26 research outputs found

    Cediranib combined with carboplatin and paclitaxel in patients with metastatic or recurrent cervical cancer (CIRCCa): a randomised, double-blind, placebo-controlled phase 2 trial

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    Background: Patients treated with standard chemotherapy for metastatic or relapsed cervical cancer respond poorly to conventional chemotherapy (response achieved in 20–30% of patients) with an overall survival of less than 1 year. High tumour angiogenesis and high concentrations of intratumoural VEGF are adverse prognostic features. Cediranib is a potent tyrosine kinase inhibitor of VEGFR1, 2, and 3. In this trial, we aimed to assess the effect of the addition of cediranib to carboplatin and paclitaxel chemotherapy in patients with metastatic or recurrent cervical cancer. Methods: In this randomised, double-blind, placebo-controlled phase 2 trial, which was done in 17 UK cancer treatment centres, patients aged 18 years or older initially diagnosed with metastatic carcinoma or who subsequently developed metastatic disease or local pelvic recurrence after radical treatment that was not amenable to exenterative surgery were recruited. Eligible patients received carboplatin AUC of 5 plus paclitaxel 175 mg/m2 by infusion every 3 weeks for a maximum of six cycles and were randomised centrally (1:1) through a minimisation approach to receive cediranib 20 mg or placebo orally once daily until disease progression. The stratification factors were disease site, disease-free survival after primary therapy or primary stage IVb disease, number of lines of previous treatment, Eastern Cooperative Oncology Group performance status, and investigational site. All patients, investigators, and trial personnel were masked to study drug allocation. The primary endpoint was progression-free survival. Efficacy analysis was by intention to treat, and the safety analysis included all patients who received at least one dose of study drug. This trial is registered with the ISCRTN registry, number ISRCTN23516549, and has been completed. Findings: Between Aug 19, 2010, and July 27, 2012, 69 patients were enrolled and randomly assigned to cediranib (n=34) or placebo (n=35). After a median follow-up of 24·2 months (IQR 21·9–29·5), progression-free survival was longer in the cediranib group (median 8·1 months [80% CI 7·4–8·8]) than in the placebo group (6·7 months [6·2–7·2]), with a hazard ratio (HR) of 0·58 (80% CI 0·40–0·85; one-sided p=0·032). Grade 3 or worse adverse events that occurred in the concurrent chemotherapy and trial drug period in more than 10% of patients were diarrhoea (five [16%] of 32 patients in the cediranib group vs one [3%] of 35 patients in the placebo group), fatigue (four [13%] vs two [6%]), leucopenia (five [16%] vs three [9%]), neutropenia (10 [31%] vs four [11%]), and febrile neutropenia (five [16%] vs none). The incidence of grade 2–3 hypertension was higher in the cediranib group than in the control group (11 [34%] vs four [11%]). Serious adverse events occurred in 18 patients in the placebo group and 19 patients in the cediranib group. Interpretation: Cediranib has significant efficacy when added to carboplatin and paclitaxel in the treatment of metastatic or recurrent cervical cancer. This finding was accompanied by an increase in toxic effects (mainly diarrhoea, hypertension, and febrile neutropenia)

    Development of a 50 W porous emitter electrospray thruster towards flight

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    A low power porous electrospray propulsion system (PET-50)has been developed and tested at the University of Southampton in collaboration with RHP Technology Austria and AVS UK.The thruster utilizes a 313-emitter array, a molybdenum extractor plate and stainless-steel porous reservoir, also working as distal electrode. The performance of the thruster has been characterized using electrical diagnostics, plume diagnostics, Time-of-Flight (ToF) mass spectrometry and direct thrust measurements. PET-50 demonstrated high beam current after onset, with maximum values of around +1.5/-1.5 mA at 3400 V. Assuming a 50 % monomer-dimer mix, the estimated thrust and specific impulse is ~180 ÎŒN and~5800 s with an input power of 5.5 W. The measured thrust time response depicted increase in thrust with increasing voltage, reaching ~175 ÎŒN at 5.5 W, in excellent agreement with that estimated solely from electrical measurements. Four thruster units operating together will produce a total thrust of ~0.7 mN consuming only ~22 W with thrust to power ratio of ~32 ÎŒN/W

    A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE)

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    DUNE Offline Computing Conceptual Design Report

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    This document describes Offline Software and Computing for the Deep Underground Neutrino Experiment (DUNE) experiment, in particular, the conceptual design of the offline computing needed to accomplish its physics goals. Our emphasis in this document is the development of the computing infrastructure needed to acquire, catalog, reconstruct, simulate and analyze the data from the DUNE experiment and its prototypes. In this effort, we concentrate on developing the tools and systems that facilitate the development and deployment of advanced algorithms. Rather than prescribing particular algorithms, our goal is to provide resources that are flexible and accessible enough to support creative software solutions as HEP computing evolves and to provide computing that achieves the physics goals of the DUNE experiment.This document describes the conceptual design for the Offline Software and Computing for the Deep Underground Neutrino Experiment (DUNE). The goals of the experiment include 1) studying neutrino oscillations using a beam of neutrinos sent from Fermilab in Illinois to the Sanford Underground Research Facility (SURF) in Lead, South Dakota, 2) studying astrophysical neutrino sources and rare processes and 3) understanding the physics of neutrino interactions in matter. We describe the development of the computing infrastructure needed to achieve the physics goals of the experiment by storing, cataloging, reconstructing, simulating, and analyzing ∌\sim 30 PB of data/year from DUNE and its prototypes. Rather than prescribing particular algorithms, our goal is to provide resources that are flexible and accessible enough to support creative software solutions and advanced algorithms as HEP computing evolves. We describe the physics objectives, organization, use cases, and proposed technical solutions

    DUNE Offline Computing Conceptual Design Report

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    This document describes Offline Software and Computing for the Deep Underground Neutrino Experiment (DUNE) experiment, in particular, the conceptual design of the offline computing needed to accomplish its physics goals. Our emphasis in this document is the development of the computing infrastructure needed to acquire, catalog, reconstruct, simulate and analyze the data from the DUNE experiment and its prototypes. In this effort, we concentrate on developing the tools and systems thatfacilitate the development and deployment of advanced algorithms. Rather than prescribing particular algorithms, our goal is to provide resources that are flexible and accessible enough to support creative software solutions as HEP computing evolves and to provide computing that achieves the physics goals of the DUNE experiment

    Reconstruction of interactions in the ProtoDUNE-SP detector with Pandora