Manipulação do genoma humano: ética e direito

A biologia molecular tem fornecido as ferramentas básicas para os geneticistas se aprofundarem nos mecanismos moleculares que influem na variação das doenças. Deve-se destacar a responsabilidade científica e moral dos pesquisadores, uma vez que os cientistas devem imaginar as consequências morais da aplicação comercial de testes genéticos, já que esse fato envolve não só o indivíduo e suas famílias, mas toda a população. Além de ser preciso, também, fazer uma reflexão sobre como essas informações do genoma humano serão utilizadas, para o bem ou mal. O objetivo desta revisão foi trazer à luz do conhecimento dados sobre características éticas da aplicação da biologia molecular, relacionando-a com os direitos do ser humano. Após análise bibliográfica, pôde-se observar que o Projeto Genoma Humano gerou várias possibilidades, como identificação de genes associados a doenças com propriedades sinergísticas, mas modificando às vezes comportamentos ao intervir geneticamente no ser humano, trazendo benefícios ou malefícios sociais. O grande desafio é decidir o que a humanidade pretende em relação a este gigantesco salto.

Laços mal-atados como efeito de funcionamento falso-self em tempos de desconfiança

A contemporaneidade contempla formas de estruturação da subjetividade amplamente perpassadas por condições de existência socioculturais e econômicas. Estas, por sua vez, têm promovido laços intersubjetivos frágeis, cujo funcionamento psíquico pode ter uma organização de base "falso-self". Autores também demonstram que diversas instituições atuais se tornaram "fluidas" na passagem da modernidade para a "modernidade líquida". Isto contribuiu para a perda de referências sólidas que, outrora, davam sentido e direcionamento para o ser humano. Em decorrência há uma interferência direta na construção da "confiança madura", visto que os sinais de angústia da contemporaneidade podem ser um desorganizador do funcionamento psíquico, além de promoverem o isolamento, a desconfiança no ambiente e no outro, laços mal-atados e funcionamentos de base "falso-self".

Causas mal definidas de morte e óbitos sem assistência

OBJETIVOS: Este trabalho estuda a distribuição dos óbitos por causas mal definidas no Brasil, no ano de 2003, entre as quais identifica a proporção de mortes sem assistência. MÉTODOS: Os dados provieram do Sistema de Informações Sobre Mortalidade, coordenado pelo Ministério da Saúde. As causas mal definidas de morte compreenderam as incluídas no "Capítulo XVIII - Sintomas, sinais e achados anormais de exames clínicos e de laboratório não classificados em outra parte" da Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde, décima revisão, capítulo este no qual a categoria R98 identificava a "morte sem assistência". RESULTADOS: No Brasil, em 2003, a causa básica de 13,3% dos óbitos foi identificada como mal definida, sendo que as proporções maiores ocorreram nas Regiões Nordeste e Norte. Do total de causas mal definidas no país, 53,3% corresponderam a mortes sem assistência, proporção esta que superou 70% nos Estados do Maranhão, Piauí, Rio Grande do Norte, Pernambuco, Bahia, Paraíba e Alagoas. CONCLUSÃO: Dada a estrutura descentralizada para o levantamento dos óbitos no país, identifica-se a maior responsabilidade dos municípios e, em seguida, dos Estados para o aprimoramento da qualidade das estatísticas de mortalidade.

A mortalidade de idosos no Brasil: a questão das causas mal definidas

O envelhecimento populacional é um fato marcante da transição demográfica. O estudo das causas básicas em idosos permite visualizar seu perfil epidemiológico, embora possa ser prejudicado pela alta proporção de causas mal definidas. O objetivo deste trabalho é descrever a mortalidade dos idosos por essas causas no Brasil. A fonte dos dados foi o Sistema de Informações sobre Mortalidade do Ministério da Saúde.Entre as variáveis, a principal modalidade foi a causa básica mal definida [ Capítulo XVIII da Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde-Décima Revisão (CID-10)]. O decréscimo desses óbitos em idosos foi de 35 por cento entre 1996 e 2005.Considerando os óbitos de 60 a 69 anos e os de 80 e mais anos, as proporções de mal definidos aumentaram em 9,9 por cento e 14,8 por cento, respectivamente, no ano de 2005. Métodos visando a sua diminuição são sugeridos, salientando-se que o fato mais importante é o de os médicos preencherem adequadamente as declarações de óbito- com as reais causas básicas, conseqüênciais e terminais-, objetivo maior dos estudiosos

