Targeting myocardial remodelling to develop novel therapies for heart failure: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology

The failing heart is characterized by complex tissue remodelling involving increased cardiomyocyte death, and impairment of sarcomere function, metabolic activity, endothelial and vascular function, together with increased inflammation and interstitial fibrosis. For years, therapeutic approaches for heart failure (HF) relied on vasodilators and diuretics which relieve cardiac workload and HF symptoms. The introduction in the clinic of drugs interfering with beta-adrenergic and angiotensin signalling have ameliorated survival by interfering with the intimate mechanism of cardiac compensation. Current therapy, though, still has a limited capacity to restore muscle function fully, and the development of novel therapeutic targets is still an important medical need. Recent progress in understanding the molecular basis of myocardial dysfunction in HF is paving the way for development of new treatments capable of restoring muscle function and targeting specific pathological subsets of LV dysfunction. These include potentiating cardiomyocyte contractility, increasing cardiomyocyte survival and adaptive hypertrophy, increasing oxygen and nutrition supply by sustaining vessel formation, and reducing ventricular stiffness by favourable extracellular matrix remodelling. Here, we consider drugs such as omecamtiv mecarbil, nitroxyl donors, cyclosporin A, SERCA2a (sarcoplasmic/endoplasmic Ca(2 +) ATPase 2a), neuregulin, and bromocriptine, all of which are currently in clinical trials as potential HF therapies, and discuss novel molecular targets with potential therapeutic impact that are in the pre-clinical phases of investigation. Finally, we consider conceptual changes in basic science approaches to improve their translation into successful clinical applications.

Prebiotic potential of a maize-based soluble fibre and impact of dose on the human gut microbiota

Dietary management of the human gut microbiota towards a more beneficial composition is one approach that may improve host health. To date, a large number of human intervention studies have demonstrated that dietary consumption of certain food products can result in significant changes in the composition of the gut microbiota i.e. the prebiotic concept. Thus the prebiotic effect is now established as a dietary approach to increase beneficial gut bacteria and it has been associated with modulation of health biomarkers and modulation of the immune system. Promitor™ Soluble Corn Fibre (SCF) is a well-known maize-derived source of dietary fibre with potential selective fermentation properties. Our aim was to determine the optimum prebiotic dose of tolerance, desired changes to microbiota and fermentation of SCF in healthy adult subjects. A double-blind, randomised, parallel study was completed where volunteers (n = 8/treatment group) consumed 8, 14 or 21 g from SCF (6, 12 and 18 g/fibre delivered respectively) over 14-d. Over the range of doses studied, SCF was well tolerated Numbers of bifidobacteria were significantly higher for the 6 g/fibre/day compared to 12g and 18g/fibre delivered/day (mean 9.25 and 9.73 Log10 cells/g fresh faeces in the pre-treatment and treatment periods respectively). Such a numerical change of 0.5 Log10 bifidobacteria/g fresh faeces is consistent with those changes observed for inulin-type fructans, which are recognised prebiotics. A possible prebiotic effect of SCF was therefore demonstrated by its stimulation of bifidobacteria numbers in the overall gut microbiota during a short-term intervention.

Stochastic simulations of the Madden-Julian oscillation activity

The Madden-Julian oscillation (MJO) is the most prominent form of tropical intraseasonal variability. This study investigated the following questions. Do inter-annual-to-decadal variations in tropical sea surface temperature (SST) lead to substantial changes in MJO activity? Was there a change in the MJO in the 1970s? Can this change be associated to SST anomalies? What was the level of MJO activity in the pre-reanalysis era? These questions were investigated with a stochastic model of the MJO. Reanalysis data (1948-2008) were used to develop a nine-state first order Markov model capable to simulate the non-stationarity of the MJO. The model is driven by observed SST anomalies and a large ensemble of simulations was performed to infer the activity of the MJO in the instrumental period (1880-2008). The model is capable to reproduce the activity of the MJO during the reanalysis period. The simulations indicate that the MJO exhibited a regime of near normal activity in 1948-1972 (3.4 events year(-1)) and two regimes of high activity in 1973-1989 (3.9 events) and 1990-2008 (4.6 events). Stochastic simulations indicate decadal shifts with near normal levels in 1880-1895 (3.4 events), low activity in 1896 1917 (2.6 events) and a return to near normal levels during 1918-1947 (3.3 events). The results also point out to significant decadal changes in probabilities of very active years (5 or more MJO events): 0.214 (1880-1895), 0.076 (1896-1917), 0.197 (1918-1947) and 0.193 (1948-1972). After a change in behavior in the 1970s, this probability has increased to 0.329 (1973-1989) and 0.510 (1990-2008). The observational and stochastic simulations presented here call attention to the need to further understand the variability of the MJO on a wide range of time scales.

