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Background: In the phase 3 SOLO1 trial, maintenance olaparib provided a significant progression-free survival benefit versus placebo in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation in response after platinum-based chemotherapy. We analysed health-related quality of life (HRQOL) and patient-centred outcomes in SOLO1, and the effect of radiological disease progression on health status. Methods: SOLO1 is a randomised, double-blind, international trial done in 118 centres and 15 countries. Eligible patients were aged 18 years or older; had an Eastern Cooperative Oncology Group performance status score of 0–1; had newly diagnosed, advanced, high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer with a BRCA mutation; and were in clinical complete or partial response to platinum-based chemotherapy. Patients were randomly assigned (2:1) to either 300 mg olaparib tablets or placebo twice per day using an interactive voice and web response system and were treated for up to 2 years. Treatment assignment was masked for patients and for clinicians giving the interventions, and those collecting and analysing the data. Randomisation was stratified by response to platinum-based chemotherapy (clinical complete or partial response). HRQOL was a secondary endpoint and the prespecified primary HRQOL endpoint was the change from baseline in the Functional Assessment of Cancer Therapy–Ovarian Cancer Trial Outcome Index (TOI) score for the first 24 months. TOI scores range from 0 to 100 (higher scores indicated better HRQOL), with a clinically meaningful difference defined as a difference of at least 10 points. Prespecified exploratory endpoints were quality-adjusted progression-free survival and time without significant symptoms of toxicity (TWiST). HRQOL endpoints were analysed in all randomly assigned patients. The trial is ongoing but closed to new participants. This trial is registered with ClinicalTrials.go

The fractional abundance of branched glycerol dialkyl glycerol tetraether (brGDGT) membrane lipids in coastal marine sediments has been posited as a proxy for the reconstruction of terrestrial temperatures on the nearby land, based on the assumption that they are produced in soils and delivered to the marine realm by rivers following erosion. Here, we test the suitability of brGDGTs as a continental paleothermometer in Pliocene age sediments from the northern Gulf of Mexico (GoM; speculated Mississippi River input) and the Ceará Rise (speculated Amazon River input). Low branched to isoprenoid tetraether (BIT) index values of 0.00–0.13 and the near absence of pollen and long-chain plant waxes in the GoM sediments suggest that the Mississippi River did not have a strong influence on the delivery of terrestrial organic matter to the site during the Pliocene and soil input was limited. Indeed, the high weighted average of cyclopentane-containing tetramethylated brGDGTs (#ringstetra) in the GoM sediments (0.50 ± 0.09) relative to that of modern soils from the Mississippi catchment (0.25 ± 0.16) indicates that the brGDGTs in the GoM sediments were mostly produced in situ in the marine realm, hampering reliable land temperature reconstruction using the global soil transferfunction. In contrast, high BIT index values (0.46 ± 0.21) and low #rings tetra (0.25 ± 0.15) in sediments from the Ceará Rise suggest that these brGDGTs are primarily derived from soils. However, reconstructed temperatures were 11–18 °C lower than modern Amazon catchment temperatures. The relative abundance of 6-methylated brGDGTs (Isomerisation Ratio; IR) in the sediments is 0.82 ± 0.10, which resembles that of suspended particulate matter (SPM) in the modern Amazon River more than that of catchment soils (IR = 0.18 ± 0.18). This reveals that brGDGTs in the Ceará Rise sediments likely have a freshwater, riverine origin. Thus, the majority of the brGDGTs in both the GoM and Ceará Ri

Accurate temperature records for the deep geological past are a vital component of paleoclimate research. Distributional changes of branched glycerol dialkyl glycerol tetraether (brGDGT) lipids in geological archives including paleosoils are a promising indicators to infer past continental air temperatures. However, the ‘orphan’ status of the brGDGTs, the potential effect of temperature-independent parameters on their relative distribution, and the uneven geographical distribution of the soils used for calibration contribute to the high uncertainty of brGDGT-based transfer functions (root mean squared error, RMSE: ±5 °C). Here, we expand the soil dataset from the previous calibration(s) with new and published soil data. We use Bayesian statistics to calibrate the relationship of the 5-methyl brGDGTs (MBT′5Me) and mean annual air temperature (MAAT). The addition of soils from warm (>28 °C) environments from India substantially increases the upper limit of the Bayesian calibration (BayMBT) from 25 to 29 °C, aiding in the generation of temperature records for past greenhouse climates, such as the Eocene. The BayMBT model also effectively minimizes the structured MAAT residuals prevalent in previous calibrations, therefore giving the opportunity to explore confounding factors on the calibration. We formulate a set of alternative calibration models to test the effect of specific environmental parameters and show that soils at mid-latitudes with temperature seasonalities >20 °C are not well described by the BayMBT model. We find that the MBT′5Me index is best correlated to the average temperature of all months >0 °C, called the BayMBT0 model. This finding supports the hypothesis that brGDGT production ceases or slows down in the winter months. However, a persistent feature of the BayMBT model and previous calibrations is the significant scatter at mid-latitudes, which is speculatively linked with a possible increase in diversity of microbial brGDGT-p

