Trophic ecology of blue whiting in the Barents Sea

Blue whiting (Micromesistius poutassou) are distributed throughout the North Atlantic, including the Norwegian and Barents Seas. In recent years, both abundance and distribution of blue whiting in the Barents Sea have increased dramatically. Therefore, to evaluate the trophic impact of this increase, we analysed the diet of the species. In all, 54 prey species or taxa were identified, the main prey being krill. However, the diet varied geographically and ontogenetically: the proportion of fish in the diet was higher in large blue whiting and in the north of the range. Blue whiting overlap geographically with other pelagic species at the edge of their distribution in the Barents Sea, with juvenile herring in the south, with polar cod in the north, and with capelin in the northeast. The overlap in diet between blue whiting and these other pelagic species ranged from 6 to 86% and was greatest with capelin in areas where both species feed on hyperiids and krill. The importance of blue whiting as prey for predatory fish was highest in the areas of greatest abundance, but overall, blue whiting were seemingly unimportant as prey of piscivorous fish in the Barents Sea

Gender and early career status: variables of participation at an international marine science conference

Conference participation is an important part of academic practice and contributes to building scientific careers. Investigating demographic differences in conference participation may reveal factors contributing to the continued under-representation of women in marine and ocean science. To explore the gender and career stage dimensions of participation in an international marine science conference, preferences of presentation type (oral/poster) as well as acceptance and rejection decisions were investigated using 5-years of data (2015–2019) from an International Marine Science Conference. It was found that early career scientists were more likely to be women, while established scientists were more likely to be men. Although overall, gender did not show a significant effect on the decisions to “downgrade” requests for oral presentations to poster presentations, early career scientists were significantly more likely to be downgraded than established scientists. Given that more women were often early career scientists, more women than men had their presentations downgraded. Other indicators and evidence from conference prize-giving and recognition awards point to a gender gap remaining at senior levels, highlighting the need for further actions as well as monitoring and researching conference participation from a gender perspective.publishedVersio

Report on the Diet of the Blue Whiting in the Barents Sea in the Summer 2005 and in the Winters of 2002 and 2006

We analyzed stomach content of blue whiting in the Barents Sea in February-March 2002 and 2006, and in August-September 2005. Krill was the most important prey for blue whiting in the Barents Sea, and constituted about 90% of diet in winter and 50% in summer. Blue whiting also fed on amphipods and fish, including blue whiting. Copepods, an important group of prey for blue whiting in the Norwegian Sea, was unimportant in the diet in the Barents Sea. NORSK SAMMENDRAG: Vi undersøkte dietten til kolmule i Barentshavet i februar-mars 2002 og 2006, og i august og september 2005. Krill var det viktigste byttet til kolmula i Barentshavet, og utgjorde ca 90% av diett om vinteren og ca 50% om sommeren. Kolmula spiste også amfipoder og fisk, inkludert kolmule. Hoppekreps som er viktig for kolmula i Norskehavet, utgjorde en ubetydelig andel av dietten

Electrocardiographic biomarkers for detection of drug-induced late sodium current block

Background Drugs that prolong the heart rate corrected QT interval (QTc) on the electrocardiogram (ECG) by blocking the hERG potassium channel and also block inward currents (late sodium or L-type calcium) are not associated with torsade de pointes (e.g. ranolazine and verapamil). Thus, identifying ECG signs of late sodium current block could aid in the determination of proarrhythmic risk for new drugs. A new cardiac safety paradigm for drug development (the ''CiPA'' initiative) will involve the preclinical assessment of multiple human cardiac ion channels and ECG biomarkers are needed to determine if there are unexpected ion channel effects in humans. Methods and Results In this study we assess the ability of eight ECG morphology biomarkers to detect late sodium current block in the presence of QTc prolongation by analyzing a clinical trial where a selective hERG potassium channel blocker (dofetilide) was administered alone and then in combination with two late sodium current blockers (lidocaine and mexiletine). We demonstrate that late sodium current block has the greatest effect on the heart-rate corrected JTpeak interval (J-Tpeakc), followed by QTc and then T-wave flatness. Furthermore, J-Tpeakc is the only biomarker that improves detection of the presence of late sodium current block compared to using QTc alone (AUC: 0.83 vs. 0.72 respectively, p<0.001). Conclusions Analysis of the J-Tpeakc interval can differentiate drug-induced multichannel block involving the late sodium current from selective hERG potassium channel block. Future methodologies assessing drug effects on cardiac ion channel currents on the ECG should use J-Tpeakc to detect the presence of late sodium current block

