79 research outputs found

    The contribution of daytime sleepiness to impaired quality of life in NAFLD in an ethnically diverse population

    Get PDF
    Health-related quality of life (HRQoL) is lower in people with NAFLD compared to the general population. Sleep disturbance resulting in daytime sleepiness is common in patients with NAFLD, but the effect of daytime sleepiness on HRQoL in NAFLD is unclear. The prevalence and natural history of NAFLD vary in different ethnic groups, but there has been limited ethnic diversity in HrQoL studies to date. We aimed to assess whether daytime sleepiness is independently associated with reduced HRQoL in an ethnically diverse UK population. We conducted HRQoL assessments using SF-36 version 2 and Epworth Sleepiness Scale (ESS) questionnaires in 192 people with NAFLD. Multivariate linear regression was used to identify factors independently affecting HRQoL scales. People with NAFLD reported significantly reduced physical health-related SF-36 scores compared to the general UK population. South Asian NAFLD patients reported impairment in physical health, but not mental health, approximately a decade before White NAFLD patients. In multivariate linear regression, daytime sleepiness (ESS score > 10), was the most significant independent predictor of reduced physical health. Age, BMI and liver stiffness score were also significantly associated. HRQoL is impaired earlier in patients of South Asian ethnicity. ESS score > 10, indicative of excessive daytime sleepiness, is an independent predictor of reduced HRQoL in people with NAFLD regardless of ethnicity. Daytime sleepiness should be considered as a contributing factor to reduced HRQoL in clinical practice and when evaluating patient-related outcomes in clinical trials.Grant from the Diabetes Wellness and Research Foundation (WA, WKS). WA was supported by a New Investigator Research Grant from the Medical Research Council

    Single-cell phenotypes of peripheral blood immune cells in early and late stages of non-alcoholic fatty liver disease

    Get PDF
    Background/Aims Immune and inflammatory cells respond to multiple pathological hits in the development of nonalcoholic steatohepatitis (NASH) and fibrosis. Relatively little is known about how their type and function change through the non-alcoholic fatty liver disease (NAFLD) spectrum. Here we used multi-dimensional mass cytometry and a tailored bioinformatic approach to study circulating immune cells sampled from healthy individuals and people with NAFLD. Methods Cytometry by time of flight using 36 metal-conjugated antibodies was applied to peripheral blood mononuclear cells (PBMCs) from biopsy-proven NASH fibrosis (late disease), steatosis (early disease), and healthy patients. Supervised and unsupervised analyses were used, findings confirmed, and mechanisms assessed using independent healthy and disease PBMC samples. Results Of 36 PBMC clusters, 21 changed between controls and disease samples. Significant differences were observed between diseases stages with changes in T cells and myeloid cells throughout disease and B cell changes in late stages. Semi-supervised gating and re-clustering showed that disease stages were associated with fewer monocytes with active signalling and more inactive NK cells; B and T cells bearing activation markers were reduced in late stages, while B cells bearing co-stimulatory molecules were increased. Functionally, disease states were associated with fewer activated mucosal-associated invariant T cells and reduced toll-like receptor-mediated cytokine production in late disease. Conclusions A range of innate and adaptive immune changes begin early in NAFLD, and disease stages are associated with a functionally less active phenotype compared to controls. Further study of the immune response in NAFLD spectrum may give insight into mechanisms of disease with potential clinical application

