47 research outputs found

    Istres – Le Castellan

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    Identifiant de l'opération archéologique : 8341 Date de l'opération : 2007 (PR) Inventeur(s) : Armit Ian (SUP) ; Horsley Tim (SUP) ; Marty Frédéric (COL) Une campagne de prospection géophysique a été conduite sur l’habitat gaulois du Castellan à Istres 1 afin de déterminer la validité des méthodes mises en œuvre pour les habitats groupés de l’âge du Fer, dans la région (Fig. n°1 : Plan du site du Castellan avec localisation de la campagne de prospection géophysique). La prospection électriqu..

    Istres – Le Castellan

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    Identifiant de l'opération archéologique : 8341 Date de l'opération : 2007 (PR) Inventeur(s) : Armit Ian (SUP) ; Horsley Tim (SUP) ; Marty Frédéric (COL) Une campagne de prospection géophysique a été conduite sur l’habitat gaulois du Castellan à Istres 1 afin de déterminer la validité des méthodes mises en œuvre pour les habitats groupés de l’âge du Fer, dans la région (Fig. n°1 : Plan du site du Castellan avec localisation de la campagne de prospection géophysique). La prospection électriqu..

    ‘Our Care through our Eyes’: a mixed methods,evaluative study of a service user,co-produced education programme to improve inpatient care of children and young people admitted following self-harm

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    Introduction: Within Europe, the UK has one of the highest rates of self-harm, with a particularly high prevalence in children and young people (CYP). CYP who are admitted to paediatric hospital wards with self-harm are cared for by registered children's nurses who have been identified to lack specific training in caring for this patient group. This may impede the delivery of high quality care. Therefore, this study aims to co-produce, implement and evaluate an education programme for registered children's nurses to improve their knowledge, attitudes and confidence when caring for CYP admitted with self-harm. Methods and analysis: This mixed-methods evaluative study will involve a three-stage design. Stage 1: A priority-setting workshop will be conducted with 19 registered children's nurses. A Delphi technique will be used to establish consensus of information needs. Stage 2: An online educational intervention will be co-produced with 25 CYP and 19 registered children's nurses based on the priorities identified in Stage 1. Stage 3: The intervention will be implemented and evaluated with 250 registered children's nurses at a single hospital. Online Likert scale questionnaires will be administered at baseline and postintervention to assess levels of knowledge, attitudes and confidence in caring for CYP who self-harm. Descriptive and inferential statistics will be used to analyse the data. Statistical significance will be assessed at the 5% (two-sided) level. One-to-one qualitative interviews will also be undertaken with approximately 25 participants to explore any perceived impact on clinical practice. An interpretive descriptive approach will guide qualitative data collection and analysis. Ethics and dissemination: This study aims to develop, trial and evaluative a service-user, co-produced education programme for acute hospital registered children's nurses to improve the care of CYP admitted due to self-harm. The study has ethical approval from the National Health Services Research Ethics Committee and full governance clearance

    Gristhorpe Man: an Early Bronze Age log-coffin burial scientifically defined

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    © 2010 Antiquity PublicationsA log-coffin excavated in the early nineteenth century proved to be well enough preserved in the early twenty-first century for the fill armoury of modern scientific investigation to give its occupants and contents new identity, new origins and a new date. In many ways the interpretation is much the same as before: a local big man buried looking out to sea. Modern analytical techniques can create a person more real, more human and more securely anchored in history. This research team shows how.The project has been funded by grants from the British Academy, British Association for the Advancement of Science, Natural Environment Research Council, Royal Archaeological Institute and Scarborough Museums Trust. CJK’s participation in this project was funded by a Leverhulme Research Fellowship (RF/6/RFG/2008/0253)

    Quantitative Trait Loci for Bone Lengths on Chromosome 5 Using Dual Energy X-Ray Absorptiometry Imaging in the Twins UK Cohort