Sex differences in drug-induced changes in ventricular repolarization

Introduction: Heart rate corrected QT (QTc) interval prolongation is a predictor of drug-induced torsade de pointes, a potentially fatal ventricular arrhythmia that disproportionately affects women. This study assesses whether there are sex differences in the ECG changes induced by four different hERG potassium channel blocking drugs. Methods and results: Twenty-two healthy subjects (11 women) received a single oral dose of dofetilide, quinidine, ranolazine, verapamil and placebo in a double-blind 5-period crossover study. ECGs and plasma drug concentrations were obtained at pre-dose and at 15 time-points post-dose. Dofetilide, quinidine and ranolazine prolonged QTc. There were no sex differences in QTc prolongation for any drug, after accounting for differences in exposure. Sex differences in any ECG biomarker were observed only with dofetilide, which caused greater J-Tpeakc prolongation (p=0.045) but lesser Tpeak-Tend prolongation (p=0.006) and lesser decrease of T wave amplitude (p=0.003) in women compared to men. Conclusions: There were no sex differences in QTc prolongation for any of the studied drugs. Moreover, no systematic sex differences in other drug-induced ECG biomarker changes were observed in this study. This study suggests that the higher torsade risk in women compared to men is not due to a larger concentration-dependent QTc prolongation

Comprehensive T wave Morphology Assessment in a Randomized Clinical Study of Dofetilide, Quinidine, Ranolazine, and Verapamil

Background Congenital long QT syndrome type 2 (abnormal hERG potassium channel) patients can develop flat, asymmetric, and notched T waves. Similar observations have been made with a limited number of hERG-blocking drugs. However, it is not known how additional calcium or late sodium block, that can decrease torsade risk, affects T wave morphology. Methods and Results Twenty-two healthy subjects received a single dose of a pure hERG blocker (dofetilide) and 3 drugs that also block calcium or sodium (quinidine, ranolazine, and verapamil) as part of a 5-period, placebo-controlled cross-over trial. At pre-dose and 15 time-points post-dose, ECGs and plasma drug concentration were assessed. Patch clamp experiments were performed to assess block of hERG, calcium (L-type) and late sodium currents for each drug. Pure hERG block (dofetilide) and strong hERG block with lesser calcium and late sodium block (quinidine) caused substantial T wave morphology changes (P<0.001). Strong late sodium current and hERG block (ranolazine) still caused T wave morphology changes (P<0.01). Strong calcium and hERG block (verapamil) did not cause T wave morphology changes. At equivalent QTc prolongation, multichannel blockers (quinidine and ranolazine) caused equal or greater T wave morphology changes compared with pure hERG block (dofetilide). Conclusions T wave morphology changes are directly related to amount of hERG block; however, with quinidine and ranolazine, multichannel block did not prevent T wave morphology changes. A combined approach of assessing multiple ion channels, along with ECG intervals and T wave morphology may provide the greatest insight into drug-ion channel interactions and torsade de pointes risk

Use of Advanced Flexible Modeling Approaches for Survival Extrapolation from Early Follow-up Data in two Nivolumab Trials in Advanced NSCLC with Extended Follow-up

