658 research outputs found

    The use of national datasets to baseline science education reform: exploring value-added approaches

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    This paper uses data from the National Pupil Database to investigate the differences in ‘performance’ across the range of science courses available following the 2006 Key Stage 4 (KS4) science reforms in England. This is a value-added exploration (from Key Stage 3 [KS3] to KS4) aimed not at the student or the school level, but rather at that of the course. Different methodological approaches to carrying out such an analysis, ranging from simple non-contextualized techniques, to more complex fully contextualized multilevel models, are investigated and their limitations and benefits are evaluated. Important differences between courses are found in terms of the typical ‘value’ they add to the students studying them with particular applied science courses producing higher mean KS4 outcomes for the same KS3 level compared with other courses. The implications of the emergence of such differences, in a context where schools are judged to a great extent on their value-added performance, are discussed. The relative importance of a variety of student characteristics in determining KS4 outcomes are also investigated. Substantive findings are that across all types of course, science prior attainment at KS3, rather than that of mathematics or English, is the most important predictor of KS4 performance in science, and that students of lower socio-economic status consistently make less progress over KS4 than might be expected, despite prior attainment being accounted for in the modelling

    Playing safe: Assessing the risk of sexual abuse to elite child athletes

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    Young athletes frequently suffer from being seen as athletes first and children second. This has consequences for their legal, civil and human rights as children (Kelly et al., 1995) and for the way in which sport organisations choose to intervene on their behalf to protect them from physical, psychological and sexual abuses (Brackenridge, 1994). Sport careers peak at different ages depending on the sport: in some, children as young as 12 or 13 may reach the highest levels of competitive performance; in others, full maturity as an athlete may come late into adulthood or even middle age. Recognition of this variation has given rise to the concept of ‘sport age’ (Kirby, 1986) referring to sport-specific athlete development. This concept is of significance in helping to identify the developmental process in terms of athletic, rather than chronological, maturity. The risk of sexual abuse in sport, formerly ignored or denied, has now been documented in a number of studies, using both quantitative and qualitative methods (Kirby & Greaves, 1996; Brackenridge, 1997; Volkwein, 1996). Drawing on data from these studies and from the previous work on sport age and athletic maturation, this paper proposes a possible means of identifying and assessing relative risk of sexual abuse to elite young athletes in selected sports. The concept of a ‘stage of imminent achievement’ (SIA) is proposed as the period of peak vulnerability of young athletes to sexual abuse

    Ocean forced variability of Totten Glacier mass loss

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    This is the author accepted manuscript. The final version is available from the Geological Society of London via the DOI in this record.A large volume of the East Antarctic Ice Sheet drains through the Totten Glacier (TG) and is thought to be a potential source of substantial global sea level rise over the coming centuries. We show the surface velocity and heightof the floating part of TG, which buttresses the grounded component, have varied substantially over two decades (1989–2011), with variations in surface height strongly anti-correlated with simulated basal melt rates (r=0.70, p<0.05). Coupled glacier/ice-shelf simulations confirm ice flow and thickness respond to both basal melting of the ice shelf and grounding on bed obstacles. We conclude the observed variability of TG is primarily ocean-driven. Ocean warming in this region will lead to enhanced ice-sheet dynamism and loss of upstream grounded ice.This work was supported by, Australian Antarctic Division projects 3103, 4077, 4287 and 4346, National Computing Infrastructure grant m68, NSF grant ANT-0733025, NASA grant NNX09AR52G (Operation Ice Bridge), NERC grant NE/F016646/1, NERC fellowship NE/G012733/2, the Jackson School of Geoscience, the Jet Propulsion Laboratory and the G. Unger Vetlesen Foundation. This research was also supported by the Australian Government’s Cooperative Research Centres Programme through the Antarctic Climate & Ecosystems Cooperative Research Centre. The work is also supported under the Australian Research Councils Special Research Initiative for Antarctic Gateway Partnership SR140300001. Landsat 4 and 7 images courtesy of the U.S. Geological Survey. This is UTIG contribution 2486. Thanks to Benoit Legresy for useful discussions

    Images and nonlocal vortex pinning in thin superfluid films

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    For thin films of superfluid adsorbed on a disordered substrate, we derive the equation of motion for a vortex in the presence of a random potential within a mean field (Hartree) description of the condensate. The compressible nature of the condensate leads to an effective pinning potential experienced by the vortex which is nonlocal, with a long range tail that smoothes out the random potential coupling the condensate to the substrate. We interpret this nonlocality in terms of images, and relate the effective potential governing the dynamics to the pinning energy arising from the expectation value of the Hamiltonian with respect to the vortex wavefunction.Comment: 19 pages, revtex, to appear Phys. Rev.

