Marine mammal distribution and abundance in an offshore sub-region of the northeastern Chukchi Sea during the open-water season

AbstractThis paper describes the distribution and abundance of marine mammals during the open-water season within and near three offshore oil and gas prospects in the northeastern Chukchi Sea, known as the Klondike, Burger, and Statoil study areas. We collected vessel-based marine mammal data during July–October 2008–2010 along line transects oriented in a north–south direction. Over this period, we surveyed ~18,600km of on-transect effort in the three study areas. Sightings of cetaceans were rare. The bowhead whale was the primary cetacean species sighted and was mostly observed in October (33 of 35 animals). Pinnipeds were the most abundant marine mammals in the study area, with 980 seals and 367 walruses recorded on transect. Most seals were observed as solitary animals, while walruses were often observed in aggregations. We calculated seal and walrus densities using species-specific detection functions corrected for probability of detection. There was high interannual variability in the abundance of seals and walruses that for some species may be related to interannual differences in ice conditions. Notwithstanding this variation, the distribution data suggest that benthic-feeding bearded seals and walruses generally were more common in the Burger and Statoil study areas, which can be characterized as more benthic-dominated ecosystems. The distribution of ringed/spotted seals did not show any statistically significant differences among the study areas, although a slight preference for the Klondike and Statoil study areas was suggested. Both of these study areas are affected by Bering Sea Water from the Central Channel and have a stronger pelagic component than the Burger study area. Continued sampling of these areas will help establish whether the observed trends in marine mammal distribution and abundance are persistent

Prospective real-world study on the pharmacokinetics of pembrolizumab in patients with solid tumors

Background Dosing schemes of pembrolizumab (anti-programmed cell death protein 1 monoclonal antibody) are solely based on pharmacokinetic (PK) modelling derived from phase I–III trials. The current study aimed to determine factors affecting PK and its relationship with clinical outcome in the real-world setting.Methods Advanced-stage cancer patients, who were treated with pembrolizumab monotherapy (2 mg/kg Q3W or 200 mg flat Q3W), were prospectively included for serial sampling to obtain trough concentrations. A PK model was generated, covariate effects assessed and internally validated by a bootstrap procedure. PK parameters were related to overall survival (OS) and the occurrence of immune-related adverse events (irAEs).Results 588 serum samples derived from 122 patients with (non-)small-cell lung cancer ([N]SCLC), malignant pleural mesothelioma (MPM), melanoma and urothelial cell cancer (UCC) were analyzed. Median follow-up was 2.2 years. A one-compartment PK model was generated: body surface area (BSA) and serum albumin had a significant effect on drug clearance (CL; covariate estimate 1.46 and −1.43, respectively), and serum lactate dehydrogenase (LDH) on the distribution volume(Vd; 0.34). A significant inverse CL–OS relationship was determined for NSCLC (HR:1.69; 95%CI1.07–2.68; p=0.024) and MPM (HR: 3.29; 95% CI 1.08 to 10.09; p=0.037), after correction for prognostic factors, which could not confirmed for melanoma (p=0.22) or UCC (p=0.34). No relationship could be determined between CL and grade >3 irAEs (p=0.70).Conclusions High interpatient variability of pembrolizumab PK is determined by BSA and serum albumin (on CL) and LDH (on Vd). A strong inverse CL–OS relationship was demonstrated for NSCLC and MPM, which could not be observed for melanoma and UCC. The findings suggest that personalized dosing should be prospectively explored