269 research outputs found

    An Investigation of the Characteristics and School Readiness of Children with Disabilities who Attend Head Start Programs

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    The purpose of this study was to examine the characteristics and school readiness of children with disabilities who attend Head Start programs, as well as the characteristics of the programs they attend and the school districts in which they receive special education. In addition, a second purpose was to determine whether there are differences in these characteristics of children who attend Head Start programs and those who attend other early childhood education programs. I used data from the Pre-Elementary Education Longitudinal Study, a study of a nationally representative sample of preschool children with disabilities. I used a subsample of the data to compare the characteristics and school readiness of children with disabilities who attended Head Start to those who attended other early childhood education programs using chi-squares, analysis of variance, and ordinary least squares regression analyses. The results suggest that there is no difference in the school readiness of children with disabilities who attended Head Start and those who attend programs in elementary schools. However, in comparison to children who attended other programs, children with developmental delays who attended Head Start had more advanced receptive language skills and those with other disabilities had less advanced pre-reading skills. Additionally, the results of this study show that there is some variation in the characteristics of children with disabilities who attend Head Start and those who attend other programs. Children who attended Head Start were more likely to be Black or Hispanic and from low socioeconomic families. They were also less likely to have disabilities other than speech impairments or developmental delays and, on average, received fewer special education services. Finally, children who attended Head Start were more likely to be from rural school districts and districts with higher rates of poverty. These findings indicate that children with disabilities who attend Head Start programs face additional risk factors that are associated with poor school readiness and emphasize the need to ensure that the programs provide services that are adequate to meet the needs of the diverse population they serve and to prepare those children for the onset of formal schooling

    Magnetic Switching of Phase-Slip Dissipation in NbSe2 Nanobelts

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    The stability of the superconducting dissipationless and resistive states in single-crystalline NbSe2 nanobelts is characterized by transport measurements in an external magnetic field (H). Current-driven electrical measurements show voltage steps, indicating the nucleation of phase-slip structures. Well below the critical temperature, the position of the voltage steps exhibits a sharp, periodic dependence as a function of H. This phenomenon is discussed in the context of two possible mechanisms: the interference of the order parameter and the periodic rearrangement of the vortex lattice within the nanobelt.Comment: 4 figure

    Modeling the distributions of tegu lizards in native and potential invasive ranges

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    Invasive reptilian predators can have substantial impacts on native species and ecosystems. Tegu lizards are widely distributed in South America east of the Andes, and are popular in the international live animal trade. Two species are established in Florida (U.S.A.)-Salvator merianae (Argentine black and white tegu) and Tupinambis teguixin sensu lato (gold tegu)-and a third has been recorded there-S. rufescens (red tegu). We built species distribution models (SDMs) using 5 approaches (logistic regression, multivariate adaptive regression splines, boosted regression trees, random forest, and maximum entropy) based on data from the native ranges. We then projected these models to North America to develop hypotheses for potential tegu distributions. Our results suggest that much of the southern United States and northern México probably contains suitable habitat for one or more of these tegu species. Salvator rufescens had higher habitat suitability in semi-arid areas, whereas S. merianae and T. teguixin had higher habitat suitability in more mesic areas. We propose that Florida is not the only state where these taxa could become established, and that early detection and rapid response programs targeting tegu lizards in potentially suitable habitat elsewhere in North America could help prevent establishment and abate negative impacts on native ecosystems.Fil: Jarnevich, Catherine S.. U.s. Geological Survey; Estados UnidosFil: Hayes, Mark A.. Cherokee Nation Technologies; Estados UnidosFil: Fitzgerald, Lee A.. Department Of Wildlife And Fisheries Sciences; Estados UnidosFil: Yackel Adams, Amy A.. U.s. Geological Survey; Estados UnidosFil: Falk, Bryan G.. U.s. Geological Survey; Estados Unidos. National Park Service; Estados UnidosFil: Collier, Michelle A. M.. National Park Service; Estados Unidos. U.s. Geological Survey; Estados UnidosFil: Bonewell, Lea` R.. U.s. Geological Survey; Estados UnidosFil: Klug, Page E.. U.s. Geological Survey; Estados Unidos. U.S. Department of Agriculture APHIS, Wildlife Services, National Wildlife Research Center, North Dakota Field Station; Estados UnidosFil: Naretto, Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; ArgentinaFil: Reed, Robert N.. U.s. Geological Survey; Estados Unido

