Developing a community HCV service: project ITTREAT (Integrated Community based Test - stage - TREAT) service for people who inject drugs

Liver disease is now the third most common cause of premature death in the UK, with chronic viral hepatitis being an important contributory factor. Often the diagnosis of chronic liver disease is only made when patients present late in the disease trajectory. This underscores the importance of near patient testing and linkage into care. The need for community based models for liver disease is in line with the recently commissioned National Liver report, which calls for assessment and treatment of high-risk individuals in the community. In this manuscript our objectives are to discuss the need for community services for individuals with hepatitis C virus (HCV) infection and give an overview of the different community models for HCV. Finally we describe our experiences in setting up a successful nurse led service for screening, stratification and treatment of HCV related liver disease at a substance misuse service. We highlight the important stages of this process including engaging with stakeholders, obtaining funding and service set up. We also explore the obstacles and challenges faced and summarise our key recommendations. A brief summary of interim clinical outcomes is also presented

Change in multimodal MRI markers predicts dementia risk in cerebral small vessel disease.

OBJECTIVE: To determine whether MRI markers, including diffusion tensor imaging (DTI), can predict cognitive decline and dementia in patients with cerebral small vessel disease (SVD). METHODS: In the prospective St George's Cognition and Neuroimaging in Stroke study, multimodal MRI was performed annually for 3 years and cognitive assessments annually for 5 years in a cohort of 99 patients with SVD, defined as symptomatic lacunar stroke and confluent white matter hyperintensities (WMH). Progression to dementia was determined in all patients. Progression of WMH, brain volume, lacunes, cerebral microbleeds, and a DTI measure (the normalized peak height of the mean diffusivity histogram distribution) as a marker of white matter microstructural damage were determined. RESULTS: Over 5 years of follow-up, 18 patients (18.2%) progressed to dementia. A significant change in all MRI markers, representing deterioration, was observed. The presence of new lacunes, and rate of increase in white matter microstructural damage on DTI, correlated with both decline in executive function and global functioning. Growth of WMH and deterioration of white matter microstructure on DTI predicted progression to dementia. A model including change in MRI variables together with their baseline values correctly classified progression to dementia with a C statistic of 0.85. CONCLUSIONS: This longitudinal prospective study provides evidence that change in MRI measures including DTI, over time durations during which cognitive change is not detectable, predicts cognitive decline and progression to dementia. It supports the use of MRI measures, including DTI, as useful surrogate biomarkers to monitor disease and assess therapeutic interventions

Oblique Shocks As The Origin Of Radio To Gamma-ray Variability In AGN

The `shock in jet' model for cm-waveband blazar variability is revisited, allowing for arbitrary shock orientation with respect to the jet flow direction, and both random and ordered magnetic field. It is shown that oblique shocks can explain events with swings in polarization position angle much less than the 90 deg. associated with transverse structures, while retaining the general characteristics of outbursts, including spectral behavior and level of peak percentage polarization. Models dominated by a force-free, minimum energy magnetic field configuration (essentially helical) display a shallow rise in percentage polarization and frequency dependent swing in polarization position angle not in agreement with the results of single-dish monitoring observations, implying that the field is predominantly random in the quiescent state. Outbursts well-explained by the `shock in jet' model are present during gamma-ray flaring in several sources, supporting the idea that shock events are responsible for activity from the radio to gamma-ray bands.Comment: 19 pages, 8 figures, accepted for publication in Ap

