4,192 research outputs found

    Enumeration of leukocyte infiltration in solid tumors by confocal laser scanning microscopy

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    BACKGROUND: Leukocytes commonly infiltrate solid tumors, and have been implicated in the mechanism of spontaneous regression in some cancers. Conventional techniques for the quantitative estimation of leukocyte infiltrates in tumors rely on light microscopy of immunostained thin tissue sections, in which an arbitrary assessment (based on low, medium or high levels of infiltration) of antigen density is made by the pathologist. These estimates are relatively subjective and often require the opinion of a second pathologist. In addition, since thin tissue sections are cut, no data regarding the three-dimensional distribution of antigen can be obtained. RESULTS: To overcome these problems, we have designed a method to enumerate leukocyte infiltration into tumors, using confocal laser scanning microscopy of fluorescently immunostained leukocytes in thick tissue sections. Using image analysis software, a threshold was applied to eliminate unstained tissue and residual noise. The total antigen volume in the scanned tissue was calculated and divided by the mean cell volume (calculated by "seeding" ten individual cells) to obtain the cell count. Using this method, we compared the calculated leukocyte counts with those obtained manually by ten laboratory personnel. There was no significant difference (P > 0.05) between the cell counts obtained by either method. We then compared leukocyte infiltration into seven tumors and matched non-malignant tissue obtained from the periphery of the resected tissue. There was a significant increase in the infiltration of all leukocyte subsets into the tumors compared to minimal numbers in the non-malignant tissue. CONCLUSION: From these results we conclude that this method may be of considerable use for the enumeration of cells in tissues. Furthermore, since it can be performed by laboratory technical staff, less time input is required by the pathologist in assessing the degree of leukocyte infiltration into tumors

    Looking inside the black box : a theory-based process evaluation alongside a randomised controlled trial of printed educational materials (the Ontario printed educational message, OPEM) to improve referral and prescribing practices in primary care in Ontario, Canada

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    Background: Randomised controlled trials of implementation strategies tell us whether (or not) an intervention results in changes in professional behaviour but little about the causal mechanisms that produce any change. Theory-based process evaluations collect data on theoretical constructs alongside randomised trials to explore possible causal mechanisms and effect modifiers. This is similar to measuring intermediate endpoints in clinical trials to further understand the biological basis of any observed effects (for example, measuring lipid profiles alongside trials of lipid lowering drugs where the primary endpoint could be reduction in vascular related deaths). This study protocol describes a theory-based process evaluation alongside the Ontario Printed Educational Message (OPEM) trial. We hypothesize that the OPEM interventions are most likely to operate through changes in physicians' behavioural intentions due to improved attitudes or subjective norms with little or no change in perceived behavioural control. We will test this hypothesis using a well-validated social cognition model, the theory of planned behaviour (TPB) that incorporates these constructs. Methods/design: We will develop theory-based surveys using standard methods based upon the TPB for the second and third replications, and survey a subsample of Ontario family physicians from each arm of the trial two months before and six months after the dissemination of the index edition of informed, the evidence based newsletter used for the interventions. In the third replication, our study will converge with the "TRY-ME" protocol (a second study conducted alongside the OPEM trial), in which the content of educational messages was constructed using both standard methods and methods informed by psychological theory. We will modify Dillman's total design method to maximise response rates. Preliminary analyses will initially assess the internal reliability of the measures and use regression to explore the relationships between predictor and dependent variable (intention to advise diabetic patients to have annual retinopathy screening and to prescribe thiazide diuretics for first line treatment of uncomplicated hypertension). We will then compare groups using methods appropriate for comparing independent samples to determine whether there have been changes in the predicted constructs (attitudes, subjective norms, or intentions) across the study groups as hypothesised, and will assess the convergence between the process evaluation results and the main trial results.The OPEM trial and OPEM process evaluation are funded by the Canadian Institute of Health Research (CIHR). The OPEM process evaluation study was developed as part of the CIHR funded interdisciplinary capacity enhancement team KT-ICEBeRG. Gaston Godin, Jeremy Grimshaw and France Légaré hold Canada Research Chairs. Louise Lemyre holds an R.S. McLaughlin Research Chair

