1,746 research outputs found

    Between a Rock and a Hard Place: Minoritized Communities, Urban School Reform, School Policies, and Mayoral Control

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    The purpose of this study is to explore a federal turnaround policy under a mayoral-controlled Northeastern school district that began in 2013. The study utilizes discourse and document analysis and interviews, as well as a life history methodology to explore the perspectives of educators, local politicians, and community activists from Black and Latinx communities, as well as other minoritized populations, within the jurisdiction of the school district. The framework for this study draws on a critical analysis of educational policy studies and utilizes Sandra Stein’s (2004) Culture of Education Policy framework to highlight discourses and language used to frame individuals and groups. This study analyzes a forced leadership change and focuses on a particular elementary school as a result of the implementation of a turnaround policy, and offers some implications for educational policy, reform, and leadership practices

    Stability effects on results of diffusion tensor imaging analysis by reduction of the number of gradient directions due to motion artifacts: an application to presymptomatic Huntington's disease.

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    In diffusion tensor imaging (DTI), an improvement in the signal-to-noise ratio (SNR) of the fractional anisotropy (FA) maps can be obtained when the number of recorded gradient directions (GD) is increased. Vice versa, elimination of motion-corrupted or noisy GD leads to a more accurate characterization of the diffusion tensor. We previously suggest a slice-wise method for artifact detection in FA maps. This current study applies this approach to a cohort of 18 premanifest Huntington's disease (pHD) subjects and 23 controls. By 2-D voxelwise statistical comparison of original FA-maps and FA-maps with a reduced number of GD, the effect of eliminating GD that were affected by motion was demonstrated.We present an evaluation metric that allows to test if the computed FA-maps (with a reduced number of GD) still reflect a "true" FA-map, as defined by simulations in the control sample. Furthermore, we investigated if omitting data volumes affected by motion in the pHD cohort could lead to an increased SNR in the resulting FA-maps.A high agreement between original FA maps (with all GD) and corrected FA maps (i.e. without GD corrupted by motion) were observed even for numbers of eliminated GD up to 13. Even in one data set in which 46 GD had to be eliminated, the results showed a moderate agreement

    Therapeutic strategies for Huntington’s disease

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    PURPOSE AND REVIEW: Huntington's disease is a fatal autosomal dominant neurodegenerative disorder caused by a trinucleotide expansion in the HTT gene, and current therapies focus on symptomatic treatment. This review explores therapeutic approaches that directly target the pathogenic mutation, disrupt HTT mRNA or its translation. RECENT FINDINGS: Zinc-finger transcription repressors and CRISPR-Cas9 therapies target HTT DNA, thereby preventing all downstream pathogenic mechanisms. These therapies, together with RNA interference (RNAi), require intraparenchymal delivery to the brain in viral vectors, with only a single delivery potentially required, though they may carry the risk of irreversible side-effects. Along with RNAi, antisense oligonucleotides (ASOs) target mRNA, but are delivered periodically and intrathecally. ASOs have safely decreased mutant huntingtin protein (mHTT) levels in the central nervous system of patients, and a phase 3 clinical trial is currently underway. Finally, orally available small molecules, acting on splicing or posttranslational modification, have recently been shown to decrease mHTT in animal models. SUMMARY: Huntingtin-lowering approaches act upstream of pathogenic mechanisms and therefore have a high a priori likelihood of modifying disease course. ASOs are already in late-stage clinical development, whereas other strategies are progressing rapidly toward human studies

    Classical and quantum spinor cosmology with signature change

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    We study the classical and quantum cosmology of a universe in which the matter source is a massive Dirac spinor field and consider cases where such fields are either free or self-interacting. We focus attention on the spatially flat Robertson-Walker cosmology and classify the solutions of the Einstein-Dirac system in the case of zero, negative and positive cosmological constant Λ\Lambda. For Λ<0\Lambda<0, these solutions exhibit signature transitions from a Euclidean to a Lorentzian domain. In the case of massless spinor fields it is found that signature changing solutions do not exist when the field is free while in the case of a self-interacting spinor field such solutions may exist. The resulting quantum cosmology and the corresponding Wheeler-DeWitt equation are also studied for both free and self interacting spinor fields and closed form expressions for the wavefunction of the universe are presented. These solutions suggest a quantization rule for the energy.Comment: 13 pages, 4 figure

