A Power-Enhanced Algorithm for Spatial Anomaly Detection in Binary Labelled Point Data Using the Spatial Scan Statistic [postprint]

This paper presents a novel modification to an existing algorithm for spatial anomaly detection in binary labeled point data sets, using the Bernoulli version of the Spatial Scan Statistic. We identify a potential ambiguity in p-values produced by Monte Carlo testing, which (by the selection of the most conservative p-value) can lead to sub-optimal power. When such ambiguity occurs, the modification uses a very inexpensive secondary test to suggest a less conservative p-value. Using benchmark tests, we show that this appears to restore power to the expected level, whilst having similarly retest variance to the original. The modification also appears to produce a small but significant improvement in overall detection performance when multiple anomalies are present

Information sheets for patients with acute chest pain: randomised controlled trial

Objectives: To determine whether providing an information sheet to patients with acute chest pain reduces anxiety, improves health related quality of life, improves satisfaction with care, or alters subsequent symptoms or actions. Design: Single centre, non-blinded, randomised controlled trial. Setting: Chest pain unit of an emergency department. Participants: 700 consecutive patients with acute chest pain and no clear diagnosis at initial presentation. Interventions: After a diagnostic assessment patients were randomised to receive either standard verbal advice or verbal advice followed by an information sheet. Main outcome measures: The primary outcome was anxiety (hospital anxiety and depression scale). Secondary outcomes were depression (hospital anxiety and depression scale), health related quality of life (SF-36), patient satisfaction, presentation with further chest pain within one month, lifestyle change (smoking cessation, diet, exercise), further information sought from other sources, and planned healthcare seeeking behaviour in response to further pain. Results 494 of 700 (70.6%) patients responded. Compared with those receiving standard verbal advice those receiving advice and an information sheet had lower mean hospital anxiety and depression scale scores for anxiety (7.61v8.63, difference 1.02, 95% confidence interval 0.20 to 1.84) and depression (4.14 v 5.28, difference 1.14, 0.41 to 1.86) and higher scores for mental health and perception of general health on the SF-36. The information sheet had no significant effect on satisfaction with care, subsequent symptoms, lifestyle change, information seeking, or planned actions in the event of further pain. Conclusions: Provision of an information sheet to patients with acute chest pain can reduce anxiety and depression and improve mental health and perception of general health but does not alter satisfaction with care or other outcomes. Trial registration Current Controlled Trials ISRCTN85248020

A spatial accuracy assessment of an alternative circular scan method for Kulldorff's spatial scan statistic

This paper concerns the Bernoulli version of Kulldorff’s spatial scan statistic, and how accurately it identifies the exact centre of approximately circular regions of increased spatial density in point data. We present an alternative method of selecting circular regions that appears to give greater accuracy. Performance is tested in an epidemiological context using manifold synthetic case-control datasets. A small, but statistically significant, improvement is reported. The power of the alternative method is yet to be assessed

A pilot inference study for a beta-Bernoulli spatial scan statistic

The Bernoulli spatial scan statistic is used to detect localised clusters in binary labelled point data, such as that used in spatial or spatio-temporal case/control studies. We test the inferential capability of a recently developed beta-Bernoulli spatial scan statistic, which adds a beta prior to the original statistic. This pilot study, which includes two test scenarios with 6,000 data sets each, suggests a marked increase in power for a given false alert rate. We suggest a more extensive study would be worthwhile to corroborate the findings. We also speculate on an explanation for the observed improvement

A graph-theory method for pattern identification in geographical epidemiology - a preliminary application to deprivation and mortality

