Sequentially testing for a gene-drug interaction in a genomewide analysis

Assaying a large number of genetic markers from patients in clinical trials is now possible in order to tailor drugs with respect to efficacy. The statistical methodology for analysing such massive data sets is challenging. The most popular type of statistical analysis is to use a univariate test for each genetic marker, once all the data from a clinical study have been collected. This paper presents a sequential method for conducting an omnibus test for detecting gene-drug interactions across the genome, thus allowing informed decisions at the earliest opportunity and overcoming the multiple testing problems from conducting many univariate tests. We first propose an omnibus test for a fixed sample size. This test is based on combining F-statistics that test for an interaction between treatment and the individual single nucleotide polymorphism (SNP). As SNPs tend to be correlated, we use permutations to calculate a global p-value. We extend our omnibus test to the sequential case. In order to control the type I error rate, we propose a sequential method that uses permutations to obtain the stopping boundaries. The results of a simulation study show that the sequential permutation method is more powerful than alternative sequential methods that control the type I error rate, such as the inverse-normal method. The proposed method is flexible as we do not need to assume a mode of inheritance and can also adjust for confounding factors. An application to real clinical data illustrates that the method is computationally feasible for a large number of SNPs. Copyright (c) 2007 John Wiley & Sons, Ltd.

Truth commissions: a barrier to the provision of judicial assistance?

Truth commissions and criminal trials have come to be perceived as complementary transitional justice mechanisms. However, where effective prosecutions are dependent on the exchange of information and transfer of suspects between states under existing mutual legal assistance and extradition arrangements, the operation of a truth commission in the state of territoriality may act as an obstacle to international cooperation. At the same time, requests for assistance from a third state pursuing prosecutions may impact negatively on the truth commission process in the requested state by inhibiting those reluctant to become involved in criminal proceedings from offering testimony. This article demonstrates a practical discord between these bodies when they operate in different states and questions whether they can truly be considered “complementary”.

The Copenhagen principles on the handling of detainees: implications for the procedural regulation of internment

The Copenhagen Principles on the Handling of Detainees in International Military Operations were released in October 2012 after a five-year long process involving states and certain organizations. The Principles address a number of issues concerning the handling and transfer of detainees. They apply in military operations conducted by states abroad in the context of non-international armed conflicts and peace operations. This article focuses on those principles that address the procedural regulation of internment (ie preventive, security detention), as it is here that the current law is particularly unclear. On the one hand, the treaty provisions applicable in non-international armed conflicts contain no rules on the procedural regulation of internment, in comparison with the law of international armed conflict. On the other hand, the relevant rules under international human rights law (IHRL) appear derogable in such situations. This article demonstrates that the approach taken to this issue in the Copenhagen Principles is one which essentially draws on the procedural rules applicable to civilian internment in the international armed conflicts. These rules adopt standards that are lower than those under IHRL. Reference is then made to other recent practice, which illustrates that the Copenhagen Principles do not apply in a legal vacuum. In particular, two recent judicial developments highlight the continued relevance of human rights law and domestic law, respectively, in regulating detention operations in the context of international military operations. Compliance with the Copenhagen Principles may not, therefore, be sufficient for detention to be lawful.

The rulB gene of plasmid pWW0 is a hotspot for the site-specific insertion of integron-like elements found in the chromosomes of environmental Pseudomonas fluorescens group bacteria

The rulAB operon of Pseudomonas spp. confers fitness traits on the host and has been suggested to be a hotspot for insertion of mobile elements that carry avirulence genes. Here, for the first time, we show that rulB on plasmid pWW0 is a hotspot for the active site-specific integration of related integron-like elements (ILEs) found in six environmental pseudomonads (strains FH1–FH6). Integration into rulB on pWW0 occurred at position 6488 generating a 3 bp direct repeat. ILEs from FH1 and FH5 were 9403 bp in length and contained eight open reading frames (ORFs), while the ILE from FH4 was 16 233 bp in length and contained 16 ORFs. In all three ILEs, the first 5.1 kb (containing ORFs 1–4) were structurally conserved and contained three predicted site-specific recombinases/integrases and a tetR homologue. Downstream of these resided ORFs of the ‘variable side’ with structural and sequence similarity to those encoding survival traits on the fitness enhancing plasmid pGRT1 (ILEFH1 and ILEFH5) and the NR-II virulence region of genomic island PAGI-5 (ILEFH4). Collectively, these ILEs share features with the previously described type III protein secretion system effector ILEs and are considered important to host survival and transfer of fitness enhancing and (a)virulence genes between bacteria.