Objectives: Immuno-oncology (IO) therapies are often associated with delayed responses that are deep and durable, manifesting as long-term survival benefits in patients with metastatic cancer. Complex hazard functions arising from IO treatments may limit the accuracy of extrapolations from standard parametric models (SPMs). We evaluated the ability of flexible parametric models (FPMs) to improve survival extrapolations using data from 2 trials involving patients with non–small-cell lung cancer (NSCLC). Methods: Our analyses used consecutive database locks (DBLs) at 2-, 3-, and 5-y minimum follow-up from trials evaluating nivolumab versus docetaxel in patients with pretreated metastatic squamous (CheckMate-017) and nonsquamous (CheckMate-057) NSCLC. For each DBL, SPMs, as well as 3 FPMs—landmark response models (LRMs), mixture cure models (MCMs), and Bayesian multiparameter evidence synthesis (B-MPES)—were estimated on nivolumab overall survival (OS). The performance of each parametric model was assessed by comparing milestone restricted mean survival times (RMSTs) and survival probabilities with results obtained from externally validated SPMs. Results: For the 2- and 3-y DBLs of both trials, all models tended to underestimate 5-y OS. Predictions from nonvalidated SPMs fitted to the 2-y DBLs were highly unreliable, whereas extrapolations from FPMs were much more consistent between models fitted to successive DBLs. For CheckMate-017, in which an apparent survival plateau emerges in the 3-y DBL, MCMs fitted to this DBL estimated 5-y OS most accurately (11.6% v. 12.3% observed), and long-term predictions were similar to those from the 5-y validated SPM (20-y RMST: 30.2 v. 30.5 mo). For CheckMate-057, where there is no clear evidence of a survival plateau in the early DBLs, only B-MPES was able to accurately predict 5-y OS (14.1% v. 14.0% observed [3-y DBL]). Conclusions: We demonstrate that the use of FPMs for modeling OS in NSCLC patients from early follow-up data can yield accurate estimates for RMST observed with longer follow-up and provide similar long-term extrapolations to externally validated SPMs based on later data cuts. B-MPES generated reasonable predictions even when fitted to the 2-y DBLs of the studies, whereas MCMs were more reliant on longer-term data to estimate a plateau and therefore performed better from 3 y. Generally, LRM extrapolations were less reliable than those from alternative FPMs and validated SPMs but remained superior to nonvalidated SPMs. Our work demonstrates the potential benefits of using advanced parametric models that incorporate external data sources, such as B-MPES and MCMs, to allow for accurate evaluation of treatment clinical and cost-effectiveness from trial data with limited follow-up. Flexible advanced parametric modeling methods can provide improved survival extrapolations for immuno-oncology cost-effectiveness in health technology assessments from early clinical trial data that better anticipate extended follow-up. Advantages include leveraging additional observable trial data, the systematic integration of external data, and more detailed modeling of underlying processes. Bayesian multiparameter evidence synthesis performed particularly well, with well-matched external data. Mixture cure models also performed well but may require relatively longer follow-up to identify an emergent plateau, depending on the specific setting. Landmark response models offered marginal benefits in this scenario and may require greater numbers in each response group and/or increased follow-up to support improved extrapolation within each subgroup

International perceptions of an integrated, multi-sectoral, ecosystem approach to management:Editor’s Choice

Abstract The Ecosystem Approach to Management (EAM) has emerged over the past decades, largely to promote biodiversity conservation, and more recently sectoral tradeoffs in the management of marine ecosystems. To ascertain the state of practice of EAM operationalization, a workshop was held, which included a pre-workshop online survey. The survey gauged international participants’ perspectives regarding capacity, knowledge, and application of EAM. When asked about the subject, most survey respondents had a general understanding of EAM, and provided a clear definition. Major perceived challenges to EAM objectives by those surveyed included limited knowledge, conflicting interests, insufficient communication, and limited organizational legal frameworks or governance structures. Of those directly involved in an ecosystem approach, the majority responded that processes were in place or developed for application of integrated knowledge toward assessing key issues within their respective sectors (i.e. fisheries, conservation, energy), and that capacity was generally high. Our results show that most respondents, irrespective of sector or geography, see value in considering an integrated, broader ecosystem approach as they manage their sector. Although many participants were from the North Atlantic region, our results suggest that much of the international community is converging toward continued understanding of broad-scale, integrated approaches to marine resource management.</jats:p