271 research outputs found

    Making a case for telehealth: measuring the carbon cost of health-related travel

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    Background: Telehealth services are promoted to reduce the cost of travel for people living in rural areas. The previous Australian Government, through the national Digital Economy Strategy, invested heavily in telehealth service development, at the same time introducing a carbon pricing mechanism. In planning a range of new telehealth services to a rural community the authors sought to quantify the travel conducted by people from one rural area in Australia to access health care, and to calculate the associated carbon emissions.Methods: A population survey was conducted over a 1-week period of health-related travel events for the year 1 July 2011 to 30 June 2012 of all households on King Island, a community situated between the Australian mainland state of Victoria and the state of Tasmania. Validated emissions calculators were sourced from the Carbon Neutral website, including the vehicle and fuel use calculator and air travel carbon calculator, to calculate the total emissions associated with the fuel burned in tonnes of carbon dioxide equivalent (tCO2e).Results: Thirty nine percent of the population (625 participants) reported a total of 511 healthcare-related travel events. Participants travelled a total of 346 573 km and generated 0.22 tCO2e per capita. Participants paid the cost of their own travel more than 70% of the time.Conclusions: Dependence on fossil fuels for transport in a carbon economy has a significant impact on total healthcare carbon emissions. Alternative models of care, such as telehealth, need be developed for an environmentally sustainable healthcare system for rural and remote areas

    Functional 3D architecture in an intrinsically disordered E3 ligase domain facilitates ubiquitin transfer

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    Funding: Wellcome Trust Investigator Awards (098391/Z/12/Z and 217196/Z/19/Z) and Cancer Research UK Programme grant (C434/A21747) to R.T.H., Wellcome Trust Studentship (109113/Z/15/Z) to P.M., Wellcome Trust Collaborative Award (215539) and multiuser equipment grant (104833) to S.J.M. Additionally J.C.P. thanks the Scottish Universities Physics Alliance (SUPA) and the University of St. Andrews for financial support.The human genome contains an estimated 600 ubiquitin E3 ligases, many of which are single-subunit E3s (ssE3s) that can bind to both substrate and ubiquitin-loaded E2 (E2~Ub). Within ssE3s structural disorder tends to be located in substrate binding and domain linking regions. RNF4 is a ssE3 ligase with a C-terminal RING domain and disordered N-terminal region containing SUMO Interactions Motifs (SIMs) required to bind SUMO modified substrates. Here we show that, although the N-terminal region of RNF4 bears no secondary structure, it maintains a compact global architecture primed for SUMO interaction. Segregated charged regions within the RNF4 N-terminus promote compaction, juxtaposing RING domain and SIMs to facilitate substrate ubiquitination. Mutations that induce a more extended shape reduce ubiquitination activity. Our result offer insight into a key step in substrate ubiquitination by a member of the largest ubiquitin ligase subtype and reveal how a defined architecture within a disordered region contributes to E3 ligase function.Publisher PDFPeer reviewe

    Structural basis for the RING catalyzed synthesis of K63 linked ubiquitin chains

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    This work was supported by grants from Cancer Research UK (C434/A13067), the Wellcome Trust (098391/Z/12/Z) and Biotechnology and Biological Sciences Research Council (BB/J016004/1).The RING E3 ligase catalysed formation of lysine 63 linked ubiquitin chains by the Ube2V2–Ubc13 E2 complex is required for many important biological processes. Here we report the structure of the RING domain dimer of rat RNF4 in complex with a human Ubc13~Ub conjugate and Ube2V2. The structure has captured Ube2V2 bound to the acceptor (priming) ubiquitin with Lys63 in a position that could lead to attack on the linkage between the donor (second) ubiquitin and Ubc13 that is held in the active “folded back” conformation by the RING domain of RNF4. The interfaces identified in the structure were verified by in vitro ubiquitination assays of site directed mutants. This represents the first view of the synthesis of Lys63 linked ubiquitin chains in which both substrate ubiquitin and ubiquitin-loaded E2 are juxtaposed to allow E3 ligase mediated catalysis.PostprintPeer reviewe

    Assessment of flatness and symmetry of megavoltage x-ray beam with an electronic portal imaging device (EPID)

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    Copyright © 2002 ACPSEM. All rights reserved. The document attached has been archived with permission from the publisher.The input/output characteristics of the Wellhofer BIS 710 electronic portal imaging device (EPID) have been investigated to establish its efficacy for periodic quality assurance (QA) applications. Calibration curves have been determined for the energy fluence incident on the detector versus the pixel values. The effect of the charge coupled device (CCD) camera sampling time and beam parameters (such as beam field size, dose rate, photon energy) on the calibration have been investigated for a region of interest (ROI) around the central beam axis. The results demonstrate that the pixel output is a linear function of the incident exposure, as expected for a video-based electronic portal imaging system. The field size effects of the BIS 710 are similar to that of an ion chamber for smaller field sizes up to 10 x 10 cm2. However, for larger field sizes the pixel value increases more rapidly. Furthermore, the system is slightly sensitive to dose rate and is also energy dependent. The BIS 710 has been used in the current study to develop a QA procedure for measurements of flatness and symmetry of a linac x-ray beam. As a two-dimensional image of the radiation field is obtained from a single exposure of the BIS 710, a technique has been developed to calculate flatness and symmetry from a defined radiation area. The flatness and symmetry values obtained are different from those calculated conventionally from major axes only (inplane, crossplane). This demonstrates that the technique can pick up the "cold" and "hot" spots in the analysed area, providing thus more information about the radiation beam. When calibrated against the water tank measurements, the BIS 710 can be used as a secondary device to monitor the x-ray beam flatness and symmetry.G. Liu, T. van Doorn and E. Beza

