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.

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.

Indicadores de Ciência, Tecnologia & Inovação : análise da produção científica e tecnológica da área de conhecimento em Engenharia Civil na Base de Dados da Web of Science

Esta dissertação trata da análise da produção científica e tecnológica internacional e brasileira na área de conhecimento Engenharia Civil, por meio de indicadores bibliométricos. A área Engenharia Civil foi escolhida em razão da sua relevância para o desenvolvimento econômico do país. No entanto, em termos absolutos e relativos, está entre os setores tecnologicamente mais atrasados da economia. A bibliometria é uma disciplina com alcance multidisciplinar que estuda o uso e os aspectos quantitativos da produção científica registrada. Os indicadores de produção científica são objeto de análise de várias áreas do conhecimento, tanto para o planejamento e a execução de políticas públicas de vários setores quanto para maior conhecimento da comunidade científica sobre o sistema em que está inserida. A metodologia utilizada para a elaboração deste estudo descritivo de caráter exploratório foi a análise documental e bibliométrica, baseada em dados das publicações científicas, no período de 1970 a 2012, e tecnológicas, no período de 2001 a 2012, da área Engenharia Civil, indexadas nas bases de dados Science Citattion Index Expanded (SCI); Social Science Citation Index (SSCI); Conference Proceedings Citation Index (CPCI) e da Derwent Innovations Index (DII), que compõem a base de dados multidisciplinar da Web of Sicence (WoS). As informações foram qualificadas e quantificadas com o auxílio do software bibliométrico VantagePoint®. Os resultados obtidos confirmaram o baixo número de publicações científicas e tecnológicas na área de conhecimento Engenharia Civil de autores filiados a instituições de ensino e pesquisa brasileiras quando comparados aos dos países industrializados. Existe um conjunto de fortes condicionantes que ultrapassam o poder de decisão e de influência da academia, dificultando e limitando a disseminação das pesquisas e patentes brasileiras relacionadas a fatores de caráter sistêmico e cultural. A possibilidade de análise de indicadores de produção científica e tecnológica na Engenharia Civil contribui para criar políticas que, se utilizadas por agências de fomento, podem subsidiar investimentos mais fundamentados por parte dos governos e da iniciativa privada, a exemplo do que é feito por outros setores industriais.

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.

The need for standardized tests to evaluate the reliability of data transport in wireless medical systems

Wireless medical systems are comprised of four stages, namely the medical device, the data transport, the data collection and the data evaluation stages. Whereas the performance of the first stage is highly regulated, the others are not. This paper concentrates on the data transport stage and argues that it is necessary to establish standardized tests to be used by medical device manufacturers to provide comparable results concerning the communication performance of the wireless networks used to transport medical data. Besides, it suggests test parameters and procedures to be used to produce comparable communication performance results.

Modelos de resposta à interação entre fármacos anestésicos : análise de regressão e análise de Clusters