Profits, malversations, restitutions. Les bénéfices des financiers durant la guerre de la Ligue d’Augsbourg et la taxe de Chamillart

Profit, embezzlement, restitution. The role of the traitants in the Nine Years War and Chamillart’s tax on financial benefits The aim of this article is to revisit the question of the financiers in Old Regime France. It starts with an analysis of the discourses about the financiers under the Absolute monarchy that underlines the complexity of their relationship with the government and the public. It then reviews the secondary literature and highlights the existence of competing historical interpretations (functional, political, utilitarian), which raise the question of their overall capacity to account for the role and impact of the financiers at different times. On this ground, the article focuses on a specific group of financiers, the so-called traitants d’affaires extraordinaires, during the Nine Years War. Further to a description of the specific role and scope of the activities of the various financiers responsible for helping the monarchy to raise the funds it needed to pay for its peace and wartime expenditure, the article examines the conditions and profits granted by the king in his contracts with the traitants whose services were hired for the purpose of selling royal offices in the public and advancing the revenue to the Treasury. It also explores the contractual arrangements of the companies established by the financiers to manage their operations as well as the rights and the responsibilities of their various stakeholders. These bases being laid, the article relies on the administrative correspondence relating to the traités during the Nine Years War to address a range of issues, in particular the extent to which these contracts, and other control procedures, were robust enough to deter fraud. The accounts of two traitants’ companies offer an opportunity to analyse and compare the structure of their income and expenditure (including the volume and cost of the promissory notes sold in the public to finance their payments to the Treasury), to explore the strategies of the contractors, to calculate their net profits and further discuss the problem of embezzlement. The article ends with the study of the context and debates which led to the introduction by finance minister Michel Chamillart, in 1700, of a shortfall tax on the financial profits of the gens d’affaires or traitants, the method used to determine its rate (50 % of the net benefits), its distribution among the various stakeholders (including the bailleurs de fonds or backers), and the related procedures. In total, the article argues that the relationship between the monarchy, society and the financiers under the Ancien Regime was not static and, therefore, suggests that the broad question of control and fraud must be examined against changing circumstances. With regard specifically to the Nine Years War, the article concludes that within the constraints of the Absolute monarchy, contractors offered valuable services by raising capital for the benefit of a king who ruled over a country which, at the time, was by far the wealthiest in Europe, and where ministers failed to foresee long wars of attrition and whose financial strategy was limited by the very existence of privilege. Overall, the traités were too costly to be a viable system of war financing. In these conditions, the substantial fortunes made by a handful of very successful traitants suffice to explain that the government easily gave in to public criticism against the wealth of the financiers and felt compelled, when peace resumed, to cancel the advantageous conditions offered in the treaties by taxing financial profits.

Interfaces in the acquisition of syntax

We introduce empirical work on Romance language acquisition with respect to the interfaces of syntax with other modules of grammar (internal interfaces) and other domains of cognition (external interfaces). We do so by choosing specific phenomena within the following interfaces: syntax-morphology, syntax-semantics and syn-tax-pragmatics. In the domain of syntax-morphology we focus on grammatical gender, with respect to the syntax-semantics interface we focus on adjectival placement (pre- and post-nominal) and with regard to the syntax-discourse/pragmatics interface we review work on the null/overt subject distribution. Finally, we summarize research on articles, suggesting that articles represent a multiple interface. We provide examples from different types of learners and across the four major Romance languages French, Italian, Portuguese and Spanish. While our central goal is to summarize and generalize across major findings, we will also point to potential problems concerning the interface approach, e.g. the association of particular phenomena with a specific interface and the assumption that internal interfaces are less problematic than external ones.

Fatty acids as trophic biomarkers in vitellogenic females in an impounded tropical river

Fatty acids have been used in marine biogeochemistry as food chain biomarkers, but in freshwater these studies are rare. In order to evaluate the fatty acid potential as biomarkers in freshwater, their profile was analyzed during vitellogenesis in two fish species, in both waterfall and reservoir environments of the Paraiba do Sul River Basin. Detrivorous Hypostomus affinis and omnivorous Geophagus brasiliensis seem to elongate and desaturate polyunsaturated fatty acids (PUFA) and transfer them to the ovaries` phospholipids. Waterfall Geophagus brasiliensis have more highly unsaturated fatty acids in the liver, but in the reservoir, accumulation mainly occurs in muscle and ovary triglycerides, suggesting trophic opportunism and a plasticity during vitellogenesis. In Hypostomus affinis, PUFA alteration occurs only in the reservoir, suggesting a high phytoplankton occurrence. Eutrophication and water speed is reflected in Hypostomus affinis ovaries by higher PUFAn3 and bacterial fatty acids. As in marine environments, analysis of mono- and polyunsaturated fatty acids during vitellogenesis can be used as a tool in food chain studies in freshwater.

