728 research outputs found

    Reductions in movement-associated fear are dependent upon graded exposure in chronic low back pain: An exploratory analysis of a modified 3-item fear hierarchy

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    Objective: To explore the effectiveness of a modified fear hierarchy on measuring improvements in movement-associated fear in chronic low back pain. Methods: A modified 3-item fear hierarchy was created and implemented based on principles of graded exposure. This study was an exploratory analysis of the modified 3-item fear hierarchy from a larger clinical trial data set. Both groups received pain education and exercise, either bodyweight or strength training. Both groups performed item one on the hierarchy, the squat. Only the strength training group performed item 2, the deadlift. Neither group performed item 3, the overhead press. Analysis of Covariance and stepwise linear regression were used to explore results. Results: Improvement in movement-associated fear was conditional upon graded exposure. Both groups improved in the squat movement (p ≀ 0.05), which both performed. Only the strength training group improved in the deadlift (p ≀ 0.01), and neither improved in the overhead press (p ≄ 0.05). Conclusion: Reductions in movement-associated fear are conditional upon graded exposure, based on the use of a novel modified 3-item fear hierarchy. Further research is needed to understand the utility of this tool in a patient-led approach to co-designing a graded exposure-based intervention

    Monoclonal antibody levels and protection from COVID-19

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    Multiple monoclonal antibodies have been shown to be effective for both prophylaxis and therapy for SARS-CoV-2 infection. Here we aggregate data from randomized controlled trials assessing the use of monoclonal antibodies (mAb) in preventing symptomatic SARS-CoV-2 infection. We use data on the in vivo concentration of mAb and the associated protection from COVID-19 over time to model the dose-response relationship of mAb for prophylaxis. We estimate that 50% protection from COVID-19 is achieved with a mAb concentration of 96-fold of the in vitro IC50 (95% CI: 32—285). This relationship provides a tool for predicting the prophylactic efficacy of new mAb and against SARS-CoV-2 variants. Finally, we compare the relationship between neutralization titer and protection from COVID-19 after either mAb treatment or vaccination. We find no significant difference between the 50% protective titer for mAb and vaccination, although sample sizes limited the power to detect a difference

    Module-Based Analysis of Robustness Tradeoffs in the Heat Shock Response System

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    Biological systems have evolved complex regulatory mechanisms, even in situations where much simpler designs seem to be sufficient for generating nominal functionality. Using module-based analysis coupled with rigorous mathematical comparisons, we propose that in analogy to control engineering architectures, the complexity of cellular systems and the presence of hierarchical modular structures can be attributed to the necessity of achieving robustness. We employ the Escherichia coli heat shock response system, a strongly conserved cellular mechanism, as an example to explore the design principles of such modular architectures. In the heat shock response system, the sigma-factor σ(32) is a central regulator that integrates multiple feedforward and feedback modules. Each of these modules provides a different type of robustness with its inherent tradeoffs in terms of transient response and efficiency. We demonstrate how the overall architecture of the system balances such tradeoffs. An extensive mathematical exploration nevertheless points to the existence of an array of alternative strategies for the existing heat shock response that could exhibit similar behavior. We therefore deduce that the evolutionary constraints facing the system might have steered its architecture toward one of many robustly functional solutions

    Geometry of open strings ending on backreacting D3-branes

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    We investigate open string theory on backreacting D3-branes using a spacetime approach. We study in detail the half-BPS supergravity solutions describing open strings ending on D3-branes, in the near horizon of the D3-branes. We recover quantitatively several non-trivial features of open string physics including the appearance of D3-brane spikes, the polarization of fundamental strings into D5-branes, and the Hanany-Witten effect. Finally we detail the computation of the gravitational potential between two open strings, and contrast it with the holographic computation of Wilson lines. We argue that the D-brane backreaction has a large influence on the low-energy gravity, which may lead to experimental tests for string theory brane-world scenarios.Comment: 64 pages, 20 figure

    Entrepreneurial sons, patriarchy and the Colonels' experiment in Thessaly, rural Greece

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    Existing studies within the field of institutional entrepreneurship explore how entrepreneurs influence change in economic institutions. This paper turns the attention of scholarly inquiry on the antecedents of deinstitutionalization and more specifically, the influence of entrepreneurship in shaping social institutions such as patriarchy. The paper draws from the findings of ethnographic work in two Greek lowland village communities during the military Dictatorship (1967–1974). Paradoxically this era associated with the spread of mechanization, cheap credit, revaluation of labour and clear means-ends relations, signalled entrepreneurial sons’ individuated dissent and activism who were now able to question the Patriarch’s authority, recognize opportunities and act as unintentional agents of deinstitutionalization. A ‘different’ model of institutional change is presented here, where politics intersects with entrepreneurs, in changing social institutions. This model discusses the external drivers of institutional atrophy and how handling dissensus (and its varieties over historical time) is instrumental in enabling institutional entrepreneurship

