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The European Space Agency (ESA) Earth Explorer satellite Aeolus provides continuous profiles of the horizontal line-of-sight wind component globally from space. It was successfully launched in August 2018 with the goal to improve numerical weather prediction (NWP). Aeolus data have already been successfully assimilated into several NWP models and have already helped to significantly improve the quality of weather forecasts. To achieve this major milestone the identification and correction of several systematic error sources were necessary. One of them is related to small fluctuations of the temperatures across the 1.5 m diameter primary mirror of the telescope which cause varying wind biases along the orbit of up to 8 m s−1. This paper presents a detailed overview of the influence of the telescope temperature variations on the Aeolus wind products and describes the approach to correct for this systematic error source in the operational near-real-time (NRT) processing. It was shown that the telescope temperature variations along the orbit are due to changes in the top-of-atmosphere reflected shortwave and outgoing longwave radiation of the Earth and the related response of the telescope's thermal control system. To correct for this effect ECMWF model-equivalent winds are used as a reference to describe the wind bias in a multiple linear regression model as a function of various temperature sensors located on the primary telescope mirror. This correction scheme has been in operational use at ECMWF since April 2020 and is capable of reducing a large part of the telescope-induced wind bias. In cases where the influence of the temperature variations is particularly strong it was shown that the bias correction can improve the orbital bias variation by up to 53 %. Moreover, it was demonstrated that the approach of using ECMWF model-equivalent winds is justified by the fact that the global bias of model u-component winds with respect to radiosondes is smaller than 0.3 m s−1. Furthermore, this paper presents the alternative of using Aeolus ground return winds which serve as a zero-wind reference in the multiple linear regression model. The results show that the approach based on ground return winds only performs 10.8 % worse than the ECMWF model-based approach and thus has a good potential for future applications for upcoming reprocessing campaigns or even in the NRT processing of Aeolus wind products.

La obra literaria y la vida de María Martínez Sierra, casi centenaria, presentan una serie de líneas maestras que atraviesan de manera coherente toda su producción, como pone de manifiesto su producción autobiográfica. María escribió y tradujo teatro, ensayo y memorias, se ocupó de tareas empresariales y tuvo militancia política, además de su destacada labor como dramaturga en colaboración con su marido, Gregorio Martínez Sierra, en el Teatro de Arte, en lo que fue una relación profesional que también la llevó a los ámbitos de la traducción, de la empresa teatral y editorial y del ensayo. No menos importante fue su incorporación a la vida política de primera línea en defensa de la Repüblica. A lo largo de su trayectoria vital y profesional prevalecen algunos rasgos de carácter que se manifiestan en su concepción del Magisterio, en el sentido de su producción dramática y en la teorización que ofrecen sus ensayos feministas y sus intervenciones parlamentarias. El análisis de su obra teatral del exilio, Fiesta en el Olimpo, permite afirmar su complementariedad autobiográfica con sus dos libros de memorias. [ABSTRACT FROM AUTHOR]

Our main objective was to analyze the role of imageability in relation to the age of acquisition (AoA) of nouns and verbs in Spanish-speaking children with Down syndrome (DS) and their peers with typical development (TD). The AoA of nouns and verbs was determined using the MacArthur-Bates CDIs adapted to the profile of children with DS. The AoA was analyzed using a linear mixed-effect model, including factors of imageability, group, and word class, and controlling for word frequency and word length. This analysis showed that high imaginable and short words were acquired early. Children with DS acquired the words later than TD peers. An interaction between imageability and group indicated that the effect of imageability was greater in the DS group. We discuss this effect considering DS children's phonological memory difficulties. The overall results confirm the role that imageability and word length play in lexical acquisition, an effect that goes beyond word class.

