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BackgroundThe resistance mutation T790M is reported in 50–60% of patients pretreated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Osimertinib has been approved in these patients, but data in octogenarians remain rare.ObjectiveThe objective of this retrospective analysis was to evaluate in real life the efficacy of osimertinib in a population of octogenarian patients.MethodsThis retrospective multicentric study included pretreated octogenarian patients with EGFR T790M-mutated advanced non-small cell lung cancer (NSCLC) in the setting of the French early access program for osimertinib. The primary endpoints were progression-free survival (PFS) and overall survival (OS) from osimertinib initiation.ResultsIn total, 43 patients were included (mean age 84.6 years; women 90.7%: adenocarcinoma 100%; never smokers 90.5%; at osimertinib initiation: performance status ≥ 2, 42.4%; stage 4, 93.0%; brain metastases 16.3%). Patients received a median of two lines of treatment before osimertinib initiation, and all received first- or second-generation EGFR TKIs before osimertinib (first line in 79.1%). Osimertinib was used as a second-line treatment in 41.9% of cases and third line or more in 58.1%. Median PFS was 17.5 (95% confidence interval [CI] 12.2–19.0) months for the entire population: 20.6 (95% CI 18.8–not reached) months in patients with brain metastases and 16.7 (95% CI 10.4–18.9) months in patients without (p = 0.1). There was no significant difference for osimertinib treatment as second or third line or more (17.1 vs. 18.6 months, respectively). OS was 22.8 (95% CI 15.7–not reached) months from osimertinib initiation.ConclusionThe efficacy of osimertinib as second-line treatment or more in octogenarian pretreated patients with EGFR T790M-mutated advanced NSCLC in a real-life setting was similar to that in randomized controlled trials.

Distribution patterns of fragile gelatinous fauna in the open ocean remain scarcely documented. Using epi-and mesopelagic video transects in the eastern tropical North Atlantic, which features a mild but intensifying midwater oxygen minimum zone (OMZ), we established one of the first regional observations of diversity and abundance of large gelatinous zooplankton. We quantified the day and night vertical distribution of 46 taxa in relation to environmental conditions. While distribution may be driven by multiple factors, abundance peaks of individual taxa were observed in the OMZ core, both above and below the OMZ, only above, or only below the OMZ whereas some taxa did not have an obvious distribution pattern. In the eastern eropical North Atlantic, OMZ expansion in the course of global climate change may detrimentally impact taxa that avoid low oxygen concentrations ( Beroe , doliolids), but favour taxa that occur in the OMZ ( Lilyopsis , phaeodarians, Cydippida, Colobonema , Haliscera conica and Halitrephes) as their habitat volume might increase. While future efforts need to focus on physiology and taxonomy of pelagic fauna in the study region, our study presents biodiversity and distribution data for the regional epi- and mesopelagic zones of Cape Verde providing a regional baseline to monitor how climate change may impact the largest habitat on the planet, the deep pelagic realm.

High primary productivity in the equatorial Atlantic and Pacific oceans is one of the key features of tropical ocean biogeochemistry and fuels a substantial flux of particulate matter towards the abyssal ocean. How biological processes and equatorial current dynamics shape the particle size distribution and flux, however, is poorly understood. Here we use high-resolution size-resolved particle imaging and Acoustic Doppler Current Profiler data to assess these influences in equatorial oceans. We find an increase in particle abundance and flux at depths of 300 to 600 m at the Atlantic and Pacific equator, a depth range to which zooplankton and nekton migrate vertically in a daily cycle. We attribute this particle maximum to faecal pellet production by these organisms. At depths of 1,000 to 4,000 m, we find that the particulate organic carbon flux is up to three times greater in the equatorial belt (1° S–1° N) than in off-equatorial regions. At 3,000 m, the flux is dominated by small particles less than 0.53 mm in diameter. The dominance of small particles seems to be caused by enhanced active and passive particle export in this region, as well as by the focusing of particles by deep eastward jets found at 2° N and 2° S. We thus suggest that zooplankton movements and ocean currents modulate the transfer of particulate carbon from the surface to the deep ocean. Vertical migration of organisms and deep currents control the transport and characteristics of particles at the equator, according to an analysis of current and particle measurements. Particles fluxes are an important part of the ocean carbon cycle.

