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.

Study of n-fold Weibull competing risk model

This paper deals with an n-fold Weibull competing risk model. A characterisation of the WPP plot is given along with estimation of model parameters when modelling a given data set. These are illustrated through two examples. A study of the different possible shapes for the density and failure rate functions is also presented. (C) 2003 Elsevier Ltd. All rights reserved.

Actively shielded multi-layer gradient coil designs with improved cooling properties

In standard cylindrical gradient coils consisting of a single layer of wires, a limiting factor in achieving very large magnetic field gradients is the rapid increase in coil resistance with efficiency. This is a particular problem in small-bore scanners, such as those used for MR microscopy. By adopting a multi-layer design in which the coil wires are allowed to spread out into multiple layers wound at increasing radii, a more favourable scaling of resistance with efficiency is achieved, thus allowing the design of more powerful gradient coils with acceptable resistance values. Previously this approach has been applied to the design of unshielded, longitudinal, and transverse gradient coils. Here, the multi-layer approach has been extended to allow the design of actively shielded multi-layer gradient coils, and also to produce coils exhibiting enhanced cooling characteristics. An iterative approach to modelling the steady-state temperature distribution within the coil has also been developed. Results indicate that a good level of screening can be achieved in multi-layer coils, that small versions of such coils can yield higher efficiencies at fixed resistance than conventional two-layer (primary and screen) coils, and that performance improves as the number of layers of increases. Simulations show that by optimising multi-layer coils for cooling it is possible to achieve significantly higher gradient strengths at a fixed maximum operating temperature. A four-layer coil of 8 mm inner diameter has been constructed and used to test the steady-state temperature model. (C) 2003 Elsevier Inc. All rights reserved.

Use of web-based formative assessment to support student learning in metabolism/nutrition unit

In 2002, an integrated basic science course was introduced into the Bachelor of Dental Sciences programme at the University of Queensland, Australia. Learning activities for the Metabolism and Nutrition unit within this integrated course included lectures, problem-based learning tutorials, computer-based self-directed learning exercises and practicals. To support student learning and assist students to develop the skills necessary to become lifelong learners, an extensive bank of formative assessment questions was set up using the commercially available package, WebCT®. Questions included short-answer, multiple-choice and extended matching questions. As significant staff time was involved in setting up the question database, the extent to which students used the formative assessment and their perceptions of its usefulness to their learning were evaluated to determine whether formative assessment should be extended to other units within the course. More than 90% of the class completed formative assessment tasks associated with learning activities scheduled in the first two weeks of the block, but this declined to less than 50% by the fourth and final week of the block. Patterns of usage of the formative assessment were also compared in students who scored in the top 10% for all assessment for the semester with those who scored in the lowest 10%. High-performing students accessed the Web-based formative assessment about twice as often as those who scored in the lowest band. However, marks for the formative assessment tests did not differ significantly between the two groups. In a questionnaire that was administered at the completion of the block, students rated the formative assessment highly, with 80% regarding it as being helpful for their learning. In conclusion, although substantial staff time was required to set up the question database, this appeared to be justified by the positive responses of the students.

Reforming the law of medical negligence: Solutions in search of a problem

The Commonwealth Government's Principles Based Review of the Law of Negligence recently recommended reforms aimed at limiting liability and damages arising from personal injury and death, in response to the growing perception that the current system of compensating personal injury had become financially unsustainable. Recent increases in medical liability and damages have eroded the confidence of doctors and their professional bodies, with fears of unprecedented desertion from and reduced recruitment into high risk areas, and one of the primary foci of the review concerned medical negligence. The article analyses proposals to redefine the principles necessary for the finding of negligence, against the terms of reference of the review. The article assumes that for the foreseeable future, Australia will persist with tort-based compensation for personal injury rather than developing a no-fault scheme. If the suggested changes to the fundamental principles of negligence are unlikely to reduce medical liability, greater attention might be given to the processes which come into play after the finding of negligence, where reform is more likely to benefit both plaintiffs and defendants.

