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State-of-the art therapy for recurrent ovarian cancer suitable for platinum-based re-treatment includes bevacizumab-containing combinations (eg, bevacizumab combined with carboplatin–paclitaxel or carboplatin–gemcitabine) or the most active non-bevacizumab regimen: carboplatin–pegylated liposomal doxorubicin. The aim of this head-to-head trial was to compare a standard bevacizumab-containing regimen versus carboplatin–pegylated liposomal doxorubicin combined with bevacizumab. This multicentre, open-label, randomised, phase 3 trial, was done in 159 academic centres in Germany, France, Australia, Austria, and the UK. Eligible patients (aged ≥18 years) had histologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with first disease recurrence more than 6 months after first-line platinum-based chemotherapy, and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were stratified by platinum-free interval, residual tumour, previous antiangiogenic therapy, and study group language, and were centrally randomly assigned 1:1 using randomly permuted blocks of size two, four, or six to receive six intravenous cycles of bevacizumab (15 mg/kg, day 1) plus carboplatin (area under the concentration curve [AUC] 4, day 1) plus gemcitabine (1000 mg/m2, days 1 and 8) every 3 weeks or six cycles of bevacizumab (10 mg/kg, days 1 and 15) plus carboplatin (AUC 5, day 1) plus pegylated liposomal doxorubicin (30 mg/m2, day 1) every 4 weeks, both followed by maintenance bevacizumab (15 mg/kg every 3 weeks in both groups) until disease progression or unacceptable toxicity. There was no masking in this open-label trial. The primary endpoint was investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy data were analysed in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug. This completed study is registered with ClinicalTrials.gov, NCT01837251. Between Aug 1, 2013, and July 31, 2015, 682 eligible patients were enrolled, of whom 345 were randomly assigned to receive carboplatin–pegylated liposomal doxorubicin–bevacizumab (experimental group) and 337 were randomly assigned to receive carboplatin–gemcitabine–bevacizumab (standard group). Median follow-up for progression-free survival at data cutoff (July 10, 2018) was 12·4 months (IQR 8·3–21·7) in the experimental group and 11·3 months (8·0–18·4) in the standard group. Median progression-free survival was 13·3 months (95% CI 11·7–14·2) in the experimental group versus 11·6 months (11·0–12·7) in the standard group (hazard ratio 0·81, 95% CI 0·68–0·96; p=0·012). The most common grade 3 or 4 adverse events were hypertension (88 [27%] of 332 patients in the experimental group vs 67 [20%] of 329 patients in the standard group) and neutropenia (40 [12%] vs 73 [22%]). Serious adverse events occurred in 33 (10%) of 332 patients in the experimental group and 28 (9%) of 329 in the standard group. Treatment-related deaths occurred in one patient in the experimental group (<1%; large intestine perforation) and two patients in the standard group (1%; one case each of osmotic demyelination syndrome and intracranial haemorrhage). Carboplatin–pegylated liposomal doxorubicin–bevacizumab is a new standard treatment option for platinum-eligible recurrent ovarian cancer. F Hoffmann-La Roche.

Stratospheric water vapour is a powerful greenhouse gas. The longest available record from balloon observations over Boulder, Colorado, USA shows increases in stratospheric water vapour concentrations that cannot be fully explained by observed changes in the main drivers, tropical tropopause temperatures and methane. Satellite observations could help resolve the issue, but constructing a reliable long-term data record from individual short satellite records is challenging. Here we present an approach to merge satellite data sets with the help of a chemistry–climate model nudged to observed meteorology. We use the models’ water vapour as a transfer function between data sets that overcomes issues arising from instrument drift and short overlap periods. In the lower stratosphere, our water vapour record extends back to 1988 and water vapour concentrations largely follow tropical tropopause temperatures. Lower and mid-stratospheric long-term trends are negative, and the trends from Boulder are shown not to be globally representative. In the upper stratosphere, our record extends back to 1986 and shows positive long-term trends. The altitudinal differences in the trends are explained by methane oxidation together with a strengthened lower-stratospheric and a weakened upper-stratospheric circulation inferred by this analysis. Our results call into question previous estimates of surface radiative forcing based on presumed global long-term increases in water vapour concentrations in the lower stratosphere. Stratospheric water vapour is a powerful greenhouse gas. Merging individual satellite data sets with a chemistry–climate model reveals that water vapour levels in the lower and mid-stratosphere have been decreasing since 1988.

