Fostering household formation: evidence from a Spanish rental subsidy

In Southern Europe youngsters leave their parental home significantly later than in Northern Europe and the United States. In this paper, we study the effect of a monthly cash subsidy on the probability that young adults live apart from parents and childbearing. The subsidy, introduced in Spain in 2008, is conditional on young adults renting accommodation, and it amounts to almost 20 percent of the average youngsters' wage. Our identification strategy exploits the subsidy eligibility age threshold to assess the causal impact of the cash transfer. Difference-in-Differences estimates show positive effects of the policy on the probability of living apart from parents, living with a romantic partner, and chidbearing for 22 year-olds compared to 21 year-olds. Results persist when the sample is expanded to include wider age ranges. The effect is larger among young adults earning lower incomes and living in high rental price areas. This is consistent with the hypothesis that youngsters delay household formation because the cost is too high relative to their income

TV or not TV? The impact of subtitling on English skills

We study the influence of television translation techniques on the quality of English spoken worldwide. We identify a large positive effect for subtitled original version broadcasts, as opposed to dubbed television, on English profficiency scores. We analyze the historical circumstances under which countries opted for one of the translation modes and use it to account for the possible endogeneity of the subtitling indicator. We disaggregate the results by type of skills and find that television works especially for listening comprehension. Our paper suggests that governments could promote subtitling as a means to improve foreign language profficiency and therefore economic performance

TV or not TV? The impact of subtitling on english skills

We study the influence of television translation techniques on the worldwide distribution of English-speaking skills. We identify a large positive effect for subtitled original version broadcasts, as opposed to dubbed television, on English proficiency scores. We analyze the historical circumstances under which countries opted for one of the translation modes and use it to account for the possible endogeneity of the subtitling indicator. We disaggregate the results by type of skills and find that television works especially well for listening comprehension. Our paper suggests that governments could promote subtitling as a means to improve foreign language proficiency

Increase in serotype 19A prevalence and amoxicillin non-susceptibility among paediatric Streptococcus pneumoniae isolates from middle ear fluid in a passive laboratory-based surveillance in Spain, 1997-2009

BACKGROUND: Conjugate vaccines, such as the 7-valent conjugate vaccine (PCV7), alter serotype nasopharyngeal carriage, potentially increasing cases of otitis media by non-vaccine serotypes. METHODS: All paediatric middle ear fluid (MEF) isolates received in the Spanish Reference Laboratory for Pneumococci through a passive, laboratory-based surveillance system from January 1997 to June 2009 were analysed. Data from 1997 to 2000 were pooled as pre-vaccination period. Trends over time were explored by linear regression analysis. RESULTS: A total of 2,077 isolates were analysed: 855 belonging to PCV7 serotypes, 466 to serotype 19A, 215 to serotype 3, 89 to serotype 6A and 452 to other serotypes ( 35% isolates) since PCV7 strains represented < 11% of total clinical isolates. CONCLUSIONS: In contrast to reports on invasive pneumococcal strains, in MEF isolates the reduction in the prevalence of PCV7 serotypes was not associated with decreases in penicillin/erythromycin non-susceptibility. The high prevalence of serotype 19A among paediatric MEF isolates and the amoxicillin non-susceptibility found in this serotype are worrisome since amoxicillin is the most common antibiotic used in the treatment of acute otitis media. These data suggest that non-PCV7 serotypes (mainly serotype 19A followed by serotypes 3 and 6A) are important etiological agents of acute otitis media and support the added value of the broader coverage of the new 13-valent conjugate vaccine.This study was supported in part by an unrestricted grant from Pfizer S.A., Madrid, Spain and PRISM-AG, Madrid, Spain. O.R. belongs to the Spanish Network for the Research in Infectious Diseases (REIPI).S

The role of beta-adrenergic system remodeling in human heart failure: A mechanistic investigation