    High-throughput screen using a single-cell tyrosine phosphatase assay reveals biologically active inhibitors of tyrosine phosphatase CD45

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    Many cellular signaling events are regulated by tyrosine phosphorylation and mediated by the opposing actions of protein tyrosine kinases and phosphatases. Protein tyrosine phosphatases are emerging as drug targets, but poor cell permeability of inhibitors has limited the development of drugs targeting these enzymes [Tautz L, et al. (2006) Expert Opin Ther Targets 10:157–177]. Here we developed a method to monitor tyrosine phosphatase activity at the single-cell level and applied it to the identification of cell-permeable inhibitors. The method takes advantage of the fluorogenic properties of phosphorylated coumaryl amino propionic acid (pCAP), an analog of phosphotyrosine, which can be incorporated into peptides. Once delivered into cells, pCAP peptides were dephosphorylated by protein tyrosine phosphatases, and the resulting cell fluorescence could be monitored by flow cytometry and high-content imaging. The robustness and sensitivity of the assay was validated using peptides preferentially dephosphorylated by CD45 and T-cell tyrosine phosphatase and available inhibitors of these two enzymes. The assay was applied to high-throughput screening for inhibitors of CD45, an important target for autoimmunity and infectious diseases [Hermiston ML, et al. (2003) Annu Rev Immunol 21:107–137]. We identified four CD45 inhibitors that showed activity in T cells and macrophages. These results indicate that our assay can be applied to primary screening for inhibitors of CD45 and of other protein tyrosine phosphatases to increase the yield of biologically active inhibitors

    Use of Elamipretide in patients assigned treatment in the compassionate use program : Case series in pediatric patients with rare orphan diseases

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    Funding Information: The authors wish to thank the patients and their families for participating, as well as Bret Fulton, RPh, and Jim Shiffer, RPh, Write On Time Medical Communications, LLC, for their writing and editorial assistance during the development of this manuscript. Mary Kay Koenig wishes to thank her research nurse, Lindsey Miller, for providing patient support and assisting with administration and education responsibilities. Publisher Copyright: © 2022 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM. © 2022 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM. © 2022 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.Several mitochondrial diseases are caused by pathogenic variants that impair membrane phospholipid remodeling, with no FDA-approved therapies. Elamipretide targets the inner mitochondrial membrane where it binds to cardiolipin, resulting in improved membrane stability, cellular respiration, and ATP production. In clinical trials, elamipretide produced clinical and functional improvements in adults and adolescents with mitochondrial disorders, such as primary mitochondrial myopathy and Barth syndrome; however, experience in younger patients is limited and to our knowledge, these are the first case reports on the safety and efficacy of elamipretide treatment in children under 12 years of age. We describe the use of elamipretide in patients with mitochondrial disorders to provide dosing parameters in patients aged <12 years.Peer reviewe

    Measures of outcome for stimulant trials: ACTTION recommendations and research agenda