Processes occurring in the tropical upper troposphere (UT), the Tropical Transition Layer (TTL), and the lower stratosphere (LS) are of importance for the global climate, for stratospheric dynamics and air chemistry, and for their influence on the global distribution of water vapour, trace gases and aerosols. In this contribution we present aerosol and trace gas (in-situ) measurements from the tropical UT/LS over Southern Brazil, Northern Australia, and West Africa. The instruments were operated on board of the Russian high altitude research aircraft M-55 \"Geophysica\" and the DLR Falcon-20 during the campaigns TROCCINOX (Araçatuba, Brazil, February 2005), SCOUT-O3 (Darwin, Australia, December 2005), and SCOUT-AMMA (Ouagadougou, Burkina Faso, August 2006). The data cover submicron particle number densities and volatility from the COndensation PArticle counting System (COPAS), as well as relevant trace gases like N2O, ozone, and CO. We use these trace gas measurements to place the aerosol data into a broader atmospheric context. Also a juxtaposition of the submicron particle data with previous measurements over Costa Rica and other tropical locations between 1999 and 2007 (NASA DC-8 and NASA WB-57F) is provided. The submicron particle number densities, as a function of altitude, were found to be remarkably constant in the tropical UT/LS altitude band for the two decades after 1987. Thus, a parameterisation suitable for models can be extracted from these measurements. Compared to the average levels in the period between 1987 and 2007 a slight increase of particle abundances was found for 2005/2006 at altitudes with potential temperatures, Θ, above 430 K. The origins of this increase are unknown except for increases measured during SCOUT-AMMA. Here the eruption of the Soufrière Hills volcano in the Caribbean caused elevated particle mixing ratios. The vertical profiles from Northern hemispheric mid-latitudes between 1999 and 2006 also are compact enough to derive a parameterisation. The tropical profiles all show a broad maximum of particle mixing ratios (between Θ≈340 K and 390 K) which extends from below the TTL to above the thermal tropopause. Thus these particles are a \"reservoir\" for vertical transport into the stratosphere. The ratio of non-volatile particle number density to total particle number density was also measured by COPAS. The vertical profiles of this ratio have a maximum of 50% above 370 K over Australia and West Africa and a pronounced minimum directly below. Without detailed chemical composition measurements a reason for the increase of non-volatile particle fractions cannot yet be given. However, half of the particles from the tropical \"reservoir\" contain compounds other than sulphuric acid and water. Correlations of the measured aerosol mixing ratios with N2O and ozone exhibit compact relationships for the tropical data from SCOUT-AMMA, TROCCINOX, and SCOUT-O3. Correlations with CO are more scattered probably because of the connection to different pollution source regions. We provide additional data from the long distance transfer flights to the campaign sites in Brazil, Australia, and West-Africa. These were executed during a time window of 17 months within a period of relative volcanic quiescence. Thus the data represent a \"snapshot picture\" documenting the status of a significant part of the global UT/LS fine aerosol at low concentration levels 15 years after the last major (i.e., the 1991 Mount Pinatubo) eruption. The corresponding latitudinal distributions of the measured particle number densities are presented in this paper to provide data of the UT/LS background aerosol for modelling purposes.

