No abstract

When children learn their native language, they have to deal with a confusing array of dependencies between various elements in an utterance. The dependent elements may be adjacent to one another or separated by intervening material. Prior studies suggest that nonadjacent dependencies are hard to learn when the intervening material has little variability, which may be due to a trade‐off between adjacent and nonadjacent learning. In this study, we investigate the statistical learning of adjacent and nonadjacent dependencies under low intervening variability using a modified serial reaction time (SRT) task. Young adults were trained on mixed sets of materials comprising equally probable adjacent and nonadjacent dependencies. Offline tests administered after training showed better performance for adjacent than nonadjacent dependencies. However, online SRT data indicated that the participants developed sensitivity to both types of dependencies during training, with no significant differences between dependency types. The results demonstrate the value of online measures of learning and suggest that adjacent and nonadjacent learning can occur together even when there is low variability in the intervening material. Open Practices This article has been awarded an Open Materials badge. All materials are publicly accessible in the IRIS digital repository at http://www.iris-database.org. Learn more about the Open Practices badges from the Center for Open Science: https://osf.io/tvyxz/wiki

a b s t r a c tThe role of attentional control in lexical ambiguity resolution was examined in two patients with damage to the left inferior frontal gyrus (LIFG) and one control patient with non-LIFG damage. Experiment 1 confirmed that the LIFG patients had attentional control deficits compared to normal controls while the non-LIFG patient was relatively unimpaired. Experiment 2 showed that all three patients did as well as normal controls in using biasing sentence context to resolve lexical ambiguities involving balanced ambiguous words, but only the LIFG patients took an abnormally long time on lexical ambiguities that resolved toward a subordinate meaning of biased ambiguous words. Taken together, the results suggest that attentional control plays an important role in the resolution of certain lexical ambiguities -those that induce strong interference from context-inappropriate meanings (i.e., dominant meanings of biased ambiguous words).

Purpose: Checkpoint kinase 1 (CHK1) plays a central role in the response to replication stress through modulation of cell-cycle checkpoints and homologous recombination (HR) repair. In BRCA-deficient cancers with de novo or acquired PARP inhibitor resistance, the addition of the CHK1 inhibitor prexasertib to the PARP inhibitor olaparib compromises replication fork stability, as well as HR proficiency, allowing for sensitization to PARP inhibition. Patients and Methods: This study followed a 3+3 design with a 7-day lead-in of olaparib alone, followed by 28-day cycles with prexasertib administered on days 1 and 15 in combination with an attenuated dose of olaparib on days 1–5 and 15–19. Pharmacokinetic blood samples were collected after olaparib alone and following combination therapy. Patients enrolled to the expansion phase of the study underwent paired tumor biopsies for pharmacodynamic (PD) assessments. Results: Twenty-nine patients were treated. DLTs included grade 3 neutropenia and grade 3 febrile neutropenia. The MTD/recommended phase 2 dose (RP2D) was prexasertib at 70 mg/m2 i.v. with olaparib at 100 mg by mouth twice daily. Most common treatment-related adverse events included leukopenia (83%), neutropenia (86%), thrombocytopenia (66%), and anemia (72%). Four of 18 patients with BRCA1-mutant, PARP inhibitor–resistant, high-grade serous ovarian cancer (HGSOC) achieved partial responses. Paired tumor biopsies demonstrated reduction in RAD51 foci and increased expression of γ-H2AX, pKAP1, and pRPA after combination exposure. Conclusions: Prexasertib combined with olaparib has preliminary clinical activity in BRCA-mutant patients with HGSOC who have previously progressed on a PARP inhibitor. PD analyses show that prexasertib compromises HR with evidence of induction of DNA damage and replication stress.

Variability in drug responsivity has prompted the development of Personalized Medicine, which has shown great promise in utilizing genotypic information to develop safer and more effective drug regimens for patients. Similarly, individual variability in learning outcomes has puzzled researchers who seek to create optimal learning environments for students. “Personalized Learning” seeks to identify genetic, neural and behavioral predictors of individual differences in learning and aims to use predictors to help create optimal teaching paradigms. Evidence for Personalized Learning can be observed by connecting research in pharmacogenomics, cognitive genetics and behavioral experiments across domains of learning, which provides a framework for conducting empirical studies from the laboratory to the classroom and holds promise for addressing learning effectiveness in the individual learners. Evidence can also be seen in the subdomain of speech learning, thus providing initial support for the applicability of Personalized Learning to language.