There is a need for cost-efficient tools to explore deep-ocean ecosystems to collect baseline biological observations on pelagic fauna (zooplankton and nekton) and establish the vertical ecological zonation in the deep sea. The Pelagic In situ Observation System (PELAGIOS) is a 3000 m rated slowly (0.5 m s−1) towed camera system with LED illumination, an integrated oceanographic sensor set (CTD-O2) and telemetry allowing for online data acquisition and video inspection (low definition). The high-definition video is stored on the camera and later annotated using software and related to concomitantly recorded environmental data. The PELAGIOS is particularly suitable for open-ocean observations of gelatinous fauna, which is notoriously under-sampled by nets and/or destroyed by fixatives. In addition to counts, diversity, and distribution data as a function of depth and environmental conditions (T, S, O2), in situ observations of behavior, orientation, and species interactions are collected. Here, we present an overview of the technical setup of the PELAGIOS as well as example observations and analyses from the eastern tropical North Atlantic. Comparisons to data from the Multiple Opening/Closing Net and Environmental Sensing System (MOCNESS) net sampling and data from the Underwater Vision Profiler (UVP) are provided and discussed.

The temporal evolution of the physical and biogeochemical structure of an oxygen-depleted anticyclonic modewater eddy is investigated over a 2-month period using high-resolution glider and ship data. A weakly stratified eddy core (squared buoyancy frequency N2  ∼  0.1  ×  10−4 s−2) at shallow depth is identified with a horizontal extent of about 70 km and bounded by maxima in N2. The upper N2 maximum (3–5  ×  10−4 s−2) coincides with the mixed layer base and the lower N2 maximum (0.4  ×  10−4 s−2) is found at about 200 m depth in the eddy centre. The eddy core shows a constant slope in temperature/salinity (T∕S) characteristic over the 2 months, but an erosion of the core progressively narrows down the T∕S range. The eddy minimal oxygen concentrations decreased by about 5 µmol kg−1 in 2 months, confirming earlier estimates of oxygen consumption rates in these eddies. Separating the mesoscale and perturbation flow components reveals oscillating velocity finestructure ( ∼  0.1 m s−1) underneath the eddy and at its flanks. The velocity finestructure is organized in layers that align with layers in properties (salinity, temperature) but mostly cross through surfaces of constant density. The largest magnitude in velocity finestructure is seen between the surface and 140 m just outside the maximum mesoscale flow but also in a layer underneath the eddy centre, between 250 and 450 m. For both regions a cyclonic rotation of the velocity finestructure with depth suggests the vertical propagation of near-inertial wave (NIW) energy. Modification of the planetary vorticity by anticyclonic (eddy core) and cyclonic (eddy periphery) relative vorticity is most likely impacting the NIW energy propagation. Below the low oxygen core salt-finger type double diffusive layers are found that align with the velocity finestructure. Apparent oxygen utilization (AOU) versus dissolved inorganic nitrate (NO3−) ratios are about twice as high (16) in the eddy core compared to surrounding waters (8.1). A large NO3− deficit of 4 to 6 µmol kg−1 is determined, rendering denitrification an unlikely explanation. Here it is hypothesized that the differences in local recycling of nitrogen and oxygen, as a result of the eddy dynamics, cause the shift in the AOU : NO3− ratio. High NO3− and low oxygen waters are eroded by mixing from the eddy core and entrain into the mixed layer. The nitrogen is reintroduced into the core by gravitational settling of particulate matter out of the euphotic zone. The low oxygen water equilibrates in the mixed layer by air–sea gas exchange and does not participate in the gravitational sinking. Finally we propose a mesoscale–submesoscale interaction concept where wind energy, mediated via NIWs, drives nutrient supply to the euphotic zone and drives extraordinary blooms in anticyclonic mode-water eddies.

