Asymmetrical gene flow, which has frequently been documented in naturally occurring hybrid zones, can result from various genetic and demographic factors. Understanding these factors is important for determining the ecological conditions that permitted hybridization and the evolutionary potential inherent in hybrids. Here, we characterized morphological, nuclear, and chloroplast variation in a putative hybrid zone between Schiedea menziesii and S. salicaria, endemic Hawaiian species with contrasting breeding systems. Schiedea menziesii is hermaphroditic with moderate selfing; S. salicaria is gynodioecious and wind-pollinated, with partially selfing hermaphrodites and largely outcrossed females. We tested three hypotheses: 1) putative hybrids were derived from natural crosses between S. menziesii and S. salicaria, 2) gene flow via pollen is unidirectional from S. salicaria to S. menziesii and 3) in the hybrid zone, traits associated with wind pollination would be favored as a result of pollen-swamping by S. salicaria. Schiedea menziesii and S. salicaria have distinct morphologies and chloroplast genomes but are less differentiated at the nuclear loci. Hybrids are most similar to S. menziesii at chloroplast loci, exhibit nuclear allele frequencies in common with both parental species, and resemble S. salicaria in pollen production and pollen size, traits important to wind pollination. Additionally, unlike S. menziesii, the hybrid zone contains many females, suggesting that the nuclear gene responsible for male sterility in S. salicaria has been transferred to hybrid plants. Continued selection of nuclear genes in the hybrid zone may result in a population that resembles S. salicaria, but retains chloroplast lineage(s) of S. menziesii.

Objective

This randomized, multisite, intent-to-treat study tested the effects of 2 levels of treatment intensity (number of hours) and 2 treatment styles on the progress of young children with autism spectrum disorder (ASD). We predicted that initial severity of developmental delay or autism symptoms would moderate the effects of intensity and style on progress in 4 domains: autism symptom severity, expressive communication, receptive language, and nonverbal ability.

Method

A total of 87 children with ASD, mean age 23.4 months, were assigned to 1 of 2 intervention styles (naturalistic developmental/behavioral or discrete trial teaching), each delivered for either 15 or 25 hours per week of 1:1 intervention for 12 months by trained research staff. All caregivers received coaching twice monthly. Children were assessed at 4 timepoints. Examiners and coders were naive to treatment assignment.

Results

Neither style nor intensity had main effects on the 4 outcome variables. In terms of moderating the effects of initial severity of developmental delay and of autism symptom severity, neither moderated the effects of treatment style on progress in any of the 4 domains. In terms of treatment intensity, initial severity moderated effect of treatment intensity on only 1 domain, namely, change in autism symptom severity; in a secondary analysis, this effect was found in only 1 site.

Conclusion

Neither treatment style nor intensity had overall effects on child outcomes in the 4 domains examined. Initial severity did not predict better response to 1 intervention style than to another. We found very limited evidence that initial severity predicted better response to 25 vs 15 hours per week of intervention in the domains studied.

Clinical trial registration information

Intervention Effects of Intensity and Delivery Style for Toddlers With Autism: https://clinicaltrials.gov/; NCT02272192.

Meningiomas are the most common primary intracranial tumor with current classification offering limited therapeutic guidance. Here, we interrogated meningioma enhancer landscapes from 33 tumors to stratify patients based upon prognosis and identify novel meningioma-specific dependencies. Enhancers robustly stratified meningiomas into three biologically distinct groups (adipogenesis/cholesterol, mesodermal, and neural crest) distinguished by distinct hormonal lineage transcriptional regulators. Meningioma landscapes clustered with intrinsic brain tumors and hormonally responsive systemic cancers with meningioma subgroups, reflecting progesterone or androgen hormonal signaling. Enhancer classification identified a subset of tumors with poor prognosis, irrespective of histologic grading. Superenhancer signatures predicted drug dependencies with superior in vitro efficacy to treatment based upon the NF2 genomic profile. Inhibition of DUSP1, a novel and druggable meningioma target, impaired tumor growth in vivo. Collectively, epigenetic landscapes empower meningioma classification and identification of novel therapies. SIGNIFICANCE: Enhancer landscapes inform prognostic classification of aggressive meningiomas, identifying tumors at high risk of recurrence, and reveal previously unknown therapeutic targets. Druggable dependencies discovered through epigenetic profiling potentially guide treatment of intractable meningiomas.This article is highlighted in the In This Issue feature, p. 1611.