47 research outputs found

    Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

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    Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

    An Integrated Transcriptomic and Meta-Analysis of Hepatoma Cells Reveals Factors That Influence Susceptibility to HCV Infection

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    Hepatitis C virus (HCV) is a global problem. To better understand HCV infection researchers employ in vitro HCV cell-culture (HCVcc) systems that use Huh-7 derived hepatoma cells that are particularly permissive to HCV infection. A variety of hyper-permissive cells have been subcloned for this purpose. In addition, subclones of Huh-7 which have evolved resistance to HCV are available. However, the mechanisms of susceptibility or resistance to infection among these cells have not been fully determined. In order to elucidate mechanisms by which hepatoma cells are susceptible or resistant to HCV infection we performed genome-wide expression analyses of six Huh-7 derived cell cultures that have different levels of permissiveness to infection. A great number of genes, representing a wide spectrum of functions are differentially expressed between cells. To focus our investigation, we identify host proteins from HCV replicase complexes, perform gene expression analysis of three HCV infected cells and conduct a detailed analysis of differentially expressed host factors by integrating a variety of data sources. Our results demonstrate that changes relating to susceptibility to HCV infection in hepatoma cells are linked to the innate immune response, secreted signal peptides and host factors that have a role in virus entry and replication. This work identifies both known and novel host factors that may influence HCV infection. Our findings build upon current knowledge of the complex interplay between HCV and the host cell, which could aid development of new antiviral strategies

    The effects of ditch dams on water‐level dynamics in tropical peatlands

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    A significant proportion of tropical peatlands has been drained for agricultural purposes, resulting in severe degradation. Hydrological restoration, which usually involves blocking ditches, is therefore a priority. Nevertheless, the influence of ditch blocking on tropical peatland hydrological functioning is still poorly understood. We studied water-level dynamics using a combination of automated and manual dipwells, and also meteorological data during dry and wet seasons over 6 months at three locations in Sebangau National Park, Kalimantan, Indonesia. The locations were a forested peatland (Forested), a drained peatland with ditch dams (Blocked), and a drained peatland without ditch dams (Drained). In the dry season, water tables at all sites were deeper than the Indonesian regulatory requirement of 40 cm from the peat surface. In the dry season, the ditches were dry and water did not flow to them. The dry season water-table drawdown rates — solely due to evapotranspiration — were 9.3 mm day−1 at Forested, 9.6 mm day−1 at Blocked, but 12.7 mm day−1 at Drained. In the wet season, the proportion of time during which water tables in the wells were deeper than the 40 cm limit ranged between 16% and 87% at Forested, 0% at Blocked, and between 0% and 38% at Drained. In the wet season, water flowed from the peatland to ditches at Blocked and Drained. The interquartile range of hydraulic gradients between the lowest ditch outlet and the farthest well from ditches at Blocked was 3.7 × 10−4 to 7.8 × 10−4 m m−1, but 1.9 × 10−3 to 2.6 × 10−3 m m−1 at Drained. Given the results from Forested, a water-table depth limit policy based on field data may be required, to reflect natural seasonal dynamics in tropical peatlands. Revised spatial designs of dams or bunds are also required, to ensure effective water-table management as part of tropical peatland restoration
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