Desmopressin for reversal of Antiplatelet drugs in Stroke due to Haemorrhage (DASH): protocol for a phase II double-blind randomised controlled feasibility trial

IntroductionIntracerebral haemorrhage can be devastating and is a common cause of death and disability worldwide. Pre-intracerebral haemorrhage antiplatelet drug use is associated with a 27% relative increase in one-month case fatality compared to patients not using antithrombotic drugs. We aim to assess the feasibility of conducting a randomised controlled testing the safety and efficacy of desmopressin for patients with antiplatelet-associated intracerebral haemorrhage.Methods and AnalysisWe aim to include 50 patients within 24 hours of spontaneous intracerebral haemorrhage onset, associated with oral antiplatelet drug(s) use in at least the preceding seven days. Patients will be randomised (1:1) to receive intravenous desmopressin 20μg in 50 mls sodium chloride 0.9% infused over 20 minutes or matching placebo. We will mask participants, relatives and outcome assessors to treatment allocation. Feasibility outcomes include proportion of patients approached being randomised, number of patients receiving allocated treatment, rate of recruitment, and adherence to treatment and follow up. Secondary outcomes include change in intracerebral haemorrhage volume at 24 hours; hyponatraemia at 24 hours, length of hospital stay, discharge destination, early death less than 28 days, death or dependency at day 90, death up to day 90, serious adverse events (including thromboembolic events) up to day 90; disability (Barthel index, day 90), quality of life (EuroQol 5D (EQ-5D], day 90), cognition (telephone mini-mental state examination day 90), and health economic assessment (EQ-5D).Ethics and disseminationThe DASH trial received ethical approval from the East Midlands - Nottingham 2 research ethics committee (18/EM/0184). The DASH trial is funded by NIHR RfPB grant: PB-PG-0816-20011. Trial results will be published in a peer reviewed academic journal and disseminated through academic conferences and through patient stroke support groups. Reporting will be in compliance with CONSORT recommendations

Home interventions and light therapy for treatment of vitiligo (HI-Light Vitiligo Trial): study protocol for a randomized controlled trial

Vitiligo is a condition resulting in white patches on the skin. People with vitiligo can suffer from low self-esteem, psychological disturbance and diminished quality of life. Vitiligo is often poorly managed, partly due to lack of high quality evidence to inform clinical care. We describe here a large, independent, randomised controlled trial (RCT) assessing the comparative effectiveness of potent topical corticosteroid, home-based hand-held narrowband ultraviolet B-light (NB-UVB) or combination of the two, for the management of vitiligo. Methods and Analysis The HI-Light Vitiligo Trial is a multi-centre, three-arm, parallel group, pragmatic, placebo-controlled RCT. 516 adults and children with actively spreading, but limited, vitiligo are randomised (1:1:1) to one of three groups: mometasone furoate 0.1% ointment plus dummy NB-UVB light, vehicle ointment plus NB-UVB light, or mometasone furoate 0.1% ointment plus NB-UVB light. Treatment of up to three patches of vitiligo is continued for up to 9 months with clinic visits at baseline, 3, 6 and 9 months and four post treatment questionnaires. The HI-Light Vitiligo Trial assesses outcomes included in the vitiligo core outcome set and places emphasis on participants’ views of treatment success. The primary outcome is proportion of participants achieving treatment success (patient-rated Vitiligo Noticeability Scale) for a target patch of vitiligo at 9 months with further independent blinded assessment using digital images of the target lesion before and after treatment. Secondary outcomes include time to onset of treatment response, treatment success by body region, percentage repigmentation, quality of life, time-burden of treatment, maintenance of response, safety, and within-trial cost effectiveness. Ethics and Dissemination Approvals were granted by East Midlands–Derby Research Ethics Committee (14/EM/1173) and the MHRA (EudraCT 2014-003473-42). The trial was registered 8th January 2015 ISRCTN (17160087). Results will be published in full as open access in the NIHR Journal library and elsewhere

The Sudbury Neutrino Observatory

The Sudbury Neutrino Observatory is a second generation water Cherenkov detector designed to determine whether the currently observed solar neutrino deficit is a result of neutrino oscillations. The detector is unique in its use of D2O as a detection medium, permitting it to make a solar model-independent test of the neutrino oscillation hypothesis by comparison of the charged- and neutral-current interaction rates. In this paper the physical properties, construction, and preliminary operation of the Sudbury Neutrino Observatory are described. Data and predicted operating parameters are provided whenever possible.Comment: 58 pages, 12 figures, submitted to Nucl. Inst. Meth. Uses elsart and epsf style files. For additional information about SNO see http://www.sno.phy.queensu.ca . This version has some new reference

Physically Similar Systems - A History of the Concept

PreprintThe concept of similar systems arose in physics, and appears to have originated with Newton in the seventeenth century. This chapter provides a critical history of the concept of physically similar systems, the twentieth century concept into which it developed. The concept was used in the nineteenth century in various fields of engineering (Froude, Bertrand, Reech), theoretical physics (van der Waals, Onnes, Lorentz, Maxwell, Boltzmann) and theoretical and experimental hydrodynamics (Stokes, Helmholtz, Reynolds, Prandtl, Rayleigh). In 1914, it was articulated in terms of ideas developed in the eighteenth century and used in nineteenth century mathematics and mechanics: equations, functions and dimensional analysis. The terminology physically similar systems was proposed for this new characterization of similar systems by the physicist Edgar Buckingham. Related work by Vaschy, Bertrand, and Riabouchinsky had appeared by then. The concept is very powerful in studying physical phenomena both theoretically and experimentally. As it is not currently part of the core curricula of STEM disciplines or philosophy of science, it is not as well known as it ought to be

