Non-alcoholic fatty liver disease (NAFLD) is projected to become the leading cause of hepatocellular carcinoma (HCC) in many countries. Many risk factors for NAFLD are also independently associated ...with HCC, including obesity, diabetes, Hispanic ethnicity and genetic polymorphisms in PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13. Steatosis-related lipotoxicity and oxidative DNA damage can induce hepatocarcinogenesis. These factors may explain the association between NAFLD and HCC, especially in the absence of cirrhosis. In fact, NAFLD/NASH is a leading cause of HCC in the absence of cirrhosis. Identifying patients with pre-cirrhotic NAFLD who have a high enough HCC risk to justify HCC screening represents one of the greatest clinical challenges in NAFLD. Validated models that combine multiple risk factors and fibrosis stage into “HCC risk calculators” are not yet available for patients with NAFLD. Development of such tools would enable risk stratification, identification of high-risk patients even in the absence of cirrhosis, and individualised (risk-based) surveillance strategies.
Lipotoxicity drives the development of progressive hepatic inflammation and fibrosis in a subgroup of patients with nonalcoholic fatty liver disease (NAFLD), causing nonalcoholic steatohepatitis ...(NASH) and even progression to cirrhosis and hepatocellular carcinoma (HCC). While the underlying molecular mechanisms responsible for the development of inflammation and fibrosis that characterize progressive NASH remain unclear, emerging evidence now suggests that hepatic free cholesterol (FC) is a major lipotoxic molecule critical in the development of experimental and human NASH. In this review, we examine the effects of excess FC in hepatocytes, Kupffer cells (KCs), and hepatic stellate cells (HSCs), and the subcellular mechanisms by which excess FC can induce cellular toxicity or proinflammatory and profibrotic effects in these cells.
HCV eradication by antiviral treatment reduces but does not eliminate HCC risk. Patients with established cirrhosis require HCC surveillance “indefinitely” after sustained virologic response (SVR) ...because they appear to have a high risk of HCC even many years after SVR. Patients without established or known cirrhosis may still require surveillance after SVR if they have a sufficiently high HCC risk. In all patients who achieve SVR, the key question is how we can reliably estimate HCC risk, and the change in HCC risk over time, to determine whether the patient might benefit from HCC surveillance. HCC risk is one of the most important factors that should inform decisions of whether and how to screen for HCC. Promising strategies for estimating HCC risk include simplified scoring systems (such as fibrosis-4), liver elastography and multivariable HCC risk calculators. Such tools may enable risk stratification and individualised, risk-based surveillance strategies (“precision HCC screening”) in the future.
Abstract
Gravitational lensing near a black hole is strong enough that light rays can circle the event horizon multiple times. Photons emitted in multiple directions at a single event, perhaps ...because of localized, impulsive heating of accreting plasma, take multiple paths to a distant observer. In the Kerr geometry, each path is associated with a distinct light travel time and a distinct arrival location in the image plane, producing black hole glimmer. This sequence of arrival times and locations uniquely encodes the mass and spin of the black hole and can be understood in terms of properties of bound photon orbits. We provide a geometrically motivated treatment of Kerr glimmer and evaluate it numerically for simple hot-spot models to show that glimmer can be measured in a finite-resolution observation. We discuss potential measurement methods and implications for tests of the Kerr hypothesis.
Biochemical adaptation Hochachka, Pater W; Hochachka, Pater W; Somero, George N
2014., 20140701, 2014, 1984, Letnik:
710
eBook
This book discusses biochemical adaptation to environments from freezing polar oceans to boiling hot springs, and under hydrostatic pressures up to 1,000 times that at sea level.
Originally published ...in 1984.
ThePrinceton Legacy Libraryuses the latest print-on-demand technology to again make available previously out-of-print books from the distinguished backlist of Princeton University Press. These paperback editions preserve the original texts of these important books while presenting them in durable paperback editions. The goal of the Princeton Legacy Library is to vastly increase access to the rich scholarly heritage found in the thousands of books published by Princeton University Press since its founding in 1905.
