Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets

Objective: To develop and externally validate a prediction model for major bleeding in patients with a TIA or ischemic stroke on antiplatelet agents. Methods: We combined individual patient data from 6 randomized clinical trials (CAPRIE, ESPS-2, MATCH, CHARISMA, ESPRIT, and PRoFESS) investigating antiplatelet therapy after TIA or ischemic stroke. Cox regression analyses stratified by trial were performed to study the association between predictors and major bleeding. A risk prediction model was derived and validated in the PERFORM trial. Performance was assessed with the c statistic and calibration plots. Results: Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed 3-year risk of major bleeding was 4.6% (95% confidence interval [CI] 4.4%–4.9%). Predictors were male sex, smoking, type of antiplatelet agents (aspirin-clopidogrel), outcome on modified Rankin Scale ≥3, prior stroke, high blood pressure, lower body mass index, elderly, Asian ethnicity, and diabetes (S2TOP-BLEED). The S2TOP-BLEED score had a c statistic of 0.63 (95% CI 0.60–0.64) and showed good calibration in the development data. Major bleeding risk ranged from 2% in patients aged 45–54 years without additional risk factors to more than 10% in patients aged 75–84 years with multiple risk factors. In external validation, the model had a c statistic of 0.61 (95% CI 0.59–0.63) and slightly underestimated major bleeding risk. Conclusions: The S2TOP-BLEED score can be used to estimate 3-year major bleeding risk in patients with a TIA or ischemic stroke who use antiplatelet agents, based on readily available characteristics. The discriminatory performance may be improved by identifying stronger predictors of major bleeding

Weather conditions, brood size and hatching order affect Common Swift Apus apus nestlings survival and growth

Capsule Hatching order negatively affected Common Swift Apus apus nestlings survival, while brood size and meteorological conditions influenced their growth patterns. Aims To investigate the influence of hatching date, age, sex, brood size and meteorological conditions on survival and growth of Common Swift nestlings from Northern Italy (Southern Europe), a relatively warm and dry part of the distribution range of this species. Methods Nestlings were weighed at regular intervals and molecularly sexed. Growth patterns were described using a double-Richards growth curve, i.e. a growth curve that also accounted for the pre-fledging mass loss. We also identified the Linear Growth Phase (i.e. when nestlings grew at the fastest rate). Results Mortality increased with hatching order and decreased with brood size. Mortality was highest for fourth-hatched nestlings, none of which survived. Nestlings hatched late in the season grew faster, experienced the fastest growth rate at a younger age, but reached a lower maximum weight than nestlings hatched early in the season. Nestlings from large broods reached a lower maximum weight than those of small ones. Nestlings gained more mass when temperature was slightly higher than that expected from the seasonal temperature trend, and on rainy and windy days. Conclusion Common Swift nestlings growth, but not survival, was affected by meteorological conditions, with moderate rainfall, moderate winds and high temperatures favouring greater mass gain. Higher intra-brood competition resulted in slower growth and lower maximum weight. Late-hatched nestlings grew faster but reached a lower maximum weight and a lower pre-fledging mass, possibly suggesting that late-hatched nestlings adaptively tune their growth pattern to the approaching onset of migration to their African wintering quarters. Our results emphasize the importance of exploring weather effects on the breeding biology of a species in different portions of its distribution range that are characterized by contrasting climatic conditions

Hayfields enhance colony size of the Barn Swallow Hirundo rustica in northern Italy

The widespread decline of farmland birds is a major issue of biological conservation in European countries. The Barn Swallow Hirundo rustica is a flagship species for farmland bird conservation owing to its aesthetic and cultural value and to the sharp decline observed in several populations. Based on a long-term monitoring project of a population in a protected area of Northern Italy, we documented a dramatic decline of 56.6% between 1999 and 2011, corresponding to a decrease of 6.59% each year. We also showed that colonies were on average larger in farms with livestock than those without livestock, and that colony size increased with increasing extent of hayfields within 200 m from the colony in farms without livestock, but not in those with livestock. Hayfield extent at greater distances did not influence population size or trend. Cessation of livestock farming therefore determined a decline in local colonies, but this decline may be buffered by an increase in hayfield extent within 200 m from the farm. However, variation in the ecological features of breeding sites explained only a fraction of the observed population decline, suggesting that ecological conditions during migration and wintering may be crucial in affecting population trends. Mean hatching date of first broods advanced in recent years, but less so in farms with, than without, livestock. Independently of year, mean hatching date advanced more in farms with greater extent of hayfields within 200 m of the colony. Reproductive success, measured as the mean number of fledged offspring per nest, declined significantly with hatching date, but was not affected by hayfield extent. Conversely, nestling quality, in terms of body mass and feather development, improved with increasing extent of hayfields around the colony, particularly in late-hatched first clutches. Our findings suggest that conservation strategies for this declining species should include both the maintenance of livestock farming and the enlargement of hayfields close to breeding colonies, particularly in farms where livestock farming has ceased