Os avanços tecnológicos e científicos, na área da saúde, têm vindo a aliar áreas como a Medicina e a Matemática, cabendo à ciência adequar de forma mais eficaz os meios de investigação, diagnóstico, monitorização e terapêutica. Os métodos desenvolvidos e os estudos apresentados nesta dissertação resultam da necessidade de encontrar respostas e soluções para os diferentes desafios identificados na área da anestesia. A índole destes problemas conduz, necessariamente, à aplicação, adaptação e conjugação de diferentes métodos e modelos das diversas áreas da matemática. A capacidade para induzir a anestesia em pacientes, de forma segura e confiável, conduz a uma enorme variedade de situações que devem ser levadas em conta, exigindo, por isso, intensivos estudos. Assim, métodos e modelos de previsão, que permitam uma melhor personalização da dosagem a administrar ao paciente e por monitorizar, o efeito induzido pela administração de cada fármaco, com sinais mais fiáveis, são fundamentais para a investigação e progresso neste campo. Neste contexto, com o objetivo de clarificar a utilização em estudos na área da anestesia de um ajustado tratamento estatístico, proponho-me abordar diferentes análises estatísticas para desenvolver um modelo de previsão sobre a resposta cerebral a dois fármacos durante sedação. Dados obtidos de voluntários serão utilizados para estudar a interação farmacodinâmica entre dois fármacos anestésicos. Numa primeira fase são explorados modelos de regressão lineares que permitam modelar o efeito dos fármacos no sinal cerebral BIS (índice bispectral do EEG – indicador da profundidade de anestesia); ou seja estimar o efeito que as concentrações de fármacos têm na depressão do eletroencefalograma (avaliada pelo BIS). Na segunda fase deste trabalho, pretende-se a identificação de diferentes interações com Análise de Clusters bem como a validação do respetivo modelo com Análise Discriminante, identificando grupos homogéneos na amostra obtida através das técnicas de agrupamento. O número de grupos existentes na amostra foi, numa fase exploratória, obtido pelas técnicas de agrupamento hierárquicas, e a caracterização dos grupos identificados foi obtida pelas técnicas de agrupamento k-means. A reprodutibilidade dos modelos de agrupamento obtidos foi testada através da análise discriminante. As principais conclusões apontam que o teste de significância da equação de Regressão Linear indicou que o modelo é altamente significativo. As variáveis propofol e remifentanil influenciam significativamente o BIS e o modelo melhora com a inclusão do remifentanil. Este trabalho demonstra ainda ser possível construir um modelo que permite agrupar as concentrações dos fármacos, com base no efeito no sinal cerebral BIS, com o apoio de técnicas de agrupamento e discriminantes. Os resultados desmontram claramente a interacção farmacodinâmica dos dois fármacos, quando analisamos o Cluster 1 e o Cluster 3. Para concentrações semelhantes de propofol o efeito no BIS é claramente diferente dependendo da grandeza da concentração de remifentanil. Em suma, o estudo demostra claramente, que quando o remifentanil é administrado com o propofol (um hipnótico) o efeito deste último é potenciado, levando o sinal BIS a valores bastante baixos.

A checkpointing-enabled and resource-aware Java Virtual Machine for efficient and robust e-Science applications in grid environments

Object-oriented programming languages presently are the dominant paradigm of application development (e. g., Java,. NET). Lately, increasingly more Java applications have long (or very long) execution times and manipulate large amounts of data/information, gaining relevance in fields related with e-Science (with Grid and Cloud computing). Significant examples include Chemistry, Computational Biology and Bio-informatics, with many available Java-based APIs (e. g., Neobio). Often, when the execution of such an application is terminated abruptly because of a failure (regardless of the cause being a hardware of software fault, lack of available resources, etc.), all of its work already performed is simply lost, and when the application is later re-initiated, it has to restart all its work from scratch, wasting resources and time, while also being prone to another failure and may delay its completion with no deadline guarantees. Our proposed solution to address these issues is through incorporating mechanisms for checkpointing and migration in a JVM. These make applications more robust and flexible by being able to move to other nodes, without any intervention from the programmer. This article provides a solution to Java applications with long execution times, by extending a JVM (Jikes research virtual machine) with such mechanisms. Copyright (C) 2011 John Wiley & Sons, Ltd.

Mantle source heterogeneity, magma generation and magmatic evolution at Terceira Island (Azoresarchipelago): Constraints from elemental and isotopic (Sr, Nd, Hf, and Pb) data

