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•DAA-induced SVR is associated with a 71% reduction in HCC risk.•SVR is associated with a similar reduction in HCC risk no matter what regimen is used to achieve it.•Treatment with ...DAAs is not associated with increased HCC risk compared with interferon.
It is unclear whether direct-acting antiviral (DAA) treatment-induced sustained virologic response (SVR) reduces the risk of hepatocellular carcinoma (HCC) in patients with HCV infection. Therefore, in the current study, our aim was to determine the impact of DAA-induced SVR on HCC risk.
We identified 62,354 patients who initiated antiviral treatment in the Veterans Affairs (VA) national healthcare system from 1 January 1999 to 31 December 2015, including 35,871 (58%) interferon (IFN)-only regimens, 4,535 (7.2%) DAA + IFN regimens, and 21,948 (35%) DAA-only regimens. We retrospectively followed patients until 15 June 2017 to identify incident cases of HCC. We used Cox proportional hazards regression to determine the association between SVR and HCC risk or between type of antiviral regimen (DAA-only vs. DAA + IFN vs. IFN-only) and HCC risk.
We identified 3,271 incident cases of HCC diagnosed at least 180 days after initiation of antiviral treatment during a mean follow-up of 6.1 years. The incidence of HCC was highest in patients with cirrhosis and treatment failure (3.25 per 100 patient-years), followed by cirrhosis and SVR (1.97), no cirrhosis and treatment failure (0.87), and no cirrhosis and SVR (0.24). SVR was associated with a significantly decreased risk of HCC in multivariable models irrespective of whether the antiviral treatment was DAA-only (adjusted hazard ratio AHR 0.29; 95% CI 0.23–0.37), DAA + IFN (AHR 0.48; 95% CI 0.32–0.73) or IFN-only (AHR 0.32; 95% CI 0.28–0.37). Receipt of a DAA-only or DAA + IFN regimen was not associated with increased HCC risk compared with receipt of an IFN-only regimen.
DAA-induced SVR is associated with a 71% reduction in HCC risk. Treatment with DAAs is not associated with increased HCC risk compared with treatment with IFN.
It was unclear whether direct-acting antiviral treatment-induced sustained virologic response reduces the risk of liver cancer in patients with HCV infection. We demonstrated that eradication of HCV infection with direct-acting antiviral agents reduces the risk of liver cancer by 71%.
Acute gastroenteritis caused by noroviruses often has a duration of 2–0 days and is characteristically self-limiting. In contrast, chronic infection caused by noroviruses in immunocompromised ...individuals can last from weeks to years, making clinical management difficult. The mechanisms by which noroviruses establish persistent infection, and the role of immunocompromised hosts as a reservoir for noroviruses in the general human population, are not known. However, study of this patient cohort may lead to new insights into norovirus biology and approaches to treatment.
Although the terrestrial biosphere absorbs about 25 per cent of anthropogenic carbon dioxide (CO
) emissions, the rate of land carbon uptake remains highly uncertain, leading to uncertainties in ...climate projections
. Understanding the factors that limit or drive land carbon storage is therefore important for improving climate predictions. One potential limiting factor for land carbon uptake is soil moisture, which can reduce gross primary production through ecosystem water stress
, cause vegetation mortality
and further exacerbate climate extremes due to land-atmosphere feedbacks
. Previous work has explored the impact of soil-moisture availability on past carbon-flux variability
. However, the influence of soil-moisture variability and trends on the long-term carbon sink and the mechanisms responsible for associated carbon losses remain uncertain. Here we use the data output from four Earth system models
from a series of experiments to analyse the responses of terrestrial net biome productivity to soil-moisture changes, and find that soil-moisture variability and trends induce large CO
fluxes (about two to three gigatons of carbon per year; comparable with the land carbon sink itself
) throughout the twenty-first century. Subseasonal and interannual soil-moisture variability generate CO
as a result of the nonlinear response of photosynthesis and net ecosystem exchange to soil-water availability and of the increased temperature and vapour pressure deficit caused by land-atmosphere interactions. Soil-moisture variability reduces the present land carbon sink, and its increase and drying trends in several regions are expected to reduce it further. Our results emphasize that the capacity of continents to act as a future carbon sink critically depends on the nonlinear response of carbon fluxes to soil moisture and on land-atmosphere interactions. This suggests that the increasing trend in carbon uptake rate may not be sustained past the middle of the century and could result in accelerated atmospheric CO
growth.
Both low soil water content (SWC) and high atmospheric dryness (vapor pressure deficit, VPD) can negatively affect terrestrial gross primary production (GPP). The sensitivity of GPP to soil versus ...atmospheric dryness is difficult to disentangle, however, because of their covariation. Using global eddy-covariance observations, here we show that a decrease in SWC is not universally associated with GPP reduction. GPP increases in response to decreasing SWC when SWC is high and decreases only when SWC is below a threshold. By contrast, the sensitivity of GPP to an increase of VPD is always negative across the full SWC range. We further find canopy conductance decreases with increasing VPD (irrespective of SWC), and with decreasing SWC on drier soils. Maximum photosynthetic assimilation rate has negative sensitivity to VPD, and a positive sensitivity to decreasing SWC when SWC is high. Earth System Models underestimate the negative effect of VPD and the positive effect of SWC on GPP such that they should underestimate the GPP reduction due to increasing VPD in future climates.