[EN] ß-adrenergic receptor antagonists (ß-blockers) are extensively used to improve cardiac performance in heart failure (HF), but the electrical improvements with these clinical treatments are not fully understood. The aim of this study was to analyze the electrophysiological effects of ß-adrenergic system remodeling in heart failure with reduced ejection fraction and the underlying mechanisms. We used a combined mathematical model that integrated ß-adrenergic signaling with electrophysiology and calcium cycling in human ventricular myocytes. HF remodeling, both in the electrophysiological and signaling systems, was introduced to quantitatively analyze changes in electrophysiological properties due to the stimulation of ß-adrenergic receptors in failing myocytes. We found that the inotropic effect of ß-adrenergic stimulation was reduced in HF due to the altered Ca2+ dynamics resulting from the combination of structural, electrophysiological and signaling remodeling. Isolated cells showed proarrhythmic risk after sympathetic stimulation because early afterdepolarizations appeared, and the vulnerability was greater in failing myocytes. When analyzing coupled cells, ß-adrenergic stimulation reduced transmural repolarization gradients between endocardium and epicardium in normal tissue, but was less effective at reducing these gradients after HF remodeling. The comparison of the selective activation of ß-adrenergic isoforms revealed that the response to ß2-adrenergic receptors stimulation was blunted in HF while ß1-adrenergic receptors downstream effectors regulated most of the changes observed after sympathetic stimulation. In conclusion, this study was able to reproduce an altered ß-adrenergic activity on failing myocytes and to explain the mechanisms involved. The derived predictions could help in the treatment of HF and guide in the design of future experiments.This work was partially supported by the "Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016" from the Ministerio de Economía, Industria y Competitividad of Spain and Fondo Europeo de Desarrollo Regional (FEDER) DPI2016-75799-R (AEI/FEDER, UE), by the "Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020" from the Ministerio de Ciencia e Innovación y Universidades (PID2019-104356RB-C41/AEI/10.13039/5011000110 33), and by the "Programa de Ayudas de Investigación y Desarrollo (PAID-01-17)" from the Universitat Politècnica de València.Mora-Fenoll, MT.; Gong, JQX.; Sobie, EA.; Trenor Gomis, BA. (2021). The role of beta-adrenergic system remodeling in human heart failure: A mechanistic investigation. 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Trayanova, Degradation of T-tubular microdomains and altered cAMP Compartmentation Lead to emergence of Arrhythmogenic triggers in heart failure Myocytes: an in silico study, Front. Physiol. 9 (2018) 1–12. doi:https://doi.org/10.3389/fphys.2018.01737.Rocchetti, M., Alemanni, M., Mostacciuolo, G., Barassi, P., Altomare, C., Chisci, R., … Zaza, A. (2008). Modulation of Sarcoplasmic Reticulum Function by PST2744 [Istaroxime; (E,Z)-3-((2-Aminoethoxy)imino) Androstane-6,17-dione Hydrochloride)] in a Pressure-Overload Heart Failure Model. Journal of Pharmacology and Experimental Therapeutics, 326(3), 957-965. doi:10.1124/jpet.108.138701Dong, X., & Thomas, D. D. (2014). Time-resolved FRET reveals the structural mechanism of SERCA–PLB regulation. Biochemical and Biophysical Research Communications, 449(2), 196-201. doi:10.1016/j.bbrc.2014.04.166Lucia, C. de, Eguchi, A., & Koch, W. J. (2018). New Insights in Cardiac β-Adrenergic Signaling During Heart Failure and Aging. 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Enhanced In Vivo Activity of Cefditoren in Pre-Immunized Mice against Penicillin-Resistant S. pneumoniae (Serotypes 6B, 19F and 23F) in a Sepsis Model