    Osteoblastic and Vascular Endothelial Niches, Their Control on Normal Hematopoietic Stem Cells, and Their Consequences on the Development of Leukemia

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    Stem cell self-renewal is regulated by intrinsic mechanisms and extrinsic signals mediated via specialized microenvironments called “niches.” The best-characterized stem cell is the hematopoietic stem cell (HSC). Self-renewal and differentiation ability of HSC are regulated by two major elements: endosteal and vascular regulatory elements. The osteoblastic niche localized at the inner surface of the bone cavity might serve as a reservoir for long-term HSC storage in a quiescent state. Whereas the vascular niche, which consists of sinusoidal endothelial cell lining blood vessel, provides an environment for short-term HSC proliferation and differentiation. Both niches act together to maintain hematopoietic homeostasis. In this paper, we provide some principles applying to the hematopoietic niches, which will be useful in the study and understanding of other stem cell niches. We will discuss altered microenvironment signaling leading to myeloid lineage disease. And finally, we will review some data on the development of acute myeloid leukemia from a subpopulation called leukemia-initiating cells (LIC), and we will discuss on the emerging evidences supporting the influence of the microenvironment on chemotherapy resistance

    Canonical wave packets in quantum cosmology

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    We discuss the construction of wave packets resulting from the solutions of a class of Wheeler-DeWitt equations in Robertson-Walker type cosmologies, for arbitrary curvature. We show that there always exists a ``canonical initial slope" for a given initial wave function, which optimizes some desirable properties of the resulting wave packet, most importantly good classical-quantum correspondence. This can be properly denoted as a canonical wave packet. We introduce a general method for finding these canonical initial slopes which is generalization of our earlier work.Comment: 19 pages, 8 figure

    Developing performance indicators for clinical governance in dimensions of risk management and clinical effectiveness

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    Objective: This study has been designed and conducted to develop domestic indicators for evaluating the performance of clinical governance in dimensions of risk management and clinical effectiveness. Design: This study implemented a 5-stage process including conducting a comprehensive literature review, expert panel (~1000 h per person per session, 11 experts), semi-structured interviews, a 2-round Delphi study (33 experts were in attendance) and a final expert panel (8 experts were in attendance). Setting: East Azerbaijan-Iran Province. Participants: Fifty-six specialists and experts in different fields of medical sciences. Main Outcome Measures: Importance and applicability of indicators. Results: Using a thorough literature review, 361 indicators (129 risk management indicators in 4 dimensions and 232 clinical effectiveness indicators in 18 dimensions) were found. After conducting expert panels and interviews, the number of indicators decreased to 168 cases (65 risk management indicators in 4 dimensions and 103 clinical effectiveness indicators in 12 dimensions). Two rounds of Delphi identified four indicators that were omitted. The members of the final expert panel agreed on 113 indicators (43 risk management indicators in 4 dimensions and 70 clinical effectiveness indicators in 11 dimensions). Conclusion: In this study, indicators for assessing clinical governance in domains of risk management and clinical effectiveness were designed that can be used by policy-makers and other authorities for improving the quality of services and evaluating the performance of clinical governance. Those indicators can be used with slight modifications in other countries having healthcare systems similar to that of Iran. © The Author 2015. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved

    Premanifest and early Huntington's disease

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    This chapter deals with the clinical features, management, and clinically relevant research findings in premanifest and early Huntington’s disease (HD). A chapter dedicated to these disease stages is included in this volume for the first time because research into the neurobiology of HD in human subjects has improved our understanding to an extent that is clinically useful in defining and managing patients undergoing the transition from symptom-free to manifest HD. Moreover, this group of patients is the main focus for current and future trials of novel therapeutics aimed at slowing the progression of HD
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