185 research outputs found

    Creating legal rights for rivers: lessons from Australia, New Zealand, and India

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    As pressures on water resources increase, the demand for innovative institutional arrangements, which address the overuse of water, and underprovision of ecosystem health, is rising. One new and emerging approach is the use of legal personality to protect water systems in law through the granting of legal rights to rivers. This constitutes a significant development in the fields of environmental law and water resources management, yet little analysis is available of how the approach has been used and applied. We critically examine the new legal rights for rivers using three case studies from Australia, New Zealand, and India. We analyze how legal rights have been created in each case, and the complexity of enforcing these legal rights to protect the rivers. We conclude that legal personality could be a useful alternative approach for river management, provided that the new legal rights are given sufficient force and effect

    Clinical report : one year of treatment of Proteus syndrome with miransertib (ARQ 092)

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    A 20-yr-old man with Proteus syndrome (PS) and somatic mosaicism of the AKT1 c.49G > A p.(E17K) variant had asymmetric overgrowth of the right frontal and facial bones, asymmetric spinal overgrowth with thoracolumbar scoliosis, dilatation of the inferior vena cava, testicular cystadenoma, bilateral knee deformities, macrodactyly, and apparent intellectual disability. Miransertib (ARQ 092) is an oral, allosteric, selective pan-AKT inhibitor initially developed for cancer therapeutics, now being evaluated for the treatment of PS. After baseline evaluation, the patient started unblinded treatment of 10 mg oral miransertib daily (∼5 mg/m2/day), escalated to 30 mg daily (∼15 mg/m2/day), and then to 50 mg daily (∼25 mg/m2/day) after 3 mo of treatment. Adverse events included dry mouth, one episode of gingivostomatitis, and loose, painful dentition due to preexisting periodontal disease, all of which resolved spontaneously. After 11 mo of treatment, the patient reported improved general well-being, increased mobility of the ankle, spine, and hands, a subjective decrease in size of the right facial bone overgrowth, and reduced areas of cerebriform connective tissue nevi on the soles. Whole-body MRI findings were stable without apparent disease progression. We conclude that 1 yr of treatment with miransertib was beneficial in this case

    What is the 'problem' that outreach work seeks to address and how might it be tackled? Seeking theory in a primary health prevention programme

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    <b>Background</b> Preventive approaches to health are disproportionately accessed by the more affluent and recent health improvement policy advocates the use of targeted preventive primary care to reduce risk factors in poorer individuals and communities. Outreach has become part of the health service response. Outreach has a long history of engaging those who do not otherwise access services. It has, however, been described as eclectic in its purpose, clientele and mode of practice; its effectiveness is unproven. Using a primary prevention programme in the UK as a case, this paper addresses two research questions: what are the perceived problems of non-engagement that outreach aims to address; and, what specific mechanisms of outreach are hypothesised to tackle these.<p></p> <b>Methods</b> Drawing on a wider programme evaluation, the study undertook qualitative interviews with strategically selected health-care professionals. The analysis was thematically guided by the concept of 'candidacy' which theorises the dynamic process through which services and individuals negotiate appropriate service use.<p></p> <b>Results</b> The study identified seven types of engagement 'problem' and corresponding solutions. These 'problems' lie on a continuum of complexity in terms of the challenges they present to primary care. Reasons for non-engagement are congruent with the concept of 'candidacy' but point to ways in which it can be expanded.<p></p> <b>Conclusions</b> The paper draws conclusions about the role of outreach in contributing to the implementation of inequalities focused primary prevention and identifies further research needed in the theoretical development of both outreach as an approach and candidacy as a conceptual framework

    Abnormal P300 in people with high risk of developing psychosis

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    Background Individuals with an “at-risk mental state” (or “prodromal” symptoms) have a 20–40% chance of developing psychosis; however it is difficult to predict which of them will become ill on the basis of their clinical symptoms alone. We examined whether neurophysiological markers could help to identify those who are particularly vulnerable. Method 35 cases meeting PACE criteria for the at-risk mental state (ARMS) and 57 controls performed an auditory oddball task whilst their electroencephalogram was recorded. The latency and amplitude of the P300 and N100 waves were compared between groups using linear regression. Results The P300 amplitude was significantly reduced in the ARMS group [8.6 ± 6.4 microvolt] compared to controls [12.7 ± 5.8 microvolt] (p < 0.01). There were no group differences in P300 latency or in the amplitude and latency of the N100. Of the at-risk subjects that were followed up, seven (21%) developed psychosis. Conclusion Reduction in the amplitude of the P300 is associated with an increased vulnerability to psychosis. Neurophysiological and other biological markers may be of use to predict clinical outcomes in populations at high risk

    Solution conformations of early intermediates in Mos1 transposition

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    DNA transposases facilitate genome rearrangements by moving DNA transposons around and between genomes by a cut-and-paste mechanism. DNA transposition proceeds in an ordered series of nucleoprotein complexes that coordinate pairing and cleavage of the transposon ends and integration of the cleaved ends at a new genomic site. Transposition is initiated by transposase recognition of the inverted repeat sequences marking each transposon end. Using a combination of solution scattering and biochemical techniques, we have determined the solution conformations and stoichiometries of DNA-free Mos1 transposase and of the transposase bound to a single transposon end. We show that Mos1 transposase is an elongated homodimer in the absence of DNA and that the N-terminal 55 residues, containing the first helix-turn-helix motif, are required for dimerization. This arrangement is remarkably different from the compact, crossed architecture of the dimer in the Mos1 paired-end complex (PEC). The transposase remains elongated when bound to a single-transposon end in a pre-cleavage complex, and the DNA is bound predominantly to one transposase monomer. We propose that a conformational change in the single-end complex, involving rotation of one half of the transposase along with binding of a second transposon end, could facilitate PEC assembly

    Deep crustal earthquakes in North Tanzania, East Africa: Interplay between tectonic and magmatic processes in an incipient rift

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    International audienceIn this study, we explore the origin of lower crustal seismicity and the factors controlling rift propagation using seismological data recorded within the youngest part of the East African Rift System, the North Tanzanian Divergence (NTD). Most earthquakes below Lake Manyara occur at depth ranging between 20 and 40 km and have a swarm-like distribution. Focal mechanisms of 26 events indicate a combination of strike-slip and normal faulting involving Archaean basement structures and forming a relay zone. The derived local stress regime is transtensive and the minimum principal stress is oriented N110°E. Crustal seismic tomography reveals low-velocity anomalies below the rifted basins in the NTD, interpreted as localized thermomechanical perturbations promoting fluid release and subsequent seismicity in the lower crust. SKS splitting analysis in the NTD indicates seismic anisotropy beneath 17 stations most likely due to aligned magma lenses and/or dikes beneath the rift and to the lithospheric fabrics. Our results favor a strain pattern intermediate between purely mechanical and purely magmatic. We suggest that melt products arising from a large asthenospheric thermal anomaly enhance lithospheric weakening and facilitate faulting and creeping on critically oriented inherited structures of the Precambrian lower crust. Although the crust is unlikely weakened at a point comparable to other parts of the East African Rift System, this deep-seated thermomechanical process is efficient enough to allow slow rift propagation within the eastern Tanzanian cratonic edge
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