Direct visualization of the trimeric structure of the ASIC1a channel, using AFM imaging.

There has been confusion about the subunit stoichiometry of the degenerin family of ion channels. Recently, a crystal structure of acid-sensing ion channel (ASIC) 1a revealed that it assembles as a trimer. Here, we used atomic force microscopy (AFM) to image unprocessed ASIC1a bound to mica. We detected a mixture of subunit monomers, dimers and trimers. In some cases, triple-subunit clusters were clearly visible, confirming the trimeric structure of the channel, and indicating that the trimer sometimes disaggregated after adhesion to the mica surface. This AFM-based technique will now enable us to determine the subunit arrangement within heteromeric ASICs.

Avaliação da autoestima de gestantes com uso da Escala de Autoestima de Rosenberg

O objetivo deste estudo descritivo e transversal foi avaliar a autoestima de 127 gestantes atendidas em programa de pré-natal de um hospital público de ensino. Os dados foram colhidos usando-se a Escala de Autoestima de Rosenberg; a autoestima insatisfatória foi relacionada a variáveis sócio-demográficas, de saúde da gestante e da presença ou não de sistemas de apoio. Os dados foram submetidos à análise estatística descritiva e análise univariada, buscando possíveis associações. As gestantes com autoestima insatisfatória totalizaram 60% da amostra. Em relação aos dados sócio-demográficos, as mulheres com menor escolaridade apresentaram maior frequência de escores de autoestima insatisfatória, divergindo de resultados de outros estudos. As gestantes que referiram gestação não planejada apresentaram maior prevalência de autoestima insatisfatória do que aquelas que referiram tê-la planejado. A ausência de apoio do parceiro para cuidar do filho após seu nascimento também esteve associada a menor autoestima nas grávidas. Não foram encontradas relações estatisticamente significativas para as demais variáveis estudadas.

Molecular phylogeny and evolution of Sorex shrews (Soricidae: insectivora) inferred from mitochondrial DNA sequence data.

Shrews of the genus Sorex are characterized by a Holarctic distribution, and relationships among extant taxa have never been fully resolved. Phylogenies have been proposed based on morphological, karyological, and biochemical comparisons, but these analyses often produced controversial and contradictory results. Phylogenetic analyses of partial mitochondrial cytochrome b gene sequences (1011 bp) were used to examine the relationships among 27 Sorex species. The molecular data suggest that Sorex comprises two major monophyletic lineages, one restricted mostly to the New World and one with a primarily Palearctic distribution. Furthermore, several sister-species relationships are revealed by the analysis. Based on the split between the Soricinae and Crocidurinae subfamilies, we used a 95% confidence interval for both the calibration of a molecular clock and the subsequent calculation of major diversification events within the genus Sorex. Our analysis does not support an unambiguous acceleration of the molecular clock in shrews, the estimated rate being similar to other estimates of mammalian mitochondrial clocks. In addition, the data presented here indicate that estimates from the fossil record greatly underestimate divergence dates among Sorex taxa.

A phase 1b study of humanized KS-interleukin-2 (huKS-IL2) immunocytokine with cyclophosphamide in patients with EpCAM-positive advanced solid tumors.

BACKGROUND: Humanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent. METHODS: Phase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300 mg/m2 on day 1), and escalating doses of huKS-IL2 (0.5-4.0 mg/m2 IV continuous infusion over 4 hours) on days 2, 3, and 4 of each 21-day cycle. Safety, pharmacokinetic profile, immunogenicity, anti-tumor and biologic activity were evaluated. RESULTS: Twenty-seven patients were treated for up to 6 cycles; 26 were evaluable for response. The MTD of huKS-IL2 in combination with 300 mg/m2 cyclophosphamide was 3.0 mg/m2. At higher doses, myelosuppression was dose-limiting. Transient lymphopenia was the most common grade 3/4 adverse event (AE). Other significant AEs included hypotension, hypophosphatemia, and increase in serum creatinine. All patients recovered from these AEs. The huKS-IL2 exposure was dose-dependent, but not dose-proportional, accumulation was negligible, and elimination half-life and systemic clearance were independent of dose and time. Most patients had a transient immune response to huKS-IL2. Immunologic activity was observed at all doses. Ten patients (38%) had stable disease as best response, lasting for ≥ 4 cycles in 3 patients. CONCLUSION: The combination of huKS-IL2 with low-dose cyclophosphamide was well tolerated. Although no objective responses were observed, the combination showed evidence of immunologic activity and 3 patients showed stable disease for ≥ 4 cycles. TRIAL REGISTRATION: http://NCT00132522.

