Curry-assisted diagnosis in the rheumatology clinic.

We report five cases of glucocorticoid-responsive mouth symptoms in polymyalgia rheumatica/giant cell arteritis (GCA); three cases of tongue pain exacerbated by hot/spicy food, a case of scalp pain made worse by eating hot/spicy food and a case of sore tongue as a presenting feature of GCA. These cases emphasize the importance of asking about mouth symptoms and changes in taste when evaluating patients with suspected GCA

The genetic landscape of amyotrophic lateral sclerosis

Next-generation sequencing (NGS) technologies have a vast number of advantages that have caused a growth in their application for uncovering the genetics of complex diseases. Amyotrophic lateral sclerosis (ALS) is one such disease that could benefit from this technique. As a rapid-onset disease, the time to diagnosis must match this speed if we want to increase our chances of finding a treatment drug that works. In a number of ALS cases, the diagnosis can be aided by genetics. However, we currently do not understand the full genetic background of ALS and so to address this issue, I have designed a screening panel to sequence 25 ALS-associated genes in 1,235 patients. This data was compared against 613 controls to perform a case-control analysis. Alongside mutation burden tests and tests for an oligogenic basis, I have additionally created a novel method, a pipeline assisted by machine learning, for uncovering high-dimensional genetic patterns that predispose an individual to ALS. The results indicate that there is an increase burden of rare variants in the UTRs of the genes SOD1, TARDBP, FUS, VCP, OPTN and UBQLN2 collectively. Additionally, we discovered an increased number of patients with two mutations in different ALS genes than would be expected by chance alone. Encompassed in these results is the finding of a novel ALS gene, MATR3, which we aided the first publication of. We have also screened CHCHD10 in ALS and frontotemporal dementia (FTD) finding confirmations of previously published mutations plus additional novel variants. A selection of 26 Argentinian ALS samples were included in the study which reveal 27 known and novel mutations across 17 patients. Lastly, machine learning methods are able to perform better than chance at predicting patients on the basis of their genetics. In conclusion, many cases of ALS, sporadic included, show a complex genetic interplay which, combined with the overall mutation burden, determine the risk and course of ALS

Correlation of retinal nerve fibre layer thickness and spontaneous retinal venous pulsations in glaucoma and normal controls

© 2015 Golzan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Purpose: To study the relationship between amplitude of spontaneous retinal venous pulsatility (SRVP) and retinal nerve fibre layer (RNFL) thickness in glaucomatous eyes, and to determine if this parameter may be a potential marker for glaucoma severity. Method: 85 subjects including 50 glaucoma (21 males, 67±10 yrs) and 35 normals (16 males, 62±11 yrs) were studied. SRVP amplitude was measured using the Dynamic Vessel Analyser (DVA, Imedos, Germany) at four regions of the retina simultaneously within one disc diameter from the optic disc - temporal-superior (TS), nasal-superior (NS), temporal-inferior (TI) and nasal-inferior (NI)). This was followed by RNFL thickness measurement using spectral domain optical coherence tomography (Spectralis OCT). The correlation between SRVP amplitude and corresponding sectoral RNFL thickness was assessed by means of non-linear regression (i.e. logarithmic). Linear regression was also applied and slopes were compared using analysis of covariance (ANCOVA). Results: Greater SRVP amplitude was associated with thicker RNFL. Global SRVP amplitude was significantly lower in glaucoma eyes compared with normals (p0.05). Since the slopes are not significantly different, it is possible to calculate one slope for all the data. The pooled slope equals 10.8 (i.e. RNFL = 10.8SRVP+41)

A review of the factors involved in older people's decision making with regard to influenza vaccination: a literature review

