Clinical trials with glycoprotein IIB/IIIA antagonists - No benefit without bleeding?

As the glycoprotein GPIIb/IIIa receptor is the final common pathway in platelet aggregation, antagonists of this receptor cause a profound inhibition of aggregation induced by any agonist. The short-term efficacy and safety of GPIIb/IIIa antagonists in patients undergoing coronary angioplasty was demonstrated with murine 7E3 Fab, but this antibody was immunogenic. Abciximab is a chimeric human-mouse monoclonal antibody that is less immunogenic. The first major trial with a GPIIb/IIIa antagonist was the EPIC trial with abciximab, which showed that abciximab reduced the ischemic complications of coronary balloon angioplasty and atherectomy in high-risk patients, but increased the risk of bleeding. Subsequent studies showed that using less concurrent heparin reduced bleeding. Abciximab also reduced the rate of revascularization. Further studies have shown that the benefits of abciximab extended to all patients undergoing angioplasty (EPILOG), including patients with unstable angina (CAPTURE) and acute myocardial infarction (RAPPORT). Clinical trials with eptifibatide and tirofiban have failed to demonstrate benefit, at the doses used, in angioplasty. Abciximab and eptifibatide, but not oral xemilofiban, improve the safety of the coronary stenting procedure. Shortterm intravenous treatment with lamifiban, eptifibatide or tirofiban is beneficial in acute coronary syndromes (unstable angina, non-Q wave myocardial infarction). Orally active GPIIb/IIIa antagonists are being developed for use in acute coronary syndromes and myocardial infarction. However, no benefit has been shown with lefradafiban in acute coronary syndromes and sibrafiban and orbofiban are harmful. Eptifibatide, lamifiban and abciximab improve coronary patency in myocardial infarction, and long-term trials of GPIIb/IIIa antagonists are being conducted in acute myocardial infarction. Abciximab can cause thrombocytopenia, and all the GPIIb/IIIa antagonists increase the incidence of bleeding, but there is no excess of intracranial hemorrhage. (C) 2001 Prous Science. All rights reserved.

A refinement calculus for logic programs

Existing refinement calculi provide frameworks for the stepwise development of imperative programs from specifications. This paper presents a refinement calculus for deriving logic programs. The calculus contains a wide-spectrum logic programming language, including executable constructs such as sequential conjunction, disjunction, and existential quantification, as well as specification constructs such as general predicates, assumptions and universal quantification. A declarative semantics is defined for this wide-spectrum language based on executions. Executions are partial functions from states to states, where a state is represented as a set of bindings. The semantics is used to define the meaning of programs and specifications, including parameters and recursion. To complete the calculus, a notion of correctness-preserving refinement over programs in the wide-spectrum language is defined and refinement laws for developing programs are introduced. The refinement calculus is illustrated using example derivations and prototype tool support is discussed.

Enriched behavioral prediction equation and its impact on structured learning and the dynamic calculus

This theoretical note describes an expansion of the behavioral prediction equation, in line with the greater complexity encountered in models of structured learning theory (R. B. Cattell, 1996a). This presents learning theory with a vector substitute for the simpler scalar quantities by which traditional Pavlovian-Skinnerian models have hitherto been represented. Structured learning can be demonstrated by vector changes across a range of intrapersonal psychological variables (ability, personality, motivation, and state constructs). Its use with motivational dynamic trait measures (R. B. Cattell, 1985) should reveal new theoretical possibilities for scientifically monitoring change processes (dynamic calculus model; R. B. Cattell, 1996b), such as encountered within psycho therapeutic settings (R. B. Cattell, 1987). The enhanced behavioral prediction equation suggests that static conceptualizations of personality structure such as the Big Five model are less than optimal.

