Bacterial growth rate and host factors as determinants of intracellular bacterial distributions in systemic Salmonella enterica infections.

Bacteria of the species Salmonella enterica cause a range of life-threatening diseases in humans and animals worldwide. The within-host quantitative, spatial, and temporal dynamics of S. enterica interactions are key to understanding how immunity acts on these infections and how bacteria evade immune surveillance. In this study, we test hypotheses generated from mathematical models of in vivo dynamics of Salmonella infections with experimental observation of bacteria at the single-cell level in infected mouse organs to improve our understanding of the dynamic interactions between host and bacterial mechanisms that determine net growth rates of S. enterica within the host. We show that both bacterial and host factors determine the numerical distributions of bacteria within host cells and thus the level of dispersiveness of the infection.

Spread of Salmonella enterica in the body during systemic infection: unravelling host and pathogen determinants.

Salmonella enterica causes a range of life-threatening diseases in humans and animals worldwide. Current treatments for S. enterica infections are not sufficiently effective, and there is a need to develop new vaccines and therapeutics. An understanding of how S. enterica spreads in tissues has very important implications for targeting bacteria with vaccine-induced immune responses and antimicrobial drugs. Development of new control strategies would benefit from a more sophisticated evaluation of bacterial location, spatiotemporal patterns of spread and distribution in the tissues, and sites of microbial persistence. We review here recent studies of S. enterica serovar Typhimurium (S. Typhimurium) infections in mice, an established model of systemic typhoid fever in humans, which suggest that continuous bacterial spread to new infection foci and host phagocytes is an essential trait in the virulence of S. enterica during systemic infections. We further highlight how infections within host tissues are truly heterogeneous processes despite the fact that they are caused by the expansion of a genetically homogeneous microbial population. We conclude by discussing how understanding the within-host quantitative, spatial and temporal dynamics of S. enterica infections might aid the development of novel targeted preventative measures and drug regimens.

Did bankruptcy reform lead to looser mortgage lending standard? : evidence from the U. S. mortgage market 2000-2007

Resumen: El presente trabajo intenta encontrar una causa exógena al deterioro, a partir de 2005, en los estándares de crédito hipotecario que contribuyeron a la crisis subprime en los Estados Unidos. Sostenemos que la nueva provisión de la prueba de medios de la ley Bankruptcy Abuse Prevention and Consumer Protection Act (BAPCPA) de 2005 fue dicho shock exógeno en el mercado hipotecario. Mostramos que la prueba de medios, que impide solicitar la bancarrota bajo Chapter 7 a los deudores con mayores ingresos relativos, causó un desplazamiento de la oferta de crédito hipotecario de deudores con mayores ingresos a deudores con menores ingresos relativos. Simultáneamente, observamos que todos los deudores debieron pagar tasas de interés más altas, independientemente del nivel de ingresos. Nuestros resultados implican que la ley BAPCPA podría ser un factor que contribuyó al deterioro en los estándares de crédito en el mercado hipotecario de los Estados Unidos.

Brazil’s patent reform : innovation towards national competitiveness

Adaptação para a língua inglesa da obra “A revisão da lei de patentes: inovação em prol da competitividade nacional

The Metabolic Core and Catalytic Switches Are Fundamental Elements in the Self-Regulation of the Systemic Metabolic Structure of Cells

19 p.

Pension system's reform in Spain: a dynamic analysis of the effects in Welfare

100 p. : graf.

An austerity-driven energy reform

In July 2013, the government approved a major overhaul of the Spanish electricity sector to correct existing imbalances that have led to an exponential increase of regulated electricity costs and a huge tariff deficit. The reform addresses the problem of financial sustainability of the sector, severely affected by weak demand and overcapacity. Previous regulation introduced in 2012 and early 2013, also aimed at restoring financial stability of the sector, failed to correct the tariff shortfall and new regulatory measures were needed to reduce the 4.5 billion euros forecasted deficit for 2013. The frequent change of the rules of the game in the sector has created regulatory uncertainty, more so as it is not clear that the present reform will be sufficient to eliminate the deficit. Moreover, the government has left the door open to new regulation that would deal with the price formation system. In general, short run financial criteria have prevailed, while efficiency principles and a long run perspective have little weight in the reform.

Randomised, crossover clinical trial, in healthy volunteers, to compare the systemic availability of two topical intranasal budesonide formulations

Background: Budesonide has a long history as intranasal drug, with many marketed products. Efforts should be made to demonstrate the therapeutic equivalence and safety comparability between them. Given that systemic availability significantly varies from formulations, the clinical comparability of diverse products comes to be of clinical interest and a regulatory requirement. The aim of the present study was to compare the systemic availability, pharmacodynamic effect, and safety of two intranasal budesonide formulations for the treatment of rhinitis. Methods: Eighteen healthy volunteers participated in this randomised, controlled, crossover, clinical trial. On two separated days, subjects received a single dose of 512 mu g budesonide (4 puffs per nostril) from each of the assayed devices (Budesonida nasal 64 (R), Aldo-Union, Spain and Rhinocort 64 (R), AstraZeneca, Spain). Budesonide availability was determined by the measurement of budesonide plasma concentration. The pharmacodynamic effect on the hypothalamic-adrenal axis was evaluated as both plasma and urine cortisol levels. Adverse events were tabulated and described. Budesonide availability between formulations was compared by the calculation of 90% CI intervals of the ratios of the main pharmacokinetic parameters describing budesonide bioavailability. Plasma cortisol concentration-time curves were compared by means of a GLM for Repeated Measures. Urine cortisol excretion between formulations was compared through the Wilcoxon's test. Results: All the enroled volunteers successfully completed the study. Pharmacokinetic parameters were comparable in terms of AUC(t) (2.6 +/- 1.5 vs 2.2 +/- 0.7), AUCi (2.9 +/- 1.5 vs 2.4 +/- 0.7), t(max) (0.4 +/- 0.1 vs 0.4 +/- 0.2), C(max)/AUC(i) (0.3 +/- 0.1 vs 0.3 +/- 0.0), and MRT (5.0 +/- 1.4 vs 4.5 +/- 0.6), but not in the case of C(max) (0.9 +/- 0.3 vs 0.7 +/- 0.2) and t(1/2) (3.7 +/- 1.8 vs 2.9 +/- 0.4). The pharmacodynamic effects, measured as the effect over plasma and urine cortisol, were also comparables between both formulations. No severe adverse events were reported and tolerance was comparable between formulations. Conclusion: The systemic availability of intranasal budesonide was comparable for both formulations in terms of most pharmacokinetic parameters. The pharmacodynamic effect on hypothalamic-pituitary-adrenal axis was also similar. Side effects were scarce and equivalent between the two products. This methodology to compare different budesonide-containing devices is reliable and easy to perform, and should be recommended for similar products intented to be marketed or already on the market.