Abstract
The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB, rcsb.org), the US data center for the global PDB archive, serves thousands of Data Depositors in the ...Americas and Oceania and makes 3D macromolecular structure data available at no charge and without usage restrictions to more than 1 million rcsb.org Users worldwide and 600 000 pdb101.rcsb.org education-focused Users around the globe. PDB Data Depositors include structural biologists using macromolecular crystallography, nuclear magnetic resonance spectroscopy and 3D electron microscopy. PDB Data Consumers include researchers, educators and students studying Fundamental Biology, Biomedicine, Biotechnology and Energy. Recent reorganization of RCSB PDB activities into four integrated, interdependent services is described in detail, together with tools and resources added over the past 2 years to RCSB PDB web portals in support of a ‘Structural View of Biology.’
The terrestrial carbon and water cycles are strongly coupled. As atmospheric carbon dioxide concentration increases, climate and the coupled hydrologic cycle are modified, thus altering the ...terrestrial water cycle and the availability of soil moisture necessary for plants' carbon dioxide uptake. Concomitantly, rising surface carbon dioxide concentrations also modify stomatal (small pores at the leaf surface) regulation as well as biomass, thus altering ecosystem photosynthesis and transpiration rates. Those coupled changes have profound implications for the predictions of the carbon and water cycles. This paper reviews the main mechanisms behind the coupling of the terrestrial water and carbon cycles. We especially focus on the key role of dryness (atmospheric dryness and terrestrial water availability) on carbon uptake, as well as the predicted impact of rising carbon dioxide on the water cycle. Challenges related to this coupling and the necessity to constrain it based on observations are finally discussed.
Background & Aims Cirrhosis and hepatocellular carcinoma (HCC) are predicted to increase in the United States but the accuracy of prior forecasts and the contributions from various liver disease ...etiologies remain unclear. We aimed to determine the burden of cirrhosis and HCC according to underlying cause from 2001 to 2013. Methods We developed a national retrospective cohort of Veterans Affairs (VA) patients with the diagnosis of cirrhosis (n = 129,998) or HCC ( n = 21,326) from 2001 to 2013. We used laboratory results, International Classification of Diseases, ninth edition (ICD-9) codes, and body mass index to identify underlying etiologies. Results In 2013, VA provided care to 5,720,614 individuals, of whom 60,553 (1.06%) had cirrhosis and 7,670 (0.13%) had HCC. Hepatitis C virus (HCV) was present in an increasing proportion of cirrhosis and HCC between 2001 and 2013, reaching 48% of cirrhosis cases and deaths and 67% of HCC cases and deaths by 2013. Cirrhosis prevalence nearly doubled from 2001 to 2013 (664 to 1058 per 100,000 enrollees), driven by HCV and nonalcoholic fatty liver disease (NAFLD). Cirrhosis incidence ranged from 159 to 193 per 100,000 patient-years. Deaths in patients with cirrhosis increased from 83 to 126 per 100,000 patient-years, largely driven by HCV. HCC incidence was 2.5-fold increased from 17 to 45 per 100,000 patient-years. HCC mortality tripled from 13 to 37 per 100,000 patient-years, driven overwhelmingly by HCV, with much smaller contributions from NAFLD and alcoholic liver disease. Conclusions Cirrhosis prevalence and mortality and HCC incidence and mortality increased from 2001 to 2013, driven by HCV, with a smaller contribution from NAFLD. If current trends continue, cirrhosis prevalence will peak in 2021. Health care systems will need to accommodate rising numbers of patients with cirrhosis and HCC.
The small extent of seasonally snow-covered Australian mountains means that there has not been a great selective pressure on the mammalian fauna for adaptations to this environment. Only one large ...marsupial, the common wombat (Vombatus ursinus (Shaw, 1800)), is widespread above the winter snowline. In the past 20 years, with snow depth and duration declining, the swamp wallaby (Wallabia bicolor (Desmarest, 1804)) has become more common above the winter snowline. The red-necked wallaby (Macropus rufogriseus (Desmarest, 1817)) is common in alpine Tasmania where seasonal snow cover is neither as deep nor as long-lasting as on the mainland, but has only been recorded regularly above the winter snowline in the mainland Snowy Mountains since 2011. This study examines morphological aspects of locomotion of these three herbivorous marsupials in snow. The wombat is the best adapted to snow, with quadrupedal gait and an expanded home range allowing it to locate and feed on the same plant groups as it does at lower elevation. Wallabies are poorly adapted to locomotion in snow, but the browsing swamp wallaby is able to maintain its dietary habit by feeding on exposed shrubs in deep snow, whereas the red-necked wallaby, which depends more on grazing, appears constrained to areas where snow is shallow.
This book examines the evidence supporting claims that America’s founding principles are based in part on religion. These claims usually center on the Puritan background to republican government ...(e.g. the Mayflower Compact), assertions of divine providence directing the leaders and events of the American Revolution, and the religious beliefs of various Founders. The book demonstrates that the notion of a Christian origin for American government is one of the nation’s leading founding myths, one that was consciously created during the early nineteenth century as part of the drive to establish a national identity. In seeking to unify the nation and proclaim its unique status to the world, proponents created the myth of America’s religious origins out of a desire to sanctify the founding. Modern-day proponents of America’s religious foundations need to understand the purposeful origins of the narrative upon which they rely.
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