Zooplankton plays a major role in ocean food webs and biogeochemical cycles, and provides major ecosystem services as a main driver of the biological carbon pump and in sustaining fish communities. Zooplankton is also sensitive to its environment and reacts to its changes. To better understand the importance of zooplankton, and to inform prognostic models that try to represent them, spatially-resolved biomass estimates of key plankton taxa are desirable. In this study we predict, for the first time, the global biomass distribution of 19 zooplankton taxa (1-50 mm Equivalent Spherical Diameter) using observations with the Underwater Vision Profiler 5, a quantitative in situ imaging instrument. After classification of 466,872 organisms from more than 3,549 profiles (0-500 m) obtained between 2008 and 2019 throughout the globe, we estimated their individual biovolumes and converted them to biomass using taxa-specific conversion factors. We then associated these biomass estimates with climatologies of environmental variables (temperature, salinity, oxygen, etc.), to build habitat models using boosted regression trees. The results reveal maximal zooplankton biomass values around 60°N and 55°S as well as minimal values around the oceanic gyres. An increased zooplankton biomass is also predicted for the equator. Global integrated biomass (0-500 m) was estimated at 0.403 PgC. It was largely dominated by Copepoda (35.7%, mostly in polar regions), followed by Eumalacostraca (26.6%) Rhizaria (16.4%, mostly in the intertropical convergence zone). The machine learning approach used here is sensitive to the size of the training set and generates reliable predictions for abundant groups such as Copepoda (R2 ≈ 20-66%) but not for rare ones (Ctenophora, Cnidaria, R2 < 5%). Still, this study offers a first protocol to estimate global, spatially resolved zooplankton biomass and community composition from in situ imaging observations of individual organisms. The underlying dataset covers a period of 10 years while approaches that rely on net samples utilized datasets gathered since the 1960s. Increased use of digital imaging approaches should enable us to obtain zooplankton biomass distribution estimates at basin to global scales in shorter time frames in the future.

Localized open-ocean low-oxygen “dead zones” in the eastern tropical North Atlantic are recently discovered ocean features that can develop in dynamically isolated water masses within cyclonic eddies (CE) and anticyclonic mode-water eddies (ACME). Analysis of a comprehensive oxygen dataset obtained from gliders, moorings, research vessels and Argo floats reveals that “dead-zone” eddies are found in surprisingly high numbers and in a large area from about 4 to 22° N, from the shelf at the eastern boundary to 38° W. In total, 173 profiles with oxygen concentrations below the minimum background concentration of 40 µmol kg−1 could be associated with 27 independent eddies (10 CEs; 17 ACMEs) over a period of 10 years. Lowest oxygen concentrations in CEs are less than 10 µmol kg−1 while in ACMEs even suboxic (< 1 µmol kg−1) levels are observed. The oxygen minimum in the eddies is located at shallow depth from 50 to 150 m with a mean depth of 80 m. Compared to the surrounding waters, the mean oxygen anomaly in the core depth range (50 and 150 m) for CEs (ACMEs) is −38 (−79) µmol kg−1. North of 12° N, the oxygen-depleted eddies carry anomalously low-salinity water of South Atlantic origin from the eastern boundary upwelling region into the open ocean. Here water mass properties and satellite eddy tracking both point to an eddy generation near the eastern boundary. In contrast, the oxygen-depleted eddies south of 12° N carry weak hydrographic anomalies in their cores and seem to be generated in the open ocean away from the boundary. In both regions a decrease in oxygen from east to west is identified supporting the en-route creation of the low-oxygen core through a combination of high productivity in the eddy surface waters and an isolation of the eddy cores with respect to lateral oxygen supply. Indeed, eddies of both types feature a cold sea surface temperature anomaly and enhanced chlorophyll concentrations in their center. The low-oxygen core depth in the eddies aligns with the depth of the shallow oxygen minimum zone of the eastern tropical North Atlantic. Averaged over the whole area an oxygen reduction of 7 µmol kg−1 in the depth range of 50 to 150 m (peak reduction is 16 µmol kg−1 at 100 m depth) can be associated with the dispersion of the eddies. Thus the locally increased oxygen consumption within the eddy cores enhances the total oxygen consumption in the open eastern tropical North Atlantic Ocean and seems to be an contributor to the formation of the shallow oxygen minimum zone.

