164 research outputs found

    Teacher Training for the Implementation of the Incredible Years at GFW Elementary School

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    The purpose of this research project was to determine whether training the Early Childhood Special Education (ECSE) teachers, paraprofessionals, and staff would increase the social and emotional literacy of the children as well as the staff in the ECSE classroom . The four areas of training & research consisted of: 1. Increasing staff’s positive attention, encouragement and praise while working as a team in the ECSE classroom; 2. Using incentives for the purpose of promoting positive attention in the classroom; 3. Using more proactive teaching techniques for the purpose of preventing behavior problems in the classroom, and 4. Increasing staff’s proficiency in teaching social skills, problem-solving skills, and anger management skills. The staff trainings served as a prerequisite for the successful implementation of the Incredible Years (IY) Child Training Program called the Dina Dinosaur Social Skills and Problem Solving curriculum. This curriculum will be fully implemented in the ECSE classroom beginning in the fall, 2010. Focus groups and grounded theory methodology were utilized to collect and analyze the data

    Sleep Apnea Is Associated with Hearing Impairment: The Hispanic Community Health Study/Study of Latinos

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    Sleep apnea (SA) may promote hearing impairment (HI) through ischemia and inflammation of the cochlea. Our objective was to assess an independent association between SA and HI in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants

    Ultra-fast yttrium hydride chemistry at high pressures via non-equilibrium states induced by x-ray free electron laser

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    Controlling the formation and stoichiometric content of desired phases of materials has become a central interest for the study of a variety of fields, notably high temperature superconductivity under extreme pressures. The further possibility of accessing metastable states by initiating reactions by x-ray triggered mechanisms over ultra-short timescales is enabled with the development of x-ray free electron lasers (XFEL). Utilizing the exceptionally high brilliance x-ray pulses from the EuXFEL, we report the synthesis of a previously unobserved yttrium hydride under high pressure, along with non-stoichiometric changes in hydrogen content as probed at a repetition rate of 4.5\,MHz using time-resolved x-ray diffraction. Exploiting non-equilibrium pathways we synthesize and characterize a hydride with yttrium cations in an \textit{A}15 structure type at 125\,GPa, predicted using crystal structure searches, with a hydrogen content between 4.0--5.75 hydrogens per cation, that is enthalpically metastable on the convex hull. We demonstrate a tailored approach to changing hydrogen content using changes in x-ray fluence that is not accessible using conventional synthesis methods, and reveals a new paradigm in metastable chemical physics

    PR1-Specific T Cells Are Associated with Unmaintained Cytogenetic Remission of Chronic Myelogenous Leukemia After Interferon Withdrawal

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    Interferon-alpha (IFN) induces complete cytogenetic remission (CCR) in 20-25% CML patients and in a small minority of patients; CCR persists after IFN is stopped. IFN induces CCR in part by increasing cytotoxic T lymphocytes (CTL) specific for PR1, the HLA-A2-restricted 9-mer peptide from proteinase 3 and neutrophil elastase, but it is unknown how CCR persists after IFN is stopped.We reasoned that PR1-CTL persist and mediate CML-specific immunity in patients that maintain CCR after IFN withdrawal. We found that PR1-CTL were increased in peripheral blood of 7/7 HLA-A2+ patients during unmaintained CCR from 3 to 88 months after IFN withdrawal, as compared to no detectable PR1-CTL in 2/2 IFN-treated CML patients not in CCR. Unprimed PR1-CTL secreted IFNgamma and were predominantly CD45RA+/-CD28+CCR7+CD57-, consistent with functional naïve and central memory (CM) T cells. Similarly, following stimulation, proliferation occurred predominantly in CM PR1-CTL, consistent with long-term immunity sustained by self-renewing CM T cells. PR1-CTL were functionally anergic in one patient 6 months prior to cytogenetic relapse at 26 months after IFN withdrawal, and in three relapsed patients PR1-CTL were undetectable but re-emerged 3-6 months after starting imatinib.These data support the hypothesis that IFN elicits CML-specific CM CTL that may contribute to continuous CCR after IFN withdrawal and suggest a role for T cell immune therapy with or without tyrosine kinase inhibitors as a strategy to prolong CR in CML

    The Speed of Sound in Methane under Conditions of the Thermal Boundary Layer of Uranus

