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Background: The identification of people at risk of cognitive impairment is essential for improving recruitment in secondary prevention trials of Alzheimer's disease. We aimed to test and qualify a biomarker risk assignment algorithm (BRAA) to identify participants at risk of developing mild cognitive impairment due to Alzheimer's disease within 5 years, and to evaluate the safety and efficacy of low-dose pioglitazone to delay onset of mild cognitive impairment in these at-risk participants. Methods: In this phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group study, we enrolled cognitively healthy, community living participants aged 65–83 years from 57 academic affiliated and private research clinics in Australia, Germany, Switzerland, the UK, and the USA. By use of the BRAA, participants were grouped as high risk or low risk. Participants at high risk were randomly assigned 1:1 to receive oral pioglitazone (0·8 mg/day sustained release) or placebo, and all low-risk participants received placebo. Study investigators, site staff, sponsor personnel, and study participants were masked to genotype, risk assignment, and treatment assignment. The planned study duration was the time to accumulate 202 events of mild cognitive impairment due to Alzheimer's disease in White participants who were at high risk (the population on whom the genetic analyses that informed the BRAA development was done). Primary endpoints were time-to-event comparisons between participants at high risk and low risk given placebo (for the BRAA objective), and between participants at high risk given pioglitazone or placebo (for the efficacy objective). The primary analysis included all participants who were randomly assigned, received at least one dose of study drug, and had at least one valid post-baseline visit, with significance set at p=0·01. The safety analysis included all participants who were randomly assigned and received at least one dose of study medication. An efficacy futility analysis was planned for when approximately 33% of the anticipated events occurred in the high-risk, White, non-Hispanic or Latino group. This trial is registered with ClinicalTrials.gov, NCT01931566. Findings: Between Aug 28, 2013, and Dec 21, 2015, we enrolled 3494 participants (3061 at high risk and 433 at low risk). Of those participants, 1545 were randomly assigned to pioglitazone and 1516 to placebo. 1104 participants discontinued treatment (464 assigned to the pioglitazone group, 501 in the placebo high risk group, and 139 in the placebo low risk group). 3399 participants had at least one dose of study drug or placebo and at least one post-baseline follow-up visit, and were included in the efficacy analysis. 3465 participants were included in the safety analysis (1531 assigned to the pioglitazone group, 1507 in the placebo high risk group, and 427 in the placebo low risk group). In the full analysis set, 46 (3·3%) of 1406 participants at high risk given placebo had mild cognitive impairment due to Alzheimer's disease, versus four (1·0%) of 402 participants at low risk given placebo (hazard ratio 3·26, 99% CI 0·85–12·45; p=0·023). 39 (2·7%) of 1430 participants at high risk given pioglitazone had mild cognitive impairment, versus 46 (3·3%) of 1406 participants at high risk given placebo (hazard ratio 0·80, 99% CI 0·45–1·40; p=0·307). In the safety analysis set, seven (0·5%) of 1531 participants at high risk given pioglitazone died versus 21 (1·4%) of 1507 participants at high risk given placebo. There were no other notable differences in adverse events between groups. The study was terminated in January, 2018, after failing to meet the non-futility threshold. Interpretation: Pioglitazone did not delay the onset of mild cognitive impairment. The biomarker algorithm demonstrated a 3 times enrichment of events in the high risk placebo group compared with the low risk placebo group, but did not reach the pre-specified significance threshold. Because we did not complete the study as planned, findings can only be considered exploratory. The conduct of this study could prove useful to future clinical development strategies for Alzheimer's disease prevention studies. Funding: Takeda and Zinfandel.

