The Efficacy of Licensed-Indication Use of Donepezil and Memantine Monotherapies for Treating Behavioural and Psychological Symptoms of Dementia in Patients with Alzheimer's Disease: Systematic Review and Meta-Analysis

Background/Aims: Behavioural and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD) greatly increase caregiver burden. The abilities of donepezil and memantine to manage BPSD within their licensed indications in AD were compared. Methods: A systematic review, random effects meta-analysis and Bucher indirect comparison were conducted. Results: Six randomised controlled studies (4 donepezil and 2 memantine) reported use within the licensed indication and had Neuropsychiatric Inventory (NPI) data suitable for meta-analysis. BPSD showed significant improvement with donepezil compared with placebo [weighted mean difference (WMD) in NPI –3.51, 95% confidence interval (CI) –5.75, –1.27], whereas this was not the case for memantine (WMD –1.65, 95% CI –4.78, 1.49). WMD in NPI for donepezil versus memantine favoured donepezil but was not statistically significant (–1.86, 95% CI –5.71, 1.99; p = 0.34). Conclusion: Within its licensed indication, donepezil is efficacious for the management of BPSD in AD compared with placebo

Discrete cilia modelling with singularity distributions

We discuss in detail techniques for modelling flows due to finite and infinite arrays of beating cilia. An efficient technique, based on concepts from previous ‘singularity models’ is described, that is accurate in both near and far-fields. Cilia are modelled as curved slender ellipsoidal bodies by distributing Stokeslet and potential source dipole singularities along their centrelines, leading to an integral equation that can be solved using a simple and efficient discretisation. The computed velocity on the cilium surface is found to compare favourably with the boundary condition. We then present results for two topics of current interest in biology. 1) We present the first theoretical results showing the mechanism by which rotating embryonic nodal cilia produce a leftward flow by a ‘posterior tilt,’ and track particle motion in an array of three simulated nodal cilia. We find that, contrary to recent suggestions, there is no continuous layer of negative fluid transport close to the ciliated boundary. The mean leftward particle transport is found to be just over 1 μm/s, within experimentally measured ranges. We also discuss the accuracy of models that represent the action of cilia by steady rotlet arrays, in particular, confirming the importance of image systems in the boundary in establishing the far-field fluid transport. Future modelling may lead to understanding of the mechanisms by which morphogen gradients or mechanosensing cilia convert a directional flow to asymmetric gene expression. 2) We develop a more complex and detailed model of flow patterns in the periciliary layer of the airway surface liquid. Our results confirm that shear flow of the mucous layer drives a significant volume of periciliary liquid in the direction of mucus transport even during the recovery stroke of the cilia. Finally, we discuss the advantages and disadvantages of the singularity technique and outline future theoretical and experimental developments required to apply this technique to various other biological problems, particularly in the reproductive system

A combined beta-beam and electron capture neutrino experiment

The next generation of long baseline neutrino experiments will aim at determining the value of the unknown mixing angle, theta_{13}, the type of neutrino mass hierarchy and the presence of CP-violation in the lepton sector. Beta-beams and electron capture experiments have been studied as viable candidates for long baseline experiments. They use a very clean electron neutrino beam from the beta-decays or electron capture decays of boosted ions. In the present article we consider an hybrid setup which combines a beta-beam with an electron capture beam by using boosted Ytterbium ions. We study the sensitivity to the CP-violating phase delta and the theta_{13} angle, the CP-discovery potential and the reach to determine the type of neutrino mass hierarchy for this type of long baseline experiment. The analysis is performed for different neutrino beam energies and baselines. Finally, we also discuss how the results would change if a better knowledge of some of the assumed parameters was achieved by the time this experiment could take place.Comment: 35 pp, 11 fig

Media and conflict: an assessment of the evidence

This article assesses the evidence used in arguments for the role of the media in conflict and post-conflict situations. It focuses on two broad areas within the literature. First, it examines literature on the contribution of media in war to peace transitions, including an assessment of the evidence used to show how the media may contribute to violent conflict and how they may provoke, or hinder, post-conflict reconstruction. Second, it assesses evidence used in arguments for the role new Information and Communication Technologies (ICTs) such as the Internet and mobile phones may have in liberation or oppression in developing country contexts. Through reviewing some of the most significant papers that were systematically selected in a literature review on media and conflict, our findings suggest that there are serious gaps in the evidence and the majority of evidence is located in the 'grey literature' or policy documents. The article concludes by suggesting future research agendas to address these gaps