    Facilitating Adolescent Well-Being: A Review of the Challenges and Opportunities and the Beneficial Roles of Parents, Schools, Neighborhoods, and Policymakers

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    Adolescents face exceptional challenges and opportunities that may have a lifelong impact on their consumption and personal and societal well-being. Parents, community members (schools and neighborhoods), and policymakers play major roles in shaping adolescents and influencing their engagement in consumption behaviors that are either developmentally problematic (e.g., drug use and unhealthy eating) or developmentally constructive (e.g., academic pursuits and extracurricular activities). In this article, we discuss two main topics: (a) the challenges and opportunities that characterize adolescence, based primarily on research in epidemiology and neuroscience, and (b) the ways that parents, community members, and policymakers can facilitate positive adolescent development, based on research from many disciplines including marketing, psychology, sociology, communications, public health, and education. Our goal is to summarize the latest scientific findings that can be used by various stakeholders to help adolescents navigate this turbulent period and become well-adjusted, thriving adults

    The effect of on-line position correction on the dose distribution in focal radiotherapy for bladder cancer

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    <p>Abstract</p> <p>Background</p> <p>The purpose of this study was to determine the dosimetric effect of on-line position correction for bladder tumor irradiation and to find methods to predict and handle this effect.</p> <p>Methods</p> <p>For 25 patients with unifocal bladder cancer intensity modulated radiotherapy (IMRT) with 5 beams was planned. The requirement for each plan was that 99% of the target volume received 95% of the prescribed dose. Tumor displacements from -2.0 cm to 2.0 cm in each dimension were simulated, using 0.5 cm increments, resulting in 729 simulations per patient. We assumed that on-line correction for the tumor was applied perfectly. We determined the correlation between the change in D<sub>99% </sub>and the change in path length, which is defined here as the distance from the skin to the isocenter for each beam. In addition the margin needed to avoid underdosage was determined and the probability that an underdosage occurs in a real treatment was calculated.</p> <p>Results</p> <p>Adjustments for tumor displacement with perfect on-line position correction resulted in an altered dose distribution. The altered fraction dose to the target varied from 91.9% to 100.4% of the prescribed dose. The mean D<sub>99% </sub>(± SD) was 95.8% ± 1.0%. There was a modest linear correlation between the difference in D<sub>99% </sub>and the change in path length of the beams after correction (R<sup>2 </sup>= 0.590). The median probability that a systematic underdosage occurs in a real treatment was 0.23% (range: 0 - 24.5%). A margin of 2 mm reduced that probability to < 0.001% in all patients.</p> <p>Conclusion</p> <p>On-line position correction does result in an altered target coverage, due to changes in average path length after position correction. An extra margin can be added to prevent underdosage.</p

    Intrafraction motion of the prostate during an IMRT session: a fiducial-based 3D measurement with Cone-beam CT

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    Background: Image-guidance systems allow accurate interfractional repositioning of IMRT treatments, however, these may require up to 15 minutes. Therefore intrafraction motion might have an impact on treatment precision. 3D geometric data regarding intrafraction prostate motion are rare; we therefore assessed its magnitude with pre- and post-treatment fiducial-based imaging with cone-beam-CT (CBCT). Methods: 39 IMRT fractions in 5 prostate cancer patients after (125)I-seed implantation were evaluated. Patient position was corrected based on the (125)I-seeds after pre-treatment CBCT. Immediately after treatment delivery, a second CBCT was performed. Differences in bone- and fiducial position were measured by seed-based grey-value matching. Results: Fraction time was 13.6 +/- 1.6 minutes. Median overall displacement vector length of (125)Iseeds was 3 mm (M = 3 mm, Sigma = 0.9 mm, sigma = 1.7 mm; M: group systematic error, Sigma: SD of systematic error, sigma: SD of random error). Median displacement vector of bony structures was 1.84 mm (M = 2.9 mm, Sigma = 1 mm, sigma = 3.2 mm). Median displacement vector length of the prostate relative to bony structures was 1.9 mm (M = 3 mm, Sigma = 1.3 mm, sigma = 2.6 mm). Conclusion: a) Overall displacement vector length during an IMRT session is &lt; 3 mm. b) Positioning devices reducing intrafraction bony displacements can further reduce overall intrafraction motion. c) Intrafraction prostate motion relative to bony structures is &lt; 2 mm and may be further reduced by institutional protocols and reduction of IMRT duration
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