4,009 research outputs found

    Surface transfer doped diamond diodes with metal oxide passivation and field-plate

    Get PDF
    Surface transfer-doping, involving hydrogen terminated diamond surfaces, has been an effective method for producing diamond devices for some years but suffered from poor device longevity and reproducibility. The emergence of metal oxides as an encapsulant has begun to change this situation. Here, HfO2 encapsulated surface transfer doped diamond Schottky diodes with stable device characteristics have been demonstrated. Ideality factor and Schottky barrier heights of the devices did not vary considerably across extended periods of use (up to 39 days). The devices showed excellent blocking capabilities, demonstrating no catastrophic breakdown under the maximum field applied and only a slight increase in leakage current at the reverse bias and field strength of 200 V and 0.167 MV cm−1 , respectively. Indeed, a large rectification ratio of up to 108 and a very low leakage current of ≈10−9 A cm−1 were maintained at this reverse bias (200 V). Furthermore, multiple devices were compared across a single substrate, something rarely reported previously for surface transfer doped diamond diodes. Leakage currents and rectification ratios were similar for all of the devices. The authors are grateful to the UKs Engineering and Physical Sciences Research Council (EPSRC) and BAE Systems Marine Ltd. for the award of a “Cooperative Awards in Science and Engineering (CASE)” Ph.D. Studentship for R.J.W. and to EPSRC for the award of related research funding (No. EP/H020055/1). A.C.P.-T. and R.B.J. also acknowledge invaluable assistance, both financial and in the form of international collaborations, from the European Commission Horizon 2020 Project “GREENDIAMOND” (H2020 Large Project under Grant No. SEP-210184415). Lambda Photometrics Ltd. and Everbeing International Corporation are gratefully acknowledged for use of a Everbeing EB-6 DC probe station. Finally, the LCN Cleanroom is acknowledged for the invaluable assistance of technicians and for the use of the ALD, evaporation, and photo-lithography tools

    A distinct plasmablast and naive B-cell phenotype in primary immune thrombocytopenia

    Get PDF
    Obtained from the Haematologica Journal website http://www.haematologica.org/content/101/6/698.full.pdf+html Material published in Haematologica is covered by copyright. All rights reserved to Ferrata Storti Foundation. Copies of articles are allowed for personal or internal use. A permission in writing by the publisher is requested for any other use.Primary funding for this study was from GSK. SMF was funded by a Translational Medicine and Therapeutics PhD studentship jointly funded by the Wellcome Trust and GSK. The UK ITP Registry (www.ukitpregistry.com) is supported through unrestricted educational grants from GSK and Amgen

    Coherent motion of stereocilia assures the concerted gating of hair-cell transduction channels

    Full text link
    The hair cell's mechanoreceptive organelle, the hair bundle, is highly sensitive because its transduction channels open over a very narrow range of displacements. The synchronous gating of transduction channels also underlies the active hair-bundle motility that amplifies and tunes responsiveness. The extent to which the gating of independent transduction channels is coordinated depends on how tightly individual stereocilia are constrained to move as a unit. Using dual-beam interferometry in the bullfrog's sacculus, we found that thermal movements of stereocilia located as far apart as a bundle's opposite edges display high coherence and negligible phase lag. Because the mechanical degrees of freedom of stereocilia are strongly constrained, a force applied anywhere in the hair bundle deflects the structure as a unit. This feature assures the concerted gating of transduction channels that maximizes the sensitivity of mechanoelectrical transduction and enhances the hair bundle's capacity to amplify its inputs.Comment: 24 pages, including 6 figures, published in 200

    Ageing memory and glassiness of a driven vortex system

    Full text link
    Many systems in nature, glasses, interfaces and fractures being some examples, cannot equilibrate with their environment, which gives rise to novel and surprising behaviour such as memory effects, ageing and nonlinear dynamics. Unlike their equilibrated counterparts, the dynamics of out-of- equilibrium systems is generally too complex to be captured by simple macroscopic laws. Here we investigate a system that straddles the boundary between glass and crystal: a Bragg glass formed by vortices in a superconductor. We find that the response to an applied force evolves according to a stretched exponential, with the exponent reflecting the deviation from equilibrium. After the force is removed, the system ages with time and its subsequent response time scales linearly with its age (simple ageing), meaning that older systems are slower than younger ones. We show that simple ageing can occur naturally in the presence of sufficient quenched disorder. Moreover, the hierarchical distribution of timescales, arising when chunks of loose vortices cannot move before trapped ones become dislodged, leads to a stretched-exponential response.Comment: 16 pages, 5 figure

    Ipl1/aurora kinase suppresses S-CDK-driven spindle formation during prophase I to ensure chromosome integrity during meiosis

