24 research outputs found

    Multifaceted role of TREX2 in the skin defense against UV-induced skin carcinogenesis

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    TREX2 is a 3'-DNA exonuclease specifically expressed in keratinocytes. Here, we investigated the relevance and mechanisms of TREX2 in ultraviolet (UV)-induced skin carcinogenesis. TREX2 expression was up-regulated by chronic UV exposure whereas it was de-regulated or lost in human squamous cell carcinomas (SCCs). Moreover, we identified SNPs in the TREX2 gene that were more frequent in patients with head and neck SCCs than in healthy individuals. In mice, TREX2 deficiency led to enhanced susceptibility to UVB-induced skin carcinogenesis which was preceded by aberrant DNA damage removal and degradation as well as reduced inflammation. Specifically, TREX2 loss diminished the up-regulation of IL12 and IFNγ, key cytokines related to DNA repair and antitumor immunity. In UV-treated keratinocytes, TREX2 promoted DNA repair and passage to late apoptotic stages. Notably, TREX2 was recruited to low-density nuclear chromatin and micronuclei, where it interacted with phosphorylated H2AX histone, which is a critical player in both DNA repair and cell death. Altogether, our data provide new insights in the molecular mechanisms of TREX2 activity and establish cell autonomous and non-cell autonomous functions of TREX2 in the UVB-induced skin response

    Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

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    Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

    Financial crisis and migrant domestic workers in Spain: employment opportunities and conditions during the Great Recession

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    This article explores the impact of the Great Recession on migrant domestic workers in Spain. We argue that the domestic service sector’s relative resistance to job destruction has transformed it to some extent into a refuge activity for unemployed women from other sectors, both migrants and native Spanish workers. This leads to intensified competition over jobs and increasing stratification among domestic workers, with serious consequences both for migrant women’s opportunities to make a living in Spain and for their migration projects at an international level. Based on 90 in-depth interviews with female migrant domestic workers and stakeholders, we find that this group of workers has been seriously affected by unemployment, underemployment, and worsened job conditions. As a consequence, new and already settled migrants find the chances to gain their livelihood in Spain substantially reduced, and many of those who migrated in order to support the family back home through remittances, or to save some money and eventually return, are at present unable to do so

    Intelligibility and Listening Effort of Spanish Oesophageal Speech

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    Communication is a huge challenge for oesophageal speakers, be it for interactions with fellow humans or with digital voice assistants. We aim to quantify these communication challenges (both human–human and human–machine interactions) by measuring intelligibility and Listening Effort (LE) of Oesophageal Speech (OS) in comparison to Healthy Laryngeal Speech (HS). We conducted two listening tests (one web-based, the other in laboratory settings) to collect these measurements. Participants performed a sentence recognition and LE rating task in each test. Intelligibility, calculated as Word Error Rate, showed significant correlation with self-reported LE ratings. Speaker type (healthy or oesophageal) had a major effect on intelligibility and effort. More LE was reported for OS compared to HS even when OS intelligibility was close to HS. Listeners familiar with OS reported less effort when listening to OS compared to nonfamiliar listeners. However, such advantage of familiarity was not observed for intelligibility. Automatic speech recognition scores were higher for OS compared to HS

    ALBAYZIN 2016 spoken term detection evaluation: an international open competitive evaluation in Spanish

