Midlife diagnosis of Refsum Disease in siblings with Retinitis Pigmentosa – the footprint is the clue: a case report

<p>Abstract</p> <p>Introduction</p> <p>Refsum disease is a potentially lethal and disabling condition associated with retinitis pigmentosa in which early treatment can prevent some of the systemic manifestations.</p> <p>Case presentation</p> <p>We present the cases of two brothers with a diagnosis of retinitis pigmentosa from childhood in whom Refsum disease was subsequently diagnosed midlife, after routine enquiry into hand and feet abnormalities. Subsequent treatment through dietary modification stabilised visual impairment and has prevented development of neurological complications to date.</p> <p>Conclusion</p> <p>It is therefore important to consider the diagnosis of Refsum disease in any patient with autosomal recessive or simplex retinitis pigmentosa, and to enquire about the presence of "unusual" feet or hands in such patients.</p

Islands of linkage in an ocean of pervasive recombination reveals two-speed evolution of human cytomegalovirus genomes

Human cytomegalovirus (HCMV) infects most of the population worldwide, persisting throughout the host's life in a latent state with periodic episodes of reactivation. While typically asymptomatic, HCMV can cause fatal disease among congenitally infected infants and immunocompromised patients. These clinical issues are compounded by the emergence of antiviral resistance and the absence of an effective vaccine, the development of which is likely complicated by the numerous immune evasins encoded by HCMV to counter the host's adaptive immune responses, a feature that facilitates frequent super-infections. Understanding the evolutionary dynamics of HCMV is essential for the development of effective new drugs and vaccines. By comparing viral genomes from uncultivated or low-passaged clinical samples of diverse origins, we observe evidence of frequent homologous recombination events, both recent and ancient, and no structure of HCMV genetic diversity at the whole-genome scale. Analysis of individual gene-scale loci reveals a striking dichotomy: while most of the genome is highly conserved, recombines essentially freely and has evolved under purifying selection, 21 genes display extreme diversity, structured into distinct genotypes that do not recombine with each other. Most of these hyper-variable genes encode glycoproteins involved in cell entry or escape of host immunity. Evidence that half of them have diverged through episodes of intense positive selection suggests that rapid evolution of hyper-variable loci is likely driven by interactions with host immunity. It appears that this process is enabled by recombination unlinking hyper-variable loci from strongly constrained neighboring sites. It is conceivable that viral mechanisms facilitating super-infection have evolved to promote recombination between diverged genotypes, allowing the virus to continuously diversify at key loci to escape immune detection, while maintaining a genome optimally adapted to its asymptomatic infectious lifecycle

Recent advances in electronic structure theory and their influence on the accuracy of ab initio potential energy surfaces

Recent advances in electronic structure theory and the availability of high speed vector processors have substantially increased the accuracy of ab initio potential energy surfaces. The recently developed atomic natural orbital approach for basis set contraction has reduced both the basis set incompleteness and superposition errors in molecular calculations. Furthermore, full CI calculations can often be used to calibrate a CASSCF/MRCI approach that quantitatively accounts for the valence correlation energy. These computational advances also provide a vehicle for systematically improving the calculations and for estimating the residual error in the calculations. Calculations on selected diatomic and triatomic systems will be used to illustrate the accuracy that currently can be achieved for molecular systems. In particular, the F+H2 yields HF+H potential energy hypersurface is used to illustrate the impact of these computational advances on the calculation of potential energy surfaces

Diffusion of an e-learning programme among Danish General Practitioners: A nation-wide prospective survey

<p>Abstract</p> <p>Background</p> <p>We were unable to identify studies that have considered the diffusion of an e-learning programme among a large population of general practitioners. The aim of this study was to investigate the uptake of an e-learning programme introduced to General Practitioners as part of a nation-wide disseminated dementia guideline.</p> <p>Methods</p> <p>A prospective study among all 3632 Danish GPs. The GPs were followed from the launching of the e-learning programme in November 2006 and 6 months forward. Main outcome measures: Use of the e-learning programme. A logistic regression model (GEE) was used to identify predictors for use of the e-learning programme.</p> <p>Results</p> <p>In the study period, a total of 192 different GPs (5.3%) were identified as users, and 17% (32) had at least one re-logon. Among responders at first login most have learnt about the e-learning programme from written material (41%) or from the internet (44%). A total of 94% of the users described their ability of conducting a diagnostic evaluation as good or excellent. Most of the respondents used the e-learning programme due to general interest (90%). Predictors for using the e-learning programme were Males (OR = 1.4, 95% CI 1.1; 2.0) and members of Danish College of General Practice (OR = 2.2, 95% CI 1.5; 3.1), whereas age, experience and working place did not seem to be influential.</p> <p>Conclusion</p> <p>Only few Danish GPs used the e-learning programme in the first 6 months after the launching. Those using it were more often males and members of Danish College of General Practice. Based on this study we conclude, that an active implementation is needed, also when considering electronic formats of CME like e-learning.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: NCT00392483.</p

Physical health behaviours and health locus of control in people with schizophrenia-spectrum disorder and bipolar disorder: a cross-sectional comparative study with people with non-psychotic mental illness

