Global, regional, and national burden of hepatitis B, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Combating viral hepatitis is part of the UN Sustainable Development Goals (SDGs), and WHO has put forth hepatitis B elimination targets in its Global Health Sector Strategy on Viral Hepatitis (WHO-GHSS) and Interim Guidance for Country Validation of Viral Hepatitis Elimination (WHO Interim Guidance). We estimated the global, regional, and national prevalence of hepatitis B virus (HBV), as well as mortality and disability-adjusted life-years (DALYs) due to HBV, as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. This included estimates for 194 WHO member states, for which we compared our estimates to WHO elimination targets. Methods: The primary data sources were population-based serosurveys, claims and hospital discharges, cancer registries, vital registration systems, and published case series. We estimated chronic HBV infection and the burden of HBV-related diseases, defined as an aggregate of cirrhosis due to hepatitis B, liver cancer due to hepatitis B, and acute hepatitis B. We used DisMod-MR 2.1, a Bayesian mixed-effects meta-regression tool, to estimate the prevalence of chronic HBV infection, cirrhosis, and aetiological proportions of cirrhosis. We used mortality-to-incidence ratios modelled with spatiotemporal Gaussian process regression to estimate the incidence of liver cancer. We used the Cause of Death Ensemble modelling (CODEm) model, a tool that selects models and covariates on the basis of out-of-sample performance, to estimate mortality due to cirrhosis, liver cancer, and acute hepatitis B. Findings: In 2019, the estimated global, all-age prevalence of chronic HBV infection was 4·1% (95% uncertainty interval [UI] 3·7 to 4·5), corresponding to 316 million (284 to 351) infected people. There was a 31·3% (29·0 to 33·9) decline in all-age prevalence between 1990 and 2019, with a more marked decline of 76·8% (76·2 to 77·5) in prevalence in children younger than 5 years. HBV-related diseases resulted in 555 000 global deaths (487 000 to 630 000) in 2019. The number of HBV-related deaths increased between 1990 and 2019 (by 5·9% [-5·6 to 19·2]) and between 2015 and 2019 (by 2·9% [-5·9 to 11·3]). By contrast, all-age and age-standardised death rates due to HBV-related diseases decreased during these periods. We compared estimates for 2019 in 194 WHO locations to WHO-GHSS 2020 targets, and found that four countries achieved a 10% reduction in deaths, 15 countries achieved a 30% reduction in new cases, and 147 countries achieved a 1% prevalence in children younger than 5 years. As of 2019, 68 of 194 countries had already achieved the 2030 target proposed in WHO Interim Guidance of an all-age HBV-related death rate of four per 100 000. Interpretation: The prevalence of chronic HBV infection declined over time, particularly in children younger than 5 years, since the introduction of hepatitis B vaccination. HBV-related death rates also decreased, but HBV-related death counts increased as a result of population growth, ageing, and cohort effects. By 2019, many countries had met the interim seroprevalence target for children younger than 5 years, but few countries had met the WHO-GHSS interim targets for deaths and new cases. Progress according to all indicators must be accelerated to meet 2030 targets, and there are marked disparities in burden and progress across the world. HBV interventions, such as vaccination, testing, and treatment, must be strategically supported and scaled up to achieve elimination. Funding: Bill & Melinda Gates Foundation

An Investigation of state changes of PSR J2021+4026 and Vela pulsar

We investigate the high energy emission activities of two bright gamma-ray pulsars, PSR~J2021+4026 and Vela. For PSR~J2021+4026, the state changes in the gamma-ray flux and spin-down rate have been observed. We report that the long-term evolution of the gamma-ray flux and timing behavior of PSR~J2021+4026 suggests a new gamma-ray flux recovery at around MJD~58910 and a flux decrease around MJD~59500. During this epoch, the staying time, the gamma-ray flux difference and spin-down rate are smaller than previous epochs in the same state. The waiting timescale of the quasi-periodic state changes is similar to the waiting timescale of the glitch events of the Vela pulsar. For the Vela pulsar, the quench of the radio pulse was in a timescale of $\sim0.2$~s after the 2016 glitch, and the glitch may disturb the structure of the magnetosphere. Nevertheless, we did not find any evidence for a long-term change in the gamma-ray emission properties using years of $Fermi$-LAT data, and therefore, no long-term magnetosphere structural change. We also conduct searching for photons above 100~GeV using 15-year $Fermi$-LAT data, and found none. Our results provide additional information for the relation between the state change of the gamma-ray emission and the glitch event.Comment: 11 pages,8 figure