Functional neurological disorder (FND) is a common and disabling disorder that is often considered difficult to treat, particularly in adults. Psychological therapies are often recommended for FND. Outcome research on psychological therapies for FND has grown in recent years but has not been systematically evaluated since 2005. This study aims to build on that by systematically reviewing the evidence-base for individual outpatient cognitive behavioural and psychodynamic psychotherapies for FND. Medical databases were systematically searched for prospective studies of individual outpatient psychotherapy for FND with at least five adult participants. Studies were assessed for methodological quality using a standardised assessment tool. Results were synthesised, and effect sizes calculated for illustrative purposes. The search strategy identified 131 relevant studies, of which 19 were eligible for inclusion: 12 examining cognitive behavioural therapy (CBT) and 7 investigating psychodynamic therapy (PDT). Eleven were pre–post studies and eight were randomised controlled trials. Most studies recruited a single symptom-based subtype rather than all presentations of FND. Effect sizes, where calculable, showed generally medium-sized benefits for physical symptoms, mental health, well-being, function and resource use for both CBT and PDT. Outcomes were broadly comparable across the two therapy types, although a lack of high-quality controlled trials of PDT is a significant limitation, as is the lack of long-term follow-up data in the majority of identified CBT trials. In conclusion, both CBT and PDT appear to potentially offer some benefit for FND, although better quality studies are needed.

Estimation of attenuation from positron emission tomography (PET) data only is of interest for hybrid PET-MR and systems where CT is not available or recommended. However, when using data from a single energy window, emission-based non-time-of-flight (TOF) PET attenuation correction (AC) methods suffer from “cross-talk” artifacts. Based on earlier work, this article explores the hypothesis that cross-talk can be reduced by using more than one energy window. We propose an algorithm for the simultaneous estimation of both activity and attenuation images, as well as, the scatter component of the measured data from a PET acquisition, using multiple energy windows. The model for the measurements is 3-D and accounts for the finite energy resolution of PET detectors; it is restricted to single scatter. The proposed energy-based simultaneous maximum likelihood reconstruction of activity and attenuation with photopeak scatter re-estimation algorithm is compared with simultaneous estimation from a single energy window simultaneous maximum likelihood reconstruction of activity and attenuation with photopeak scatter re-estimation. The evaluation is based on simulations using the characteristics of the Siemens mMR scanner. Phantoms of different complexity were investigated. In particular, a 3-D XCAT torso phantom was used to assess the inpainting of attenuation values within the lung region. Results show that the cross-talk present in non-TOF maximum likelihood reconstruction of activity and attenuation reconstructions is significantly reduced when using multiple energy windows and indicate that the proposed approach warrants further investigation.

Objectives: There has been extensive research in evaluating chronic pain in the context of litigation while considering the implications that it can have on healthcare outcomes and rehabilitation progress. The aim of this article is to present retrospective observational data about the levels of disability and distress reported by patients with ongoing litigation at the start and following a UK-based multi-disciplinary pain management programme (PMP) when compared with those without litigation. Method: Between June 2014 and September 2017, 859 patients attended and completed a 16-day PMP at a tertiary-level National Health Service (UK) pain clinic. Patients were split into two groups: (1) litigation (n = 110) and (2) non-litigation (n = 749). As a part of the assessment procedure, the patients were given a battery of psychological and physical measures to complete over two time points. Results: Patients with litigation are statistically significantly more distressed at assessment but make comparable clinically meaningful change in PMP intervention when compared with a non-litigation sample. A very small proportion of the variance in depression scores post-treatment is accounted for by the context of litigation (0.5%), which may be accounted for by employment status. There was no effect of litigation on physical outcome post-intervention. Discussion: This article concludes that it is not appropriate to merely assume that the context of litigation results in limited positive psychological and physical outcomes post-PMP. There are some limitations to the clinical sample presented in respect to the conclusions.

Highlights • Novel methodology and software for MR-PET registration uncertainty analysis. • Registration software had the biggest effect on MR-PET registration precision, followed by reconstruction parameters (i.e., iterations, smoothing) and PET count level. • PVC can significantly improve the PET signal, but since it relies on precise MR-PET registration, it also increases PET signal variability and hence care should be taken when using it., Accurate regional brain quantitative PET measurements, particularly when using partial volume correction, rely on robust image registration between PET and MR images. We argue here that the precision, and hence the uncertainty, of MR-PET image registration is mainly driven by the registration implementation and the quality of PET images due to their lower resolution and higher noise compared to the structural MR images. We propose a dedicated uncertainty analysis for quantifying the precision of MR-PET registration, centred around the bootstrap resampling of PET list-mode events to generate multiple PET image realisations with different noise (count) levels. The effects of PET image reconstruction parameters, such as the use of attenuation and scatter corrections and different number of iterations, on the precision and accuracy of MR-PET registration were investigated. In addition, the performance of four software packages with their default settings for rigid inter-modality image registration were considered: NiftyReg, Vinci, FSL and SPM. Four distinct PET image distributions made of two early time frames (similar to cortical FDG) and two late frames using two amyloid PET dynamic acquisitions of one amyloid positive and one amyloid negative participants were investigated. For the investigated four PET frames, the biggest impact on the uncertainty was observed between registration software packages (up to 10-fold difference in precision) followed by the reconstruction parameters. On average, the lowest uncertainty for different PET frames and brain regions was observed with SPM and two iterations of fully quantitative image reconstruction. The observed uncertainty for the varying PET count-level (from 5% to 60%) was slightly lower than for the reconstruction parameters. We also observed that the registration uncertainty in quantitative PET analysis depends on amyloid status of the considered PET frames, with increased uncertainty (up to three times) when using post-reconstruction partial volume correction. This analysis is applicable for PET data obtained from either PET/MR or PET/CT scanners.

