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Departing from the notion that labour legislation should be founded in the generation of job stability a model for recruitment is presented in which the employer is likened to the holder of an investment portfolio containing two real derivatives – swap or the option of sale. This model allows us on one hand to analyze sensitivity to the variables that are at play in an employment contract and, on the other, look at the effects that the most recent reforms in Spanish labour laws have had on contracting decisions made by employers. The results are clear: social security benefits are shown to be the most sensitive variable on the work contract, and applying the changes proposed in the latest labour reforms, this effect is upheld. The study concludes that reducing the costs of dismissal does not increase the likelihood of employers' taking on new staff. ; Dada la situación actual y partiendo del supuesto que como herramienta para una correcta política de empleo la legislación laboral debe sentar las bases sólidas para que en el momento de recuperación económica se generen puestos de trabajo estables, se presenta un modelo de simulación de contratación que nos va a permitir un análisis de sensibilidad de las distintas variables a tener en cuenta en una regulación del mercado laboral. El modelo consiste en asimilar el comportamiento del empresario al del propietario de una cartera de inversión compuesta por dos derivados reales, un swap y una opción de venta americana. Este modelo nos permite, por un lado, hacer un análisis de sensibilidad de las diferentes variables que intervienen en la contratación, y, por otro lado, analizar los efectos que la última reforma laboral española tiene sobre la decisión de contratar del empresario. Los resultados son claros, la variable que más sensibilidad presenta sobre la contratación es la cuota patronal de la seguridad social, y aplicando los cambios propuestos en esta última reforma laboral, se concretan estos efectos y también se concluye que la reducción de los costes de despido no acelera la decisión de contratar. ; Dada a situação atual e partindo do suposto que como ferramenta para uma correta política de emprego, a legislação laboral deve instituir as bases sólidas para que, no momento da recuperação econômica, se gerem postos de trabalho estáveis, se apresentem um modelo de simulação de contratação que nos permitirá uma análise de sensibilidade das diferentes variáveis a considerar em uma regulação do mercado laboral. O modelo consiste em assimilar o comportamento do empresário ao do proprietário de uma carteira de investimento composto por dois derivados reais, um swap e uma opção de venda americana. Esse modelo nos permite, por um lado, fazer uma análise de sensibilidade das diferentes variáveis que intervêm na contratação e, por outro lado, analisar os efeitos que a última reforma laboral espanhola tem sobre a decisão de contratar do empresário. Os resultados são claros, a variável que mais sensibilidade apresenta sobre a contratação é a cota patronal da previdência social e aplicando as mudanças propostas nesta última reforma laboral, concretizam-se esses efeitos e também se conclui que a redução dos custos de demissão não acelera a decisão de contratar

Departing from the notion that labour legislation should be founded in the generation of job stability a model for recruitment is presented in which the employer is likened to the holder of an investment portfolio containing two real derivatives – swap or the option of sale. This model allows us on one hand to analyze sensitivity to the variables that are at play in an employment contract and, on the other, look at the effects that the most recent reforms in Spanish labour laws have had on contracting decisions made by employers. The results are clear: social security benefits are shown to be the most sensitive variable on the work contract, and applying the changes proposed in the latest labour reforms, this effect is upheld. The study concludes that reducing the costs of dismissal does not increase the likelihood of employers' taking on new staff. ; Dada la situación actual y partiendo del supuesto que como herramientapara una correcta política de empleo la legislación laboral debe sentar las basessólidas para que en el momento de recuperación económica se generen puestosde trabajo estables, se presenta un modelo de simulación de contratación quenos va a permitir un análisis de sensibilidad de las distintas variables a teneren cuenta en una regulación del mercado laboral. El modelo consiste en asimilar el comportamiento del empresario al delpropietario de una cartera de inversión compuesta por dos derivados reales, unswap y una opción de venta americana. Este modelo nos permite, por un lado,hacer un análisis de sensibilidad de las diferentes variables que intervienen en lacontratación, y, por otro lado, analizar los efectos que la última reforma laboralespañola tiene sobre la decisión de contratar del empresario. Los resultadosson claros, la variable que más sensibilidad presenta sobre la contratación esla cuota patronal de la seguridad social, y aplicando los cambios propuestos enesta última reforma laboral, se concretan estos efectos y también se concluyeque la reducción de los costes de despido no acelera la decisión de contratar. ; Dada a situação atual e partindo do suposto que como ferramenta para uma correta política de emprego, a legislação laboral deve instituir as bases sólidas para que, no momento da recuperação econômica, se gerem postos de trabalho estáveis, se apresentem um modelo de simulação de contratação que nos permitirá uma análise de sensibilidade das diferentes variáveis a considerar em uma regulação do mercado laboral. O modelo consiste em assimilar o comportamento do empresário ao do proprietário de uma carteira de investimento composto por dois derivados reais, um swap e uma opção de venda americana. Esse modelo nos permite, por um lado, fazer uma análise de sensibilidade das diferentes variáveis que intervêm na contratação e, por outro lado, analisar os efeitos que a última reforma laboral espanhola tem sobre a decisão de contratar do empresário. Os resultados são claros, a variável que mais sensibilidade apresenta sobre a contratação é a cota patronal da previdência social e aplicando as mudanças propostas nesta última reforma laboral, concretizam-se esses efeitos e também se conclui que a redução dos custos de demissão não acelera a decisão de contratar.

