Fitting genetic models to twin data with binary and ordered categorical responses: A comparison of structural equation modelling and Bayesian hierarchical models

We compare Bayesian methodology utilizing free-ware BUGS (Bayesian Inference Using Gibbs Sampling) with the traditional structural equation modelling approach based on another free-ware package, Mx. Dichotomous and ordinal (three category) twin data were simulated according to different additive genetic and common environment models for phenotypic variation. Practical issues are discussed in using Gibbs sampling as implemented by BUGS to fit subject-specific Bayesian generalized linear models, where the components of variation may be estimated directly. The simulation study (based on 2000 twin pairs) indicated that there is a consistent advantage in using the Bayesian method to detect a correct model under certain specifications of additive genetics and common environmental effects. For binary data, both methods had difficulty in detecting the correct model when the additive genetic effect was low (between 10 and 20%) or of moderate range (between 20 and 40%). Furthermore, neither method could adequately detect a correct model that included a modest common environmental effect (20%) even when the additive genetic effect was large (50%). Power was significantly improved with ordinal data for most scenarios, except for the case of low heritability under a true ACE model. We illustrate and compare both methods using data from 1239 twin pairs over the age of 50 years, who were registered with the Australian National Health and Medical Research Council Twin Registry (ATR) and presented symptoms associated with osteoarthritis occurring in joints of the hand.

Predicting the HER2 status of breast cancer from basic histopathology data: an analysis of 1500 breast cancers as part of the HER2000 International Study

The tests that are currently available for the measurement of overexpression of the human epidermal growth factor-2 (HER2) in breast cancer have shown considerable problems in accuracy and interlaboratory reproducibility. Although these problems are partly alleviated by the use of validated, standardised 'kits', there may be considerable cost involved in their use. Prior to testing it may therefore be an advantage to be able to predict from basic pathology data whether a cancer is likely to overexpress HER2. In this study, we have correlated pathology features of cancers with the frequency of HER2 overexpression assessed by immunohistochemistry (IHC) using HercepTest (Dako). In addition, fluorescence in situ hybridisation (FISH) has been used to re-test the equivocal cancers and interobserver variation in assessing HER2 overexpression has been examined by a slide circulation scheme. Of the 1536 cancers, 1144 (74.5%) did not overexpress HER2. Unequivocal overexpression (3+ by IHC) was seen in 186 cancers (12%) and an equivocal result (2+ by IHC) was seen in 206 cancers (13%). Of the 156 IHC 3+ cancers for which complete data was available, 149 (95.5%) were ductal NST and 152 (97%) were histological grade 2 or 3. Only 1 of 124 infiltrating lobular carcinomas (0.8%) showed HER2 overexpression. None of the 49 'special types' of carcinoma showed HER2 overexpression. Re-testing by FISH of a proportion of the IHC 2+ cancers showed that only 25 (23%) of those assessable exhibited HER2 gene amplification, but 46 of the 47 IHC 3+ cancers (98%) were confirmed as showing gene amplification. Circulating slides for the assessment of HER2 score showed a moderate level of agreement between pathologists (kappa 0.4). As a result of this study we would advocate consideration of a triage approach to HER-2 testing. Infiltrating lobular and special types of carcinoma may not need to be routinely tested at presentation nor may grade 1 NST carcinomas in which only 1.4% have been shown to overexpress HER2. Testing of these carcinomas may be performed when HER2 status is required to assist in therapeutic or other clinical/prognostic decision-making. The highest yield of HER2 overexpressing carcinomas is seen in the grade 3 NST subgroup in which 24% are positive by IHC. (C) 2003 Elsevier Science Ltd. All rights reserved.

