Bimodal distribution of free tropospheric ozone over the tropical western Pacific revealed by airborne observations

A recent airborne field campaign over the remote western Pacific obtained the first intensive in situ ozone sampling over the warm pool region from oceanic surface to 15-km altitude (near 360-K potential temperature level). The new data set quantifies ozone in the tropical tropopause layer under significant influence of convective outflow. The analysis further reveals a bimodal distribution of free tropospheric ozone mixing ratio. A primary mode, narrowly distributed around 20-ppbv, dominates the troposphere from the surface to 15-km. A secondary mode, broadly distributed with a 60-ppbv modal value, is prominent between 3 and 8-km (320-K to 340-K potential temperature levels). The latter mode occurs as persistent layers of ozone-rich drier air and is characterized by relative humidity under 45%. Possible controlling mechanisms are discussed. These findings provide new insight into the physical interpretation of the >S>-shaped mean ozone profiles in the tropics.Peer Reviewe

Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study

Background: Generalized myasthenia gravis (gMG) is a chronic, unpredictable disease associated with high treatment and disease burdens, with a need for more effective and well-tolerated treatments. Objectives: To evaluate the long-term safety, tolerability, and efficacy of zilucoplan in a mild-to-severe, acetylcholine receptor autoantibody-positive (AChR+) gMG population. Design: Ongoing, multicenter, phase III open-label extension (OLE) study. Methods: Eligible patients had completed a qualifying randomized, placebo-controlled phase II or phase III zilucoplan study and received daily, self-administered subcutaneous 0.3 mg/kg zilucoplan. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Secondary efficacy endpoints included change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Results: In total, 200 patients enrolled. At the cut-off date (8 September 2022), median (range) exposure to zilucoplan in RAISE-XT was 1.2 (0.11–4.45) years. Mean age at OLE baseline was 53.3 years. A total of 188 (94%) patients experienced a TEAE, with the most common being MG worsening (n = 52, 26%) and COVID-19 (n = 49, 25%). In patients who received zilucoplan 0.3 mg/kg in the parent study, further improvements in MG-ADL score continued through to Week 24 (least squares mean change [95% confidence interval] from double-blind baseline −6.06 [−7.09, −5.03]) and were sustained through to Week 60 (−6.04 [−7.21, −4.87]). In patients who switched from placebo in the parent study, rapid improvements in MG-ADL score were observed at the first week after switching to zilucoplan; further improvements were observed at Week 24, 12 weeks after switching (−6.46 [−8.19, −4.72]), and were sustained through to Week 60 (−6.51 [−8.37, −4.65]). Consistent results were observed in other efficacy endpoints. Conclusion: Zilucoplan demonstrated a favorable long-term safety profile, good tolerability, and sustained efficacy through to Week 60 with consistent benefits in a broad AChR+ gMG population. Additional long-term data will be available in future analyses. Trial registration: ClinicalTrials.gov identifier: NCT04225871 (https://clinicaltrials.gov/ct2/show/NCT04225871

BrO and inferred Bry profiles over the western Pacific: Relevance of inorganic bromine sources and a Bry minimum in the aged tropical tropopause layer

We report measurements of bromine monoxide (BrO) and use an observationally constrained chemical box model to infer total gas-phase inorganic bromine (Br) over the tropical western Pacific Ocean (tWPO) during the CONTRAST field campaign (January-February 2014). The observed BrO and inferred Br profiles peak in the marine boundary layer (MBL), suggesting the need for a bromine source from sea-salt aerosol (SSA), in addition to organic bromine (CBr). Both profiles are found to be C-shaped with local maxima in the upper free troposphere (FT). The median tropospheric BrO vertical column density (VCD) was measured as 1.6×1013 molec cm-2, compared to model predictions of 0.9×1013 molec cm-2 in GEOS-Chem (CBr but no SSA source), 0.4×1013 molec cm-2 in CAM-Chem (CBr and SSA), and 2.1×1013 molec cm-2 in GEOS-Chem (CBr and SSA). Neither global model fully captures the C-shape of the Br profile. A local Br maximum of 3.6 ppt (2.9-4.4 ppt; 95 % confidence interval, CI) is inferred between 9.5 and 13.5 km in air masses influenced by recent convective outflow. Unlike BrO, which increases from the convective tropical tropopause layer (TTL) to the aged TTL, gas-phase Br decreases from the convective TTL to the aged TTL. Analysis of gas-phase Br against multiple tracers (CFC-11, H2O-O3 ratio, and potential temperature) reveals a Br minimum of 2.7 ppt (2.3-3.1 ppt; 95 % CI) in the aged TTL, which agrees closely with a stratospheric injection of 2.6 ± 0.6 ppt of inorganic Br (estimated from CFC-11 correlations), and is remarkably insensitive to assumptions about heterogeneous chemistry. Br increases to 6.3 ppt (5.6-7.0 ppt; 95 % CI) in the stratospheric >middleworld> and 6.9 ppt (6.5-7.3 ppt; 95 % CI) in the stratospheric >overworld>. The local Br minimum in the aged TTL is qualitatively (but not quantitatively) captured by CAM-Chem, and suggests a more complex partitioning of gas-phase and aerosol Br species than previously recognized. Our data provide corroborating evidence that inorganic bromine sources (e.g., SSA-derived gas-phase Br) are needed to explain the gas-phase Br budget in the upper free troposphere and TTL. They are also consistent with observations of significant bromide in Upper Troposphere-Lower Stratosphere aerosols. The total Br budget in the TTL is currently not closed, because of the lack of concurrent quantitative measurements of gas-phase Br species (i.e., BrO, HOBr, HBr, etc.) and aerosol bromide. Such simultaneous measurements are needed to (1) quantify SSA-derived Br in the upper FT, (2) test Br partitioning, and possibly explain the gas-phase Br minimum in the aged TTL, (3) constrain heterogeneous reaction rates of bromine, and (4) account for all of the sources of Br to the lower stratosphere.Peer Reviewe