European Union directive 2014/85/EU on driver licensing in obstructive sleep apnoea:early experiences with its application in the UK

OSA patients’ risk of RTA should be assessed using detailed driving history with specific focus on “red flags” http://ow.ly/mxPi305isn

Clinical audit of subjects with snoring & sleep apnoea/hypopnoea syndrome fitted with mandibular repositioning splint

SummarySnoring and obstructive sleep apnoea/hypopnoea syndrome (OSAHS) are often treated with mandibular repositioning splints (MRS), but the efficacy and satisfaction of them has not been comprehensively addressed. A survey on the use of and satisfaction with MRS was posted to 177 patients referred by a hospital orthodontic department for custom-fitting of a MRS. Data were analysed using non-parametric techniques. The response rate was 81% (n=144). Responders (30F, 114M) had mean (SD) age of 51 (11) years, apnoea+hypopnoea index (AHI) of 24 (21) per hr and Epworth Score of 10 (5) at diagnosis, and had been supplied with their MRS a median 7 (IQR 5–11) months previously. Fifty of the 144 patients (35%) had been offered continuous positive airway pressure (CPAP) treatment but had declined or abandoned this. Self-reported MRS use was 5 (2) h/night, with 74 of the 144 patients (51%) continuing to use MRS at least occasionally at a median 7 months after fitting. Survival analysis showed 12% still using MRS at 12 months. Epworth score fell slightly with MRS therapy [−2.4 (3.5); P=0.005] and 7 daytime and 2 nocturnal symptoms improved in MRS users (all P<0.05). Marital satisfaction did not change with MRS. Problems preventing MRS use in 70 non-users included: non-retention (n=12), sore mouth (n=13) or jaw (n=7), difficulties falling asleep (n=10) or breathing (n=7), excessive salivation (n=4), dental damage (n=4) and other problems (n=3). Continued use of MRS therapy was associated with a higher number of teeth, low marital satisfaction perceived by partners and greater improvement in symptoms reported by patients and partners. Continuance with MRS may be low and linked to tolerance problems

Adult vitamin D deficiency leads to behavioural and brain neurochemical alterations in C57BL/6J and BALB/c mice

Epidemiological evidence suggests that low levels of vitamin D may predispose people to develop depression and cognitive impairment. While rodent studies have demonstrated that prenatal vitamin D deficiency is associated with altered brain development, there is a lack of research examining adult vitamin D (AVD) deficiency. The aim of this study was to examine the impact of AVD deficiency on behaviour and brain function in the mouse. Ten-week old male C57BL/6J and BALB/c mice were fed a control or vitamin D deficient diet for 10 weeks prior to, and during behavioural testing. We assessed a broad range of behavioural domains, excitatory and inhibitory neurotransmission in brain tissue, and, in separate groups of mice, locomotor response to d-amphetamine and MK-801. Overall, AVD deficiency resulted in hyperlocomotion in a novel open field and reduced GAD65/67 levels in brain tissue. AVD-deficient BALB/c mice had altered behaviour on the elevated plus maze, altered responses to heat, sound and shock, and decreased levels of glutamate and glutamine, and increased levels of GABA and glycine. By contrast C57BL/6J mice had a more subtle phenotype with no further behavioural changes but significant elevations in serine, homovanillic acid and 5-hydroxyindoleacetic acid. Although the behavioural phenotype of AVD did not seem to model a specific disorder, the overall reduction in GAD65/67 levels associated with AVD deficiency may be relevant to a number of neuropsychiatric conditions. This is the first study to show an association between AVD deficiency and prominent changes in behaviour and brain neurochemistry in the mouse

General Relativity in Electrical Engineering

In electrical engineering metamaterials have been developed that offer unprecedented control over electromagnetic fields. Here we show that general relativity lends the theoretical tools for designing devices made of such versatile materials. Given a desired device function, the theory describes the electromagnetic properties that turn this function into fact. We consider media that facilitate space-time transformations and include negative refraction. Our theory unifies the concepts operating behind the scenes of perfect invisibility devices, perfect lenses, the optical Aharonov-Bohm effect and electromagnetic analogs of the event horizon, and may lead to further applications

Local-metrics error-based Shepard interpolation as surrogate for highly non- linear material models in high dimensions

Many problems in computational materials science and chemistry require the evaluation of expensive functions with locally rapid changes, such as the turn-over frequency of first principles kinetic Monte Carlo models for heterogeneous catalysis. Because of the high computational cost, it is often desirable to replace the original with a surrogate model, e.g., for use in coupled multiscale simulations. The construction of surrogates becomes particularly challenging in high-dimensions. Here, we present a novel version of the modified Shepard interpolation method which can overcome the curse of dimensionality for such functions to give faithful reconstructions even from very modest numbers of function evaluations. The introduction of local metrics allows us to take advantage of the fact that, on a local scale, rapid variation often occurs only across a small number of directions. Furthermore, we use local error estimates to weigh different local approximations, which helps avoid artificial oscillations. Finally, we test our approach on a number of challenging analytic functions as well as a realistic kinetic Monte Carlo model. Our method not only outperforms existing isotropic metric Shepard methods but also state-of-the-art Gaussian process regression