Background: Graph theoretical methods are extensively used in the field of computational chemistry to search datasets of compounds to see if they contain particular molecular substructures or patterns. We describe a preliminary application of a graph theoretical method, developed in computational chemistry, to geographical epidemiology in relation to testing a prior hypothesis. We tested the methodology on the hypothesis that if a socioeconomically deprived neighbourhood is situated in a wider deprived area, then that neighbourhood would experience greater adverse effects on mortality compared with a similarly deprived neighbourhood which is situated in a wider area with generally less deprivation. Methods: We used the Trent Region Health Authority area for this study, which contained 10,665 census enumeration districts (CED). Graphs are mathematical representations of objects and their relationships and within the context of this study, nodes represented CEDs and edges were determined by whether or not CEDs were neighbours (shared a common boundary). The overall area in this study was represented by one large graph comprising all CEDs in the region, along with their adjacency information. We used mortality data from 1988-1998, CED level population estimates and the Townsend Material Deprivation Index as an indicator of neighbourhood level deprivation. We defined deprived CEDs as those in the top 20% most deprived in the Region. We then set out to classify these deprived CEDs into seven groups defined by increasing deprivation levels in the neighbouring CEDs. 506 (24.2%) of the deprived CEDs had five adjacent CEDs and we limited pattern development and searching to these CEDs. We developed seven query patterns and used the RASCAL (Rapid Similarity Calculator) program to carry out the search for each of the query patterns. This program used a maximum common subgraph isomorphism method which was modified to handle geographical data. Results: Of the 506 deprived CEDs, 10 were not identified as belonging to any of the seven groups because they were adjacent to a CED with a missing deprivation category quintile, and none fell within query Group 1 (a deprived CED for which all five adjacent CEDs were affluent). Only four CEDs fell within Group 2, which was defined as having four affluent adjacent CEDs and one non-affluent adjacent CED. The numbers of CEDs in Groups 3-7 were 17, 214, 95, 81 and 85 respectively. Age and sex adjusted mortality rate ratios showed a non-significant trend towards increasing mortality risk across Groups (Chi-square = 3.26, df = 1, p = 0.07). Conclusion: Graph theoretical methods developed in computational chemistry may be a useful addition to the current GIS based methods available for geographical epidemiology but further developmental work is required. An important requirement will be the development of methods for specifying multiple complex search patterns. Further work is also required to examine the utility of using distance, as opposed to adjacency, to describe edges in graphs, and to examine methods for pattern specification when the nodes have multiple attributes attached to them

Pharmacological treatment and prevention of cerebral small vessel disease: a review of potential interventions

Small vessel disease encompasses lacunar stroke, white matter hyperintensities, lacunes and microbleeds. It causes a quarter of all ischemic strokes, is the commonest cause of vascular dementia, and the cause is incompletely understood. Vascular prophylaxis, as appropriate for large artery disease and cardioembolism, includes antithrombotics, and blood pressure and lipid lowering; however, these strategies may not be effective for small vessel disease, or are already used routinely so precluding further detailed study. Further, intensive antiplatelet therapy is known to be hazardous in small vessel disease through enhanced bleeding. Whether acetylcholinesterase inhibitors, which delay the progression of Alzheimer's dementia, are relevant in small vessel disease remains unclear. Potential prophylactic and treatment strategies might be those that target brain microvascular endothelium and the blood brain barrier, microvascular function and neuroinflammation. Potential interventions include endothelin antagonists, neurotrophins, nitric oxide donors and phosphodiesterase 5 inhibitors, peroxisome proliferator-activated receptor-gamma agonists, and prostacyclin mimics and phosphodiesterase 3 inhibitors. Several drugs that have relevant properties are licensed for other disorders, offering the possibility of drug repurposing. Others are in development. Since influencing multiple targets may be most effective, using multiple agents and/or those that have multiple effects may be preferable. We focus on potential small vessel disease mechanistic targets, summarize drugs that have relevant actions, and review data available from randomized trials on their actions and on the available evidence for their use in lacunar stroke

The ‘total cost of publication’ in a hybrid open-access environment: Institutional approaches to funding journal article-processing charges in combination with subscriptions

As open-access (OA) publishing funded by article-processing charges (APCs) becomes more widely accepted, academic institutions need to be aware of the ‘total cost of publication’, comprising subscription costs plus APCs and additional administration costs. This study analyses data from 23 UK institutions covering the period 2007 to 2014 modelling the total cost of publication (TCP). It shows a clear rise in centrally-managed APC payments from 2012 onwards, with payments projected to increase further. As well as evidencing the growing availability and acceptance of OA publishing, these trends reflect particular UK policy developments and funding arrangements intended to accelerate the move towards OA publishing (‘Gold’ OA). Whilst the mean value of APCs has been relatively stable, there was considerable variation in APC prices paid by institutions since 2007. In particular, ‘hybrid’ subscription/OA journals were consistently more expensive than fully-OA journals. Most APCs were paid to large ‘traditional’ commercial publishers who also received considerable subscription income. New administrative costs reported by institutions varied considerably. The total cost of publication modelling shows that APCs are now a significant part of the TCP for academic institutions, in 2013 already constituting an average of 10% of the TCP (excluding administrative costs)