In vivo DNA electrotransfer

The use of electrotransfer for DNA delivery to prokaryotic cells, and eukaryotic cells in vitro, has been well known and widely used for many years. However, it is only recently that electric fields have been used to enhance DNA transfer to animal cells in vivo, and this is known as DNA electrotransfer or in vivo DNA electroporation. Some of the advantages of this method of somatic cell gene transfer are that it is a simple method that can be used to transfer almost any DNA construct to animal cells and tissues in vivo; multiple constructs can be co-transfected; it is equally applicable to dividing and nondividing cells; the DNA of interest does not need to be subeloned into a specific viral transfer vector and there is no need for the production of high titre viral stocks; and, as no viral genes are expressed there is less chance of an adverse immunologic reaction to vector sequences. The ease with which efficient in vivo gene transfer can be achieved with in vivo DNA electrotransfer is now allowing genetic analysis to be applied to a number of classic animal model systems where transgenic and embryonic stem cell techniques are not well developed, but for which a wealth of detailed descriptive embryological information is available, or surgical manipulation is much more feasible. As well as exciting applications in developmental biology, in vivo DNA electrotransfer is also being used to transfer genes to skeletal muscle and drive expression of therapeutically active proteins, and to examine exogenous gene and protein function in normal adult cells situated within the complex environment of a tissue and organ system in vivo. Thus, in effect providing the in vivo equivalent of the in vitro transient transfection assay. As the widespread use of in vivo electroporation has really only just begun, it is likely that the future will hold many more applications for this technology in basic research, biotechnology and clinical research areas.

Enhancing the immunogenicity and modulating the fine epitope recognition of antisera to a helical group A streptococcal peptide vaccine candidate from the M protein using lipid-core peptide technology

A conserved helical peptide vaccine candidate from the M protein of group A streptococci, p145, has been described. Minimal epitopes within p145 have been defined and an epitope recognized by protective antibodies, but not by autoreactive T cells, has been identified. When administered to mice, p145 has low immunogenicity. Many boosts of peptide are required to achieve a high antibody titre (> 12 800). To attempt to overcome this low immunogenicity, lipid-core peptide technology was employed. Lipid-core peptides (LCP) consist of an oligomeric polylysine core, with multiple copies of the peptide of choice, conjugated to a series of lipoamino acids, which acts as an anchor for the antigen. Seven different LCP constructs based on the p145 peptide sequence were synthesized (LCP1-->LCP7) and the immunogenicity of the compounds examined. The most immunogenic constructs contained the longest alkyl side-chains. The number of lipoamino acids in the constructs affected the immunogenicity and spacing between the alkyl side-chains increased immunogenicity. An increase in immunogenicity (enzyme-linked immunosorbent assay (ELISA) titres) of up to 100-fold was demonstrated using this technology and some constructs without adjuvant were more immunogenic than p145 administered with complete Freund's adjuvant (CFA). The fine specificity of the induced antibody response differed for the different constructs but one construct, LCP4, induced antibodies of identical fine specificity to those found in endemic human serum. Opsonic activity of LCP4 antisera was more than double that of p145 antisera. These data show the potential for LCP technology to both enhance immunogenicity of complex peptides and to focus the immune response towards or away from critical epitopes.

Exploring the role of market learning capability in competitive strategy

It has been argued that a firm's capacity to learn from its market is a source of both innovation and competitive advantage. However, past research has failed to conceptualize market-focused learning activity as a capability having the potential to contribute to competitive advantage. Prior innovation research has been biased toward technological innovation. However, there is evidence to suggest that both technological and non-technological innovations contribute to competitive advantage reflecting the need for a broader conceptualization of the innovation construct. Past research has also overlooked the critical role of entrepreneurship in the capability building process. Competitive advantage has been predominantly measured in terms of financial indicators of performance. In general, the literature reflects the need for comprehensive measures of organizational innovation and competitive advantage. This paper examines the role of market-focused learning capability in organizational innovation-based competitive strategy. The paper contributes to the strategic marketing theory by developing and refining measures of entrepreneurship, market-focused learning capability, organizational innovation and sustained competitive advantage, testing relationships among these constructs.

Direction of Causation Modeling Between Cross-Sectional Measures of Parenting and Psychological Distress in Female Twins

Under certain conditions, cross-sectional analysis of cross-twin intertrait correlations can provide important information about the direction of causation (DOC) between two variables. A community-based sample of Australian female twins aged 18 to 45 years was mailed an extensive Health and Lifestyle Questionnaire (HLQ) that covered a wide range of personality and behavioral measures. Included were self-report measures of recent psychological distress and perceived childhood environment (PBI). Factor analysis of the PBI yielded three interpretable dimensions: Coldness, Overprotection, and Autonomy. Univariate analysis revealed that parental Overprotection and Autonomy were best explained by additive genetic, shared, and nonshared environmental effects (ACE), whereas the best-fitting model for PBI Coldness and the three measures of psychological distress (Depression, Phobic Anxiety, and Somatic Distress) included only additive genetic and nonshared environmental effects (AE). A common pathway model best explained the covariation between (1) the three PBI dimensions and (2) the three measures of psychological distress. DOC modeling between latent constructs of parenting and psychological distress revealed that a model which specified recollected parental behavior as the cause of psychological distress provided a better fit than a model which specified psychological distress as the cause of recollected parental behavior. Power analyses and limitations of the findings are discussed.

