262 research outputs found

    False-negative PD-L1 immunostaining in ethanol-fixed EBUS-TBNA specimens of non-small cell lung cancer patients

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    Aims Programmed death-ligand 1 (PD-L1) immunostaining is used to predict which non-small-cell lung cancer (NSCLC) patients will respond best to treatment with programmed cell death protein 1/PD-L1 inhibitors. PD-L1 immunostaining is sometimes performed on alcohol-fixed cytological specimens instead of on formalin-fixed paraffin-embedded (FFPE) biopsies or resections. We studied whether ethanol prefixation of clots from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) results in diminished PD-L1 immunostaining as compared with formalin fixation. Methods and results FFPE cell blocks from EBUS-TBNA specimens of 54 NSCLC patients were identified. For each case, paired samples were available, consisting of clots directly immersed in formalin and clots prefixed in Fixcyt (50% ethanol). Serial sections were immunostained for PD-L1 by use of the standardised SP263 assay and the 22C3 antibody as a laboratory-developed test (LDT). PD-L1 positivity was determined with two cut-offs (1% and 50%). Concordance of PD-L1 positivity between the formalin-fixed (gold standard) and ethanol-prefixed material was assessed. When the 22C3 LDT was used, 30% and 36% of the ethanol-prefixed specimens showed false-negative results at the 1% and 50% cut-offs, respectively (kappa 0.64 and 0.68). When SP263 was used, 22% of the ethanol-prefixed specimens showed false-negative results at the 1% cut-off (kappa 0.67). At the 50% cut-off, concordance was higher (kappa 0.91), with 12% of the ethanol-prefixed specimens showing false-negative results. Conclusion Ethanol fixation of EBUS-TBNA specimens prior to formalin fixation can result in a considerable number of false-negative PD-L1 immunostaining results when a 1% cut-off is used and immunostaining is performed with SP263 or the 22C3 LDT. The same applies to use of the 50% cut-off when immunostaining is performed with the 22C3 LDT

    A educação na 'Constelação pós-nacional': o enfraquecimento da legitimação e do controle democrático, "expertocrático" e ético-profissional

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    The article discusses current transformations in the education systems worldwide. Focusing on the European Union (EU) and the Organisation for Economic Cooperation and Development (OECD) as policy actors, it argues that these transformations imply a triple economization of education policy which can be observed at all levels of the education sector. The increasing importance of these organizations in educational issues marks a transition to a "postnational constellation" also in the education field insofar as the national educational sovereignty is being at least readjusted. The economization of education policy is however not restricted to bringing education closer to the needs of the economy and to turning its services into tradable goods. Rather, it also impinges on the operative level of education. A logics of production is being implemented in the self-description of the institutions of the education system, which are no longer bureaucratically administered establishments, but are rather conceived of as managerially conducted production business in which entrepreneurial action is needed. This new governance raises the problem of democratic legitimation of political decisions which ideally combines three elements: democratic, expertocratic, and ethico-professional. The article discusses the consequences of a shift in the balance of the three components with reference to Germany.O presente artigo discute as atuais transformações nos sistemas educacionais em todo o mundo. Tendo como foco a União Europeia (UE) e a Organização para a Cooperação e o Desenvolvimento Econômico (OCDE) como atores de políticas, seu argumento é que tais transformações implicam uma tripla "economização" da política educacional, que pode ser constatada em todos os níveis da área educacional. A importância cada vez maior dessas organizações nas questões educacionais configura uma transição para uma "constelação pós-nacional" também na área educacional, na medida em que a soberania educacional nacional está, no mínimo, passando por reajustes. No entanto, a "economização" das políticas educacionais não se limita a aproximar a educação das necessidades da economia e a transformar seus serviços em mercadorias comercializáveis. Ela também afeta o nível operacional da educação. Uma lógica de produção está sendo implementada na descrição realizada pelas próprias instituições do sistema educacional, que deixaram de ser estabelecimentos burocraticamente administrados para ser concebidos como uma atividade comercial gerencialmente controlada, uma atividade na qual uma ação empresarial se faz necessária. Esse novo tipo de administração faz surgir o problema da legitimação democrática das decisões políticas que, em termos ideais, combina três elementos: o democrático, o "expertocrático" e o ético-profissional. O artigo discute as consequências de uma mudança no equilíbrio desses três elementos no caso da Alemanha