Background Specific antibodies are likely to be present before S. pneumoniae infection. We explored cefditoren (CDN) total and free values of serum concentrations exceeding the MIC (t>MIC) related to efficacy in a mice sepsis model, and the effect of specific gammaglobulins on in-vitro phagocytosis and in-vivo efficacy. Methodology/Principal Findings We used three pneumococcal isolates (serotype, MIC of CDN): Strain 1 (6B, 1 µg/ml), Strain 2 (19F, 2 µg/ml) and Strain 3 (23F, 4 µg/ml). Hyperimmune serum (HS) was obtained from mice immunized with heat-inactivated strains. In-vitro, phagocytosis by HS diluted 1/10 in presence/absence of sub-inhibitory concentrations was measured by flow cytometry including fluorescent bacteria and a neutrophil cell line. In-vivo dose-ranging experiments with HS (dilutions 1/2–1/16) and CDN (6.25 mg/kg–100 mg/kg tid for 48 h) were performed to determine the minimal protective dilution/dose (highest survival) and the non-protective highest dilution/dose (highest mortality: HS-np dilution and CDN-np dose) over 7 days. Efficacy of CDN-np in animals pre-immunized with HS-np (combined strategy) was explored and blood bacterial clearance determined. The CDN measured protein binding was 86.9%. In-vitro, CDN significantly increased phagocytosis (vs. HS 1/10). In non pre-immunized animals, t>MIC values for CDN of ≈35% (total) and ≈19% (free) were associated with 100% survival. Significant differences in survival were found between HS-np alone (≤20%) or CDN-np alone (≤20%) vs. the combined strategy (90%, 60% and 60% for Stains 1, 2 and 3), with t>MIC (total/free) of 22.8%/14.3%, 26.8%/16.0%, and 22.4%/12.7% for Strains 1, 2 and 3, respectively. Prior to the second dose (8 h), median bacterial counts were significantly lower in animals surviving vs. dead at day 7. Conclusions/Significance In mice (CDN protein binding similar to humans) total t>MIC values of ≈35% (≈19% free) were efficacious, with a decrease in the required values in pre-immunized animals. This reinforces that immunoprotection to overcome resistance may provide lifesaving strategies.This study was supported by an unrestricted grant from Tedec-Meiji Farma S.A., Madrid, Spain. Tedec-Meiji Farma S.A. had a role in providing reagents, materials and analysis toolsPeer reviewe

Disease isolates of Streptococcus pseudopneumoniae and non-typeable S. pneumoniae presumptively identified as atypical S. pneumoniae in Spain

We aimed to obtain insights on the nature of a collection of isolates presumptively identified as atypical Streptococcus pneumoniae recovered from invasive and non-invasive infections in Spain. One-hundred and thirty-two isolates were characterized by: optochin susceptibility in ambient and CO2-enriched atmosphere; bile solubility; PCR-based assays targeting pneumococcal genes lytA, ply, pspA, cpsA, Spn9802, aliB-like ORF2, and a specific 16S rRNA region; multilocus sequence analysis; and antimicrobial susceptibility. By multilocus sequence analysis, 61 isolates were S. pseudopneumoniae, 34 were pneumococci, 13 were S. mitis, and 24 remained unclassified as non-pneumococci. Among S. pseudopneumoniae isolates, 51 (83.6%) were collected from respiratory tract samples; eight isolates were obtained from sterile sources. High frequency of non-susceptibility to penicillin (60.7%) and erythromycin (42.6%) was found. Only 50.8% of the S. pseudopneumoniae isolates displayed the typical optochin phenotype originally described for this species. None harbored the cpsA gene or the pneumococcal typical lytA restriction fragment length polymorphism. The Spn9802 and the specific 16S rRNA regions were detected among the majority of the S. pseudopneumoniae isolates (n = 59 and n = 49, respectively). The ply and pspA genes were rarely found. A high genetic diversity was found and 59 profiles were identified. Among the S. pneumoniae, 23 were capsulated and 11 were non-typeable. Three non-typeable isolates, associated to international non-capsulated lineages, were recovered from invasive disease sources. In conclusion, half of the atypical pneumococcal clinical isolates were, in fact, S. pseudopneumoniae and one-fourth were other streptococci. We identified S. pseudopneumoniae and non-typeable pneumococci as cause of disease in Spain including invasive disease