<p>Abstract</p> <p>Background</p> <p>People with mental illness experience high levels of morbidity and mortality from physical disease compared to the general population. Our primary aim was to compare how people with severe mental illness (SMI; i.e. schizophrenia-spectrum disorders and bipolar disorder) and non-psychotic mental illness perceive their: (i) global physical health, (ii) barriers to improving physical health, (iii) physical health with respect to important aspects of life and (iv) motivation to change modifiable high-risk behaviours associated with coronary heart disease. A secondary aim was to determine health locus of control in these two groups of participants.</p> <p>Methods</p> <p>People with SMI and non-psychotic mental illness were recruited from an out-patient adult mental health service in London. Cross-sectional comparison between the two groups was conducted by means of a self-completed questionnaire.</p> <p>Results</p> <p>A total of 146 people participated in the study, 52 with SMI and 94 with non-psychotic mental illness. There was no statistical difference between the two groups with respect to the perception of global physical health. However, physical health was considered to be a less important priority in life by people with SMI (OR 0.5, 95% CI 0.2-0.9, <it>p </it>= 0.029). There was no difference between the two groups in their desire to change high risk behaviours. People with SMI are more likely to have a health locus of control determined by powerful others (<it>p </it>< 0.001) and chance (<it>p </it>= 0.006).</p> <p>Conclusions</p> <p>People with SMI appear to give less priority to their physical health needs. Health promotion for people with SMI should aim to raise awareness of modifiable high-risk lifestyle factors. Findings related to locus of control may provide a theoretical focus for clinical intervention in order to promote a much needed behavioural change in this marginalised group of people.</p

SuperCLASS - III. Weak lensing from radio and optical observations in Data Release 1

We describe the first results on weak gravitational lensing from the SuperCLASS survey: the first survey specifically designed to measure the weak lensing effect in radio-wavelength data, both alone and in cross-correlation with optical data. We analyse 1.53deg2 of optical data from the Subaru telescope and 0.26deg2 of radio data from the e-MERLIN and VLA telescopes (the DR1 data set). Using standard methodologies on the optical data only we make a significant (10σ) detection of the weak lensing signal (a shear power spectrum) due to the massive supercluster of galaxies in the targeted region. For the radio data we develop a new method to measure the shapes of galaxies from the interferometric data, and we construct a simulation pipeline to validate this method. We then apply this analysis to our radio observations, treating the e-MERLIN and VLA data independently. We achieve source densities of 0.5 arcmin−2 in the VLA data and 0.06 arcmin−2 in the e-MERLIN data, numbers which prove too small to allow a detection of a weak lensing signal in either the radio data alone or in cross-correlation with the optical data. Finally, we show preliminary results from a visibility-plane combination of the data from e-MERLIN and VLA which will be used for the forthcoming full SuperCLASS data release. This approach to data combination is expected to enhance both the number density of weak lensing sources available, and the fidelity with which their shapes can be measured

Synergy between the Large Synoptic Survey Telescope and the Square Kilometre Array

We provide an overview of the science benefits of combining information from the Square Kilometre Array (SKA) and the Large Synoptic Survey Telescope (LSST). We first summarise the capabilities and timeline of the LSST and overview its science goals. We then discuss the science questions in common between the two projects, and how they can be best addressed by combining the data from both telescopes. We describe how weak gravitational lensing and galaxy clustering studies with LSST and SKA can provide improved constraints on the causes of the cosmological acceleration. We summarise the benefits to galaxy evolution studies of combining deep optical multi-band imaging with radio observations. Finally, we discuss the excellent match between one of the most unique features of the LSST, its temporal cadence in the optical waveband, and the time resolution of the SKA

Strong Ultraviolet Pulse From a Newborn Type Ia Supernova

Type Ia supernovae are destructive explosions of carbon oxygen white dwarfs. Although they are used empirically to measure cosmological distances, the nature of their progenitors remains mysterious, One of the leading progenitor models, called the single degenerate channel, hypothesizes that a white dwarf accretes matter from a companion star and the resulting increase in its central pressure and temperature ignites thermonuclear explosion. Here we report observations of strong but declining ultraviolet emission from a Type Ia supernova within four days of its explosion. This emission is consistent with theoretical expectations of collision between material ejected by the supernova and a companion star, and therefore provides evidence that some Type Ia supernovae arise from the single degenerate channel.Comment: Accepted for publication on the 21 May 2015 issue of Natur

Visualisation of trust and quality information for geospatial dataset selection and use:Drawing trust presentation comparisons with B2C e-Commerce

The evaluation of geospatial data quality and trustworthiness presents a major challenge to geospatial data users when making a dataset selection decision. Part of the problem arises from the inconsistent and patchy nature of data quality information, which makes intercomparison very difficult. Over recent years, the production and availability of geospatial data has significantly increased, facilitated by the recent explosion of Web-based catalogues, portals, standards and services, and by initiatives such as INSPIRE and GEOSS. Despite this significant growth in availability of geospatial data and the fact that geospatial datasets can, in many respects, be considered commercial products that are available for purchase online, consumer trust has to date received relatively little attention in the GIS domain. In this paper, we discuss how concepts of trust, trust models, and trust indicators (largely derived from B2C e-Commerce) apply to the GIS domain and to geospatial data selection and use. Our research aim is to support data users in more efficient and effective geospatial dataset selection on the basis of quality, trustworthiness and fitness for purpose. To achieve this, we propose a GEO label – a decision support mechanism that visually summarises availability of key geospatial data informational aspects. We also present a Web service that was developed to support generation of dynamic GEO label representations for datasets by combining producer metadata (from standard catalogues or other published locations) with structured user feedback