Scientific program of the Radioactive Ion Beams Facility in Brasil (RIBRAS)

The RIBRAS facility (Radioactive Ion Beams in Brasil) is installed in connection with the 8MV Pelletron tandem of the University of Sao Paulo Physics Institute. It consists of two superconducting solenoids which focalize light radioactive secondary beams of low energy, produced by transfer reactions. Recent experimental results include the elastic scattering and transfer reactions of (6)He halo nucleus on (9)Be, (27)Al, (51)V and (120)Sn targets. The elastic scattering and transfer of (8)Li and (7)Be on several targets is also being studied. The transfer reaction (8)Li(p,alpha)(5)He of astrophysical interest was also Studied in the E(cm)=0.2-2.5 MeV energy range.

Escolhas estratégicas e guerra fiscal: competição ou cooperação no caso do Estado do Rio de Janeiro

Este estudo tem por objetivo analisar as tendências atuais para a cooperação ou competição entre os estados brasileiros, nos jogos predatórios para atração de investimentos privados. Investigamos o processo de construção de agendas, relacionado às opções do Estado, no momento em que se debate a reforma tributária e o fim da "guerra fiscal". A pesquisa apresenta as razões históricas da questão e enfoca as condições estratégicas nas quais o Governo do Estado do Rio de Janeiro pode se inserir nessa agenda política. Os resultados revelam que, sem a superação de um conjunto de fragilidades na estrutura federativa e no sistema tributário nacional, mesmo com fortes lideranças políticas e mecanismos regulatórios, o jogo competitivo entre os estados não alcançará, em curto ou médio prazo, um padrão salutar.

Controle em tempo real de robôs através de redes IP

Com o intuito de utilizar uma rede com protocolo IP para a implementação de malhas fechadas de controle, este trabalho propõe-se a realizar um estudo da operação de um sistema de controle dinâmico distribuído, comparando-o com a operação de um sistema de controle local convencional. Em geral, a decisão de projetar uma arquitetura de controle distribuído é feita baseada na simplicidade, na redução dos custos e confiabilidade; portanto, um diferencial bastante importante é a utilização da rede IP. O objetivo de uma rede de controle não é transmitir dados digitais, mas dados analógicos amostrados. Assim, métricas usuais em redes de computadores, como quantidade de dados e taxa de transferências, tornam-se secundárias em uma rede de controle. São propostas técnicas para tratar os pacotes que sofrem atrasos e recuperar o desempenho do sistema de controle através da rede IP. A chave para este método é realizar a estimação do conteúdo dos pacotes que sofrem atrasos com base no modelo dinâmico do sistema, mantendo o sistema com um nível adequado de desempenho. O sistema considerado é o controle de um manipulador antropomórfico com dois braços e uma cabeça de visão estéreo totalizando 18 juntas. Os resultados obtidos mostram que se pode recuperar boa parte do desempenho do sistema.

A cooperação trilateral brasileira em Moçambique: um estudo de caso comparado: o ProALIMENTOS e o ProSAVANA

A arquitetura do sistema de ajuda internacional passa por um processo de transformação, no qual as barreiras Norte e Sul tornam-se cada vez mais indefinidas, e a cooperação trilateral, que une as práticas opostas da cooperação Norte-Sul com a cooperação Sul-Sul, emerge como uma nova modalidade da cooperação técnica brasileira. Com o objetivo de compreender esse cenário, esta tese almeja identificar e contrastar as motivações e as práticas dos agentes da cooperação trilateral brasileira por meio de um estudo de caso comparado de dois projetos, desenvolvidos pela Agência Brasileira de Cooperação (ABC), no setor agrícola em Moçambique: o ProALIMENTOS, parceria entre a United States Agency for International Development (USAID- -Brasil) e ABC, e o ProSAVANA, parceria entre Japan International Cooperation Agency (JICA) e ABC. Para isso, a pesquisa parte dos pressupostos da actor-oriented approach para estabelecer uma análise multinível, que cria desta forma um elo entre o agente e a estrutura, a prática e a política, com um olhar sobre o contexto macro, meso e micro. A utilização da metodologia qualitativa aplicada a essa investigação combinou a técnica de participação observante com a técnica de análise documental, acrescentando à análise 59 entrevistas semiestruturadas, realizadas principalmente entre os meses de março e junho de 2013, em Moçambique. Os resultados da pesquisa indicam que, no caso do ProALIMENTOS, há ganhos em complementaridade e troca de conhecimento para as três contrapartes, porém há a sobreposição das práticas Norte-Sul de cooperação para o desenvolvimento internacional sobre as práticas da cooperação Sul-Sul. Enquanto que, no caso do ProSAVANA, não há qualquer ganho de complementariedade, uma vez que o Programa enfrenta desafios internos e externos. A falta de harmonização e coordenação técnica no âmbito interno intensificam o embate externo com os representantes da sociedade civil ao gerar constantes falhas de comunicação, o que coloca em xeque a própria continuidade do ProSAVANA. Por último, a pesquisa mostra que é necessário um maior comprometimento do governo brasileiro nos projetos de Cooperação Trilateral, uma vez que os resultados desses projetos podem impactar e afetar a credibilidade do Brasil como um novo prestador de ajuda internacional.