A novel therapeutic approach for glioblastoma multiforme (GBM) therapy has been carried out through in vitro and in vivo testing by using the prodrug camptothecin-20- O -(5-aminolevulinate) (CPT-ALA). The incorporation of ALA to CPT may promote uptake of the cytotoxic molecule by glioblastoma cells where the heme synthesis pathway is active, improving the therapeutic action and reducing the side effects over healthy tissue. The antitumor properties of CPT-ALA have been tested on different GBM cell lines (U87, U251, and C6) as well as in an orthotopic GBM model in rat, where potential toxicity in central nervous system cells was analyzed. In vitro results indicated no significant differences in the cytotoxic effect over the different GBM cell lines for CPT and CPT-ALA, albeit cell mortality induced by CPT over normal cell lines was significantly higher than CPT-ALA. Moreover, intracranial GBM in rat was significantly reduced (30% volume) with 2 weeks of CPT-ALA treatment with no significant side effects or alterations to the well-being of the animals tested. 5-ALA moiety enhances CPT diffusion into tumors due to solubility improvement and its metabolic-based targeting, increasing the CPT cytotoxic effect on malignant cells while reducing CPT diffusion to other proliferative healthy tissue. We demonstrate that CPT-ALA blocks proliferation of GBM cells, reducing the infiltrative capacity of GBM and promoting the success of surgical removal, which improves life expectancy by reducing tumor recurrence.

Purpose: Joint attention is considered a prerequisite for language development. Although language is one of the most impaired domains in Down syndrome (DS), few studies have examined the relationship between caregiver behavior during episodes of joint attention and vocabulary development in these children. Consequently, our primary aim was to analyze the behaviors of caregivers of children with DS and of children with typical development (TD) in the early stages of vocabulary development. A second objective was to examine the kind of words that caregivers use to refer to the object that is the focus of attention. We also consider the concurrent relationship between joint attention and vocabulary development in both groups of children., Method: We studied 28 children with DS and 28 children with TD, individually matched on mental age and gender, and their respective caregivers. The mean mental age for children with DS and children with TD was around 12 months. The mean chronological age of caregivers of children with DS and children with TD was around 35 years. Each child and his or her caregiver were video-recorded during a free-play session involving different objects., Results: Although the total time engaged in joint attention was greater among caregivers of children with DS, caregivers of both groups of children were more likely to direct than follow their child's attentional focus. The caregivers of children with DS used a greater number of appropriate terms to refer to the object of attention. We found no significant correlation in either group of children between vocabulary development and joint attention behaviors., Conclusions: The results may be due to the fact that the children studied are still very young in developmental terms and have yet to develop all the skills required for joint attention. At this early stage, directing the child's attention would promote the development of joint attention. A possible explanation for the lack of a correlation between vocabulary development and joint attention is that children may use an associative mechanism in the early stages of lexical learning, and hence the learning of new words is a slow process., (Copyright © 2020 Elsevier Inc. All rights reserved.)

