Students with high-functioning autism spectrum disorders (ASDs) are increasingly included in general education and are expected to access core content, including science. Development of science content knowledge, scientific literacy, and scientific thinking are areas emphasized in legislation as well as the National Science Education Standards as critical for all students, particularly as they progress to middle and high school. However, participation in science discourse is often challenging for students with ASD given their difficulties with communication. Moreover, evidence on teaching academic content, such as science, to students with disabilities is limited. In this article, the use of visual supports is described as an evidence-based practice to promote engagement in science discussions among students with high-functioning ASD.
Background In 2018-2019, large outbreaks of measles occurred in Israel and in New York City, driven in part by travel of unimmunized children between the 2 communities. Methods A retrospective chart review was conducted for children tested for measles (March 2018-September 2019) at NYU Langone Health in New York, NY, and in Ramla subdistrict, Israel. Vaccination records were reviewed to determine vaccination status for measles, mumps, and rubella (MMR) at the time of measles testing and 1-year post-testing. Results A total of 264 children were tested for measles, and 102 (38.6%) had confirmed measles. Only 20 (19.6%) of measles-positive cases received a full 2-dose course of vitamin A. 82.4% of children with measles were ≥1 year at the time of diagnosis and fully eligible for MMR vaccine. Of the 100 measles-positive cases with available vaccine records, 63 were unvaccinated at testing, and 27 remained unimmunized against MMR 1 year later. At testing, measles-negative children were significantly more likely to have received MMR than measles-positive children (65.4% vs 37%, P < .01). One year later, 70.4% of measles-negative cases and only 57.1% of measles-positive cases had received MMR vaccine (P = .18). Conclusions The majority of measles cases occurred in unimmunized children eligible for vaccination, and >25% of children in both measles-positive and -negative groups remained unimmunized for MMR 1-year post-outbreak. Our results suggest the need for novel, longitudinal vaccination strategies and increased awareness of the role of vitamin A.
Background: Neuroblastoma is a childhood malignancy of the peripheral nervous system, and most patients with high-risk disease are not cured. Exportin 1 (XPO1; Chromosome Region Maintenance 1 Protein Homolog, CRM1) is the sole nuclear exporter of TP53, FOXO1, RB1, CDKN1A, and other critical tumor suppressor proteins (TSPs) and is abundantly expressed in high-risk neuroblastoma. In addition, these major tumor suppressor proteins are rarely mutated in neuroblastoma, and thus inhibition of XPO1 is a rational anti-neuroblastoma strategy. The orally bioavailable drug selinexor (KPT-330) is a selective inhibitor of nuclear export that forms a slowly reversible covalent bond to XPO1 and inhibits XPO1-mediated nuclear export. We previously showed that selinexor showed cytotoxicity with sensitivity independent of MYCN amplification status resulting in decreased Myc family protein levels and activation of apoptotic pathways. In addition, flank xenograft models and mouse models of metastatic disease showed significant tumor growth inhibition across multiple neuroblastoma cell lines. Methods: A time course microarray experiment was performed to discover temporal effects across four neuroblastoma cell lines following exposure to selinexor. Models were selected at the extremes of drug sensitivity and expression profiles were generated after 8 and 24 hours of selinexor exposure. Results: The intersection of linear and K-clustering methods revealed genes that followed a consecutively increasing or decreasing profile with respect to time. There were 4 genes in common to all cell lines, 29 genes across 3 cell lines, and 88 between the two most sensitive cell lines. Based off these observations, MAST3, GPRIN1, SMACRD2, and SENP5 were further explored in a larger cohort of neuroblastoma cell lines. In addition, gene set enrichment analysis revealed a doxorubicin-sensitivity expression profile in more resistant lines after exposure to selinexor. The combination of selinexor and doxorubicin resulted in synergistic increases in cell death. Chromatin remodeling genes were significantly disrupted by selinexor across all models, and the combination of selinexor and the bromodomain inhibitor JQ1 resulted in decreased MYCN protein levels and also showed evidence of synergy in vitro. Conclusions: Expression profiling of neuroblastoma cell lines following selinexor exposure has uncovered candidate biomarkers of activity and sensitivity. The potent synergy with other chemotherapeutic agents provides evidence for rational drug combinations. Selinexor is currently in pediatric phase 1 trials and has the potential to be rapidly translated into a novel therapeutic approach for children with neuroblastoma. Citation Format: Pietro J. Ranieri, Rebecca Trillo, Yosef Landesman, William Senapedis, Dilara McCauley, Sharon Shacham, Michael Kauffman, John M. Maris, Edward F. Attiyeh. Inhibition of exportin 1 (XPO1) by selinexor (KPT-330) synergistically suppresses growth of neuroblastoma in combination with doxorubicin or bromodomain inhibition. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 501. doi:10.1158/1538-7445.AM2015-501
Objectives Antenatal corticosteroids (ACS) administered to mothers at risk for preterm delivery before 34 weeks has been standard care to improve neonatal outcomes. After introducing a new obstetric policy based on updated recommendations advising the administration of ACS to pregnant women at risk for late preterm (LPT) delivery (34–36 6/7 weeks), we set out to determine the short-term clinical impact on those LPT neonates. Methods Retrospective chart review of LPT neonates delivered at NYU Langone Medical Center both one year before and after the policy went into place. We excluded subjects born to mothers with pre-gestational diabetes, multiple gestations, and those with congenital/genetic abnormalities. We also excluded subjects whose mothers already received ACS previously in pregnancy. Subjects were divided into pre-policy and post-policy groups. Neonatal and maternal data were compared for both groups. Results 388 subjects; 180 in the pre-policy and 208 in the post-policy group. This policy change resulted in a significant increase in ACS administration to mothers who delivered LPT neonates (67.3 vs. 20.6%, p<0.001). In turn, there was a significant reduction in LPT neonatal intensive care unit (NICU) admissions (44.2 vs. 54.4%, p=0.04) and need for respiratory support (27.9 vs. 42.8%, p<0.01). However, we also found an increased incidence of hypoglycemia (49.5 vs. 28.3%, p<0.001). Conclusions This LPT ACS policy appears effective in reducing the need for LPT NICU level care overall. However, clinicians must be attentive to monitor for adverse effects like hypoglycemia, and there remains a need for better understanding of potential long-term impacts.
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