Capillaries within compartments: Microvascular interpretation of dynamic positron emission tomography data

Measurement of exchange of substances between blood and tissue has been a long-lasting challenge to physiologists, and considerable theoretical and experimental accomplishments were achieved before the development of the positron emission tomography (PET). Today, when modeling data from modern PET scanners, little use is made of earlier microvascular research in the compartmental models, which have become the standard model by which the vast majority of dynamic PET data are analysed. However, modern PET scanners provide data with a sufficient temporal resolution and good counting statistics to allow estimation of parameters in models with more physiological realism. We explore the standard compartmental model and find that incorporation of blood flow leads to paradoxes, such as kinetic rate constants being time-dependent, and tracers being cleared from a capillary faster than they can be supplied by blood flow. The inability of the standard model to incorporate blood flow consequently raises a need for models that include more physiology, and we develop microvascular models which remove the inconsistencies. The microvascular models can be regarded as a revision of the input function. Whereas the standard model uses the organ inlet concentration as the concentration throughout the vascular compartment, we consider models that make use of spatial averaging of the concentrations in the capillary volume, which is what the PET scanner actually registers. The microvascular models are developed for both single- and multi-capillary systems and include effects of non-exchanging vessels. They are suitable for analysing dynamic PET data from any capillary bed using either intravascular or diffusible tracers, in terms of physiological parameters which include regional blood flow. (C) 2003 Elsevier Ltd. All rights reserved.

An EM-based Semi-Parametric Mixture Model Approach to the Regression Analysis of Competing-Risks Data

We consider a mixture model approach to the regression analysis of competing-risks data. Attention is focused on inference concerning the effects of factors on both the probability of occurrence and the hazard rate conditional on each of the failure types. These two quantities are specified in the mixture model using the logistic model and the proportional hazards model, respectively. We propose a semi-parametric mixture method to estimate the logistic and regression coefficients jointly, whereby the component-baseline hazard functions are completely unspecified. Estimation is based on maximum likelihood on the basis of the full likelihood, implemented via an expectation-conditional maximization (ECM) algorithm. Simulation studies are performed to compare the performance of the proposed semi-parametric method with a fully parametric mixture approach. The results show that when the component-baseline hazard is monotonic increasing, the semi-parametric and fully parametric mixture approaches are comparable for mildly and moderately censored samples. When the component-baseline hazard is not monotonic increasing, the semi-parametric method consistently provides less biased estimates than a fully parametric approach and is comparable in efficiency in the estimation of the parameters for all levels of censoring. The methods are illustrated using a real data set of prostate cancer patients treated with different dosages of the drug diethylstilbestrol. Copyright (C) 2003 John Wiley Sons, Ltd.

Effect of changing data collection parameters on statistical motor unit number estimates

The effect of number of samples and selection of data for analysis on the calculation of surface motor unit potential (SMUP) size in the statistical method of motor unit number estimates (MUNE) was determined in 10 normal subjects and 10 with amyotrophic lateral sclerosis (ALS). We recorded 500 sequential compound muscle action potentials (CMAPs) at three different stable stimulus intensities (10–50% of maximal CMAP). Estimated mean SMUP sizes were calculated using Poisson statistical assumptions from the variance of 500 sequential CMAP obtained at each stimulus intensity. The results with the 500 data points were compared with smaller subsets from the same data set. The results using a range of 50–80% of the 500 data points were compared with the full 500. The effect of restricting analysis to data between 5–20% of the CMAP and to standard deviation limits was also assessed. No differences in mean SMUP size were found with stimulus intensity or use of different ranges of data. Consistency was improved with a greater sample number. Data within 5% of CMAP size gave both increased consistency and reduced mean SMUP size in many subjects, but excluded valid responses present at that stimulus intensity. These changes were more prominent in ALS patients in whom the presence of isolated SMUP responses was a striking difference from normal subjects. Noise, spurious data, and large SMUP limited the Poisson assumptions. When these factors are considered, consistent statistical MUNE can be calculated from a continuous sequence of data points. A 2 to 2.5 SD or 10% window are reasonable methods of limiting data for analysis. Muscle Nerve 27: 320–331, 2003

Model-based clustering in gene expression microarrays: An application to breast cancer data