MIL-100(Fe) and MIL-101(Fe) metal-organic frameworks (MOFs) are excellent vehicles for drug delivery systems (DDSs) due to their high biocompatibility and stability in physiological fluids, as well as their pore diameter in the mesoporous range. Although they are appropriate for the internal diffusion of 20-(S)-camptothecin (CPT), a strongly cytotoxic molecule with excellent antitumor activity, no stable delivery system has been proposed so far for this drug based in MOFs. We here present novel DDSs based in amine functionalized MIL-100(Fe) and MIL-101(Fe) nanoMOFs with covalently bonded CPT. These CPT nanoplatforms are able to incorporate almost 20% of this molecule and show high stability at physiological pH, with no non-specific release. Based on their surface charge, some of these CPT loaded nanoMOFs present improved cell internalization in in vitro experiments. Moreover, a strong response to acid pH is observed, with up to four fold drug discharge at pH 5, which boost intracellular release by endosomolytic activity. These novel DDSs will help to achieve safe delivery of the very cytotoxic CPT, allowing to reduce the therapeutic dose and minimizing drug secondary effects., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: The primary aim of this study was to analyze the acquisition of different classes of words in Spanish-speaking children with Down syndrome (DS), with special emphasis on nouns and verbs. A second objective was to compare the results obtained with those reported by Checa et al. (2016), who used a different measure to study vocabulary composition., Method: We studied 108 children with DS and 108 children with typical development (TD), with mental ages between 9 and 29 months (DS M = 21;26 months;days, TD M = 20;23) and chronological ages between 8;24 and 68;19 months;days (mean = 41;11 and 20;19 for DS and TD, respectively). Children were matched individually for size of productive vocabulary and gender. Data were gathered using the MacArthur-Bates CDIs, adapted to the profile of children with DS (the CDI-Down). Relative proportions were used as the measure of vocabulary., Results: The results differed from those obtained by Checa et al. (2016) when using absolute proportions to examine vocabulary composition. The most significant difference was the trend among children with DS to produce fewer verbs and closed-class words (articles, prepositions, pronouns, conjunctions, and auxiliaries). There were no differences in the production of nouns and social words., Conclusions: The tendency of children with DS to produce fewer verbs and closed-class words could be due to difficulties with morphology and syntax. This underlines the importance of morphosyntactic skills for learning these classes of words. The methodological and clinical implications of the results are discussed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The development of contrast agents (CAs) for Magnetic Resonance Imaging (MRI) with T1-T2 dual-mode relaxivity requires the accurate assembly of T1 and T2 magnetic centers in a single structure. In this context, we have synthesized a novel hybrid material by monitoring the formation of Prussian Blue analogue Gd(H2O)4[Fe(CN)6] nanoparticles with tailored shape (from nanocrosses to nanorods) and size, and further protection with a thin and homogeneous silica coating through hydrolysis and polymerization of silicate at neutral pH. The resulting Gd(H2O)4[Fe(CN)6]@SiO2 magnetic nanoparticles are very stable in biological fluids. Interestingly, this combination of Gd and Fe magnetic centers closely packed in the crystalline network promotes a magnetic synergistic effect, which results in significant improvement of longitudinal relaxivity with regards to soluble Gd3+ chelates, whilst keeping the high transversal relaxivity inherent to the iron component. As a consequence, this material shows excellent activity as MRI CA, improving positive and negative contrasts in T1- and T2-weighted MR images, both in in vitro (e.g., phantom) and in vivo (e.g., Sprague-Dawley rats) models. In addition, this hybrid shows a high biosafety profile and has strong ability to incorporate organic molecules on the surface with variable functionality, displaying great potential for further clinical application.

Purpose: There are very few studies, and at present none in Spanish, on vocabulary composition in children with Down syndrome (DS). Nor has the topic been widely assessed in Spanish-speaking children with typical development (TD). This study analyzed the composition of early vocabularies in a large sample of Spanish-speaking children with DS and compared it with that of children with TD., Method: We studied 108 children with DS and 108 children with TD with mental ages between 8 and 29 months, matched for size of productive vocabulary and gender. The MacArthur-Bates Communicative Development Inventories (Fenson et al., 1993, 2007), adapted to the language development profile of children with DS, were used. The categories examined were nouns, predicates, closed-class words, and social words., Results: The performance of children with DS was similar to that of children with TD with the same vocabulary size. The only significant difference was the larger production of nouns by children with DS. The trends of development in the different classes of words were also similar., Conclusions: The strategies used by children with DS to learn vocabulary may be similar to those used by children with TD in the first stages of language learning.

The physical microenvironment of tumours is characterized by heterotypic cell interactions and physiological gradients of nutrients, waste products and oxygen. This tumour microenvironment has a major impact on the biology of cancer cells and their response to chemotherapeutic agents. Despite this, most in vitro cancer research still relies primarily on cells grown in 2D and in isolation in nutrient- and oxygen-rich conditions. Here, a microfluidic device is presented that is easy to use and enables modelling and study of the tumour microenvironment in real-time. The versatility of this microfluidic platform allows for different aspects of the microenvironment to be monitored and dissected. This is exemplified here by real-time profiling of oxygen and glucose concentrations inside the device as well as effects on cell proliferation and growth, ROS generation and apoptosis. Heterotypic cell interactions were also studied. The device provides a live 'window' into the microenvironment and could be used to study cancer cells for which it is difficult to generate tumour spheroids. Another major application of the device is the study of effects of the microenvironment on cellular drug responses. Some data is presented for this indicating the device's potential to enable more physiological in vitro drug screening.

