607 research outputs found

    Extending an Effective Classroom-Based Math Board Game Intervention to Preschoolers’ Homes

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    The preschool years are a critical time for math development. Unfortunately, children from low-income backgrounds often enter kindergarten with lower math skills than middle-income peers, perhaps due to less math exposure at home. Few home-based math interventions are available for preschool age children; those that do exist are costly and difficult to implement. Interventions conducted in children’s schools using linear numeric board games developed by researchers have been particularly successful with low-income preschool children. Researchers have suggested they may be adapted for home-use by using commercially available board games, such as Chutes and Ladders, and teaching parents how to play. The two studies described in this paper explored the effectiveness of using Chutes and Ladders with a specialized counting procedure with Head Start families. Implementation proved to be challenging and children did not improve as much as in previous classroom-based interventions

    Healthcare professionals’ perceptions of risk in the context of genetic testing for the prediction of chronic disease: a qualitative metasynthesis

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    Advances in genomic technologies and a growing trend towards stratified and preventive approaches to medicine mean that increasing numbers of individuals may have access to information about their genetic makeup, and their risk of developing diseases. This is likely to impact on healthcare professionals involved in the delivery of genetic tests, or in supporting patients who are affected by a disease with a genetic risk factor. It is therefore important to understand health-care professionals’ perceptions about providing these services, and how they feel about communicating information about genetic risk to patients. This paper provides a systematic review and metasynthesis of qualitative research exploring healthcare professionals’ perceptions of genetic risk in the context of predictive genetic testing for chronic disease. Healthcare professionals expressed a range of reservations about the utility of predictive testing in this context. Professionals judged patients’ understanding of risk information to be limited and subject to bias and a range of sociocultural influences. Concerns about the psychosocial impact of genetic risk information were frequently cited, both in relation to individual patients and the wider impact on their families and communities. The need for provision of multidisciplinary support was described. The concept of responsibility was also an important theme. Healthcare professionals recognized the responsibility that accompanies risk knowledge, and that ultimately this responsibility lies with the patient, not the provider. Our analysis suggests that professionals’ evaluation of the utility of predictive genetic testing is influenced not only by resource deficits, but may also be interpreted as a response to challenging ethical and social issues associated with genetic risk, that are not well aligned with current medical practice

    Engineering tyrosine electron transfer pathways decreases oxidative toxicity in hemoglobin: implications for blood substitute design

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    Hemoglobin (Hb)-based oxygen carriers (HBOC) have been engineered to replace or augment the oxygen-carrying capacity of erythrocytes. However, clinical results have generally been disappointing due to adverse side effects linked to intrinsic heme-mediated oxidative toxicity and nitric oxide (NO) scavenging. Redox-active tyrosine residues can facilitate electron transfer between endogenous antioxidants and oxidative ferryl heme species. A suitable residue is present in the α-subunit (Y42) of Hb, but absent from the homologous position in the β-subunit (F41). We therefore replaced this residue with a tyrosine (βF41Y, Hb Mequon). The βF41Y mutation had no effect on the intrinsic rate of lipid peroxidation as measured by conjugated diene and singlet oxygen formation following the addition of ferric(met) Hb to liposomes. However, βF41Y significantly decreased these rates in the presence of physiological levels of ascorbate. Additionally, heme damage in the β-subunit following the addition of the lipid peroxide hydroperoxyoctadecadieoic acid was five-fold slower in βF41Y. NO bioavailability was enhanced in βF41Y by a combination of a 20% decrease in NO dioxygenase activity and a doubling of the rate of nitrite reductase activity. The intrinsic rate of heme loss from methemoglobin was doubled in the β-subunit, but unchanged in the α-subunit. We conclude that the addition of a redox-active tyrosine mutation in Hb able to transfer electrons from plasma antioxidants decreases heme-mediated oxidative reactivity and enhances NO bioavailability. This class of mutations has the potential to decrease adverse side effects as one component of a HBOC product.</jats:p

    Sesso nel Rinascimento

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    Questo volume propone un discorso critico sulla sessualità e sulla cultura visiva dell’Italia rinascimentale. I saggi raccolti tentano di fare luce su una serie di zone d’ombra, dando spazio a tutte quelle pratiche o preferenze considerate in genere come alternative o anomalie, e a un’ampia varietà di scenari “scandalosi”. Particolare attenzione è stata riservata all’aspetto materiale della cultura sessuale, dalle modalità di rappresentazione erotica del corpo agli oggetti e agli strumenti associati all’attività sessuale. Ne emerge un quadro completamente nuovo della sessualità rinascimentale, che spazza via secoli di manipolazioni ed equivoci socio-culturali, svelando scenari finora trascurati o volutamente nascosti. Diciassette saggi provocatori, con incursioni nel campo dell’arte, della letteratura, della storia, e persino della filosofia, organizzati intorno a quattro assi fondamentali: la pratica, la performance, la perversione e la punizione. Questo volume rivela un panorama molto più complesso e una visione del sesso e della sessualità rinascimentali carica di nuove sfumature

    The Maunakea Spectroscopic Explorer Book 2018

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    (Abridged) This is the Maunakea Spectroscopic Explorer 2018 book. It is intended as a concise reference guide to all aspects of the scientific and technical design of MSE, for the international astronomy and engineering communities, and related agencies. The current version is a status report of MSE's science goals and their practical implementation, following the System Conceptual Design Review, held in January 2018. MSE is a planned 10-m class, wide-field, optical and near-infrared facility, designed to enable transformative science, while filling a critical missing gap in the emerging international network of large-scale astronomical facilities. MSE is completely dedicated to multi-object spectroscopy of samples of between thousands and millions of astrophysical objects. It will lead the world in this arena, due to its unique design capabilities: it will boast a large (11.25 m) aperture and wide (1.52 sq. degree) field of view; it will have the capabilities to observe at a wide range of spectral resolutions, from R2500 to R40,000, with massive multiplexing (4332 spectra per exposure, with all spectral resolutions available at all times), and an on-target observing efficiency of more than 80%. MSE will unveil the composition and dynamics of the faint Universe and is designed to excel at precision studies of faint astrophysical phenomena. It will also provide critical follow-up for multi-wavelength imaging surveys, such as those of the Large Synoptic Survey Telescope, Gaia, Euclid, the Wide Field Infrared Survey Telescope, the Square Kilometre Array, and the Next Generation Very Large Array.Comment: 5 chapters, 160 pages, 107 figure

    Developing a Research Data Policy Framework for All Journals and Publishers

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    More journals and publishers – and funding agencies and institutions – are introducing research data policies. But as the prevalence of policies increases, there is potential to confuse researchers and support staff with numerous or conflicting policy requirements. We define and describe 14 features of journal research data policies and arrange these into a set of six standard policy types or tiers, which can be adopted by journals and publishers to promote data sharing in a way that encourages good practice and is appropriate for their audience’s perceived needs. Policy features include coverage of topics such as data citation, data repositories, data availability statements, data standards and formats, and peer review of research data. These policy features and types have been created by reviewing the policies of multiple scholarly publishers, which collectively publish more than 10,000 journals, and through discussions and consensus building with multiple stakeholders in research data policy via the Data Policy Standardisation and Implementation Interest Group of the Research Data Alliance. Implementation guidelines for the standard research data policies for journals and publishers are also provided, along with template policy texts which can be implemented by journals in their Information for Authors and publishing workflows. We conclude with a call for collaboration across the scholarly publishing and wider research community to drive further implementation and adoption of consistent research data policies

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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