The effects of a tier 2 reading comprehension intervention aligned to tier 1 instruction for fourth graders with inattention and reading difficulties.

This study reports a secondary analysis from a quasi-experimental design study (N = 13 schools) to examine the effects of aligned Tier 1 (T1) and Tier 2 (T2) instruction for a subsample of fourth graders with inattention and reading difficulties. Of this sample (N = 63 students), 100% received free- or reduced-price lunch, 92% identified as Hispanic, and 22% received special education services. T1 instruction focused on implementing practices to support reading comprehension and content learning during social studies instruction. The aligned T2 intervention focused on remediating reading comprehension difficulties using the same evidence-based practices implemented in T1, thus supporting students with connecting learning and applying skills across settings. Schools were assigned to one of three conditions: (a) aligned T1-T2 instruction; (b) nonaligned T1-T2 instruction, in which T1 and T2 practices were not intentionally aligned; or (c) business-as-usual (BaU) T1 and T2 practices. No significant differences were detected between the nonaligned T1-T2 and BaU conditions on student outcomes. However, large, statistically significant effects were detected in favor of the aligned T1-T2 condition compared to BaU on measures of content knowledge (Unit 1 ES = 0.85; Unit 2 ES = 1.46; Unit 3 ES = 0.79), vocabulary (Unit 1 ES = 0.88; Unit 2 ES = 0.85), and content reading comprehension (ES = 0.79). The aligned T1-T2 condition also outperformed the nonaligned T1-T2 condition on content knowledge (Unit 2 ES = 1.35; Unit 3 ES = 0.56), vocabulary (Unit 1 ES = 0.82), and the content reading comprehension assessment (ES = 0.69). Various effect sizes were not different from zero after correcting for clustered data. Although the magnitude of the effect sizes suggested promise, additional research is needed to fully understand the effects of aligned instruction on the reading outcomes of students with inattention and reading difficulty.

Synergistic induction of mitogen-activated protein kinase phosphatase-1 by thrombin and epidermal growth factor requires vascular endothelial growth factor receptor-2.

OBJECTIVE: To determine the molecular mechanism underlying the synergistic response of mitogen-activated protein kinase phosphatase-1 (MKP-1), which is induced by thrombin and epidermal growth factor (EGF). METHODS AND RESULTS: MKP-1 induction by thrombin (approximately 6-fold) was synergistically increased (approximately 18-fold) by cotreatment with EGF in cultured endothelial cells. EGF alone did not induce MKP-1 substantially (<2-fold). The synergistic induction of MKP-1 was not mediated by matrix metalloproteinases. The EGF receptor kinase inhibitor AG1478 blocked approximately 70% of MKP-1 induction by thrombin plus EGF (from 18- to 6-fold) but not the response to thrombin alone. An extracellular signal-regulated kinase (ERK)-dependent protease-activated receptor-1 (PAR-1) signal was required for the thrombin alone effect; an ERK-independent PAR-1 signal was necessary for the approximately 12-fold MKP-1 induction by thrombin plus EGF. VEGF induction of MKP-1 was also approximately 12-fold and c-Jun N-terminal kinase (JNK) dependent. Inhibitors of extracellular signal-regulated kinase and JNK activation blocked thrombin plus EGF-induced MKP-1 completely. Furthermore, VEGF receptor 2 depletion blocked the synergistic response without affecting the induction of MKP-1 by thrombin alone. CONCLUSIONS: We have identified a novel signaling interaction between protease-activated receptor-1 and EGF receptor that is mediated by VEGF receptor 2 and results in synergistic MKP-1 induction.