Purpose: The MacArthur-Bates Communicative Development Inventories are widely used to study early language and communicative development. We recently developed a Spanish version for children with Down syndrome (the CDI-Down) adapted to their particular profile of linguistic and communicative development. The principal aims of this study are to assess the concurrent validity and test-retest reliability of the vocabulary section of this adaptation., Method: Validation for productive vocabulary (Study 1) was achieved by correlating CDI-Down scores on expressive vocabulary and measures on the basis of spontaneous speech samples (n = 29). Validation for receptive vocabulary (Study 2) was achieved by correlating CDI-Down scores on receptive vocabulary and measures derived from language items of the Brunet-Lézine Scale (Josse, 1997; n = 70). Reliability (Study 3) was measured with a subset of parents who completed the same inventory 4 months after the original sampling (n = 26)., Results: CDI-Down expressive and receptive vocabulary scores showed a significant positive relationship with their comparison measures, thereby demonstrating convergent validity. A significant positive relationship was also found between test-retest measures for productive and receptive vocabularies, thus supporting the reliability of the adaptation., Conclusion: The results demonstrate that the CDI-Down is a valid and reliable tool that could be useful for parents, teachers, clinicians, and researchers.

We describe the synthesis, characterization and application as contrast agents in magnetic resonance imaging of a novel type of magnetic nanoparticle based on Gd-Si oxide, which presents high Gd 3+ atom density. For this purpose, we have used a Prussian Blue analogue as the sacrificial template by reacting with soluble silicate, obtaining particles with nanorod morphology and of small size (75 nm). These nanoparticles present good biocompatibility and higher longitudinal and transversal relaxivity values than commercial Gd 3+ solutions, which significantly improves the sensitivity of in vivo magnetic resonance images.

The objective of this work was to analyze morphosyntactic development in a wide sample of children with Down syndrome (DS) (n = 92) and children with typical development (TD) (n = 92) with a mental age (MA) of 20 to 29 months. Children were individually matched for gender and MA (Analysis 1) and for vocabulary size (Analysis 2). Information about morphosyntax was obtained using an adaptation of the CDI for children with DS. In both analyses, the number of children with DS and with TD who combined words was similar. Analysis 1 showed that children with DS produced shorter utterances, with less morphosyntactic complexity and less morphological suffixes than children with TD, despite having the same mental age. The developmental pattern was similar, although slower in children with DS. Analysis 2 showed that the performance of children with DS was lower than the performance of children with TD in relation to morphosyntactic complexity and morphological suffixes.

Background: Our main purpose was to compare the lexical development of Spanish children with Down syndrome (DS) and children with typical development (TD) to investigate the relationship between cognitive and vocabulary development in comprehension and oral and gestural production., Method: Participants were 186 children with DS and 186 children with TD, with a mental age (MA) of 8-29 months and matched on gender and MA. Information about vocabulary was obtained using a new Spanish adaptation of the MacArthur-Bates CDI for children with DS., Results: No significant differences in oral production were found. Lexical comprehension and gestural production of children with DS were superior. Similar to children with TD, gestural production in children with DS decreased as oral production increased., Conclusion: Our study provides evidence to support that lexical comprehension and gesture production are strengths in children with DS. With respect to oral production, our results do not support a specific dissociation between cognitive and lexical development.

