Measurement properties of the Dizziness Handicap Inventory by cross-sectional and longitudinal designs

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Representing spatial variability of snow water equivalent in hydrologic and land-surface models: a review

This paper evaluates the use of field data on the spatial variability of snow water equivalent (SWE) to guide the design of distributed snow models. An extensive reanalysis of results from previous field studies in different snow environments around the world is presented, followed by an analysis of field data on spatial variability of snow collected in the headwaters of the Jollie River basin, a rugged mountain catchment in the Southern Alps of New Zealand. In addition, area-averaged simulations of SWE based on different types of spatial discretization are evaluated. Spatial variability of SWE is shaped by a range of different processes that occur across a hierarchy of spatial scales. Spatial variability at the watershed-scale is shaped by variability in near-surface meteorological fields (e.g., elevation gradients in temperature) and, provided suitable meteorological data is available, can be explicitly resolved by spatial interpolation/extrapolation. On the other hand, spatial variability of SWE at the hillslope-scale is governed by processes such as drifting, sloughing of snow off steep slopes, trapping of snow by shrubs, and the nonuniform unloading of snow by the forest canopy, which are more difficult to resolve explicitly. Subgrid probability distributions are often capable of representing the aggregate-impact of unresolved processes at the hillslope-scale, though they may not adequately capture the effects of elevation gradients. While the best modeling strategy is case-specific, the analysis in this paper provides guidance on both the suitability of several common snow modeling approaches and on the choice of parameter values in subgrid probability distributions.Martyn P. Clark, Jordy Hendrikx, Andrew G. Slater, Dmitri Kavetski, Brian Anderson, Nicolas J. Cullen, Tim Kerr, Einar Örn Hreinsson and Ross A. Wood

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

BACKGROUND Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. METHODS In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. FINDINGS Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). INTERPRETATION Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes. FUNDING Intercept Pharmaceuticals

I'm Learning ... how you go about stirring things up-in a consultative manner: social capital and action competence in two community catchment groups

The contributions of local community action groups to environmental care and restoration is usually justified and evaluated in terms of improvements to environmental quality. This article explores social benefits in the form of increases in social capital and action competence that also flow from their actions, benefits that may not only help restore degraded but also contribute to the stock of good will and skill in the community that may even prevent or minimise future environmental problems. This article documents the emergence of action competence and social capital in two community catchment groups in South-East Queensland. The findings suggest that social capital is enhanced through processes of community participation in the catchment consultation processes. The article concludes that the relationship between social capital and action competence is complementary, with social capital and action competence being mutually enhanced by the social learning that accrues from the process of community participation

Preparing for school: Report of the Queensland Preparing for School Trials 2003/4

This report details the External Evaluation of the 2003 Preparing for School Trials carried out by the Queensland Early Childhood Consortium based at the School of Early Childhood at Queensland University of Technology. \ud The findings of the study were consistent and clear. They indicated that the preparatory program is highly successful in promoting children's development in all the five domains examined (social-emotional, communication, numeracy, literacy, and motor). The effectiveness of the preparatory program was most notable in promoting social-emotional and communication development. As children entered school in 2004 those who had experienced a preparatory program were judged by Year 1 teachers as more socially adjusted to formal schooling than those who had attended preschool

Preparing for school: Report of the Queensland Preparing for School Trials 2003/4

This report details the External Evaluation of the 2003 Preparing for School Trials carried out by the Queensland Early Childhood Consortium based at the School of Early Childhood at Queensland University of Technology. The findings of the study were consistent and clear. They indicated that the preparatory program is highly successful in promoting children's development in all the five domains examined (social-emotional, communication, numeracy, literacy, and motor). The effectiveness of the preparatory program was most notable in promoting social-emotional and communication development. As children entered school in 2004 those who had experienced a preparatory program were judged by Year 1 teachers as more socially adjusted to formal schooling than those who had attended preschool

Macrophage secretory products induce an inflammatory phenotype in hepatocytes

AIM: To investigate the influence of macrophages on hepatocyte phenotype and function