1,326 research outputs found

    Translating tumor biology into personalized treatment planning: analytical performance characteristics of the Oncotype DX® Colon Cancer Assay

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    <p>Abstract</p> <p>Background</p> <p>The Onco<it>type </it>DX<sup>® </sup>Colon Cancer Assay is a new diagnostic test for determining the likelihood of recurrence in stage II colon cancer patients after surgical resection using fixed paraffin embedded (FPE) primary colon tumor tissue. Like the Onco<it>type </it>DX Breast Cancer Assay, this is a high complexity, multi-analyte, reverse transcription (RT) polymerase chain reaction (PCR) assay that measures the expression levels of specific cancer-related genes. By capturing the biology underlying each patient's tumor, the Onco<it>type </it>DX Colon Cancer Assay provides a Recurrence Score (RS) that reflects an individualized risk of disease recurrence. Here we describe its analytical performance using pre-determined performance criteria, which is a critical component of molecular diagnostic test validation.</p> <p>Results</p> <p>All analytical measurements met pre-specified performance criteria. PCR amplification efficiency for all 12 assays was high, ranging from 96% to 107%, while linearity was demonstrated over an 11 log<sub>2 </sub>concentration range for all assays. Based on estimated components of variance for FPE RNA pools, analytical reproducibility and precision demonstrated low SDs for individual genes (0.16 to 0.32 C<sub>T</sub>s), gene groups (≤0.05 normalized/aggregate C<sub>T</sub>s) and RS (≤1.38 RS units).</p> <p>Conclusions</p> <p>Analytical performance characteristics shown here for both individual genes and gene groups in the Onco<it>type </it>DX Colon Cancer Assay demonstrate consistent translation of specific biology of individual tumors into clinically useful diagnostic information. The results of these studies illustrate how the analytical capability of the Onco<it>type </it>DX Colon Cancer Assay has enabled clinical validation of a test to determine individualized recurrence risk after colon cancer surgery.</p

    Cell-Free DNA and CXCL10 Derived from Bronchoalveolar Lavage Predict Lung Transplant Survival.

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    Standard methods for detecting chronic lung allograft dysfunction (CLAD) and rejection have poor sensitivity and specificity and have conventionally required bronchoscopies and biopsies. Plasma cell-free DNA (cfDNA) has been shown to be increased in various types of allograft injury in transplant recipients and CXCL10 has been reported to be increased in the lung tissue of patients undergoing CLAD. This study used a novel cfDNA and CXCL10 assay to evaluate the noninvasive assessment of CLAD phenotype and prediction of survival from bronchoalveolar lavage (BAL) fluid. A total of 60 BAL samples (20 with bronchiolitis obliterans (BOS), 20 with restrictive allograft syndrome (RAS), and 20 with stable allografts (STA)) were collected from 60 unique lung transplant patients; cfDNA and CXCL10 were measured by the ELISA-based KIT assay. Median cfDNA was significantly higher in BOS patients (6739 genomic equivalents (GE)/mL) versus STA (2920 GE/mL) and RAS (4174 GE/mL) (p &lt; 0.01 all comparisons). Likelihood ratio tests revealed a significant association of overall survival with cfDNA (p = 0.0083), CXCL10 (p = 0.0146), and the interaction of cfDNA and CXCL10 (p = 0.023) based on multivariate Cox proportional hazards regression. Dichotomizing patients based on the median cfDNA level controlled for the mean level of CXCL10 revealed an over two-fold longer median overall survival time in patients with low levels of cfDNA. The KIT assay could predict allograft survival with superior performance compared with traditional biomarkers. These data support the pursuit of larger prospective studies to evaluate the predictive performance of cfDNA and CXCL10 prior to lung allograft failure

    Humour and laughter in meetings: influence, decision-making and the emergence of leadership