Diet heteogeneity and antioxidant defence in Barn Swallow Hirundo rustica nestlings

Populations of several farmland bird species have suffered sharp declines linked to increased environmental homogeneity and reduced biodiversity, particularly of insects, upon which several farmland birds feed. Diet, in turn, has a crucial role in organism fitness. Antioxidants acquired through diet, in particular, help by protecting the organisms against the effects of Reactive Oxygen Species, which originate as a natural by-product of metabolism. Here we investigated the relationships among environmental heterogeneity, diet composition, and oxidative status by using Barn Swallow (Hirundo rustica) nestling as a model. By analysing chitin fragments extracted from faecal sacs, we found that nestlings\u2019 diet was mainly composed by four insect families: Formicidae (Hymenoptera), Aphodidae (Coleoptera), Tabanidae and Syrphidae (Diptera). We also observed body parts of Diabrotica virgifera, the most important insect pest of maize (Zea mais) in the world. Nestling diet composition varied with environmental heterogeneity in the foraging range of adult Barn Swallow (i.e. 200 m from each colony). The antioxidant capacity (AOC) of nestlings, which was assessed using the OXY-Adsorbent test on blood plasma samples, peaked at intermediate values of diet diversity, suggesting that it can be mediated by the composition of the nestlings\u2019 diet. Heterogeneous environments may offer a wide array of pray, and this may allow foraging Barn Swallow to feed their nestling with selected prey that may enhance their oxidative status. Similar mechanisms may act for a wide array of farmland birds, thus shading light on the mechanisms that link habitat homogenization and bird population declines

Effects of different routes of administration on the immunogenicity of the Tat protein and a Tat-derived peptide.

Abstract The use of the Tat protein of HIV in vaccines against AIDS showed promising results in primate and human studies. To characterize the impact of the administration route on the induction of humoral responses at systemic and mucosal levels, we compared intradermal, intramuscular and mucosal immunizations with Tat and a Tat-derived peptide. Mice were immunized with the Tat protein by different routes and the titer and isotype of anti-Tat antibodies were assessed in serum and mucosal lavages. Intramuscular and intradermal administrations showed comparable immunogenicity, while the mucosal administration was unable to induce IgM in serum and IgG at mucosal sites but showed superior immunogenicity in terms of IgA induction. Anti-Tat antibodies were also obtained upon vaccination with the immunodominant Tat 1-20 peptide which was, however, less immunogenic than the whole Tat protein

Impact of miniaturized geolocators on barn swallow Hirundo rustica fitness traits

Miniaturized light-level geolocators may revolutionise the study of avian migration. However, there are increasing concerns that they might negatively affect fitness. We investigated the impact of two miniaturized geolocator models (SOI-GDL2.10, deployed in 2010, and SOI-GDL2.11, deployed in 2011) on fitness traits of the barn swallow Hirundo rustica, one of the smallest migratory species to which geolocators have been applied to date. The 2011 model was lighter (by 0.09 g) and had a shorter light stalk compared to the 2010 model. Using data from 640 geolocator and 399 control individuals from three geographical populations, we found that geolocators reduced annual survival probabilities (control birds: 0.19-0.63; geolocator birds: 0.08-0.40, depending on year, sex, and how birds that lost the device were considered), with more markedly negative effects on females equipped with the 2010 model. In addition, among birds equipped with the 2010 model, onset of reproduction in the subsequent year was delayed (by 12 d) and females laid smaller first clutches (by 1.5 eggs, i.e. a 30% reduction) compared to controls. Equipping parents with geolocators while they were attending their brood did not affect nestling body mass or fledging success. A reduction of geolocator weight and drag by shortening the light stalk slightly enhanced the survival of females but not that of males, and mitigated the negative carry-over effects on subsequent reproduction. Our study shows that geolocators can have a negative impact on survival and reproduction, and that even minor differences in weight and drag can make the difference. We suggest that studies aiming at deploying geolocators or other year-round tagging devices should be preceded by pilot experiments to test for fitness effects

