Surface magnetism in ZnO/Co3O4 mixtures

We recently reported the observation of room temperature ferromagnetism in mixtures of ZnO and Co3O4 despite the diamagnetic and antiferromagnetic character of these oxides respectively. Here we present a detailed study on the electronic structure of this material in order to account for this unexpected ferromagnetism. Electrostatic interactions between both oxides lead to a dispersion of Co3O4 particles over the surface of ZnO larger ones. As a consequence, the reduction of Co+3 to Co2+ at the particle surface takes place as evidenced by XAS measurements and optical spectrocopy. This reduction allows to xplain the observed ferromagnetic signal within the well established theories of magnetism.Comment: Accepted in Journal of Applied Physic

Mortality attributable to extreme temperatures in Spain: A comparative analysis by city

BACKGROUND: The Low Temperature Days (LTD) have attracted far less attention than that of High Temperature Days (HTD), though its impact on mortality is at least comparable. This lower degree of attention may perhaps be due to the fact that its influence on mortality is less pronounced and longer-term, and that there are other concomitant infectious winters factors. In a climate-change scenario, the studies undertaken to date report differing results. The aim of this study was to analyse mortality attributable to both thermal extremes in Spain's 52 provinces across the period 2000-2009, and estimate the related economic cost to show the benefit or "profitability" of implementing prevention plans against LTD. METHODS: Previous studies enabled us: to obtain the maximum daily temperature above which HTD occurred and the minimum daily temperature below which LTD occurred in the 52 provincial capitals analysed across the same study period; and to calculate the relative and attributable risks (%) associated with daily mortality in each capital. These measures of association were then used to make different calculations to obtain the daily mean mortality attributable to both thermal extremes. To this end, we obtained a summary of the number of degrees whereby the temperature exceeded (excess °C) or fell short (deficit °C) of the threshold temperature for each capital, and calculated the respective number of extreme temperatures days. The economic estimates rated the prevention plans as being 68% effective. RESULTS: Over the period considered, the number of HTD (4373) was higher than the number of LTD (3006) for Spain as a whole. Notwithstanding this, in every provincial capital the mean daily mortality attributable to heat was lower (3deaths/day) than that attributable to cold (3.48deaths/day). In terms of the economic impact of the activation of prevention plans against LTD, these could be assumed to avoid 2.37 deaths on each LTD, which translated as a saving of €0.29M. Similarly, in the case of heat, 2.04 deaths could be assumed to be avoided each day on which the prevention plan against HTD was activated, amounting to a saving of €0.25M. While the economic cost of cold-related mortality across the ten-year period 2000-2009 was €871.7M, that attributable to heat could be put at €1093.2M. CONCLUSION: The effect of extreme temperatures on daily mortality was similar across the study period for Spain overall. The lower number of days with LTD meant, however, that daily cold-related mortality was higher than daily heat-related mortality, thereby making prevention plans against LTD more "profitable" prevention plans against HTD in terms of avoidable mortality.This study was supported by grants FIS ENPY 1001/13 & SEPY 1037/14 from Spain's Health Research Fund.S

Physiological lentiviral vectors for the generation of improved CAR-T cells

Anti-CD19 chimeric antigen receptor (CAR)-T cells have achieved impressive outcomes for the treatment of relapsed and refractory B-lineage neoplasms. However, important limitations still remain due to severe adverse events (i.e., cytokine release syndrome and neuroinflammation) and relapse of 40%-50% of the treated patients. Most CAR-T cells are generated using retroviral vectors with strong promoters that lead to high CAR expression levels, tonic signaling, premature exhaustion, and overstimulation, reducing efficacy and increasing side effects. Here, we show that lentiviral vectors (LVs) expressing the transgene through a WAS gene promoter (AW-LVs) closely mimic the T cell receptor (TCR)/CD3 expression kinetic upon stimulation. These AW-LVs can generate improved CAR-T cells as a consequence of their moderate and TCR-like expression profile. Compared with CAR-T cells generated with human elongation factor alpha (EF1 alpha)-driven-LVs, AW-CAR-T cells exhibited lower tonic signaling, higher proportion of naive and stem cell memory T cells, less exhausted phenotype, and milder secretion of tumor necrosis factor alpha (TNF-alpha) and interferon (IFN)-gamma after efficient destruction of CD19(+) lymphoma cells, both in vitro and in vivo. Moreover, we also showed their improved efficiency using an in vitro CD19(+) pancreatic tumor model. We finally demonstrated the feasibility of large-scale manufacturing of AW-CAR-T cells in guanosine monophosphate (GMP)-like conditions. Based on these data, we propose the use of AWLVs for the generation of improved CAR-T products

