7 research outputs found

    From BASE-ASIA Toward 7-SEAS: A Satellite-Surface Perspective of Boreal Spring Biomass-Burning Aerosols and Clouds in Southeast Asia

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    In this paper, we present recent field studies conducted by NASA's SMART-COMMIT (and ACHIEVE, to be operated in 2013) mobile laboratories, jointly with distributed ground-based networks (e.g., AERONET, http://aeronet.gsfc.nasa.gov/ and MPLNET, http://mplnet.gsfc.nasa.gov/) and other contributing instruments over northern Southeast Asia. These three mobile laboratories, collectively called SMARTLabs (cf. http://smartlabs.gsfc.nasa.gov/, Surface-based Mobile Atmospheric Research & Testbed Laboratories) comprise a suite of surface remote sensing and in-situ instruments that are pivotal in providing high spectral and temporal measurements, complementing the collocated spatial observations from various Earth Observing System (EOS) satellites. A satellite-surface perspective and scientific findings, drawn from the BASE-ASIA (2006) field deployment as well as a series of ongoing 7-SEAS (2010-13) field activities over northern Southeast Asia are summarized, concerning (i) regional properties of aerosols from satellite and in situ measurements, (ii) cloud properties from remote sensing and surface observations, (iii) vertical distribution of aerosols and clouds, and (iv) regional aerosol radiative effects and impact assessment. The aerosol burden over Southeast Asia in boreal spring, attributed to biomass burning, exhibits highly consistent spatial and temporal distribution patterns, with major variability arising from changes in the magnitude of the aerosol loading mediated by processes ranging from large-scale climate factors to diurnal meteorological events. Downwind from the source regions, the tightly coupled-aerosolecloud system provides a unique, natural laboratory for further exploring the micro- and macro-scale relationships of the complex interactions. The climatic significance is presented through large-scale anti-correlations between aerosol and precipitation anomalies, showing spatial and seasonal variability, but their precise cause-and-effect relationships remain an open-ended question. To facilitate an improved understanding of the regional aerosol radiative effects, which continue to be one of the largest uncertainties in climate forcing, a joint international effort is required and anticipated to commence in springtime 2013 in northern Southeast Asia

    Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

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    Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB
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