Gradually increasing context-sensitivity shapes the development of children's verb marking: A corpus study.

There is substantial evidence that children's apparent omission of grammatical morphemes in utterances such as "She play tennis" and "Mummy eating" is in fact errors of commission in which contextually licensed unmarked forms encountered in the input are reproduced in a context-blind fashion. So how do children stop making such errors? In this study, we test the assumption that children's ability to recover from error is related to their developing sensitivity to longer-range dependencies. We use a pre-registered corpus analysis to explore the predictive value of different cues with regards to children's verb-marking errors and observe a developmental pattern consistent with this account. We look at context-independent cues (the identity of the specific verb being used) and at the relative value of context-dependent cues (the identity of the specific subject+verb sequence being used). We find that the only consistent effect across a group of 2- to 3-year-olds and a group of 3- to 4-year-olds is the relative frequency of unmarked forms of specific subject+verb sequences being used. The relative frequency of unmarked forms of the verb alone is predictive only in the younger age group. This is consistent with an account in which children recover from making errors by becoming progressively more sensitive to context, at first the immediately preceding lexical contexts (e.g., the subject that precedes the verb) and eventually more distant grammatical markers (e.g., the fronted auxiliary that precedes the subject in questions). RESEARCH HIGHLIGHTS: We provide a corpus analysis investigating input effects on young children's verb-marking errors (e.g., Mummy go) across development (between 2 and 4 years of age). We find evidence that these apparent errors of omission are in fact input-driven errors of commission that persist into the third year of life. We compare the relative effect on error rates of context-independent (e.g., verb) and context-dependent (e.g., subject+verb sequence) cues across developmental time. Our findings support the proposal that children recover from making verb-marking errors by becoming progressively more sensitive to preceding context.

Suicidal ideation is associated with safety behavior usage among trauma-exposed individuals.

BACKGROUND: Long-standing theoretical perspectives on suicidal ideation (SI) have posited that SI arises, in part, as a way to obtain relief from intense emotional pain. Yet, little research has examined whether SI is linked with other relief-driven behaviors. The present study sought to provide preliminary support for the link between SI and relief-driven safety behavior usage, a commonly used strategy for managing distress among trauma-exposed individuals. METHODS: Trauma-exposed participants (n = 95) recruited for a larger study assessing mechanisms of posttraumatic stress disorder symptomology and completed a battery of self-report measures, including SI and their use of safety behaviors. Zero-inflated negative binomial regressions were utilized to examine the association of safety behavior usage with the presence/absence of SI (i.e., zero-inflation) and SI severity. RESULTS: In bivariate models, safety behaviors were associated with a greater likelihood of experiencing any SI and reporting more severe SI. When covariates were added to the model, safety behavior usage remained significantly and positively associated with SI severity. LIMITATIONS: The present study employed cross-sectional analyses of self-report data. Future research should use neurobehavioral tasks and intensive longitudinal data to test whether an underlying sensitivity to, or propensity to engage in, relief-driven behaviors contributes to SI. DISCUSSION: Among trauma-exposed individuals, those who more frequently engage in negatively reinforced safety behaviors also report more severe SI. These findings dovetail with theoretical foundations of suicide linking SI with relief-driven motivations and provide further support that a propensity to engage in relief-driven behaviors is associated with SI.

Combined aromatase, CDK4/6 and PI3K blockade using letrozole/abemaciclib/LY3023414 in endometrial cancer.

Several lines of preclinical evidence indicate that combining PI3K and CDK4/6 inhibitors may further enhance the efficacy of hormonal therapy by overcoming de novo and acquired resistance to PI3K and CDK4/6 blockade. We evaluated the combination of abemaciclib, letrozole and LY3023414 (an orally available, selective inhibitor of the class I PI3K isoforms and mTORC1/2) in recurrent endometrial cancer (EC). This study was terminated prematurely after 5 patients initiated protocol therapy due to discontinuation of further development of LY3023414. We report our findings from these patients, including one with recurrent endometrioid EC with AKT1, CTNNB1 and ESR1 hotspot mutations who had previously progressed through letrozole/everolimus and achieved a partial response to letrozole/abemaciclib/LY3023414.

Randomized Phase II Study of Gemcitabine With or Without ATR Inhibitor Berzosertib in Platinum-Resistant Ovarian Cancer: Final Overall Survival and Biomarker Analyses.

PURPOSE: The multicenter, open-label, randomized phase 2 NCI-9944 study (NCT02595892) demonstrated that addition of ATR inhibitor (ATRi) berzosertib to gemcitabine increased progression-free survival (PFS) compared to gemcitabine alone (hazard ratio [HR]=0.57, one-sided log-rank P = .044, which met the one-sided significance level of 0.1 used for sample size calculation). METHODS: We report here the final overall survival (OS) analysis and biomarker correlations (ATM expression by immunohistochemistry, mutational signature 3 and a genomic biomarker of replication stress) along with post-hoc exploratory analyses to adjust for crossover from gemcitabine to gemcitabine/berzosertib. RESULTS: At the data cutoff of January 27, 2023 (>30 months of additional follow-up from the primary analysis), median OS was 59.4 weeks with gemcitabine/berzosertib versus 43.0 weeks with gemcitabine alone (HR 0.79, 90% CI 0.52 to 1.2, one-sided log-rank P = .18). An OS benefit with addition of berzosertib to gemcitabine was suggested in patients stratified into the platinum-free interval ≤3 months (N = 26) subgroup (HR, 0.48, 90% CI 0.22 to 1.01, one-sided log-rank P =.04) and in patients with ATM-negative/low (N = 24) tumors (HR, 0.50, 90% CI 0.23 to 1.08, one-sided log-rank P = .06). CONCLUSION: The results of this follow-up analysis continue to support the promise of combined gemcitabine/ATRi therapy in platinum resistant ovarian cancer, an active area of investigation with several ongoing clinical trials.