    Measurement of the Deuteron Structure Function F2 in the Resonance Region and Evaluation of Its Moments

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    Inclusive electron scattering off the deuteron has been measured to extract the deuteron structure function F2 with the CEBAF Large Acceptance Spectrometer (CLAS) at the Thomas Jefferson National Accelerator Facility. The measurement covers the entire resonance region from the quasi-elastic peak up to the invariant mass of the final-state hadronic system W~2.7 GeV with four-momentum transfers Q2 from 0.4 to 6 (GeV/c)^2. These data are complementary to previous measurements of the proton structure function F2 and cover a similar two-dimensional region of Q2 and Bjorken variable x. Determination of the deuteron F2 over a large x interval including the quasi-elastic peak as a function of Q2, together with the other world data, permit a direct evaluation of the structure function moments for the first time. By fitting the Q2 evolution of these moments with an OPE-based twist expansion we have obtained a separation of the leading twist and higher twist terms. The observed Q2 behaviour of the higher twist contribution suggests a partial cancellation of different higher twists entering into the expansion with opposite signs. This cancellation, found also in the proton moments, is a manifestation of the "duality" phenomenon in the F2 structure function

    Conformational changes during human P2X7 receptor activation examined by structural modelling and cysteine-based cross-linking studies

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    The P2X7 receptor (P2X7R) is important in mediating a range of physiological functions and pathologies associated with tissue damage and inflammation and represents an attractive therapeutic target. However, in terms of their structure-function relationships, the mammalian P2X7Rs remain poorly characterised compared to some of their other P2XR counterparts. In this study, combining cysteine-based cross-linking and whole-cell patch-clamp recording, we examined six pairs of residues (A44/I331, D48/I331, I58/F311, S60/L320, I75/P177 and K81/V304) located in different parts of the extracellular and transmembrane domains of the human P2X7R. These residues are predicted to undergo substantial movement during the transition of the receptor ion channel from the closed to the open state, predictions which are made based on structural homology models generated from the crystal structures of the zebrafish P2X4R. Our results provide evidence that among the six pairs of cysteine mutants, D48C/I133C and K81C/V304C formed disulphide bonds that impaired the channel gating to support the notion that such conformational changes, particularly those in the outer ends of the transmembrane domains, are critical for human P2X7R activation

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    Paroxetine suppresses recombinant human P2X7 responses

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    P2X7 receptor (P2X7) activity may link inflammation to depressive disorders. Genetic variants of human P2X7 have been linked with major depression and bipolar disorders, and the P2X7 knockout mouse has been shown to exhibit anti-depressive-like behaviour. P2X7 is an ATP-gated ion channel and is a major regulator of the pro-inflammatory cytokine interleukin 1β (IL-1β) secretion from monocytes and microglia. We hypothesised that antidepressants may elicit their mood enhancing effects in part via modulating P2X7 activity and reducing inflammatory responses. In this study, we determined whether common psychoactive drugs could affect recombinant and native human P2X7 responses in vitro. Common antidepressants demonstrated opposing effects on human P2X7-mediated responses; paroxetine inhibited while fluoxetine and clomipramine mildly potentiated ATP-induced dye uptake in HEK-293 cells stably expressing recombinant human P2X7. Paroxetine inhibited dye uptake mediated by human P2X7 in a concentration-dependent manner with an IC50 of 24 μM and significantly reduces ATP-induced inward currents. We confirmed that trifluoperazine hydrochloride suppressed human P2X7 responses (IC50 of 6.4 μM). Both paroxetine and trifluoperazine did not inhibit rodent P2X7 responses, and mutation of a known residue (F 95L) did not alter the effect of either drug, suggesting neither drug binds at this site. Finally, we demonstrate that P2X7-induced IL-1β secretion from lipopolysaccharide (LPS)-primed human CD14+ monocytes was suppressed with trifluoperazine and paroxetine

    Impact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation

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    Pre-surgical studies allow study of the relationship between mutations and response of oestrogen receptor-positive (ER+) breast cancer to aromatase inhibitors (AIs) but have been limited to small biopsies. Here in phase I of this study, we perform exome sequencing on baseline, surgical core-cuts and blood from 60 patients (40 AI treated, 20 controls). In poor responders (based on Ki67 change), we find significantly more somatic mutations than good responders. Subclones exclusive to baseline or surgical cores occur in ∼30% of tumours. In phase II, we combine targeted sequencing on another 28 treated patients with phase I. We find six genes frequently mutated: PIK3CA, TP53, CDH1, MLL3, ABCA13 and FLG with 71% concordance between paired cores. TP53 mutations are associated with poor response. We conclude that multiple biopsies are essential for confident mutational profiling of ER+ breast cancer and TP53 mutations are associated with resistance to oestrogen deprivation therapy
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