Aims and objectives. The aim of this paper was to develop an understanding of the factors involved in older people's decision making with regard to influenza vaccination to inform strategies to improve vaccine uptake and reduce morbidity and mortality. Background. Influenza is a major cause of morbidity and mortality world-wide. In the UK, it accounts for 3000–6000 deaths annually; 85% of these deaths are people aged 65 and over. Despite this, and the widespread and costly annual government campaigns, some older people at risk of influenza and the associated complications remain reluctant to take advantage of the offer of vaccination. Methods. A review of the English language literature referring to older people published between 1996 and 2005 was the method used. Inclusion and exclusion criteria were identified and applied. Results. The majority of the literature was quantitative in nature, investigating personal characteristics thought to be predictors of uptake, such as age, sex, co-morbidity, educational level, income and area of residence. However, there was little discussion of the possible reasons for the significance of these factors and conflict between findings was often evident, particularly between studies employing different methodologies. Other factors identified were prior experience, concerns about the vaccine, perceived risk and advice and information. Relevance to clinical practice. The wealth of demographic information available will be useful at a strategic level in targeting groups identified as being unlikely to accept vaccination. However, the promotion of person-centred ways of working that value the health beliefs, attitudes, perceptions and subjective experiences of older people is likely to be more successful during individual encounters designed to promote acceptance. Without more research in investigating these concepts, our understanding is inevitably limited

Evaluation of genomic island predictors using a comparative genomics approach

<p>Abstract</p> <p>Background</p> <p>Genomic islands (GIs) are clusters of genes in prokaryotic genomes of probable horizontal origin. GIs are disproportionately associated with microbial adaptations of medical or environmental interest. Recently, multiple programs for automated detection of GIs have been developed that utilize sequence composition characteristics, such as G+C ratio and dinucleotide bias. To robustly evaluate the accuracy of such methods, we propose that a dataset of GIs be constructed using criteria that are independent of sequence composition-based analysis approaches.</p> <p>Results</p> <p>We developed a comparative genomics approach (IslandPick) that identifies both very probable islands and non-island regions. The approach involves 1) flexible, automated selection of comparative genomes for each query genome, using a distance function that picks appropriate genomes for identification of GIs, 2) identification of regions unique to the query genome, compared with the chosen genomes (positive dataset) and 3) identification of regions conserved across all genomes (negative dataset). Using our constructed datasets, we investigated the accuracy of several sequence composition-based GI prediction tools.</p> <p>Conclusion</p> <p>Our results indicate that AlienHunter has the highest recall, but the lowest measured precision, while SIGI-HMM is the most precise method. SIGI-HMM and IslandPath/DIMOB have comparable overall highest accuracy. Our comparative genomics approach, IslandPick, was the most accurate, compared with a curated list of GIs, indicating that we have constructed suitable datasets. This represents the first evaluation, using diverse and, independent datasets that were not artificially constructed, of the accuracy of several sequence composition-based GI predictors. The caveats associated with this analysis and proposals for optimal island prediction are discussed.</p

Achieving consensus on minimum data items (including core outcome domains) for a longitudinal observational cohort study in rheumatoid arthritis

Objectives: To obtain consensus on minimum data items for an observational cohort study in rheumatoid arthritis (RA) in the UK and to make available the process for similar studies and other rheumatic conditions. Methods: Individuals with a diverse range of expertise and backgrounds were invited to participate in a process to propose a minimal core dataset (MCD) for research studies, commissioned by Arthritis Research UK as part of the larger INBANK project. The group included patients and representatives from clinical and academic rheumatology, outcomes science, stratified medicine, health economics, national professional and academic bodies/ committees. A process was devised based on Outcome Measures in Rheumatology Clinical Trials (OMERACT) principles to review aims/objectives, definition of scope, identification of important research questions, and selection of key domains. Results: Following the initial multi-stakeholder meeting, subsequent teleconferences and email communications, consensus was obtained on: 1. Most important and relevant research questions; 2. Agreement on how the OMERACT Core Areas (life impact, pathophysiological manifestations, resource use and death) could form the basis of a MCD; 3. Consensus on 22 items for inclusion into a MCD. Workshops were undertaken for two essential items which required further exploration: work/social participation and co-morbidity. Conclusions: Consensus for proposed minimal data items for long-term observational cohort studies of RA in the UK posed novel challenges and opportunities, and was largely successful. Further work is needed to select instruments for two important items and to achieve compatibility with other UK national initiatives, and more widely across Europe

Lagrange Anchor for Bargmann-Wigner equations

A Poincare invariant Lagrange anchor is found for the non-Lagrangian relativistic wave equations of Bargmann and Wigner describing free massless fields of spin s > 1/2 in four-dimensional Minkowski space. By making use of this Lagrange anchor, we assign a symmetry to each conservation law.Comment: A contribution to Proceedings of the XXXI Workshop on the Geometric Methods in Physic