Drug‐induced liver injury (DILI) is the most frequent reason cited for the withdrawal of approved drugs from the market and accounts for up to 15% of the cases of acute liver failure. Investigators ...around the globe have begun to identify and study patients with DILI; several large registries and tissue banks are being established. In order to gain the maximum scientific benefit from these efforts, the definitions and terminology related to the clinical phenotypes of DILI must be harmonized. For this purpose, an international DILI Expert Working Group of clinicians and scientists reviewed current DILI terminology and diagnostic criteria so as to develop more uniform criteria that would define and characterize the spectrum of clinical syndromes that constitute DILI. Consensus was established with respect to the threshold criteria for definition of a case as being DILI, the pattern of liver injury, causality assessment, severity, and chronicity. Consensus was also reached on approaches to characterizing DILI in the setting of chronic liver diseases, including autoimmune hepatitis (AIH).
Clinical Pharmacology & Therapeutics (2011) 89 6, 806–815. doi:10.1038/clpt.2011.58
Two-dimensional (2D) materials are not expected to be metals at low temperature owing to electron localization1. Consistent with this, pioneering studies on thin lms reported only superconducting and ...insulating ground states, with a direct transition between the two as a function of disorder or magnetic eld26. However, more recent works have revealed the presence of an intermediate quantum metallic state occupying a substantial region of the phase diagram710, whose nature is intensely debated1117. Here, we observe such a state in the disorder-free limit of a crystalline 2D superconductor, produced by mechanical co-lamination of NbSe2 in an inert atmosphere. Under a small perpendicular magnetic eld, we induce a transition from superconductor to the quantum metal. We nd a unique power-law scaling with eld in this phase, which is consistent with the Bose-metal model where metallic behaviour arises from strong phase uctuations caused by the magnetic field1114.
Projections of climate change impacts on crop yields are inherently uncertain1. Uncertainty is often quantified when projecting future greenhouse gas emissions and their influence on climate2. ...However, multi-model uncertainty analysis of crop responses to climate change is rare because systematic and objective comparisons among process-based crop simulation models1, 3 are difficult4. Here we present the largest standardized model intercomparison for climate change impacts so far. We found that individual crop models are able to simulate measured wheat grain yields accurately under a range of environments, particularly if the input information is sufficient. However, simulated climate change impacts vary across models owing to differences in model structures and parameter values. A greater proportion of the uncertainty in climate change impact projections was due to variations among crop models than to variations among downscaled general circulation models. Uncertainties in simulated impacts increased with CO2 concentrations and associated warming. These impact uncertainties can be reduced by improving temperature and CO2 relationships in models and better quantified through use of multi-model ensembles. Less uncertainty in describing how climate change may affect agricultural productivity will aid adaptation strategy development and policymaking.
Transgenic maize engineered to express insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) has become widely adopted in U.S. agriculture. In 2009, Bt maize was planted on more than ...22.2 million hectares, constituting 63% of the U.S. crop. Using statistical analysis of per capita growth rate estimates, we found that areawide suppression of the primary pest Ostrinia nubilalis (European corn borer) is associated with Bt maize use. Cumulative benefits over 14 years are an estimated $3.2 billion for maize growers in Illinois, Minnesota, and Wisconsin, with more than $2.4 billion of this total accruing to non-Bt maize growers. Comparable estimates for Iowa and Nebraska are $3.6 billion in total, with $1.9 billion for non-Bt maize growers. These results affirm theoretical predictions of pest population suppression and highlight economic incentives for growers to maintain non-Bt maize refugia for sustainable insect resistance management.
The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and ...presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.
Improvements in water productivity and yield arise from interactions between varieties (G) and their management (M). Most GxM interactions considered by breeders and physiologists focus on in-crop ...management (e.g. sowing time, plant density, N management). However, opportunities exist to capture more water and use it more effectively that involve judicious management of prior crops and fallows (e.g. crop sequence, weed control, residue management). The dry-land wheat production system of southern Australia, augmented by simulation studies, is used to demonstrate the relative impacts and interactions of a range of pre-crop and in-crop management decisions on water productivity. A specific case study reveals how a novel genetic trait, long coleoptiles that enable deeper sowing, can interact with different management options to increase the water-limited yield of wheat from 1.6 t ha⁻¹ to 4.5 t ha⁻¹, reflecting the experience of leading growers. Understanding such interactions will be necessary to capture benefits from new varieties within the farming systems of the future.
Guidelines for the use of chemotherapy and endocrine therapy recently recommended that estrogen receptor (ER) status be considered positive if ≥1% of tumor cells demonstrate positive nuclear staining ...by immunohistochemistry. In clinical practice, a range of thresholds are used; a common one is 10% positivity. Data addressing the optimal threshold with regard to the efficacy of endocrine therapy are lacking. In this study, we compared patient, tumor, treatment and survival differences among breast cancer patients using ER-positivity thresholds of 1% and 10%.
The study population consisted of patients with primary breast carcinoma treated at our center from January 1990 to December 2011 and whose records included complete data on ER status. Patients were separated into three groups: ≥10% positive staining for ER (ER-positive ≥10%), 1%–9% positive staining for ER (ER-positive 1%–9%) and <1% positive staining (ER-negative).
