PALLAS : limiting indications for dronedarone treatment of atrial fibrillation.

Atrial fibrillation increases the risk of stroke. Dronedarone has been shown to reduce the composite of hospitalizations due to cardiovascular events or death, in subjects with intermittent atrial fibrillation or flutter. Recently, dronedarone has been tested in subjects with permanent atrial fibrillation in the PALLAS (permanent atrial fibrillation outcome study using dronedarone on top of standard therapy) trial, and this clinical trial is evaluated in this paper. PALLAS was stopped early as there was an increased incidence of cardiovascular events in the dronedarone group. Dronedarone also increased the rate of hospitalizations in PALLAS. As a result of PALLAS, dronedarone has been contraindicated in permanent atrial fibrillation. The outcomes of PALLAS highlight a discontinuity between dronedarone actions in permanent and intermittent atrial fibrillation. The mechanism(s) underlying the detrimental effects of dronedarone in permanent atrial fibrillation are unknown at present and need to be investigated.

Candidate gene analysis for quantitative traits using the transmission disequilibrium test : the example of the melanocortin 4-receptor in pigs

Population-wide associations between loci due to linkage disequilibrium can be used to map quantitative trait loci (QTL) with high resolution. However, spurious associations between markers and QTL can also arise as a consequence of population stratification. Statistical methods that cannot differentiate between loci associations due to linkage disequilibria from those caused in other ways can render false-positive results. The transmission-disequilibrium test (TDT) is a robust test for detecting QTL. The TDT exploits within-family associations that are not affected by population stratification. However, some TDTs are formulated in a rigid-form, with reduced potential applications. In this study we generalize TDT using mixed linear models to allow greater statistical flexibility. Allelic effects are estimated with two independent parameters: one exploiting the robust within-family information and the other the potentially biased between-family information. A significant difference between these two parameters can be used as evidence for spurious association. This methodology was then used to test the effects of the fourth melanocortin receptor (MC4R) on production traits in the pig. The new analyses supported the previously reported results; i.e., the studied polymorphism is either causal of in very strong linkage disequilibrium with the causal mutation, and provided no evidence for spurious association.

Genome-wide search for markers associated with bovine spongiform encephalopathy

A genome-wide search for markers associated with BSE incidence was performed by using Transmission-Disequilibrium Tests (TDTs). Significant segregation distortion, i.e., unequal transmission probabilities of alleles within a locus, was found for three marker loci on Chromosomes (Chrs) 5, 10, and 20. Although TDTs are robust to false associations owing to hidden population substructures, it cannot distinguish segregation distortion caused by a true association between a marker and bovine spongiform encephalopathy (BSE) from a population-wide distortion. An interaction test and a segregation distortion analysis in half-sib controls were used to disentangle these two alternative hypotheses. None of the markers showed any significant interaction between allele transmission rates and disease status, and only the marker on Chr 10 showed a significant segregation distortion in control individuals. Nevertheless, the control group may have been a mixture of resistant and susceptible but unchallenged individuals. When new genotypes were generated in the vicinity of these three markers, evidence for an association with BSE was confirmed for the locus on Chr 5.

Cardiac safety concerns for ondansetron, an antiemetic commonly used for nausea linked to cancer treatment and following anaesthesia

Introduction: Ondansetron is a 5-HT3 receptor antagonist commonly used as an anti-emetic to prevent the nausea and vomiting associated with anti-cancer drugs, cancer radiotherapy, or postoperatively. Recently, the US Food and Drug Administration (FDA) issued a warning for ondansetron due to a potential for prolongation of the QT interval of the electrocardiogram (ECG), a phenomenon that is associated with an increased risk of the potentially fatal arrhythmia torsade de pointes. Areas covered: We undertook a review of the cardiac safety of ondansetron. Our primary sources of information were PubMed (with downloading of full articles), and the internet. Expert opinion: The dose of ondansetron that the FDA has concerns about is 32 mg iv (or several doses that are equivalent to this), which is only used in preventing nausea and vomiting associated with cancer chemotherapy. This suggests that ondansetron may be safe in the lower doses used to prevent the nausea and vomiting in radiation treatment or postoperatively. However, as there is a report that a lower dose of ondansetron prolonged the QT interval in healthy volunteers, this needs to be clarified by the FDA. More research needs to be undertaken of the relationship between QT prolongation and torsades in order that the FDA can produce clear-cut evidence of pro-arrhythmic risk when introducing warnings for this.

