A global action agenda for turning the tide on fatty liver disease

Background and Aims: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care. Approach and Results: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of “agree” responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% “agree”). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. Conclusions: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce fatty liver disease prevalence and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels

A combined geochemical and hydrological approach for understanding macronutrient sources

This study employed complementary geochemical techniques and distributed hydrological modelling to investigate multiple sources of catchment macronutrients and characterise their changes in contrasting storm and baseflow conditions. This approach was demonstrated for the Beult catchment in the county of Kent (England), a designated Site of Special Scientific Interest (SSSI) indentified as failing to meet water quality standards for key nutrients under the Water Framework Directive. Significant changes in nutrient stoichiometry and bioavailability are observed for surface waters under contrasting flow regimes. Soluble reactive phosphorus (SRP) concentrations are approximately twice as high during baseflow compared to high flow, while the inverse is true for particulate, colloidal and dissolved hydrolysable phosphorus, dissolved organic carbon and nitrate. Nitrogen (N):phosphorus (P) ratios are lower during baseflow for most surface waters impacted by diffuse sources of pollution. Fluorescence indices of dissolved organic matter (DOM) show that waste water inputs may be locally important sources of more complex low molecular weight DOM, particularly during baseflow. Nitrate N and O isotope signatures, combined with other dissolved chemical tracers, confirm the dominance of wastewater N inputs at sites downsteam of sewerage treatment works during baseflow, with a shift towards the soil N pool in surface waters across the catchment during high flow. Distributed hydrological modelling using the Grid-to-Grid model reveal areas with the greatest runoff also export higher N and P concentrations, and hence deliver a greater flux of macronutrients, while forested areas with low nutrient concentrations reduce runoff and nutrient fluxes. During periods of high runoff, nested sampling indicates that nutrient fluxes scale with catchment area. This combined approach enables a more thorough assessment of the macronutrient sources and dynamics, better informing management options in nutrient impacted catchments

Synthesis of polyanionic C5-modified 2'-deoxyuridine and 2'-deoxycytidine-5'-triphosphates and their properties as substrates for DNA polymerases

Modified 2'-deoxyribonucleotide triphosphates (dNTPs) have widespread applications in both existing and emerging biomolecular technologies. For such applications it is an essential requirement that the modified dNTPs be substrates for DNA polymerases. To date very few examples of C5-modified dNTPs bearing negatively charged functionality have been described, despite the fact that such nucleotides might potentially be valuable in diagnostic applications using Si-nanowire-based detection systems. Herein we have synthesised C5-modified dUTP and dCTP nucleotides each of which are labelled with an dianionic reporter group. The reporter group is tethered to the nucleobase via a polyethylene glycol (PEG)-based linkers of varying length. The substrate properties of these modified dNTPs with a variety of DNA polymerases have been investigated to study the effects of varying the length and mode of attachment of the PEG linker to the nucleobase. In general, nucleotides containing the PEG linker tethered to the nucleobase via an amide rather than an ether linkage proved to be the best substrates, whilst nucleotides containing PEG linkers from PEG6 to PEG24 could all be incorporated by one or more DNA polymerase. The polymerases most able to incorporate these modified nucleotides included Klentaq, Vent(exo-) and therminator, with incorporation by Klenow(exo-) generally being very poor

A metabolomic study on the responses of daphnia magna exposed to silver nitrate and coated silver nanoparticles

Conservation Biolog

Effects of Impurity Content on the Sintering Characteristics of Plasma-Sprayed Zirconia

