1,446 research outputs found

    Counterfactual reasoning for regretted situations involving controllable versus uncontrollable events: The modulating role of contingent self-esteem

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    We report a study that examined the modulating impact of contingent self-esteem on regret intensity for regretted outcomes associated with controllable versus uncontrollable events. The Contingent Self-Esteem Scale (e.g., Kernis & Goldman, 2006) was used to assess the extent to which a person’s sense of self-worth is based on self and others’ expectations. We found that there was an influence of self-esteem contingency for controllable but not for uncontrollable regret types. For controllable regret types individuals with a high contingent (i.e., unstable) self-esteem reported greater regret intensity than those with a low contingent (i.e., stable) self-esteem. We interpret this finding as reflecting a functional and adaptive role of high contingent self-esteem in terms of mobilizing the application of counterfactual reasoning and planning mechanisms that can enable personal expectations to be achieved in the future

    Evaluation of Existing Models to Estimate Sorption Coefficients for Ionisable Pharmaceuticals in Soils and Sludge

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    In order to assess the environmental risk of a pharmaceutical, information is needed on the sorption of the compound to solids. Here we use a high-quality database of measured sorption coefficients, all determined following internationally recognised protocols, to evaluate models that have been proposed for estimating sorption of pharmaceuticals from chemical structure, some of which are already being used for environmental risk assessment and prioritization purposes. Our analyses demonstrate that octanol-water partition coefficient (Kow) alone is not an effective predictor of ionisable pharmaceutical sorption in soils. Polyparameter models based on pharmaceutical characteristics in combination with key soil properties, such as cation exchange capacity, increase model complexity but yield an improvement in the predictive capability of soil sorption models. Nevertheless, as the models included in this analysis were only able to predict a maximum of 71% and 67% of the sorption coefficients for the compounds to within one log unit of the corresponding measured value in soils and sludge, respectively, there is a need for new models to be developed to better predict the sorption of ionisable pharmaceuticals in soil and sludge systems. The variation in sorption coefficients, even for a single pharmaceutical across different solid types, makes this an inherently difficult task, and therefore requires a broad understanding of both chemical and sorbent properties driving the sorption process

    The actin-myosin regulatory MRCK kinases: regulation, biological functions and associations with human cancer

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    The contractile actin-myosin cytoskeleton provides much of the force required for numerous cellular activities such as motility, adhesion, cytokinesis and changes in morphology. Key elements that respond to various signal pathways are the myosin II regulatory light chains (MLC), which participate in actin-myosin contraction by modulating the ATPase activity and consequent contractile force generation mediated by myosin heavy chain heads. Considerable effort has focussed on the role of MLC kinases, and yet the contributions of the myotonic dystrophy-related Cdc42-binding kinases (MRCK) proteins in MLC phosphorylation and cytoskeleton regulation have not been well characterized. In contrast to the closely related ROCK1 and ROCK2 kinases that are regulated by the RhoA and RhoC GTPases, there is relatively little information about the CDC42-regulated MRCKα, MRCKβ and MRCKγ members of the AGC (PKA, PKG and PKC) kinase family. As well as differences in upstream activation pathways, MRCK and ROCK kinases apparently differ in the way that they spatially regulate MLC phosphorylation, which ultimately affects their influence on the organization and dynamics of the actin-myosin cytoskeleton. In this review, we will summarize the MRCK protein structures, expression patterns, small molecule inhibitors, biological functions and associations with human diseases such as cancer

    A systematic review of vestibular stimulation in post-stroke visual neglect.

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    Unilateral visual neglect is a condition that negatively impacts the lives of many stroke survivors. Studies have investigated different forms of vestibular stimulation as a potential therapy, but evidence is yet to be systematically reviewed. We therefore reviewed the effects of vestibular stimulation on outcomes of neglect and activities of daily living (ADL) for people with visual neglect. We searched relevant databases up until September 2022. Eligible articles included any form of vestibular stimulation, study design, or control condition. Included participants were 18 years or older, presenting with neglect following a haemorrhagic or ischaemic stroke. Relevant outcomes were clinically validated measures of neglect and ADL. Cochrane risk of bias tools were used to assess study quality. Meta-analyses and narrative methods were used to synthesize the data. Our search returned 17 relevant studies comprising 180 participants. Meta-analyses showed no difference between galvanic vestibular stimulation and sham conditions on outcomes, whereas caloric vestibular stimulation led to improvement compared to pre-stimulation scores. Narrative syntheses showed mixed results. Clinical and methodological heterogeneity was found both within and between studies. Overall, results were inconsistent regarding the effects of vestibular stimulation as a treatment for neglect. Further trials are warranted but require more careful methodological planning