An update on the lithogenic mechanisms of cholecystokinin a receptor (Cckar), an important gallstone gene for lith13

The cholecystokinin A receptor (CCKAR) is expressed predominantly in the gallbladder and small intestine in the digestive system, where it is responsible for CCK’s regulation of gallbladder and small intestinal motility. The effect of CCKAR on small intestinal transit is a physiological response for regulating intestinal cholesterol absorption. The Cckar gene has been identified to be an important gallstone gene, Lith13, in inbred mice by a powerful quantitative trait locus analysis. Knockout of the Cckar gene in mice enhances cholesterol cholelithogenesis by impairing gallbladder contraction and emptying, promoting cholesterol crystallization and crystal growth, and increasing intestinal cholesterol absorption. Clinical and epidemiological studies have demonstrated that several variants in the CCKAR gene are associated with increased prevalence of cholesterol cholelithiasis in humans. Dysfunctional gallbladder emptying in response to exogenously administered CCK-8 is often found in patients with cholesterol gallstones, and patients with pigment gallstones display an intermediate degree of gallbladder motility defect. Gallbladder hypomotility is also revealed in some subjects without gallstones under several conditions: pregnancy, total parenteral nutrition, celiac disease, oral contraceptives and conjugated estrogens, obesity, diabetes, the metabolic syndrome, and administration of CCKAR antagonists. The physical–chemical, genetic, and molecular studies of Lith13 show that dysfunctional CCKAR enhances susceptibility to cholesterol gallstones through two primary mechanisms: impaired gallbladder emptying is a key risk factor for the development of gallbladder hypomotility, biliary sludge (the precursor of gallstones), and microlithiasis, as well as delayed small intestinal transit augments cholesterol absorption as a major source for the hepatic hypersecretion of biliary cholesterol and for the accumulation of excess cholesterol in the gallbladder wall that further worsens impaired gallbladder motor function. If these two defects in the gallbladder and small intestine could be prevented by the potent CCKAR agonists, the risk of developing cholesterol gallstones could be dramatically reduced

Prediction of a positive surgical margin and biochemical recurrence after robot-assisted radical prostatectomy

The positive surgical margin (PSM) and biochemical recurrence (BCR) are two main factors associated with poor oncotherapeutic outcomes after prostatectomy. This is an Asian population study based on a single-surgeon experience to deeply investigate the predictors for PSM and BCR. We retrospectively included 419 robot-assisted radical prostatectomy cases. The number of PSM cases was 126 (30.1%), stratified as 22 (12.2%) in stage T2 and 103 (43.6%) in stage T3. Preoperative prostate-specific antigen (PSA) > 10 ng/mL (p = 0.047; odds ratio [OR] 1.712), intraoperative blood loss > 200 mL (p = 0.006; OR 4.01), and postoperative pT3 stage (p  10 ng/mL (p  3 (p = 0.02; HR 1.964), and PSM (p = 0.027; HR 1.725) were four significant predictors for BCR in multivariable analysis. PSMs occurred mostly in the posterolateral regions (73.8%) which were associated with nerve-sparing procedures (p = 0.012) while apical PSMs were correlated intraoperative bleeding (p  3 (p = 0.002; HR 2.689) was a significant BCR predictor. These results indicate that PSA and pathological status are key factors influencing PSM and BCR

Superconductivity in TTF[Ni(dmit)2]2 films

We report on the observation of a superconducting transition in a fiber-like film of the TTF[Ni(dmit)2]2 phase electrodeposited on silicon substrates. Superconductivity is evidenced by a broad drop of the resistance below 0.8K under the application of a hydrostatic pressure of 7.7 kbar. Zero resistance is not reached due to the contribution of inter-fiber resistance. Superconductivity is confirmed by the application of a magnetic field perpendicular to the plane of the film. The critical field determined on the film is in agreement with that obtained in bulk single crystals