without elevated transaminases after treatment with corticosteroids and vincristine for dendritic cell neoplasm, 38 months after withdrawal of the antiviral treatment. Regarding clinical outcome, a patient with cirrhosis developed hepatocellular carcinoma, 6.6 years after discontinuing treatment. None of the patients had hepatic decompensation or underwent liver transplantation. [Conclusion]: HBsAg clearance after discontinuing NAs in patients with CHB is persistent and associated with good prognosis. The risk for developing hepatocellular carcinoma persists among patients with cirrhosis

The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70

J-domain proteins tune the specificity of Hsp70s, engaging them in precise functions. Despite their essential role, the structure and function of many J-domain proteins remain largely unknown. We explore human DNAJA2, finding that it reversibly forms highly-ordered, tubular structures that can be dissociated by Hsc70, the constitutively expressed Hsp70 isoform. Cryoelectron microscopy and mutational studies reveal that different domains are involved in self-association. Oligomer dissociation into dimers potentiates its interaction with unfolded client proteins. The J-domains are accessible to Hsc70 within the tubular structure. They allow binding of closely spaced Hsc70 molecules that could be transferred to the unfolded substrate for its cooperative remodelling, explaining the efficient recovery of DNAJA2-bound clients. The disordered C-terminal domain, comprising the last 52 residues, regulates its holding activity and productive interaction with Hsc70. These in vitro findings suggest that the association equilibrium of DNAJA2 could regulate its interaction with client proteins and Hsc70.This research was supported by grants PID2019-111068GB-I00 (AEI/FEDER, UE) to A.M., PID2020-117752RB-I00 (AEI/FEDER, UE) to J.M.B., and PID2019-105872GB-I00 and PID2022-137175NB-I00 (AEI/FEDER, UE) to J.M.V. and J.C., and by the Basque Government (grants IT1201-19 and IT1745-22 to F.M.).Peer reviewe

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High efficacy of Sofosbuvir plus Simeprevir in a large cohort of Spanish cirrhotic patients infected with genotypes 1 and 4

[Abstract] Background and Aims. Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real‐world clinical practice, showed high rates of sustained virological response (SVR) in non‐cirrhotic genotype (GT)‐1 and GT‐4 patients. These results were slightly lower in cirrhotic patients. We investigated real‐life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients. Methods. This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV‐GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January‐2014 and December‐2015. Demographic, clinical, virological and safety data were analysed. Results. Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12 weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×109/L, transient elastography≥21 Kpa) showed significantly lower SVR rates (84.4%‐91.9%) than patients with less advanced liver disease (93.8%‐95.9%, P<.01 in all cases). In the multivariate analysis, the use of RBV, female gender, baseline albumin≥35 g/L, MELD<10 and lack of exposure to a triple therapy regimen were independent predictors of SVR (P<.05). Serious adverse events (SAEs) and SAE‐associated discontinuation events occurred in 5.9% and 2.6%. Conclusions. In this large cohort of cirrhotic patients managed in the real‐world setting in Spain, SOF/SMV±RBV yielded to excellent SVR rates, especially in patients with compensated liver cirrhosis. In addition, this combination showed to be safe, with low rates of SAEs and early discontinuations.Instituto de Salud Carlos III; PI15/0015

A Case of Bicuspid Aorta with Stanford Type a Aortic Dissection

Bicuspid aortic valve disease (BAV) is a congenital disease that frequently produces complications during adulthood, and is considered not only a problem of valvulogenesis, but also a more complex genetic alteration that involves the development of the heart and the aorta, which entails a high morbidity and mortality in these patients. In 50% of adults with this pathology, non-valvular anomalies are observed, with dilation of the ascending aorta being the most common. Genes such as NOTCH1, UFDL1, ACTA2, eNOS, among others, have been identified as responsible for the appearance of aneurysms, which increases the risk in these patients of complications such as aortic dissection and its subsequent rupture. Painless aortic dissection may be seen in less than 5% of patients and may have an atypical clinical presentation. A case and review of the literature is presented in which we can observe the great complexity of this pathology, in the case of a patient with BAV, annulo-ectatic dilation of the aortic root and ascending aorta who developed heart failure, syncope and presented as a complication Stanford type A aortic dissection, requiring highly specialized surgical treatment