1,108 research outputs found

    Sequential Implementation of Monte Carlo Tests with Uniformly Bounded Resampling Risk

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    This paper introduces an open-ended sequential algorithm for computing the p-value of a test using Monte Carlo simulation. It guarantees that the resampling risk, the probability of a different decision than the one based on the theoretical p-value, is uniformly bounded by an arbitrarily small constant. Previously suggested sequential or non-sequential algorithms, using a bounded sample size, do not have this property. Although the algorithm is open-ended, the expected number of steps is finite, except when the p-value is on the threshold between rejecting and not rejecting. The algorithm is suitable as standard for implementing tests that require (re-)sampling. It can also be used in other situations: to check whether a test is conservative, iteratively to implement double bootstrap tests, and to determine the sample size required for a certain power.Comment: Major Revision 15 pages, 4 figure

    Photoredox catalysis under shear using thin film vortex microfluidics

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    Open Access Article. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.A microfluidic vortex fluidic device (VFD) operating in either confined or continuous mode is effective in high yielding photoredox reactions involving Rose Bengal, with short reaction times. This processing can be translated to multi-components reactions, also with significantly reduced processing times relative to batch processing and channel microfluidic processing, with comparable or improved yields

    ‘Our voice started off as a whisper and now it is a great big roar’ : The Salford Dementia Associate Panel as a model of involvement in research activities

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    This paper presents the work of the ‘Salford Dementia Associate Panel’, based at the Salford Institute for Dementia, Salford University (UK). We discuss the roles of the Dementia Associates, in particular around the areas of engagement and research. The panel is made up of people living with dementia, and current and former care partners. It highlights the development of this group over a four-year period and demonstrates over time how the role of a Dementia Associate member has evolved. The panel is involved in research, education and public engagement activities conducted by staff and students within the Institute. The motivations for becoming involved are clearly articulated and demonstrate how the personal backgrounds of individuals have driven the collective involvement and desire to bring about change. The benefits and challenges associated with working as part of a panel are discussed. We conclude by bringing together our experiences as a set of suggestions for others who may wish to create a similar forum to promote the involvement of people living with dementia and former and current care partners

    Biodesalination: an emerging technology for targeted removal of Na+and Cl−from seawater by cyanobacteria

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    Although desalination by membrane processes is a possible solution to the problem of freshwater supply, related cost and energy demands prohibit its use on a global scale. Hence, there is an emerging necessity for alternative, energy and cost-efficient methods for water desalination. Cyanobacteria are oxygen-producing, photosynthetic bacteria that actively grow in vast blooms both in fresh and seawater bodies. Moreover, cyanobacteria can grow with minimal nutrient requirements and under natural sunlight. Taking these observations together, a consortium of five British Universities was formed to test the principle of using cyanobacteria as ion exchangers, for the specific removal of Na+ and Cl− from seawater. This project consisted of the isolation and characterisation of candidate strains, with central focus on their potential to be osmotically and ionically adaptable. The selection panel resulted in the identification of two Euryhaline strains, one of freshwater (Synechocystis sp. Strain PCC 6803) and one of marine origin (Synechococcus sp. Strain PCC 7002) (Robert Gordon University, Aberdeen). Other work packages were as follows. Genetic manipulations potentially allowed for the expression of a light-driven, Cl−-selective pump in both strains, therefore, enhancing the bioaccumulation of specific ions within the cell (University of Glasgow). Characterisation of surface properties under different salinities (University of Sheffield), ensured that cell–liquid separation efficiency would be maximised post-treatment, as well as monitoring the secretion of mucopolysaccharides in the medium during cell growth. Work at Newcastle University is focused on the social acceptance of this scenario, together with an assessment of the potential risks through the generation and application of a Hazard Analysis and Critical Control Points plan. Finally, researchers in Imperial College (London) designed the process, from biomass production to water treatment and generation of a model photobioreactor. This multimodal approach has produced promising first results, and further optimisation is expected to result in mass scaling of this process

    Brain Neprilysin Activity and Susceptibility to Transgene-Induced Alzheimer Amyloids

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    Neprilysin (NEP) is a zinc metalloproteinase that degrades enkephalins, endothelins, and the Alzheimer’s disease amyloid ß (Aß) peptides. NEP-deficient mice possess increased levels of brain Aß1-40 and Aß1-42. The objective of this study was to determine whether tissue NEP specific activity differs according to age and/or across mouse strains, especially those strains predisposed toward formation of Aß-amyloid plaques following overexpression of the human Alzheimer amyloid precursor protein (APP). The C57Bl/6J mouse strain appears to be relatively susceptible to cerebral amyloidosis, whereas the Swiss Webster (SW) strain appears more resistant. We investigated whether NEP specific activity in brain and kidney homogenates from SW and C57 mice of 6, 40, and 80 weeks old varied according to mouse strain, age, and gender. Among the variables tested, NEP specific activity varied most dramatically across mouse strain, with the kidney and brain of SW mice displaying the highest activities. Aging was associated with a reduction in brain NEP specific activity in both trains. Gender-specific differences were identified in kidney but not in brain. We conclude that aging- and strain-dependent ifferences in NEP specific activity may play a role in the differential susceptibility of some mouse strains for developing cerebral amyloidosis following human APP overexpression

    Including Aortic Valve Morphology in Computational Fluid Dynamics Simulations: Initial Findings and Application to Aortic Coarctation

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    Computational fluid dynamics (CFD) simulations quantifying thoracic aortic flow patterns have not included disturbances from the aortic valve (AoV). 80% of patients with aortic coarctation (CoA) have a bicuspid aortic valve (BAV) which may cause adverse flow patterns contributing to morbidity. Our objectives were to develop a method to account for the AoV in CFD simulations, and quantify its impact on local hemodynamics. The method developed facilitates segmentation of the AoV, spatiotemporal interpolation of segments, and anatomic positioning of segments at the CFD model inlet. The AoV was included in CFD model examples of a normal (tricuspid AoV) and a post-surgical CoA patient (BAV). Velocity, turbulent kinetic energy (TKE), time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) results were compared to equivalent simulations using a plug inlet profile. The plug inlet greatly underestimated TKE for both examples. TAWSS differences extended throughout the thoracic aorta for the CoA BAV, but were limited to the arch for the normal example. OSI differences existed mainly in the ascending aorta for both cases. The impact of AoV can now be included with CFD simulations to identify regions of deleterious hemodynamics thereby advancing simulations of the thoracic aorta one step closer to reality

    Treating anxiety and depression in older adults: Randomised controlled trial comparing guided V. Self-guided internet-delivered cognitive-behavioural therapy

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    © 2016 The Royal College of Psychiatrists. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. Background Symptoms of anxiety and depression are prevalent in older adults. Aims To compare clinician-guided and self-guided versions of a transdiagnostic internet-delivered cognitive-behavioural therapy (iCBT) intervention for adults aged 60 years and above. Method Adults (n=433) with symptoms of anxiety and depression were randomly allocated to: (1) clinician-guided treatment (n=153); (2) initial clinician interview followed by self-guided treatment (n=140); or (3) self-guided treatment without interview (n=140). Results Large reductions (d ≥1.00) in symptoms of depression and anxiety were observed across groups, and sustained at follow-up. No differences were observed in clinical outcomes or satisfaction ratings. Age did not affect outcomes. Conclusions Carefully developed iCBT interventions may significantly reduce symptoms of anxiety and depression in older adults when delivered in either clinician-guided or self-guided formats
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