In microarray studies, the application of clustering techniques is often used to derive meaningful insights into the data. In the past, hierarchical methods have been the primary clustering tool employed to perform this task. The hierarchical algorithms have been mainly applied heuristically to these cluster analysis problems. Further, a major limitation of these methods is their inability to determine the number of clusters. Thus there is a need for a model-based approach to these. clustering problems. To this end, McLachlan et al. [7] developed a mixture model-based algorithm (EMMIX-GENE) for the clustering of tissue samples. To further investigate the EMMIX-GENE procedure as a model-based -approach, we present a case study involving the application of EMMIX-GENE to the breast cancer data as studied recently in van 't Veer et al. [10]. Our analysis considers the problem of clustering the tissue samples on the basis of the genes which is a non-standard problem because the number of genes greatly exceed the number of tissue samples. We demonstrate how EMMIX-GENE can be useful in reducing the initial set of genes down to a more computationally manageable size. The results from this analysis also emphasise the difficulty associated with the task of separating two tissue groups on the basis of a particular subset of genes. These results also shed light on why supervised methods have such a high misallocation error rate for the breast cancer data.

Zygosity Diagnosis in the Absence of Genotypic Data: An Approach Using Latent Class Analysis

For zygosity diagnosis in the absence of genotypic data, or in the recruitment phase of a twin study where only single twins from same-sex pairs are being screened, or to provide a test for sample duplication leading to the false identification of a dizygotic pair as monozygotic, the appropriate analysis of respondents' answers to questions about zygosity is critical. Using data from a young adult Australian twin cohort (N = 2094 complete pairs and 519 singleton twins from same-sex pairs with complete responses to all zygosity items), we show that application of latent class analysis (LCA), fitting a 2-class model, yields results that show good concordance with traditional methods of zygosity diagnosis, but with certain important advantages. These include the ability, in many cases, to assign zygosity with specified probability on the basis of responses of a single informant (advantageous when one zygosity type is being oversampled); and the ability to quantify the probability of misassignment of zygosity, allowing prioritization of cases for genotyping as well as identification of cases of probable laboratory error. Out of 242 twins (from 121 like-sex pairs) where genotypic data were available for zygosity confirmation, only a single case was identified of incorrect zygosity assignment by the latent class algorithm. Zygosity assignment for that single case was identified by the LCA as uncertain (probability of being a monozygotic twin only 76%), and the co-twin's responses clearly identified the pair as dizygotic (probability of being dizygotic 100%). In the absence of genotypic data, or as a safeguard against sample duplication, application of LCA for zygosity assignment or confirmation is strongly recommended.

Systematic characterization of mutations in yeast acetohydroxyacid synthase: Interpretation of herbicide-resistance data

Acetohydroxyacid synthase (AHAS, EC 4.1.3.18) catalyses the first step in branched-chain amino acid biosynthesis and is the target for sulfonylurea and imidazolinone herbicides, which act as potent and specific inhibitors. Mutants of the enzyme have been identified that are resistant to particular herbicides. However, the selectivity of these mutants towards various sulfonylureas and imidazolinones has not been determined systematically. Now that the structure of the yeast enzyme is known, both in the absence and presence of a bound herbicide, a detailed understanding of the molecular interactions between the enzyme and its inhibitors becomes possible. Here we construct 10 active mutants of yeast AHAS, purify the enzymes and determine their sensitivity to six sulfonylureas and three imidazolinones. An additional three active mutants were constructed with a view to increasing imidazolinone sensitivity. These three variants were purified and tested for their sensitivity to the imidazolinones only. Substantial differences are observed in the sensitivity of the 13 mutants to the various inhibitors and these differences are interpreted in terms of the structure of the herbicide-binding site on the enzyme.

Data Mart para apoio ?? capacita????o em gest??o de pol??ticas p??blicas voltado para uma Escola de Administra????o P??blica

Este trabalho consiste num estudo de caso que se destina ao desenvolvimento de um Data Mart que possibilite a Escola Nacional de Administra????o P??blica ??? ENAP conhecer o perfil e o panorama geral da situa????o funcional dos servidores p??blicos federais que se capacitaram na Escola nos ??ltimos 7 anos. O aplicativo foi desenvolvido cruzando o banco de dados do sistema gerenciador dos cursos ministrados pela ENAP, onde est??o armazenadas informa????es sobre os alunos capacitados, os cursos realizados, os resultados alcan??ados, o perfil dos docentes e demais informa????es relativas ??s atividades da Escola, com os dados gerados pelo Sistema Integrado de Administra????o de Recursos Humanos ??? SIAPE, cuja extra????o de dados foi direcionada para os registros sobre a situa????o funcional, cargos, carreiras, fun????es, ??rg??os e alguns dados pessoais dos alunos, servidores p??blicos federais que se encontram registrados no SIAPE

