Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

The ATLAS fast tracKer system

The ATLAS Fast TracKer (FTK) was designed to provide full tracking for the ATLAS high-level trigger by using pattern recognition based on Associative Memory (AM) chips and fitting in high-speed field programmable gate arrays. The tracks found by the FTK are based on inputs from all modules of the pixel and silicon microstrip trackers. The as-built FTK system and components are described, as is the online software used to control them while running in the ATLAS data acquisition system. Also described is the simulation of the FTK hardware and the optimization of the AM pattern banks. An optimization for long-lived particles with large impact parameter values is included. A test of the FTK system with the data playback facility that allowed the FTK to be commissioned during the shutdown between Run 2 and Run 3 of the LHC is reported. The resulting tracks from part of the FTK system covering a limited η-ϕ region of the detector are compared with the output from the FTK simulation. It is shown that FTK performance is in good agreement with the simulation. © The ATLAS collaboratio

Enseñanza de la comunicación: La legitimación de una profesión como campo intelectual

Más que una “ponencia” lo que sigue es el dibujo de un gesto provocador. Provocación a pensar los problemas curriculares en la enseñanza de la comunicación desde un modelo de trabajo más cercano de la “obra abierta” que de la tecnología educativa, incitación a salir del enredo, maniqueo o dialéctico, que sigue dominando el debate sobre las proporciones que en nuestros planes de estudio debe darse a la teoría y la práctica, a los Saberes y a las destrezas, a la investigación o la producción

Communication sciences: academic field, intellectual project, ethics

This paper, taken from a book (Oficio de cartógrafo. Travesías latinomericanas de la comunicación en la cultura, Fondo de cultura económica, México, 2002), describes the transformations in the field of communication sciences. Transformations in technology and transnationalisation mean old paradigms no longer suffice to describe communication. Communication might be «the» vantage point from which society as a whole may be studied once mediacentrism and all-embracing claims have been discarded. Then the social and moral responsibility of the communication specialist is proven to become fundamental.Dans ce texte tiré d'un ouvrage (Oficio de cartógrafo. Travesias latinomericanas de la comunicación en la cultura, Fondo de cultura económica, México, 2002), l'auteur décrit les transformations du champ. Face à la technologie et à la transnationalisation, les paradigmes anciens ne suffisent plus à décrire la communication. Celle-ci permet d'observer l'ensemble de la société, une fois abandonnés le médiacentrisme et les idéologies globalisantes. La responsabilité sociale et morale du spécialiste en communication devient alors fondamentale

Public connection through media consumption: between oversocialization and de-socialization?

This article reviews the ongoing contribution of Personal Influence to our understanding of media' social consequences from the perspective of recent research (the London School of Economics “Public Connection” project, 2003-2006, conducted by the authors and Sonia Livingstone) into the extent to which shared habits of media consumption help sustain, or not, U.K. citizens' orientation to a public world. As well as reviewing specific findings of the Public Connection project that intersect with themes of Personal Influence(particularly on citizens' networks of social interaction and the available discursive contexts in which they can put their mediated knowledge of the public world to use), the article reviews the methodological similarities and differences between this recent project and that of Katz and Lazarsfeld. The result, the authors conclude, is to confirm the continued salience of the questions about the social embeddedness of media influences that Katz and Lazarsfeld posed

Importance of the Polarity of the Glycosaminoglycan Chain on the Interaction with Fgf-1

Heparin-like saccharides play an essential role in binding to the FGF-1 and to their membrane receptors FGFR forming a ternary complex that is responsible of the internalization of the signal, via the dimerization of the intracellular regions of the receptor. In this study we report the binding affinities between five synthetic hexasaccharides with human FGF-1 obtained by Surface Resonance Plasmon (SPR) experiments, and compare with the induced mitogenic activity previously obtained. These five oligosaccharides differ in the sulphation pattern and in the sequence. We have previously demonstrated that all the five hexasaccharides have similar 3D structure of the backbone. Consequently, the differences in binding affinity should have their origin in the substitution pattern. Subsequently, the different capacity for induction of mitogenic activity can be, at least partially, explained from these binding affinities. Interestingly, one of the oligosaccharides lacking of axially symmetry (3) was biologically inactive whereas the other (2) was the most active. The difference between both compounds is the order of the FGF binding motifs along the chain relative to the carbohydrate polarity. We can conclude that the directionality of the GAG chain is essential for the binding and subsequent activation. The relative biological activity of the compounds with regular substitution pattern can be inferred from their values of IC50. Remarkably, the sulphate in position 6 of D-Glucosamine was essential for the mitogenic activity but not for the interaction with FGF-1

Disrupting the media frame at Greenham Common: a new chapter in the history of mediations?

Drawing on Martin-Barbero's insistence on analysing the media's complex processes of social `mediation' and Scannell's insistence on grasping the phenomenal complexity of the media frame and how people interact with it, it is argued that an important, relatively neglected, dimension of the disruptive power of the Greenham Common Women's Peace Camp (1981-) has been its challenge to the terms of the media frame, the `struggle for visibility' it represents. This struggle for visibility is examined in two stages - in relation to the early years of intense media coverage and in relation to the later years of media silence. In the concluding section, connections are opened up between Greenham Common and recent, more obviously `mediated' forms of protest action