678 research outputs found

    Proton induced leakage current in CCDs

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    The effect of different proton fluences on the performance of two E2V Technologies CCD47-20 devices was investigated with particular emphasis given to the analysis of 'random telegraph signal' (RTS) generation, bright pixel generation and induced changes in base dark current level. The results show that bright pixel frequency increases as the mean energy of the proton beam is increased, and that the base dark current level after irradiation scales with the level of ionization damage. For the RTS study, 500 pixels on one device were monitored over a twelve hour period. This data set revealed a number of distinct types of pixel change level fluctuation and a system of classification has been devised. Previously published RTS data is discussed and reviewed in light of the new data

    Low noise charge injection in the CCD22

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    The inclusion of a charge injection structure on a charge coupled device (CCD) allows for the mitigation of charge transfer loss which can be caused by radiation induced charge trapping defects. Any traps present in the pixels of the CCD are filled by the injected charge as it is swept through the device and consequently, the charge transfer efficiency is improved in subsequently acquired images. To date, a number of different types of CCD have been manufactured featuring a variety of charge injection techniques. The e2v Technologies CCD22, used in the EPIC MOS focal plane instruments of XMM-Newton, is one such device and is the subject of this paper. A detailed understanding of charge injection operation and the use of charge injection to mitigate charge transfer losses resulting from radiation damage to CCDs will benefit a number of space projects planned for the future, including the ESA GAIA and X-ray Evolving Universe Spectrometry (XEUS) missions.The charge injection structure and mode of operation of the CCD22 are presented, followed by a detailed analysis of the uniformity and repeatability of the charge injection amplitude across the columns of the device. The effects of proton irradiation on the charge injection characteristics are also presented, in particular the effect of radiation induced bright pixels on the injected charge level

    MOS CCDs for the wide field imager on the XEUS spacecraft

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    In recent years the XEUS mission concept has evolved and has been the subject of several industrial studies. The mission concept has now matured to the point that it could be proposed for a Phase A study and subsequent flight programme. The key feature of XEUS will be its X-ray optic with collecting area ~30-100x that of XMM. The mission is envisaged at an orbit around the L2 point in space, and is formed from two spacecraft; one for the mirrors, and the other for the focal plane detectors. With a focal length of 50m, the plate scale of the optic is 6.5x that of XMM, which using existing focal plane technology will reduce the effective field of view to a few arc minutes. Cryogenic instrumentation, with detector sizes of a few mm can only be used for narrow field studies of target objects, and a wide field instrument is under consideration using a DEPFET pixel array to image out to a diameter of 5 arcminutes, requiring an array of dimension 70mm. It is envisaged to extend this field of view possibly out to 15 arcminutes through the use of an outer detection ring comprised of MOS CCD

    Operational research in Malawi: making a difference with cotrimoxazole preventive therapy in patients with tuberculosis and HIV.

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    BACKGROUND: In Malawi, high case fatality rates in patients with tuberculosis, who were also co-infected with HIV, and high early death rates in people living with HIV during the initiation of antiretroviral treatment (ART) adversely impacted on treatment outcomes for the national tuberculosis and ART programmes respectively. This article i) discusses the operational research that was conducted in the country on cotrimoxazole preventive therapy, ii) outlines the steps that were taken to translate these findings into national policy and practice, iii) shows how the implementation of cotrimoxazole preventive therapy for both TB patients and HIV-infected patients starting ART was associated with reduced death rates, and iv) highlights lessons that can be learnt for other settings and interventions. DISCUSSION: District and facility-based operational research was undertaken between 1999 and 2005 to assess the effectiveness of cotrimoxazole preventive therapy in reducing death rates in TB patients and subsequently in patients starting ART under routine programme conditions. Studies demonstrated significant reductions in case fatality in HIV-infected TB patients receiving cotrimoxazole and in HIV-infected patients about to start ART. Following the completion of research, the findings were rapidly disseminated nationally at stakeholder meetings convened by the Ministry of Health and internationally through conferences and peer-reviewed scientific publications. The Ministry of Health made policy changes based on the available evidence, following which there was countrywide distribution of the updated policy and guidelines. Policy was rapidly moved to practice with the development of monitoring tools, drug procurement and training packages. National programme performance improved which showed a significant decrease in case fatality rates in TB patients as well as a reduction in early death in people with HIV starting ART. SUMMARY: Key lessons for moving this research endeavour through to policy and practice were the importance of placing operational research within the programme, defining relevant questions, obtaining "buy-in" from national programme staff at the beginning of projects and having key actors or "policy entrepreneurs" to push forward the policy-making process. Ultimately, any change in policy and practice has to benefit patients, and the ultimate judge of success is whether treatment outcomes improve or not

    Cyclooxygenase activity mediates colorectal cancer cell resistance to the omega-3 polyunsaturated fatty acid eicosapentaenoic acid

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    Purpose The naturally-occurring omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) is safe, well-tolerated and inexpensive, making it an attractive anti-cancer intervention. However, EPA has only modest anti-colorectal cancer (CRC) activity, when used alone. Both cyclooxygenase (COX) isoforms metabolise EPA and are over-expressed in CRC cells. We investigated whether COX inhibition increases the sensitivity of CRC cells to growth inhibition by EPA. Methods A panel of 18 human and mouse CRC cell lines was used to characterize the differential sensitivity of CRC cells to the growth inhibitory effects of EPA. The effect of CRISPR-Cas9 genetic deletion and pharmacological inhibition of COX-1 and COX-2 on the anti-cancer activity of EPA was determined using in vitro and in vivo models. Results Genetic ablation of both COX isoforms increased sensitivity of CT26 mouse CRC cells to growth inhibition by EPA in vitro and in vivo. The non-selective COX inhibitor aspirin and the selective COX-2 inhibitor celecoxib increased sensitivity of several human and mouse CRC cell lines to EPA in vitro. However, in a MC38 mouse CRC cell tumour model, with dosing that mirrored low-dose aspirin use in humans, thereby producing significant platelet COX-1 inhibition, there was ineffective intra-tumoral COX-2 inhibition by aspirin and no effect on EPA sensitivity of MC38 cell tumours. Conclusion Cyclooxygenase inhibition by non-steroidal anti-inflammatory drugs represents a therapeutic opportunity to augment the modest anti-CRC activity of EPA. However, intra-tumoral COX inhibition is likely to be critical for this drug-nutrient interaction and careful tissue pharmacodynamic profiling is required in subsequent pre-clinical and human studies

    Corrigendum to “Synovial volume vs synovial measurements from dynamic contrast enhanced MRI as measures of response in osteoarthritis” [Osteoarthritis Cartilage 24(8) (2016) 1392–1398](S106345841630005X)(10.1016/j.joca.2016.03.015)

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    © 2017 We have been notified by the authors that there was an error in the second sentence of the paragraph headed ‘Image analysis: segmentation’ on p. 1394 of the above article. The term interobserver should have been intraobserver. The correct sentence is as follows: Manual segmentation of the synovial tissue layer was performed on these sagittal post-contrast knee images by a single observer (intraobserver ICC = 0.94), who assessed baseline and follow-up visit MR images paired, but blinded to order. The authors would like to apologise for any inconvenience caused
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