1,994 research outputs found

    Mitoxantrone is superior to doxorubicin in a multiagent weekly regimen for patients older than 60 with high-grade lymphoma: results of a BNLI randomized trial of PAdriaCEBO versus PMitCEBO

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    A prospective, multicenter, randomized trial was undertaken to compare the efficacy and toxicity of adriamycin with mitoxantrone within a 6-drug combination chemotherapy regimen for elderly patients (older than 60 years) with high-grade non-Hodgkin lymphoma (HGL) given for a minimum of 8 weeks. A total of 516 previously untreated patients aged older than 60 years were randomized to receive 1 of 2 anthracycline-containing regimens: adriamycin, 35 mg/m2 intravenously (IV) on day 1 (n = 259), or mitoxantrone, 7 mg/m2 IV on day 1 (n = 257); with prednisolone, 50 mg orally on days 1 to 14; cyclophosphamide, 300 mg/m2 IV on day 1; etoposide, 150 mg/m2 IV on day 1; vincristine, 1.4 mg/m2 IV on day 8; and bleomycin, 10 mg/m2 IV on day 8. Each 2-week cycle was administered for a minimum of 8 weeks in the absence of progression. Forty-three patients were ineligible for analysis. The overall and complete remission rates were 78% and 60% for patients receiving PMitCEBO and 69% and 52% for patients receiving PAdriaCEBO (P = .05, P = .12, respectively). Overall survival was significantly better with PMitCEBO than PAdriaCEBO (P = .0067). However, relapse-free survival was not significantly different (P = .16). At 4 years, 28% of PAdriaCEBO patients and 50% of PMitCEBO patients were alive (P = .0001). Ann Arbor stage III/IV, World Health Organization performance status 2-4, and elevated lactate dehydrogenase negatively influenced overall survival from diagnosis. In conclusion, the PMitCEBO 8-week combination chemotherapy regimen offers high response rates, durable remissions, and acceptable toxicity in elderly patients with HGL

    A core outcome set for localised prostate cancer effectiveness trials : protocol for a systematic review of the literature and stakeholder involvement through interviews and a Delphi survey

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    Acknowledgements We would like to thank Professor Craig Ramsay, Professor Luke Vale, and Professor Vikki Entwistle for their comments on earlier drafts of the protocol. This study is funded by the Cancer Research Aberdeen and North East Scotland (CRANES) charity. Paula Williamson would like to acknowledge funding from the European Union Seventh Framework Programme (FP7/2007-2013, FP7/2007-2011) under grant agreement number 305081 for the COMET initiative, which provided support for this work.Peer reviewedPublisher PD

    Effects of present-day deglaciation in Iceland on mantle melt production rates

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    Ongoing deglaciation in Iceland not only causes uplift at the surface but also increases magma production at depth due to decompression of the mantle. Here we study glacially induced decompression melting using 3‐D models of glacial isostatic adjustment in Iceland since 1890. We find that the mean glacially induced pressure rate of change in the mantle increases melt production rates by 100–135%, or an additional 0.21–0.23 km3 of magma per year beneath Iceland. Approximately 50% of this melt is produced underneath central Iceland. The greatest volumetric increase is found directly beneath Iceland's largest ice cap, Vatnajökull, colocated with the most productive volcanoes. Our models of the effect of deglaciation on mantle melting predict a significantly larger volumetric response than previous models which only considered the effect of deglaciation of Vatnajökull, and only mantle melting directly below Vatnajökull. Although the ongoing deglaciation significantly increases the melt production rate, the increase in melt supply rate at the base of the lithosphere is delayed and depends on the melt ascent velocity through the mantle. Assuming that 25% of the melt reaches the surface, the upper limit on our deglaciation‐induced melt estimates for central Iceland would be equivalent to an eruption the size of the 2010 Eyjafjallajökull summit eruption every seventh year

    Nontyphoidal salmonella disease: current status of vaccine research and development

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    Among more than 2500 nontyphoidal Salmonella enterica (NTS) serovars, S. enterica serovar Typhimurium and S. enterica serovar Enteritidis account for approximately fifty percent of all human isolates of NTS reported globally. The global incidence of NTS gastroenteritis in 2010 was estimated to be 93 million cases, approximately 80 million of which were contracted via food-borne transmission. It is estimated that 155,000 deaths resulted from NTS in 2010. NTS also causes severe, extra-intestinal, invasive bacteremia, referred to as invasive nontyphoidal Salmonella (iNTS) disease. iNTS disease usually presents as a febrile illness, frequently without gastrointestinal symptoms, in both adults and children. Symptoms of iNTS are similar to malaria, often including fever (\u3e90%) and splenomegaly (\u3e40%). The underlying reasons for the high rates of iNTS disease in Africa are still being elucidated. Evidence from animal and human studies supports the feasibility of developing a safe and effective vaccine against iNTS. Both antibodies and complement can kill Salmonella species in vitro. Proof-of-principle studies in animal models have demonstrated efficacy for live attenuated and subunit vaccines that target the O-antigens, flagellin proteins, and other outer membrane proteins of serovars Typhimurium and Enteritidis. More recently, a novel delivery strategy for NTS vaccines has been developed: the Generalized Modules for Membrane Antigens (GMMA) technology which presents surface polysaccharides and outer membrane proteins in their native conformation. GMMA technology is self-adjuvanting, as it delivers multiple pathogen-associated molecular pattern molecules. GMMA may be particularly relevant for low- and middle-income countries as it has the potential for high immunologic potency at a low cost and involves a relatively simple production process without the need for complex conjugation. Several vaccines for the predominant NTS serovars Typhimurium and Enteritidis, are currently under development
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