A global health problem caused by arsenic from natural sources

Arsenic is a carcinogen to both humans and animals. Arsenicals have been associated with cancers of the skin, lung, and bladder. Clinical manifestations of chronic arsenic poisoning include non-cancer end point of hyper- and hypo-pigmentation, keratosis, hypertension, cardiovascular diseases and diabetes. Epidemiological evidence indicates that arsenic concentration exceeding 50 mug l(-1) in the drinking water is not public health protective. The current WHO recommended guideline value for arsenic in drinking water is 10 mug l(-1), whereas many developing countries are still having a value of 50 mug 1(-1). It has been estimated that tens of millions of people are. at risk exposing to excessive levels of arsenic from both contaminated water and arsenic-bearing coal from natural sources. The global health implication and possible intervention strategies were also discussed in this review article. (C) 2003 Elsevier Ltd. All rights reserved.

Unraveling the barriers to reconceptualization of the problem in chronic pain: The actual and perceived ability of patients and health professionals to understand the neurophysiology

To identify why reconceptualization of the problem is difficult in chronic pain, this study aimed to evaluate whether (1) health professionals and patients can understand currently accurate information about the neurophysiology of pain and (2) health professionals accurately estimate the ability of patients to understand the neurophysiology of pain. Knowledge tests were completed by 276 patients with chronic pain and 288 professionals either before (untrained) or after (trained) education about the neurophysiology of pain. Professionals estimated typical patient performance on the test. Untrained participants performed poorly (mean +/- standard deviation, 55% +/- 19% and 29% +/- 12% for professionals and patients, respectively), compared to their trained counterparts (78% +/- 21% and 61% +/- 19%, respectively). The estimated patient score (46% +/- 18%) was less than the actual patient score (P < .005). The results suggest that professionals and patients can understand the neurophysiology of pain but professionals underestimate patients' ability to understand. The implications are that (1) a poor knowledge of currently accurate information about pain and (2) the underestimation of patients' ability to understand currently accurate information about pain represent barriers to reconceptualization of the problem in chronic pain within the clinical and lay arenas. (C) 2003 by the American Pain Society.

Avan??os desiguais e inten????es indefinidas: a reforma do estado do M??xico e a estrat??gia de gerenciamento

Este paper defende duas id??ias. A primeira, ?? apresentar os diferentes processos da reforma do Estado mexicano, analisados sob as prioridades diversas no decorrer do tempo. As reformas econ??mica, pol??tica, social e administrativa tiveram prioridades e objetivos divergentes. A reforma econ??mica foi sistem??tica e congruente, a pol??tica foi defensiva e pouco abrangente, e a social foi problem??tica e confusa. A reforma administrativa foi, comparativamente, limitada. Uma proposta para desenvolver um sistema administrativo respons??vel pelo servi??o p??blico foi postergada nos ??ltimos 12 anos at?? que, em maio de 1997, finalmente a atual administra????o prop??s um programa de moderniza????o. A segunda id??ia ?? que, mesmo que a atual administra????o tenha a inten????o de desenvolver um novo sistema de accountability e um plano de carreira para o servi??o p??blico, parece plaus??vel que a tradicional pol??tica de controle, atrav??s da estrutura administrativa, possa ser prejudicada se essas propostas realmente reduzirem o poder discricion??rio dos altos cargos p??blicos e submeterem reservas p??blicas a um esquema de controle social mais aberto e formal. Logo, ?? poss??vel dizer que a alternativa escolhida pelos reformistas foi usar uma abordagem gerenciadora, onde a melhoria dos procedimentos e a implementa????o de algumas t??cnicas administrativas avan??adas substituem, pelo menos at?? agora, uma transforma????o mais profunda da estrutura administrativa. Uma estrat??gia de gerenciamento permite, pelo menos at?? o momento, a melhoria dos servi??os atrav??s do aumento da participa????o de servidores p??blicos, sem prejudicar a atual administra????o, como um instrumento para implementar diferentes agendas pol??ticas usando recursos p??blicos. Nosso argumento ?? que, como o programa de moderniza????o est?? sendo implantado, ?? importante estudar minuciosamente as possibilidades de se implementar a reforma do servi??o p??blico e melhorar a responsabilidade do sistema, dada a particular rela????o que existe entre a administra????o p??blica e o sistema pol??tico no M??xico.

