485 research outputs found

    Terahertz underdamped vibrational motion governs protein-ligand binding in solution

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    Low-frequency collective vibrational modes in proteins have been proposed as being responsible for efficiently directing biochemical reactions and biological energy transport. However, evidence of the existence of delocalized vibrational modes is scarce and proof of their involvement in biological function absent. Here we apply extremely sensitive femtosecond optical Kerr-effect spectroscopy to study the depolarized Raman spectra of lysozyme and its complex with the inhibitor triacetylchitotriose in solution. Underdamped delocalized vibrational modes in the terahertz frequency domain are identified and shown to blue-shift and strengthen upon inhibitor binding. This demonstrates that the ligand-binding coordinate in proteins is underdamped and not simply solvent-controlled as previously assumed. The presence of such underdamped delocalized modes in proteins may have significant implications for the understanding of the efficiency of ligand binding and protein–molecule interactions, and has wider implications for biochemical reactivity and biological function

    Quality of care and its determinants in longer term mental health facilities across Europe; a cross-sectional analysis.

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    BACKGROUND: The Quality Indicator for Rehabilitative Care (QuIRC) is an international, standardised quality tool for the evaluation of mental health facilities that provide longer term care. Completed by the service manager, it comprises 145 items that assess seven domains of care: living environment; treatments and interventions; therapeutic environment; self-management and autonomy; social interface; human rights; and recovery based practice. We used the QuIRC to investigate associations between characteristics of longer term mental health facilities across Europe and the quality of care they delivered to service patients. METHODS: QuIRC assessments were completed for 213 longer term mental health units in ten countries that were at various stages of deinstitutionalisation of their mental health services. Associations between QuIRC domain scores and unit descriptive variables were explored using simple and multiple linear regression that took into account clustering at the unit and country level. RESULTS: We found wide variation in QuIRC domain scores between individual units, but across countries, fewer than a quarter scored below 50 % on any domains. The quality of care was higher in units that were smaller, of mixed sex, that had a defined expected maximum length of stay and in which not all patients were severely disabled. CONCLUSIONS: This is the first time longer term mental health units across a number of European countries have been compared using a standardised measure. Further use of the QuIRC will allow greater understanding of the quality of care in these units across Europe and provide an opportunity to monitor pan-European quality standards of care for this vulnerable patient group

    The beginning of time? Evidence for catastrophic drought in Baringo in the early nineteenth century

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    New developments in the collection of palaeo-data over the past two decades have transformed our understanding of climate and environmental history in eastern Africa. This article utilises instrumental and proxy evidence of historical lake-level fluctuations from Baringo and Bogoria, along with other Rift Valley lakes, to document the timing and magnitude of hydroclimate variability at decadal to century time scales since 1750. These data allow us to construct a record of past climate variation not only for the Baringo basin proper, but also across a sizable portion of central and northern Kenya. This record is then set alongside historical evidence, from oral histories gathered amongst the peoples of northern Kenya and the Rift Valley and from contemporary observations recorded by travellers through the region, to offer a reinterpretation of human activity and its relationship to environmental history in the nineteenth century. The results reveal strong evidence of a catastrophic drought in the early nineteenth century, the effects of which radically alters our historical understanding of the character of settlement, mobility and identity within the Baringo–Bogoria basin

    Quality of Longer Term Mental Health Facilities in Europe: Validation of the Quality Indicator for Rehabilitative Care against Service Users’ Views