Low-energy d plus d fusion reactions via the Trojan Horse Method

The bare nucleus S(E) factors for the (2)H(d, p)(3)H and (2)H(d.n)(3)He reactions have been measured for the first time via the Trojan Horse Method off the proton in (3)He from 1.5 MeV down to 2 key. This range overlaps with the relevant region for Standard Big Bang Nucleosynthesis as well as with the thermal energies of future fusion reactors and deuterium burning in the Pre-Main-Sequence phase of stellar evolution. This is the first pioneering experiment in quasi free regime where the charged spectator is detected. Both the energy dependence and the absolute value of the S(E) factors deviate by more than 15% from available direct data with new S(0) values of 57.4 +/- 1.8 MeVb for (3)H + p and 60.1 +/- 1.9 MeV b for (3)He + n. None of the existing fitting curves is able to provide the correct slope of the new data in the full range, thus calling for a revision of the theoretical description. This has consequences in the calculation of the reaction rates with more than a 25% increase at the temperatures of future fusion reactors. (C) 2011 Elsevier By. All rights reserved.

Obfuscation and Strict Online Anonymity

I consider the case for genuinely anonymous web searching. Big data seems to have it in for privacy. The story is well known, particularly since the dawn of the web. Vastly more personal information, monumental and quotidian, is gathered than in the pre-digital days. Once gathered it can be aggregated and analyzed to produce rich portraits, which in turn permit unnerving prediction of our future behavior. The new information can then be shared widely, limiting prospects and threatening autonomy. How should we respond? Following Nissenbaum (2011) and Brunton and Nissenbaum (2011 and 2013), I will argue that the proposed solutions—consent, anonymity as conventionally practiced, corporate best practices, and law—fail to protect us against routine surveillance of our online behavior. Brunton and Nissenbaum rightly maintain that, given the power imbalance between data holders and data subjects, obfuscation of one’s online activities is justified. Obfuscation works by generating “misleading, false, or ambiguous data with the intention of confusing an adversary or simply adding to the time or cost of separating good data from bad,” thus decreasing the value of the data collected (Brunton and Nissenbaum, 2011). The phenomenon is as old as the hills. Natural selection evidently blundered upon the tactic long ago. Take a savory butterfly whose markings mimic those of a toxic cousin. From the point of view of a would-be predator the data conveyed by the pattern is ambiguous. Is the bug lunch or potential last meal? In the light of the steep costs of a mistake, the savvy predator goes hungry. Online obfuscation works similarly, attempting for instance to disguise the surfer’s identity (Tor) or the nature of her queries (Howe and Nissenbaum 2009). Yet online obfuscation comes with significant social costs. First, it implies free riding. If I’ve installed an effective obfuscating program, I’m enjoying the benefits of an apparently free internet without paying the costs of surveillance, which are shifted entirely onto non-obfuscators. Second, it permits sketchy actors, from child pornographers to fraudsters, to operate with near impunity. Third, online merchants could plausibly claim that, when we shop online, surveillance is the price we pay for convenience. If we don’t like it, we should take our business to the local brick-and-mortar and pay with cash. Brunton and Nissenbaum have not fully addressed the last two costs. Nevertheless, I think the strict defender of online anonymity can meet these objections. Regarding the third, the future doesn’t bode well for offline shopping. Consider music and books. Intrepid shoppers can still find most of what they want in a book or record store. Soon, though, this will probably not be the case. And then there are those who, for perfectly good reasons, are sensitive about doing some of their shopping in person, perhaps because of their weight or sexual tastes. I argue that consumers should not have to pay the price of surveillance every time they want to buy that catchy new hit, that New York Times bestseller, or a sex toy.

