No abstract

Social interactions often have major fitness consequences, but little is known about how specific interacting phenotypes affect the strength of natural selection. Social influences on the evolutionary process can be assessed using a multilevel selection approach that partitions the effects of social partner phenotypes on fitness (referred to as social or group selection) from those of the traits of a focal individual (nonsocial or individual selection). To quantify the contribution of social selection to total selection affecting a trait, the patterns of phenotypic association among interactants must also be considered. We estimated selection gradients on male body size in a wild population of forked fungus beetles (Bolitotherus cornutus). We detected positive nonsocial selection and negative social selection on body size operating through differences in copulation success, indicating that large males with small social partners had highest fitness. In addition, we found that, in low-density demes, the phenotypes of focal individuals were negatively correlated with those of their social partners. This pattern reversed the negative effect of group selection on body size and led to stronger positive selection for body size. Our results demonstrate multilevel selection in nature and stress the importance of considering social selection whenever conspecific interactions occur nonrandomly. K E Y W O R D S :Bolitotherus cornutus, contextual analysis, interacting phenotypes, multilevel selection, sexual selection, social evolution.

Objective Many forms of epilepsy are associated with aberrant neuronal connections, but the relationship between such pathological connectivity and the underlying physiological predisposition to seizures is unclear. We sought to characterize the cortical excitability profile of a developmental form of epilepsy known to have structural and functional connectivity abnormalities. Methods We employed transcranial magnetic stimulation (TMS) with simultaneous EEG recording in eight patients with epilepsy from periventricular nodular heterotopia (PNH) and matched healthy controls. We used connectivity imaging findings to guide TMS targeting and compared the evoked responses to single-pulse stimulation from different cortical regions. Results Heterotopia patients with active epilepsy demonstrated a relatively augmented late cortical response that was greater than that of matched controls. This abnormality was specific to cortical regions with connectivity to subcortical heterotopic gray matter. Topographic mapping of the late response differences showed distributed cortical networks that were not limited to the stimulation site, and source analysis in one subject revealed that the generator of abnormal TMS-evoked activity overlapped with the spike and seizure onset zone. Interpretation Our findings indicate that patients with epilepsy from gray matter heterotopia have altered cortical physiology consistent with hyperexcitability, and that this abnormality is specifically linked to the presence of aberrant connectivity. These results support the idea that TMS-EEG could be a useful biomarker in epilepsy in gray matter heterotopia, expand our understanding of circuit mechanisms of epileptogenesis, and have potential implications for therapeutic neuromodulation in similar epileptic conditions associated with deep lesions.

Importance: Ovarian cancer is a highly fatal malignancy with few modifiable risk factors. Results from case-control studies have reported a modest reduced risk of ovarian cancer among women who frequently use aspirin or regularly use low-dose aspirin. We sought to confirm these findings in a large, prospective study with detailed information on NSAID use. Objective: To evaluate whether regular aspirin or non-aspirin NSAID use, and patterns of use, are associated with lower ovarian cancer risk. Design: We included women from two prospective cohorts, the Nurses’ Health Study (NHS) and NHSII. Setting: NHS/NHSII participants were followed 1980–2014 (NHS) and 1989–2015 (NHSII). Participants: Participants in NHS (N=93,664) and NHSII (N=111,834), including 1054 cases of incident epithelial ovarian cancer. Exposures: For each analgesic type, aspirin, low-dose aspirin, non-aspirin NSAIDs and acetaminophen, we evaluated timing, duration, frequency, and number of tablets used; exposure information was updated every 2–4 years. Main Outcome(s) and Measure(s): We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of aspirin, non-aspirin NSAIDs, and acetaminophen with risk of epithelial ovarian cancer. All statistical tests were two-sided, with a significance level of 0.05. Results: We did not observe significant associations between aspirin and ovarian cancer risk when we evaluated current versus non-use of any aspirin, regardless of dose (HR=0.99, 95%CI=0.83–1.19). However, when we evaluated low-dose (≤100mg) and standard-dose (325mg) aspirin separately, we observed an inverse association for low-dose aspirin (HR=0.77, 95%CI=0.61–0.96), but no association for standard-dose aspirin (HR=1.17, 95%CI=0.92–1.49). Current use of non-aspirin NSAIDs was positively associated with risk of ovarian cancer compared to non-use (HR=1.19, 95%CI=1.00–1.41), and we observed significant positive trends for duration of use (p-trend=0.02) and cumulative average tablets per week (p-trend=0.03). There were no clear associations for acetaminophen. Conclusions and Relevance: Our results were consistent with case-control studies showing a reduced risk of ovarian cancer among regular users of low-dose aspirin. We observed an increased risk of ovarian cancer with long-term high-quantity use of other analgesics, particularly non-aspirin NSAIDs, though this finding requires confirmation.