A molecular mechanism for mRNA trafficking in neuronal dendrites

Specific neuronal mRNAs are localized in dendrites, often concentrated in dendritic spines and spine synapses, where they are translated. The molecular mechanism of localization is mostly unknown. Here we have explored the roles of A2 response element (A2RE), a cis-acting signal for oligodendrocyte RNA trafficking, and its cognate trans-acting factor, heterogeneous nuclear ribonucleoprotein ( hnRNP) A2, in neurons. Fluorescently labeled chimeric RNAs containing A2RE were microinjected into hippocampal neurons, and RNA transport followed using confocal laser scanning microscopy. These RNA molecules, but not RNA lacking the A2RE sequence, were transported in granules to the distal neurites. hnRNP A2 protein was implicated as the cognate trans-acting factor: it was colocalized with RNA in cytoplasmic granules, and RNA trafficking in neurites was compromised by A2RE mutations that abrogate hnRNP A2 binding. Coinjection of antibodies to hnRNP A2 halved the number of trafficking cells, and treatment of neurons with antisense oligonucleotides also disrupted A2RE - RNA transport. Colchicine inhibited trafficking, whereas cells treated with cytochalasin were unaffected, implicating involvement of microtubules rather than microfilaments. A2RE-like sequences are found in a subset of dendritically localized mRNAs, which, together with these results, suggests that a molecular mechanism based on this cis-acting sequence may contribute to dendritic RNA localization.

Physical activity and sedentary behavior: A population-based study of barriers, enjoyment, and preference

The associations of physical activity and sedentary behavior with barriers, enjoyment, and preferences were examined in a population-based mail survey of 1,332 adults. Respondents reporting high enjoyment and preference for physical activity were more likely to report high levels of activity. Those reporting cost, the weather, and personal barriers to physical activity were less likely to be physically active. Preference for sedentary behavior was associated with the decreased likelihood of being physically active, and the weather as a barrier to physical activity was associated with the increased likelihood of sedentary behavior. These constructs can be used to examine individual and environmental influences on physical activity and sedentary behavior in specific populations and could inform the development of targeted interventions.

Mobilidade social e empoderamento: a percep????o das mulheres benefici??rias do programa Bolsa Fam??lia em Minas Gerais

Esse trabalho teve como objetivo analisar os efeitos relacionados ?? mobilidade social e ao empoderamento das benefici??rias do Programa Bolsa Fam??lia em Minas Gerais. Foram utilizados procedimentos metodol??gicos anal??ticos, em um estudo de caso m??ltiplo com abordagem quantitativa. Foi realizada a valida????o dos constructos de mobilidade social e empoderamento, permitindo-se mensurar a intensidade da rela????o entre essas diferentes dimens??es. Os resultados demonstram a melhoria significativa na vida das benefici??rias, o que pode possibilitar ascend??ncia social. Contudo, observou-se, como fator limitante, o baixo grau de escolaridade das benefici??rias, mostrando-se a necessidade de conex??o dos programas sociais com atividades educacionais e de gera????o de trabalho e renda, para inser????o das mulheres no mercado de trabalho. Dessa forma, considera-se que o Programa Bolsa Fam??lia pode influenciar significativamente tanto no empoderamento quanto na mobilidade social das benefici??rias. Ademais, a articula????o com atividades educacionais e produtivas pode avigorar os resultados de pol??ticas p??blicas que defendam a justi??a social e a diminui????o das desigualdades existentes entre g??neros e classes sociais.