Anton Nyström's Defense of Homosexuality

In 1919 Anton Nyström became the first person in Sweden to publish a comprehensive defense of homosexuality. He believed that its classification as a mental illness was erroneous and that Sweden's law against homosexual sex was both irrational and cruel. Nyström was a physician whose work in the medical area dealt primarily with dermatology, psychiatry and human sexuality; however he was also a prolific historian, who took a staunchly anti-Christian view in his analysis of how Christianity affected European culture, especially in the area of sexual morality. In fact, much of Nyström's medical texts dealing with human sexuality consisted of anti-Christian cultural and historical commentary. The object of this "C-uppsats" is to analyze Nyström's pamphlet, Om Homosexualitet och Hermafroditi: Belysning af Missförstådda Existenser and illustrate how its defensive structure was consistent with the pattern used by the author in his other books and articles on human sexuality. Specifically, that irrational and neurotic Christian beliefs caused both mental and physical suffering and were the source of deleterious forms of morality. Additionally, this paper will also show that the solution Nyström had for the problem of negative and erroneous attitudes towards homosexuality was to replace the sodomitic view of homosexuality with one based upon a more rational and naturalistic belief system, the basis of which could be found in the pre-Christian cultures of Europe, most especially in Greece. This new conception was to be constructed primarily out of historical example and cultural analyses. For Nyström, history writing was used both as a weapon to fight the source of negative attitudes towards homosexuality, as well as a tool that could be used to build a positive cultural model which would be beneficial for homosexuals.

- Ni får gärna hoppa på golvet om ni vill hoppa : En studie om pedagogers bemötande av barns egna initativ i förskola och förskoleklass

The purpose of this survey was to discern possible similarities and difference between how teachers in preschool and pre-class respond to children’s own initiative out of a power perspective. The results of this study is collect by observations that we have done in free and planned activity in both preschool and pre-class as well as a few interviews with some of the teachers. The results have shown that teacher’s responses to children’s own initiatives in preschool and pre-class to most part is similar, despite the difference in their commission. The biggest differences are that teachers in preschool prioritize children’s care before allowing the children to pursue their own initiatives, which haven’t emerged from the observations in the pre-class. Another difference is that the teachers in pre-class are more flexible during the planned activities and utilize the children’s own initiatives.

Sociologin i Grekland : från 1907 fram till Metaxas-diktaturen (1936–1940) och andra världskriget

Sociology in Greece from 1907 to the Metaxas dictatorship (1936–40) and the Second World War This paper focuses on pre-conditions for sociology to develop and the subject matters of emerging sociology in Greece. Pre-conditions were at hand but without continuity, and the opportunity for sociology to develop was lost. Sociology is said to have started in 1907 with the book The Social Question by Georgos Skliros. He presented sociology and Marxism as identical and deals with Greek society and (among other things) the language issue, all of which triggered off a vibrant debate. Sociological associations and journals were started. However, the initially reformist perspective of social science was gradually replaced by an approach that was more socio-philosophical, influenced by classical sociology, German sociology in particular. This turn was associated with the institutionalization of sociology at the universities during the 1920’s. The Metaxas dictatorship in 1936 put a stop to any further development of sociology for a long time.

Materialising bodies : there is nothing more material than a socially constructed body.

Over the last one of two decades, researchers within the physical education (PE) and sport pedagogy research frequently use the concept ‘the material body’. An initial purpose of this article is to explore what a concept of a ‘material body’ might mean. What other bodies are there? Who would dispute the materiality of bodies? I suggest that the use of a concept as ‘the material body’ suggests a hesitation before the radicalism of the linguistic turn in the sense that the concept ‘discourse’ does not include a material dimension. In this way ‘the material body’ relates to an interpretation of ‘the socially (or discursively) constructed body’ as void of matter. A further purpose with the article is to re-inscribe matter in the concept of ‘discourse’. This is done by way of discussing what theorists like Michel Foucault and, in particular, Judith Butler, has to say about the materiality of the body. In their writings, discourse should not be limited to spoken and/or written language. Rather, discourse is understood in terms of actions and events that create meanings—that matters. One conclusion of the article is that it is important to problematise the mundane view of discourse as ‘verbal interchange’ because it reinforces the promise of an objective knowledge that will eventually shed light on the ‘real’ body and the mysteries of sexual difference, what its origins are, what causes it. Another conclusion is that the PE and sport pedagogy research should pay less attention to the body as an object (what it ‘is’), and pay more attention to how the body matters, and e.g. how movements make bodies matter.

Definitioner av våld i överlevandes berättelser efter kriget i Bosnien

Definitions of violence in stories of survivors from the Bosnian war Previous research on violence during the war in Bosnia and Herzegovina presents a one-sided picture of the phenomenon ”war violence.” Researchers have emphasized the importance of narratives but they have not focused on stories about war violence, nor have they analyzed the stories of war violence being a product of interpersonal interaction. This article tries to fill this knowledge gap by analyzing the narratives told by survivors of the war in northwestern Bosnia in the 1990s. The aim is to analyze how the survivors describe violence during the war, and also to analyze those discursive patterns that contribute in constructing the category ”war violence.” The construction of the category ”war violence” is made visible in the empirical material when the interviewees talk about (1) a new social order in the society, (2) human suffering, (3) sexual violence, and (4) human slaughter. All interviewees define war violence as morally reprehensible. In narratives on the phenomena ”war violence” a picture emerges which shows a disruption of the social order existing in the pre-war society. The violence practiced during the war is portrayed as organized and ritualized and this creates a picture that the violence practice became a norm in the society, rather than the exception. Narratives retelling violent situations, perpetrators of violence and subjected to violence do not only exist as a mental construction. The stories live their lives after the war, and thus have real consequences for individuals and society.