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    BACKGROUND: The Quality Indicator for Rehabilitative Care (QuIRC) is a staff rated, international toolkit that assesses care in longer term hospital and community based mental health facilities. The QuIRC was developed from review of the international literature, an international Delphi exercise with over 400 service users, practitioners, carers and advocates from ten European countries at different stages of deinstitutionalisation, and review of the care standards in these countries. It can be completed in under an hour by the facility manager and has robust content validity, acceptability and inter-rater reliability. In this study, we investigated the internal validity of the QuIRC. Our aim was to identify the QuIRC domains of care that independently predicted better service user experiences of care. METHOD: At least 20 units providing longer term care for adults with severe mental illness were recruited in each of ten European countries. Service users completed standardised measures of their experiences of care, quality of life, autonomy and the unit's therapeutic milieu. Unit managers completed the QuIRC. Multilevel modelling allowed analysis of associations between service user ratings as dependent variables with unit QuIRC domain ratings as independent variables. RESULTS: 1750/2495 (70%) users and the managers of 213 units from across ten European countries participated. QuIRC ratings were positively associated with service users' autonomy and experiences of care. Associations between QuIRC ratings and service users' ratings of their quality of life and the unit's therapeutic milieu were explained by service user characteristics (age, diagnosis and functioning). A hypothetical 10% increase in QuIRC rating resulted in a clinically meaningful improvement in autonomy. CONCLUSIONS: Ratings of the quality of longer term mental health facilities made by service managers were positively associated with service users' autonomy and experiences of care. Interventions that improve quality of care in these settings may promote service users' autonomy

    Sensory cutaneous papillae in the sea lamprey (Petromyzonmarinus L.) : I. Neuroanatomy and physiology

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    Molecules present in an animal's environment can indicate the presence of predators,food, or sexual partners and consequently, induce migratory, reproductive, foraging,or escape behaviors. Three sensory systems, the olfactory, gustatory, and solitarychemosensory cell (SCC) systems detect chemical stimuli in vertebrates. While agreat deal of research has focused on the olfactory and gustatory system over theyears, it is only recently that significant attention has been devoted to the SCC sys-tem. The SCCs are microvillous cells that were first discovered on the skin of fish,and later in amphibians, reptiles, and mammals. Lampreys also possess SCCs that areparticularly numerous on cutaneous papillae. However, little is known regarding theirprecise distribution, innervation, and function. Here, we show that sea lampreys(Petromyzon marinus L.) have cutaneous papillae located around the oral disk, nostril,gill pores, and on the dorsal fins and that SCCs are particularly numerous on thesepapillae. Tract-tracing experiments demonstrated that the oral and nasal papillae areinnervated by the trigeminal nerve, the gill pore papillae are innervated by branchialnerves, and the dorsal fin papillae are innervated by spinal nerves. We also character-ized the response profile of gill pore papillae to some chemicals and showed thattrout-derived chemicals, amino acids, and a bile acid produced potent responses.Together with a companion study (Suntres et al., Journal of Comparative Neurology,this issue), our results provide new insights on the function and evolution of the SCCsystem in vertebrates

    New D1-D5-P geometries from string amplitudes

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    We derive the long range supergravity fields sourced by a D1-D5-P bound state from disk amplitudes for massless closed string emission. We suggest that since the parameter controlling the string perturbation expansion for this calculation decreases with distance from the bound state, the resulting asymptotic fields are valid even in the regime of parameters in which there is a classical black hole solution with the same charges. The supergravity fields differ from the black hole solution by multipole moments and are more general than those contained within known classes of solutions in the literature, whilst still preserving four supersymmetries. Our results support the conjecture that the black hole solution should be interpreted as a coarse-grained description rather than an exact description of the gravitational field sourced by D1-D5-P bound states in this regime of parameters.Comment: 48 pages, 2 figures, v2: typos correcte

    The political ontology of collaborative water governance

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    This article examines the various definitions of, and analytical approaches to, collaborative water governance (CWG). While the concept’s usage has increased over the past decade, there lacks any deep engagement with the concept of the political at the heart of CWG. This article argues that contemporary approaches to CWG risk emptying the concept of its utility and coherence. Correcting this deficiency requires a focus on the social and ideational constructions of water. This will strengthen future collaborative water arrangements and enable deeper appreciation of the ways the political makes and remakes what is possible in water governance
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