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    Recent constructions view leadership as a process of social influence which coordinates processes of change. Moreover, such processes are not necessarily linked to role hierarchy but may be emergent and distributed within teams. However, the micro-processes through which this occurs are not well understood. The significance of the paper lies in its contribution to an understanding of the emergence of leadership in teams, and in particular how humour and laughter are drawn on as a resource by which to exert social influence. Here, we use the construct of the play frame, &lsquo;non serious&rsquo; talk in which participants jointly construct extended humorous sequences as improvisations, to analyse how team members manoeuvre in order to accomplish influence, decision-making and leadership. In taking this approach we are not concerned with considerations of how managers use jokes to exercise control, or workers use humour to subvert management. Rather, we examine how humour, and particularly the laughter it engenders, can contribute to an understanding of organizations as centred on communication and founded on the precept that organizations are &lsquo;talked into being&rsquo;. Here we show how talk in a play frame institutes a context which can be utilised by participants to exert influence and we demonstrate the highly contingent and contextual nature of the emergence of leadership within teams

    Integrating technology into complex intervention trial processes: a case study

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    This is the final version of the article. Available from BioMed Central via the DOI in this record.Background Trials of complex interventions are associated with high costs and burdens in terms of paperwork, management, data collection, validation, and intervention fidelity assessment occurring across multiple sites. Traditional data collection methods rely on paper-based forms, where processing can be time-consuming and error rates high. Electronic source data collection can potentially address many of these inefficiencies, but has not routinely been used in complex intervention trials. Here we present the use of an on-line system for managing all aspects of data handling and for the monitoring of trial processes in a multicentre trial of a complex intervention. We custom built a web-accessible software application for the delivery of ENGAGE-HD, a multicentre trial of a complex physical therapy intervention. The software incorporated functionality for participant randomisation, data collection and assessment of intervention fidelity. It was accessible to multiple users with differing levels of access depending on required usage or to maintain blinding. Each site was supplied with a 4G-enabled iPad for accessing the system. The impact of this system was quantified through review of data quality and collation of feedback from site coordinators and assessors through structured process interviews. Results The custom-built system was an efficient tool for collecting data and managing trial processes. Although the set-up time required was significant, using the system resulted in an overall data completion rate of 98.5% with a data query rate of 0.1%, the majority of which were resolved in under a week. Feedback from research staff indicated that the system was highly acceptable for use in a research environment. This was a reflection of the portability and accessibility of the system when using the iPad and its usefulness in aiding accurate data collection, intervention fidelity and general administration. Conclusions A combination of commercially available hardware and a bespoke online database designed to support data collection, intervention fidelity and trial progress provides a viable option for streamlining trial processes in a multicentre complex intervention trial. There is scope to further extend the system to cater for larger trials and add further functionality such as automatic reporting facilities and participant management support.The ENGAGE-HD trial was funded by Health and Social Care Wales, United Kingdom. The South East Wales Trials Unit is funded by the Wales Assembly Government through Health and Care Research Wales

    A Far-Ultraviolet Survey of 47 Tucanae.II The Long-Period Cataclysmic Variable AKO 9

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    We present time-resolved, far-ultraviolet (FUV) spectroscopy and photometry of the 1.1 day eclipsing binary system AKO 9 in the globular cluster 47 Tucanae. The FUV spectrum of AKO 9 is blue and exhibits prominent C IV and He II emission lines. The spectrum broadly resembles that of long-period, cataclysmic variables in the galactic field. Combining our time-resolved FUV data with archival optical photometry of 47 Tuc, we refine the orbital period of AKO 9 and define an accurate ephemeris for the system. We also place constraints on several other system parameters, using a variety of observational constraints. We find that all of the empirical evidence is consistent with AKO 9 being a long-period dwarf nova in which mass transfer is driven by the nuclear expansion of a sub-giant donor star. We therefore conclude that AKO 9 is the first spectroscopically confirmed cataclysmic variable in 47 Tuc. We also briefly consider AKO 9's likely formation and ultimate evolution. Regarding the former, we find that the system was almost certainly formed dynamically, either via tidal capture or in a 3-body encounter. Regarding the latter, we show that AKO 9 will probably end its CV phase by becoming a detached, double WD system or by exploding in a Type Ia supernova.Comment: 40 pages, 11 figures, to appear in the Dec 20 issue of ApJ; minor changes to match final published versio

