Current research into brain barriers and the delivery of therapeutics for neurological diseases: a report on CNS barrier congress London, UK, 2017.

This is a report on the CNS barrier congress held in London, UK, March 22-23rd 2017 and sponsored by Kisaco Research Ltd. The two 1-day sessions were chaired by John Greenwood and Margareta Hammarlund-Udenaes, respectively, and each session ended with a discussion led by the chair. Speakers consisted of invited academic researchers studying the brain barriers in relation to neurological diseases and industry researchers studying new methods to deliver therapeutics to treat neurological diseases. We include here brief reports from the speakers

Potential impact of a maternal vaccine for RSV: a mathematical modelling study

Respiratory syncytial virus (RSV) is a major cause of respiratory morbidity and one of the main causes of hospitalisation in young children. While there is currently no licensed vaccine for RSV, a vaccine candidate for pregnant women is undergoing phase 3 trials. We developed a compartmental age-structured model for RSV transmission, validated using linked laboratory-confirmed RSV hospitalisation records for metropolitan Western Australia. We adapted the model to incorporate a maternal RSV vaccine, and estimated the expected reduction in RSV hospitalisations arising from such a program. The introduction of a vaccine was estimated to reduce RSV hospitalisations in Western Australia by 6-37% for 0-2month old children, and 30-46% for 3-5month old children, for a range of vaccine effectiveness levels. Our model shows that, provided a vaccine is demonstrated to extend protection against RSV disease beyond the first three months of life, a policy using a maternal RSV vaccine could be effective in reducing RSV hospitalisations in children up to six months of age, meeting the objective of a maternal vaccine in delaying an infant's first RSV infection to an age at which severe disease is less likely

Acupuncture Point Localization Varies Among Acupuncturists

Background: Studies assessing the point-specific effect of acupuncture or the characteristics of acupuncture points (APs) tend to yield inconclusive results. In order to identify a possible confounding factor, we aimed to examine the variability in AP localization by means of a survey. Material and Methods: Attendees of the 14th ICMART (International Council of Medical Acupuncture and Related Techniques) congress as well as DAGfA (German Medical Society of Acupuncture) lecturers and students were asked to locate and mark the APs LI 10 and TH 5 on a research assistant's arm. Identified points were transferred into a coordinate system, and the respective bivariate distribution function was calculated. Additionally, participants filled out a questionnaire about their acupuncture education and experience, the acupuncture style and point localization techniques used most frequently, and their estimation of the size of an AP. Results: The areas of the ellipses, theoretically containing 95% of AP localizations, varied between 44.49 and 5.18 cm(2). The largest distance between 2 identified points was 8.45 cm for LI 10 and 5.3 cm for TH 5. Apart from being trained at the same school, no other factor could be identified that determined the variability in AP localization. Conclusion: Our results indicate that congruity of AP localization among experienced acupuncturists might be low. Although there are some limitations to our results, this possible bias should be taken into account when conducting acupuncture trials and interpreting results of previous acupuncture studies

A consensus on the use of daylight photodynamic therapy in the UK

Background: Actinic keratoses (AKs) are a consequence of chronic exposure to ultraviolet radiation. Treatment of chronically photo-damaged skin and AKs is driven by risk of progression to squamous cell carcinoma, as well as for symptomatic relief. Conventional photodynamic therapy (c-PDT) is indicated when AKs are multiple or confluent and if patients respond poorly or are unable to tolerate other therapies. c-PDT is limited by the field size that can be treated in single sessions and can cause significant discomfort.Objective: Recent studies investigated daylight illumination to activate protoporphyrin IX and daylight-PDT (d-PDT) is now licensed in the UK for face and scalp AKs. A group of experts met to discuss application of d-PDT with methyl aminolevulinate (MAL) and develop a UK consensus statement, specific to UK weather conditions.Methods: The UK consensus recommendations were reached among eight experts, who reviewed recent studies on d-PDT, assessed UK meteorological data and discussed personal experiences of d-PDT for AKs.Results: Recommendations from these discussions provide guidance on d-PDT use, specifically regarding patient selection, therapeutic indications, when to treat, skin preparation, MAL application and daylight exposure for patients with AKs.Conclusions: This UK expert consensus provides practical guidance for UK application of d-PDT

Continuous, Semi-discrete, and Fully Discretized Navier-Stokes Equations

The Navier--Stokes equations are commonly used to model and to simulate flow phenomena. We introduce the basic equations and discuss the standard methods for the spatial and temporal discretization. We analyse the semi-discrete equations -- a semi-explicit nonlinear DAE -- in terms of the strangeness index and quantify the numerical difficulties in the fully discrete schemes, that are induced by the strangeness of the system. By analyzing the Kronecker index of the difference-algebraic equations, that represent commonly and successfully used time stepping schemes for the Navier--Stokes equations, we show that those time-integration schemes factually remove the strangeness. The theoretical considerations are backed and illustrated by numerical examples.Comment: 28 pages, 2 figure, code available under DOI: 10.5281/zenodo.998909, https://doi.org/10.5281/zenodo.99890