Art as everyday practice: A study of gongfu tea in Chaoshan, China

This study explores the place of traditional Chinese tea culture in a society undergoing changes both culturally, with the rise of consumerism, and structurally, with the growth of a market economy and globalization. It does so by examining tea drinking in the Chaoshan region of eastern Guangdong Province. Chaoshan is the home of a style of preparing and drinking tea known as 'gongfu' tea, involving preparation of strong tea in small pots, and drinking repeated brews in small cups. As well as being an important part of the regional food and drink culture, gongfu tea has been adopted outside Chaoshan as a refined form of tea culture, and even represented outside China as an authentic 'Chinese tea ceremony'. It therefore provides an appropriate case study through which to examine both local practices and the processes through which local cultural objects are appropriated and transformed for use in other contexts. The study pursues two lines of inquiry. The first examines the development of a contemporary discourse representing Chaoshan gongfu tea as a manifestation of a continuous tradition dating back more than 1,000 years to the Tang Dynasty. I argue that, while tea has long been consumed in Chaoshan, this representation is not supported by historical evidence, and is an example of an invented tradition. The second line of inquiry is a study of contemporary gongfu tea-drinking practices, both among people born in Chaoshan, and among non-Chaoshan people who have taken it up as an acquired practice. Methodologically, the study uses sociological ethnography, in which the ‘field’ of research is not a specific locality but a field of inquiry defined by pursuing linkages relevant to the research questions. Findings are based on fieldwork involving semi-structured interviews with, and observations among, a snowball sample of 32 individuals plus one family that was treated, for analytical purposes, as a single unit. Fieldwork was conducted in four visits to the region between 2010 and 2017. The study found that, among people born in Chaoshan, gongfu tea is experienced as an integral part of everyday life, rather than a form of tea art. As a practice, it entails close attention to detail in preparing, serving and drinking tea, on the one hand and, on the other, a high level of creativity, rather than slavish adherence to a prescriptive model. People who have taken up gongfu tea as an acquired practice exhibit similar skills, but for them, gongfu tea is unlikely to be woven into the fabric of everyday life. Some people choose to cultivate additional knowledge and skills in order to enhance their gongfu tea practice as tea art. The study concludes by considering the relationship between Chaoshan gongfu tea as a cultural object created through discourse, and contemporary tea-drinking practices. I argue that the relationship is not as close as literary accounts imply. While each is informed by the other, neither is a mirror of the other, and each is a product of distinctive social processes: the discourse, by the activities of academics, entrepreneurs and others, each pursuing their own interests; tea-drinking practices, by the opportunities and constraints generated through economic and social processes emanating from the wider society

Mechanisms of Cognitive Impairment in Cerebral Small Vessel Disease: Multimodal MRI Results from the St George's Cognition and Neuroimaging in Stroke (SCANS) Study.

Cerebral small vessel disease (SVD) is a common cause of vascular cognitive impairment. A number of disease features can be assessed on MRI including lacunar infarcts, T2 lesion volume, brain atrophy, and cerebral microbleeds. In addition, diffusion tensor imaging (DTI) is sensitive to disruption of white matter ultrastructure, and recently it has been suggested that additional information on the pattern of damage may be obtained from axial diffusivity, a proposed marker of axonal damage, and radial diffusivity, an indicator of demyelination. We determined the contribution of these whole brain MRI markers to cognitive impairment in SVD. Consecutive patients with lacunar stroke and confluent leukoaraiosis were recruited into the ongoing SCANS study of cognitive impairment in SVD (n = 115), and underwent neuropsychological assessment and multimodal MRI. SVD subjects displayed poor performance on tests of executive function and processing speed. In the SVD group brain volume was lower, white matter hyperintensity volume higher and all diffusion characteristics differed significantly from control subjects (n = 50). On multi-predictor analysis independent predictors of executive function in SVD were lacunar infarct count and diffusivity of normal appearing white matter on DTI. Independent predictors of processing speed were lacunar infarct count and brain atrophy. Radial diffusivity was a stronger DTI predictor than axial diffusivity, suggesting ischaemic demyelination, seen neuropathologically in SVD, may be an important predictor of cognitive impairment in SVD. Our study provides information on the mechanism of cognitive impairment in SVD

Wet scavenging of soluble gases in DC3 deep convective storms using WRF-Chem simulations and aircraft observations

We examine wet scavenging of soluble trace gases in storms observed during the Deep Convective Clouds and Chemistry (DC3) field campaign. We conduct high-resolution simulations with the Weather Research and Forecasting model with Chemistry (WRF-Chem) of a severe storm in Oklahoma. The model represents well the storm location, size, and structure as compared with Next Generation Weather Radar reflectivity, and simulated CO transport is consistent with aircraft observations. Scavenging efficiencies (SEs) between inflow and outflow of soluble species are calculated from aircraft measurements and model simulations. Using a simple wet scavenging scheme, we simulate the SE of each soluble species within the error bars of the observations. The simulated SEs of all species except nitric acid (HNO_3) are highly sensitive to the values specified for the fractions retained in ice when cloud water freezes. To reproduce the observations, we must assume zero ice retention for formaldehyde (CH_2O) and hydrogen peroxide (H_2O_2) and complete retention for methyl hydrogen peroxide (CH_3OOH) and sulfur dioxide (SO_2), likely to compensate for the lack of aqueous chemistry in the model. We then compare scavenging efficiencies among storms that formed in Alabama and northeast Colorado and the Oklahoma storm. Significant differences in SEs are seen among storms and species. More scavenging of HNO_3 and less removal of CH_3OOH are seen in storms with higher maximum flash rates, an indication of more graupel mass. Graupel is associated with mixed-phase scavenging and lightning production of nitrogen oxides (NO_x), processes that may explain the observed differences in HNO_3 and CH_3OOH scavenging

