3,038 research outputs found

    Urgent News From The Front

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    This creative thesis is an original work in the genres of fiction and poetry. It consists of three short stories and a chapbook of poems. My work focuses on the ways we find to survive, to create meaning, and to connect to ourselves, to those around us, and to the world in which we live. Advisor: Jonis Age

    Urgent News From The Front

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    This creative thesis is an original work in the genres of fiction and poetry. It consists of three short stories and a chapbook of poems. My work focuses on the ways we find to survive, to create meaning, and to connect to ourselves, to those around us, and to the world in which we live. Advisor: Jonis Age

    Synchronous vs Asynchronous Chain Motion in α-Synuclein Contact Dynamics

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    α-Synuclein (α-syn) is an intrinsically unstructured 140-residue neuronal protein of uncertain function that is implicated in the etiology of Parkinson’s disease. Tertiary contact formation rate constants in α-syn, determined from diffusion-limited electron-transfer kinetics measurements, are poorly approximated by simple random polymer theory. One source of the discrepancy between theory and experiment may be that interior-loop formation rates are not well approximated by end-to-end contact dynamics models. We have addressed this issue with Monte Carlo simulations to model asynchronous and synchronous motion of contacting sites in a random polymer. These simulations suggest that a dynamical drag effect may slow interior-loop formation rates by about a factor of 2 in comparison to end-to-end loops of comparable size. The additional deviations from random coil behavior in α-syn likely arise from clustering of hydrophobic residues in the disordered polypeptide

    Kentucky Vehicle License Plate Study

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    This study assesses Kentucky’s options for potentially re-plating all motor vehicles registered in the Commonwealth. The report begins with a background and discussion of Kentucky’s plate production processes, the difference between flat and embossed plates, and the structure of license plate labor at the Kentucky State Reformatory in La Grange. It details current plate production costs and processes, along with fees and production numbers. It evaluates three scenarios for future plate production: flat plate production, a hybrid system with embossed general issue plates and flat specialty plates, and an embossed plate system with in-house printed sheeting. Also included is an analysis of the effects of license plate characteristics on automated license plate reader accuracy, which has implications for automated screening and tolling. From there, the policies and approaches of other states are discussed. The report ends with a discussion of implementation costs, challenges, and strategies for state officials

    Identification of Trypanocidal Activity for Known Clinical Compounds Using a New <i>Trypanosoma cruzi</i> Hit-Discovery Screening Cascade

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    <div><p>Chagas disease is a significant health problem in Latin America and the available treatments have significant issues in terms of toxicity and efficacy. There is thus an urgent need to develop new treatments either via a repurposing strategy or through the development of new chemical entities. A key first step is the identification of compounds with anti-<i>Trypanosoma cruzi</i> activity from compound libraries. Here we describe a hit discovery screening cascade designed to specifically identify hits that have the appropriate anti-parasitic properties to warrant further development. The cascade consists of a primary imaging-based assay followed by newly developed and appropriately scaled secondary assays to predict the cidality and rate-of-kill of the compounds. Finally, we incorporated a cytochrome P450 CYP51 biochemical assay to remove compounds that owe their phenotypic response to inhibition of this enzyme. We report the use of the cascade in profiling two small libraries containing clinically tested compounds and identify Clemastine, Azelastine, Ifenprodil, Ziprasidone and Clofibrate as molecules having appropriate profiles. Analysis of clinical derived pharmacokinetic and toxicity data indicates that none of these are appropriate for repurposing but they may represent suitable start points for further optimisation for the treatment of Chagas disease.</p></div

    A longitudinal study of influences on alcohol consumption and related harm in Central Australia: with a particular emphasis on the role of price.

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    Made available by the Northern Territory Library via the Publications (Legal Deposit) Act 2004 (NT).Northern Territory, Department of Health, Central Australian Aboriginal Congres

    Dinuclear Ce(IV) Aryloxides: Highly Active Catalysts for Anhydride/Epoxide Ring-Opening Copolymerization

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    A library of new dinuclear CeIV complexes of the type [NEt4]2[Ce2X6(TP)(sol)2] (X = Cl, ODipp, OSiMe3; sol = py, THF), where TP represents a family of tetraphenolate ligands that control intermetallic distance, are readily made in good yields. The ligands strongly stabilize the cerium +4 oxidation state and allow the incorporation of alkylammonium cocations in an "ate"complex formulation that enables them to be used as soluble, single-component catalysts for the ring-opening copolymerization (ROCOP) of a variety of anhydrides and epoxides. High turnover frequencies (TOFs) are achieved with high ester linkage selectivity, low dispersities, and rates that are highly tunable by the intermetallic distance enforced by the TP ligand, demonstrating that a closely coupled di-CeIV unit provides excellent rates of ROCOP catalysis and that, more generally, rare-earth complexes deserve further attention as ROCOP initiators

    Study protocol: Phase III single-blinded fast-track pragmatic randomised controlled trial of a complex intervention for breathlessness in advanced disease.

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    BACKGROUND: Breathlessness in advanced disease causes significant distress to patients and carers and presents management challenges to health care professionals. The Breathlessness Intervention Service (BIS) seeks to improve the care of breathless patients with advanced disease (regardless of cause) through the use of evidence-based practice and working with other healthcare providers. BIS delivers a complex intervention (of non-pharmacological and pharmacological treatments) via a multi-professional team. BIS is being continuously developed and its impact evaluated using the MRC's framework for complex interventions (PreClinical, Phase I and Phase II completed). This paper presents the protocol for Phase III. METHODS/DESIGN: Phase III comprises a pragmatic, fast-track, single-blind randomised controlled trial of BIS versus standard care. Due to differing disease trajectories, the service uses two broad service models: one for patients with malignant disease (intervention delivered over two weeks) and one for patients with non-malignant disease (intervention delivered over four weeks). The Phase III trial therefore consists of two sub-protocols: one for patients with malignant conditions (four week protocol) and one for patients with non-malignant conditions (eight week protocol). Mixed method interviews are conducted with patients and their lay carers at three to five measurement points depending on randomisation and sub-protocol. Qualitative interviews are conducted with referring and non-referring health care professionals (malignant disease protocol only). The primary outcome measure is 'patient distress due to breathlessness' measured on a numerical rating scale (0-10). The trial includes economic evaluation. Analysis will be on an intention to treat basis. DISCUSSION: This is the first evaluation of a breathlessness intervention for advanced disease to have followed the MRC framework and one of the first palliative care trials to use fast track methodology and single-blinding. The results will provide evidence of the clinical and cost-effectiveness of the service, informing its longer term development and implementation of the model in other centres nationally and internationally. It adds to methodological developments in palliative care research where complex interventions are common but evidence sparse. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00678405ISRCTN: ISRCTN04119516.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

    Screening for type 2 diabetes in a multiethnic setting using known risk factors to identify those at high risk: a cross-sectional study

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    Screening enables the identification of type 2 diabetes mellitus (T2DM) during its asymptomatic stage and therefore allows early intervention which may lead to fewer complications and improve outcomes. A targeted screening program was carried out in a United Kingdom (UK) multiethnic population to identify those with abnormal glucose tolerance
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