40 research outputs found

    Progressive Focusing and Trustworthiness in Qualitative Research: The Enabling Role of Computer-Assisted Qualitative Data Analysis Software (CAQDAS)

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    * The business and management community increasingly recognises that qualitative research is a ‘messy’, non-linear and often unpredictable undertaking. Yet, a considerable proportion of the qualitative research published in top journals is still presented as the result of a linear, predictable research process, thus wrongly suggesting deductive reasoning. * In this paper, we focus on a particular type of ‘messiness’ where during fieldwork, the research context is revealed to be more complex than anticipated, forcing the researcher to gradually refine/shift their focus to reflect ‘what really matters’. We adopt Stake’s notion of progressive focusing for this gradual approach. * Progressive focusing is well-suited to qualitative research in international business requiring complex iteration between theory and data, and the truthful yet coherent presentation of the research process. We propose that this dual challenge of complexity and trustworthiness may be addressed by using computer-assisted qualitative data analysis software (CAQDAS). * We present conceptual considerations and guidelines and offer a view on a ‘messy’, non-linear doctoral research project conducted using a progressive focusing approach, to demonstrate how CAQDAS can help to develop and re-negotiate insights from theory and interview data, as well as enhance trustworthiness, transparency and publication potential

    A robust immunoassay for anti-interferon autoantibodies that is highly specific for patients with autoimmune polyglandular syndrome type 1

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    A robust immunoassay for anti-interferon autoantibodies that is highly specific for patients with autoimmune polyglandular syndrome type 1

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    High titer antibodies to type 1 interferons have been recently reported as being highly specific for patients with autoimmune polyglandular syndrome type 1 (APS1) in Finnish and Norwegian patients with mutations in the AIRE gene. Those studies employed a complex neutralization assay to define the type 1 interferon autoantibodies. Here we have established a competitive europium time resolved fluorescence assay for IFN-alpha autoantibodies and measured sera from subjects with APS1, first degree relatives of APS1 patients, patients with Addison's disease or Type 1 diabetes. The europium-based immunoassay utilizes plate bound human IFN-alpha incubated with sera with or without competition with fluid phase IFN-alpha, followed by anti-IgG biotinytated antibody and detection with streptavidin-europium. The index of IFN-alpha Ab was calculated as (CPS (Counts per second) without competition-CPS with competition) / (CPS positive standard sera without competition-CPS positive standard sera with competition). Results are reported for raw CPS and indices and are compared across the different subjects. Results: For normal controls (n=100) CPS without competition were 31,237 17,328 CPS while after subtracting the competition value, the results were -6563 +/- 10,303 CPS. The initial APS1 patient (used to create the index as 1.0) gave 394,063 CPS without competition and a delta of 363,662 31,587 CPS with competition. Scatchard plot analysis of this patient sample revealed a high avidity for IFN-alpha (K-d of 0.5 nM). The CPS, delta, and index for 6/7 APS1 patients were strongly positive and 3 standard deviations or more above that of the normal controls. Using a cut-off of 2 standard deviations above normal controls, relatives of APS1 patients were negative for type I interferon autoantibodies as were 71 patients with Addison's disease (non-APS1) and 141 Type 1 diabetes patients. This simple high throughput competitive europium time resolved fluorescence assay had a sensitivity of >= 86% or greater and a specificity of >99.5%. (C) 2007 Elsevier Inc. All rights reserved

    Atovaquone: An Inhibitor of Oxidative Phosphorylation as Studied in Gynecologic Cancers

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    Oxidative phosphorylation is an active metabolic pathway in cancer. Atovaquone is an oral medication that inhibits oxidative phosphorylation and is FDA-approved for the treatment of malaria. We investigated its potential anti-cancer properties by measuring cell proliferation in 2D culture. The clinical formulation of atovaquone, Mepron, was given to mice with ovarian cancers to monitor its effects on tumor and ascites. Patient-derived cancer stem-like cells and spheroids implanted in NSG mice were treated with atovaquone. Atovaquone inhibited the proliferation of cancer cells and ovarian cancer growth in vitro and in vivo. The effect of atovaquone on oxygen radicals was determined using flow and imaging cytometry. The oxygen consumption rate (OCR) in adherent cells was measured using a Seahorse XFe96 Extracellular Flux Analyzer. Oxygen consumption and ATP production were inhibited by atovaquone. Imaging cytometry indicated that the majority of the oxygen radical flux triggered by atovaquone occurred in the mitochondria. Atovaquone decreased the viability of patient-derived cancer stem-like cells and spheroids implanted in NSG mice. NMR metabolomics showed shifts in glycolysis, citric acid cycle, electron transport chain, phosphotransfer, and metabolism following atovaquone treatment. Our studies provide the mechanistic understanding and preclinical data to support the further investigation of atovaquone’s potential as a gynecologic cancer therapeutic
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