Sarcoidosis, alveolar β-actin and pulmonary fibrosis

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown aetiology. Proteins present within the alveolar space early in sarcoidosis disease may provide an insight into novel mechanisms for the development of fibrotic disease and in particular pulmonary fibrosis.

METHODS: A modified two-dimensional difference gel electrophoresis protocol was applied to the human bronchoalveolar lavage fluid (hBALF) of four patients with non-persistent pulmonary interstitial disease at 4-year follow-up (defined as mild disease) and four patients who developed pulmonary interstitial disease at 4-year follow-up (defined as severe disease). The protein β-actin was identified by LC-MS/MS from a preparative gel and found to be significantly elevated in early lavages from the severe disease group. To look at the potential pro-fibrotic effects of this protein, primary human pulmonary fibroblasts (CCD-19Lu) were treated with recombinant β-actin following which qPCR and ELISA assays were used to measure any effects.

RESULTS: We found that β-actin levels were significantly elevated in early hBALF samples in patients who subsequently developed severe disease when compared to the mild group. Treating primary human pulmonary fibroblasts with recombinant β-actin led to enhanced gene expression of the pro-fibrotic markers alpha smooth muscle actin and collagen 1 as well as the increased secretion of interleukin-13 and metalloproteinases 3 and 9.

CONCLUSION: Free β-actin within the lungs of sarcoidosis patients potentially may contribute to disease pathogenesis particularly in the context of abnormal remodelling and the development of pulmonary fibrosis.

Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial

BACKGROUND: Prostate cancer might have high radiation-fraction sensitivity that would give a therapeutic advantage to hypofractionated treatment. We present a pre-planned analysis of the efficacy and side-effects of a randomised trial comparing conventional and hypofractionated radiotherapy after 5 years follow-up.

METHODS: CHHiP is a randomised, phase 3, non-inferiority trial that recruited men with localised prostate cancer (pT1b-T3aN0M0). Patients were randomly assigned (1:1:1) to conventional (74 Gy delivered in 37 fractions over 7·4 weeks) or one of two hypofractionated schedules (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3·8 weeks) all delivered with intensity-modulated techniques. Most patients were given radiotherapy with 3-6 months of neoadjuvant and concurrent androgen suppression. Randomisation was by computer-generated random permuted blocks, stratified by National Comprehensive Cancer Network (NCCN) risk group and radiotherapy treatment centre, and treatment allocation was not masked. The primary endpoint was time to biochemical or clinical failure; the critical hazard ratio (HR) for non-inferiority was 1·208. Analysis was by intention to treat. Long-term follow-up continues. The CHHiP trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN97182923.

FINDINGS: Between Oct 18, 2002, and June 17, 2011, 3216 men were enrolled from 71 centres and randomly assigned (74 Gy group, 1065 patients; 60 Gy group, 1074 patients; 57 Gy group, 1077 patients). Median follow-up was 62·4 months (IQR 53·9-77·0). The proportion of patients who were biochemical or clinical failure free at 5 years was 88·3% (95% CI 86·0-90·2) in the 74 Gy group, 90·6% (88·5-92·3) in the 60 Gy group, and 85·9% (83·4-88·0) in the 57 Gy group. 60 Gy was non-inferior to 74 Gy (HR 0·84 [90% CI 0·68-1·03], pNI=0·0018) but non-inferiority could not be claimed for 57 Gy compared with 74 Gy (HR 1·20 [0·99-1·46], pNI=0·48). Long-term side-effects were similar in the hypofractionated groups compared with the conventional group. There were no significant differences in either the proportion or cumulative incidence of side-effects 5 years after treatment using three clinician-reported as well as patient-reported outcome measures. The estimated cumulative 5 year incidence of Radiation Therapy Oncology Group (RTOG) grade 2 or worse bowel and bladder adverse events was 13·7% (111 events) and 9·1% (66 events) in the 74 Gy group, 11·9% (105 events) and 11·7% (88 events) in the 60 Gy group, 11·3% (95 events) and 6·6% (57 events) in the 57 Gy group, respectively. No treatment-related deaths were reported.

INTERPRETATION: Hypofractionated radiotherapy using 60 Gy in 20 fractions is non-inferior to conventional fractionation using 74 Gy in 37 fractions and is recommended as a new standard of care for external-beam radiotherapy of localised prostate cancer.

FUNDING: Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network.