    The masses of the cataclysmic variables AC Cancri and V363 Aurigae

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    We present time-resolved spectroscopy and photometry of the double-lined eclipsing cataclysmic variables AC Cnc and V363 Aur (= Lanning 10). There is evidence of irradiation on the inner hemisphere of the secondary star in both systems, which we correct for using a model that reproduces the observations remarkably well. We find the radial velocity of the secondary star in AC Cnc to be KR= 176 ± 3 km s−1 and its rotational velocity to be v sin i= 135 ± 3 km s−1. From these parameters we obtain masses of M1= 0.76 ± 0.03 M⊙ for the white-dwarf primary and M2= 0.77 ± 0.05 M⊙ for the K2 ± 1V secondary star, giving a mass ratio of q= 1.02 ± 0.04. We measure the radial and rotational velocities of the G7 ± 2V secondary star in V363 Aur to be KR= 168 ± 5 km s−1 and v sin i= 143 ± 5 km s−1, respectively. The component masses of V363 Aur are M1= 0.90 ± 0.06 M⊙ and M2= 1.06 ± 0.11 M⊙, giving a mass ratio of q= 1.17 ± 0.07. The mass ratios for AC Cnc and V363 Aur fall within the theoretical limits for dynamically and thermally stable mass transfer. Both systems are similar to the SW Sex stars, exhibiting single-peaked emission lines with transient absorption features, high-velocity S-wave components and phase-offsets in their radial-velocity curves. The Balmer lines in V363 Aur show a rapid increase in flux around phase 0 followed by a rapid decrease, which we attribute to the eclipse of an optically thick region at the centre of the disc. This model could also account for the behaviour of other SW Sex stars where the Balmer lines show only a shallow eclipse compared to the continuum

    The component masses of the cataclysmic variable V347 Puppis

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    We present time-resolved spectroscopy and photometry of the double-lined eclipsing cataclysmic variable V347 Pup (=LB 1800). There is evidence of irradiation on the inner hemisphere of the secondary star, which we correct for using a model to give a secondary-star radial velocity of KR= 198 ± 5 km s−1. The rotational velocity of the secondary star in V347 Pup is found to be v sin i= 131 ± 5 km s−1 and the system inclination is i= 840 ± 23. From these parameters we obtain masses of M1= 0.63 ± 0.04 M⊙ for the white dwarf primary and M2= 0.52 ± 0.06 M⊙ for the M0.5V secondary star, giving a mass ratio of q= 0.83 ± 0.05. On the basis of the component masses, and the spectral type and radius of the secondary star in V347 Pup, we find tentative evidence for an evolved companion. V347 Pup shows many of the characteristics of the SW Sex stars, exhibiting single-peaked emission lines, high-velocity S-wave components and phase-offsets in the radial velocity curve. We find spiral arms in the accretion disc of V347 Pup and measure the disc radius to be close to the maximum allowed in a pressureless disc

    The dynamics of power and resistance in police interview discourse

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    This is a study of police interviewing using an integrated approach, drawing on CA, CDA and pragmatics. The study focuses on the balance of power and control, finding that in particular the institutional status of the participants, the discursive roles assigned to them by the context, and their relative knowledge, are significant factors affecting the dynamics of the discourse. Four discursive features are identified as particularly significant, and a detailed analysis of the complex interplay of these features shows that power and control are constantly under negotiation, and are always open to challenge and resistance. Further it is shown that discursive dominance is not necessarily advantageous to participants, due to the specific goals and purposes of the police interview context. A wider consideration of the context illustrates the contribution that linguistics can make to the use of police interview data as evidence in the UK criminal justice system
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