    Fucking failures: The future of fat sex

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    In the context of the obesity ‘epidemic’ fat people’s sex lives are cast as sterile, sexually dysfunctional or just plain non-existent. This article analyzes medical discourses of obesity and sex in order to argue that fat sex is constructed as a type of failure. Using insights from antisocial queer theory, fat sex is further shown to be queer in its failure to adhere to the specifically heteronormative dictates of what Edelman (2004) calls ‘reproductive futurism’. The analysis finally engages with Halberstam’s (2011) notion of queer failure to demonstrate how deconstructing notions of success and failure might offer fat political projects new ways to imagine the future of fat sex

    Application of theory to enhance audit and feedback interventions to increase the uptake of evidence-based transfusion practice: an intervention development protocol

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    Background: Audits of blood transfusion demonstrate around 20% transfusions are outside national recommendations and guidelines. Audit and feedback is a widely used quality improvement intervention but effects on clinical practice are variable, suggesting potential for enhancement. Behavioural theory, theoretical frameworks of behaviour change and behaviour change techniques provide systematic processes to enhance intervention. This study is part of a larger programme of work to promote the uptake of evidence-based transfusion practice. Objectives: The objectives of this study are to design two theoretically enhanced audit and feedback interventions; one focused on content and one on delivery, and investigate the feasibility and acceptability. Methods: Study A (Content): A coding framework based on current evidence regarding audit and feedback, and behaviour change theory and frameworks will be developed and applied as part of a structured content analysis to specify the key components of existing feedback documents. Prototype feedback documents with enhanced content and also a protocol, describing principles for enhancing feedback content, will be developed. Study B (Delivery): Individual semi-structured interviews with healthcare professionals and observations of team meetings in four hospitals will be used to specify, and identify views about, current audit and feedback practice. Interviews will be based on a topic guide developed using the Theoretical Domains Framework and the Consolidated Framework for Implementation Research. Analysis of transcripts based on these frameworks will form the evidence base for developing a protocol describing an enhanced intervention that focuses on feedback delivery. Study C (Feasibility and Acceptability): Enhanced interventions will be piloted in four hospitals. Semi-structured interviews, questionnaires and observations will be used to assess feasibility and acceptability. Discussion: This intervention development work reflects the UK Medical Research Council’s guidance on development of complex interventions, which emphasises the importance of a robust theoretical basis for intervention design and recommends systematic assessment of feasibility and acceptability prior to taking interventions to evaluation in a full-scale randomised study. The work-up includes specification of current practice so that, in the trials to be conducted later in this programme, there will be a clear distinction between the control (usual practice) conditions and the interventions to be evaluated

    Linear-T resistivity and change in Fermi surface at the pseudogap critical point of a high-Tc superconductor

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    A fundamental question of high-temperature superconductors is the nature of the pseudogap phase which lies between the Mott insulator at zero doping and the Fermi liquid at high doping p. Here we report on the behaviour of charge carriers near the zero-temperature onset of that phase, namely at the critical doping p* where the pseudogap temperature T* goes to zero, accessed by investigating a material in which superconductivity can be fully suppressed by a steady magnetic field. Just below p*, the normal-state resistivity and Hall coefficient of La1.6-xNd0.4SrxCuO4 are found to rise simultaneously as the temperature drops below T*, revealing a change in the Fermi surface with a large associated drop in conductivity. At p*, the resistivity shows a linear temperature dependence as T goes to zero, a typical signature of a quantum critical point. These findings impose new constraints on the mechanisms responsible for inelastic scattering and Fermi surface transformation in theories of the pseudogap phase.Comment: 24 pages, 6 figures. Published in Nature Physics. Online at http://www.nature.com/nphys/journal/vaop/ncurrent/full/nphys1109.htm
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