391 research outputs found

    Measurement-induced focusing and the magnitude of loss aversion:The difference between comparing gains to losses and losses to gains

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    Research has identified loss aversion as a strong and robust phenomenon, but has also revealed some moderators affecting the magnitude of its effect on decision making. In the current article, we draw attention to the fact that even the measurement of loss aversion itself may affect its magnitude by inducing a focus on either losses or gains. In three studies, we provide empirical evidence for such a measurement-induced focus. In all studies we used coin-toss gambles---in which there is a 50/50 chance to win or to lose---to assess gain/loss ratios as a measure of loss aversion. Participants either filled out the loss side or the gain side of this gain/loss ratio. The studies consistently showed that---using within- and between-subject designs and anticipated and real coin-toss gambles---the strength of loss aversion depended on the measurement format (fill-in-the-loss versus fill-in-the-gain); filling in the loss side increased loss aversion. Moreover, loss aversion was more affected by the stakes of the gamble in the fill-in-the-loss format than in the fill-in-the-gain format

    Loss of treatment benefit due to low compliance with bisphosphonate therapy

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    Among 8,822 new female bisphosphonate users, non-compliant bisphosphonate use was associated with a 45% increased risk of osteoporotic fracture compared to compliant use (MPR ≥80%). Classifying compliance into five categories, fracture risk gradually increased with poorer compliance. These results emphasize the importance of treatment compliance in obtaining maximal treatment benefit. Introduction: Bisphosphonates are widely used to treat osteoporosis and reduce fracture risk. Low compliance is frequent and will limit treatment benefit. Methods: New female users of alendronate or risedronate between 1999-2004, aged ≥45 years were identified from PHARMO-RLS, including drug-dispensing and hospitalization data of ≥2 million residents of the Netherlands. Patients were followed until first hospitalisation for an osteoporotic fracture, death, or end of study period. Compliance with bisphosphonates during follow-up was measured over 90-day intervals using Medication Possession Ratio (MPR). The association between compliance and fracture risk was analyzed using time-dependent Cox-regression. Results: The study cohort included 8,822 new female bisphosphonate users, contributing in total 22,484 person-years of follow-up. During follow-up, 176 osteoporotic fractures occurred (excluding the first six months). Non-compliant bisphosphonate use was associated with a 45% increased fracture risk compared to compliant use (MPR ≥80%). Classifying compliance into five categories, fracture risk gradually increased with poorer compliance (p-value <0.05 for trend). A MPR <20% was associated with an 80% increased fracture risk compared to a MPR ≥90%. Conclusions: These results show a statistically significant association between level of compliance with bisphosphonates and level of fracture risk, emphasizing the importance of treatment compliance in obtaining maximal treatment benefit

    Computer investigation of the energy landscape of amorphous silica

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    The multidimensional topography of the collective potential energy function of a so-called strong glass former (silica) is analyzed by means of classical molecular dynamics calculations. Features qualitatively similar to those of fragile glasses are recovered at high temperatures : in particular an intrinsic characteristic temperature Tc3500T_c\simeq 3500K is evidenced above which the system starts to investigate non-harmonic potential energy basins. It is shown that the anharmonicities are essentially characterized by a roughness appearing in the potential energy valleys explored by the system for temperatures above TcT_c.Comment: 5 pages; accepted for publication in PR

    Convergence of cMyc and β-catenin on Tcf7l1 enables endoderm specification.

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    The molecular machinery that directs formation of definitive endoderm from pluripotent stem cells is not well understood. Wnt/β-catenin and Nodal signalling have been implicated, but the requirements for lineage specification remain incompletely defined. Here, we demonstrate a potent effect of inhibiting glycogen synthase kinase 3 (GSK3) on definitive endoderm production. We find that downstream of GSK3 inhibition, elevated cMyc and β-catenin act in parallel to reduce transcription and DNA binding, respectively, of the transcriptional repressor Tcf7l1. Tcf7l1 represses FoxA2, a pioneer factor for endoderm specification. Deletion of Tcf7l1 is sufficient to allow upregulation of FoxA2 in the presence of Activin. In wild-type cells, cMyc contributes by reducing Tcf7l1 mRNA, while β-catenin acts on Tcf7l1 protein. GSK3 inhibition is further required for consolidation of endodermal fate via upregulation of Sox17, highlighting sequential roles for Wnt signalling. The identification of a cMyc/β-catenin-Tcf7l1-FoxA2 axis reveals a de-repression mechanism underlying endoderm induction that may be recapitulated in other developmental and patho-logical contexts.This study was funded by the Juvenile Diabetes Research Foundation International, the European Commission FP7 project BetaCellTherapy (agreement No. 241883), a core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute, and a University of Edinburgh Chancellor’s Fellowship awarded to GM. GM was a JDRF advanced postdoctoral fellow. AS is a Medical Research Council Professor.This is the final version of the article. It was first available from Wiley via http://dx.doi.org/10.15252/embj.20159211