    Teacher quality in the twenty first century: new lives, old truths

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    This chapter is based upon a keynote address to the first global teacher education summit, organised by Beijing Normal University in 2011, in which research across the world about influences which affect teachers' sense of professional identity, capacity for compassion, commitment, resilience and effectiveness long after they have graduated from their pre-service education and training programmes in universities and colleges were shared. The findings suggest that teaching pre-service students about how the conditions in which they work may enhance or diminish their capacity to teach to their best and how they might act to mediate these is a key part of the work of all teacher educators and an important focus for the work of educational researchers

    Fruit crops: a summary of research, 1998

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    Pesticide deposition in orchards: effects of pesticide type, tree canopy, timing, cultivar, and leaf type / Franklin R. Hall, Jane A. Cooper, and David C. Ferree -- The influence of a synthetic foraging attractant, Bee-Scent™, on the number of honey bees visiting apple blossoms and on subsequent fruit production / James E. Tew and David C. Ferree -- The reliability of three traps vs. a single trap for determining population levels of codling moth in commercial northern Ohio apple orchards / Ted W. Gastier -- Evaluation of an empirical model for predicting sooty blotch and flyspeck of apples in Ohio / Michael A. Ellis, Laurence V. Madden, and L. Lee Wilson -- Influence of pesticides and water stress on photosynthesis and transpiration of apple / David C. Ferree, Franklin R. Hall, Charles R. Krause, Bruce R. Roberts, and Ross D. Brazee -- Influence of temporary bending and heading on branch development and flowering of vigorous young apple trees / David C. Ferree and John C. Schmid -- The effect of apple fruit bruising on total returns / Richard C. Funt, Ewen A. Cameron, and Nigel H. Banks -- Yield, berry quality, and economics of mechanical berry harvest in Ohio / Richard C. Funt, Thomas E. Wall, and Joseph C. Scheerens -- Monitoring flower thrips activities in strawberry fields at two Ohio locations / Roger N. Williams, M. Sean Ellis, Dan S. Fickle, and Carl M. Pelland -- Cluster thinning effects on fruit weight, juice quality, and fruit skin characteristics in 'Reliance' grapes / Yu Gao and Garth A. Cahoon -- Effects of various fungicide programs on powdery mildew control, percent berry sugar, yield, and vine vigor of 'Concord' grapes in Ohio / Michael A. Ellis, Laurence V. Madden, L. Lee Wilson, and Gregory R. Johns -- Influence of growth regulators, cropping, and number on replacement trunks of winter-injured 'Vidal Blanc' grapes / David C. Ferree, David M. Scurlock, and Rick Evans -- Effect of new herbicides on tissue-cultured black raspberry plants / Richard C. Funt, Thomas E. Wall, and B. Dale Stokes -- Investigating the relationship between vine vigor and berry set of field-grown 'Seyval Blanc' grapevines / Steven J. McArtney and David C. Ferree -- Summary of Ohio Fruit Growers Society apple cider competition, 1993-1997 / Winston Bash and Diane Mille

    Anxiety can significantly explain bolus perception in the context of hypotensive esophageal motility: Results of a large multicenter study in asymptomatic individuals