    Variable-temperature, variable-field magnetic circular dichroism spectroscopic study of NifEN-bound precursor and “FeMoco”

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    NifEN plays a key role in the biosynthesis of the iron–molybdenum cofactor (FeMoco) of nitrogenase. A scaffold protein that hosts the conversion of a FeMoco precursor to a mature cofactor, NifEN can assume three conformations during the process of FeMoco maturation. One, designated ΔnifB NifEN, contains only two permanent [Fe4S4]-like clusters. The second, designated NifENPrecursor, contains the permanent clusters and a precursor form of FeMoco. The third, designated NifEN“FeMoco”, contains the permanent [Fe4S4]-like clusters and a fully complemented, “FeMoco”-like structure. Here, we report a variable-temperature, variable-field magnetic circular dichroism spectroscopic investigation of the electronic structure of the metal clusters in the three forms of dithionite-reduced NifEN. Our data indicate that the permanent [Fe4S4]-like clusters are structurally and electronically conserved in all three NifEN species and exhibit spectral features of classic [Fe4S4]+ clusters; however, they are present in a mixed spin state with a small contribution from the S > œ spin state. Our results also suggest that both the precursor and “FeMoco” have a conserved Fe/S electronic structure that is similar to the electronic structure of FeMoco in the MoFe protein, and that the “FeMoco” in NifEN“FeMoco” exists, predominantly, in an S = 3/2 spin state with spectral parameters identical to those of FeMoco in the MoFe protein. These observations provide strong support to the outcome of our previous EPR and X-ray absorption spectroscopy/extended X-ray absorption fine structure analysis of the three NifEN species while providing significant new insights into the unique electronic properties of the precursor and “FeMoco” in NifEN

    Quantum Gravity in Everyday Life: General Relativity as an Effective Field Theory

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    This article is meant as a summary and introduction to the ideas of effective field theory as applied to gravitational systems. Contents: 1. Introduction 2. Effective Field Theories 3. Low-Energy Quantum Gravity 4. Explicit Quantum Calculations 5. ConclusionsComment: 56 pages, 2 figures, JHEP style, Invited review to appear in Living Reviews of Relativit

    An exploration of parents’ preferences for foot care in juvenile idiopathic arthritis: a possible role for the discrete choice experiment

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    Background: An increased awareness of patients’ and parents’ care preferences regarding foot care is desirable from a clinical perspective as such information may be utilised to optimise care delivery. The aim of this study was to examine parents’ preferences for, and valuations of foot care and foot-related outcomes in juvenile idiopathic arthritis (JIA).<p></p> Methods: A discrete choice experiment (DCE) incorporating willingness-to-pay (WTP) questions was conducted by surveying 42 parents of children with JIA who were enrolled in a randomised-controlled trial of multidisciplinary foot care at a single UK paediatric rheumatology outpatients department. Attributes explored were: levels of pain; mobility; ability to perform activities of daily living (ADL); waiting time; referral route; and footwear. The DCE was administered at trial baseline. DCE data were analysed using a multinomial-logit-regression model to estimate preferences and relative importance of attributes of foot care. A stated-preference WTP question was presented to estimate parents’ monetary valuation of health and service improvements.<p></p> Results: Every attribute in the DCE was statistically significant (p < 0.01) except that of cost (p = 0.118), suggesting that all attributes, except cost, have an impact on parents’ preferences for foot care for their child. The magnitudes of the coefficients indicate that the strength of preference for each attribute was (in descending order): improved ability to perform ADL, reductions in foot pain, improved mobility, improved ability to wear desired footwear, multidisciplinary foot care route, and reduced waiting time. Parents’ estimated mean annual WTP for a multidisciplinary foot care service was £1,119.05.<p></p> Conclusions: In terms of foot care service provision for children with JIA, parents appear to prefer improvements in health outcomes over non-health outcomes and service process attributes. Cost was relatively less important than other attributes suggesting that it does not appear to impact on parents’ preferences.<p></p&gt

    Moduli backreaction and supersymmetry breaking in string-inspired inflation models

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    We emphasize the importance of effects from heavy fields on supergravity models of inflation. We study, in particular, the backreaction of stabilizer fields and geometric moduli in the presence of supersymmetry breaking. Many effects do not decouple even if those fields are much heavier than the inflaton field. We apply our results to successful models of Starobinsky-like inflation and natural inflation. In most scenarios producing a plateau potential it proves difficult to retain the flatness of the potential after backreactions are taken into account. Some of them are incompatible with non-perturbative moduli stabilization. In natural inflation there exist a number of models which are not constrained by backreactions at all. In those cases the correction terms from heavy fields have the same inflaton-dependence as the uncorrected potential, so that inflation may be possible even for very large gravitino masses.Comment: 29 pages, 1 figure, comments added, subsection 2.3 added, published versio
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