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    Human height is a highly heritable and complex trait but finding important genes has proven more difficult than expected. One reason might be the composite measure of height which may add heterogeneity and noise. The aim of this study was to conduct a genome-wide linkage scan to identify quantitative trait loci (QTL) for lengths of spine, femur, tibia, humerus and radius. These were investigated as alternative measures for height in a large, population–based twin sample with the potential to find genes underlying bone size and bone diseases. 3,782 normal Caucasian females, 18–80 years old, with whole body dual energy X-ray absorptiometry (DXA) images were used. A novel and reproducible method, linear pixel count (LPC) was used to measure skeletal sizes on DXA images. Intraclass correlations and heritability estimates were calculated for lengths of spine, femur, tibia, humerus and radius on monozygotic (MZ; n = 1,157) and dizygotic (DZ; n = 2,594) twins. A genome-wide linkage scan was performed on 2000 DZ twin subjects. All skeletal sites excluding spine were highly correlated. Intraclass correlations showed results for MZ twins to be significantly higher than DZ twins for all traits. Heritability results were as follows: spine, 66%; femur, 73%; tibia, 65%; humerus, 57%; radius, 68%. Results showed reliable evidence of highly suggestive linkage on chromosome 5 for spine (LOD score  =  3.0) and suggestive linkage for femur (LOD score  =  2.19) in the regions of 105cM and 155cM respectively. We have shown strong heritability of all skeletal sizes measured in this study and provide preliminary evidence that spine length is linked to the chromosomal region 5q15-5q23.1. Bone size phenotype appears to be more useful than traditional height measures to uncover novel genes. Replication and further fine mapping of this region is ongoing to determine potential genes influencing bone size and diseases affecting bone

    A Method for Determining Skeletal Lengths from DXA Images

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    <p>Abstract</p> <p>Background</p> <p>Skeletal ratios and bone lengths are widely used in anthropology and forensic pathology and hip axis length is a useful predictor of fracture. The aim of this study was to show that skeletal ratios, such as length of femur to height, could be accurately measured from a DXA (dual energy X-ray absorptiometry) image.</p> <p>Methods</p> <p>90 normal Caucasian females, 18–80 years old, with whole body DXA data were used as subjects. Two methods, linear pixel count (LPC) and reticule and ruler (RET) were used to measure skeletal sizes on DXA images and compared with real clinical measures from 20 subjects and 20 x-rays of the femur and tibia taken in 2003.</p> <p>Results</p> <p>Although both methods were highly correlated, the LPC inter- and intra-observer error was lower at 1.6% compared to that of RET at 2.3%. Both methods correlated positively with real clinical measures, with LPC having a marginally stronger correlation coefficient (r<sup>2 </sup>= 0.94; r<sup>2 </sup>= 0.84; average r<sup>2 </sup>= 0.89) than RET (r<sup>2 </sup>= 0.86; r<sup>2 </sup>= 0.84; average r<sup>2 </sup>= 0.85) with X-rays and real measures respectively. Also, the time taken to use LPC was half that of RET at 5 minutes per scan.</p> <p>Conclusion</p> <p>Skeletal ratios can be accurately and precisely measured from DXA total body scan images. The LPC method is easy to use and relatively rapid. This new phenotype will be useful for osteoporosis research for individuals or large-scale epidemiological or genetic studies.</p

    Identification of PLCL1 Gene for Hip Bone Size Variation in Females in a Genome-Wide Association Study

