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.

Promiscuous CTL recognition of viral epitopes on multiple human leukocyte antigens: Biological validation of the proposed HLA A24 supertype

Multiple HLA class I alleles can bind peptides with common sequence motifs due to structural similarities in the peptide binding cleft, and these groups of alleles have been classified into supertypes. Nine major HLA supertypes have been proposed, including an A24 supertype that includes A*2301, A*2402, and A*3001. Evidence for this A24 supertype is limited to HLA sequence homology and/or similarity in peptide binding motifs for the alleles. To investigate the immunological relevance of this proposed supertype, we have examined two viral epitopes (from EBV and CMV) initially defined as HLA-A*2301-binding peptides. The data clearly demonstrate that each peptide could be recognized by CTL clones in the context of A*2301 or A*2402; thus validating the inclusion of these three alleles within an A24 supertype. Furthermore, CTL responses to the EBV epitope were detectable in both A*2301(+) and A*2402(+) individuals who had been previously exposed to this virus. These data substantiate the biological relevance of the A24 supertype, and the identification of viral epitopes with the capacity to bind promiscuously across this supertype could aid efforts to develop CTL-based vaccines or immunotherapy. The degeneracy in HLA restriction displayed by some T cells in this study also suggests that the dogma of self-MHC restriction needs some refinement to accommodate foreign peptide recognition in the context of multiple supertype alleles.

(-)-CGP 12177 increases contractile force and hastens relaxation of human myocardial preparations through a propranolol-resistant state of the beta1-adrenoceptor

Two forms of the activated beta(1)-adrenoceptor exist, one that is stabilized by (-)-noradrenaline and is sensitive to blockade by (-)-propranolol and another which is stabilized by partial agonists such as (-)-pindolol and (-)-CGP 12177 but is relatively insensitive to (-)-propranolol. We investigated the effects of stimulation of the propranolol-resistant PI-adrenoceptor in the human heart. Myocardium from non-failing and failing human hearts were set up to contract at 1 Hz. In right atrium from non-ailing hearts in the presence of 200 nM (-)-propranolol, (-)-CGP 12177 caused concentration-dependent increases in contractile force (-logEC(50)[M] 7.3+/-0.1, E-max 23+/-1% relative to maximal (-)-isoprenaline stimulation of beta(1)- and beta(2)-adrenoceptors, n=86 patients), shortening of the time to reach peak force (-logEC(50)[M] 7.4+/-0.1, E-max 37+/-5%, n=61 patients) and shortening of the time to reach 50% relaxation (t(50%), -logEC(50)[M] 7.3+/-0.1, E-max 33+/-2%, n=61 patients). The potency and maxima of the positive inotropic effects were independent of Ser49Gly- and Gly389Arg-beta(1)-adrenoceptor polymorphisms but were potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (-logEC(50)[M] 7.7+/-0.1, E-max 68+/-6%, n=6 patients, P

Mechatronic system for ABO human blood typing

In medical emergency situations, when a patient needs a blood transfusion, the universal blood type O− is administered. This procedure may lead to the depletion of stock reserves of O− blood. Nowadays, there is no commercial equipment capable of determining the patient's blood type in situ, in a fast and reliable process. Human blood typing is usually performed through the manual test, which involves a macroscopic observation and interpretation of the results by an analyst. This test, despite of having a fast response time, may lead to human errors, which sometimes can be fatal to the patient. This paper presents the development of an automatic mechatronic prototype for determining human blood typing (ABO and Rh systems) through image processing techniques. The prototype design takes into account the characteristics of reliability of analysis, portability, and response time allowing the system to be used in emergency situations. The developed prototype performs blood and reagents mixture acquires the resultant image and processes the data (based on image processing techniques) to determine the sample blood type. It was tested in a laboratory, using cataloged samples of blood types, provided by the Portuguese Institute of Blood and Transplantation. Hereafter, it is expected to test and validate the prototype in clinical environments.

O aluno com deficiência motora e a acessibilidade arquitectónica no Ensino Básico : um estudo de caso : o concelho de Guimarães