Electric-Field Dependence of the Effective Dielectric Constant in Graphene

Not Available

Inovação no Setor de Serviços em São Caetano do Sul (SP): mensuração e oportunidades de desenvolvimento local

Com o objetivo de mensurar o grau de inovação e verificar os fatores influenciadores a inovação no setor de serviços, este trabalho investigou 358 em micro e pequenas empresas na cidade de São Caetano do Sul, região metropolitana de São Paulo. A pesquisa quantitativa foi realizada por meio de Regressão Logística Binária. Constatou-se que o grau de inovação foi de 0, 109. 34,9% das empresas pesquisadas não apresentaram evidências de inovação. Os fatores mais relevantes na classificação das micro e pequenas empresas como inovadoras são: pesquisa de fornecedores; uso de crédito de fonte formal; treinamento e capacitação e política de remuneração e benefícios aos funcionários. Quanto maior a intensidade da prática dos comportamentos e procedimentos, maior a probabilidade da empresa integrar-se ao grupo inovador. Os resultados obtidos apontam que a inovação não é um elemento prioritário na agenda dos empresários, o que pode ser observado em razão da maioria das empresas investigadas não adotar práticas que poderiam caracterizá-las como inovadoras.

Futures Shock: Are Greedy Brokers Ruining The Economy?

[Excerpt] In a recent public relations document, the New York Stock Exchange defines its mission statement as to: “Support the capital-raising and asset management process by providing the highest quality and most cost-effective, self-regulated marketplace for the trading of financial instruments.” The common thread that runs through this and similar statements made by organized financial markets from Frankfurt to Tokyo is that they hold as their primary goals to help companies raise capital and to provide a liquid and efficient aftermarket for those securities.

Are physical measures good indicators of image quality at low dose levels? A pilot study

Purpose: To evaluate if physical measures of noise predict image quality at high and low noise levels. Method: Twenty-four images were acquired on a DR system using a Pehamed DIGRAD phantom at three kVp settings (60, 70 and 81) across a range of mAs values. The image acquisition setup consisted of 14 cm of PMMA slabs with the phantom placed in the middle at 120 cm SID. Signal-to-noise ratio (SNR) and Contrast-tonoise ratio (CNR) were calculated for each of the images using ImageJ software and 14 observers performed image scoring. Images were scored according to the observer`s evaluation of objects visualized within the phantom. Results: The R2 values of the non-linear relationship between objective visibility score and CNR (60kVp R2 = 0.902; 70Kvp R2 = 0.913; 80kVp R2 = 0.757) demonstrate a better fit for all 3 kVp settings than the linear R2 values. As CNR increases for all kVp settings the Object Visibility also increases. The largest increase for SNR at low exposure values (up to 2 mGy) is observed at 60kVp, when compared with 70 or 81kVp.CNR response to exposure is similar. Pearson r was calculated to assess the correlation between Score, OV, SNR and CNR. None of the correlations reached a level of statistical significance (p>0.01). Conclusion: For object visibility and SNR, tube potential variations may play a role in object visibility. Higher energy X-ray beam settings give lower SNR but higher object visibility. Object visibility and CNR at all three tube potentials are similar, resulting in a strong positive relationship between CNR and object visibility score. At low doses the impact of radiographic noise does not have a strong influence on object visibility scores because in noisy images objects could still be identified.

Violência contra a mulher: estudo das ocorrências registradas na Delegacia Especializada de atendimento às mulheres – Rio Grande-RS

Introdução: no Brasil, a violência contra a mulher foi reconhecida somente com a Convenção Belém do Pará, em 1995. A partir daí, inúmeras medidas para prevenção e combate foram instituídas, entre elas a criação das Delegacias Especializadas de Atendimento às Mulheres (DEAM) e a Lei Maria da Penha. No entanto, muitas mulheres ainda são vitimadas, na maioria das vezes dentro do próprio lar. Objetivos: delinear o perfil das mulheres vítimas de violência; identificar as formas de violência registradas na DEAM da cidade do Rio Grande/RS; identificar os motivos que levam à prática da violência e descrever os atos violentos perpetrados, por parceiro íntimo, às mulheres que registraram ocorrência na DEAM. Metodologia: estudo documental, quanti e qualitativo, de natureza exploratória, descritiva e delineamento transversal. Fizeram parte do estudo todas as ocorrências cujas vítimas eram mulheres com 18 anos ou mais. O espaço temporal adotado estendeu-se de agosto de 2009, quando foi implantada a delegacia, a dezembro de 2011. Os dados foram coletados entre outubro de 2011 e março de 2012. Para a coleta, foi elaborado e aprovado, após testagem, um instrumento contendo informações acerca do agressor, da vítima, bem como do tipo de violência praticada. Os dados foram digitados em planilhas do tipo Excel. A análise quantitativa foi efetuada por meio de estatística descritiva e do software estatístico SPSS versão 17.0. Para o estudo qualitativo utilizou-se a análise de conteúdo. Esse projeto foi aprovado pelo Comitê de Ética em Pesquisa na Área da Saúde, da Universidade Federal do Rio Grande sob Parecer no 137/2011. Resultados: estão descritos em dois artigos. Analisaram-se 902 ocorrências policiais evidenciando-se que a maioria das vitimas eram mulheres brancas, jovens, com baixa escolaridade. Ainda foi possível identificar que o Centro da cidade ocupou a segunda posição como local de moradia das vítimas, desmitificando a idéia de que a violência predomina na periferia. A violência física prevaleceu nos registros notificados, seguida do descumprimento de ordem judicial. Além disso, encontrou-se a reincidência de denúncias, o que pode estar atrelado à morosidade judicial. Observou-se também, que existem diversos motivos desencadeadores da violência, no entanto todos eles apresentam como pano de fundo as questões associadas ao gênero. A simultaneidade da violência bem como a extensão aos filhos, família e sociedade retratam a gravidade do fenômeno e a necessidade de se rever a resolutividade das medidas protetivas e das penas atribuídas aos agressores. Conclusões: este estudo expôs, parcialmente, a situação da violência contra a mulher no município, pois se sabe que existem muitos casos velados que não chegam a ser notificados. Entretanto, evidenciou-se o predomínio da violência física cometida por parceiro íntimo repercutindo em graves consequências à vida das vítimas. Assim, julga-se ímpar a implementação de uma rede efetiva de apoio a essas mulheres bem como a atuação de equipe multidisciplinar capacitada, coesa e sensível ao problema, incluindo os profissionais da saúde, que precisam, ainda, estar ciente da obrigatoriedade da notificação compulsória, fundamental para a formulação de novas políticas públicas de combate e prevenção a esse fenômeno.