Causal explanations and scientific realism in particle physics

Particle physics studies highly complex processes which cannot be directly observed. Scientific realism claims that we are nevertheless warranted in believing that these processes really occur and that the objects involved in them really exist. This dissertation defends a version of scientific realism, called causal realism, in the context of particle physics. I start by introducing the central theses and arguments in the recent philosophical debate on scientific realism (chapter 1), with a special focus on an important presupposition of the debate, namely common sense realism. Chapter 2 then discusses entity realism, which introduces a crucial element into the debate by emphasizing the importance of experiments in defending scientific realism. Most of the chapter is concerned with Ian Hacking's position, but I also argue that Nancy Cartwright's version of entity realism is ultimately preferable as a basis for further development. In chapter 3,1 take a step back and consider the question whether the realism debate is worth pursuing at all. Arthur Fine has given a negative answer to that question, proposing his natural ontologica! attitude as an alternative to both realism and antirealism. I argue that the debate (in particular the realist side of it) is in fact less vicious than Fine presents it. The second part of my work (chapters 4-6) develops, illustrates and defends causal realism. The key idea is that inference to the best explanation is reliable in some cases, but not in others. Chapter 4 characterizes the difference between these two kinds of cases in terms of three criteria which distinguish causal from theoretical warrant. In order to flesh out this distinction, chapter 5 then applies it to a concrete case from the history of particle physics, the discovery of the neutrino. This case study shows that the distinction between causal and theoretical warrant is crucial for understanding what it means to "directly detect" a new particle. But the distinction is also an effective tool against what I take to be the presently most powerful objection to scientific realism: Kyle Stanford's argument from unconceived alternatives. I respond to this argument in chapter 6, and I illustrate my response with a discussion of Jean Perrin's experimental work concerning the atomic hypothesis. In the final part of the dissertation, I turn to the specific challenges posed to realism by quantum theories. One of these challenges comes from the experimental violations of Bell's inequalities, which indicate a failure of locality in the quantum domain. I show in chapter 7 how causal realism can further our understanding of quantum non-locality by taking account of some recent experimental results. Another challenge to realism in quantum mechanics comes from delayed-choice experiments, which seem to imply that certain aspects of what happens in an experiment can be influenced by later choices of the experimenter. Chapter 8 analyzes these experiments and argues that they do not warrant the antirealist conclusions which some commentators draw from them. It pays particular attention to the case of delayed-choice entanglement swapping and the corresponding question whether entanglement is a real physical relation. In chapter 9,1 finally address relativistic quantum theories. It is often claimed that these theories are incompatible with a particle ontology, and this calls into question causal realism's commitment to localizable and countable entities. I defend the commitments of causal realism against these objections, and I conclude with some remarks connecting the interpretation of quantum field theory to more general metaphysical issues confronting causal realism.