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    We present the first direct observations of acoustic waves in warm dense matter. We analyze wavenumber- and energy-resolved X-ray spectra taken from warm dense methane created by laser-heating a cryogenic liquid jet. X-ray diffraction and inelastic free electron scattering yield sample conditions of 0.3±\pm0.1 eV and 0.8±\pm0.1 g/cm3^3, corresponding to a pressure of \sim13 GPa and matching the conditions predicted in the thermal boundary layer between the inner and outer envelope of Uranus. Inelastic X-ray scattering was used to observe the collective oscillations of the ions. With a highly improved energy resolution of \sim50 meV, we could clearly distinguish the Brillouin peaks from the quasi-elastic Rayleigh feature. Data at different wavenumbers were used to obtain a sound speed of 5.9±\pm0.5 km/s, which enabled us to validate the use of Birch's law in this new parameter regime.Comment: 7 pages, 4 figures with supplementary informatio

    Clinical Outcomes by Race and Ethnicity in the Systolic Blood Pressure Intervention Trial (SPRINT): A Randomized Clinical Trial

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    BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure (SBP) of ≤ 120 mm Hg (intensive treatment) reduced cardiovascular disease (CVD) events compared to SBP of ≤ 140 mm Hg (standard treatment); however, it is unclear if this effect is similar in all racial/ethnic groups. METHODS: We analyzed SPRINT data within non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic subgroups to address this question. High-risk nondiabetic hypertensive patients (N = 9,361; 30% NHB; 11% Hispanic) 50 years and older were randomly assigned to intensive or standard treatment. Primary outcome was a composite of the first occurrence of a myocardial infarction, acute coronary syndrome, stroke, decompensated heart failure, or CVD death. RESULTS: Average postbaseline SBP was similar among NHW, NHB, and Hispanics in both treatment arms. Hazard ratios (HRs) (95% confidence interval) (intensive vs. standard treatment groups) for primary outcome were 0.70 (0.57–0.86), 0.71 (0.51–0.98), 0.62 (0.33–1.15) (interaction P value = 0.85) in NHW, NHB, and Hispanics. CVD mortality HRs were 0.49 (0.29–0.81), 0.77 (0.37–1.57), and 0.17 (0.01–1.08). All-cause mortality HRs were 0.61 (0.47–0.80), 0.92 (0.63–1.35), and 1.58 (0.73–3.62), respectively. A test for differences among racial/ethnic groups in the effect of treatment assignment on all-cause mortality was not significant (Hommel-adjusted P value = 0.062) after adjustment for multiple comparisons. CONCLUSION: Targeting a SBP goal of ≤ 120 mm Hg compared to ≤ 140 mm Hg led to similar SBP control and was associated with similar benefits and risks among all racial ethnic groups, though NHBs required an average of ~0.3 more medications

    Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci

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    Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: Rs13422522 (NYAP2; P = 8.87 × 10-11), rs12454712 (BCL2; P = 2.7 × 10-8), and rs10506418 (FAM19A2; P = 1.9 × 10-8). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci

    Genome-wide associations for birth weight and correlations with adult disease

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    Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P\textit{P}  < 5 × 108^{-8}). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (R\textit{R}g_{g} = -0.22, P\textit{P}  = 5.5 × 1013^{-13}), T2D (R\textit{R}g_{g} = -0.27, P\textit{P}  = 1.1 × 106^{-6}) and coronary artery disease (R\textit{R}g_{g} = -0.30, P\textit{P}  = 6.5 × 109^{-9}). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P\textit{P} = 1.9 × 104^{-4}). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.For a full list of the funders pelase visit the publisher's website and look at the supplemetary material provided. Some of the funders are: British Heart Foundation, Cancer Research UK, Medical Research Council, National Institutes of Health, Royal Society and Wellcome Trust

    Genome-wide associations for birth weight and correlations with adult disease

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    Birth weight (BW) is influenced by both foetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease1. These lifecourse associations have often been attributed to the impact of an adverse early life environment. We performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where foetal genotype was associated with BW (P <5x10-8). Overall, ˜15% of variance in BW could be captured by assays of foetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (rg-0.22, P =5.5x10-13), T2D (rg-0.27, P =1.1x10-6) and coronary artery disease (rg-0.30, P =6.5x10-9) and, in large cohort data sets, demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P =1.9x10-4). We have demonstrated that lifecourse associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and have highlighted some of the pathways through which these causal genetic effects are mediated
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