A snapshot of cancer-associated thromboembolic disease in 2018-2019: First data from the TESEO prospective registry

BACKGROUND: The ever-growing complexity of cancer-associated thrombosis (CAT), with new antineoplastic drugs and anticoagulants, distinctive characteristics, and decisions with low levels of evidence, justifies this registry. METHOD: TESEO is a prospective registry promoted by the Spanish Society of Medical Oncology to which 34 centers contribute cases. It seeks to provide an epidemiological description of CAT in Spain. RESULTS: Participants (N=939) with CAT diagnosed between July 2018 and December 2019 were recruited. Most subjects had advanced colon (21.4%), non-small cell lung (19.2%), and breast (11.1%) cancers, treated with dual-agent chemotherapy (28.4%), monochemotherapy (14.4%), or immune checkpoint inhibitors (3.6%). Half (51%) were unsuspected events, albeit only 57.1% were truly asymptomatic. Pulmonary embolism (PE) was recorded in 571 (58.3%); in 120/571 (21.0%), there was a concurrent deep venous thromboembolism (VTE). Most initially received low molecular weight heparin (89.7%). Suspected and unsuspected VTE had an OS rate of 9.9 (95% CI, 7.3-non-computable) and 14.4 months (95% CI, 12.6-non-computable) (p=0.00038). Six-month survival was 80.9%, 55.9%, and 55.5% for unsuspected PE, unsuspected PE admitted for another reason, and suspected PE, respectively (p<0.0001). The 12-month cumulative incidence of venous rethrombosis was 7.1% (95% CI, 4.7-10.2) in stage IV vs 3.0% (95% CI, 0.9-7.1) in stages I-III. The 12-month cumulative incidence of major/clinically relevant bleeding was 9.6% (95% CI, 6.1-14.0) in the presence of risk factors. CONCLUSION: CAT continues to be a relevant problem in the era of immunotherapy and targeted therapies. The initial TESEO data highlight the evolution of CAT, with new agents and thrombotic risk factors

Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin

Single immune checkpoint blockade has shown limited activity in patients with neuroendocrine neoplasms (NENs). Here the authors report the results of a phase II clinical trial of durvalumab (anti-PD-L1) and tremelimumab (anti CTLA-4) in patients with advanced NENs of gastroenteropancreatic and lung origin. Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS

Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP-associated CpGs are enriched for environmental response genes, growth-factor signaling, and inflammation, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth

Multisensor experiments over vineyard: new challenges for the GNSS-R technique

An airborne campaign was performed during August, 2014 in an agricultural area in the Duero basin (Spain) in order to appraise the synergy between very different sources of Earth Observation imagery, and very different instruments for soil moisture retrieval. During the flight, an intensive field campaign comprising soil, plant and spectral measurements was carried out. An innovative sensor based on the Global Navigation Satellite Systems Reflectometry (GNSS-R) was on board the manned vehicle, the Light Airborne Reflectometer for GNSS-R Observations (LARGO) engineered by the Universitat Politècnica de Catalunya. While the synergy between thermal, optical and passive microwave spectra observations is well known for vegetation parameters and soil moisture retrievals, the experiment aimed to evaluate the synergy of GNSS-R reflectivity with a time-collocated Landsat 8 imagery for soil moisture retrieval under semiarid climatic conditions. LARGO estimates, field measurements, and optical, NIR, SWIR and thermal bands from Landsat 8 were compared. Results showed that the joint use of GNSS-R reflectivity with vegetation and water indices together with thermal maps from Landsat 8 thoroughly improved the soil moisture estimation.Peer ReviewedPostprint (published version

Transformación de olivo con el gen AtNPR1 para inducir tolerancia a patógenos fúngicos.

