Chakravarthy U.,Queens University of Belfast
Bevacizumab has been suggested to have similar effectiveness to ranibizumab for treatment of neovascular age-related macular degeneration. The Inhibition of VEGF in Age-related choroidal Neovascularisation (IVAN) trial was designed to compare these drugs and different regimens. Here, we report the findings at the prespecified 2-year timepoint. In a multicentre, 2×2 factorial, non-inferiority randomised trial, we enrolled adults aged at least 50 years with active, previously untreated neovascular age-related macular degeneration and a best corrected distance visual acuity (BCVA) of at least 25 letters from 23 hospitals in the UK. Participants were randomly assigned (1:1:1:1) to intravitreal injections of ranibizumab (0·5 mg) or bevacizumab (1·25 mg) in continuous (every month) or discontinuous (as needed) regimens, with monthly review. Study participants and clinical assessors were masked to drug allocation. Allocation to continuous or discontinuous treatment was masked up to 3 months, at which point investigators and participants were unmasked. The primary outcome was BCVA at 2 years, with a prespecified non-inferiority limit of 3·5 letters. The primary safety outcome was arterial thrombotic event or hospital admission for heart failure. Analyses were by modified intention to treat. This trial is registered, number ISRCTN92166560. Between March 27, 2008, and Oct 15, 2010, 628 patients underwent randomisation. 18 were withdrawn; 610 received study drugs (314 ranibizumab; 296 bevacizumab) and were included in analyses. 525 participants reached the visit at 2 years: 134 ranibizumab in continuous regimen, 137 ranibizumab in discontinuous regimen, 127 bevacizumab in continuous regimen, and 127 bevacizumab in discontinuous regimen. For BCVA, bevacizumab was neither non-inferior nor inferior to ranibizumab (mean difference -1·37 letters, 95% CI -3·75 to 1·01; p=0·26). Discontinuous treatment was neither non-inferior nor inferior to continuous treatment (-1·63 letters, -4·01 to 0·75; p=0·18). Frequency of arterial thrombotic events or hospital admission for heart failure did not differ between groups given ranibizumab (20 [6%] of 314 participants) and bevacizumab (12 [4%] of 296; odds ratio [OR] 1·69, 95% CI 0·80-3·57; p=0·16), or those given continuous (12 [4%] of 308) and discontinuous treatment (20 [7%] of 302; 0·56, 0·27-1·19; p=0·13). Mortality was lower with continuous than discontinuous treatment (OR 0·47, 95% CI 0·22-1·03; p=0·05), but did not differ by drug group (0·96, 0·46-2·02; p=0·91). Ranibizumab and bevacizumab have similar efficacy. Reduction in the frequency of retreatment resulted in a small loss of efficacy irrespective of drug. Safety was worse when treatment was administered discontinuously. These findings highlight that the choice of anti-VEGF treatment strategy is less straightforward than previously thought. UK National Institute for Health Research Health Technology Assessment programme. Copyright © 2013 Chakravarthy et al. Open Access article distributed under the terms of CC BY-NC-SA. Published by Elsevier Ltd. All rights reserved. Source
Blaauw M.,Queens University of Belfast
Quaternary Science Reviews
Tuning is a widespread technique to combine, date and interpret multiple fossil proxy archives through aligning supposedly synchronous events between the archives. The approach will be reviewed by discussing a number of literature examples, ranging from peat and tephra layers to orbital tuning and δ 18O series from marine and ice deposits. Potential problems will be highlighted such as the dangers of circular reasoning and unrecognised chronological uncertainties, and some solutions suggested. Fossil proxy research could become enhanced if tuning were approached in a more quantitative, reliable and objective way, and especially if individual proxy archives were non-tuned and kept on independent time-scales. © 2010 Elsevier Ltd. Source
Queen's University of Belfast | Date: 2014-04-09
This invention relates to base oils for lubricating compositions. In particular, the present invention provides a process for the selective oligomerisation of C
Queen's University of Belfast | Date: 2014-04-30
A method of ageing a catalyst material includes at least the steps of: (a) heating a gaseous stream; (b) adding a least one pure hydrocarbon gas and an oxygen-containing gas to the heated gaseous stream to provide a combined stream; and (c) passing the combined stream through the catalyst material. The use of at least one pure hydrocarbon gas and an oxygen-containing gas allows maximum re-circulation of the exit stream from the catalyst material for reuse, while maintaining the correct C, H and O proportions being provided in the combined stream to replicate realistic use of the catalyst material.
Queen's University of Belfast | Date: 2013-12-09
The present invention is directed to an amphipathic peptide and methods of using the amphipathic peptide for delivering small molecule agents to a cell. Ideally, the amphipathic cell penetrating peptide comprises less than approximately 50 amino acid residues with at least 6 arginine residues, at least 12 Alanine Residues, at least 6 leucine resiues, optionally at least one cysteine residue, and at least two but no greater than three glutamic acids wherein the arginine residues are evenly distributed along the length of the peptide; and the peptide has a defined ratio of arginine to negatively charged amino acid residues and a defined ratio of hydrophilic amino acid residues to hydrophobic amino acid residues. The present invention is also directed to a nanoparticle and cell delivery system comprising the amph ipathic cell penetrating peptide of the invention. The peptide, nanoparticle or cell delivery sys tem of the invention may be used in therapy. For example, the peptide may be used as a therapeutic agent delivery system, in which the therapeutic agent may include nucleic acids or other small molecules.