Background: Serum tumor markers are considered a negative prognostic factor in early-stages NSCLC but its role in advanced disease is controversial. The aim of this study is to analyze the prognostic value of tumor markers in advanced NSCLC., Patients and Methods: Two hundred and seventy seven patients diagnosed in our institution were retrospectively reviewed. Baseline prognostic factors analyzed were gender, histology and brain metastases., Results: Baseline patients characteristics: median age 63 years (30-81 years); males 84.4%, stage IV: 61.7%; adenocarcinoma 38.6%, squamous carcinoma 22.4%. High levels of CEA, CYFRA21-1, and CA125 levels were detected in 179 (55.9%), 119 (65%), and 129 (46.6%) patients respectively. Significant higher levels of CEA and CA125 at baseline were present in adenocarcinoma (P < .05). PFS in patients with elevated CEA, CYFRA21-1, and CA125 was 5.3 months (m), 3.5 m and 4.6 m versus 7.4 m, 6.2 m and 7.5 m in patients with normal levels (P < .05). The OS in patients with high and normal levels of tumor markers was 10.0 m vs 14.0 m (P = 0.085) for CEA; 5.6 vs 12.1 m for CYFRA21-1 (P = .002), and 8.7 vs 14.0 (P = .03) for CA125. In the multivariate analysis high levels of tumor markers, histology and clinical stage were significant correlated with worse prognostic. Patients with all the tumor markers elevated presented the worst prognosis (3.6 m for PFS and 7.1 m for OS, P < .001)., Conclusion: In our analysis, high levels of tumor markers at baseline are correlated with worse survival in stage III-IV NSCLC patients., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: It is generally assumed that children with Down syndrome (DS) present a deficit in lexical production relative to their cognitive abilities. However, the literature on this topic has recently shown several contradictory results. In addition, most studies only consider vocabulary production in its vocal modality. However it is also necessary to take into account gesture production, since this is a strength in children with DS. Our main purpose in this study, therefore, was to investigate the relationship between cognitive development and vocabulary size in both its vocal and gestural modalities in a broad sample of Spanish children with DS., Method: Participants in the study were 66 children with DS and 66 children with typical development (TD), with a mental age (MA) of 14-28 months (divided into five groups with a MA of 14-16, 17-19, 20-22, 23-25 and 26-28 months). Children were matched on the basis of their gender and MA. Productive vocabularies were collected using an adaptation of the MacArthur-Bates CDI for children with DS., Results: In vocal modality, the number of words produced by children with DS and children with TD is similar. As in previous studies, our data confirmed that gestural communication is superior in children with DS. However, when words and gestures are combined, the performance of both groups of children is practically equal., Conclusion: Our results do not support a specific dissociation between cognitive and lexical development in children with DS.

Objectives: To investigate the results of metabolic control among type-2 diabetics who practise self-monitoring of their blood glucose (MBG) and compare them with those who do not; the adequacy of MBG prescription according to clinical criteria and frequency of use; and to analyse the presence of factors predicting metabolic control., Design: Descriptive and retrospective study covering 1995, 1996 and 1997., Setting: The seven health districts in the territorial ambit of Tortosa Primary Care., Patients: 597 type-2 diabetes patients were evaluated: 286 practising MBG, and 311 not doing so. All of them belonged to the health districts reference population. The sample was systematized and stratified by health districts in order to obtain data through a pre-designed data collection form., Measurements and Main Results: 41.06% of diabetics practised MBG on a stable basis, without any significant differences showing in either HbA1c percentage, in any of the biological variables defining metabolic control in relation to the practice or otherwise of MBG, or in its frequency. An inverse relationship (p = 0.012) between the frequency of MBG and age was shown. Some clinical indication for prescribing MBG existed in 78.22% of the total diabetic population. In the diabetic population using MBG, inappropriate use of quantity was 54.89% (84.07% by too little, 15.92% in excess). Only 37.9% displayed quantitative and qualitative concordance simultaneously. The logistic model applied to the total diabetic population predicted 73.19% metabolic control with the variables of BMI (OR = 1.0542). Karnofsky index (OR = 0.9768) and presence of macroangiopathy (OR = 0.4249)., Conclusions: 1. The practice of MBG is questionable, since the effectiveness found was not superior. 2. There is an imbalance between the real practice of MBG according to the clinical recommendations and consumption, which tends to be deficient. 3. The results do not seem to depend so much on MBG practice as on other linked circumstances which cannot be modified by MBG practice.

Most work on acquisition of lexical meaning in developmental psycholinguistics is based on the idea of the relevance of the adult model, which is generally described in relation to certain theoretical semantic analyses. Up to the present, adult behavior itself has not been examined and its validity as a model for children has been taken for granted. This paper analyzes the knowledge of spatial terms, namely dimensional terms, shown by a group of 20 adults. The results show that the adult subjects used in our study--supposedly linguistically competent--committed errors, significantly varying their strategies for naming dimensions from one case to another, and showing a lack of consistency between them. The results are discussed in terms of assumed theoretical validity with regard to theoretical semantic analysis, as well as the methods of research about the acquisition of lexical meaning.