The future for diagnostic tests of acute kidney injury in critical care: evidence synthesis, care pathway analysis and research prioritisation

Background: Acute kidney injury (AKI) is highly prevalent in hospital inpatient populations, leading to significant mortality and morbidity, reduced quality of life and high short- and long-term health-care costs for the NHS. New diagnostic tests may offer an earlier diagnosis or improved care, but evidence of benefit to patients and of value to the NHS is required before national adoption. Objectives: To evaluate the potential for AKI in vitro diagnostic tests to enhance the NHS care of patients admitted to the intensive care unit (ICU) and identify an efficient supporting research strategy. Data sources: We searched ClinicalTrials.gov, The Cochrane Library databases, Embase, Health Management Information Consortium, International Clinical Trials Registry Platform, MEDLINE, metaRegister of Current Controlled Trials, PubMed and Web of Science databases from their inception dates until September 2014 (review 1), November 2015 (review 2) and July 2015 (economic model). Details of databases used for each review and coverage dates are listed in the main report. Review methods: The AKI-Diagnostics project included horizon scanning, systematic reviewing, meta-analysis of sensitivity and specificity, appraisal of analytical validity, care pathway analysis, model-based lifetime economic evaluation from a UK NHS perspective and value of information (VOI) analysis. Results: The horizon-scanning search identified 152 potential tests and biomarkers. Three tests, Nephrocheck® (Astute Medical, Inc., San Diego, CA, USA), NGAL and cystatin C, were subjected to detailed review. The meta-analysis was limited by variable reporting standards, study quality and heterogeneity, but sensitivity was between 0.54 and 0.92 and specificity was between 0.49 and 0.95 depending on the test. A bespoke critical appraisal framework demonstrated that analytical validity was also poorly reported in many instances. In the economic model the incremental cost-effectiveness ratios ranged from £11,476 to £19,324 per quality-adjusted life-year (QALY), with a probability of cost-effectiveness between 48% and 54% when tests were compared with current standard care. Limitations: The major limitation in the evidence on tests was the heterogeneity between studies in the definitions of AKI and the timing of testing. Conclusions: Diagnostic tests for AKI in the ICU offer the potential to improve patient care and add value to the NHS, but cost-effectiveness remains highly uncertain. Further research should focus on the mechanisms by which a new test might change current care processes in the ICU and the subsequent cost and QALY implications. The VOI analysis suggested that further observational research to better define the prevalence of AKI developing in the ICU would be worthwhile. A formal randomised controlled trial of biomarker use linked to a standardised AKI care pathway is necessary to provide definitive evidence on whether or not adoption of tests by the NHS would be of value. Study registration: The systematic review within this study is registered as PROSPERO CRD42014013919. Funding: The National Institute for Health Research Health Technology Assessment programme

Dirac Equation with Spin Symmetry for the Modified P\"oschl-Teller Potential in DD-dimensions

We present solutions of the Dirac equation with spin symmetry for vector and scalar modified P\"oschl-Teller potential within framework of an approximation of the centrifugal term. The relativistic energy spectrum is obtained using the Nikiforov-Uvarov method and the two-component spinor wavefunctions are obtain are in terms of the Jacobi polynomials. It is found that there exist only positive-energy states for bound states under spin symmetry, and the energy levels increase with the dimension and the potential range parameter $\alpha$.Comment: 9 pages and 1tabl

R-mode oscillations and rocket effect in rotating superfluid neutron stars. I. Formalism

We derive the hydrodynamical equations of r-mode oscillations in neutron stars in presence of a novel damping mechanism related to particle number changing processes. The change in the number densities of the various species leads to new dissipative terms in the equations which are responsible of the {\it rocket effect}. We employ a two-fluid model, with one fluid consisting of the charged components, while the second fluid consists of superfluid neutrons. We consider two different kind of r-mode oscillations, one associated with comoving displacements, and the second one associated with countermoving, out of phase, displacements.Comment: 10 page

Aquatic community response to volcanic eruptions on the Ecuadorian Andean flank: evidence from the palaeoecological record