Experiencias persuasivas: construcción de un protocolo para el análisis de la persuasión en los videojuegos

A pesar de que cada vez son más las investigaciones vinculadas al análisis de los videojuegos, pocas son las orientadas a determinar la articulación de su dimensión persuasiva. Partiendo principalmente de los trabajos de Ian Bogost y Gonzalo Frasca sobre la persuasión, se resiguen las carencias metodológicas de los modelos planteados y se proponen una serie de hipótesis orientadas a la búsqueda de una metodología que posibilite dar respuesta a la siguiente pregunta: ¿Cómo y dónde se articula la dimensión persuasiva de los videojuegos?En este sentido se trata de estudiar la dimensión persuasiva en los videojuegos de manera integral. La supuesta capacidad de las reglas de juego, propiedad intrínseca de los juegos y videojuegos, de determinar tanto la estructura narrativa como la parte audio/visual del texto (videojuego), así como su condición esencial de ser las portadoras de la carga persuasiva, permite apuntar como objetivo fundamental el diseño de un protocolo integral de la persuasión en los videojuegos

Conflito no desempenho do papel de mãe em estudos com mães de recém-nascidos hospitalizados: revisão integrativa

A hospitalização de um recém-nascido provoca a separação entre mãe e filho quando o contato é fundamental para o desenvolvimento do papel materno. Assim, as mães tendem a se sentir incapazes de atender as necessidades dos filhos, enfrentando dificuldades para lidar com seus sentimentos e com as demandas dos familiares. O objetivo deste estudo foi identificar as Características Definidoras do Diagnóstico de Enfermagem Conflito no desempenho do papel de mãe em estudos sobre a experiência de ser mãe na unidade neonatal. Trata-se de uma revisão integrativa da literatura, que utilizou 15 estudos qualitativos, publicados de 2004 a 2009 em periódicos indexados na Literatura Latino-Americana e do Caribe em Ciências da Saúde e Medical LiteratureandRetrieval System OnLine. Este diagnóstico é um fenômeno de enfermagem a ser estudado por enfermeiros neonatais para que possam reconhecer e propor intervenções às necessidades maternas, visto que nove das dez Características Definidoras foram identificadas nos depoimentos das mães.

Earthquake impacts in old-growth Nothofagus forests in New Zealand

Six stands located on different land forms in mixed old-growth Nothofagus forests in the Matiri Valley (northwest of South Island. New Zealand) were sampled to examine the effects of two recent large earthquakes on tree establishment and tree-ring growth, and how these varied across land forms. 50 trees were cor ed in each stand to determine age structure and the cores were cross-dated to precisely date unusual periods of radial growth. The 1968 earthquake (M = 7.1, epicentre 35 km from the study area) had no discernible impact on the sampled stands. The impact of the 1929 earthquake (M = 7.7, epicentre 20 kin from the study area) varied between stands, depending on whether or not they had been damaged by soil or rock movement. In all stands, the age structures showed a pulse of N. fusca establishment following the 1929 earthquake, with this species dominating establishment in large gaps created by landslides. Smaller gaps, created by branch or tree death, were closed by both N. fusca and N. menziesii. The long period of releases (1929-1945) indicates that direct earthquake damage was not the only cause of tree death, and that many trees died subsequently most likely of pathogen attack or a drought in the early 1930s. The impacts of the 1929 earthquake are compared to a storm in 1905 and a drought in 1974-1978 which also affected forests in the region. Our results confirm that earthquakes are an important factor driving forest dynamics in this tectonically active region, and that the diversity of earthquake impacts is a major source of heterogeneity in forest structure and regeneration.

Educação interprofissional: formação de profissionais de saúde para o trabalho em equipe com foco nos usuários

São analisados os constructos teóricos da educação interprofissional com base em duas revisões de literatura, considerado o contexto da formação dos profissionais de saúde no Brasil. Identificam-se três tipos de formação: uniprofissional, multiprofissional e interprofissional, com predomínio da primeira, que ocorre entre estudantes de uma mesma profissão de forma isolada; a segunda, entre estudantes de duas ou mais profissões de forma paralela, sem haver interação, e na terceira há aprendizagem compartilhada, com interação entre estudantes e/ou profissionais de diferentes áreas. Destaca-se a distinção entre interprofissionalidade e interdisciplinaridade, referidas, respectivamente, como a integração das práticas profissionais e das disciplinas ou áreas de conhecimento. Mediante a análise apresentada, conclui-se que no contexto brasileiro, a educação interprofissional, base para o trabalho em equipe colaborativo, ainda está restrita a iniciativas recentes, que merecem estudo.