Yttria-stabilized zirconia powders, containing different levels of SiO2 and Al2O3, have been plasma sprayed onto metallic substrates. The coatings were detached from their substrates and a dilatometer was used to monitor the dimensional changes they exhibited during prolonged heat treatments. It was found that specimens containing higher levels of silica and alumina exhibited higher rates of linear contraction, in both in-plane and through-thickness directions. The in-plane stiffness and the through-thickness thermal conductivity were also measured after different heat treatments and these were found to increase at a greater rate for specimens with higher impurity (silica and alumina) levels. Changes in the pore architecture during heat treatments were studied using Mercury Intrusion Porosimetry (MIP). Fine scale porosity (<_50 nm) was found to be sharply reduced even by relatively short heat treatments. This is correlated with improvements in inter-splat bonding and partial healing of intra-splat microcracks, which are responsible for the observed changes in stiffness and conductivity, as well as the dimensional changes

A pragmatic approach to evaluate alternative indicators to GDP

The serious economic crisis broken out in 2008 highly stressed the limitations of GDP used as a well-being indicator and as a predictive tool for economy. This induced the need to identify new indicators able to link the economic prosperity of a country to aspects of sustainable development and externalities, both positive and negative, in the long run. The aim of this paper is to introduce a structured approach which supports the choice or the construction of alternative indicators to GDP. The starting point is the definition of what a well-being indicator actually should represent according to the Recommendations of the Stiglitz-Sen-Fitoussi Report on the measurement of economic performance and social progress. Then the paper introduces a systematic procedure for the analysis of well-being indicators. The different phases of this procedure entail the checking of indicators technical properties and their effect on the representational efficacy. Finally, some of the most representative well-being indicators drawn from the literature are compared and a detailed application example is propose

Global Reconstruction of Naturalized River Flows at 2.94 Million Reaches

Spatiotemporally continuous global river discharge estimates across the full spectrum of stream orders are vital to a range of hydrologic applications, yet they remain poorly constrained. Here we present a carefully designed modeling effort (Variable Infiltration Capacity land surface model and Routing Application for Parallel computatIon of Discharge river routing model) to estimate global river discharge at very high resolutions. The precipitation forcing is from a recently published 0.1° global product that optimally merged gauge-, reanalysis-, and satellite-based data. To constrain runoff simulations, we use a set of machine learning-derived, global runoff characteristics maps (i.e., runoff at various exceedance probability percentiles) for grid-by-grid model calibration and bias correction. To support spaceborne discharge studies, the river flowlines are defined at their true geometry and location as much as possible—approximately 2.94 million vector flowlines (median length 6.8 km) and unit catchments are derived from a high-accuracy global digital elevation model at 3-arcsec resolution (~90 m), which serves as the underlying hydrography for river routing. Our 35-year daily and monthly model simulations are evaluated against over 14,000 gauges globally. Among them, 35% (64%) have a percentage bias within ±20% (±50%), and 29% (62%) have a monthly Kling-Gupta Efficiency ≥0.6 (0.2), showing data robustness at the scale the model is assessed. This reconstructed discharge record can be used as a priori information for the Surface Water and Ocean Topography satellite mission's discharge product, thus named “Global Reach-level A priori Discharge Estimates for Surface Water and Ocean Topography”. It can also be used in other hydrologic applications requiring spatially explicit estimates of global river flows

Reionization by active sources and its effects on the cosmic microwave background

We investigate the possible effects of reionization by active sources on the cosmic microwave background. We concentrate on the sources themselves as the origin of reionization, rather than early object formation, introducing an extra period of heating motivated by the active character of the perturbations. Using reasonable parameters, this leads to four possibilities depending on the time and duration of the energy input: delayed last scattering, double last scattering, shifted last scattering and total reionization. We show that these possibilities are only very weakly constrained by the limits on spectral distortions from the COBE FIRAS measurements. We illustrate the effects of these reionization possibilities on the angular power spectrum of temperature anisotropies and polarization for simple passive isocurvature models and simple coherent sources, observing the difference between passive and active models. Finally, we comment on the implications of this work for more realistic active sources, such as causal white noise and topological defect models. We show for these models that non-standard ionization histories can shift the peak in the CMB power to larger angular scales.Comment: 21 pages LaTeX with 11 eps figures; replaced with final version accepted for publication in Phys. Rev.