Stroke outcome in clinical trial patients deriving from different countries

<p><b>Background and Purpose:</b> Stroke incidence and outcome vary widely within and across geographical locations. We examined whether differences in index stroke severity, stroke risk factors, mortality, and stroke outcome across geographical locations remain after adjusting for case mix.</p> <p><b>Methods:</b> We analyzed 3284 patients from the Virtual International Stroke Trials Archive (VISTA). We used logistic regression to examine the incidence of mild index stroke, functional, and neurological outcomes after accounting for age, medical history, year of trial recruitment, and initial stroke severity in the functional and neurological outcome analyses. We examined mortality between geographical regions using a Cox proportional hazards model, accounting for age, initial stroke severity, medical history, and year of trial recruitment.</p> <p><b>Results</b> Patients enrolled in the USA and Canada had the most severe index strokes. Those recruited in Austria and Switzerland had the best functional and neurological outcomes at 90 days (P<0.05), whereas those enrolled in Germany had the worst functional outcome at 90 days (P=0.013). Patients enrolled in Austria, Switzerland, Belgium, Netherlands, Finland, Germany, Greece, Israel, Spain, and Portugal had a significantly better survival rate when compared with those enrolled in USA and Canada. Patients enrolled in trials after 1998 had more severe index strokes, with no significant difference in outcome compared with those enrolled before 1998.</p> <p><b>Conclusion:</b> We identified regional variations in index stroke severity, outcome, and mortality for patients enrolled in ischemic stroke clinical trials over the past 13 years that were not fully explained by case mix. Index stroke severity was greater in patients enrolled after 1998, with no significant improvement in outcomes compared to those enrolled before 1998.</p&gt

On the Correlated X-ray and Optical Evolution of SS Cygni

We have analyzed the variability and spectral evolution of the prototype dwarf nova system SS Cygni using RXTE data and AAVSO observations. A series of pointed RXTE/PCA observations allow us to trace the evolution of the X-ray spectrum of SS Cygni in unprecedented detail, while 6 years of optical AAVSO and RXTE/ASM light curves show long-term patterns. Employing a technique in which we stack the X-ray flux over multiple outbursts, phased according to the optical light curve, we investigate the outburst morphology. We find that the 3-12 keV X-ray flux is suppressed during optical outbursts, a behavior seen previously, but only in a handful of cycles. The several outbursts of SS Cygni observed with the more sensitive RXTE/PCA also show a depression of the X-rays during optical outburst. We quantify the time lags between the optical and X-ray outbursts, and the timescales of the X-ray recovery from outburst. The optical light curve of SS Cygni exhibits brief anomalous outbursts. During these events the hard X-rays and optical flux increase together. The long-term data suggest that the X-rays decline between outburst. Our results are in general agreement with modified disk instability models (DIM), which invoke a two-component accretion flow consisting of a cool optically thick accretion disk truncated at an inner radius, and a quasi-spherical hot corona-like flow extending to the surface of the white dwarf. We discuss our results in the framework of one such model, involving the evaporation of the inner part of the optically thick accretion disk, proposed by Meyer & Meyer-Hofmeister (1994).Comment: 24 pages, 8 figures, 2 tables, accepted for publication in Ap

Pharyngeal electrical stimulation for treatment of poststroke dysphagia: individual patient data meta-analysis of randomised controlled trials

Background. Dysphagia after stroke is common, associated independently with poor outcome, and has limited treatment options. Pharyngeal electrical stimulation (PES) is a novel treatment being evaluated for treatment of poststroke dysphagia. Methods. We searched electronically for randomised controlled trials of PES in dysphagic patients within 3 months of stroke. Individual patient data were analysed using regression, adjusted for trial, age, severity, and baseline score. The coprimary outcomes were radiological aspiration (penetration aspiration score, PAS) and clinical dysphagia (dysphagia severity rating scale, DSRS) at 2 weeks; secondary outcomes included functional outcome, death, and length of stay in hospital. Results. Three completed trials were identified: 73 patients, age 72 (12) years, severity (NIHSS) 11 (6), DSRS 6.7 (4.3), mean PAS 4.3 (1.8). Compared with no/sham stimulation, PES was associated with lower PAS, 3.4 (1.7) versus 4.1 (1.7), mean difference −0.9 (), and lower DSRS, 3.5 (3.8) versus 4.9 (4.4), mean difference −1.7 (). Length of stay in hospital tended to be shorter: 50.2 (25.3) versus 71.2 (60.4) days (). Functional outcome and death did not differ between treatment groups. Conclusions. PES was associated with less radiological aspiration and clinical dysphagia and possibly reduced length of stay in hospital across three small trials