A BEM model applied to failure analysis of multi-fractured structures

Due to manufacturing or damage process, brittle materials present a large number of micro-cracks which are randomly distributed. The lifetime of these materials is governed by crack propagation under the applied mechanical and thermal loadings. In order to deal with these kinds of materials, the present work develops a boundary element method (BEM) model allowing for the analysis of multiple random crack propagation in plane structures. The adopted formulation is based on the dual BEM, for which singular and hyper-singular integral equations are used. An iterative scheme to predict the crack growth path and crack length increment is proposed. This scheme enables us to simulate the localization and coalescence phenomena, which are the main contribution of this paper. Considering the fracture mechanics approach, the displacement correlation technique is applied to evaluate the stress intensity factors. The propagation angle and the equivalent stress intensity factor are calculated using the theory of maximum circumferential stress. Examples of multi-fractured domains, loaded up to rupture, are considered to illustrate the applicability of the proposed method. (C) 2011 Elsevier Ltd. All rights reserved.

BEM formulation for von Karman plates

This work deals with nonlinear geometric plates in the context of von Karman`s theory. The formulation is written such that only the boundary in-plane displacement and deflection integral equations for boundary collocations are required. At internal points, only out-of-plane rotation, curvature and in-plane internal force representations are used. Thus, only integral representations of these values are derived. The nonlinear system of equations is derived by approximating all densities in the domain integrals as single values, which therefore reduces the computational effort needed to evaluate the domain value influences. Hyper-singular equations are avoided by approximating the domain values using only internal nodes. The solution is obtained using a Newton scheme for which a consistent tangent operator was derived. (C) 2009 Elsevier Ltd. All rights reserved.

An extended BEM formulation for plates reinforced by rectangular beams

This article presents a BEM formulation developed particularly for analysis of plates reinforced by rectangular beams. This is an extended version of a Previous paper that only took into account bending effects. The problem is now re-formulated to consider bending and membrane force effects. The effects of the reinforcements are taken into account by using a simplified scheme that requires application of ail initial stress field to locally correct the bending and stretching stiffness of the reinforcement regions. The domain integrals due to the presence of the reinforcements are then transformed to the reinforcement/plate interface. To reduce the number of degrees of freedom related to the presence of the reinforcement, the proposed model was simplified to consider only bending and stretching rigidities in the direction of the beams. The complete model can be recovered by applying all six internal force correctors, corresponding to six degrees of freedom per node. Examples are presented to confirm the accuracy of the formulation and to illustrate the level of simplification introduced by this strong reduction in the number of degrees of freedom. (C) 2008 Elsevier Ltd. All rights reserved.

BEM formulation for reinforced plates

This article presents a BEM formulation developed to analyse reinforced plate bending. The reinforcements are formulated using a simplified scheme based on applying an initial moment field adopted to locally correct the stiffness of the reinforcement regions. The domain integrals due to the presence of the reinforcements are then transformed to the reinforcement/plate interface. The increase in system stiffness due to the reinforcements can be taken into account independently for each coefficient. Thus, one can conveniently reduce the number of degrees of freedom required in considering the reinforcement. Only one degree-of-freedom is required at each internal node when taking into account only the flexural stiffness of beams. Examples are presented to confirm the accuracy of the formulation. (C) 2009 Elsevier Ltd. All rights reserved.