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    This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving'. © 2017 John Wiley & Sons, Inc. All rights reserved. This author accepted manuscript is made available following 12 month embargo from date of publication (May 2017) in accordance with the publisher’s archiving policyBackground Previous studies have not been able to correlate manometry findings with bolus perception. The aim of this study was to evaluate correlation of different variables, including traditional manometric variables (at diagnostic and extreme thresholds), esophageal shortening, bolus transit, automated impedance manometry (AIM) metrics and mood with bolus passage perception in a large cohort of asymptomatic individuals. Methods High resolution manometry (HRM) was performed in healthy individuals from nine centers. Perception was evaluated using a 5‐point Likert scale. Anxiety was evaluated using Hospitalized Anxiety and Depression scale (HAD). Subgroup analysis was also performed classifying studies into normal, hypotensive, vigorous, and obstructive patterns. Key Results One hundred fifteen studies were analyzed (69 using HRM and 46 using high resolution impedance manometry (HRIM); 3.5% swallows in 9.6% of volunteers were perceived. There was no correlation of any of the traditional HRM variables, esophageal shortening, AIM metrics nor bolus transit with perception scores. There was no HRM variable showing difference in perception when comparing normal vs extreme values (percentile 1 or 99). Anxiety but not depression was correlated with perception. Among hypotensive pattern, anxiety was a strong predictor of variance in perception (R2 up to .70). Conclusion and Inferences Bolus perception is less common than abnormal motility among healthy individuals. Neither esophageal motor function nor bolus dynamics evaluated with several techniques seems to explain differences in bolus perception. Different mechanisms seem to be relevant in different manometric patterns. Anxiety is a significant predictor of bolus perception in the context of hypotensive motility

    Activation of Aryl Hydrocarbon Receptor (AhR) Leads to Reciprocal Epigenetic Regulation of FoxP3 and IL-17 Expression and Amelioration of Experimental Colitis

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    Aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family, is well characterized to regulate the biochemical and toxic effects of environmental chemicals. More recently, AhR activation has been shown to regulate the differentiation of Foxp3(+) Tregs as well as Th17 cells. However, the precise mechanisms are unclear. In the current study, we investigated the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AhR ligand, on epigenetic regulation leading to altered Treg/Th17 differentiation, and consequent suppression of colitis.Dextran sodium sulphate (DSS) administration induced acute colitis in C57BL/6 mice, as shown by significant weight loss, shortening of colon, mucosal ulceration, and increased presence of CXCR3(+) T cells as well as inflammatory cytokines. Interestingly, a single dose of TCDD (25 µg/kg body weight) was able to attenuate all of the clinical and inflammatory markers of colitis. Analysis of T cells in the lamina propria (LP) and mesenteric lymph nodes (MLN), during colitis, revealed decreased presence of Tregs and increased induction of Th17 cells, which was reversed following TCDD treatment. Activation of T cells from AhR(+/+) but not AhR (-/-) mice, in the presence of TCDD, promoted increased differentiation of Tregs while inhibiting Th17 cells. Analysis of MLN or LP cells during colitis revealed increased methylation of CpG islands of Foxp3 and demethylation of IL-17 promoters, which was reversed following TCDD treatment.These studies demonstrate for the first time that AhR activation promotes epigenetic regulation thereby influencing reciprocal differentiation of Tregs and Th17 cells, and amelioration of inflammation

    School Effects on the Wellbeing of Children and Adolescents

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    Well-being is a multidimensional construct, with psychological, physical and social components. As theoretical basis to help understand this concept and how it relates to school, we propose the Self-Determination Theory, which contends that self-determined motivation and personality integration, growth and well-being are dependent on a healthy balance of three innate psychological needs of autonomy, relatedness and competence. Thus, current indicators involve school effects on children’s well-being, in many diverse modalities which have been explored. Some are described in this chapter, mainly: the importance of peer relationships; the benefits of friendship; the effects of schools in conjunction with some forms of family influence; the school climate in terms of safety and physical ecology; the relevance of the teacher input; the school goal structure and the implementation of cooperative learning. All these parameters have an influence in promoting optimal functioning among children and increasing their well-being by meeting the above mentioned needs. The empirical support for the importance of schools indicates significant small effects, which often translate into important real-life effects as it is admitted at present. The conclusion is that schools do make a difference in children’s peer relationships and well-being
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