Development of a decision support tool to facilitate primary care management of patients with abnormal liver function tests without clinically apparent liver disease [HTA03/38/02]. Abnormal Liver Function Investigations Evaluation (ALFIE)

Liver function tests (LFTs) are routinely performed in primary care, and are often the gateway to further invasive and/or expensive investigations. Little is known of the consequences in people with an initial abnormal liver function (ALF) test in primary care and with no obvious liver disease. Further investigations may be dangerous for the patient and expensive for Health Services. The aims of this study are to determine the natural history of abnormalities in LFTs before overt liver disease presents in the population and identify those who require minimal further investigations with the potential for reduction in NHS costs

Patterns of democracy: Coalition governance and majoritarian modification in the United Kingdom, 2010–2015

The UK is often regarded as the archetype of Westminster democracy and as the empirical antithesis of the power-sharing coalitions of Western Europe. Yet, in recent years a different account has emerged that focuses on the subtler institutional dynamics which limit the executive. It is to this body of scholarship that this article responds, locating the recent chapter of coalition government within the wider context of the UK’s democratic evolution. To do so, the article draws Lijphart’s two-dimensional typology of democracies, developing a refined framework that enables systematic comparison over time. The article demonstrates that between over the course of the 2010-15 Parliament, the UK underwent another period of majoritarian modification, driven by factors including the long-term influence of the constitutional forces unleashed under Labour and the short-term impact of coalition management. The article makes several important contributions, salient in the UK and beyond. Theoretically, it offers a critical rejoinder to debates regarding the relationship between institutional design and democratic performance. Methodologically, it demonstrates that the tools of large-scale comparison can be effectively scaled-down to facilitate withincase analysis. Empirically, it provides a series of conclusions regarding the tenability of the UK’s extant democratic architecture under the weight of pressures to which it continues to be subject

P-rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments

Expression of the Rac-guanine nucleotide exchange factor (RacGEF), P-Rex1 is a key determinant of progression to metastasis in a number of human cancers. In accordance with this proposed role in cancer cell invasion and metastasis, we find that ectopic expression of P-Rex1 in an immortalised human fibroblast cell line is sufficient to drive multiple migratory and invasive phenotypes. The invasive phenotype is greatly enhanced by the presence of a gradient of serum or platelet-derived growth factor, and is dependent upon the expression of functional PDGF receptor β. Consistently, the invasiveness of WM852 melanoma cells, which endogenously express P-Rex1 and PDGFRβ, is opposed by siRNA of either of these proteins. Furthermore, the current model of P-Rex1 activation is advanced through demonstration of P-Rex1 and PDGFRβ as components of the same macromolecular complex. These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes

Morphological characterization of the blood cells in the endangered Sicilian endemic pond turtle,Emys trinacris(Testudines: Emydidae)

In this study, measurements of morphological parameters, sizes and frequencies of peripheral blood cells (erythrocytes, leukocytes, thrombocytes) on blood smear preparation devices stained with May-Grünwald stain were evaluated for both sexes in 20 Emys trinacris (Testudines: Emydidae) specimens. Erythrocytes were higher in male than in female specimens. The leukocyte of E. trinacris contains eosinophil, basophil, monocyte, heterophil and lymphocyte. The eosinophil was higher in males than in females whereas lymphocytes were higher in females than in males. The erythrocyte morphological parameters (EL [erythrocyte length], EW [erythrocyte width], L/W [length/width], ES [erythrocyte size]) were compared with the same data from Emys orbicularis s.l, and from species belonging to other chelonian genera. The erythrocyte size did not vary within the studied Palearctic Emys taxa, whereas it proved to differ from that observed in other chelonians

Dynamics of trimming the content of face representations for categorization in the brain

To understand visual cognition, it is imperative to determine when, how and with what information the human brain categorizes the visual input. Visual categorization consistently involves at least an early and a late stage: the occipito-temporal N170 event related potential related to stimulus encoding and the parietal P300 involved in perceptual decisions. Here we sought to understand how the brain globally transforms its representations of face categories from their early encoding to the later decision stage over the 400 ms time window encompassing the N170 and P300 brain events. We applied classification image techniques to the behavioral and electroencephalographic data of three observers who categorized seven facial expressions of emotion and report two main findings: (1) Over the 400 ms time course, processing of facial features initially spreads bilaterally across the left and right occipito-temporal regions to dynamically converge onto the centro-parietal region; (2) Concurrently, information processing gradually shifts from encoding common face features across all spatial scales (e.g. the eyes) to representing only the finer scales of the diagnostic features that are richer in useful information for behavior (e.g. the wide opened eyes in 'fear'; the detailed mouth in 'happy'). Our findings suggest that the brain refines its diagnostic representations of visual categories over the first 400 ms of processing by trimming a thorough encoding of features over the N170, to leave only the detailed information important for perceptual decisions over the P300