Calcium in the initiation, progression and as an effector of Alzheimer's disease pathology.

The cause(s) of sporadic Alzheimer's disease (sAD) are complex and currently poorly understood. They likely result from a combination of genetic, environmental, proteomic and lipidomic factors that crucially occur only in the aged brain. Age-related changes in calcium levels and dynamics have the potential to increase the production and accumulation of both amyloid-beta peptide (Abeta) and tau pathologies in the AD brain, although these two pathologies themselves can induce calcium dyshomeostasis, particularly at synaptic membranes. This review discuses the evidence for a role for calcium dyshomeostasis in the initiation of pathology, as well as the evidence for these pathologies themselves disrupting normal calcium homeostasis, which lead to synaptic and neuronal dysfunction, synaptotoxicity and neuronal loss, underlying the dementia associated with the disease

A tale of two cinnamons: A comparative review of the clinical evidence of Cinnamomum verum and C. cassia as diabetes interventions

Objective: This review investigates the effectiveness of two cinnamon species, Cinnamomum verum and C. cassia, in diabetes management; their impact on related health conditions and relevant parameters in healthy individuals and safety issues. Methods: PubMed, Cochrane Library, and ScienceDirect were searched from 2000 up to April 2018 for clinical trials using either C. verum or C. cassia in controlling blood glucose and other diabetes-related parameters and conditions. Results: A total of twenty-five studies (n=997) were included for reviewing clinical evidence. Among these trials, fifteen studies investigated the effects on type II diabetes mellitus (T2DM) patients (n=831), four investigated subjects with related clinical conditions (n=82), and six investigated healthy individuals (n=84). Nineteen studies used C. cassia and six used C. verum. Results suggested C. cassia helped manage diabetes at 3-6g, while the effectiveness of C. verum remained inconclusive. In addition, the chemical properties of C. cassia and C. verum differ considerably. Of note, C. cassia contains high levels of the potentially hepatotoxic constituent coumarin. A skin rash was the only adverse event reported. Conclusion: While evidence supports the therapeutic benefit of C. cassia, interchangeability of C. cassia and C. verum remains inconclusive. Further research is warranted to address the effectiveness and safety of these cinnamon species. Given the potential hepatotoxicity of C. cassia, RCTs that include liver function tests are required. Robust RCTs on C. verum are recommended to establish if its efficacy can match its safety profile

Measurements of a rotor flow in ground effect and visualization of the brown-out phenomenon

Quantitative and qualitative results of a series of experiments conducted on a rotor in ground effect at low forward speeds are presented. The velocity over a wide area of the ground effect wake was measured using Particle Image Velocimetry (PIV), and the evolution of the flow is described as the forward speed increases. Helicopter brown-out was simulated through a series of flow visualisation experiments. The technique involved sprinkling a fine powder on the ground below and ahead of the rotor. This helps to validate the experimental simulation of the brown-out phenomenon. Larger dust clouds were observed at lower advance ratio, and the dust cloud penetrated into the areas of the flow including those where vorticity levels were of low or negligible magnitude

Non-renormalisation Conditions in Type II String Theory and Maximal Supergravity

This paper considers general features of the derivative expansion of Feynman diagram contributions to the four-graviton scattering amplitude in eleven-dimensional supergravity compactified on a two-torus. These are translated into statements about interactions of the form D^2k R^4 in type II superstring theories, assuming the standard M-theory/string theory duality relationships, which provide powerful constraints on the effective interactions. In the ten-dimensional IIA limit we find that there can be no perturbative contributions beyond k string loops (for k>0). Furthermore, the genus h=k contributions are determined exactly by the one-loop eleven-dimensional supergravity amplitude for all values of k. A plausible interpretation of these observations is that the sum of h-loop Feynman diagrams of maximally extended supergravity is less divergent than might be expected and could be ultraviolet finite in dimensions d < 4 + 6/h -- the same bound as for N=4 Yang--Mills.Comment: 30 pages, 4 figures. v3 Some rewording, typos corrected and some references added. v4: Abstract rephrased. More typos corrected. Version to be publishe