Análise não linear física e geométrica de pórticos espaciais

Apresenta-se uma formulação do tipo incrementaliterativa destinada a análise não linear de pórticos espaciais. Considera-se os efeitos não lineares introduzidos pelas mudanças de configuração geométrica da estrutura e também pela combinação destes efeitos com aqueles inerentes ao comportamento plástico exibido pelo material. As relações cinemáticas empregadas permitem a consideração de deslocamentos arbitrariamente grandes, acompanhadas de pequenas deformações . A modelagem do comportamento plástico do material é efetuada através do conceito de rótula plástica, estabelecido a partir de um critério de plastificação generalizado. Adota-se uma matriz de rigidez geométrica de barra baseada em momentos semitangenciais. Para elementos com extremos plastificados, é deduzida uma matriz de rigidez elasto-plástica. Emprega-se um método numérico do tipo incremental-iterativo, que utiliza como condição básica de controle da análise a constância do trabalho realizado pelos incrementos de cargas, em cada passo incremental (Método de Controle por Trabalho).A formulação permite uma descricão completa do desempenho mecânico da estrutura, inclusive em estágio de deformação pós-crítico em que ocorre regressão do carregamento com aumento de deslocamentos, ou vice-versa. A formulação foi implementada em um programa computacional elaborado em linguagem FORTRAN. Vários exemplos numéricos são apresentados para mostrar a eficiência das procedimentos propostos.

Consumo para obtenção de status: estudo empírico entre meninas pré-dolescentes de São Luis do Maranhão

The consumption of goods from brands in vogue, which symbolize status, popularity, success and social distinction, among those from the same social group in a pre-teenage girls¿ environment, has been a topic for academic studies as well as the market, due to their relevant consumption power for the companies worldwide. This paper aims to check out the use of these goods by them in São Luís, in order to become popular, succesful and socially distinguished; and the relation of the consumption for status with the brand image consumed and the pre-teenage girl self image; how familiar with the goods and the brand they are; and their attitude concerning their qualities. The empirical metodology had two phases: a qualitative and a quantitative one. The first one started with a specific group of 8 (eight) pre-teenage girls from high and medium classes, with the purpose of collecting some basis in order to reinforce the theory once the hypothesis were elaborated and used to guide the quantitative research as well as to adapt some North American scales. In the second stage of the qualitative research, a survey was applied in a convenience sample of 300 (three hundred) pre-teenage girls from São Luís, all from the high, medium high and low classes. The main result showed the pre-teenage girls from São Luís consume goods and brands for status, so they could get prestige, success, and social distinction, however, they do not define themselves or judge the social status of those from their social group based only on the clothes they wear and the brands which indicate their consumption power. Some other status symbols are important too, like, housing, the family car, the neighborhood where they dwell, the parents¿ occupation; the school they go to, the long and straight hair, how correct they speak Portuguese and their holiday trips. Another result highlighted was the strong relation of the brand image with their self image in the consumption for status.

Comportamento de pares de ações no mercado brasileiro sob a ótica da cointegração, para preços intra-diários

Esta dissertação estuda o movimento do mercado acionário brasileiro com o objetivo de testar a trajetória de preços de pares de ações, aplicada à estratégia de pair trading. Os ativos estudados compreendem as ações que compõem o Ibovespa e a seleção dos pares é feita de forma unicamente estatística através da característica de cointegração entre ativos, sem análise fundamentalista na escolha. A teoria aqui aplicada trata do movimento similar de preços de pares de ações que evoluem de forma a retornar para o equilíbrio. Esta evolução é medida pela diferença instantânea dos preços comparada à média histórica. A estratégia apresenta resultados positivos quando a reversão à média se efetiva, num intervalo de tempo pré-determinado. Os dados utilizados englobam os anos de 2006 a 2010, com preços intra-diários para as ações do Ibovespa. As ferramentas utilizadas para seleção dos pares e simulação de operação no mercado foram MATLAB (seleção) e Streambase (operação). A seleção foi feita através do Teste de Dickey-Fuller aumentado aplicado no MATLAB para verificar a existência da raiz unitária dos resíduos da combinação linear entre os preços das ações que compõem cada par. A operação foi feita através de back-testing com os dados intra-diários mencionados. Dentro do intervalo testado, a estratégia mostrou-se rentável para os anos de 2006, 2007 e 2010 (com retornos acima da Selic). Os parâmetros calibrados para o primeiro mês de 2006 puderam ser aplicados com sucesso para o restante do intervalo (retorno de Selic + 5,8% no ano de 2006), para 2007, onde o retorno foi bastante próximo da Selic e para 2010, com retorno de Selic + 10,8%. Nos anos de maior volatilidade (2008 e 2009), os testes com os mesmos parâmetros de 2006 apresentaram perdas, mostrando que a estratégia é fortemente impactada pela volatilidade dos retornos dos preços das ações. Este comportamento sugere que, numa operação real, os parâmetros devem ser calibrados periodicamente, com o objetivo de adaptá-los aos cenários mais voláteis.