    Get PDF
    Cells coordinate spindle formation with DNA repair and morphological modifications to chromosomes prior to their segregation to prevent cell division with damaged chromosomes. Here we uncover a novel and unexpected role for Aurora kinase in preventing the formation of spindles by Clb5-CDK (S-CDK) during meiotic prophase I and when the DDR is active in budding yeast. This is critical since S-CDK is essential for replication during premeiotic S-phase as well as double-strand break induction that facilitates meiotic recombination and, ultimately, chromosome segregation. Furthermore, we find that depletion of Cdc5 polo kinase activity delays spindle formation in DDR-arrested cells and that ectopic expression of Cdc5 in prophase I enhances spindle formation, when Ipl1 is depleted. Our findings establish a new paradigm for Aurora kinase function in both negative and positive regulation of spindle dynamics

    Study protocol: evaluation of a parenting and stress management programme: a randomised controlled trial of Triple P discussion groups and stress control

    Get PDF
    <br>Background: Children displaying psychosocial problems are at an increased risk of negative developmental outcomes. Parenting practices are closely linked with child development and behaviour, and parenting programmes have been recommended in the treatment of child psychosocial problems. However, parental mental health also needs to be addressed when delivering parenting programmes as it is linked with parenting practices, child outcomes, and treatment outcomes of parenting programmes. This paper describes the protocol of a study examining the effects of a combined intervention of a parenting programme and a cognitive behavioural intervention for mental health problems.</br> <br>Methods: The effects of a combined intervention of Triple P Discussion Groups and Stress Control will be examined using a randomised controlled trial design. Parents with a child aged 3?8?years will be recruited to take part in the study. After obtaining informed consent and pre-intervention measures, participants will be randomly assigned to either an intervention or a waitlist condition. The two primary outcomes for this study are change in dysfunctional/ineffective parenting practices and change in symptoms of depression, anxiety, and stress. Secondary outcomes are child behaviour problems, parenting experiences, parental self-efficacy, family relationships, and positive parental mental health. Demographic information, participant satisfaction with the intervention, and treatment fidelity data will also be collected. Data will be collected at pre-intervention, mid-intervention, post-intervention, and 3-month follow-up.</br> <br>Discussion: The aim of this paper is to describe the study protocol of a randomised controlled trial evaluating the effects of a combined intervention of Triple P Discussion Groups and Stress Control in comparison to a waitlist condition. This study is important because it will provide evidence about the effects of this combined intervention for parents with 3?8?year old children. The results of the study could be used to inform policy about parenting support and support for parents with mental health problems. Trial registration ClinicalTrial.gov: NCT01777724, UTN: U1111-1137-1053.</br&gt

