Chemotherapy-induced dynamic gene expression changes in vivo are prognostic in ovarian cancer

This work was supported by Medical Research Scotland (FRG353 to VAS), the FP7-Directorate-General for Research and Innovation of the European Commission (EU HEALTH-F4-2012-305033 to Coordinating Action Systems Medicine to DJH); the Chief Scientist Office of Scotland (to DJH) and the Scottish Funding Council (to DJH and SPL).Background: The response of ovarian cancer patients to carboplatin and paclitaxel is variable, necessitating identification of biomarkers that can reliably predict drug sensitivity and resistance. In this study, we sought to identify dynamically controlled genes and pathways associated with drug response and its time dependence. Methods: Gene expression was assessed for 14 days post-treatment with carboplatin or carboplatin–paclitaxel in xenografts from two ovarian cancer models: platinum-sensitive serous adenocarcinoma-derived OV1002 and a mixed clear cell/endometrioid carcinoma-derived HOX424 with reduced sensitivity to platinum. Results: Tumour volume reduction was observed in both xenografts, but more dominantly in OV1002. Upregulated genes in OV1002 were involved in DNA repair, cell cycle and apoptosis, whereas downregulated genes were involved in oxygen-consuming metabolic processes and apoptosis control. Carboplatin–paclitaxel triggered a more comprehensive response than carboplatin only in both xenografts. In HOX424, apoptosis and cell cycle were upregulated, whereas Wnt signalling was inhibited. Genes downregulated after day 7 from both xenografts were predictive of overall survival. Overrepresented pathways were also predictive of outcome. Conclusions: Late expressed genes are prognostic in ovarian tumours in a dynamic manner. This longitudinal gene expression study further elucidates chemotherapy response in two models, stressing the importance of delayed biomarker detection and guiding optimal timing of biopsies.Publisher PDFPeer reviewe

Correlations vs connectivity in R-charge

The holographic relation between quantum correlations and connectivity of spacetime is explored for single R-charged AdS$_5$ black holes and their half-BPS limits (superstars). In a two boundary set-up, the wormhole between both universes reduces to a designable and computable quantum mechanical correlation between the dual microscopic degrees of freedom in the BPS limit. This quantum connectivity is seen as a naked singularity by a single sided observer. In a single boundary set-up, as a small step towards the description of entangled black holes, we describe quantum teleportation between two labs in different locations of the transverse 5-sphere using entangled gravitons in a reference state that provides a classical channel between both labs.Comment: 53 pages + appendices, 29 figures v2: few corrections and added a conclusion sectio

A three-model comparison of the relationship between quality, satisfaction and loyalty: an empirical study of the Chinese healthcare system

<p>Abstract</p> <p>Background</p> <p>Previous research has addressed the relationship between customer satisfaction, perceived quality and customer loyalty intentions in consumer markets. In this study, we test and compare three theoretical models of the quality–satisfaction–loyalty relationship in the Chinese healthcare system.</p> <p>Methods</p> <p>This research focuses on hospital patients as participants in the process of healthcare procurement. Empirical data were obtained from six Chinese public hospitals in Shanghai. A total of 630 questionnaires were collected in two studies. Study 1 tested the research instruments, and Study 2 tested the three models. Confirmatory factor analysis was used to assess the scales’ construct validity by testing convergent and discriminant validity. A structural equation model (SEM) specified the distinctions between each construct. A comparison of the three theoretical models was conducted via AMOS analysis.</p> <p>Results</p> <p>The results of the SEM demonstrate that quality and satisfaction are distinct concepts and that the first model (satisfaction mediates quality and loyalty) is the most appropriate one in the context of the Chinese healthcare environment.</p> <p>Conclusions</p> <p>In this study, we test and compare three theoretical models of the quality–satisfaction–loyalty relationship in the Chinese healthcare system. Findings show that perceived quality improvement does not lead directly to customer loyalty. The strategy of using quality improvement to maintain patient loyalty depends on the level of patient satisfaction. This implies that the measurement of patient experiences should include topics of importance for patients’ satisfaction with health care services.</p