The Stratosphere-troposphere Processes and their Role in Climate (SPARC) Data Initiative (SPARC, 2017) performed the first comprehensive assessment of currently available stratospheric composition measurements obtained from an international suite of space-based limb sounders. The initiative's main objectives were (1) to assess the state of data availability, (2) to compile time series of vertically resolved, zonal monthly mean trace gas and aerosol fields, and (3) to perform a detailed intercomparison of these time series, summarizing useful information and highlighting differences among datasets. The datasets extend over the region from the upper troposphere to the lower mesosphere (300–0.1 hPa) and are provided on a common latitude–pressure grid. They cover 26 different atmospheric constituents including the stratospheric trace gases of primary interest, ozone (O3) and water vapor (H2O), major long-lived trace gases (SF6, N2O, HF, CCl3F, CCl2F2, NOy), trace gases with intermediate lifetimes (HCl, CH4, CO, HNO3), and shorter-lived trace gases important to stratospheric chemistry including nitrogen-containing species (NO, NO2, NOx, N2O5, HNO4), halogens (BrO, ClO, ClONO2, HOCl), and other minor species (OH, HO2, CH2O, CH3CN), and aerosol. This overview of the SPARC Data Initiative introduces the updated versions of the SPARC Data Initiative time series for the extended time period 1979–2018 and provides information on the satellite instruments included in the assessment: LIMS, SAGE I/II/III, HALOE, UARS-MLS, POAM II/III, OSIRIS, SMR, MIPAS, GOMOS, SCIAMACHY, ACE-FTS, ACE-MAESTRO, Aura-MLS, HIRDLS, SMILES, and OMPS-LP. It describes the Data Initiative's top-down climatological validation approach to compare stratospheric composition measurements based on zonal monthly mean fields, which provides upper bounds to relative inter-instrument biases and an assessment of how well the instruments are able to capture geophysical features of the stratosphere. An update to previously published evaluations of O3 and H2O monthly mean time series is provided. In addition, example trace gas evaluations of methane (CH4), carbon monoxide (CO), a set of nitrogen species (NO, NO2, and HNO3), the reactive nitrogen family (NOy), and hydroperoxyl (HO2) are presented. The results highlight the quality, strengths and weaknesses, and representativeness of the different datasets. As a summary, the current state of our knowledge of stratospheric composition and variability is provided based on the overall consistency between the datasets. As such, the SPARC Data Initiative datasets and evaluations can serve as an atlas or reference of stratospheric composition and variability during the “golden age” of atmospheric limb sounding. The updated SPARC Data Initiative zonal monthly mean time series for each instrument are publicly available and accessible via the Zenodo data archive (Hegglin et al., 2020).

Within the framework of the second SPARC (Stratosphere-troposphere Processes And their Role in Climate) water vapour assessment (WAVAS-II), profile-to-profile comparisons of stratospheric and lower mesospheric water vapour were performed by considering 33 data sets derived from satellite observations of 15 different instruments. These comparisons aimed to provide a picture of the typical biases and drifts in the observational database and to identify data-set-specific problems. The observational database typically exhibits the largest biases below 70 hPa, both in absolute and relative terms. The smallest biases are often found between 50 and 5 hPa. Typically, they range from 0.25 to 0.5 ppmv (5 % to 10 %) in this altitude region, based on the 50 % percentile over the different comparison results. Higher up, the biases increase with altitude overall but this general behaviour is accompanied by considerable variations. Characteristic values vary between 0.3 and 1 ppmv (4 % to 20 %). Obvious data-set-specific bias issues are found for a number of data sets. In our work we performed a drift analysis for data sets overlapping for a period of at least 36 months. This assessment shows a wide range of drifts among the different data sets that are statistically significant at the 2σ uncertainty level. In general, the smallest drifts are found in the altitude range between about 30 and 10 hPa. Histograms considering results from all altitudes indicate the largest occurrence for drifts between 0.05 and 0.3 ppmv decade−1. Comparisons of our drift estimates to those derived from comparisons of zonal mean time series only exhibit statistically significant differences in slightly more than 3 % of the comparisons. Hence, drift estimates from profile-to-profile and zonal mean time series comparisons are largely interchangeable. As for the biases, a number of data sets exhibit prominent drift issues. In our analyses we found that the large number of MIPAS data sets included in the assessment affects our general results as well as the bias summaries we provide for the individual data sets. This is because these data sets exhibit a relative similarity with respect to the remaining data sets, despite the fact that they are based on different measurement modes and different processors implementing different retrieval choices. Because of that, we have by default considered an aggregation of the comparison results obtained from MIPAS data sets. Results without this aggregation are provided on multiple occasions to characterise the effects due to the numerous MIPAS data sets. Among other effects, they cause a reduction of the typical biases in the observational database.

As part of European Space Agency's (ESA) climate change initiative, high vertical resolution ozone profiles from three instruments all aboard ESA's Envisat (GOMOS, MIPAS, SCIAMACHY) and ESA's third party missions (OSIRIS, SMR, ACE-FTS) are to be combined in order to create an essential climate variable data record for the last decade. A prerequisite before combining data is the examination of differences and drifts between the data sets. In this paper, we present a detailed analysis of ozone profile differences based on pairwise collocated measurements, including the evolution of the differences with time. Such a diagnosis is helpful to identify strengths and weaknesses of each data set that may vary in time and introduce uncertainties in long-term trend estimates. The analysis reveals that the relative drift between the sensors is not statistically significant for most pairs of instruments. The relative drift values can be used to estimate the added uncertainty in physical trends. The added drift uncertainty is estimated at about 3 % decade−1 (1σ). Larger differences and variability in the differences are found in the lowermost stratosphere (below 20 km) and in the mesosphere.