Pharmacokinetics and safety of co-administered paritaprevir plus ritonavir, ombitasvir, and dasabuvir in hepatic impairment

Background & Aims: Paritaprevir, ombitasvir, and dasabuvir are direct-acting antivirals for treatment of chronic hepatitis C virus (HCV) infection. The aim of this study was to characterize the effects of mild, moderate, and severe hepatic impairment on the pharmacokinetics of these drugs. Methods: HCV-negative subjects with normal hepatic function (n = 7) or mild (Child-Pugh A, n = 6), moderate (Child-Pugh B, n = 6), or severe (Child-Pugh C, n = 5) hepatic impairment received a single-dose of the combination of paritaprevir plus ritonavir (paritaprevir/r, 200/100 mg), ombitasvir (25 mg), and dasabuvir (400 mg). Plasma samples were collected through 144 hours after administration for pharmacokinetic assessments. Results: Paritaprevir, ombitasvir, dasabuvir, and ritonavir exposures (maximal plasma concentration, C max , and area under the concentration-time curve, AUC) were minimally affected in subjects with mild or moderate hepatic impairment. Differences in exposures between healthy controls and subjects with mild or moderate hepatic impairment were less than 35%, except for 62% higher paritaprevir AUC in subjects with moderate hepatic impairment. Paritaprevir and dasabuvir AUC were significantly higher in subjects with severe hepatic impairment (950% and 325%, respectively). However, ombitasvir AUC was 54% lower and ritonavir AUC was comparable. Adverse events included eye stye, insomnia, and pain from an infiltrated intravenous line. Conclusions: The changes observed in paritaprevir, ritonavir, ombitasvir, and dasabuvir exposures in subjects with mild or moderate hepatic impairment do not necessitate dose adjustment. Subjects with severe hepatic impairment had substantially higher paritaprevir and dasabuvir exposures.

Factors driving the implementation of the ‘Local New Year’ policy to prevent COVID-19 in China

Abstract This study examines the contradiction caused by the ‘local new year’ policy, that is, the conflict between the pandemic prevention policies and people’s emotional demands during the Spring Festival, based on the normalisation of pandemic prevention and control. It focuses on the scientific logical relationship with the contradiction that people voluntarily support ‘local new year’, to explore the primary driving factors of their willingness. By evaluating the migrant workers in large cities, the primary influencing factors were screened, and the primary dynamic factors and their relationship were obtained using the Logit logical selection model and maximum-likelihood estimation. The study identified, ‘whether social and entertainment activities are planned in migrant cities’, as the primary driving factor, followed by ‘whether there are relatives (elderly /children) at home’, and ‘contracting the infection during travel’. In view of this conclusion, this study further proposes corresponding policy suggestions: Relevant measures should be adopted according to different regions and the current situation of the pandemic in combination with the characteristics of the episodic and local nature of the pandemic. ‘Local new year’ is encouraged from the perspective of enriching people’s emotional needs for spiritual entertainment and care. This study provides a new perspective and theoretical basis for the research and formulation of policies related to the normalisation of pandemic prevention and control in China and worldwide, and has a certain practical reference value

Mode-Locked Double Active Region Laser Diode

We present the first monolithic mode-locked laser diode with two quantum well active regions connected by a GaAs tunnel junction (PiNPiN). Picosecond pulses were achieved at 1040 nm, with a 24 GHz repetition rate

DCMS review of the efficiency and effectiveness of the Government-sponsored museums and galleries Appenidx C: excellence studies - visitor information; 27 August 1999

SIGLEAvailable from British Library Document Supply Centre-DSC:99/35940 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

760-nm semiconductor passively mode-locked monolithic laser for picosecond pulse generation

We report a novel semiconductor passively mode-locked edge-emitting laser based on a multi-quantum-well structure, emitting at 766 nm and enabling the generation of a stable 19.4 GHz pulse train with a pulse duration of ~5 ps

Semiconductor monolithic mode-locked laser for ultrashort pulse generation at 750 nm

No abstract available

980-nm external-cavity passively mode-locked laser with extremely narrow RF linewidth

This paper reports on the mode-locked operation of a 980-nm external-cavity passively mode-locked laser with extremely narrow RF linewidth. Optical pulses with 10-ps pulse duration were generated at a repetition rate of 955 MHz, with an average output power of 39.3 mW – which corresponds to a peak power of 4.1 W, generated directly from the oscillator. The RF spectrum displays a -3dB RF linewidth of only ~40 Hz, as well as a 60-dB dynamic contrast, revealing the exceptionally low-noise fundamental mode-locked operation of this laser. At a repetition rate of ~1 GHz, the highest peak power of 5.26 W was achieved, albeit with an increased -3dB RF linewidth of ~100 Hz. The two-section chip incorporated an active region with a dual InGaAs quantum well sandwiched by an asymmetrical waveguide, and was operated at room temperature. By taking advantage of the broad tunability of the repetition rate which externalcavity lasers can afford, we also investigated the limits of stable fundamental mode-locked operation at the lowest repetition rates (or maximum external cavity lengths). © (2013) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only