Climate change has profound ecological effects in birds, with the clearest effect a shift in timing, or phenology, of avian reproduction. To assess the consequences of these shifts, we performed a literature search and compared the rates of phenological change in the reproduction of birds with that of the food for their offspring. While in some areas the rate of change of the birds and their food was similar, there were also areas where the birds' shift lagged behind that of their food. In these cases, this will lead to a phenological mismatch, which will affect the fitness of the brood. There are two hypotheses explaining why climate change leads to mismatched reproduction: either the cues used no longer accurately predict the peak in food abundance (the cues hypothesis) or the fitness costs of egg production and/or incubation of laying early enough to match reproduction are substantial in early spring and are not compensated by the fitness benefits of a better matched reproduction (constraint hypothesis). In the latter case, the phenological mismatch is adaptive. We present a simple mathematical model to show that this may be the case if there are fitness costs of egg laying and/or incubation under cold conditions and if the temperatures that determine the peak in food abundance increase stronger than the temperatures affecting the costs of egg laying and incubation, as is the case in the Netherlands. Whether or not a phenological mismatch is adaptive has important consequences for natural selection acting on timing of reproduction. If the mismatch is not adaptive, timing of reproduction will be under direct natural selection, while, if the mismatch is adaptive, selection is likely to be on the costs of egg production, possibly on egg size or adult size. In all cases, a mismatch is expected to have negative population consequences and, especially when the mismatch is adaptive, these consequences cannot be reduced by a response to natural selection on timing directly. This makes experimental studies on laying date, which can determine whether the mismatch is adaptive, of crucial importance.Keywords Timing Á Phenological mismatch Á Climate change Á Reproduction Zusammenfassung Adaptive phänotypische Fehlanpassungen zwischen Vögeln und ihrer Nahrung in Zeiten der ErderwärmungDer Klimawandel hat tiefgreifende Auswirkungen auf die Ö kologie von Vögeln, wobei der deutlichste Effekt eine Verschiebung des Timings, oder der Phänologie, der Fortpflanzung ist. Um die Konsequenzen einer solchen Verlagerung zu untersuchen haben wir eine Literatursuche durchgeführt und die Rate der phänologischen Veränderung im Brutverhalten der Vögel mit denen der Nestlingsnahrung verglichen. Während in manchen Fällen die Veränderungsraten der Vögel und Nahrungsquelle ähnlich waren gab es auch Nahrungsketten in denen die Rate der Vögel hinter der ihrer Nahrung zurückblieb. Daraus resultiert eine phänologische Fehlabstimmung (mismatch), die die Fitness der Brut beeinträchtigt. Zwei Hypothesen können erklären warum der Klimawandel z...

Bird breeding and spring migration phenology have advanced in response to climate change, but the effects differ between sites. Here, we examine the geographical variation in layingdate trends in a short-distance migrant, the European starling Sturnus vulgaris, and a long-distance migrant, the pied flycatcher Ficedula hypoleuca. We model the trend in laying date for these 2 species -between 1980 and 2004 for most of their European breeding areas -by combining geographical variation in mean laying date, the effect of temperature on laying date, and spatial variation in temperature change. Starlings are predicted to have advanced breeding over most of their range, with the greatest advance in north-eastern Europe. In contrast, pied flycatchers have delayed their laying in northern Europe, but have advanced their laying in western and central Europe. The species differ because pied flycatchers lay their eggs 25 d later at each site than starlings, and temperatures during these 2 periods show different trends. Temperatures during migration have also changed differently for populations heading to different breeding areas. This was most pronounced for pied flycatchers; northern populations experience an increase in temperatures during migration, while more southern populations presently still migrate at temperatures similar to those experienced 25 yr ago. As a consequence the southern population may be constrained in adapting to climate change by low temperatures during migration. There is a large contrast in how circumstances during migration and at the breeding grounds have changed: populations that advanced breeding most were subjected to the lowest temperature increases during migration. The temporal and spatial variation in temperature change has important consequences on how migrants adapt to ongoing climate change.

Phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations are frequently observed in primary breast cancer. We evaluated their prognostic relevance by performing a pooled analysis of individual patient data. Patients and MethodsAssociations between PIK3CA status and clinicopathologic characteristics were tested by applying Cox regression models adjusted for age, tumor size, nodes, grade, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, treatment, and study. Invasive diseasefree survival (IDFS) was the primary end point; distant disease-free survival (DDFS) and overall survival (OS) were also assessed, overall and by breast cancer subtypes. ResultsData from 10,319 patients from 19 studies were included (median OS follow-up, 6.9 years); 1,787 patients (17%) received chemotherapy, 4,036 (39%) received endocrine monotherapy, 3,583 (35%) received both, and 913 (9%) received none or their treatment was unknown. PIK3CA mutations occurred in 32% of patients, with significant associations with ER positivity, increasing age, lower grade, and smaller size (all P , .001). Prevalence of PIK3CA mutations was 18%, 22%, and 37% in the ER-negative/HER2-negative, HER2-positive, and ER-positive/HER2-negative subtypes, respectively. In univariable analysis, PIK3CA mutations were associated with better IDFS (HR, 0.77; 95% CI, 0.71 to 0.84; P , .001), with evidence for a stronger effect in the first years of follow-up (0 to 5 years: HR, 0.73; 95% CI, 0.66 to 0.81; P , .001; 5 to 10 years: HR, 0.82; 95% CI, 0.68 to 0.99; P = .037); . 10 years: (HR, 1.15; 95% CI, 0.84 to 1.58; P = .38; P heterogeneity = .02). In multivariable analysis, PIK3CA genotype remained significant for improved IDFS (P = .043), but not for the DDFS and OS end points. ConclusionIn this large pooled analysis, PIK3CA mutations were significantly associated with a better IDFS, DDFS, and OS, but had a lesser prognostic effect after adjustment for other prognostic factors.J Clin Oncol 36:981-990.