Educação e lutas sociais na colonização dirigida: o Alto Turi maranhense: 1962-1984

Proposta de compreensao da relação entre educaçao e lutas sociais no contexto histórico da Colonização Dirigida. O trabalho de campo realizou-se na região do Alto Turi, na pré-Amazônia maranhense, onde se desenvolve o Projeto de Colonização do Alto Turi(PCAT), executado pela Companhia de Colonização do Nordeste (COLONE), empresa mista, subsidiária da Superintendência de Desenvolvimento do Nordeste (SUDENE). A questão fundamental do estudo é como os colonos se educam e se transformam, de produtores passivos e dependentes de relações assistencialistas e paterna por mudanças no PCAT. A análise do processo educativo, da reflexão e da ação desenvolvida pelos colonos, passa pela compreensão do processo histórico do Alto Turi Maranhense, isto é: do movimento migratório nordestino a partir da década de 50; da resposta a esse movimento dada pela SUDENE com a criação, em 1962, do projeto de colonização da região; da continuação do processo migratório introduzindo novos personagens (fazendeiros e comerciantes); da criação, em 1972, da COLONE, substituindo a SUDENE na execução do PCAT; da análise dos trabalhos de organização de comunidades, educação, extensão rural e cooperativismo oferecidos pela SUDENE e, posteriormente, pela COLONE à população nucleada. Esta linha de trabalho ainda implica, metodologicamente, em analisar a estrutura de classes da região, verificando o papel político e o peso social do grupo formado pelos colonos, assim como compreender as contradições que dinamizam a luta de classes na região, percebendo esse movimento no interior do processo social mais amplo, regional e nacional.

Poder judiciário fluminense e capixaba diante do comércio internacional e do pré-sal: novos desafios

As transformações recentes das relações sociais e econômicas incrementados pelo dinamismo do comércio internacional, sua crescente complexidade e as recémdescobertas reservas petrolíferas na camada pré-sal, aliadas ao fenômeno da globalização, contribuem para o processo de internacionalização do Direito. Esse cenário tem demandado, ainda, novos instrumentos de solução dos conflitos e de controle social, exigindo dos magistrados brasileiros maior expertise no julgamento das demandas contemporâneas. Diante desse cenário, é necessário construir alternativas que realmente busquem modificar as estruturas vigentes na teoria, na práxis e no ensino do Direito. Assim, o objetivo geral desta pesquisa é contribuir para a eficiência da prestação jurisdicional dos magistrados, seja no âmbito estadual ou federal, que atuam no Estado do Rio de Janeiro e Espírito Santo, diante dos novos desafios que terão em face do comércio internacional e do pré-sal. Com a finalidade de alcançar seu escopo, a pesquisa, no Capítulo 1, trata dos conceitos, princípios e metodologia para atingir o objetivo geral da pesquisa. O Capítulo 2 ocupa-se da abordagem das disciplinas relevantes para uma eficiente prestação jurisdicional do pré-sal e do comércio internacional. Em seguida, o Capítulo 3 trata de analisar o conteúdo das disciplinas ministradas nas Escolas de Magistratura Estadual do Rio de Janeiro e Federal da 2ª Região, bem como as provas para ingresso à carreira da magistratura federal e estadual do Rio de Janeiro e Espírito Santo, no que tange à existência de disciplinas como Direito do Petróleo, Gás e Energia, Direito Econômico, Direito Internacional Público e Privado, Exploração & Produção, Direito do Mar, Direito Marítimo, Direito da Navegação Marítima, Direito Portuário, Direito Aduaneiro e Direito Ambiental. Por fim, serão feitas algumas considerações e apresentadas as referências da pesquisa.