23 research outputs found
Artificial tektites: an experimental technique for capturing the shapes of spinning drops
Determining the shapes of a rotating liquid droplet bound by surface tension is an archetypal problem in the study of the equilibrium shapes of a spinning and charged droplet, a problem that unites models of the stability of the atomic nucleus with the shapes of astronomical-scale, gravitationally-bound masses. The shapes of highly deformed droplets and their stability must be calculated numerically. Although the accuracy of such models has increased with the use of progressively more sophisticated computational techniques and increases in computing power, direct experimental verification is still lacking. Here we present an experimental technique for making wax models of these shapes using diamagnetic levitation. The wax models resemble splash-form tektites, glassy stones formed from molten rock ejected from asteroid impacts. Many tektites have elongated or ‘dumb-bell’ shapes due to their rotation mid-flight before solidification, just as we observe here. Measurements of the dimensions of our wax ‘artificial tektites’ show good agreement with equilibrium shapes calculated by our numerical model, and with previous models. These wax models provide the first direct experimental validation for numerical models of the equilibrium shapes of spinning droplets, of importance to fundamental physics and also to studies of tektite formation
Transpapillary biliary biopsy for malignant biliary strictures: comparison between cholangiocarcinoma and pancreatic cancer
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Long-term open-label vebicorvir for chronic HBV infection: Safety and off-treatment responses
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Deeper virologic suppression with the addition of vebicorvir, a first-generation hepatitis B core inhibitor, to entecavir correlates with reduced inflammation and fibrosis-4 index in treatment naïve patients with HBeAg positive chronic hepatitis B
Improved Accuracy of Percutaneous Biopsy Using “Cross and Push” Technique for Patients Suspected with Malignant Biliary Strictures
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Antiviral activity and safety of the hepatitis B core inhibitor ABI-H0731 administered with a nucleos(t)ide reverse transcriptase inhibitor in patients with HBeAg-positive chronic hepatitis B infection in a long-term extension study
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Safety and efficacy of vebicorvir in virologically suppressed patients with chronic hepatitis B virus infection
HBV nucleos(t)ide reverse transcriptase inhibitors (NrtIs) do not completely suppress HBV replication. Previous reports indicate persistent viremia during NrtI treatment despite HBV DNA being undetectable. HBV core inhibitors may enhance viral suppression when combined with NrtIs. This phase II trial (NCT03576066) evaluated the efficacy and safety of the investigational core inhibitor, vebicorvir (VBR), in virologically- suppressed patients on NrtIs.
Non-cirrhotic, NrtI-suppressed patients with chronic HBV were randomised to VBR 300 mg once daily or matching placebo (PBO) for 24 weeks. Treatment was stratified by hepatitis B e antigen (HBeAg) status. The primary endpoint was change from Baseline in serum HBeAg or hepatitis B surface antigen (HBsAg) after 24 weeks.
Of 73 patients enrolled, 47 were HBeAg positive and 26 were HBeAg negative. In HBeAg-positive and -negative patients, there were no differences in the change from Baseline at Week 24 for HBsAg or HBeAg. Using a novel, high-sensitivity assay to detect HBV DNA, a greater proportion of patients with detectable HBV DNA at Baseline achieved undetectable HBV DNA at Week 24 in the VBR+NrtI vs. PBO+NrtI group. In HBeAg-positive patients, a greater change from Baseline in HBV pregenomic (pg)RNA was observed at Week 24 with VBR+NrtI vs. PBO+NrtI. Treatment-emergent adverse events (TEAEs) in VBR+NrtI patients included upper respiratory tract infection, nausea, and pruritus. No serious adverse events, Grade 4 TEAEs, or deaths were reported.
In this 24-week study, VBR+NrtI demonstrated a favourable safety and tolerability profile. While there were no significant changes in viral antigen levels, enhanced viral suppression was demonstrated by greater changes in DNA and pgRNA with the addition of VBR compared to NrtI alone.
NCT03576066.
Core inhibitors represent a novel approach for the treatment of chronic hepatitis B virus (HBV) infection, with mechanisms of action distinct from existing treatments. In this study, vebicorvir added to existing therapy reduced HBV replication to a greater extent than existing treatment and was generally safe and well tolerated.
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•Complete suppression of HBV replication is essential for finite treatment regimens.•Vebicorvir (VBR) is a novel inhibitor of the HBV core protein.•VBR interferes with two additional steps in HBV replication than NrtIs.•Added to NrtI, VBR did not significantly change mean HBV antigens over 24 weeks.•Added to NrtI, VBR further reduced HBV DNA and pgRNA by high-sensitivity PCR assays