    Path integral Monte Carlo simulations of silicates

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    We investigate the thermal expansion of crystalline SiO2_2 in the β\beta-- cristobalite and the β\beta-quartz structure with path integral Monte Carlo (PIMC) techniques. This simulation method allows to treat low-temperature quantum effects properly. At temperatures below the Debye temperature, thermal properties obtained with PIMC agree better with experimental results than those obtained with classical Monte Carlo methods.Comment: 27 pages, 10 figures, Phys. Rev. B (in press

    In thumb base osteoarthritis structural damage is more strongly associated with pain than synovitis

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    Objective: Osteoarthritis in thumb base joints (first carpometacarpal (CMC-1), scaphotrapeziotrapezoid (STT)) is prevalent and disabling, yet focussed studies are scarce. Our aim was to investigate associations between ultrasonographic and magnetic resonance imaging (MRI) inflammatory features, radiographic osteophytes, and thumb base pain in hand osteoarthritis patients. Design: Cross-sectional analyses were performed in cohorts with MRI (n = 202) and ultrasound measurements (n = 87). Pain upon thumb base palpation was assessed. Radiographs were scored for CMC-1/STT osteophytes. Synovial thickening, effusion and power Doppler signal in CMC-1 joints were assessed with ultrasound. MRIs were scored for synovitis and bone marrow lesions (BMLs) in CMC-1 and STT joints using OMERACT-TOMS. Associations between ultrasound/MRI features, osteophytes, and thumb base pain were assessed. Interaction between MRI features and osteophytes was explored. Results: In 289 patients (mean age 60.2, 83% women) 139/376 thumb bases were painful. Osteophyte presence was associated with pain (MRI cohort: odds ratio (OR) 5.1 (2.7-9.8)). Ultrasound features were present in 25-33% of CMC-1 joints, though no associations were seen with pain. MRI-synovitis and BMLs grade >= 2 were scored in 25% and 43% of thumb bases, and positively associated with pain (OR 3.6 (95% CI 1.7-7.6) and 3.0 (1.6-5.5)). Associations attenuated after adjustment for osteophyte presence. Combined presence of osteophytes and MRI-synovitis had an additive effect. Conclusions: Ultrasonographic and MRI inflammatory features were often present in the thumb base. Osteophytes were more strongly associated with thumb base pain than inflammatory features, in contrast to findings in finger OA studies, supporting thumb base osteoarthritis as a distinct phenotype. (c) 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.Dutch Arthritis Foundatio

    Photoelasticity of crystalline and amorphous silica from first principles

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    Based on density-functional perturbation theory we have computed from first principles the photoelastic tensor of few crystalline phases of silica at normal conditions and high pressure (quartz, α\alpha-cristobalite, β\beta-cristobalite) and of models of amorphous silica (containig up to 162 atoms), obtained by quenching from the melt in combined classical and Car-Parrinello molecular dynamics simulations. The computational framework has also been checked on the photoelastic tensor of crystalline silicon and MgO as prototypes of covalent and ionic systems. The agreement with available experimental data is good. A phenomenological model suitable to describe the photoelastic properties of different silica polymorphs is devised by fitting on the ab-initio data.Comment: ten figure

    Mouse visual cortex contains a region of enhanced spatial resolution.

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    The representation of space in mouse visual cortex was thought to be relatively uniform. Here we reveal, using population receptive-field (pRF) mapping techniques, that mouse visual cortex contains a region in which pRFs are considerably smaller. This region, the "focea," represents a location in space in front of, and slightly above, the mouse. Using two-photon imaging we show that the smaller pRFs are due to lower scatter of receptive-fields at the focea and an over-representation of binocular regions of space. We show that receptive-fields of single-neurons in areas LM and AL are smaller at the focea and that mice have improved visual resolution in this region of space. Furthermore, freely moving mice make compensatory eye-movements to hold this region in front of them. Our results indicate that mice have spatial biases in their visual processing, a finding that has important implications for the use of the mouse model of vision

    Relationship between Structure, Entropy and Diffusivity in Water and Water-like Liquids

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    Anomalous behaviour of the excess entropy (SeS_e) and the associated scaling relationship with diffusivity are compared in liquids with very different underlying interactions but similar water-like anomalies: water (SPC/E and TIP3P models), tetrahedral ionic melts (SiO2_2 and BeF2_2) and a fluid with core-softened, two-scale ramp (2SRP) interactions. We demonstrate the presence of an excess entropy anomaly in the two water models. Using length and energy scales appropriate for onset of anomalous behaviour, the density range of the excess entropy anomaly is shown to be much narrower in water than in ionic melts or the 2SRP fluid. While the reduced diffusivities (DD^*) conform to the excess entropy scaling relation, D=Aexp(αSe)D^* =A\exp (\alpha S_e) for all the systems (Y. Rosenfeld, Phys. Rev. A {\bf 1977}, {\it 15}, 2545), the exponential scaling parameter, α\alpha, shows a small isochore-dependence in the case of water. Replacing SeS_e by pair correlation-based approximants accentuates the isochore-dependence of the diffusivity scaling. Isochores with similar diffusivity scaling parameters are shown to have the temperature dependence of the corresponding entropic contribution. The relationship between diffusivity, excess entropy and pair correlation approximants to the excess entropy are very similar in all the tetrahedral liquids.Comment: 24 pages, 4 figures, to be published in Journal of Physical Chemistry
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