    A frequentist framework of inductive reasoning

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    Reacting against the limitation of statistics to decision procedures, R. A. Fisher proposed for inductive reasoning the use of the fiducial distribution, a parameter-space distribution of epistemological probability transferred directly from limiting relative frequencies rather than computed according to the Bayes update rule. The proposal is developed as follows using the confidence measure of a scalar parameter of interest. (With the restriction to one-dimensional parameter space, a confidence measure is essentially a fiducial probability distribution free of complications involving ancillary statistics.) A betting game establishes a sense in which confidence measures are the only reliable inferential probability distributions. The equality between the probabilities encoded in a confidence measure and the coverage rates of the corresponding confidence intervals ensures that the measure's rule for assigning confidence levels to hypotheses is uniquely minimax in the game. Although a confidence measure can be computed without any prior distribution, previous knowledge can be incorporated into confidence-based reasoning. To adjust a p-value or confidence interval for prior information, the confidence measure from the observed data can be combined with one or more independent confidence measures representing previous agent opinion. (The former confidence measure may correspond to a posterior distribution with frequentist matching of coverage probabilities.) The representation of subjective knowledge in terms of confidence measures rather than prior probability distributions preserves approximate frequentist validity.Comment: major revisio

    Study of Bc+B_c^+ decays to the K+Kπ+K^+K^-\pi^+ final state and evidence for the decay Bc+χc0π+B_c^+\to\chi_{c0}\pi^+

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    A study of Bc+K+Kπ+B_c^+\to K^+K^-\pi^+ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 fb1\mathrm{fb}^{-1} collected by the LHCb experiment in pppp collisions at centre-of-mass energies of 77 and 88 TeV. Evidence for the decay Bc+χc0(K+K)π+B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+ is reported with a significance of 4.0 standard deviations, resulting in the measurement of σ(Bc+)σ(B+)×B(Bc+χc0π+)\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+) to be (9.83.0+3.4(stat)±0.8(syst))×106(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}. Here B\mathcal{B} denotes a branching fraction while σ(Bc+)\sigma(B_c^+) and σ(B+)\sigma(B^+) are the production cross-sections for Bc+B_c^+ and B+B^+ mesons. An indication of bˉc\bar b c weak annihilation is found for the region m(Kπ+)<1.834GeV ⁣/c2m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

    Search for the standard model Higgs boson at LEP

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    A modified sequence capture approach allowing standard and methylation analyses of the same enriched genomic DNA sample

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    Background: Bread wheat has a large complex genome that makes whole genome resequencing costly. Therefore, genome complexity reduction techniques such as sequence capture make re-sequencing cost effective. With a high-quality draft wheat genome now available it is possible to design capture probe sets and to use them to accurately genotype and anchor SNPs to the genome. Furthermore, in addition to genetic variation, epigenetic variation provides a source of natural variation contributing to changes in gene expression and phenotype that can be profiled at the base pair level using sequence capture coupled with bisulphite treatment. Here, we present a new 12 Mbp wheat capture probe set, that allows both the profiling of genotype and methylation from the same DNA sample. Furthermore, we present a method, based on Agilent SureSelect Methyl-Seq, that will use a single capture assay as a starting point to allow both DNA sequencing and methyl-seq. Results: Our method uses a single capture assay that is sequentially split and used for both DNA sequencing and methyl-seq. The resultant genotype and epi-type data is highly comparable in terms of coverage and SNP/methylation site identification to that generated from separate captures for DNA sequencing and methyl-seq. Furthermore, by defining SNP frequencies in a diverse landrace from the Watkins collection we highlight the importance of having genotype data to prevent false positive methylation calls. Finally, we present the design of a new 12 Mbp wheat capture and demonstrate its successful application to re-sequence wheat. Conclusions: We present a cost-effective method for performing both DNA sequencing and methyl-seq from a single capture reaction thus reducing reagent costs, sample preparation time and DNA requirements for these complementary analyses
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