High Protein Binding and Cidal Activity against Penicillin-Resistant S. pneumoniae: A Cefditoren In Vitro Pharmacodynamic Simulation

BACKGROUND: Although protein binding is a reversible phenomenon, it is assumed that antibacterial activity is exclusively exerted by the free (unbound) fraction of antibiotics. METHODOLOGY/PRINCIPAL FINDINGS: Activity of cefditoren, a highly protein bound 3(rd) generation cephalosporin, over 24h after an oral 400 mg cefditoren-pivoxil bid regimen was studied against six S. pneumoniae strains (penicillin/cefditoren MICs; microg/ml): S1 (0.12/0.25), S2 (0.25/0.25), S3 and S4 (0.5/0.5), S5 (1/0.5) and S6 (4/0.5). A computerized pharmacodynamic simulation with media consisting in 75% human serum and 25% broth (mean albumin concentrations = 4.85+/-0.12 g/dL) was performed. Protein binding was measured. The cumulative percentage of a 24h-period that drug concentrations exceeded the MIC for total (T > MIC) and unbound concentrations (fT > MIC), expressed as percentage of the dosing interval, were determined. Protein binding was 87.1%. Bactericidal activity (> or = 99.9% initial inocula reduction) was obtained against strains S1 and S2 at 24h (T > MIC = 77.6%, fT > MIC = 23.7%). With T > MIC of 61.6% (fT > MIC = 1.7%), reductions against S3 and S4 ranged from 90% to 97% at 12h and 24h; against S5, reduction was 45.1% at 12h and up to 85.0% at 24h; and against S6, reduction was 91.8% at 12h, but due to regrowth of 52.9% at 24h. Cefditoren physiological concentrations exerted antibacterial activity against strains exhibiting MICs of 0.25 and 0.5 microg/ml under protein binding conditions similar to those in humans. CONCLUSIONS/SIGNIFICANCE: The results of this study suggest that, from the pharmacodynamic perspective, the presence of physiological albumin concentrations may not preclude antipneumococcal activity of highly bound cephalosporins as cefditoren

REA 3D-dynamic analysis in Almaraz NPP with RELAP5/PARCS v2.7 and SIMTAB cross-sections tables

[EN] The Rod Ejection Accident (REA) belongs to the Reactivity-Initiated Accidents (RIA) category of accidents and it is part of the licensing basis accident analyses required for pressurized water reactors (PWR). The REA at Hot Zero Power (HZP) is characterized by a single rod ejection from a core position with a very low power level. The evolution consists basically of a continuous reactivity insertion. The main feature limiting the consequences of the accident in a PWR is the Doppler Effect. To check the performance of the coupled code RELAP5/PARCS v2.7 a REA in Almaraz NPP is simulated. These analyses will allow knowing more accurately the PWR real plant phenomenology in the RIA most limiting conditions.This work has been partially supported by the Spanish Ministerio de Educación y Ciencia under project PHB2007-0067-PC and by the Brazilian Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) under project CAPES/DGU 159/08. This work has also been partially supported by the Spanish Ministerio de Educación y Ciencia under project ENE2008-02669, the Generalitat Valenciana under project ACOMP/2009/058, and the Universitat Politècnica de València under project PAID-05-09-4285. The authors wish to acknowledge the technical and financial support of the Almaraz-Trillo AIE for this work.Barrachina Celda, TM.; Garcia-Fenoll, M.; Ánchel Añó, FC.; Miró Herrero, R.; Verdú Martín, GJ.; Pereira, C.; Da Silva, C.... (2011). REA 3D-dynamic analysis in Almaraz NPP with RELAP5/PARCS v2.7 and SIMTAB cross-sections tables. Progress in Nuclear Energy. 53(8):1167-1180. https://doi.org/10.1016/j.pnucene.2011.07.012S1167118053