Departing from the notion that labour legislation should be founded in the generation of job stability a model for recruitment is presented in which the employer is likened to the holder of an investment portfolio containing two real derivatives – swap or the option of sale. This model allows us on one hand to analyze sensitivity to the variables that are at play in an employment contract and, on the other, look at the effects that the most recent reforms in Spanish labour laws have had on contracting decisions made by employers. The results are clear: social security benefits are shown to be the most sensitive variable on the work contract, and applying the changes proposed in the latest labour reforms, this effect is upheld. The study concludes that reducing the costs of dismissal does not increase the likelihood of employers' taking on new staff. ; Dada la situación actual y partiendo del supuesto que como herramientapara una correcta política de empleo la legislación laboral debe sentar las basessólidas para que en el momento de recuperación económica se generen puestosde trabajo estables, se presenta un modelo de simulación de contratación quenos va a permitir un análisis de sensibilidad de las distintas variables a teneren cuenta en una regulación del mercado laboral. El modelo consiste en asimilar el comportamiento del empresario al delpropietario de una cartera de inversión compuesta por dos derivados reales, unswap y una opción de venta americana. Este modelo nos permite, por un lado,hacer un análisis de sensibilidad de las diferentes variables que intervienen en lacontratación, y, por otro lado, analizar los efectos que la última reforma laboralespañola tiene sobre la decisión de contratar del empresario. Los resultadosson claros, la variable que más sensibilidad presenta sobre la contratación esla cuota patronal de la seguridad social, y aplicando los cambios propuestos enesta última reforma laboral, se concretan estos efectos y también se concluyeque la reducción de los costes de despido no acelera ...

Recent network and system biology analyses suggest that most complex diseases are regulated by robust and highly interconnected pathways that could be better modulated by small molecules binding to multiple biological targets. These pieces of evidence recently led to devote efforts on identifying single chemical entities that bind to two different disease-relevant targets. Here, we first predicted in silico and later confirmed in vitro that UPF 1069, a known bioactive poly(ADP-ribose) polymerase-1/2 (PARP1/2) molecule, and hydroxyfasudil, a known bioactive Rho-associated protein kinase-1/2 (ROCK1/2) molecule, have low-micromolar cross-affinity for ROCK1/2 and PARP1/2, respectively. These molecules can now be regarded as chemical seeds from which pharmacological tools could be generated to study the impact of dual inhibition of PARPs and ROCKs in preclinical models of a variety of complex diseases where both targets are involved. ; This research was funded by the People Program (Marie Curie Actions) of the 7th Framework Program of the European Union (FP7/2007−2013) under REA grant agreement no. 600388 (TECNIOspring program) (A.A.A.); the Agency of Business Competitiveness of the Government of Catalonia ACCIO (A.A.A.); the Wellcome Trust Sir Henry Wellcome Postdoctoral Fellowship (204735/Z/16/Z) (A.A.A.); and the Spanish Ministerio de Economia y Competitividad grant BIO2014-54404-R (J.M.).

BACKGROUND: Many risk behaviours in adolescence are socially patterned. However, it is unclear to what extent socioeconomic position (SEP) influences adolescent drinking in various parts of Europe. We examined how alcohol consumption is associated with parental SEP and adolescents' own SEP among students aged 14-17 years. METHODS: Cross-sectional data were collected in the 2013 SILNE study. Participants were 8705 students aged 14-17 years from 6 European cities. The dependent variable was weekly binge drinking. Main independent variables were parental SEP (parental education level and family affluence) and adolescents' own SEP (student weekly income and academic achievement). Multilevel Poisson regression models with robust variance and random intercept were fitted to estimate the association between adolescent drinking and SEP. RESULTS: Prevalence of weekly binge drinking was 4.2% (95%CI = 3.8-4.6). Weekly binge drinking was not associated with parental education or family affluence. However, weekly binge drinking was less prevalent in adolescents with high academic achievement than those with low achievement (PR = 0.34; 95%CI = 0.14-0.87), and more prevalent in adolescents with >€50 weekly income compared to those with ≤€5/week (PR = 3.14; 95%CI = 2.23-4.42). These associations were found to vary according to country, but not according to gender or age group. CONCLUSIONS: Across the six European cities, adolescent drinking was associated with adolescents' own SEP, but not with parental SEP. Socio-economic inequalities in adolescent drinking seem to stem from adolescents' own situation rather than that of their family. ; This study is part of the SILNE-R project, which is supported by the European Union's Horizon 2020 research and innovation programme, under grant agreement 635056; and of the project 'Tackling socio-economic inequalities in smoking (SILNE)', which is funded by the European Commission, Directorate-General for Research and Innovation, under the FP7-Health-2011 programme, with grant agreement number 278273. This work was also supported by the Spanish Network on Addictive Disorders [grant number RD12/0028/0018]

Large efforts dedicated to detect somatic alterations across tumor genomes/exomes are expected to produce significant improvements in precision cancer medicine. However, high inter-tumor heterogeneity is a major obstacle to developing and applying therapeutic targeted agents to treat most cancer patients. Here, we offer a comprehensive assessment of the scope of targeted therapeutic agents in a large pan-cancer cohort. We developed an in silico prescription strategy based on identification of the driver alterations in each tumor and their druggability options. Although relatively few tumors are tractable by approved agents following clinical guidelines (5.9%), up to 40.2% could benefit from different repurposing options, and up to 73.3% considering treatments currently under clinical investigation. We also identified 80 therapeutically targetable cancer genes. ; We acknowledge funding from the Spanish Ministry of Economy and Competitiveness (grant number SAF2012-36199), La Fundació la Marató de TV3, and the Spanish National Institute of Bioinformatics (INB). C.R.-P. and M.P.S. are supported by an FPI fellowship. D.T. is supported by the People Programme (Marie Curie Actions) of the Seventh Framework Programme of the European Union (FP7/2007-2013) under REA grant agreement number 600388 and by the Agency of Competitiveness for Companies of the Government of Catalonia, ACCIÓ. A.G.-P. is supported by a Ramón y Cajal contract.