Yang–Mills solutions and dyons on cylinders over coset spaces with Sasakian structure

We present solutions of the Yang–Mills equation on cylinders R×G/HR×G/H over coset spaces of odd dimension 2m+12m+1 with Sasakian structure. The gauge potential is assumed to be SU(m)SU(m)-equivariant, parameterized by two real, scalar-valued functions. Yang–Mills theory with torsion in this setup reduces to the Newtonian mechanics of a point particle moving in R2R2 under the influence of an inverted potential. We analyze the critical points of this potential and present an analytic as well as several numerical finite-action solutions. Apart from the Yang–Mills solutions that constitute SU(m)SU(m)-equivariant instanton configurations, we construct periodic sphaleron solutions on S1×G/HS1×G/H and dyon solutions on iR×G/HiR×G/H.

Ageing in a non-heterosexual context.

There is increasing recognition of the importance of social and cultural differences in shaping the diversity of the ageing experience in contemporary Britain. Various social and cultural factors, such as those associated with class, ethnicity, gender and disability, influence people’s living circumstances and sources of support in later life. While they have been the subject of considerable speculation, ageing in a non-heterosexual context remains remarkably under-studied. This paper examines the difference that being non-heterosexual makes to how people experience ageing and later life. It draws on quantitative and qualitative data gathered for a British study of the living circumstances of non-heterosexuals aged between the fifties and the eighties. Previous work has overwhelmingly emphasised how individuals manage their sexual identities, but this paper focuses on the factors that shape the non-heterosexual experience of ageing and later life. Particular attention is paid to the relational and community contexts in which non-heterosexuals negotiate personal ageing. This not only provides insights into the specific challenges that ageing presents for non-heterosexuals, but also offers insights into the challenges faced by ageing non-heterosexuals and heterosexuals in ‘ detraditionalised ’ settings.

A method for the estimation of potential evapotranspiration and/or open pan evaporation over Brazil.

This paper presents a simple regression model to estimate potential evapotranspiration and/or open pan evaporation data for a wide network of stations in Brazil. The model uses the readily available data sets like geocoordinates (latitude) and precipitation as inputs. Potential evapotranspiration presents a high correlation with the precipitation during summer months and with latitude during winter months. It also shows association with longitude and elevation; the magnitude of variation appears to be very small. This model gave a R2 varying from 0.460 to 0.902 for different months. The model is also extended to weekly periods of individual years ant tested with the open pan evaporation data of Bebedouro and Mandacaru. The agreement between observed and predicted values appears to be good.

Spatial choice is biased by chemical cues from conspecifics in the speckeled worm eel Myrophis punctatus

A enguia mirongo-mirim Myrophis punctatus vive em agrupamentos de alta densidade populacional e comumente se enterra ou permanece sob o substrato. Esses comportamentos podem levar a marcas químicas no subtrato e podem, portanto, modular o uso do espaço nessa espécie. Neste estudo, testamos a hipótese de que a preferência espacial da enguia mirongo-mirim é influenciada pela presença de odor do animal coespecífico no subtrato. Mostramos que as enguias evitam a área que contém tal odor, indicando que as decisões de ocupação espacial podem ser influenciadas por pistas químicas de coespecíficos. As enguias claramente detectaram o odor de um animal coespecífico e essa percepção poderia ser um indicativo da presença de um coespecífico enterrado no substrato. Visto que elas evitam uma área contendo tal odor, sugerimos que isso poderia ser uma resposta para evitar invadir o território de um animal residente.