    Immunosuppressive treatment for proliferative lupus nephritis

    Get PDF
    Background Cyclophosphamide, in combination with corticosteroids, has been first-line treatment for inducing disease remission for proliferative lupus nephritis, reducing death at five years from over 50% in the 1950s and 1960s to less than 10% in recent years. Several treatment strategies designed to improve remission rates and minimise toxicity have become available. Treatments, including mycophenolate mofetil (MMF) and calcineurin inhibitors, alone and in combination, may have equivalent or improved rates of remission, lower toxicity (less alopecia and ovarian failure) and uncertain effects on death, end-stage kidney disease (ESKD) and infection. This is an update of a Cochrane review first published in 2004 and updated in 2012. Objectives Our objective was to assess the evidence and evaluate the benefits and harms of different immunosuppressive treatments in people with biopsy-proven lupus nephritis. The following questions relating to management of proliferative lupus nephritis were addressed: 1) Are new immunosuppressive agents superior to or as effective as cyclophosphamide plus corticosteroids? 2) Which agents, dosages, routes of administration and duration of therapy should be used? 3) Which toxicities occur with the different treatment regimens? Search methods We searched the Cochrane Kidney and Transplant Specialised Register up to 2 March 2018 with support from the Cochrane Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria Randomised controlled trials (RCTs) and quasi-RCTs comparing any immunosuppressive treatment for biopsy-proven class III, IV, V+III and V+VI lupus nephritis in adult or paediatric patients were included. Data collection and analysis Data were abstracted and the risks of bias were assessed independently by two authors. Dichotomous outcomes were calculated as risk ratio (RR) and measures on continuous scales calculated as mean differences (MD) with 95% confidence intervals (CI). The primary outcomes were death (all causes) and complete disease remission for induction therapy and disease relapse for maintenance therapy. Evidence certainty was determined using GRADE. Main results In this review update, 26 new studies were identified, to include 74 studies involving 5175 participants overall. Twenty-nine studies included children under the age of 18 years with lupus nephritis, however only two studies exclusively examined the treatment of lupus nephritis in patients less than 18 years of age. Induction therapy Sixty-seven studies (4791 participants; median 12 months duration (range 2.5 to 48 months)) reported induction therapy. The effects of all treatment strategies on death (all causes) and ESKD were uncertain (very low certainty evidence) as this outcome occurred very infrequently. Compared with intravenous (IV) cyclophosphamide, MMF may have increased complete disease remission (RR 1.17, 95% CI 0.97 to 1.42; low certainty evidence), although the range of effects includes the possibility of little or no difference. Compared to IV cyclophosphamide, MMF is probably associated with decreased alopecia (RR 0.29, 95% CI 0.19 to 0.46; 170 less (129 less to 194 less) per 1000 people) (moderate certainty evidence), increased diarrhoea (RR 2.42, 95% CI 1.64 to 3.58; 142 more (64 more to 257 more) per 1000 people) (moderate certainty evidence) and may have made little or no difference to major infection (RR 1.02, 95% CI 0.67 to 1.54; 2 less (38 less to 62 more) per 1000 people) (low certainty evidence). It is uncertain ifMMF decreased ovarian failure compared to IV cyclophosphamide because the certainty of the evidence was very low (RR 0.36, 95% CI 0.06 to 2.18; 26 less (39 less to 49 more) per 1000 people). Studies were not generally designed to measure ESKD. MMF combined with tacrolimus may have increased complete disease remission (RR 2.38, 95% CI 1.07 to 5.30; 336 more (17 to 1048 more) per 1000 people (low certainty evidence) compared with IV cyclophosphamide, however the effects on alopecia, diarrhoea, ovarian failure, and major infection remain uncertain. Compared to standard of care, the effects of biologics on most outcomes were uncertain because of low to very low certainty of evidence. Maintenance therapy Nine studies (767 participants; median 30 months duration (range 6 to 63 months)) reported maintenance therapy. In maintenance therapy, disease relapse is probably increased with azathioprine compared with MMF (RR 1.75, 95% CI 1.20 to 2.55; 114 more (30 to 236 more) per 1000 people (moderate certainty evidence).Multiple other interventions were compared as maintenance therapy, but patient-outcome data were sparse leading to imprecise estimates. Authors’ conclusions In this review update, studies assessing treatment for proliferative lupus nephritis were not designed to assess death (all causes) or ESKD. MMF may lead to increased complete disease remission compared with IV cyclophosphamide, with an acceptable adverse event profile, although evidence certainty was low and included the possibility of no difference. Calcineurin combined with lower dose MMF may improve induction of disease remission compared with IV cyclophosphamide, but the comparative safety profile of these therapies is uncertain. Azathioprine may increase disease relapse as maintenance therapy compared with MMF.Internal support - Cochrane Kidney and Transplant, Australia. External support - Cochrane Review Support Programme 2017, UK

    Assessing the outcomes of participatory research: protocol for identifying, selecting, appraising and synthesizing the literature for realist review

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Participatory Research (PR) entails the co-governance of research by academic researchers and end-users. End-users are those who are affected by issues under study (<it>e.g.</it>, community groups or populations affected by illness), or those positioned to act on the knowledge generated by research (<it>e.g.</it>, clinicians, community leaders, health managers, patients, and policy makers). Systematic reviews assessing the generalizable benefits of PR must address: the diversity of research topics, methods, and intervention designs that involve a PR approach; varying degrees of end-user involvement in research co-governance, both within and between projects; and the complexity of outcomes arising from long-term partnerships.</p> <p>Methods</p> <p>We addressed the above mentioned challenges by adapting realist review methodology to PR assessment, specifically by developing inductively-driven identification, selection, appraisal, and synthesis procedures. This approach allowed us to address the non-uniformity and complexity of the PR literature. Each stage of the review involved two independent reviewers and followed a reproducible, systematic coding and retention procedure. Retained studies were completed participatory health interventions, demonstrated high levels of participation by non-academic stakeholders (<it>i.e.</it>, excluding studies in which end-users were not involved in co-governing throughout the stages of research) and contained detailed descriptions of the participatory process and context. Retained sets are being mapped and analyzed using realist review methods.</p> <p>Results</p> <p>The librarian-guided search string yielded 7,167 citations. A total of 594 citations were retained after the identification process. Eighty-three papers remained after selection. Principle Investigators (PIs) were contacted to solicit all companion papers. Twenty-three sets of papers (23 PR studies), comprising 276 publications, passed appraisal and are being synthesized using realist review methods.</p> <p>Discussion</p> <p>The systematic and stage-based procedure addressed challenges to PR assessment and generated our robust understanding of complex and heterogeneous PR practices. To date, realist reviews have focussed on evaluations of relatively uniform interventions. In contrast our PR search yielded a wide diversity of partnerships and research topics. We therefore developed tools to achieve conceptual clarity on the PR field, as a beneficial precursor to our theoretically-driven synthesis using realist methods. Findings from the ongoing review will be provided in forthcoming publications.</p
    corecore