    Jurassic sedimentation in the Cleveland Basin : a review

    Get PDF
    This review combines two Presidential Addresses (2005, 2006) and aims to provides an up-to-date overview of the stratigraphy and sedimentation of the Jurassic sequence of the Cleveland Basin (Yorkshire), including poorly known data from the western outcrop. These fascinating rocks have been the focus of geological research since the 18th Century and have had a profound influence on the development of the geological sciences. Throughout the 20th Century, the excellent coastal exposures have acted as a magnet for palaeontologists, stratigraphers, sedimentologists and geochemists, as a natural geological laboratory, and in recent decades, the coastal exposures received increased scientific interest as a result of their analogy with hydrocarbon source and reservoir rocks in the North Sea. Designation of the international Global Stratotype Section and Point (GSSP) for the Sinemurian–Pliensbachian stage boundary in Robin Hood's Bay, the establishment of the Dinosaur Coast, and development of the Rotunda Museum in Scarborough have all given the regional geology additional importance. The Lias Group (Hettangian–Toarcian age; 199.6–175.6 Ma), exposed in the well known coastal sections, is illustrated by the fully cored Felixkirk Borehole, located at the western margin of the outcrop, and is one of the best examples of shallow marine sedimentation in an epeiric shelf-sea setting. It comprises two large-scale, upward coarsening cycles, namely the Redcar Mudstone to Staithes Sandstone cycle, followed by the Cleveland Ironstone to Blea Wyke Sandstone cycle. Within this broad pattern, smaller scale transgressive–regressive cycles are described from stratigraphically expanded and reduced successions. Detailed ammonite biostratigraphy provides a finely calibrated temporal framework to study the variations in sedimentation, which include storm-generated limestones and sandstones (‘tempestites’) interbedded with mudstone deposited during fair-weather periods. Hemipelagic mud, occasionally organic-rich, reflects deeper-water anoxic events that may indicate a response to global climate change. In cores, the tempestite beds (Hettangian–Sinemurian) are characterized by sharp bases that, at outcrop, are often masked by downward penetrating burrows. Cyclicity on a centimetre scale in the overlying Pliensbachian ‘Banded Shales’ may be the result of orbitally induced, climatic cycles. Gradational upward coarsening to the Staithes Sandstone Formation marks a transition to sand-rich tempestite deposits, characterized by low angle and swaley cross-lamination, interbedded with sand-starved units (striped siltstones). The sands were probably deposited from sediment-laden, storm-surge and ebb currents in inner- and mid-shelf settings; the sandy substrate was, at some levels, extensively bioturbated by deposit feeding organisms that produced a spectacular range of trace fossil assemblages characteristic of shoreface, inner-, mid-, and outer-shelf settings. Intrabasinal tectonics was a controlling factor during deposition of both the Staithes Sandstone and the overlying Cleveland Ironstone (Late Pliensbachian). The influx of sand is attributed to hinterland uplift and increased sediment flux. More marked intraformational uplift during deposition of the Cleveland Ironstone is manifested in a much attenuated succession in the west of the basin (Felixkirk); southwards, towards the Market Weighton High, the Pecten/Main Seam of the ironstone oversteps unconformably onto progressively older beds to rest on the lower part of the Redcar Mudstone Formation. Ironstone, in the form of berthierine ooids and sideritic mud, was deposited during 5–6 cycles (in coastal exposures) of high sea-level stands that cut off siliciclastic influx from the low-gradient hinterland; regressive, upward-shoaling intervals are marked by interbedded, bioturbated siltstone and fine-grained sandstone. The Toarcian succession (Whitby Mudstone and Blea Wyke Sandstone formations) continues the second upward coarsening cycle in response to increased subsidence, rising sea-level, and an influx of siliciclastic sand. Oxygenated, open marine mud was deposited during the initial deepening phase, followed by bituminous mud, attributed to ocean-water stratification and the establishment of anoxic bottom conditions; in the west of the basin an upward shoaling sequence suggests that water depths were not as great. Recent research on the geochemistry and stable isotope signatures across this early Toarcian interval indicates a widespread, global anoxic event, possibly attributed to the release of methane hydrate on the ocean floor. The Alum Shale Member represents increasingly oxygenated bottom conditions and an upward coarsening motif with passage to the Blea Wyke Sandstone Formation, which is preserved only in the Peak Trough, an actively subsiding graben. Basin uplift accompanied by gentle folding in late Toarcian to Aalenian times removed much of the late Toarcian succession so that the Middle Jurassic Dogger Formation (Aalenian), a complex, condensed, shallow water unit rests unconformably on beds as low as the Alum Shale over much of the basin. Deep boreholes and revision mapping by the British Geological Survey (BGS) in the west of the outcrop have allowed a fuller, basin-wide synthesis of the palaeoenvironments and the influence of intra-Jurassic tectonics during Mid- to Late Jurassic times. During Mid-Jurassic times the low-lying, paralic coastal plain, typified by braided and meandering fluvial systems and lacustrine deposits was invaded by marine incursions from the south and east. Each transgressive event was different in its geographical penetration across the coastal plain, resulting in varied lithofacies and palaeoenvironments including ooidal ironstone and lime mud (Eller Beck Formation), peloid and ooid carbonate shoals (Lebberston Member), and tidal sand bars, pelloidal limestones and nearshore marine muds (Scarborough Formation). Trace fossils, including dinosaur footprints, and macro-plant fossils tell us much about the palaeoenvironments on the coastal plain, during this time interval (175.6–164.7 Ma) that was characterized by a warm, seasonal climate. The basin wide transgression and marked global sea-level rise represented by the Cornbrash Formation, marks deposition in a shallow marine environment during the Callovian, followed by sand (Osgodby Formation) and deeper water muds (Oxford Clay Formation) that spread northwards from the East Midlands over the Market Weighton High during the Oxfordian. Subsequent shallowing of the basin resulted in the establishment of a carbonate/siliciclastic platform typified by ooidal shoals, coral patch reefs and sponge spicule-rich marine sands (Corallian Group). Their complex sedimentation pattern was influenced by local infra-Oxfordian tectonics related to the Howardian–Flamborough Fault Belt. Although the Ampthill Clay and Kimmeridge Clay formations, the latter representing the most important regional hydrocarbon source rock, are not well-exposed, recent boreholes in the Cleveland Basin have allowed a much better understanding of the hemi-pelagic marine environment (both oxic and anoxic) during this phase of sedimentation which marks a global sea-level rise. Although well-studied by world standards, the Jurassic sediments of the Cleveland Basin continue to throw up surprises and advances in our understanding of the Earth as a dynamic system over a period of c. 30 million years. These studies have directly and indirectly influenced our understanding of the Earth as a system, and have played an important role in educating non-specialists, undergraduates and professional geologists over many decades

    A new method for orthoscopic adjustment with the Fedorov stage

    No full text

    On the atomic volume relations in certain isomorphous series. III.

    No full text

    Notes on a new occurrence of stilpnomelane from North Wales

    No full text

    Direct measurement of standard reflectances with the microphotometer

    No full text
    • …
    corecore