Cardiac safety concerns for domperidone, an antiemetic and prokinetic, and galactogogue medicine

Introduction: Domperidone is a dopamine D2-receptor antagonist developed as an antiemetic and prokinetic agents. Oral domperidone is not approved in the US, but is used in many countries to treat nausea and vomiting, gastroparesis, and as a galactogogue (to promote lactation). The US Food and Drug Administration (FDA) have issued a warning about the cardiac safety of domperidone. Areas covered: The authors undertook a review of the cardiac safety of oral domperidone. Expert opinion: The data from preclinical studies are unambiguous in identifying domperidone as able to produce marked hERG channel inhibition and action potential prolongation at clinically relevant concentrations. The compound’s propensity to augment instability of action potential duration and action potential triangulation are also indicative of proarrhythmic potential. Domperidone should not be administered to subjects with pre-existing QT prolongation/LQTS, subjects receiving drugs that inhibit CYP3A4, subjects with electrolyte abnormalities or with other risk factors for QT-prolongation. With these provisos, it is possible that domperidone may be used as a galactogogue without direct risk to healthy breast feeding women but more safety information should be sought in this situation. Also, more safety information is required regarding risk to breast feeding infants or before domperidone is routinely used in gastroparesis or gastroesphageal reflux in children.

Plasma polymerization of 1,1,1-trichloroethane yields a coating with robust antibacterial surface properties

Novel, highly chlorinated surface coatings were produced via a one-step plasma polymerization (pp) of 1,1,1-trichloroethane (TCE), exhibiting excellent antimicrobial properties against the vigorously biofilm-forming bacterium Staphylococcus epidermidis.

The top 100 questions of importance to the future of global agriculture

Despite a significant growth in food production over the past half-century, one of the most important challenges facing society today is how to feed an expected population of some nine billion by the middle of the 20th century. To meet the expected demand for food without significant increases in prices, it has been estimated that we need to produce 70-100 per cent more food, in light of the growing impacts of climate change, concerns over energy security, regional dietary shifts and the Millennium Development target of halving world poverty and hunger by 2015. The goal for the agricultural sector is no longer simply to maximize productivity, but to optimize across a far more complex landscape of production, rural development, environmental, social justice and food consumption outcomes. However, there remain significant challenges to developing national and international policies that support the wide emergence of more sustainable forms of land use and efficient agricultural production. The lack of information flow between scientists, practitioners and policy makers is known to exacerbate the difficulties, despite increased emphasis upon evidence-based policy. In this paper, we seek to improve dialogue and understanding between agricultural research and policy by identifying the 100 most important questions for global agriculture. These have been compiled using a horizon-scanning approach with leading experts and representatives of major agricultural organizations worldwide. The aim is to use sound scientific evidence to inform decision making and guide policy makers in the future direction of agricultural research priorities and policy support. If addressed, we anticipate that these questions will have a significant impact on global agricultural practices worldwide, while improving the synergy between agricultural policy, practice and research. This research forms part of the UK Government's Foresight Global Food and Farming Futures project.

Non più mesta accanto al fuoco : floración operística del mito de Cenicienta

Resumen: Este artículo se aboca a un análisis comparativo de tres óperas basadas en el mito de Cenicienta, a partir de las versiones literarias canónicas de Basile, Perrault y Grimm: La Cenerentola de Rossini-Ferretti (1817), Cendrillon de Massenet-Cain (1899), y ¡Cenicientaaa...! de Lambertini (2008). Consideramos aspectos míticos del relato, como el combate cosmogónico, la unión hierogámica, la rivalidad fraterna y el complejo edípico, y estudiamos su vigencia y sus mutaciones a través de las sucesivas estéticas que corresponden a las tres óperas señaladas: iluminismo, romanticismo, posmodernidad.

Medidas antielisivas na instituição de cobrança do imposto sobre grandes fortunas (IGF)

Analisa experiências internacionais relativamente à definição da base de cálculo e dos sujeitos passivos do imposto sobre a renda.

