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Using a 3.19 fb−1 data sample collected at an 𝑒+𝑒− center-of-mass energy of 𝐸cm=4.178 GeV with the BESIII detector, we measure the branching fraction of the leptonic decay 𝐷+𝑠→𝜇+𝜈𝜇 to be ℬ𝐷+𝑠→𝜇+𝜈𝜇=(5.49±0.16stat±0.15syst)×10−3. Combining our branching fraction with the masses of the 𝐷+𝑠 and 𝜇+ and the lifetime of the 𝐷+𝑠, we determine 𝑓𝐷+𝑠|𝑉𝑐𝑠|=246.2±3.6stat±3.5syst MeV. Using the 𝑐→𝑠 quark mixing matrix element |𝑉𝑐𝑠| determined from a global standard model fit, we evaluate the 𝐷+𝑠 decay constant 𝑓𝐷+𝑠=252.9±3.7stat±3.6syst MeV. Alternatively, using the value of 𝑓𝐷+𝑠 calculated by lattice quantum chromodynamics, we find |𝑉𝑐𝑠|=0.985±0.014stat±0.014syst. These values of ℬ𝐷+𝑠→𝜇+𝜈𝜇, 𝑓𝐷+𝑠|𝑉𝑐𝑠|, 𝑓𝐷+𝑠 and |𝑉𝑐𝑠| are each the most precise results to date.
BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are commonly prescribed to treat acid-related disorders. Some direct-acting antiviral regimens for chronic hepatitis C virus (HCV) infection have reduced efficacy in patients taking concomitant acid-reducing agents, including PPIs, due to interactions between drugs. We analyzed data from 9 multicenter, phase 2 and 3 trials to determine the efficacy and pharmacokinetics of an HCV therapeutic regimen comprising glecaprevir and pibrentasvir (glecaprevir/pibrentasvir) in patients taking concomitant acid-reducing agents.
METHODS: We analyzed data from 2369 patients infected with HCV genotypes 1-6 and compensated liver disease treated with an all-oral regimen of glecaprevir/pibrentasvir for 8-16 weeks. We compared efficacy and pharmacokinetics among patients receiving at least 1 dose of an acid-reducing agent (a PPI, an H2 blocker, or antacid). High-dose PPI was defined as daily dose greater than 20 mg omeprazole dose equivalent. The objectives were to evaluate rate of sustained virologic response 12 weeks post-treatment (SVR12) and to assess steady-state glecaprevir and pibrentasvir exposures in patients on acid-reducing agents.
RESULTS: Of the 401 patients (17%) who reported use of acid-reducing agents, 263 took PPIs (11%; 109 patients took a high-dose PPI and 154 patients took a low-dose PPI). Rates of SVR12 were 97.0% among patients who used acid-reducing agents and 97.5% among those not using acid-reducing agents (P = .6). An SVR12 was achieved in 96.3% taking a high-dose PPI and 97.4% taking a low-dose PPI, with no virologic failures in those receiving a high-dose PPI (P = .7). Glecaprevir, but not pibrentasvir, bioavailability was affected; its exposure decreased by 41% in patients taking a high-dose PPI.
CONCLUSIONS: In an analysis of data from 9 clinical trials, we observed a high rate of SVR12 (approximately 97%) among patients treated with glecaprevir/pibrentasvir for HCV infection-even among patients taking concomitant ARA or high-dose PPI. This was despite decreased glecaprevir exposures in patients when on high-dose PPIs. ClinicalTrials.gov numbers, NCT02243280 (SURVEYOR-I), NCT02243293 (SURVEYOR-II), NCT02604017 (ENDURANCE-1), NCT02640482 (ENDURANCE-2), NCT02640157 (ENDURANCE-3), NCT02636595 (ENDURANCE-4), NCT02642432 (EXPEDITION-1), NCT02651194 (EXPEDITION-4), NCT02446717 (MAGELLAN-I).
Yuanmou Basin of Yunnan, SW China, is a famous locality with hominids, hominoids, mammals and plant fossils. Based on the published megaflora and palynoflora data from Yuanmou Basin, the climate of Late Pliocene is reconstructed using the Coexistence Approach. The results indicate a warm and humid subtropical climate with a mean annual temperature of ca. 16–17°C and a mean annual precipitation of ca. 1500–1600 mm in the Late Pliocene rather than a dry, hot climate today, which may be due to the local tectonic change and gradual intensification of India monsoon. The comparison of Late Pliocene climate in Eryuan, Yangyi, Longling, and Yuanmou Basin of Yunnan Province suggests that the mean annual temperatures generally show a latitudinal gradient and fit well with their geographic position, while the mean annual precipitations seem to be related to the different geometries of the valleys under the same monsoon system.