Integrating historical, geomorphological and sedimentological insights to reconstruct past floods: Insights from Kea Point, Mt. Cook Village, Aotearoa New Zealand

Flood reconstruction is essential for establishing magnitude-frequency relationships and assessments of contemporary geohazards and risks. Traditionally, flood reconstructions rely upon the analysis of evidence acquired from a single discipline. This lack of integration limits the insights into a flood's source, pathway, and receptors (i.e. impacts). Here, our aim is to test the integration of qualitative historical documentary material with quantitative geomorphological and sedimentological evidence to reconstruct glacial lake outburst floods (GLOFs) in 1913 at Kea Point, Mount Cook National Park, Aotearoa New Zealand. Written documentary records show that, following heavy rainfall, GLOF events occurred in January and March, after the temporary impoundment of water between the glacier surface and lateral moraine. Peak flood discharge was estimated from slope-area and exposed boulder measurements as 316–1077 m3s−1 and 496–1622 m3s−1 respectively. Sedimentological information, combined with geomorphic mapping, a DEM derived from Structure from Motion (SfM) photogrammetry, and satellite imagery was used to describe the overall physical impact of the GLOF. Information from written documentary records, however, enabled a more detailed reconstruction of the timeline of the two floods and their impacts proximate to the original ‘Hermitage Hotel’, which was subsequently relocated. Our integrated approach exemplifies the informative level of multi-faceted detail that can be retrieved for historical flood events. We propose a framework for future studies that seek to reconstruct flood events and their source, pathway and receptors through combining evidence from historical documents/artefacts, sedimentological/geomorphological data, and integration with environmental monitoring/modelling outputs

No impact of malaria infection or immunisation on the expression of the immune GTPase GIMAP1 at the protein or mRNA levels (Article no. 53)

GIMAP (GTPase of the immunity-associated protein family) proteins are a family of putative GTPases believed to be regulators of cell death in lymphomyeloid cells. GIMAP1 was the first reported member of this gene family, identified as a gene up-regulated at the RNA level in the spleens of mice infected with the malarial parasite, Plasmodium chabaudi. Methods A monoclonal antibody against mouse GIMAP1 was developed and was used to analyse the expression of the endogenous protein in tissues of normal mice and in defined sub-populations of cells prepared from lymphoid tissues using flow cytometry. It was also used to assess the expression of GIMAP1 protein after infection and/or immunization of mice with P. chabaudi. Real-time PCR analysis was employed to measure the expression of GIMAP1 for comparison with the protein level analysis. Results GIMAP1 protein expression was detected in all lineages of lymphocytes (T, B, NK), in F4/80+ splenic macrophages and in some lymphoid cell lines. Additional evidence is presented suggesting that the strong expression by mature B cells of GIMAP1 and other GIMAP genes and proteins seen in mice may be a species-dependent characteristic. Unexpectedly, no increase was found in the expression of GIMAP1 in P. chabaudi infected mice at either the mRNA or protein level, and this remained so despite applying a number of variations to the protocol. Conclusion The model of up-regulation of GIMAP1 in response to infection/immunization with P. chabaudi is not a robustly reproducible experimental system. The GIMAP1 protein is widely expressed in lymphoid cells, with an interesting increase in expression in the later stages of B cell development. Alternative approaches will be required to define the functional role of this GTPase in immune cells

The role of incentive mechanisms in promoting forest restoration

Forest restoration has been proposed as a scalable nature-based solution to achieve global environmental and socio-economic outcomes and is central to many policy initiatives, such as the Bonn Challenge. Restored forests contain appreciable biodiversity, improve habitat connectivity and sequester carbon. Incentive mechanisms (e.g. payments for ecosystem services and allocation of management rights) have been a focus of forest restoration efforts for decades. Yet, there is still little understanding of their role in promoting restoration success. We conducted a systematic literature review to investigate how incentive mechanisms are used to promote forest restoration, outcomes, and the biophysical and socio-economic factors that influence implementation and program success. We found that socio-economic factors, such as governance, monitoring systems and the experience and beliefs of participants, dominate whether or not an incentive mechanism is successful. We found that approximately half of the studies report both positive ecological and socio-economic outcomes. However, reported adverse outcomes were more commonly socio-economic than ecological. Our results reveal that achieving forest restoration at a sufficient scale to meet international commitments will require stronger assessment and management of socio-economic factors that enable or constrain the success of incentive mechanisms. This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’.Anazelia M. Tedesco, Pedro H. S. Brancalion, Michelle L. Hak Hepburn, Khalil Walji, Kerrie A. Wilson, Hugh P. Possingham, Angela J. Dean, Nick Nugent, Katerina Elias-Trostmann, Katharina-Victoria Perez-Hammerle, and Jonathan R. Rhode