The relation of body mass index and abdominal adiposity with dyslipidemia in 27 general populations of the WHO MONICA Project.

The association between adiposity measures and dyslipidemia has seldom been assessed in a multipopulational setting. 27 populations from Europe, Australia, New Zealand and Canada (WHO MONICA project) using health surveys conducted between 1990 and 1997 in adults aged 35-64 years (n = 40,480). Dyslipidemia was defined as the total/HDL cholesterol ratio >6 (men) and >5 (women). Overall prevalence of dyslipidemia was 25% in men and 23% in women. Logistic regression showed that dyslipidemia was strongly associated with body mass index (BMI) in men and with waist circumference (WC) in women, after adjusting for region, age and smoking. Among normal-weight men and women (BMI<25 kg/m(2)), an increase in the odds for being dyslipidemic was observed between lowest and highest WC quartiles (OR = 3.6, p < 0.001). Among obese men (BMI ≥ 30), the corresponding increase was smaller (OR = 1.2, p = 0.036). A similar weakening was observed among women. Classification tree analysis was performed to assign subjects into classes of risk for dyslipidemia. BMI thresholds (25.4 and 29.2 kg/m(2)) in men and WC thresholds (81.7 and 92.6 cm) in women came out at first stages. High WC (>84.8 cm) in normal-weight men, menopause in women and regular smoking further defined subgroups at increased risk. standard categories of BMI and WC, or their combinations, do not lead to optimal risk stratification for dyslipidemia in middle-age adults. Sex-specific adaptations are necessary, in particular by taking into account abdominal obesity in normal-weight men, post-menopausal age in women and regular smoking in both sexes.

Financiamento dos Sistema de Saude

Este Relatório sobre a Saúde no Mundo foi produzido sob a direcção geral de Carissa Etienne, Assistente do Director-Geral, Sistemas e Serviços de Saúde e Anarfi Asamoa-Baah, Director Geral Adjunto. Os redactores principais froam David B Evans, Riku Elovainio e Gary Humphreys; com contribuições de Daniel Chisholm, Joseph Kutzin, Sarah Russell, Priyanka Saksena e Ke Xu. Contribuições sob a forma de caixas de texto e análises foram fornecidos por: Ole Doetinchem, Adelio Fernandes Antunes, Justine Hsu, Chandika K. Indikadahena, Jeremy Lauer, Nathalie van de Maele, Belgacem Sabri, Hossein Salehi, Xenia Scheil-Adlung (ILO) and Karin Stenberg. Sugestões e comentários foram recebidos dos Directores Regionais, Assistentes do Director-Geral e respectivas equipas. Análises, dados e revisões da organização do texto, vários rascunhos ou secções específicas foram fornecidos por (em adição às pessoas jáacima mencionadas): Dele Abegunde, Michael Adelhardt, Hector Arreola, Guitelle Baghdadi-Sabeti, Dina Balabanova, Dorjsuren Bayarsaikhan, Peter Berman, Melanie Bertram, Michael Borowitz, Reinhard Busse, Alexandra Cameron, Guy Carrin, Andrew Cassels, Eleonora Cavagnero, John Connell, David de Ferranti, Don de Savigny, Varatharajan Durairaj, Tamás Evetovits, Josep Figueras, Emma Fitzpatrick, Julio Frenk, Daniela Fuhr, Ramiro Guerrero, Patricia Hernandez Pena, Hans V Hogerzeil, Kathleen Holloway, Melitta Jakab, Elke Jakubowski, Christopher James, Mira Johri, Matthew Jowett, Joses Kirigia, Felicia Knaul, Richard Laing, Nora Markova, Awad Mataria, Inke Mathauer, Don Matheson, Anne Mills, Eduardo Missoni, Laurent Musango, Helena Nygren-Krug, Ariel Pablos-Mendez, Anne-Marie Perucic, Claudia Pescetto, Jean Perrot, Alexander Preker, Magdalena Rathe, Dag Rekve, Ritu Sadana, Rocio Saenz, Thomas Shakespeare, Ian Smith, Peter C Smith, Alaka Singh, Ruben Suarez Berenguela, Tessa Tan-Torres Edejer, Richard Scheffler, Viroj Tangcharoensathien, Fabrizio Tediosi, Sarah Thomson, Ewout van Ginneken, Cornelis van Mosseveld e Julia Watson. A redacção do Relatório foi informada por muitos indivíduos de várias instituições que forneceram documentos de suporte; estes documentos de suporte podem ser encontrados em: http://www.who.int/healthsystems/topics/financing/healthreport/whr_background/en Michael Reid editou as cópias do Relatório, Gaël Kernen produziu as figuras e Evelyn Omukubi forneceu o valioso apoio secretarial e administrativo. O desenho e paginação foi feito por Sophie Guetaneh Aguettant e Cristina Ortiz. Ilustração por Edel Tripp (http://edeltripp.daportfolio.com). A tradução foi realizada por Jorge Cabral e Aurélio Floriano e revista por Aurélio Floriano e Paulo Ferrinho, do Instituto de Higiene e Medicina Tropical, da Universidade Nova de Lisboa - Lisboa, Portugal. A publicação foi produzida com o apoio da Comunidade dos Países de Língua Portuguesa (CPLP), sob autorização do Director Geral da Organização Mundial da Saúde (OMS). As informações contidas neste Relatório não podem, de forma alguma, ser tomadas como a expressão das posições da CPLP

