4 research outputs found

    Microfossil evidence for trophic changes during the Eocene-Oligocene transition in the South Atlantic (ODP Site 1263, Walvis Ridge)

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    The biotic response of calcareous nannoplankton to environmental and climatic changes during the Eocene-Oligocene transition was investigated at a high resolution at Ocean Drilling Program (ODP) Site 1263 (Walvis Ridge, southeast Atlantic Ocean) and compared with a lower-resolution benthic foraminiferal record. During this time interval, global climate, which had been warm under high levels of atmospheric CO2 (pCO(2)) during the Eocene, transitioned into the cooler climate of the Oligocene, at overall lower pCO(2). At Site 1263, the absolute nannofossil abundance (coccoliths per gram of sediment; N g(-1)) and the mean coccolith size decreased distinctly after the E-O boundary (EOB; 33.89 Ma), mainly due to a sharp decline in abundance of large-sized Reticulofenestra and Dictyococcites, occurring within a time span of similar to 47 kyr. Carbonate dissolution did not vary much across the EOB; thus, the decrease in abundance and size of nannofossils may reflect an overall decrease in their export production, which could have led to variations in the food availability for benthic foraminifers. The benthic foraminiferal assemblage data are consistent with a global decline in abundance of rectilinear species with complex apertures in the latest Eocene (similar to 34.5 Ma), potentially reflecting changes in the food source, i.e., phytoplankton. This was followed by a transient increased abundance of species indicative of seasonal delivery of food to the sea floor (Epistominella spp.; similar to 33.9-33.4 Ma), with a short peak in overall food delivery at the EOB (buliminid taxa; similar to 33.8 Ma). Increased abundance of Nuttallides umbonifera (at similar to 33.3 Ma) indicates the presence of more corrosive bottom waters and possibly the combined arrival of less food at the sea floor after the second step of cooling (Step 2). The most important changes in the calcareous nannofossil and benthic communities occurred similar to 120 kyr after the EOB. There was no major change in nannofossil abundance or assemblage composition at Site 1263 after Step 2 although benthic foraminifera indicate more corrosive bottom waters during this time. During the onset of latest-Eocene-earliest-Oligocene climate change, marine phytoplankton thus showed high sensitivity to fast-changing conditions as well as to a possibly enhanced, pulsed nutrient supply and to the crossing of a climatic threshold (e.g., pCO(2) decline, high-latitude cooling and changes in ocean circulation)

    Nintedanib in patients with progressive fibrosing interstitial lung diseases—subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial

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    Background: The INBUILD trial investigated the efficacy and safety of nintedanib versus placebo in patients with progressive fibrosing interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF). We aimed to establish the effects of nintedanib in subgroups based on ILD diagnosis. Methods: The INBUILD trial was a randomised, double-blind, placebo-controlled, parallel group trial done at 153 sites in 15 countries. Participants had an investigator-diagnosed fibrosing ILD other than IPF, with chest imaging features of fibrosis of more than 10% extent on high resolution CT (HRCT), forced vital capacity (FVC) of 45% or more predicted, and diffusing capacity of the lung for carbon monoxide (DLco) of at least 30% and less than 80% predicted. Participants fulfilled protocol-defined criteria for ILD progression in the 24 months before screening, despite management considered appropriate in clinical practice for the individual ILD. Participants were randomly assigned 1:1 by means of a pseudo-random number generator to receive nintedanib 150 mg twice daily or placebo for at least 52 weeks. Participants, investigators, and other personnel involved in the trial and analysis were masked to treatment assignment until after database lock. In this subgroup analysis, we assessed the rate of decline in FVC (mL/year) over 52 weeks in patients who received at least one dose of nintedanib or placebo in five prespecified subgroups based on the ILD diagnoses documented by the investigators: hypersensitivity pneumonitis, autoimmune ILDs, idiopathic non-specific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, and other ILDs. The trial has been completed and is registered with ClinicalTrials.gov, number NCT02999178. Findings: Participants were recruited between Feb 23, 2017, and April 27, 2018. Of 663 participants who received at least one dose of nintedanib or placebo, 173 (26%) had chronic hypersensitivity pneumonitis, 170 (26%) an autoimmune ILD, 125 (19%) idiopathic non-specific interstitial pneumonia, 114 (17%) unclassifiable idiopathic interstitial pneumonia, and 81 (12%) other ILDs. The effect of nintedanib versus placebo on reducing the rate of FVC decline (mL/year) was consistent across the five subgroups by ILD diagnosis in the overall population (hypersensitivity pneumonitis 73\ub71 [95% CI 128\ub76 to 154\ub78]; autoimmune ILDs 104\ub70 [21\ub71 to 186\ub79]; idiopathic non-specific interstitial pneumonia 141\ub76 [46\ub70 to 237\ub72]; unclassifiable idiopathic interstitial pneumonia 68\ub73 [ 1231\ub74 to 168\ub71]; and other ILDs 197\ub71 [77\ub76 to 316\ub77]; p=0\ub741 for treatment by subgroup by time interaction). Adverse events reported in the subgroups were consistent with those reported in the overall population. Interpretation: The INBUILD trial was not designed or powered to provide evidence for a benefit of nintedanib in specific diagnostic subgroups. However, its results suggest that nintedanib reduces the rate of ILD progression, as measured by FVC decline, in patients who have a chronic fibrosing ILD and progressive phenotype, irrespective of the underlying ILD diagnosis. Funding: Boehringer Ingelheim
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