Tolerance of Bearded Vultures to Human Activities: Response to Comor et al. (2019)

The bearded vulture (Gypaetus barbatus) is listed as vulnerable in Europe on the International Union for Conservation of Nature Red List because of population declines over multiple generations. Vulture population declines have been attributed to shooting, use of toxicants, and changes in land use, which have resulted in habitat degradation and increased anthropogenic disturbances. Concomitantly, conservation authorities have restricted practices deemed harmful to the species and have established protection buffers around occupied vulture breeding sites to mitigate the impacts of anthropogenic disturbances on breeding success. Comor et al. (2019) compared bearded vulture breeding success over 6 years within and outside areas with restricted activities in the western French Pyrenees and assessed distances between vultures and hunting parties. They concluded that hunting was not a threat to species conservation and may even benefit vultures by providing alternative food resource. We dispute the conclusions of Comor et al. (2019) and present concerns about the data used, the study design, and the inferences taken from some of the data presented. Herein we provide arguments and rationale to support our opinion

Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT

International audienceBackground: The stem cell factor receptor, KIT, is a target for the treatment of cancer, mastocytosis, and inflammatory diseases. Here, we characterise the in vitro and in vivo profiles of masitinib (AB1010), a novel phenylaminothiazole-type tyrosine kinase inhibitor that targets KIT. Methodology/Principal Findings: In vitro, masitinib had greater activity and selectivity against KIT than imatinib, inhibiting recombinant human wild-type KIT with an half inhibitory concentration (IC50) of 200 ± 40 nM and blocking stem cell factor-induced proliferation and KIT tyrosine phosphorylation with an IC50 of 150 ± 80 nM in Ba/F3 cells expressing human or mouse wild-type KIT. Masitinib also potently inhibited recombinant PDGFR and the intracellular kinase Lyn, and to a lesser extent, fibroblast growth factor receptor 3. In contrast, masitinib demonstrated weak inhibition of ABL and c-Fms and was inactive against a variety of other tyrosine and serine/threonine kinases. This highly selective nature of masitinib suggests that it will exhibit a better safety profile than other tyrosine kinase inhibitors; indeed, masitinib-induced cardiotoxicity or genotoxicity has not been observed in animal studies. Molecular modelling and kinetic analysis suggest a different mode of binding than imatinib, and masitinib more strongly inhibited degranulation, cytokine production, and bone marrow mast cell migration than imatinib. Furthermore, masitinib potently inhibited human and murine KIT with activating mutations in the juxtamembrane domain. In vivo, masitinib blocked tumour growth in mice with subcutaneous grafts of Ba/F3 cells expressing a juxtamembrane KIT mutant. Conclusions: Masitinib is a potent and selective tyrosine kinase inhibitor targeting KIT that is active, orally bioavailable in vivo, and has low toxicit

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Effect of human activities on bearded vulture behaviour and breeding success in the French Pyrenees

The bearded vulture is a threatened species for which human disturbance has been suggested as an important factor potentially influencing breeding success. Additionally, disturbance remains one of the few factors that is possible to control through directed policy. We evaluated the effect of human activities on the behaviour and breeding success of bearded vultures breeding in the French Pyrenees. Human activities influenced bearded vulture behaviour (primarily through a decrease in nest attendance), but this effect varied in relation to the type of activities and the distance to the nest. Very noisy activities and hunting most frequently provoked nest unattendance even when occurring far (>1.5 km) from the nest. People on foot or cars/planes only affected bearded vulture behaviour if close (<500–700 m) to the nest. We also found a significant relationship between human activities and vulture breeding success: the probability of failure increased with the frequency of human activities. In particular, there was a significant relationship between the probability of failure and the frequency of very noisy activities. We discuss the implications of our results for management schemes and conservation of this species

Sources of variation in mortality of the Bearded Vulture Gypaetus barbatus in Europe

We analyse the causes of mortality for the Bearded Vulture in Europe. Shooting (31%), intentional poisoning (26%), collision (18%) and unintentional poisoning (12%) were the most important causes of mortality. No differences were found between sexes or age classes (non-adults and adults) for any of the causes of death. When the four main categories of mortality were grouped in periods of 3 years from 1986 (coinciding with the species' reintroduction to the Alps) to 2006, mortality showed significant temporal variation. The results suggest that while the number of collision/electrocution deaths has remained stable or increased slightly, the number of cases of shooting has declined during the last 6 years, while at the same time intentional and unintentional poisonings have increased. We found substantial differences between causes of mortality recorded for birds located by chance (75% related to shootings and collisions with powerlines) and radio-tagged birds (86% related to intentional and unintentional poisoning), suggesting biases in methodology for monitoring mortality. The results suggest that human persecution continues to be the main factor contributing to unnatural mortality for European Bearded Vultures. Future management actions should concentrate on the creation of protocols for the collection of carcasses and detailed analyses to determine and mitigate anthropogenic sources of mortality.This study was jointly funded by the Dirección General para la Biodiversidad of Ministerio de Medio Ambiente, Departament de Medi Ambient i Habitatge of Generalitat de Catalunya and Ministere de l’Ecologie et du Developpement Durable and Ligue pour la Protection des Oiseaux (LPO).Peer reviewe

VIGILANCE POISON: Illegal poisoning and lead intoxication are the main factors affecting avian scavenger survival in the Pyrenees (France)