Maintenance of livestock farming may buffer population decline of the Barn Swallow Hirundo rustica

Populations of farmland and long-distance migratory birds have suffered steep, often dramatic, declines in the last few decades. The Barn Swallow Hirundo rustica is a small migratory farmland bird that breeds synanthropically in farms, particularly where livestock is reared. Populations of this species have suffered marked declines in different parts of its European breeding range. Here, we first report a dramatic decline of 8.4% per year of the number of breeding pairs and the extinction of 19.6% of the colonies in three agricultural areas in Northern Italy, which differ in general ecological conditions. This decline was estimated on a very large sample of 190 randomly chosen farms where breeding pairs were censused both in 2001 and 2010, and occurred at different rates in the three study areas. Barn Swallows declined most (9.3% per year) in an intensively cultivated area where colonies are widespread, and least (1.3% per year) in a hilly area with a comparatively small density of colonies. Variation in livestock farming significantly influenced population dynamics. Specifically, cessation of livestock farming at a given farm between the two census years resulted in a significantly steeper decline in the number of breeding pairs compared to farms where livestock farming was maintained. Our findings highlight the fact that European populations of Barn Swallows breeding in intensively cultivated agro-ecosystems may become significantly depleted in the next decades, and indicate that maintenance of livestock farming may contribute to buffering the population decline of this species

Migratory connectivity and effects of winter temperatures on migratory behaviour of the European robin Erithacus rubecula : a continent-wide analysis

Many partially migratory species show phenotypically divergent populations in terms of migratory behaviour, with climate hypothesized to be a major driver of such variability through its differential effects on sedentary and migratory individuals. Based on long-term (1947-2011) bird ringing data, we analysed phenotypic differentiation of migratory behaviour among populations of the European robin Erithacus rubecula across Europe. We showed that clusters of populations sharing breeding and wintering ranges varied from partial (British Isles and Western Europe, NW cluster) to completely migratory (Scandinavia and north-eastern Europe, NE cluster). Distance migrated by birds of the NE (but not of the NW) cluster decreased through time because of a north-eastwards shift in the wintering grounds. Moreover, when winter temperatures in the breeding areas were cold, individuals from the NE cluster also migrated longer distances, while those of the NW cluster moved over shorter distances. Climatic conditions may therefore affect migratory behaviour of robins, although large geographical variation in response to climate seems to exist

The HIV-1 Tat protein induces the activation of CD8+ T cells and affects in vivo the magnitude and kinetics of antiviral responses.

T cells are functionally compromised during HIV infection despite their increased activation and proliferation. Although T cell hyperactivation is one of the best predictive markers for disease progression, its causes are poorly understood. Anti-tat natural immunity as well as anti-tat antibodies induced by Tat immunization protect from progression to AIDS and reverse signs of immune activation in HIV-infected patients suggesting a role of Tat in T cell dysfunctionality. The Tat protein of HIV-1 is known to induce, in vitro, the activation of CD4+ T lymphocytes, but its role on CD8+ T cells and how these effects modulate, in vivo, the immune response to pathogens are not known. To characterize the role of Tat in T cell hyperactivation and dysfunction, we examined the effect of Tat on CD8+ T cell responses and antiviral immunity in different ex vivo and in vivo models of antigenic stimulation, including HSV infection. We demonstrate for the first time that the presence of Tat during priming of CD8+ T cells favors the activation of antigen-specific CTLs. Effector CD8+ T cells generated in the presence of Tat undergo an enhanced and prolonged expansion that turns to a partial dysfunctionality at the peak of the response, and worsens HSV acute infection. Moreover, Tat favors the development of effector memory CD8+ T cells and a transient loss of B cells, two hallmarks of the chronic immune activation observed in HIV-infected patients. Our data provide evidence that Tat affects CD8+ T cell responses to co-pathogens and suggest that Tat may contribute to the CD8+ T cell hyperactivation observed in HIV-infected individuals