121 research outputs found

    Running Strong After All These Years: How A Five Year CAPE School Sustains and Continuously Improves into Year Eight, 2000

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    A central component of our evaluation and inquiry agenda for the Chicago Arts Partnershipsin Education (CAPE) during the school year 1999-2000 was a quest for understanding the reasons for the ability of programs to survive after the sponsor funding ceased. Why do some programs survive well beyond their original funding and support?This is an absolutely crucial question for the sponsors of most any program entering schools with goals of long term or permanent change. This question equally impacts foundations, government agencies, and individual philanthropists. Sponsors of funded programs in our schools generally have as their highest hope that their investments willspawn change, and not just expenditure of money.To seek information and suggested answersto the critical issue of sustainability,we interviewed parents, teachers, and administrators. We also surveyed key players and asked them to enumerate what they saw to be important longevity factors for their CAPE programs.We uncovered many things in this process. One component of our work that turned out remarkably well was interviews with key teachers involved in the CAPE programs that have lived in since CAPE's very start. Our team invited a teacher, perhaps the most experienced and thoughtful witness to the whole project, to compose a narrative account of the development of the program at her school. What resulted was a very lucid account of the complex processed of launching and institutionalizing a program ignited by an outside sponsor: the successes and pitfalls, the leaders and resisters. It is a compelling story about the long-term evolution of a school community and its central conversations

    Chicago Arts Partnerships in Education Summary Evaluation

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    The purpose of this monograph is to highlight the development of CAPE and its effects through the multiple inquiry lenses trained on the program over its first six years. The story is one of development and learning by school communities, teachers, and artists as they became increasingly and more deeply involved in arts-integrated instruction. It is also a story of increasingly tangible and measurable effects on student learning as the program matured

    Holography of a Composite Inflaton

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    We study the time evolution of a brane construction that is holographically dual to a strongly coupled gauge theory that dynamically breaks a global symmetry through the generation of an effective composite Higgs vev. The D3/D7 system with a background magnetic field or non-trivial gauge coupling (dilaton) profile displays the symmetry breaking. We study motion of the D7 brane in the background of the D3 branes. For small field inflation in the field theory the effective Higgs vev rolls from zero to the true vacuum value. We study what phenomenological dilaton profile generates the slow rolling needed, hence learning how the strongly coupled gauge theory's coupling must run. We note that evolution of our configuration in the holographic direction, representing the phyiscs of the strong interactions, can provide additional slowing of the roll time. Inflation seems to be favoured if the coupling changes by only a small amount or very gently. We speculate on how such a scenario could be realized away from N=4 gauge theory, for example, in a walking gauge theory.Comment: 13 pages, 12 figures; v2: Added reference

    New Insights in the Contribution of Voltage-Gated Nav Channels to Rat Aorta Contraction

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    BACKGROUND: Despite increasing evidence for the presence of voltage-gated Na(+) channels (Na(v)) isoforms and measurements of Na(v) channel currents with the patch-clamp technique in arterial myocytes, no information is available to date as to whether or not Na(v) channels play a functional role in arteries. The aim of the present work was to look for a physiological role of Na(v) channels in the control of rat aortic contraction. METHODOLOGY/PRINCIPAL FINDINGS: Na(v) channels were detected in the aortic media by Western blot analysis and double immunofluorescence labeling for Na(v) channels and smooth muscle alpha-actin using specific antibodies. In parallel, using real time RT-PCR, we identified three Na(v) transcripts: Na(v)1.2, Na(v)1.3, and Na(v)1.5. Only the Na(v)1.2 isoform was found in the intact media and in freshly isolated myocytes excluding contamination by other cell types. Using the specific Na(v) channel agonist veratridine and antagonist tetrodotoxin (TTX), we unmasked a contribution of these channels in the response to the depolarizing agent KCl on rat aortic isometric tension recorded from endothelium-denuded aortic rings. Experimental conditions excluded a contribution of Na(v) channels from the perivascular sympathetic nerve terminals. Addition of low concentrations of KCl (2-10 mM), which induced moderate membrane depolarization (e.g., from -55.9+/-1.4 mV to -45.9+/-1.2 mV at 10 mmol/L as measured with microelectrodes), triggered a contraction potentiated by veratridine (100 microM) and blocked by TTX (1 microM). KB-R7943, an inhibitor of the reverse mode of the Na(+)/Ca(2+) exchanger, mimicked the effect of TTX and had no additive effect in presence of TTX. CONCLUSIONS/SIGNIFICANCE: These results define a new role for Na(v) channels in arterial physiology, and suggest that the TTX-sensitive Na(v)1.2 isoform, together with the Na(+)/Ca(2+) exchanger, contributes to the contractile response of aortic myocytes at physiological range of membrane depolarization

    Complex Langevin dynamics in the SU(3) spin model at nonzero chemical potential revisited

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    The three-dimensional SU(3) spin model is an effective Polyakov loop model for QCD at nonzero temperature and density. It suffers from a sign problem at nonzero chemical potential. We revisit this model using complex Langevin dynamics and assess in particular the justification of this approach, using analyticity at small mu^2 and the criteria for correctness developed recently. Finite-stepsize effects are discussed in some detail and a higher-order algorithm is employed to eliminate leading stepsize corrections. Our results strongly indicate that complex Langevin dynamics is reliable in this theory in both phases, including the critical region. This is in sharp contrast to the case of the XY model, where correct results were obtained in only part of the phase diagram.Comment: 23 pages, several figures, minor typos corrected, to appear in JHE

    The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

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    We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

    Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

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    BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council
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