International audienceA specific surveillance program has been set up to monitor avian scavenger populations in the French Pyrenean Mountains, hosting a high proportion of the French populations. The two main purposes of the study were to identify all causes of death and to investigate poisoning cases. All 170 birds found dead during the 7-year program were submitted to full necropsy, X-Ray, parasitological investigations and consistent analytical toxicology screenings (Cholinesterase inhibitors, anticoagulant rodenticides, organochlorine insecticides, Pb, Cd). Over the study period, 8 Bearded Vultures, 120 Griffon Vultures, 8 Egyptian Vultures and 34 Red kites were eventually collected. Mortality events were often multifactorial, but poisoning was by far the most common cause of death (24.1%), followed by trauma/fall (12%), bacterial diseases and starvation (8%) and electrocution (6%). Illicit use of banned pesticides was identified as a common cause of poisoning (53% of all poisoning cases) and lead poisoning was also identified as a significant toxicant issue (17% of all poisoning cases). Lead isotopic signature could be associated primarily with ammunition. Last, a positive association between trauma and lead contamination was detected, indicating that lead could be a significant contributor to different causes of death. These results urge for severe restrictions on the use of lead ammunition to prevent scavengers from detrimental exposure

Population expansion and breeding success of Bearded Vultures Gypaetus barbatus in the French Pyrenees: results from long‐term population monitoring

Based on monitoring of Bearded Vultures over 24 years in the French Pyrenees, we assessed factors explaining temporal and spatial variations in numbers and breeding performance. The number of territorial pairs increased throughout the study period from 16 in 1994 to 44 in 2017. No significant negative trends in mean productivity (fledglings per territorial pair) were detected with increasing population size. Colonization probability increased significantly with breeding population size the previous year and with the regular provision of supplementary food in the territory the winter when colonization occurred. Colonization of new territories simultaneously increased the distribution range and local densities, but we found no effect of number of near neighbours on productivity. Pairs having bred less than 5 years together had a much lower probability of laying clutches, and higher lay rates were observed inside or close to protected areas after accounting for pair‐bond length, so productivity of territories inside protected areas was significantly higher. Nest success decreased with advanced lay date and increased with winter food abundance. Nesting failures in the study area were frequently associated with harsh weather. Additionally, disturbance by human activities was the second most important identified cause of breeding failure. The probability of failing due to disturbance was higher in western areas (where breeding areas are more accessible to humans), outside protected areas, and has increased with time. After a failure due to disturbance, there was a significantly higher probability of not producing a clutch the following year as compared with pairs that had not failed or had failed due to other causes, indicating deferred effects of disturbance. Our results show the benefits of conservation management actions, such as implementation of protected areas or designed supplementary food programmes in winter, to help range expansion. On the other hand, we did not find a significant effect of winter supplementary food on productivity. Management of feeding sites should be adapted to more specific planning, being used only in areas where natural food availability is scarce, avoiding its use close to breeding sites when juveniles disperse, and targeted mainly to help range expansion. Our results also highlight the importance of maintaining or enhancing good populations of wild ungulates and regulating human activities around nesting sites of this threatened species.The monitoring programme was mostly funded by national and regional public subsidies, as well as European funds.Peer reviewe

Tolerance of bearded vultures to human activities: response to Comor et al. (2019)

The bearded vulture (Gypaetus barbatus) is listed as vulnerable in Europe on the International Union for Conservation of Nature Red List because of population declines over multiple generations. Vulture population declines have been attributed to shooting, use of toxicants, and changes in land use, which have resulted in habitat degradation and increased anthropogenic disturbances. Concomitantly, conservation authorities have restricted practices deemed harmful to the species and have established protection buffers around occupied vulture breeding sites to mitigate the impacts of anthropogenic disturbances on breeding success. Comor et al. (2019) compared bearded vulture breeding success over 6 years within and outside areas with restricted activities in the western French Pyrenees and assessed distances between vultures and hunting parties. They concluded that hunting was not a threat to species conservation and may even benefit vultures by providing alternative food resource. We dispute the conclusions of Comor et al. (2019) and present concerns about the data used, the study design, and the inferences taken from some of the data presented. Herein we provide arguments and rationale to support our opinion.Peer reviewe

An assessment of population size and demographic drivers of the Bearded Vulture using integrated population models

Conventional approaches for the assessment of population abundance or trends are usually based on a single source of information, such as counts or changes in demographic parameters. However, these approaches usually neglect some of the information needed to properly understand the population as a whole, such as assessments of the non-breeding proportion of the population and the drivers of population change. The Bearded Vulture Gypaetus barbatus is a threatened species and its Pyrenean population (the largest in Europe) inhabits parts of Spain, Andorra, and France. We developed an Integrated Population Model (IPM) using data from a long-term study (1987–2016) in the three countries, including capture–mark–recapture of 150 marked individuals, to assess population size and age structure at the whole population scale, and obtain estimates of survival and breeding parameters of this population. The breeding population experienced a geometric mean population increase of 3.3% annually, falling to 2.3% during the last 10 yr. The adult proportion of the population increased with time, from 61% to 73%. There were 365 (95% Bayesian credible interval [BCI]: 354–373) adult breeding birds in 2016, representing 49% of the adult population and 36% of the total population (estimated at 1,026 individuals, 95% BCI: 937–1,119). The large number of non-breeding adults probably led to higher mean age of first reproduction than previously estimated, and to an estimated 30–35% of territories occupied by polyandrous trios. Population growth rate was positively and strongly correlated with adult survival, which had a much greater effect on population growth than productivity. The effects of subadult and juvenile survival on population growth were weaker. We found strong evidence for a density-dependent decrease in juvenile survival, productivity and adult survival, leading to reduced population growth with increased population size. Our approach allowed us to identify important conservation issues related to the management of supplementary feeding sites and geographic expansion of this population. Our study supports the use of IPMs as a tool to understand long-lived species, allowing simultaneous estimates of the non-breeding size of the population (which is critical for understanding population functioning), better estimates of population parameters, and assessment of demographic drivers