Comparing families of dynamic causal models

Mathematical models of scientific data can be formally compared using Bayesian model evidence. Previous applications in the biological sciences have mainly focussed on model selection in which one first selects the model with the highest evidence and then makes inferences based on the parameters of that model. This “best model” approach is very useful but can become brittle if there are a large number of models to compare, and if different subjects use different models. To overcome this shortcoming we propose the combination of two further approaches: (i) family level inference and (ii) Bayesian model averaging within families. Family level inference removes uncertainty about aspects of model structure other than the characteristic of interest. For example: What are the inputs to the system? Is processing serial or parallel? Is it linear or nonlinear? Is it mediated by a single, crucial connection? We apply Bayesian model averaging within families to provide inferences about parameters that are independent of further assumptions about model structure. We illustrate the methods using Dynamic Causal Models of brain imaging data

The non-evolving internal structure of early-type galaxies: the case study SDSS J0728+3835 at z = 0.206

We study the internal dynamical structure of the early-type lens galaxy SDSS J0728+3835 at z = 0.206. The analysis is based on two-dimensional kinematic maps extending out to 1.7 effective radii obtained from Keck spectroscopy, on lensing geometry and on stellar mass estimates obtained from multiband Hubble Space Telescope imaging. The data are modelled under the assumptions of axial symmetry supported by a two-integral distribution function (DF), by applying the combined gravitational lensing and stellar dynamics code CAULDRON, and yielding high-quality constraints for an early-type galaxy at cosmological redshifts. Modelling the total density profile as a power-law of the form rho_tot ~ 1/r^{gamma}, we find that it is nearly isothermal (logarithmic slope gamma = 2.08^{+0.04}_{-0.02}), and quite flattened (axial ratio q = 0.60^{+0.08}_{-0.03}). The galaxy is mildly anisotropic (delta = 0.08 +/- 0.02) and shows a fair amount of rotational support, in particular towards the outer regions. We determine a dark matter fraction lower limit of 28 per cent within the effective radius. The stellar contribution to the total mass distribution is close to maximal for a Chabrier initial mass function (IMF), whereas for a Salpeter IMF the stellar mass exceeds the total mass within the galaxy inner regions. We find that the combination of a NFW dark matter halo with the maximally rescaled luminous profile provides a remarkably good fit to the total mass distribution over a broad radial range. Our results confirm and expand the findings of the SLACS survey for early-type galaxies of comparable velocity dispersion (sigma_SDSS = 214 +/- 11 km/s). The internal structure of J0728 is consistent with that of local early-type galaxies of comparable velocity dispersion as measured by the SAURON project, suggesting lack of evolution in the past two billion years.Comment: 13 pages, 10 figures. MNRAS in press. Revised to match accepted versio

Deep and Frequent Phenotyping study protocol: an observational study in prodromal Alzheimer's disease.

INTRODUCTION: Recent failures of potential novel therapeutics for Alzheimer's disease (AD) have prompted a drive towards clinical studies in prodromal or preclinical states. However, carrying out clinical trials in early disease stages is extremely challenging-a key reason being the unfeasibility of using classical outcome measures of dementia trials (eg, conversion to dementia) and the lack of validated surrogate measures so early in the disease process. The Deep and Frequent Phenotyping (DFP) study aims to resolve this issue by identifying a set of markers acting as indicators of disease progression in the prodromal phase of disease that could be used as indicative outcome measures in proof-of-concept trials. METHODS AND ANALYSIS: The DFP study is a repeated measures observational study where participants will be recruited through existing parent cohorts, research interested lists/databases, advertisements and memory clinics. Repeated measures of both established (cognition, positron emission tomography (PET) imaging or cerebrospinal fluid (CSF) markers of pathology, structural MRI markers of neurodegeneration) and experimental modalities (functional MRI, magnetoencephalography and/or electroencephalography, gait measurement, ophthalmological and continuous smartphone-based cognitive and other assessments together with experimental CSF, blood, tear and saliva biomarkers) will be performed. We will be recruiting male and female participants aged >60 years with prodromal AD, defined as absence of dementia but with evidence of cognitive impairment together with AD pathology as assessed using PET imaging or CSF biomarkers. Control participants without evidence of AD pathology will be included at a 1:4 ratio. ETHICS AND DISSEMINATION: The study gained favourable ethical opinion from the South Central-Oxford B NHS Research Ethics Committee (REC reference 17/SC/0315; approved on 18 August 2017; amendment 13 February 2018). Data will be shared with the scientific community no more than 1 year following completion of study and data assembly.NIH