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    Osteoporosis, the most prevalent metabolic bone disease among older people, increases risk for low trauma hip fractures (HF) that are associated with high morbidity and mortality. Hip bone size (BS) has been identified as one of the key measurable risk factors for HF. Although hip BS is highly genetically determined, genetic factors underlying the trait are still poorly defined. Here, we performed the first genome-wide association study (GWAS) of hip BS interrogating ∼380,000 SNPs on the Affymetrix platform in 1,000 homogeneous unrelated Caucasian subjects, including 501 females and 499 males. We identified a gene, PLCL1 (phospholipase c-like 1), that had four SNPs associated with hip BS at, or approaching, a genome-wide significance level in our female subjects; the most significant SNP, rs7595412, achieved a p value of 3.72×10−7. The gene's importance to hip BS was replicated using the Illumina genotyping platform in an independent UK cohort containing 1,216 Caucasian females. Two SNPs of the PLCL1 gene, rs892515 and rs9789480, surrounded by the four SNPs identified in our GWAS, achieved p values of 8.62×10−3 and 2.44×10−3, respectively, for association with hip BS. Imputation analyses on our GWAS and the UK samples further confirmed the replication signals; eight SNPs of the gene achieved combined imputed p values<10−5 in the two samples. The PLCL1 gene's relevance to HF was also observed in a Chinese sample containing 403 females, including 266 with HF and 177 control subjects. A SNP of the PLCL1 gene, rs3771362 that is only ∼0.6 kb apart from the most significant SNP detected in our GWAS (rs7595412), achieved a p value of 7.66×10−3 (odds ratio = 0.26) for association with HF. Additional biological support for the role of PLCL1 in BS comes from previous demonstrations that the PLCL1 protein inhibits IP3 (inositol 1,4,5-trisphosphate)-mediated calcium signaling, an important pathway regulating mechanical sensing of bone cells. Our findings suggest that PLCL1 is a novel gene associated with variation in hip BS, and provide new insights into the pathogenesis of HF

    VX-659–Tezacaftor–Ivacaftor in patients with cystic fibrosis and one or two Phe508del alleles

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    BACKGROUND: The next-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector VX-659, in triple combination with tezacaftor and ivacaftor (VX-659–tezacaftor–ivacaftor), was developed to restore the function of Phe508del CFTR protein in patients with cystic fibrosis. METHODS: We evaluated the effects of VX-659–tezacaftor–ivacaftor on the processing, trafficking, and function of Phe508del CFTR protein using human bronchial epithelial cells. A range of oral VX-659–tezacaftor–ivacaftor doses in triple combination were then evaluated in randomized, controlled, double-blind, multicenter trials involving patients with cystic fibrosis who were heterozygous for the Phe508del CFTR mutation and a minimal-function CFTR mutation (Phe508del–MF genotypes) or homozygous for the Phe508del CFTR mutation (Phe508del–Phe508del genotype). The primary end points were safety and the absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV1). RESULTS: VX-659–tezacaftor–ivacaftor significantly improved the processing and trafficking of Phe508del CFTR protein as well as chloride transport in vitro. In patients, VX-659–tezacaftor–ivacaftor had an acceptable safety and side-effect profile. Most adverse events were mild or moderate. VX-659–tezacaftor–ivacaftor resulted in significant mean increases in the percentage of predicted FEV1 through day 29 (P<0.001) of up to 13.3 points in patients with Phe508del–MF genotypes; in patients with the Phe508del–Phe508del genotype already receiving tezacaftor–ivacaftor, adding VX-659 resulted in a further 9.7-point increase in the percentage of predicted FEV1. The sweat chloride concentrations and scores on the respiratory domain of the Cystic Fibrosis Questionnaire–Revised improved in both patient populations. CONCLUSIONS: Robust in vitro activity of VX-659–tezacaftor–ivacaftor targeting Phe508del CFTR protein translated into improvements for patients with Phe508del–MF or Phe508del–Phe508del genotypes. VX-659 triple-combination regimens have the potential to treat the underlying cause of disease in approximately 90% of patients with cystic fibrosis. (Funded by Vertex Pharmaceuticals; VX16-659-101 and VX16-659-001 ClinicalTrials.gov numbers, NCT03224351. opens in new tab and NCT03029455. opens in new tab.

    Academic research into marketing: many publications, but little impact?

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    This article reviews some issues associated with the way in which academic research into marketing is evaluated by UK education authorities using their Research Excellence Framework (REF), in particular the impact component of the assessment. It discusses the extent to which research by marketing academics published in leading academic journals is relevant to the concerns of marketing management and how this relevance or lack of it may be reflected in the relative paucity of impact submissions in marketing. It considers the model of impact assessment used in the REF and how this differs from how marketing academics work in practice, giving three examples of significant impact that would not be acceptable under current rules. It concludes by suggesting that alternative models for impact should be investigated and suggests that using more practical models might result in better engagement of marketing academics with business, leading to greater relevance in teaching and employability of marketing graduates
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