An alternative multi-region BEM technique for three-dimensional elastic problems

The main objective of this work is to present an alternative boundary element method (BEM) formulation for the static analysis of three-dimensional non-homogeneous isotropic solids. These problems can be solved using the classical boundary element formulation, analyzing each subregion separately and then joining them together by introducing equilibrium and displacements compatibility. Establishing relations between the displacement fundamental solutions of the different domains, the alternative technique proposed in this paper allows analyzing all the domains as one unique solid, not requiring equilibrium or compatibility equations. This formulation also leads to a smaller system of equations when compared to the usual subregion technique, and the results obtained are even more accurate. (C) 2008 Elsevier Ltd. All rights reserved.

QUADRANT-SEARCHING: A NEW TECHNIQUE TO REDUCE THE SEARCH SPACE OF THE INVERSE PROBLEM OF EIT USING BEM TO THE DIRECT PROBLEM

The image reconstruction using the EIT (Electrical Impedance Tomography) technique is a nonlinear and ill-posed inverse problem which demands a powerful direct or iterative method. A typical approach for solving the problem is to minimize an error functional using an iterative method. In this case, an initial solution close enough to the global minimum is mandatory to ensure the convergence to the correct minimum in an appropriate time interval. The aim of this paper is to present a new, simple and low cost technique (quadrant-searching) to reduce the search space and consequently to obtain an initial solution of the inverse problem of EIT. This technique calculates the error functional for four different contrast distributions placing a large prospective inclusion in the four quadrants of the domain. Comparing the four values of the error functional it is possible to get conclusions about the internal electric contrast. For this purpose, initially we performed tests to assess the accuracy of the BEM (Boundary Element Method) when applied to the direct problem of the EIT and to verify the behavior of error functional surface in the search space. Finally, numerical tests have been performed to verify the new technique.

Heterozygosity for the S180L Variant of MAL/TIRAP, a Gene Expressing an Adaptor Protein in the Toll-Like Receptor Pathway, Is Associated with Lower Risk of Developing Chronic Chagas Cardiomyopathy

Background. Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. Among T. cruzi-infected individuals, only a subgroup develops severe chronic Chagas cardiomyopathy (CCC); the majority remain asymptomatic. T. cruzi displays numerous ligands for the Toll-like receptors (TLRs), which are an important component of innate immunity that lead to the transcription of proinflammatory cytokines by nuclear factor-kappa B. Because proinflammatory cytokines play an important role in CCC, we hypothesized that single-nucleotide polymorphisms (SNPs) in the genes that encode proteins in the TLR pathway could explain differential susceptibility to CCC among T. cruzi-infected individuals. Methods. For 169 patients with CCC and 76 T. cruzi-infected, asymptomatic individuals, we analyzed SNPs by use of polymerase chain reaction-restriction fragment length polymorphism analysis for the genes TLR1, TLR2, TLR4, TLR5, TLR9, and MAL/TIRAP, which encodes an adaptor protein. Results. Heterozygous carriers of the MAL/TIRAP variant S180L were more prevalent in the asymptomatic group (24 [32%] of 76 subjects) than in the CCC group (21 [12%] of 169) (chi(2) = 12.6; P = .0004 [adjusted P (P(c)) = .0084]; odds ratio [OR], 0.31 [95% confidence interval {CI}, 0.16-0.60]). Subgroup analysis showed a stronger association when asymptomatic patients were compared with patients who had severe CCC (i.e., patients with left-ventricular ejection fraction <= 40%) (chi(2) = 11.3; P = .0008 [P(c) = .017]; OR, 0.22 [95% CI, 0.09-0.56]) than when asymptomatic patients were compared with patients who had mild CCC (i.e., patients with left-ventricular ejection fraction >40%) (chi(2) = 7.7; P = .005 [P(c) = .11]; OR, 0.33 [95% CI, 0.15-0.73]). Conclusion. T. cruzi-infected individuals who are heterozygous for the MAL/TIRAP S180L variant that leads to a decrease in signal transduction upon ligation of TLR2 or TLR4 to their respective ligand may have a lower risk of developing CCC.