ITTREAT (Integrated Community Test - stage - TREAT) Hepatitis C service for people who use drugs: real world outcomes

Background/aims: Direct acting antivirals (DAA) provide an unprecedented opportunity for a “find-and-treat strategy”. We aimed to report real-world clinical, patient reported and health economic outcomes of community-based HCV screening/treatment in people who use drugs (PWUD). Methods: Project ITTREAT (2013-2021), established at a drug and alcohol treatment centre, offered a comprehensive service. Generic (SF-12v2 and EQ-5D-5L) and liver-specific (SFLDQoL) health related quality of life (HRQoL) were assessed before and after HCV treatment. Costs/case detected and cured were calculated. Primary outcome measure was sustained virological response (SVR) (intention to treat). Results: Till March 2018, 573 individuals recruited, 462 (81%) males, mean age 40.5 + 10.0 years. Of the 125 treated, 115 (92%) had past/current history of injecting drug use, 88 (70%) were receiving opioid agonist treatment and 50 (40%) were homeless. Twenty-six percent received interferon-based and 74% DAA-only regimens. SVR (ITT) was 87% (90% with DAAs). Service uptake/HCV treatment completion rates were > 95%, HCV reinfection being 2.63/100 person years (95% CI 0.67-10.33). HRQoL improved significantly at end of treatment in those with SVR: SFLDQoL (symptoms, memory, distress, loneliness, hopelessness, sleep and stigma) (p</= 0.011); SF-12 v2 physical and mental health domains (p<0.001); and EQ-5D-5L composite profile score (p= 0.009) and visual analogue scale, p<0.001. Cost (British pounds 2018) per case detected was £171; mean cost per cure (excluding medication) was £702 + 188. Conclusions: Excellent real-world SVRs in PWUD with significant improvement in HRQoL can be achieved at modest costs. Project ITTREAT endorses community-based integrated services to help achieve HCV elimination

Mnemonic function in small vessel disease and associations with white matter tract microstructure.

Cerebral small vessel disease (SVD) is associated with deficits in working memory, with a relative sparing of long-term memory; function may be influenced by white matter microstructure. Working and long-term memory were examined in 106 patients with SVD and 35 healthy controls. Microstructure was measured in the uncinate fasciculi and cingula. Working memory was more impaired than long-term memory in SVD, but both abilities were reduced compared to controls. Regression analyses found that having SVD explained the variance in memory functions, with additional variance explained by the cingula (working memory) and uncinate (long-term memory). Performance can be explained in terms of integrity loss in specific white matter tract associated with mnemonic functions

Evolution of the Toarcian (Early Jurassic) carbon-cycle and global climatic controls on local sedimentary processes (Cardigan Bay Basin, UK)

The late Early Jurassic Toarcian Stage represents the warmest interval of the Jurassic Period, with an abrupt rise in global temperatures of up to ∼7 °C in mid-latitudes at the onset of the early Toarcian Oceanic Anoxic Event (T-OAE; ∼183 Ma). The T-OAE, which has been extensively studied in marine and continental successions from both hemispheres, was marked by the widespread expansion of anoxic and euxinic waters, geographically extensive deposition of organic-rich black shales, and climatic and environmental perturbations. Climatic and environmental processes following the T-OAE are, however, poorly known, largely due to a lack of study of stratigraphically well-constrained and complete sedimentary archives. Here, we present integrated geochemical and physical proxy data (high-resolution carbon-isotope data (δ13C), bulk and molecular organic geochemistry, inorganic petrology, mineral characterisation, and major- and trace-element concentrations) from the biostratigraphically complete and expanded entire Toarcian succession in the Llanbedr (Mochras Farm) Borehole, Cardigan Bay Basin, Wales, UK. With these data, we (1) construct the first high-resolution biostratigraphically calibrated chemostratigraphic reference record for nearly the complete Toarcian Stage, (2) establish palaeoceanographic and depositional conditions in the Cardigan Bay Basin, (3) show that the T-OAE in the hemipelagic Cardigan Bay Basin was marked by the occurrence of gravity-flow deposits that were likely linked to globally enhanced sediment fluxes to continental margins and deeper marine (shelf) basins, and (4) explore how early Toarcian (tenuicostatum and serpentinum zones) siderite formation in the Cardigan Bay Basin may have been linked to low global oceanic sulphate concentrations and elevated supply of iron (Fe) from the hinterland, in response to climatically induced changes in hydrological cycling, global weathering rates and large-scale sulphide and evaporite deposition