Aquatic ecosystems in the tropical Andes are under increasing pressure from human modification of the landscape (deforestation and dams) and climatic change (increase of extreme events and 1.5 °C on average temperatures are projected for AD 2100). However, the resilience of these ecosystems to perturbations is poorly understood. Here we use a multi-proxy palaeoecological approach to assess the response of aquatic ecosystems to a major mechanism for natural disturbance, volcanic ash deposition. Specifically, we present data from two Neotropical lakes located on the eastern Andean flank of Ecuador. Laguna Pindo (1°27.132′S–78°04.847′W) is a tectonically formed closed basin surrounded by a dense mid-elevation forest, whereas Laguna Baños (0°19.328′S–78°09.175′W) is a glacially formed lake with an inflow and outflow in high Andean Páramo grasslands. In each lake we examined the dynamics of chironomids and other aquatic and semi-aquatic organisms to explore the effect of thick (> 5 cm) volcanic deposits on the aquatic communities in these two systems with different catchment features. In both lakes past volcanic ash deposition was evident from four large tephras dated to c.850 cal year BP (Pindo), and 4600, 3600 and 1500 cal year BP (Baños). Examination of the chironomid and aquatic assemblages before and after the ash depositions revealed no shift in composition at Pindo, but a major change at Baños occurred after the last event around 1500 cal year BP. Chironomids at Baños changed from an assemblage dominated by Pseudochironomus and Polypedilum nubifer-type to Cricotopus/Paratrichocladius type-II, and such a dominance lasted for approximately 380 years. We suggest that, despite potential changes in the water chemistry, the major effect on the chironomid community resulted from the thickness of the tephra being deposited, which acted to shallow the water body beyond a depth threshold. Changes in the aquatic flora and fauna at the base of the trophic chain can promote cascade effects that may deteriorate the ecosystem, especially when already influenced by human activities, such as deforestation and dams, which is frequent in the high Andes

Flavour physics from an approximate U(2)^3 symmetry

The quark sector of the Standard Model exhibits an approximate U(2)^3 flavour symmetry. This symmetry, broken in specific directions dictated by minimality, can explain the success of the Cabibbo-Kobayashi-Maskawa picture of flavour mixing and CP violation, confirmed by the data so far, while allowing for observable deviations from it, as expected in most models of ElectroWeak Symmetry Breaking. Building on previous work in the specific context of supersymmetry, we analyze the expected effects and we quantify the current bounds in a general Effective Field Theory framework. As a further relevant example we then show how the U(2)^3 symmetry and its breaking can be implemented in a generic composite Higgs model and we make a first analysis of its peculiar consequences. We also discuss how some partial extension of U(2)^3 to the lepton sector can arise, both in general and in composite Higgs models. An optimistic though conceivable interpretation of the considerations developed in this paper gives reasons to think that new physics searches in the flavour sector may be about to explore an interesting realm of phenomena.Comment: 29 pages, 5 figure

Functional Silver-Coated Colloidosomes as Targeted Carriers for Small Molecules

Colloidosomes have attracted great interest in recent years because of their capability for storage and delivery of small molecules for medical and pharmaceutical applications. However, traditional polymer shell colloidosomes leak low molecular weight drugs due to their intrinsic shell permeability. Here, we report aqueous core colloidosomes with a silver shell, which seals the core and makes the shell impermeable. The silver-coated colloidosomes were prepared by reacting l-ascorbic acid in the microcapsule core with silver nitrate in the wash solution. The silver shell colloidosomes were then modified by using 4,4′-dithiodibutyric acid and cross-linked with rabbit Immunoglobulin G (IgG). Label-free surface plasmon resonance was used to test the specific targeting of the functional silver shell with rabbit antigen. To break the shells, ultrasound treatment was used. The results demonstrate that a new type of functional silver-coated colloidosome with immunoassay targeting, nonpermeability, and ultrasound sensitivity could be applied to many medical applications.Qian Sun, Ziyan Zhao, and Hui Gao are grateful to the China Scholarship Council for funding. Yao Du is grateful to the Agency for Science Technology and Research (A*STAR) Singapore for funding

Implementation of routine outcome measurement in child and adolescent mental health services in the United Kingdom: a critical perspective

The aim of this commentary is to provide an overview of clinical outcome measures that are currently recommended for use in UK Child and Adolescent Mental Health Services (CAMHS), focusing on measures that are applicable across a wide range of conditions with established validity and reliability, or innovative in their design. We also provide an overview of the barriers and drivers to the use of Routine Outcome Measurement (ROM) in clinical practice