New species of Bakeriella (Hymenoptera, Bethylidae) from the New World and new data on geographic distribution

Bakeriella lata sp. nov. (Brazil, Rondônia), Bakeriella aurata sp. nov. (Brazil, Amazonas) and Bakeriella sulcaticeps sp. nov. (Brazil, Amazonas) are described and illustrated. New geographic records and variation data for B. cristata Evans, 1964, B. floridana Evans, 1964, B. flavicornis Kieffer, 1910, B. incompleta Azevedo, 1994, B. mira Evans, 1997, B. montivaga (Kieffer, 1910), B. olmeca Evans, 1964 and B. subcarinata Evans, 1965 are provided. The male of B. incompleta is described for the first time.

As políticas de proteção social no contexto escolar

Esta dissertação teve o objetivo de investigar como a formalização das políticas de proteção social via programas e projetos socioeducativos se articulam com a educação escolarizada. Realiza uma discussão conceitual acerca das políticas de proteção social e “vulnerabilidade e risco social” a partir de aspectos históricos situando-as na lógica societária das desigualdades e complexificações das refrações da questão social do modelo capitalista de produção e reprodução social, sobretudo no contexto das reformas do Estado brasileiro enquanto demanda dos ajustes neoliberais. O lócus da pesquisa foi uma escola da rede pública municipal de Serra/ES. As investigações foram realizadas em duas etapas. A primeira constituiu-se de um estudo exploratório de caráter qualitativo. Por meio das análises abstraídas dessa fase, foi realizado um estudo de caso como segunda etapa da pesquisa. Os instrumentos utilizados, análise de documentos, observação participante e entrevistas, evidenciam que os programas e projetos socioeducativos desenvolvidos no espaço escolar visando a uma suposta proteção social, não guardam relação concreta com a melhoria dos processos de aprendizagem dos alunos, logo, seus efeitos na vida escolar desses alunos não foram evidenciados. Verificou-se ainda profunda desarticulação entre as propostas pedagógicas da escola e dos docentes com os programas e projetos investigados. A partir dos dados da pesquisa, pudemos ainda constatar que tais programas e projetos adentram o espaço escolar por meio de demandas externas envolvendo a Secretaria Municipal de Educação e a iniciativa privada. Concluímos que a proteção social no espaço escolar via programas e projetos socioeducativos necessita voltar-se à articulação com políticas públicas que ultrapassem os muros da escola e que de fato garantam o acesso a bens materiais e simbólicos com vista à melhoria das condições de vida material e sociocultural dos alunos a quem são destinados e, consequentemente, a melhoria da qualidade da educação escolarizada.

A educação em cena : a Revista de Educação como circulação de representações sobre saberes educacionais no Espírito Santo (1934-1937)

Este estudo analisa os processos de circulação e apropriação das representações sobre os saberes da educação escolarizada difundidos pela Revista de Educação do Espírito Santo, entre os anos de 1934 e 1937. Como referencial teórico baseamo- nos em Chartier (1990) acerca do conceito de representação, em Balandier (1982) em relação ao conceito de encenação de poder instituído que assume visibilidade quando circula na Revista, concedendo publicização aos feitos políticos realizados por dado grupo social, e em Julia (2001), junto ao conceito de cultura escolar. A partir desse arcabouço teórico, empreendemos metodologia de pesquisa a partir da análise histórica da fonte, dialogando, para tanto, com diferentes documentos e registros que configuram uma série de dados que constituem nossa fonte. Trata-se da análise das representações travadas no debate sobre a formação, divulgação e apropriação do conjunto de práticas e saberes pedagógicos dirigido aos professores, por parte de um grupo de intelectuais locais que se apresentava como portador do projeto de modernização do Espírito Santo inserido no contexto nacional. A Revista de Educação/ES tinha entre seus principais objetivos o de (in)formar os professores, ou seja, enquadrar suas práticas às novas demandas educacionais. Deste modo, a Revista esteve atrelada a um projeto educacional em que os intelectuais corroboravam a ampla circulação de um conjunto de representações sobre a modernidade, utilizando a Revista como suporte, visto que, desde as capas, são expostos “monumentos de modernização”, como os prédios escolares e todo um complexo arranjo de artefatos simbólicos, traduzidos muitas vezes em festas e rituais escolares que evocavam “um novo tempo para a Educação do Estado”, ou seja, fazendo da educação escolarizada um espetáculo.