Branched glycerol dialkyl glycerol tetraethers (brGDGTs) are bacterial membrane lipids thought to be predominantly produced on land. They are used as a terrestrial paleothermometer based on an empirical relation between their molecular composition and air temperature in surface soils worldwide. The proxy has been applied in continental margin sediments based on the assumption that all brGDGTs originate from land and are transported to marine sediments predominantly by rivers. However, this assumption has been challenged by the discovery of in situ brGDGT production in the coastal marine environment. To better understand marine brGDGT production, we examined newly collected marine surface sediments from the Krossfjorden and Kongsfjorden in Svalbard with a chromatography method to separate previously co-eluting 5- and 6-methylated brGDGT isomers. ‘Living’ intact polar lipid (IPL)-derived and ‘fossil’ core lipid (CL) brGDGTs were also studied for a subset of fjord sediments. The relative proportion of cyclopentane moieties in tetramethylated brGDGTs, used as indicator for brGDGT production in coastal marine settings, is much higher in the fjord sediments (#ringstetra = 0.65–0.93 for CL and 0.24–0.79 for IPL-derived brGDGTs) compared to those in nearby soils (#ringstetra = 0.00–0.37), and confirms the predominantly marine source of the brGDGTs in the fjord. Surprisingly, however, IPL-derived brGDGTs have a substantially lower #ringstetra (up to 0.52 offset) compared to that of CL-brGDGTs in the same sediment. This suggests that brGDGTs are produced in situ in different distributions throughout the year, of which the CL distribution in the sediment is an integrated signal. The offset in #ringstetra between IPL-derived and CL brGDGTs varies between 0.15 and 0.52 and increases towards the open ocean, possibly linking brGDGT production to the natural salinity gradient and associated microbial community changes.

It is not an easy task for paleoscientists to communicate the relevance of their research to policy makers and funders. However, an increase in catastrophic environmental calamities related to climate change (e.g. landslide, droughts, flooding) demands a response both in terms of policy-making and future governmental decisions. Often, climate change in the recent past was linked to major shifts in human behavior, which masks the relative contribution of humans and nature. For example, the 4.2 ka BP aridification event was so severe that it may have triggered the collapse of several large civilizations (the Old Kingdom in Egypt and the Akkadian Empire in Mesopotamia; Gibbons 1993). Compilations of long-term records of past variability can help reduce the uncertainties on past, present and future climate changes, and thus support informed societal decisions. Therefore, policymakers should (and some may argue, must) consider the long-term perspective provided by paleoscience research.

The Pliocene (5.3 – 2.6 Ma) is seen as a good analogue for the climate of the near future, due to slightly higher global temperatures (i.e. 2-3 °C) and similar atmospheric CO2 concentrations (400 ppm) compared to the present. However, reliable data are needed to validate models that make projections of future climate. In this study, we have used sediments from a core in the coastal North Sea to test and compare three sea surface temperature (SST) proxies based on biomarkers: i.e. UK’37, TEX86H and LDI, on their ability to reconstruct SSTs of the Pliocene North Sea. The SSTs are compared with the continental mean air temperature record of the same site produced using biomarkers (branched GDGTs). The influence of sea level changes and terrestrial input are also investigated. The SST proxy comparison demonstrates that the UK’37 and LDI proxies respond to the same driver, i.e. temperature, but to a different extent, probably due to different production seasons of the biomarkers used in the proxies. The TEX86H proxy shows trends not consistent with the other two SST proxies, and is therefore assumed not reliable in this setting. Large fluctuations in SSTs are seen, most likely caused by changes in the configuration of the North Atlantic current. Finally, comparison of the marine and terrestrial climates shows that they are decoupled. The mechanism for this decoupling could be a result of regional ocean currents influencing marine climate, while the terrestrial climate largely follows global climate fluctuations.