Annual chronotypes functionally link life histories and life cycles in birds

Abstract 1.Life-history responses to ecological selection pressures can be described by a slow-fast life-history axis. Along this axis, fast-living animals usually invest in high breeding output, while slow-living ones prioritize their own survival. 2.Birds may solve the trade-off between reproduction and survival by optimising their seasonal schedules. Breeding early tends to facilitate reproductive success, whereas breeding late increases the chances to survive. On the basis of this argument, short- and long-lived birds should benefit from initiating spring activities earlier and later, respectively. 3.The timing of seasonal activities, all else being equal, depends on the architecture of endogenous circannual clocks. Particularly, the length of the circannual period relative to the 365-day environmental year facilitates either the anticipation of seasonal activities (in case of periods shorter than 365 days) or represents a responsive mode (when periods are longer than 365 days). The two alternatives will be manifested by early or late annual chronotypes, respectively. 4.We hypothesise that, in birds, annual chronotype will correspond with position on the ‘pace-of-life scale’. Species with low survival probability, and thus a poor chance of breeding in a next season, should show early annual chronotypes facilitated by circannual clock periods shorter than 365 days. In contrast, species with high survival rates should benefit from relatively long circannual periods. 5.We predicted that circannual period lengths should correlate positively with species-specific adult annual survival rates. Using published data for 16 wild bird species, we confirmed the predicted correlation. In our analysis, we accounted for the possible metabolic nature of circannual clocks, a correlation between rate of metabolism and survival, and phylogenetic relationships. 6.Based on our finding, we propose that evolutionary responsive circannual clocks help birds cope with temporal variation in environment in ways that are most appropriate for their life-history and life-table attributes. This article is protected by copyright. All rights reserved

Longer wings for faster springs – wing length relates tospring phenology in a long-distanc e migrant across its range

In migratory birds, morphological adaptations for efficient migratory flight often oppose morphological adaptations for efficient behavior during resident periods. This includes adaptations in wing shape for either flying long distances or foraging in the vegetation and in climate-driven variation of body size. In addition, the timing of migratory flights and particularly the timely arrival at local breeding sites is crucial because fitness prospects depend on site-specific phenology. Thus, adaptations for efficient long-distance flights might be also related to conditions at destination areas. For an obligatory long-distance migrant, the common nightingale, we verified that wing length as the aerodynamically important trait, but not structural body size increased from the western to the eastern parts of the species range. In contrast with expectation from aerodynamic theory, however, wing length did not increase with increasing migration distances. Instead, wing length was associated with the phenology at breeding destinations, namely the speed of local spring green-up. We argue that longer wings are beneficial for adjusting migration speed to local conditions for birds breeding in habitats with fast spring green-up and thus short optimal arrival periods. We suggest that the speed of spring green-up at breeding sites is a fundamental variable determining the timing of migration that fine tune phenotypes in migrants across their range

A mode-of-action ontology model for safety evaluation of chemicals: outcome of a series of workshops on repeated dose toxicity

Repeated dose toxicity evaluation aims at assessing the occurrence of adverse effects following chronic or repeated exposure to chemicals. Non-animal approaches have gained importance in the last decades because of ethical considerations as well as due to scientific reasons calling for more human-based strategies. A critical aspect of this challenge is linked to the capacity to cover a comprehensive set of interdependent mechanisms of action, link them to adverse effects and interpret their probability to be triggered in the light of the exposure at the (sub)cellular level. Inherent to its structured nature, an ontology addressing repeated dose toxicity could be a scientific and transparent way to achieve this goal. Additionally, repeated dose toxicity evaluation through the use of a harmonized ontology should be performed in a reproducible and consistent manner, while mimicking as accurately as possible human physiology and adaptivity. In this paper, the outcome of a series of workshops organized by Cosmetics Europe on this topic is reported. As such, this manuscript shows how experts set critical elements and ways of establishing a mode-of-action ontology model as a support to risk assessors aiming to perform animal-free safety evaluation of chemicals based on repeated dose toxicity data

Clinical outcome of patients with metastatic melanoma of unknown primary in the era of novel therapy

Melanoma of unknown primary (MUP) is considered different from melanoma of known primary (MKP), and it is unclear whether these patients benefit equally from novel therapies. In the current study, characteristics and overall survival (OS) of patients with advanced and metastatic MUP and MKP were compared in the era of novel therapy. Patients were selected from the prospective nation-wide Dutch Melanoma Treatment Registry (DMTR). The following criteria were applied: diagnosis of stage IIIc unresectable or IV cutaneous MKP (cMKP) or MUP between July 2012 and July 2017 and treatment with immune checkpoint inhibition and/or targeted therapy. OS was estimated using the Kaplan-Meier method. The stratified multivariable Cox regression model was used for adjusted analysis. A total of 2706 patients were eligible including 2321 (85.8%) patients with cMKP and 385 (14.2%) with MUP. In comparative analysis, MUP patients more often presented with advanced and metastatic disease at primary diagnosis with poorer performance status, higher LDH, and central nervous system metastases. In crude analysis, median OS of cMKP or MUP patients was 12 months (interquartile range [IQR] 5 - 44) and 14 months (IQR 5 - not reached), respectively (P = 0.278). In adjusted analysis, OS in MUP patients was superior (hazard rate 0.70, 95% confidence interval 0.58-0.85; P < 0.001). As compared to patients with advanced and metastatic cMKP, MUP patients have superior survival in adjusted analysis, but usually present with poorer prognostic characteristics. In crude analysis, OS was comparable indicating that patients with MUP benefit at least equally from treatment with novel therapies