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    Within search-on-speech, Spoken Term Detection (STD) aims to retrieve data from a speech repository given a textual representation of a search term. This paper presents an international open evaluation for search-on-speech based on STD in Spanish and an analysis of the results. The evaluation has been designed carefully so that several analyses of the main results can be carried out. The evaluation consists in retrieving the speech files that contain the search terms, providing their start and end times, and a score value that reflects the confidence given to the detection. Two different Spanish speech databases have been employed in the evaluation: MAVIR database, which comprises a set of talks from workshops, and EPIC database, which comprises a set of European Parliament sessions in Spanish. We present the evaluation itself, both databases, the evaluation metric, the systems submitted to the evaluation, the results, and a detailed discussion. Five different research groups took part in the evaluation, and ten different systems were submitted in total. We compare the systems submitted to the evaluation and make a deep analysis based on some search term properties (term length, within-vocabulary/out-of-vocabulary terms, single-word/multi-word terms, and native (Spanish)/foreign terms)Xunta de Galicia | Ref. ED431G/01Ministerio de Economía y Competitividad | Ref. TEC2015-67163-C2-1-RMinisterio de Economía y Competitividad | Ref. TIN2014-54288-C4-1-RMinisterio de Economía y Competitividad | Ref. TEC2015-68172-C2-1-

    ALBAYZIN 2016 spoken term detection evaluation: an international open competitive evaluation in Spanish

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    Abstract Within search-on-speech, Spoken Term Detection (STD) aims to retrieve data from a speech repository given a textual representation of a search term. This paper presents an international open evaluation for search-on-speech based on STD in Spanish and an analysis of the results. The evaluation has been designed carefully so that several analyses of the main results can be carried out. The evaluation consists in retrieving the speech files that contain the search terms, providing their start and end times, and a score value that reflects the confidence given to the detection. Two different Spanish speech databases have been employed in the evaluation: MAVIR database, which comprises a set of talks from workshops, and EPIC database, which comprises a set of European Parliament sessions in Spanish. We present the evaluation itself, both databases, the evaluation metric, the systems submitted to the evaluation, the results, and a detailed discussion. Five different research groups took part in the evaluation, and ten different systems were submitted in total. We compare the systems submitted to the evaluation and make a deep analysis based on some search term properties (term length, within-vocabulary/out-of-vocabulary terms, single-word/multi-word terms, and native (Spanish)/foreign terms)

    Esbossos del Jordi. Les nostres imatges, la seva imatge

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    La gran influència d'en Jordi Domènech en les històries professionals de molts i moltes docents és un fet inqüestionable. En aquest article, algunes integrants del grup de treball Ecofemisteam fem l'exercici d'identificar, reconèixer i agrair els moments en què el Jordi, amb les seves propostes, ha promogut un punt d'inflexió en la manera de mirar i exercir la nostra feina. Algunes vam coincidir amb ell en algun grup de treball entre iguals i vam copsar en aquell company una lucidesa i un caliu que destacava entre els altres sense fer-los ombra; d'altres, vam tenir la sort de tenir-lo com a formador i vam descobrir les seves claus mestres de la didàctica de les ciències, bastides universals per a pensar i per a comunicar la ciència escolar d'una manera senzilla, lleugera i alhora profunda i rigorosa, un fet del qual ja no hi ha volta enrere. La majoria potser no el vam poder conèixer personalment però treballar a diari amb els seus materials, llegir els seus llibres, els seus articles i els seus tuits, ha revolucionat la nostra manera d'ensenyar i pensar sobre el que fem de tal manera que ha generat un salt qualitatiu en les nostres propostes a l'aula. L'inici, el final i cada petita història d'aquest mosaic va acompanyada d'una carta del joc Dixit que la representa, i també pretén ser una inspiració i una invitació per al futur, cap a altres cartes que es dibuixaran gràcies al tauler de joc que ens ha deixat en Jordi.Jordi Domènech's great influence on the professional stories of many teachers is an unquestionable fact. In this article, some members of the Ecofemisteam working group are doing the exercise of identifying, recognising and thanking the moments in which Jordi, with his proposals, has promoted a turning point in the way we look at and carry out our work. Some of us coincided with him in some peer working group and captured in that companion a lucidity and warmth that stood out among others without outshine them; others, we were lucky to have him as a teacher and we discovered his master keys to science teaching, universal scaffolding to think and to communicate school science in a simple, light and at the same time deep and rigorous, a fact from which there is no turning back. Most of us may not have been able to meet him personally but working daily with his materials, reading his books, his articles and his tweets, has revolutionized our way of teaching and thinking about what we do in such a way that it has generated a qualitative leap in our proposals in the classroom. The beginning, the end and every little story of this mosaic is accompanied by a card from the game Dixit that represents it, and it also aims to be an inspiration and an invitation for the future, towards other cards that will be drawn thanks to the game board that Jordi has left us.La gran influencia que ha ejercido Jordi Domènech en las historias profesionales de muchas y muchos docentes es incuestionable. En este artículo, algunas integrantes del grupo de trabajo Ecofemisteam hacemos el ejercicio de identificar, reconocer y agradecer los momentos en los que Jordi, con sus propuestas, ha promovido un punto de inflexión en la forma de mirar y ejercer nuestra profesión. Algunas coincidimos con él en algún grupo de trabajo entre iguales y captamos en aquel compañero a una persona lúcida y acogedora que destacaba entre las otras sin hacerles sombra; otras, tuvimos la suerte de tenerle como formador y descubrimos sus llaves maestras de la didáctica de las ciencias, andamios universales para pensar y para comunicar la ciencia escolar de un modo sencillo, ligero y a la vez profundo y riguroso, hecho del que ya no hay vuelta atrás. La mayoría quizás no lo pudimos conocer personalmente, pero trabajar a diario con sus materiales, leer sus libros, sus artículos y sus tuits, ha revolucionado nuestra forma de enseñar y pensar sobre ello, de modo que ha generado un salto cualitativo en nuestras propuestas en el aula. El inicio, el final y cada breve historia de este mosaico va acompañada de una carta del juego Dixit que la representa, y también pretende ser una inspiración y una invitación hacia el futuro, hacia otras cartas que se dibujaran gracias al tablero de juego que nos ha dejado Jordi

