Guidelines on the management of abnormal liver blood tests

These updated guidelines on the management of abnormal liver blood tests have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines, which this document supersedes, were written in 2000 and have undergone extensive revision by members of the Guidelines Development Group (GDG). The GDG comprises representatives from patient/carer groups (British Liver Trust, Liver4life, PBC Foundation and PSC Support), elected members of the BSG liver section (including representatives from Scotland and Wales), British Association for the Study of the Liver (BASL), Specialist Advisory Committee in Clinical Biochemistry/Royal College of Pathology and Association for Clinical Biochemistry, British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN), Public Health England (implementation and screening), Royal College of General Practice, British Society of Gastrointestinal and Abdominal Radiologists (BSGAR) and Society of Acute Medicine. The quality of evidence and grading of recommendations was appraised using the AGREE II tool. These guidelines deal specifically with the management of abnormal liver blood tests in children and adults in both primary and secondary care under the following subheadings: (1) What constitutes an abnormal liver blood test? (2) What constitutes a standard liver blood test panel? (3) When should liver blood tests be checked? (4) Does the extent and duration of abnormal liver blood tests determine subsequent investigation? (5) Response to abnormal liver blood tests. They are not designed to deal with the management of the underlying liver disease.</p

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Early development of infants with neurofibromatosis type 1: a case series

Background Prospective studies of infants at familial risk for autism spectrum disorder (ASD) have yielded insights into the earliest signs of the disorder but represent heterogeneous samples of unclear aetiology. Complementing this approach by studying cohorts of infants with monogenic syndromes associated with high rates of ASD offers the opportunity to elucidate the factors that lead to ASD. Methods We present the first report from a prospective study of ten 10-month-old infants with neurofibromatosis type 1 (NF1), a monogenic disorder with high prevalence of ASD or ASD symptomatology. We compared data from infants with NF1 to a large cohort of infants at familial risk for ASD, separated by outcome at age 3 of ASD (n = 34), atypical development (n = 44), or typical development (n = 89), and low-risk controls (n = 75). Domains assessed at 10 months by parent report and examiner observation include cognitive and adaptive function, sensory processing, social engagement, and temperament. Results Infants with NF1 showed striking impairments in motor functioning relative to low-risk infants; this pattern was seen in infants with later ASD from the familial cohort (HR-ASD). Both infants with NF1 and the HR-ASD group showed communication delays relative to low-risk infants. Conclusions Ten-month-old infants with NF1 show a range of developmental difficulties that were particularly striking in motor and communication domains. As with HR-ASD infants, social skills at this age were not notably impaired. This is some of the first information on early neurodevelopment in NF1. Strong inferences are limited by the sample size, but the findings suggest implications for early comparative developmental science and highlight motor functioning as an important domain to inform the development of relevant animal models. The findings have clinical implications in indicating an important focus for early surveillance and remediation in this early diagnosed genetic disorder

The role of map animation in geographic visualization

Geographic Visualization: Concepts, Tools and Applications is a ‘state-of-the-art’ review of the latest developments in the subject. It examines how new concepts, methods and tools can be creatively applied to solve problems relevant to a wide range of topics. The text covers the impact of three-dimensional displays on user interaction along with the potentialities in animation and clearly explains how to create temporally sensitive visualizations. It also explores the potential for handling mobile data and representing uncertainty; as well as the role of participatory visualization systems and exploratory methods

Visualizing Change: Using Cartographic Animation to Explore Remotely-Sensed Data

This research describes a geovisualization tool that is designed to facilitate exploration of satellite time-series data. Current change-detection techniques are insufficient for the task of representing the complex behaviors and motions of geographic processes because they emphasize the outcomes of change rather than depict the process of change itself. Cartographic animation of satellite data is proposed as a means of visually summarizing the complex behaviors of geographic entities. Animation provides a means for better understanding the complexity of geographic change because it can represent both the state of a geographic system at a given time (i.e. its space-time structure) and the behavior of that system over time (i.e. trends). However, a simple animation of satellite time-series data is often insufficient for this task because it overwhelms the viewer with irrelevant detail or presents data at an inappropriate temporal and spatial resolution. To solve this problem, dynamic temporal and spatial aggregation tools are implemented with the geovisualization system to allow analysts to change the resolution of their data on the fly. These tools provide (1) a means of detecting structures or trends that may be exhibited only at certain scales and (2) a method for smoothing or filtering unwanted noise from the satellite data. This research is grounded in a delineation of the nature of change, and proposes a framework of four kinds of geographic change: location, size/extent, attribute and existence. Each of these kinds of change may be continuous (a process) or discrete (an event)

A comparison of distribution patterns in British and Irish mosses and liverworts

We classified 747 species of British and Irish mosses into 10 clusters, based on their recorded distribution in 10610 km grid squares (hectads). We generated the clusters in a two-stage process using the CLUSTASPEC program, the method that we had earlier used for British and Irish liverworts and hornworts. The clusters are named after the species with distributions which are most similar to those of the clusters as a whole. Clusters of widespread species (Bryum capillare), southern, lowland species (Rhynchostegium confertum), widespread calcifuges (Pleurozium schreberi), upland species (Blindia acuta), and montane calcifuges (Kiaeria falcata) closely match clusters recognised in the liverworts. The remaining clusters (Tortella flavovirens, Weissia longifolia, Mnium stellare, Encalypta alpina, Mnium lycopodioides) are less similar. The classification of mosses into 15 and 20 clusters generates additional clusters of hyperoceanic and montane mosses which also resemble liverwort clusters. The influence of calcareous bedrock has a more marked effect in determining moss distributions and, unlike the liverworts, the 10 moss clusters include one which is predominantly coastal. Mosses tend to be a less upland group than liverworts; a smaller proportion of their species have northern and western distributions and the lowland clusters are characterised by more extreme environmental conditions. As with the liverworts, geographically restricted clusters of species with predominantly Mediterranean-Atlantic, Arctic-montane and Boreo-arctic Montane world ranges include marked concentrations of threatened species, and species which are not recorded as fruiting in the British Isles