Impactos econômicos das mudanças do PIS-COFINS utilizando um modelo de equilíbrio geral computável

Neste artigo é apresentada uma avaliação dos impacto da reforma tributária do PIS/PASEP e da COFINS, que passaram a ser coletados através de dois regimes associados aos fluxos domésticos (cumulativo e não cumulativo - misto) e a incidir sobre importações de bens e serviços. A metodologia adotada utiliza um modelo de Equilíbrio Geral Computável (CGE), adaptado para as novas características do sistema fiscal e especificado para simular os impactos sobre indicadores de bem-estar no Brasil. Estes impactos foram avaliados em duas etapas: a mudança do regime cumulativo para o novo regime tributário e a reforma completa. Os resultados mostram que esta reforma teria provocado deterioração dos indicadores macroeconômicos, de mercado de trabalho e de bem-estar.

O Conselho Federal de Cultura e o Instituto Histórico e Geográfico Brasileiro: um estudo de caso da política de financiamento à cultura (1966-1974).

Esta dissertação analisa a política de financiamento do Conselho Federal de Cultura (CFC), órgão responsável pelas políticas públicas de cultura da ditadura civil-militar, diretamente ligado ao Ministério da Educação e Cultura. O CFC estabeleceu convênios com diversas instituições culturais, como o Instituto Histórico e Geográfico Brasileiro (IHGB). No período de 1966 a 1974 atuou com exclusividade, o que permitia estabelecer regras para requisição e repasse de recursos às instituições culturais. Buscaremos aqui, entender, a partir das publicações da Revista Cultura e, posteriormente, do Boletim do Conselho Federal de Cultura, as normas que possibilitavam a liberação de recursos para instituições privadas, como os Institutos Históricos. Averiguaremos a importância da produção intelectual e cultural do IHGB. Para um aprofundamento dessas questões, selecionamos convênios do CFC estabelecidos com o IHGB que visavam dois tipos de financiamento: obras de infraestrutura e atividade cultural.

A gestão da informação sob a luz do Enterprise Content Management (ECM): um estudo de caso em uma universidade pública

This work involves the organization and content perspectives on Enterprise Content Management (ECM) framework. The case study at the Federal University of Rio Grande do Norte was based on ECM model to analyse the information management provided by the three main administrative systems: The Integrated Management of Academic Activities (SIGAA), Integrated System of Inheritance, and Contracts Administration (SIPAC) and the Integrated System for Administration and Human Resources (SIGRH). A case study protocol was designed to provide greater reliability to research process. Four propositions were examined in order to reach the specific objectives of identification and evaluation of ECM components from UFRN perspective. The preliminary phase provided the guidelines for the data collection. In total, 75 individuals were interviewed. Interviews with four managers directly involved on systems design were recorded (average duration of 90 minutes). The 70 remaining individuals were approached in random way in UFRN s units, including teachers, administrative-technical employees and students. The results showed the presence of many ECM elements in the management of UFRN administrative information. The technological component with higher presence was "management of web content / collaboration". But initiatives of other components (e.g. email and document management) were found and are in continuous improvement. The assessment made use of eQual 4.0 to examine the effectiveness of applications under three factors: usability, quality of information and offered service. In general, the quality offered by the systems was very good and walk side by side with the obtained benefits of ECM strategy adoption in the context of the whole institution

Mudança dos processos de negócios e adequação da TI nas empresas em decorrência da implantação do sistema público de escrituração digital SPED: um estudo de casos múltiplos

Companies have always been organized by processes, often imperceptible to its employees. With the advancement of technology, organizational processes currently run an organization through computers, and thus generate immediate information that is available to each sector. With the objective of seeking business information in real time, the government created the SPED - Public System of Digital, which involves three subsystems, which are the Electronic Invoice, Digital Accounting Bookkeeping and Digital Tax Bookkeeping. This system is revolutionizing the business structures when gathering, in an innovative way, all information and interlinked business processes. For the implementation of SPED, a revision in the organizational processes is required, since the information is generated and is sent online to the government, without mistakes. Thus the study aimed to analyze the change brought about by the implementation of the Public System of Digital SPED in the main business processes. In order to do so, we have performed a multiple case study involving three companies in the state of Para, two operate in wholesale and one explores agribusiness. The Data collection was performed by accounting professionals, IT and managers. According to the results obtained, it was found that in two companies, the IT infrastructure was capable of deploying the new system without major problems, while one company had more difficulties to cope with the new system. However, all companies had to examine its processes to make the customizations needed to fit. It was also observed that there is no IT Governance in two companies. Therefore, we recommend the use of an appropriate model, not only for the implementation of SPED, but as a way to manage and extract better results from investment in information technology