El gen NPR1 codifica un componente esencial de la respuesta SAR mediada por ácido salicílico (AS). Tras la infección por el patógeno, la acumulación de AS libera los monómeros NPR1 en el citoplasma, los cuáles son translocados al núcleo activando la expresión de genes relacionados con la patogénesis (PR). La sobreexpresión del gen NPR1 de Arabidopsis thaliana ha incrementado la resistencia a hongos, bacterias y virus, en distintas especies. El objetivo de esta investigación fue sobreexpresar este gen en olivo con objeto de evaluar su efecto en la tolerancia a dos hongos de suelo, el hemibiotrofo Verticillium dahliae (Vd), una de las mayores amenazas del cultivo y el necrotrofo Rosellinia necatrix, un patógeno emergente en nuevas plantaciones. Se obtuvieron 3 líneas transgénicas, a partir de una línea embriogénica derivada de semilla del cv. Picual. Las líneas mostraron diferencias en el nivel de expresión del transgen en hoja, aunque estas diferencias no afectaron a los niveles de actividad endoquitinasa basal, similar a la de plantas control. La respuesta a Vd varió con el patotipo; así, todas las plantas murieron 50 días tras su inoculación con la cepa defoliante (D) V-138. Por otra parte, la respuesta a patotipos no defoliantes (ND) también fue variable, en función de la raza; tras la inoculación con la cepa V1242 (ND, raza 2), los síntomas aparecieron transcurridos 44-55 días, siendo la línea NPR1-780, con mayor expresión del transgen, la que mostró menor índice de severidad de la enfermedad. Esta línea también mostró un comportamiento superior al control tras la inoculación con la cepa V1558 (ND, raza 1), aunque las diferencias no fueron tan acusadas. En la respuesta a R. necatrix, las líneas transgénicas mostraron un ligero retraso en el desarrollo de la enfermedad con valores AUDPC entre 7-15% inferiores al control.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Desarrollo de productos avanzados para la misión SEOSAT/Ingenio

Revista oficial de la Asociación Española de Teledetección[EN] SEOSAT/Ingenio is the future Spanish Earth Observation high spatial resolution mission in the optical domain. While Level 1 products, at-sensor geo-referenced radiances, are in an advanced phase of development under the framework of an industrial contractor, Level 2 products must be developed by the users. This fact limits the use of the satellite images only to the scientific community, restricting their use in other applications. The need to alleviate this limitation motivated this work, developed under the framework of a coordinate project, which aimed at offering a list of Level2 products to the Ingenio/SEOSAT user community. In this paper, we present the different methodologies developed to produce the proposed Level2 products, from surface reflectance at nominal sensor spatial resolution to images with higher spatial resolution or the possibility to create spatial and temporal mosaics. On the one side, for the surface reflectance product, we proposed an atmospheric correction algorithm based on using the spatial information, linked to a cloud screening algorithm and including morphological and topographic shadow corrections. On the other side, to enhance the image spatial resolution, we applied different fusion techniques using the multispectral and the panchromatic band, as well as some of the so-called “super-resolution” techniques. Finally, we provided different tools to develop spatial mosaics and temporal composites, directed to users interested on the exploitation of the Ingenio/ SEOSAT images.[ES] SEOSAT/Ingenio es la futura misión española de observación de la Tierra en el óptico en alta resolución es-pacial. Mientras que los productos de imagen a Nivel 1, radiancias geo-referenciadas a nivel de sensor, se encuentran en una fase avanzada de desarrollo existiendo para ello un contrato industrial, los productos de Nivel 2 deben ser de-sarrollados por los propios usuarios. Este hecho limita el uso de las imágenes a la comunidad científica, restringiendo sus posibles aplicaciones fuera de ésta. Así pues, bajo el marco de un proyecto coordinado y motivados por ofrecer productos de Ingenio/SEOSAT de Nivel 2 a disposición de cualquier usuario, se origina y desarrolla este trabajo. En este artículo se presentan los diferentes procesos desarrollados para la elaboración de productos a Nivel 2, desde reflectividades en superficie a la resolución nominal del sensor hasta imágenes con información espacial realzada y la posibilidad de crear mosaicos espaciales y compuestos temporales. Por una parte, en el caso de los productos de reflectividad en superficie se propone una técnica de corrección atmosférica basada en el uso de la información es-pacial, previo enmascaramiento de las nubes y una exhaustiva corrección de sombras morfológicas y/o topográficas. Por otra parte, para el realce de la información espacial, han sido evaluados diferentes métodos basados en la fusión de bandas multiespectrales con una banda pancromática así como la aplicación de técnicas llamadas de “Super-re-solución”. Finalmente, se proporcionan las herramientas necesarias para la realización de mosaicos tanto espaciales como temporales para todo tipo de usuarios interesados en la explotación de las imágenesEste artículo ha sido posible gracias al proyecto coordinado “Generación de Productos de Nivel 2 para la Misión INGENIO/SEOSAT”, ESP2013- 48458-C4-1-P, subvencionado por el Ministerio de Economia y Competitividad dentro del Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia.Sabater, N.; Ruiz-Verdú, A.; Delegido, J.; Fernández-Beltrán, R.; Latorre-Carmona, P.; Pla, F.; González-Audícana, M.... (2016). Development of advanced products for the SEOSAT/Ingenio mission. Revista de Teledetección. (47):23-40. https://doi.org/10.4995/raet.2016.6569SWORD234047Blesius, L., & Weirich, F. (2005). The use of the Minnaert correction for land‐cover classification in mountainous terrain. 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