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  • 1
    Publication Date: 2016-04-17
    Description: Introduction The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of ‘isotoxic’ radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable. Methods and analysis Isotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5 years. Ethics and dissemination The study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West—Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally. Trial registration number NCT01836692; Pre-results.
    Keywords: Open access, Evidence based practice, Oncology, Radiology and imaging, Respiratory medicine
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 2
    Publication Date: 2014-08-21
    Description: Genetic diversity is the amount of variation observed between DNA sequences from distinct individuals of a given species. This pivotal concept of population genetics has implications for species health, domestication, management and conservation. Levels of genetic diversity seem to vary greatly in natural populations and species, but the determinants of this variation, and particularly the relative influences of species biology and ecology versus population history, are still largely mysterious. Here we show that the diversity of a species is predictable, and is determined in the first place by its ecological strategy. We investigated the genome-wide diversity of 76 non-model animal species by sequencing the transcriptome of two to ten individuals in each species. The distribution of genetic diversity between species revealed no detectable influence of geographic range or invasive status but was accurately predicted by key species traits related to parental investment: long-lived or low-fecundity species with brooding ability were genetically less diverse than short-lived or highly fecund ones. Our analysis demonstrates the influence of long-term life-history strategies on species response to short-term environmental perturbations, a result with immediate implications for conservation policies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Romiguier, J -- Gayral, P -- Ballenghien, M -- Bernard, A -- Cahais, V -- Chenuil, A -- Chiari, Y -- Dernat, R -- Duret, L -- Faivre, N -- Loire, E -- Lourenco, J M -- Nabholz, B -- Roux, C -- Tsagkogeorga, G -- Weber, A A-T -- Weinert, L A -- Belkhir, K -- Bierne, N -- Glemin, S -- Galtier, N -- England -- Nature. 2014 Nov 13;515(7526):261-3. doi: 10.1038/nature13685. Epub 2014 Aug 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] UMR 5554, Institute of Evolutionary Sciences, University Montpellier 2, Centre national de la recherche scientifique, Place E. Bataillon, 34095 Montpellier, France [2] Department of Ecology and Evolution, Biophore, University of Lausanne, 1015 Lausanne, Switzerland. ; 1] UMR 5554, Institute of Evolutionary Sciences, University Montpellier 2, Centre national de la recherche scientifique, Place E. Bataillon, 34095 Montpellier, France [2] UMR 7261, Institut de Recherches sur la Biologie de l'Insecte, Centre national de la recherche scientifique, Universite Francois-Rabelais, 37200 Tours, France. ; UMR 5554, Institute of Evolutionary Sciences, University Montpellier 2, Centre national de la recherche scientifique, Place E. Bataillon, 34095 Montpellier, France. ; Aix-Marseille Universite, Institut Mediterraneen de Biodiversite et d'Ecologie marine et continentale (IMBE) - CNRS - IRD - UAPV, 13007 Marseille, France. ; Department of Biology, University of South Alabama, Mobile, Alabama 36688-0002, USA. ; UMR 5558, Laboratoire de Biometrie et Biologie Evolutive, Universite Lyon 1, CNRS, 69622 Lyon, France. ; 1] UMR 5554, Institute of Evolutionary Sciences, University Montpellier 2, Centre national de la recherche scientifique, Place E. Bataillon, 34095 Montpellier, France [2] The School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK. ; 1] UMR 5554, Institute of Evolutionary Sciences, University Montpellier 2, Centre national de la recherche scientifique, Place E. Bataillon, 34095 Montpellier, France [2] Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25141177" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ecology ; *Evolution, Molecular ; Genetic Variation/*genetics ; *Genetics, Population ; Genome/*genetics ; *Genomics ; *Phylogeny
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2016-10-25
    Description: The fixation probability of a recessive beneficial mutation is increased on the X or Z chromosome, relative to autosomes, because recessive alleles carried by X or Z are exposed to selection in the heterogametic sex. This leads to an increased dN/dS ratio on sex chromosomes relative to autosomes, a pattern called the "fast-X" or "fast-Z" effect. Besides positive selection, the strength of genetic drift and the efficacy of purifying selection, which affect the rate of molecular evolution, might differ between sex chromosomes and autosomes. Disentangling the complex effects of these distinct forces requires the genome-wide analysis of polymorphism, divergence and gene expression data in a variety of taxa. Here we study the influence of hemizygosity of the Z chromosome in Maniola jurtina and Pyronia tithonus , two species of butterflies (Lepidoptera, Nymphalidae, Satyrinae). Using transcriptome data, we compare the strength of positive and negative selection between Z and autosomes accounting for sex-specific gene expression. We show that M. jurtina and P. tithonus do not experience a faster, but rather a slightly slower evolutionary rate on the Z than on autosomes. Our analysis failed to detect a significant difference in adaptive evolutionary rate between Z and autosomes, but comparison of male-biased, unbiased and female-biased Z-linked genes revealed an increased efficacy of purifying selection against recessive deleterious mutations in female-biased Z-linked genes. This probably contributes to the lack of fast-Z evolution of satyrines. We suggest that the effect of hemizygosity on the fate of recessive deleterious mutations should be taken into account when interpreting patterns of molecular evolution in sex chromosomes vs. autosomes.
    Electronic ISSN: 1759-6653
    Topics: Biology
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