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    BACKGROUND: The development and approval of an efficacious pharmacotherapy for stimulant use disorders has been limited by the lack of a meaningful indicator of treatment success, other than sustained abstinence. METHODS: In March, 2015, a meeting sponsored by Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) was convened to discuss the current state of the evidence regarding meaningful outcome measures in clinical trials for stimulant use disorders. Attendees included members of academia, funding and regulatory agencies, pharmaceutical companies, and healthcare organizations. The goal was to establish a research agenda for the development of a meaningful outcome measure that may be used as an endpoint in clinical trials for stimulant use disorders. RESULTS AND CONCLUSIONS: Based on guidelines for the selection of clinical trial endpoints, the lessons learned from prior addiction clinical trials, and the process that led to identification of a meaningful indicator of treatment success for alcohol use disorders, several recommendations for future research were generated. These include a focus on the validation of patient reported outcome measures of functioning, the exploration of patterns of stimulant abstinence that may be associated with physical and/or psychosocial benefits, the role of urine testing for validating self-reported measures of stimulant abstinence, and the operational definitions for reduction-based measures in terms of frequency rather than quantity of stimulant use. These recommendations may be useful for secondary analyses of clinical trial data, and in the design of future clinical trials that may help establish a meaningful indicator of treatment success

    Advancing dendrochronological studies of fire in the United States

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    © 2018 by the authors. Licensee MDPI, Basel, Switzerland. Dendroecology is the science that dates tree rings to their exact calendar year of formation to study processes that influence forest ecology (e.g., Speer 2010 [1], Amoroso et al., 2017 [2]). Reconstruction of past fire regimes is a core application of dendroecology, linking fire history to population dynamics and climate effects on tree growth and survivorship. Since the early 20th century when dendrochronologists recognized that tree rings retained fire scars (e.g., Figure 1), and hence a record of past fires, they have conducted studies worldwide to reconstruct [2] the historical range and variability of fire regimes (e.g., frequency, severity, seasonality, spatial extent), [3] the influence of fire regimes on forest structure and ecosystem dynamics, and [4] the top-down (e.g., climate) and bottom-up (e.g., fuels, topography) drivers of fire that operate at a range of temporal and spatial scales. As in other scientific fields, continued application of dendrochronological techniques to study fires has shaped new trajectories for the science. Here we highlight some important current directions in the United States (US) and call on our international colleagues to continue the conversation with perspectives from other countries

    Epigenetic regulation of F2RL3 associates with myocardial infarction and platelet function

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    DNA hypomethylation at the F2RL3 (F2R like thrombin or trypsin receptor 3) locus has been associated with both smoking and atherosclerotic cardiovascular disease; whether these smoking-related associations form a pathway to disease is unknown. F2RL3 encodes protease-activated receptor 4, a potent thrombin receptor expressed on platelets. Given the role of thrombin in platelet activation and the role of thrombus formation in myocardial infarction, alterations to this biological pathway could be important for ischemic cardiovascular disease. METHODS: We conducted multiple independent experiments to assess whether DNA hypomethylation at F2RL3 in response to smoking is associated with risk of myocardial infarction via changes to platelet reactivity. Using cohort data (N=3205), we explored the relationship between smoking, DNA hypomethylation at F2RL3, and myocardial infarction. We compared platelet reactivity in individuals with low versus high DNA methylation at F2RL3 (N=41). We used an in vitro model to explore the biological response of F2RL3 to cigarette smoke extract. Finally, a series of reporter constructs were used to investigate how differential methylation could impact F2RL3 gene expression. RESULTS: Observationally, DNA methylation at F2RL3 mediated an estimated 34% of the smoking effect on increased risk of myocardial infarction. An association between methylation group (low/high) and platelet reactivity was observed in response to PAR4 (protease-activated receptor 4) stimulation. In cells, cigarette smoke extract exposure was associated with a 4.9% to 9.3% reduction in DNA methylation at F2RL3 and a corresponding 1.7-(95% CI, 1.2–2.4, P=0.04) fold increase in F2RL3 mRNA. Results from reporter assays suggest the exon 2 region of F2RL3 may help control gene expression. CONCLUSIONS: Smoking-induced epigenetic DNA hypomethylation at F2RL3 appears to increase PAR4 expression with potential downstream consequences for platelet reactivity. Combined evidence here not only identifies F2RL3 DNA methylation as a possible contributory pathway from smoking to cardiovascular disease risk but from any feature potentially influencing F2RL3 regulation in a similar manner
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