A constru????o da Lei de Acesso ?? Informa????o P??blica no Brasil: desafios na implementa????o de seus princ??pios

Nos ??ltimos anos, diversos pa??ses t??m feito grandes modifica????es em suas legisla????es, na tentativa de proteger o direito de acesso ?? informa????o e adequar sua legisla????o interna ??s exig??ncias impostas por tratados internacionais. A Lei de Acesso ?? Informa????o brasileira (Lei n?? 12.527, de 2011) foi constru??da a partir dos par??metros internacionalmente reconhecidos. Esses par??metros incorporam novos conceitos que ampliam o entendimento comum sobre o princ??pio da publicidade e recomendam a ado????o do princ??pio da m??xima transpar??ncia. A nova lei ?? essencial para melhorar as condi????es de acesso ??s informa????es governamentais no Brasil, como ser?? mostrado na an??lise feita da experi??ncia dos Estados Unidos da Am??rica e do M??xico. Contudo, devido a dificuldades relacionadas especialmente ?? burocracia administrativa, o direito de acesso ?? informa????o tender?? a permanecer incompleto, enquanto n??o for incorporado a uma pol??tica p??blica capaz de traduzir esse direito em um conjunto de a????es governamentais que garantam sua efetividade.

Basis set convergence in Hartree-Fock calculations of some diatomic molecules containing first and second-row atoms

Investiga-se a convergência de conjuntos de bases em direção ao limite numérico da energia Hartree-Fock (HF) total para as seqüências hierárquicas dos conjuntos de bases XZP e ccpVXZ. Para as duas hierarquias, melhoramentos significativos são obtidos com cada incremento em X. Para estimar o limite do conjunto de base completo, uma forma exponencial foi usada. Entre as várias aproximações consideradas aqui, uma extrapolação exponencial de três parâmetros aplicada aos resultados TZP, QZP e 5ZP deu os limites do conjunto de bases mais precisos. Em adição, energias HF dos orbitais moleculares ocupados mais altos de algumas moléculas diatômicas foram calculadas com o conjunto 5ZP e comparadas com as correspondentes obtidas com o conjunto cc-pV5Z e com um método numérico HF.

Gravitational waves : a 100-year tool applied to the dark energy problem

Recent observations from type Ia Supernovae and from cosmic microwave background (CMB) anisotropies have revealed that most of the matter of the Universe interacts in a repulsive manner, composing the so-called dark energy constituent of the Universe. Determining the properties of dark energy is one of the most important tasks of modern cosmology and this is the main motivation for this work. The analysis of cosmic gravitational waves (GW) represents, besides the CMB temperature and polarization anisotropies, an additional approach in the determination of parameters that may constrain the dark energy models and their consistence. In recent work, a generalized Chaplygin gas model was considered in a flat universe and the corresponding spectrum of gravitational waves was obtained. In the present work we have added a massless gas component to that model and the new spectrum has been compared to the previous one. The Chaplygin gas is also used to simulate a L-CDM model by means of a particular combination of parameters so that the Chaplygin gas and the L-CDM models can be easily distinguished in the theoretical scenarios here established. We find that the models are strongly degenerated in the range of frequencies studied. This degeneracy is in part expected since the models must converge to each other when some particular combinations of parameters are considered.

Metodologia para obtenção do hidrograma de escoamento superficial em encostas e canais. Parte I: desenvolvimento e avaliação

Desenvolveu-se uma metodologia que permite obter o hidrograma de escoamento superficial e a vazão máxima para qualquer posição ao longo de uma encosta e para seções transversais de canais utilizando o modelo de ondas cinemáticas. A área da encosta é dividida num sistema matricial composto por 100 linhas e 100 colunas. Na encosta, considera-se que o escoamento ocorre na direção da declividade e que a vazão de cada pixel é a soma da vazão produzida nesse com a vazão advinda dos pixels que contribuem com o escoamento superficial para o pixel em análise. No canal, a vazão é calculada pela soma dos hidrogramas advindos das colunas do sistema reticulado. A comparação entre os valores de lâmina e vazão máxima de escoamento superficial obtidas experimentalmente e calculadas em duas condições (encosta e bacia) permitiu evidenciar que a metodologia, comparada aos métodos Racional e do Número da Curva, ofereceu boas estimativas tanto da lâmina quanto da vazão máxima de escoamento superficial.