Of 9639 patients included, 80.5% had tumors that were ER-positive ≥10%, 2.6% had tumors that were ER-positive 1%–9% and 16.9% had tumors that were ER-negative. Patients with ER-positive 1%–9% tumors were younger with more advanced disease compared with patients with ER-positive ≥10% tumors. At a median follow-up of 5.1 years, patients with ER-positive 1%–9% tumors had worse survival rates than did patients with ER-positive ≥10% tumors, with and without adjustment for clinical stage and grade. Survival rates did not differ significantly between patients with ER-positive 1%–9% and ER-negative tumors.
Patients with tumors that are ER-positive 1%–9% have clinical and pathologic characteristics different from those with tumors that are ER-positive ≥10%. Similar to patients with ER-negative tumors, those with ER-positive 1%–9% disease do not appear to benefit from endocrine therapy; further study of its clinical benefit in this group is warranted. Also, there is a need to better define which patients of this group belong to basal or luminal subtypes.
Conditionally sampled measurements with particle image velocimetry (PIV) of a turbulent round submerged liquid jet in a laboratory have been taken at Re = 2 × 103 between 60 and 100 nozzle diameters ...from the nozzle in order to investigate the dynamics and transport processes at the continuous and well-defined bounding interface between the turbulent and non-turbulent regions of flow. The jet carries a fluorescent dye measured with planar laser-induced fluorescence (LIF), and the surface discontinuity in the scalar concentration is identified as the fluctuating turbulent jet interface. Thence the mean outward ‘boundary entrainment’ velocity is derived and shown to be a constant fraction (about 0.07) of the the mean jet velocity on the centreline. Profiles of the conditional mean velocity, mean scalar and momentum flux show that at the interface there are clear discontinuities in the mean axial velocity and mean scalar and a tendency towards a singularity in mean vorticity. These actual or asymptotic discontinuities are consistent with the conditional mean momentum and scalar transport equations integrated across the interface. Measurements of the fluxes of turbulent kinetic energy and enstrophy are consistent with computations by Mathew & Basu (Phys. Fluids, vol. 14, 2002, pp. 2065–2072) in showing that for a jet flow (without forcing) the entrainment process is dominated by small-scale eddying at the highly sheared interface (‘nibbling’), with large-scale engulfing making a small (less than 10%) contribution consistent with concentration measurements showing that the interior of the jet is well mixed. (Turbulent jets differ greatly from the free shear layer in this respect.) To explain the difference between velocity and scalar profiles, their conditional mean gradients are defined in terms of a local eddy viscosity and eddy diffusivity and the momentum and scalar fluxes inside the interface. Since the eddy diffusivity is larger than the eddy viscosity, the scalar profile is flatter inside the interface so that the scalar discontinuity is relatively greater than the mean velocity discontinuity. Theoretical arguments, following Hunt, Eames & Westerweel (in Proc. of the IUTAM Symp. on Computational Physics and New Perspectives in Turbulence, ed. Y. Kaneda, vol. 4, 2008, pp. 331–338, Springer), are proposed for how the vortex sheet develops, how the internal structure of the interface layer relates to the inhomogeneous rotational and irrotational motions on each side and why the dominant entrainment process of jets and wakes differs from that of free shear layers.
•A novel method for defining optimal flowering periods (OFP) has been described.•OFPs are defined by combined effects of drought, radiation, frost and heat.•OFPs for wheat in south-eastern Australia ...vary with site and season.•Findings can guide research for adapting wheat production to declining autumn rainfall.
Across the Australian wheat belt, the time at which wheat flowers is a critical determinant of yield. In all environments an optimal flowering period (OFP) exists which is defined by decreasing frost risk, and increasing water and heat stress. Despite their critical importance, OFPs have not been comprehensively defined across south eastern Australia’s (SEA) cropping zone using yield estimates incorporating temperature, radiation and water-stress. In this study, the widely validated cropping systems model APSIM was used to simulate wheat yield and flowering date, with reductions in yield applied for frost and heat damage based on air temperatures during sensitive periods. Simulated crops were sown at weekly intervals from April 1 to July 15 of each year. The relationship between flowering date and grain yield was established for 28 locations using 51-years (1963–2013) of climate records. We defined OFPs as the flowering period which was associated with a mean yield of≥95% of maximum yield from the combination of 51 seasons and 16 sowing dates. OFPs for wheat in SEA varied with site and season and the relative importance of seasonal water supply and demand and extremes of temperature in defining the window also varied. Quantifying OFPs will be a vital first step to identify suitable genotype x sowing date combinations to maximise yield in different locations, particularly given recent and predicted regional climate shifts including the decline in autumn rainfall.
Aims
. We present the design and pre-launch performance of the Solar Orbiter Heliospheric Imager (SoloHI) which is an instrument prepared for inclusion in the ESA/NASA Solar Orbiter mission, ...currently scheduled for launch in 2020.
Methods
. The goal of this paper is to provide details of the SoloHI instrument concept, design, and pre-flight performance to give the potential user of the data a better understanding of how the observations are collected and the sources that contribute to the signal.
Results
. The paper discusses the science objectives, including the SoloHI-specific aspects, before presenting the design concepts, which include the optics, mechanical, thermal, electrical, and ground processing. Finally, a list of planned data products is also presented.
Conclusions
. The performance measurements of the various instrument parameters meet or exceed the requirements derived from the mission science objectives. SoloHI is poised to take its place as a vital contributor to the science success of the Solar Orbiter mission.
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