Environmental fiscal reform and unemployment in Spain in the presence of an informal sector

4 p.

Environmental Fiscal Reform and Unemployment in Spain

22 p.

Reform of Spain's profesional services market: Implementation of the EU Services Directive

The implementation of the European Commission Services Directive initiated the modernization process of services markets within the European Union. The objective was to guarantee the creation of a single market by ensuring the freedom of establishment and circulation. The transposition of the Directive in Spain triggered an initial wave of reforms in the Spanish legal system. A second package of reforms is currently underway, following recommendations by the EC, IMF and OECD, which highlight the relative lack of competition in Spain’s services as one of the major imbalances in its economy, alongside the public deficit and unemployment. Both the implemented and planned reforms represent a major step forward. Nevertheless, the government has recently announced modifications to the draft bill of the Professional Services and Associations Law, which is expected to soon be submitted for parliamentary debate and approval. Taking into consideration modifications already introduced, together with anticipated further changes, it will be important to maintain the main points of the draft bill and to introduce a deeper review of the legal framework for professional services, of the professional associations themselves, and for the activities that are subject to compulsory membership within a professional association. Spain’s territorial map of professional associations must too be redrawn.

Repolitizando a política externa financeira: uma análise da formulação da política externa brasileira para o setor financeiro pós 2008

O trabalho identifica quais os fatores sistêmicos e domésticos que influenciam na formulação da política externa brasileira para o setor financeiro, com foco no período posterior à crise financeira de 2008. Para esse fim, a pesquisa analisa os atores domésticos que atuam no processo decisório de formulação da política externa para o setor financeiro, assim como seus interesses. Os órgãos federais ? nomeadamente o Ministério da Fazenda, o Banco Central e o Ministério das Relações Exteriores ? são os atores mais influentes nesse processo. O setor privado, apesar de dispor de capacidades políticas, delega a sua participação ao governo, assumindo uma postura reativa. Por sua vez, a sociedade civil tem pouca influência nesse processo. O cenário internacional tem papel de destaque nesse processo, pois restringe as ações do país, de acordo com a posição na hierarquia de poder. Após a estabilização econômica brasileira e a crise que abalou os mercados do Norte, o Brasil encontra-se mais livre em sua atuação internacional. Com isso, há um processo de repolitização da política externa para o setor financeiro, em que, no plano internacional, o Brasil coopera com outros países emergentes para demandar a redistribuição de poder decisório; e no plano doméstico, atores que antes não exerciam grande influência passam a ter.

Brasil rumo aos padrões internacionais de contabilidade para o setor público: uma análise sob a ótica do Financial Management Reform Process Model de Lüder.

O termo Sistema Contábil define toda a modelagem pela qual são tratados os dados internos e externos, de forma estruturada, para atender às demandas atribuídas à profissão contábil (tanto nos sistemas privados como nos governamentais), englobando fatores intrínsecos e extrínsecos da contabilidade e seus inter-relacionamentos. As variações desses fatores levam ao desenvolvimento de sistemas nacionalmente específicos. Nas classificações internacionais desses sistemas, são identificadas influências como a dos Estados Unidos, a do Reino Unido e a da Europa, ou ainda uma orientação micro ou macro, também definidas como modelo anglo-saxão e modelo continental. Observa-se, ainda, uma relação entre os níveis de desenvolvimento contábil públicos e privados. As principais causas determinantes da diversidade contábil se relacionam com as variáveis do modelo proposto por Lüder para se avaliar reformas governamentais financeiras (o FMR) e esse fato, por conseguinte, determinou a escolha do referido modelo para realizar as análises deste estudo. A pesquisa foi realizada com procedimentos metodológicos de natureza teórica com caráter exploratório e descritivo, através da qual se pode observar que a IFAC tem sido considerada responsável pelos principais esforços no processo de harmonização contábil do setor público e que boa parte dos países vem aceitando a IFAC como órgão emissor de padrões contábeis internacionais, ainda que os países que adotam integralmente esses padrões sem adaptações, sejam exceções. Os padrões de contabilidade governamental emitidos pela IFAC (IPSAS), na verdade, têm servido como um padrão de qualidade, e não como uma norma a ser adotada integralmente. A análise das principais características nacionais determinantes da diversidade contábil frente à adoção ou adaptação dos padrões internacionais da IFAC para o setor público, sob a ótica do FMR, indica que, no Brasil, o sistema contábil do setor público é mais propício a um processo de convergência aos padrões internacionais de Contabilidade da IFAC.