This work addresses the present-day (<100 ka) mantle heterogeneity in the Azores region through the study of two active volcanic systems from Terceira Island. Our study shows that mantle heterogeneities are detectable even when "coeval" volcanic systems (Santa Barbara and Fissural) erupted less than 10 km away. These volcanic systems, respectively, reflect the influence of the Terceira and D. Joao de Castro Bank end-members defined by Beier et at (2008) for the Terceira Rift Santa Barbara magmas are interpreted to be the result of mixing between a HIMU-type component, carried to the upper mantle by the Azores plume, and the regional depleted MORB magmas/source. Fissural lavas are characterized by higher Ba/Nb and Nb/U ratios and less radiogenic Pb-206/Pb-204, Nd-143/Nd-144 and Hf-176/Hf-177, requiring the small contribution of delaminated sub-continental lithospheric mantle residing in the upper mantle. Published noble gas data on lavas from both volcanic systems also indicate the presence of a relatively undegassed component, which is interpreted as inherited from a lower mantle reservoir sampled by the ascending Azores plume. As inferred from trace and major elements, melting began in the garnet stability field, while magma extraction occurred within the spinel zone. The intra-volcanic system's chemical heterogeneity is mainly explained by variable proportions of the above-mentioned local end-members and by crystal fractionation processes. (C) 2011 Elsevier By. All rights reserved.

A data-mining based methodology for wind forecasting

In many countries the use of renewable energy is increasing due to the introduction of new energy and environmental policies. Thus, the focus on the efficient integration of renewable energy into electric power systems is becoming extremely important. Several European countries have already achieved high penetration of wind based electricity generation and are gradually evolving towards intensive use of this generation technology. The introduction of wind based generation in power systems poses new challenges for the power system operators. This is mainly due to the variability and uncertainty in weather conditions and, consequently, in the wind based generation. In order to deal with this uncertainty and to improve the power system efficiency, adequate wind forecasting tools must be used. This paper proposes a data-mining-based methodology for very short-term wind forecasting, which is suitable to deal with large real databases. The paper includes a case study based on a real database regarding the last three years of wind speed, and results for wind speed forecasting at 5 minutes intervals.

Interpretation of gravity data to delineate structural features connected to low-temperature geothermal resources at Northeastern Portugal

A great number of low-temperature geothermal fields occur in Northern-Portugal related to fractured rocks. The most important superficial manifestations of these hydrothermal systems appear in pull-apart tectonic basins and are strongly conditioned by the orientation of the main fault systems in the region. This work presents the interpretation of gravity gradient maps and 3D inversion model produced from a regional gravity survey. The horizontal gradients reveal a complex fault system. The obtained 3D model of density contrast puts into evidence the main fault zone in the region and the depth distribution of the granitic bodies. Their relationship with the hydrothermal systems supports the conceptual models elaborated from hydrochemical and isotopic water analyses. This work emphasizes the importance of the role of the gravity method and analysis to better understand the connection between hydrothermal systems and the fractured rock pattern and surrounding geology. (c) 2013 Elsevier B.V. All rights reserved.

On clustering interval data with different scales of measures : experimental results

This article is is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. Attribution-NonCommercial (CC BY-NC) license lets others remix, tweak, and build upon work non-commercially, and although the new works must also acknowledge & be non-commercial.

Hierarchical cluster analysis of groups of individuals : application to business data

3rd SMTDA Conference Proceedings, 11-14 June 2014, Lisbon Portugal.

On cluster analysis of complex and heterogeneous data

3rd SMTDA Conference Proceedings, 11-14 June 2014, Lisbon Portugal.

Leptogenesis, CP violation and neutrino data: what can we learn?

A detailed analytic and numerical study of baryogenesis through leptogenesis is performed in the framework of the standard model of electroweak interactions extended by the addition of three right-handed neutrinos, leading to the seesaw mechanism. We analyze the connection between GUT-motivated relations for the quark and lepton mass matrices and the possibility of obtaining a viable leptogenesis scenario. In particular, we analyze whether the constraints imposed by SO(10) GUTs can be compatible with all the available solar, atmospheric and reactor neutrino data and, simultaneously, be capable of producing the required baryon asymmetry via the leptogenesis mechanism. It is found that the Just-So(2) and SMA solar solutions lead to a viable leptogenesis even for the simplest SO(10) GUT, while the LMA, LOW and VO solar solutions would require a different hierarchy for the Dirac neutrino masses in order to generate the observed baryon asymmetry. Some implications on CP violation at low energies and on neutrinoless double beta decay are also considered. (C) 2002 Elsevier Science B.V. All rights reserved.