Abstract. Bigeye tuna are known for remarkable daytime vertical migrations between deep water, where food is abundant but the water is cold, and the surface, where water is warm but food is relatively scarce. Here we investigate if these dive patterns can be explained by dynamic optimal foraging theory, where the tuna maximizes its energy harvest rate. We assume that foraging efficiency increases with body temperature, so that the vertical migrations are thermoregulatory. The tuna's state is characterized by its mean body temperature and depth, and we solve the optimization problem numerically using dynamic programming. With little calibration of model parameters, our results are consistent with observed data on vertical movement: we find that small tuna should display constant-depth strategies while large tuna should display vertical migrations. The analysis supports the hypothesis that the tuna behaves such as to maximize its energy gains. The model therefore provides insight into the processes underlying observed behavioral patterns and allows generating predictions of foraging behavior in unobserved environments.

Data collected during the SMART-7™ study revealed no treatment-related safety issues and no FVII-binding antibodies for patients treated with NovoSeven under real-world conditions.

Introduction: SMART-7™ (NCT01220141) was a prospective, post-authorization, single-arm, multinational, multi-center, non-interventional study investigating the safety and effectiveness of room temperature stable rFVIIa (NovoSeven®) in patients with hemophilia A or B with inhibitors in a real-world setting. Here, we present a subgroup analysis of the hemostatic response of bleeding episodes to treatment with rFVIIa. Methods: Study medication was not provided; use was at the discretion of the treating physician in accordance with the local label. Bleeding history was collected at the initiation visit. Information on bleeding episodes, including home treatment, was recorded in patient diaries during the study. Patients evaluated the status of bleeding episodes after treatment as 'bleed stopped', 'bleed slowed', or 'no change/worsened'. Overall bleed outcome was defined as the last given patient evaluation of the bleed. Patients were observed until they had achieved ≥25 exposure days, defined as any exposure to rFVIIa during one 24 h period. Results: From November 2010 to March 2015, 51 patients were enrolled at 24 sites in 14 countries; 31 (60.8%) patients completed the study and 20 discontinued (11 of these due to global study discontinuation, a decision endorsed by the European Medicines Agency). Patients were aged 1.6-69.5 years (median 22.0 years) with an historical median bleeding rate of 1.0 episode per month. During the study, 48 patients experienced a total of 618 bleeding episodes: median number of bleeding episodes per patient was 10.5; median study duration per patient was 13.9 months. 63.4% of bleeding episodes occurred spontaneously and 31.2% were categorized as traumatic. Effectiveness evaluation at end of treatment was available for 609 bleeding episodes: 569 (93.4%) resolved, 35 (5.7%) slowed and 5 (0.8%) were unchanged/worsened. Nine bleeds had no reported outcome. A total of 538 bleeds were treated with rFVIIa monotherapy: 507 (94.2%) resolved, 27 (5.0%) slowed and 4 (0.7%) were unchanged/worsened. In a post-hoc analysis in which the data were divided by time to first treatment into 3 groups, the best hemostatic response (96.5%) was observed when rFVIIa treatment was initiated ≤1 h after onset of bleed; effectiveness was also high (93.1%) for bleeds treated >1-≤4 h of onset, decreasing for those treated >4 h after onset (87.3%; representing 13.1% of bleeds). Early treatment (≤1 h) with rFVIIa monotherapy was effective for both joint and muscle bleeds (96.2% and 97.3%, respectively). The initial rFVIIa dose administered was comparable for bleeds treated ≤1 h and those treated >1-≤4 h or >4 h after onset (Table). The median number of rFVIIa doses was higher for bleeds treated >4 h after onset than for those treated within 4 h, however these data should be interpreted with caution due to the low number of bleeds represented (13.1% of total) (Table). Conclusion: A subanalysis of the SMART-7™ study demonstrates higher effectiveness of early treatment with rFVIIa, with 96.5% of bleeds resolved when treatment was initiated ≤1 h after bleed onset, and remaining high (93.1%) for bleeding treatment >1-≤4 h. Total effectiveness was >87% in bleeds treated >4 hours after bleed onset. Disclosures Benson: Novo Nordisk: Consultancy. Benchikh El Fegoun:Novo Nordisk: Employment. Cepo:Novo Nordisk: Employment. Sommer:Novo Nordisk: Employment. Kavakli:Novo Nordisk: Other: Steering committee meetings.