Tecnologia assistiva e computacional : contribuições para o atendimento educacional especializado e desafios na formação de professores

Neste trabalho, analisamos aspectos relacionados a como a tecnologia computacional é utilizada no Atendimento Educacional Especializado (AEE) e como se deu a formação de professores para utilizar esses recursos. Para tanto, delimitamos os seguintes objetivos específicos: investigar a utilização da tecnologia assistiva (TA) computacional no âmbito das salas de recursos multifuncionais (SRM); problematizar as tensões, dificuldades e possibilidades relacionadas à TA com ênfase na tecnologia computacional para o AEE; analisar a formação do professor de educação especial para o AEE tendo como recurso a TA com ênfase na tecnologia computacional, visando à mediação dos processos de aprendizagem. O aporte teórico deste trabalho foi a abordagem histórico-cultural, tomando por referência os estudos de Vigotski e seus colaboradores. Trata-se de uma pesquisa qualitativa que fez uso de diferentes instrumentos metodológicos como, os grupos focais, o questionário online e a entrevista semiestruturada. Para desenvolvê-lo, realizamos a coleta de dados em diferentes contextos, começando pelos grupos focais da pesquisa inaugural do Oneesp, que serviram como dispositivo para esta pesquisa, seguida da aplicação de um questionário aos professores participantes da pesquisa-formação desenvolvida como um desdobramento no estado do Espírito Santo da pesquisa inaugural do Oneesp pelos integrantes do Oeeesp e da aplicação in loco de entrevistas semiestruturadas com professores de educação especial, de uma SRM do Tipo II. Foram oitenta e nove professores participantes na pesquisa do Oneesp, trinta professores na pesquisa-formação do Oeeesp e dois professores para aplicação da entrevista semiestruturada in loco, respectivamente. Esses dois professores participaram tanto da pesquisa do Oneesp como da pesquisa do Oeeesp. Analisamos esses três momentos, dos quais emergiram os apontamentos que nos proporcionaram pensar, com base nas narrativas orais e escritas dos professores: sua formação para uso da TA computacional; seu entendimento sobre sua formação para este fim; seus anseios por uma formação mais direcionada; a forma como utilizam a tecnologia na sala de recursos; seus entendimentos sobre as dificuldades e possibilidades relacionadas a TA com ênfase na tecnologia computacional para o AEE. Após essas análises, concluímos que poucos professores que atuam nas SRM tiveram uma formação que possibilitasse a aplicação das tecnologias computacionais em sua mediação pedagógica, aliando teoria e prática, com momentos de formação que privilegiassem os momentos presenciais e em laboratórios, onde possam interagir com os computadores e suas ferramentas simbólicas. Sem essa familiaridade com os recursos computacionais, os professores acabam sentindo-se inseguros para utilizá-los, deixando de potencializar, pela via desses recursos, os processos de ensinoaprendizagem do aluno com deficiência. Faz-se necessário um investimento nesse tipo de formação e, mais do que isso, que se viabilize para os professores que atuam ou que pretendem atuar nas SRM. A partir de uma formação apropriada é possível fazer com que os professores utilizem os recursos computacionais como mediadores dos processos de ensino-aprendizagem de seus alunos.

Privacy and Data Protection in Elderly Healthcare: Threats and Legal Warranties

The progressive aging of the population requires new kinds of social and medical intervention and the availability of different services provided to the elder population. New applications have been developed and some services are now provided at home, allowing the older people to stay home instead of having to stay in hospitals. But an adequate response to the needs of the users will imply a high percentage of use of personal data and information, including the building up and maintenance of user profiles, feeding the systems with the data and information needed for a proactive intervention in scheduling of events in which the user may be involved. Fundamental Rights may be at stake, so a legal analysis must also be considered.