93 research outputs found

    Employment generation by small firms in Spain

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    Despite the relevance in terms of policy, we still know little in Spain about where and by whom jobs are created, and how that is affecting the size distribution of firms. The main innovation of this paper is to use a rich database that overcomes the problems encountered by other firm-level studies to shed some light on the employment generation of small firms in Spain. We find that small firms contribute to employment disproportionately across all sectors of the economy although the difference between their employment and job creation share is largest in the manufacturing sector. The job creators in that sector are both new and established firms whereas only new small firms outperform their larger counterparts in the service sector. The large annual job creation of the small firm size class is shifting the firm size distribution towards the very small production units, although not uniformly across industries of different technology intensit

    Automated High-Content Live Animal Drug Screening Using C. elegans Expressing the Aggregation Prone Serpin α1-antitrypsin Z

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    The development of preclinical models amenable to live animal bioactive compound screening is an attractive approach to discovering effective pharmacological therapies for disorders caused by misfolded and aggregation-prone proteins. In general, however, live animal drug screening is labor and resource intensive, and has been hampered by the lack of robust assay designs and high throughput work-flows. Based on their small size, tissue transparency and ease of cultivation, the use of C. elegans should obviate many of the technical impediments associated with live animal drug screening. Moreover, their genetic tractability and accomplished record for providing insights into the molecular and cellular basis of human disease, should make C. elegans an ideal model system for in vivo drug discovery campaigns. The goal of this study was to determine whether C. elegans could be adapted to high-throughput and high-content drug screening strategies analogous to those developed for cell-based systems. Using transgenic animals expressing fluorescently-tagged proteins, we first developed a high-quality, high-throughput work-flow utilizing an automated fluorescence microscopy platform with integrated image acquisition and data analysis modules to qualitatively assess different biological processes including, growth, tissue development, cell viability and autophagy. We next adapted this technology to conduct a small molecule screen and identified compounds that altered the intracellular accumulation of the human aggregation prone mutant that causes liver disease in α1-antitrypsin deficiency. This study provides powerful validation for advancement in preclinical drug discovery campaigns by screening live C. elegans modeling α1-antitrypsin deficiency and other complex disease phenotypes on high-content imaging platforms

    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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    RICORS2040 : The need for collaborative research in chronic kidney disease

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    Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

    Facile access to completely deuterated single-chain nanoparticles enabled by intramolecular azide photodecomposition

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    Access to completely deuterated single-chain nanoparticles (dSCNPs) has remained an unresolved issue. Herein, the first facile and efficient procedure to produce dSCNPs is reported, which comprises: i) the use of commercially available perdeuterated cyclic ether monomers as starting reagents, ii) a ring-opening copolymerization process performed in bulk to produce a neat dSCNP precursor, iii) a standard azidation reaction to decorate this precursor with azide moieties, and iv) a facile intramolecular azide photodecomposition step carried out under UV irradiation at high dilution providing with highly valuable, completely deuterated soft nano-objects from the precursor. dSCNPs are used to investigate by means of neutron-scattering measurements the form factor (radius of gyration, scaling exponent) of polyethylene oxide (PEO) chains in nanocomposites with different amounts of dSCNPs. Moreover, to illustrate the possibilities offered by the synthetic route disclosed in this communication for potential applications, the significant reduction in viscosity observed in a pure melt of polyether-based single-chain nanoparticles when compared to a melt of the corresponding linear polymer chains is shown.Financial support by the Spanish Ministry “Ministerio de Economia y Competitividad,” MAT2015‐63704‐P (MINECO/FEDER, UE), the Basque Government, IT‐654‐13, and the Gipuzkoako Foru Aldundia, Programa Red Guipuzcoana de Ciencia, and Tecnología e Innovación 2017 (RED 101/17) is acknowledged

    Actualización en el diagnóstico de las infecciones de transmisión sexual.

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    Sexually transmitted infections (STIs) are one of the most frequent and universal Public Health problems. Health professionals should be aware of the possibility of STIs due to their high morbidity and the presence of sequelae. The delay in the diagnosis is one of the factors that justifies the difficulty to infections control. Diagnostic tests allow the introduction of aetiological treatment and also lead to treating symptomatic and asymptomatic patients more effectively, as well as to interrupt the epidemiological transmission chain without delay. In this review we have made an update of the main existing diagnostic methods for the more important STIs

    Mesoscale dynamics in melts of single-chain Polymeric Nanoparticles

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    Through a combination of neutron scattering, dielectric spectroscopy, and rheological measurements we study the impact of purely intramolecular cross-linking on a melt fully made of polymeric single-chain nanoparticles (SCNPs) - a novel class of ultrasoft nano-objects. While the α-relaxation is unaffected with respect to the reference melt of linear chains, the emerging polymer/colloid duality of SCNPs leads to the almost complete smearing out of the rubbery plateau. This is the opposite effect to the creation of a permanent 3D network by intermolecular bonds. In addition, neutron scattering shows that a new relaxation mechanism slower than the α-relaxation appears at intermediate length scales. These are beyond the interchain distance but yet far from the hydrodynamic regime. This new slow relaxation - also detected by dielectric spectroscopy - contributes to the hierarchy of processes needed for the full relaxation of the SCNP melt and is tentatively related to the heterogeneities provoked by the internal multiloop topology of the SCNPs and the segregation of their internal domains.The authors gratefully acknowledge the financial support of the BasqueGovernment, code IT-1175-19, and the Ministerio de Economia y Competitividad, code PGC2018-094548-B-I00 (MINECO/FEDER, UE). This work is based on experiments performed at the FOCUS instrument operated by the Swiss Spallation Neutron Source SINQ, Paul Scherrer Institute, Villigen, Switzerland, and has been supported by the European Commission under the seventh Framework Programme through the “Research Infrastructures” action of the“Capacities” Programme, NMI3-II Grant Number 283883
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