RESUMO:Para que o sucesso educativo se verifique, a escola tem de ajustar a sua prática educativa a todos os alunos, incluindo os que apresentam necessidades educativas especiais (NEE). Portugal dispõe de legislação que assegura o direito à educação e à igualdade de oportunidades, consignados na Constituição da República Portuguesa (artigos 71º, 73º e 74º), em consonância com a Declaração Universal dos Direitos do Homem e na Lei de Bases do Sistema Educativo (artigos 2º, 7º, 17º e 18º). O nosso país subscreveu também a Declaração de Salamanca, a qual reuniu, em 1994, o consenso de noventa e dois governos e de vinte e cinco organizações internacionais, reafirmando o direito à educação para todos. A construção da escola inclusiva passa pela responsabilização da escola por todos os alunos, na perspectiva de educação para todos, exigindo a sua concretização novas estratégias e resposta a novos desafios. Há que alterar práticas para atender à diversidade. Assim, as escolas precisam de estar arquitectonicamente adaptadas às necessidades dos alunos que utilizam a cadeira de rodas como forma de mobilidade, respeitando o direito à diferença e possibilitando, em igualdade de oportunidades, o sucesso escolar e educativo. Levar à prática as medidas previstas na lei portuguesa e implementar, em cada escola, a inclusão do aluno com mobilidade condicionada, implica equipar as escolas com adaptações, meios e recursos educativos facilitadores do seu processo ensino/aprendizagem. A constatação do que efectivamente acontece no terreno educativo no que concerne aos alunos com deficiência motora que usam a cadeira de rodas para se movimentarem assume toda a centralidade da nossa investigação, que tem o cariz de um estudo de caso. Incide sobre a compreensão mais aprofundada de como se processa o acesso arquitectónico nas escolas do Ensino Básico da Zona Norte e mais concretamente do Concelho de Guimarães. Recolhemos dados através de questionários dirigidos aos professores de apoio educativo e coordenadores de escola; ouvimos os alunos com deficiência motora pronunciar-se sobre as dificuldades que sentiam; observámos o seu quotidiano escolar e, finalmente, escutámos as entidades locais, através de uma entrevista realizada à Vereadora da Cultura do Concelho de Guimarães. Os resultados obtidos serão, como foi acordado, divulgados aos intervenientes com responsabilidades directas no campo da educação que se prontificaram a partilhar connosco a sua informação e saber, no sentido de os sensibilizar para a necessidade de rever o aspecto das acessibilidades arquitectónicas nas instituições educativas que servem o seu concelho, pois, como verificámos, muito há ainda a fazer para que o Ensino Básico, universal e obrigatório, se traduza numa igualdade de oportunidades de acesso e sucesso educativo para os alunos que utilizam a cadeira de rodas para se movimentarem no espaço escolar. ABSTRACT: For the educational success of a school it has to adjust its educational practice so that it includes those with special needs. According to the Portuguese law, disabled people have the right to education and equal opportunities, well expressed in the Constitution of the Portuguese Republic (articles 71st, 73rd, and 74th), in consonance with the Universal Declaration of Human Rights, and in the main law the educational system (articles 2nd, 7th, 17th and 18th). Our country has also subscribed the Declaration of Salamanca, which was written in 1994 with the agreement of Representatives from ninety-two governments and twenty-five International Organizations, where was reaffirmed the right of education for all. It is necessary that school increases its responsibility in what concerns the education of all its students. Educating all and every student demands new strategies to face new challenges and so some practices have to be changed to respond to diversity. Schools must be architecturally adapted to give the disabled students, who use a wheel chair, equal opportunities to achieve educational success. Taking the measures foreseen in Portuguese law into practice, and implementing in each school the inclusion of students with conditioned mobility, involves equipping schools with adaptations, equipment and educational resources that facilitate the teaching / learning process. The observation of what actually happens on educative ground, regarding to pupils with motor disabilities who use a wheelchair to move, assumes the centrality of our research, which is a case study. It focuses on the deeper understanding of the way the architectonic access in primary schools of the North, and more specifically the Municipality of Guimarães, is processed. We collected data through questionnaires addressed to educational support teachers and school coordinators; heard students with motor disabilities to comment on the difficulties they felt; observed their daily school life, and finally heard the local authorities, through an interview the Councillor of Culture of the Municipality of Guimarães. As agreed, the results will be communicated to intervenients with direct responsibilities in the field of education who were willing to share with us their information and knowledge in order to raise awareness of the need of looking over the aspect of architectural accessibility in educational institutions that serve their county, because, as noted, much remains to be done so that the basic education, universal and compulsory, will result in equality of educational opportunities in access and success for students who use a wheelchair to move in school space.

Human cryptosporidiosis: detection of specific antibodies in the serum by an indirect immunofluorescence

Cryptosporidium sp., a coccidian parasite usually found in the faeces of cattle, has been recently implicated as an agent of human intestinal disease, mainly in immunocompromised patients. In the study realized, by an indirect immunofluorescence technique, specific immunoglobulins (IgG and IgM) have been demonstrated in human serum against Cryptosporidium oocysts. Purified oocysts were used as antigens in the indirect immunofluorecence assay. After analyzing this test in sera from selected groups of patients, the frequency of both specific IgG and IgM of immunocompetent children who were excreting oocysts in their faeces was 62% and in children with negative excretion of oocysts was 20% and 40%, respectively. In adults infected with the human immunodeficiency virus (HIV) and who were excreting Cryptosporidium in their stools, the frequency was 57% for IgG but only 2% for IgM. Twenty three percent of immunocompromised adults with not determined excretion of oocysts in their stools had anti-Cryptosporidium IgG in their sera. Children infected with human immunodeficiency virus had no IgM and only 14% had IgG detectable in their sera. The indirect immunoflorescence assay, when used with other parasitological techniques appears to be useful for retrospective population studies and for diagnosis of acute infection. The humoral immune response of HIV positive patients to this protozoan agent needs clarification.