Medida Provisória nº 685, de 2015

Descreve o conteúdo da Medida Provisória nº 685, de 21 de julho de 2015, publicada pelo Poder Executivo no Diário Oficial da União em 22 de julho de 2015. Trata da criação e regulamentação do Programa de Redução de litígios tributários.

Imposto sobre grandes fortunas, fuga de capitais e crescimento econômico

Visa responder ao questionamento acerca da existência de uma causalidade necessária entre a instituição do IGF em uma determinada matriz tributária nacional – em especial a brasileira – e o efeito da fuga de capitais produtivos. Também visa comparar a receita pública auferida com a instituição do imposto em face das perdas econômicas na fuga de capitais para o exterior.

Tributação de lucros e dividendos no Brasil : uma perspectiva comparada

Traça um panorama dos diversos modelos de tributação dos lucros e dividendos no mundo, bem como descrever a evolução da política fiscal brasileira sobre o tema.

Alegia klasikoak euskaraz: Isopeteko, La Fontaineren eta Samaniegoren alegien berridazketen azterketa

521 p.

Feminismo, luta de classes e consciência militante feminista no Brasil

A formação da consciência na sociedade capitalista é atravessada por relações de alienação e pela ideologia dominante que dificultam o desenvolvimento da consciência revolucionária, desenvolvida na militância coletiva voltada para a transformação social. Na particularidade das mulheres, esse processo é mais difícil por estarem envolvidas em relações patriarcais de dominação, apropriação e exploração advindas, fundamentalmente, da divisão sexual do trabalho que, associadas a uma ideologia de uma suposta natureza feminina, as constitui como submissas, subservientes, passivas e apolíticas. Por isso, partimos da pergunta: como ocorre o processo de formação da consciência militante feminista em uma sociedade patriarcal e capitalista? O sentido geral desta tese é compreender a formação da consciência militante feminista e seus principais desdobramentos na luta de classes no Governo Lula. A delimitação do estudo no Governo Lula é motivada pela necessidade de compreensão do feminismo na contemporaneidade, mas, também, pela inquietação de analisar a capacidade de envolvimento político desse governo no campo dos movimentos feministas. A apreensão da lógica transformista que preside esse governo é fundamental para análise das lutas feministas, pois, se por um lado o Brasil presenciou a institucionalização de políticas sociais para as mulheres; por outro, muitos entraves ocorreram para a efetivação das mesmas, desde a falta de orçamento até a dificuldade da incorporação de uma perspectiva verdadeiramente feminista por parte do projeto de governo petista. A tese busca apreender a consciência militante feminista e a sua relação com a luta de classes no governo Lula, em uma perspectiva de totalidade, com o esforço de ir além da sua aparência fenomênica, mas, no seio das relações sociais de classe, raça e sexo inseridas na dinâmica dos projetos societários em disputa: o patriarcal-capitalista e o feminista-socialista. Realizamos uma pesquisa bibliográfica, documental e de campo. Essa última foi desenvolvida por meio de entrevistas com 7 militantes orgânicas de cada um dos seguintes movimentos feministas: Articulação de Mulheres Brasileiras; Marcha Mundial de Mulheres e o Movimento de Mulheres Camponesas. Totalizamos, portanto, 21 entrevistas que articuladas à pesquisa documental de materiais produzidos por esses movimentos, bem como com a base teórica adquirida na pesquisa bibliográfica, obtivemos como principais conclusões: 1. O processo de formação da consciência militante feminista envolve como elementos indispensáveis às mulheres: (a) a apropriação de si e a ruptura com a naturalização do sexo; (b) o sair de casa; (c) a identificação na outra da sua condição de mulher; (d) a importância do grupo e da militância política em um movimento social; (e) a formação política associada às lutas concretas de reivindicação e de enfrentamento; 2. O feminismo contribui com a radicalização da democracia e com o tensionamento das relações de hierarquia presentes, inclusive, no interior de organizações de esquerda; 3. As políticas públicas para as mulheres no governo Lula, não corresponderam a uma perspectiva feminista, pois, não romperam com a responsabilização da mulher pela reprodução social antroponômica, tendo em vista o caráter familista das mesmas; 4. A autonomia política e financeira é o principal desafio para os movimentos feministas no Brasil.