Gerenciamento proteano de carreira entre universitários

A partir da segunda metade do século XX, mudanças no modo de produção capitalista começaram a afetar a relação que as empresas estabeleciam com o trabalhador. Diante de um mercado imprevisível, a carreira tradicional, marcada, entre outros aspectos, por empregos duradouros e com possibilidade de ascensão na hierarquia da organização, tornou-se menos recorrente. Paralelamente, começaram a despontar novas concepções sobre carreira, tendo a maioria um enfoque individualista. Dentre as novas proposições, o presente estudo tomou como referência a concepção de carreira proteana. Esse modelo, de origem norte-americana, tem como ideia central a noção de uma carreira que é gerida pelo indivíduo, e tem como meta o alcance do sucesso psicológico. Desta forma, ancora-se em duas principais dimensões: autogerenciamento e direcionamento para valores. Considerando os diversos estudos que descrevem as dificuldades enfrentadas por estudantes na transição da universidade para o mercado de trabalho, esta pesquisa objetivou compreender aspectos do gerenciamento proteano de carreira entre universitários brasileiros que já tinham concluído, pelo menos, a primeira metade do curso de graduação. Para tanto, o estudo foi dividido em dois artigos. O primeiro foi destinado ao desenvolvimento e validação da Escala de Atitudes de Carreira Proteana para universitários, tendo sido realizado com uma amostra de 1016 estudantes de 37 cursos diferentes, com idade variando entre 18 e 65 anos, e média de 24,52 (DP = 6,69 anos). O instrumento, denominado neste estudo de Escala de Gerenciamento Proteano de Carreira para Universitários (EGPC-U) atestou a estrutura de duas dimensões, evidenciada também na versão original da medida. Os índices de confiabilidade foram satisfatórios e superiores a 12 0,61, tendo o instrumento a possibilidade de ser utilizado em serviços de orientação profissional ou de carreira. O segundo artigo objetivou compreender como as dimensões do modelo proteano se relacionam com variáveis sóciodemográficas e com construtos psicossociais: personalidade, lócus de controle, saúde e satisfação com a vida, e envolveu alunos de duas áreas de conhecimento: humanas e exatas. A amostra foi composta por 525 alunos, sendo 245 da área de humanas e 280 de exatas, sendo 52% do sexo masculino. A idade dos participantes variou entre 18 e 30 anos e média de 22,59 anos (DP = 2,66 anos). A partir dos resultados do estudo 2, constatou-se que alunos da área de humanas, quando comparados a estudantes de exatas, tendem a apresentar média superior na dimensão de direcionamento para valores. Verificou-se ainda que os aspectos de conscienciosidade e lócus de controle interno são preditores significativos do autogerenciamento tanto entre alunos de humanas como de exatas e que a adoção de atitudes proteanas tende a impactar positivamente aspectos da saúde e da satisfação com a vida do indivíduo. O estudo, de um modo geral, permitiu verificar a existência de características proteanas entre universitários, como também possibilitou conhecer variáveis relacionadas às atitudes de autogerenciamento e direcionamento para valores. Destaca-se, porém, a necessidade de pesquisas complementares com a exploração de outras variáveis psicossociais que possam estar relacionadas ao gerenciamento proteano entre graduandos.

A gestão da capacitação baseada na gestão por competência : um estudo da viabilidade de implantação do sistema de capacitação do governo federal na UFES

A administração desde seu início desenvolveu vários modelos de gestão a fim de obter eficiência. Treinar, capacitar e desenvolver o pessoal esteve na maioria desses modelos como algo imprescindível para se alcançar os resultados desejados. O governo que há vários anos busca um serviço público profissional e de qualidade publicou o decreto n. 5.707/2006 que regulamenta o desenvolvimento de pessoal da administração pública autárquica e fundacional. Neste decreto ele institui que o desenvolvimento de servidores deverá seguir o modelo de Gestão por Competências. Este trabalho trata de verificar a possibilidade da implantação desse novo modelo de gestão para confeccionar o programa de capacitação dos servidores técnicos administrativos em educação da Universidade Federal do Espírito Santo (UFES) elaborando uma proposta de projeto. Nesse sentido, faz-se uma revisão dos conceitos de treinamento, capacitação, desenvolvimento, competências e gestão por competências e através de seus constructos levanta-se a viabilidade de implantação de um programa de capacitação que inter-relacione as exigências do cargo com as habilidades e competências apresentadas ou não pelo servidor e o conteúdo dos treinamentos e cursos oferecidos pelo Departamento de Desenvolvimento de Pessoas da UFES.

