Eavesdropping on Gulf of Maine Cetaceans in the Vicinity of Mount Desert Rock

Passive acoustic monitoring, the recording and analysis of biological sound, is a standard method of research into the distribution and behavior of cetaceans worldwide. Acoustic monitoring is reliant upon a thorough reference catalog of species vocalizations and an understanding of the temporal and geographic parameters in which vocalizations occur. This study combined a standard cetacean passive acoustic monitoring survey with a concurrent visual survey at a known baleen whale summer feeding ground to determine the annual species and vocal composition, compare species detection rates using each method, and identify and attribute novel vocalizations to species. The survey took place at the Mount Desert Rock marine research station, Gulf of Maine, from July to October 2015 and 2016. Visual and acoustic detections of fin (Balaenoptera physalus), minke (Balaenoptera acutorostrata), humpback (Megaptera Noavaeangliae), right (Eubalaena glacialis), and sei (Balaenoptera borealis) whales were assessed. Minke whales were the most frequently seen species (71% of days), followed by fin (51%), humpback (40%), and right (4%). Visual detections of minke and fin whales were more restricted by distance than humpbacks, and fin and humpbacks were sighted significantly more frequently in the northeast quadrant of the survey space, suggesting each species may have fine scale spatial preferences within the survey space. Stereotyped vocalizations of fin, minke, right, and sei whales were recorded, and automatic template detectors were used to evaluate daily and annual occurrence. Fin whales were the most frequently detected (31% of days), followed by minke (22%), right (15%), and sei (2%). Fin and minke whales vocalized primarily in evening and night-time hours, and right whales vocalized primarily during the day. Instances of multi-hour vocalization bouts were also recorded for fin, minke, and right whales. The number of days where each species was detected both visually and acoustically was low, meaning the use of only one method or the other may have resulted in a less precise census. Five novel vocalizations were identified in the acoustic dataset that occurred on days when only fin or minke whales were visually detected. These were 74 to 34-Hz suspected fin whale downsweeps, 268 to 448-Hz short upsweeps, 415-Hz “whip-cracks”, 498 to 363-Hz long downsweeps, and 257 to 164-Hz long downsweeps. The 74 to 34-Hz downsweep was found to be statistically associated with fin whales (p = 0.040, Φ = 0.129), while all other statistical tests were inconclusive. Spatial comparisons between all visually detected fin and minke whales and all locations of novel vocalizations from the study period showed very little spatial overlap, a potential complication to the statistical results. Potential violations of statistical assumptions included non-vocalizing whales, whales vocalizing outside of the observation range, and vocalizations that occurred at night. The findings of this study suggest that while visual and acoustic surveys are both effective stand-alone techniques for detecting the presence and behavior of baleen whales, a more precise census is achieved when the two are combined. Concurrent visual and acoustic surveys are also an effective method for the identification and attribution of novel baleen whale vocalizations, though species composition, detection probability, and vocalization behavior must be accounted for

Determination of the most appropriate method for extrapolating overall survival data from a placebo-controlled clinical trial of lenvatinib for progressive, radioiodine-refractory differentiated thyroid cancer

Background: Cost-effectiveness models for the treatment of long-term conditions often require information on survival beyond the period of available data. Objectives: This paper aims to identify a robust and reliable method for the extrapolation of overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer receiving lenvatinib or placebo. Methods: Data from 392 patients (lenvatinib: 261, placebo: 131) from the SELECT trial are used over a 34-month period of follow-up. A previously published criterion-based approach is employed to ascertain credible estimates of OS beyond the trial data. Parametric models with and without a treatment covariate and piecewise models are used to extrapolate OS, and a holistic approach, where a series of statistical and visual tests are considered collectively, is taken in determining the most appropriate extrapolation model. Results: A piecewise model, in which the Kaplan–Meier survivor function is used over the trial period and an extrapolated tail is based on the Exponential distribution, is identified as the optimal model. Conclusion: In the absence of long-term survival estimates from clinical trials, survival estimates often need to be extrapolated from the available data. The use of a systematic method based on a priori determined selection criteria provides a transparent approach and reduces the risk of bias. The extrapolated OS estimates will be used to investigate the potential long-term benefits of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer patients and populate future cost-effectiveness analyses

Induction of systemic oxidative stress leads to brain oedema in portacaval shunted rats

Background & Aims The pathogenesis of hepatic encephalopathy (HE) is multifactorial and often associated with the development of brain oedema. In addition to ammonia playing a central role, systemic oxidative stress is believed to aggravate the neuropsychological effects of ammonia in patients with chronic liver disease (CLD). The aim of this study was to (i) induce systemic oxidative stress in hyperammonaemic portacaval anastomosed (PCA) rats by inhibiting the antioxidant glutathione using Dimethyl maleate (DEM) and (ii) investigate whether a synergistic relationship between ammonia and oxidative stress contributes to the pathogenesis of brain oedema in CLD. Methods Four-week PCA and sham-operated rats received DEM (0.4–4 mg/kg/day) for the last 10 days before sacrifice when oxidative stress markers [reactive oxygen species (ROS) and malondialdehyde (MDA)] were assessed in blood and frontal cortex. Brain water content was measured using a specific gravimetric technique. Results Dimethyl maleate induced an increase in ROS and MDA in the blood, but not in the brain, of the PCA rats, compared with non-treated PCA rats. This was accompanied with an increase in brain water content (PCA+DEM: 78.45 ± 0.13% vs. PCA: 77.38 ± 0.11%, P < 0.001). Higher doses of DEM induced systemic oxidative stress in sham-operated controls, but brain oedema did not develop. Conclusions Dimethyl maleate provoked systemic, not central, oxidative stress in PCA rats, resulting in the development of brain oedema. Independently, hyperammonaemia and systemic oxidative stress do not precipitate brain oedema; therefore, our findings sustain that a synergistic effect between hyperammonaemia and systemic oxidative stress is responsible for the development of brain oedema in HE