The high-strength aluminium alloys EN AW-6082 and -7075 are characterized by low density and high strength but also limited cold formability and pronounced springback behaviour in the ultra-high-strength T6 state. In order to exploit their lightweight design potential, temperature-supported process routes such as warm or hot forming are applied. Alternatively, there is the possibility of cold forming preconditioned semi-finished products at the expense of the initial material properties. Common to all variants are complex interrelationships due to linked plant periphery resulting from up- and downstream heat treatments. In addition, occurring heat transfers in temperature-supported process routes or strain hardening effects during cold forming lead to reduced formability. Especially for multi-stage forming processes, as they are required for complex components, the above-mentioned process routes reach their limits. The different requirements of the four single-stages (deep drawing, blanking, collar drawing and upsetting) for the production of a demonstrator geometry with adapted wall thicknesses make a new type of temperature control necessary. This paper shows that the combination of temperature-supported and multi-stage forming contributes to a significant increase in formability. The temperature-controlled forming tool used for this purpose enables an inline heating of the components during the process, so that an industrially feasible and economical overall process chain for the fabrication of the demonstrator geometry out of those alloys is convertible.

The Humboldt Current Upwelling System (HCS) is the most productive eastern boundary upwelling system (EBUS) in terms of fishery yield on the planet. EBUSs are considered hotspots of climate change with predicted expansion of mesopelagic oxygen minimum zones (OMZs) and related changes in the frequency and intensity of upwelling of nutrient-rich, low-oxygen deep water. To increase our mechanistic understanding of how upwelling impacts plankton communities and trophic links, we investigated mesozooplankton community succession and gut fluorescence, fatty acid and elemental compositions (C, N, O, P), and stable isotope (δ13C, δ15N) ratios of dominant mesozooplankton and microzooplankton representatives in a mesocosm setup off Callao (Peru) after simulated upwelling with OMZ water from two different locations and different N:P signatures (moderate and extreme treatments). An oxycline between 5 and 15 m with hypoxic conditions (<50 µmol L−1) below ∼10 m persisted in the mesocosms throughout the experiment. No treatment effects were determined for the measured parameters, but differences in nutrient concentrations established through OMZ water additions were only minor. Copepods and polychaete larvae dominated in terms of abundance and biomass. Development and reproduction of the dominant copepod genera Paracalanus sp., Hemicyclops sp., Acartia sp., and Oncaea sp. were hindered as evident from accumulation of adult copepodids but largely missing nauplii. Failed hatching of nauplii in the hypoxic bottom layer of the mesocosms and poor nutritional condition of copepods suggested from very low gut fluorescence and fatty acid compositions most likely explain the retarded copepod development. Correlation analysis revealed no particular trophic relations between dominant copepods and phytoplankton groups. Possibly, particulate organic matter with a relatively high C:N ratio was a major diet of copepods. C:N ratios of copepods and polychaetes ranged 4.8–5.8 and 4.2–4.3, respectively. δ15N was comparatively high (∼13 ‰–17 ‰), potentially because the injected OMZ source water was enriched in δ15N as a result of anoxic conditions. Elemental ratios of dinoflagellates deviated strongly from the Redfield ratio. We conclude that opportunistic feeding of copepods may have played an important role in the pelagic food web. Overall, projected changes in the frequency and intensity of upwelling hypoxic waters may make a huge difference for copepod reproduction and may be further enhanced by varying N:P ratios of upwelled OMZ water masses.