Simulacro e retórica : construção de ethé e do humor em artigos de opinião de Elio Gaspari

Esta pesquisa propõe um estudo sobre a construção de ethé e do humor em artigos de opinião intergenéricos assinados por Elio Gaspari. Partindo da hipótese de que, nos textos, a construção discursiva de ethé alheios constitui a principal estratégia argumentativa, buscamos verificar como, pela utilização de recursos retóricos e humorísticos, é possível construir ethé de figuras expressivas da política brasileira. Para tanto, selecionamos oito artigos de opinião publicados em forma de e-mail no jornal Folha de S. Paulo. Uma vez estruturados a partir do processo intergenérico, esses artigos de opinião simulam trocas de e-mail entre personalidades políticas, evidenciando ethé dessas personalidades, o que os torna um lugar propício para se observar o ponto de vista retórico da construção de imagem. Assim, ao mostrar como se dá a construção de ethé dos políticos nos artigos intergenéricos, este trabalho se torna relevante na medida em que pode ampliar reflexões em torno dos artifícios utilizados em textos opinativos para levar o auditório a aderir ao posicionamento do orador. Para a condução deste estudo, adotamos os construtos teóricos desenvolvidos por estudiosos da Retórica (Retórica aristotélica e Nova Retórica), dos gêneros e do humor. As análises revelaram a constituição, pelo viés do humor, de ethé positivos dos políticos que atuam como remetentes dos e-mails e de um ethos negativo daqueles que desempenham o papel de destinatário. Ainda foi possível constatar que, ao construir ethé de outras personagens, o orador acaba construindo representações de si. Concluímos, assim, que é por meio do recurso ao ethos e ao humor que o orador busca obter a adesão de seu auditório, levando-o a partilhar seu posicionamento crítico acerca da política brasileira.

A estratégia como prática social : um estudo sobre a relação das práticas sociais dos gestores no “fazer estratégia” em uma empresa familiar

Este trabalho tem como objetivo compreender o “fazer estratégia” no seio de uma empresa familiar a partir das práticas sociais que envolvem os seus gestores. As práticas sociais são concebidas como um fenômeno social, o qual nasce e se desenvolve da interação e do relacionamento entre indivíduos em seu grupo social. Este grupo ou mundo social do indivíduo encontra-se em um processo constante de transformações em virtude da infinidade de interconexões sociais ali compartilhadas. Já o “fazer estratégia” apresenta-se aqui sob a ótica da estratégia como prática social que contempla “[...] como os praticantes de estratégia realmente agem e interagem [...]” (WHITTINGTON, 1996, p. 731), ou seja, a confluência entre as construções e práticas sociais cotidianas sobre seu “fazer estratégia”. A contemplação desses constructos teóricos possibilitou a formação de um esquema conceitual que por intermédio de um estudo de caso favoreceu o entendimento de “como as práticas sociais dos gestores se relacionam com o seu ‘fazer estratégia’ na empresa familiar?”. Para coleta de dados utilizou-se das técnicas: pesquisa documental, observação não-participante e entrevista semiestruturada (TRIVIÑOS, 1987). Os dados foram tratados através da técnica de Análise de Conteúdo na abordagem temática (BARDIN, 1977). Conclui-se com este estudo que as práticas sociais dos mais variados contextos nos quais os gestores da Empresa X se inserem, como o contexto familiar, interferem e se inter-relacionam diretamente no seu agir cotidiano e consequentemente no seu "fazer estratégia" a frente da empresa familiar, confirmando, estranhando e transformando a construção social dos sujeitos.

Profiling consumer behaviour in cross-border tourism destinations

Tourism is a phenomenon that moves millions of people around the world, taking as a major driver of the global economy. Such relevance is reflected in the proliferation of studies in the overall area known as tourism, under various perspectives and backgrounds. In the light of such multitude of insights our study aims at gaining a deeper understanding of customer profiling and behavior in cross-border tourism destinations. Previous studies conducted in such contexts suggest that cross-border regions (CBRs) are an attractive and desirable idea, yet requiring further theoretical and empirical research. The new configuration of many CBRs calls for a debate on issues concerning its development, raising up important dimensions, such as, organization and planning of common tourism destinations. There is still a gap in the understanding of destination management in CBRs and the customer profile and motivations. Overall this research aims at attaining a deeper understanding of the profile and behavior of consumers in tourism settings, addressing the predisposition for the destination. The study addresses the following research question: “What factors influence customer behavior and attitudes in a CBRs tourism destination?” To address our question we will take an interdisciplinary perspective bringing together inputs from marketing, tourism and local economics. When addressing consumer behavior in tourism previous studies considered the following constructs: involvement, place attachment, satisfaction and destination loyalty. In order to establish the causal relationships in our theoretical model, we intend to develop a predominant quantitative design, yet we plan to conduct exploratory interviews. In the analysis and discussion of results, we intend to use Structural Equation Modeling. It will further allow understanding how the constructs in the research model relate to each other in the specified context. Results are also expected to have managerial implications. Consequently our results may assist decision makers in developing their local policies.