Impacts of plug-in hybrid vehicles and combined heat and power technologies on electric and gas distribution network losses

Distribution network operators (DNOs) require strategies that can offset the tradeoffs new embedded technologies have on their assets. This paper employs modelling to show that through control device manipulation, gas and electric (G&E) network operators can influence savings in energy losses under the presence of plug-in hybrid vehicles (PHEVs) and combined heat and power technologies (CHPs). An integrated gas and electric optimal power flow (OPF) tool is introduced to undertake various case studies. The OPF tool evaluates the technical impacts experienced in the networks when DNOs apply a "plug and forget" operation strategy and then compares the results against a "loss minimisation" strategy. Results show the benefits in applying different strategies are more considerable in electric networks than in gas networks. The study corroborates that an integrated G&E analysis offers a fresh perspective for stakeholders in evaluating energy service networks performance under different operation strategies

SIMLA: Simulating laser-particle interactions via classical and quantum electrodynamics

We present the Fortran code SIMLA, which is designed for the study of charged particle dynamics in laser and other background fields. This can be done classically via the Landau-Lifshitz equation, or alternatively, via the simulation of photon emission events determined by strong-field quantum-electrodynamics amplitudes and implemented using Monte-Carlo type routines. Multiple laser fields can be included in the simulation and the propagation direction, beam shape (plane wave, focussed paraxial, constant crossed, or constant magnetic), and time envelope of each can be independently specified.Comment: Submitted to Comp. Phys. Comm. The associated computer program and corresponding manual will be made available on the CPC librar

Transverse spreading of electrons in high-intensity laser fields

We show that for collisions of electrons with a high-intensity laser, discrete photon emissions introduce a transverse beam spread which is distinct from that due to classical (or beam shape) effects. Via numerical simulations, we show that this quantum induced transverse momentum gain of the electron is manifest in collisions with a realistic laser pulse of intensity within reach of current technology, and we propose it as a measurable signature of strong-field quantum electrodynamics.Comment: 5 pages, 3 figures. Accepted for publication in Physical Review Letter

Identification of factors that support successful implementation of care bundles in the acute medical setting: a qualitative study

Background Clinical guidelines offer an accessible synthesis of the best evidence of effectiveness of interventions, providing recommendations and standards for clinical practice. Many guidelines are relevant to the diagnosis and management of the acutely unwell patient during the first 24–48 h of admission. Care bundles are comprised of a small number of evidence-based interventions that when implemented together aim to achieve better outcomes than when implemented individually. Care bundles that are explicitly developed from guidelines to provide a set of related evidence-based actions have been shown to improve the care of many conditions in emergency, acute and critical care settings. This study aimed to review the implementation of two distinct care bundles in the acute medical setting and identify the factors that supported successful implementation. Methods Two initiatives that had used a systematic approach to quality improvement to successfully implement care bundles within the acute medical setting were selected as case studies. Contemporaneous data generated during the initiatives included the review reports, review minutes and audio recordings of the review meetings at different time points. Data were subject to deductive analysis using three domains of the Consolidated Framework for Implementation Research to identify factors that were important in the implementation of the care bundles. Results Several factors were identified that directly influenced the implementation of the care bundles. Firstly, the availability of resources to support initiatives, which included training to develop quality improvement skills within the team and building capacity within the organisation more generally. Secondly, the perceived sustainability of changes by stakeholders influenced the embedding new care processes into existing clinical systems, maximising their chance of being sustained. Thirdly, senior leadership support was seen as critical not just in supporting implementation but also in sustaining longer-term changes brought about by the initiative. Lastly, practitioner incentives were identified as potential levers to engage junior doctors, a crucial part of the acute medical work force and essential to the initiatives, as there is currently little recognition or reward for involvement Conclusions The factors identified have been shown to be supportive in the successful implementation of care bundles as a mechanism for implementing clinical guidelines. Addressing these factors at a practitioner and organisational level, alongside the use of a systematic quality improvement approach, should increase the likelihood that care bundles will be implemented successfully to deliver evidence based changes in the acute medical setting