Sociological and philosophical aspects of human interaction with technology: advancing concepts

It is not possible to imagine our lives today without technology. From the moment we get up in the morning until the time that we go to bed at night, technology is present in almost every moment, even if we are not aware of it. Some of the most basic activities we need to perform regularly could not be carried out without technology. Sociological and Philosophical Aspects of Human Interaction with Technology: Advancing Concepts presents a careful blend of conceptual, theoretical and applied research in regards to the relationship between technology and humans. This book explores the importance of these interactions, aspects related with trust, communication, data protection, usability concerning organizational change, and e-learning. The advancement of these theories and practices will benefit from this publication as it provides a voice for the users.

Protein-ligand docking study: diterpenes from Juniperus brevifolia as anticancer and antimicrobial agentes

REDCAT: Natural Products and related Redox Catalysts: Basic Research and Applications in Medicine and Agriculture, Aveiro, 25-27 Novembro de 2012.

Perceção da contemporaneidade pelos pré-adolescentes: o que se aprende com a obra de arte

Dissertação apresentada à Escola Superior de Educação de Lisboa para obtenção de grau de mestre em Educação Artística, na Especialização de Artes Plásticas na Educação

Records of predatory, con-specific and human induced mauls on fish from the Northeast Atlantic and Black Sea

Present study aims to describe records of mauled and con-specific injures in various fish inhabiting different environment and to discuss possible impacts on fish behavior and ontogenesis. The fish specimens were collected from the Black Sea and Azores Islands (NE Atlantic). Individuals of European flounder, Pleuronectes flesus, common stingray, Dasyatis pastinaca and turbot, Scophthalmus maximus with missing dorsal and caudal fins and flesh, were found in the Black Sea. Specimens with severe mauls of the ocean sunfish, Mola mola, almaco jack, Seriola rivoliana and sargo, Diplodus sargus were recorded from the Azores Islands. All of them were caught alive and survived severe mauls caused by predators or by accidents with propellers, fishing nets. The NE Atlantic records, although possibly caused by natural predation, are more probably than not the result of negative interactions with human activity. Numerous records of mauled fish species from both regions show that the problem with adverse effects of fisheries is quite important. Predatory and con-specific injuries obviously are compatible with basic fish vital functions of described cases. The problem with negative anthropogenic interactions seems to be insufficiently investigated and need more attention by responsible managers and decision makers.

Designing market-based instruments for biodiversity conservation: learning with the Australian experience and evaluating Portugal's potential

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para a obtenção do grau de Mestre em Engenharia do Ambiente, perfil Gestão de Sistemas Ambientais

Human and climatic change impact modelling on the habitat suitability for the chimpanzee (Pan troglodytes ellioti) – Case study: The proposed Mount Cameroon National Park

Dissertation submitted in partial fulfilment of the requirements for the Degree of Master of Science in Geospatial Technologies

Is ambient intelligence a truly human-centric paradigm in industry? Current research and application scenario

Based on the paper presented at the International Conference “Autonomous Systems: inter-relations of technical and societal issues”, organized by IET with the support of the Portuguese-German collaboration project on “Technology Assessment of Autonomous Robotics” (DAAD/CRUP) at FCT-UNL, Biblioteca da UNL, Campus de Caparica on 5-6 November 2009.

Pathology of periportal fibrosis involution in human schistosomiasis

Optical and electron microscopical evidences of focal matrix degradation were frequently seen in liver sections of periportal fibrosis caused by schistosomiasis mansoni in man. The material came from 14 wedge hepatic biopsies taken from patients with chronic advanced hepatosplenic disease and undergoing operations for the relief of portal hypertension. Besides the presence of focal areas of rarefaction, fragmentation and dispersion of collagen fibers, the enlarged portal spaces also showed hyperplasia of elastic tissue and disarray of smooth muscle fibers following destruction of portal vein branches. Eggs were scanty in the tissue sections, and matrix degradation probably represented involuting changes related to the progressive diminution of parasite-related aggression, which occurs spontaneously with age or after cure by chemotherapy. The changes indicative of matrix degradation now described are probably the basic morphological counterpart of periportal fibrosis involution currently being documented by ultrasonography in hepatosplenic patients submitted to curative chemotherapy.