Fertile soils have been an essential resource for humanity for 10,000 y, but the ecological mechanisms involved in the creation and restoration of fertile soils, and especially the role of plant ...diversity, are poorly understood. Here we use results of a long-term, unfertilized plant biodiversity experiment to determine whether biodiversity, especially plant functional biodiversity, impacted the regeneration of fertility on a degraded sandy soil. After 23 y, plots containing 16 perennial grassland plant species had, relative to monocultures of these same species, ∼30 to 90% greater increases in soil nitrogen, potassium, calcium, magnesium, cation exchange capacity, and carbon and had ∼150 to 370% greater amounts of N, K, Ca, and Mg in plant biomass. Our results suggest that biodiversity, likely in combination with the increased plant productivity caused by higher biodiversity, led to greater soil fertility. Moreover, plots with high plant functional diversity, those containing grasses, legumes, and forbs, accumulated significantly greater N, K, Ca, and Mg in the total nutrient pool (plant biomass and soil) than did plots containing just one of these three functional groups. Plant species in these functional groups had trade-offs between their tissue N content, tissue K content, and root mass, suggesting why species from all three functional groups were essential for regenerating soil fertility. Our findings suggest that efforts to regenerate soil C stores and soil fertility may be aided by creative uses of plant diversity.
Direct-acting antiviral (DAA) regimens are safe and effective at eradicating hepatitis C virus (HCV) infection. Unfortunately, DAAs remain expensive, so treatment of all HCV-infected patients would ...substantially affect health care costs. It is therefore important to continue to assess the hepatic and extrahepatic benefits of a DAA-induced sustained virologic response (SVR). A DAA-induced SVR reduces a patient’s risk of cirrhosis and hepatocellular carcinoma and extrahepatic manifestations of HCV infection; there are also data to indicate that an SVR can reduce mortality. SVR is a relevant clinical end point, but further analyses are required to confirm its importance among diverse HCV-infected populations and to document the public health benefits of HCV elimination at the population level. We review the evidence for the benefits associated with SVRs in different clinical settings and challenges to data collection.
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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%.
Renewable energy plays a vital role in achieving environmental sustainability, however, the mitigating effect varies across countries depending on the share of renewables in the energy mix. Herein, ...we analyze the effect of renewable energy consumption, energy prices, and trade on emissions in G-7 countries. The results demonstrate that renewable energy and energy prices exert negative pressure on CO2 emissions while trade volume exerts a robust positive pressure on CO2 emissions. The country-specific estimation results provide evidence of a negative effect of energy prices on CO2 emissions. While the environmental Kuznets curve hypothesis is validated at the panel and country-specific levels, the effect of renewable energy consumption and trade, are disparate across countries. The panel Granger causality shows a mono-directional causality flowing from energy prices, GDP, the quadratic term of GDP and trade to CO2 emissions. Renewable energy consumption, however, has no causal relationship with CO2 emissions but indirectly affects CO2 emissions through its direct effect on energy prices. Joint action on trade, energy prices, and country-specific renewable energy policies have implications for environmental sustainability and the attainment of the Sustainable Development Goals (SDGs).
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•Assessment of renewable energy usage, energy prices and trade in G-7 countries.•Renewable energy consumption and energy price exert negative pressure CO2 emissions.•The EKC hypothesis is validated in both panel and country-specific levels.•Effects of renewable energy consumption and trade are disparate across countries.•Renewable energy affects energy prices while energy prices affect CO2 emissions.
Food allergy is a public health concern especially after recognizing its constantly increased prevalence and severity. Despite careful reading of food ingredient statements, food allergic individuals ...may experience reactions caused by "hidden", "masked", or "contaminated" proteins that are known major allergens. Many techniques have been developed to detect even small traces of food allergens, for clinical or laboratory purposes. Enzyme-linked immunosorbent assay (ELISA) is one of the best validated and most routinely used immunoassay in allergy research, in allergy diagnosis in allergy-related quality control in various industries. Although as a technique it has been implemented for the last 45 years, the evolution in biochemistry allowed the development of ultrasensitive ELISA variations that are capable of measuring quantities in the scale of picograms, rendering ELISA attractive, robust, and very famous.
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