    A patient-reported outcome measure for patients with pituitary adenoma undergoing transsphenoidal surgery.

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    Funder: Wellcome TrustPURPOSE: Pituitary adenomas affect patients' quality-of-life (QoL) across several domains, with long-term implications even following gross-total resection or disease remission. While clinical outcomes can assess treatment efficacy, they do not capture variations in QoL. We present the development and validation of a patient reported outcome measure (PROM) for patients with pituitary adenomas undergoing transsphenoidal surgery. METHODS: The COSMIN checklist informed the development of the pituitary outcome score (POS). Consecutive patients undergoing surgical treatment for suspected pituitary adenoma at a single centre were included prospectively. An expert focus group and patient interviews informed item generation. Item reduction was conducted through exploratory factor analysis and expert consensus, followed by assessment of the tool's validity, reliability, responsiveness, and interpretability. RESULTS: 96 patients with a median age of 50 years validated the POS. The final questionnaire included 25 questions with four subscales: EQ-5D-5L-QoL, Visual Symptoms, Endocrine Symptoms and Nasal Symptoms. CONCLUSION: The POS is the first validated PROM for patients undergoing transsphenoidal surgery for a pituitary adenoma. This PROM could be integrated into contemporary practice to provide patient-centred outcomes assessment for this patient group, aligning more closely with patient objectives

    Guia per a l’abordatge de la patologia infecciosa del tracte respiratori baix a l’atenció primària

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    Patologia infecciosa; Tracte respiratori baix; Bronquitis; Penumònia; BronquiolitisPatología infecciosa; Tracto respiratorio inferior; Bronquitis; Neumonía; BronquiolitisInfectious pathology; Lower respiratory tract; Bronchitis; Penumonia; BronchiolitisAquest document aporta una revisió acurada del coneixement científic actualment disponible sobre la patologia infecciosa del tracte respiratori baix, i el tradueix en recomanacions per a la pràctica diària. Pel seu contingut docent, la Guia constitueix també un valuós document per facilitar l’adquisició de competències clíniques que ha de caracteritzar el desenvolupament dels professionals de l’Institut Català de la Salut
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