Phylogenetic structures of the Holarctic Sorex araneus group and its relationships with S-samniticus, as inferred from mtDNA sequences

The shrews of the Sorex araneus group, characterized by the sexual chromosome complex XY1, Y2 have been intensively studied by morphological, karyotypical, and biochemical analyses. Nevertheless, the phylogenetic relationships among the species belonging to the araneus complex are still under debate, as different approaches gave often contradictory results. In this paper, partial nucleotide sequences of the mitochondrial DNA cytochrome b gene (1011 bp) were determined for 6 species of the araneus group from Eurasia and North America. We also included in the data set the sequences of Sorex samniticus, whose relationships with the araneus group remain controversial. Three other species representing two major karyological groups were also examined. Both parsimony and distance trees strongly support the monophyly of the araneus group. Sorex sumniticus is significantly more closely related to the araneus complex than to the other species included in the analysis. Based on the branching pattern within the araneus group, an attempt has been made to reconstruct the colonization history of the Holarctic region.

The European dimension for the mouse genome mutagenesis program.

The European Mouse Mutagenesis Consortium is the European initiative contributing to the international effort on functional annotation of the mouse genome. Its objectives are to establish and integrate mutagenesis platforms, gene expression resources, phenotyping units, storage and distribution centers and bioinformatics resources. The combined efforts will accelerate our understanding of gene function and of human health and disease.

The maritime shrew, Sorex maritimensis (Insectivora : Soricidae): a newly recognized Canadian endemic.

Previous morphological and cytological analyses have suggested that the arctic shrew (Sorex arcticus) as currently recognized may be two distinct species. Specifically, those studies demonstrated considerable differentiation between the putative subspecies S. a. maritimensis and one or both of the other two subspecies, S. a. arcticus and S. a. laricorum. Phylogenetic analysis of 546 base pairs of cytochrome b sequence data from 10 arctic shrews from across Canada indicates that maritimensis is the sister-group to arcticus + laricorum. Furthermore, there is considerable genetic divergence between maritimensis and the other two putative subspecies (similar to8-9%; Kimura's two-parameter distance). Given that maritimensis and arcticus + laricorum appear to be reciprocally monophyletic clades with considerable genetic divergence (i.e., greater than that between other recognized pairs of sister-species within the S. araneus-arcticus group), we propose that S. maritimensis be recognized as a distinct species. The proportion of third-position transversion substitutions between S. arcticus and S. maritimensis suggests that these two species shared a common ancestor approximately 2.4 million years ago.