ObjectiveResponsiveness to direct verbal suggestions (suggestibility) has long been hypothesized to represent a predisposing factor for functional neurological disorder (FND) but previous research has yielded conflicting results. The aim of this study was to quantitatively evaluate whether FND patients display elevated suggestibility relative to controls via meta-analysis.MethodsFour electronic databases were searched in November 2019, with the search updated in April 2020, for original studies assessing suggestibility using standardized behavioural scales or suggestive symptom induction protocols in FND patients and controls. The meta-analysis followed Cochrane, PRISMA, and MOOSE guidelines. Data extraction and study quality coding were performed by two independent reviewers. Standardized suggestibility scores and responsiveness to symptom induction protocols were used to calculate standardized mean differences (SMDs) between groups.ResultsOf 26,643 search results, 19 articles presenting 11 standardized suggestibility datasets (FND: n = 316; control: n = 360) and 11 symptom suggestibility datasets (FND: n = 1285; control: n = 1409) were included in random-effects meta-analyses. Meta-analyses revealed that FND patients displayed greater suggestibility than controls on standardized behavioural scales (SMD, 0.48 [95% CI, 0.15, 0.81]) and greater responsiveness to suggestive symptom induction (SMD, 1.39 [95% CI, 0.92, 1.86]). Moderation analyses presented mixed evidence regarding the extent to which effect sizes covaried with methodological differences across studies. No evidence of publication bias was found.ConclusionsThese results corroborate the hypothesis that FND is characterized by heightened responsiveness to verbal suggestion. Atypical suggestibility may confer risk for FND and be a cognitive marker that can inform diagnosis and treatment of this condition.

A dualistic mind-body understanding of functional neurological disorders (FNDs), also known as conversion disorders, has led to the view that the cause of the symptom should be either psychological (psychogenic) or physical (neurogenic-"organic"). One of the most influential psychological approaches is the Freudian model of conversion, which suggests that FNDs arise from a defense process in which emotional stress is converted into physical symptoms. This conversion theory has been challenged in recent years, accompanied by a shift in emphasis toward neuropathophysiological models of FND and away from historical psychological concepts. In this review, the authors consider the contemporary relevance of the conversion model from the neuroscientific perspective to reconcile the role of both psychological and biological factors in FND. A narrative review of recent neuroscientific findings pertaining to the conversion model of FND, encompassing neuroimaging, cognitive psychology, biological markers, and epigenetic studies, was performed. Research on the role of psychological stressors is discussed. Neurobiological mechanisms of repression of traumatic memories and their translation into physical symptoms are then explored. Finally, the role of physical symptoms as a potential protective defense mechanism against social stressors is considered. The authors argue that the conversion concept is consistent with recent neuroscientific research findings, and the model allows psychological and neurobiological concepts to be reconciled within a single account of FND that begins to resolve the dualistic mind-body dichotomy.

ObjectivesWe aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes.MethodsA systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group.ResultsFive FND-specific measures were identified—three clinician-rated and two patient-rated—but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost–utility (eg, healthcare resource use and quality-adjusted life years).ConclusionsThere are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population.

With the availability of improved hardware and local point-spread function modelling, the presence of patient motion has become a major barrier to further improvements in the quality of PET images and their clinical efficacy. Although numerous approaches to compensate for patient motion have been proposed and are even commercially available, the additional hardware and extended setup time can preclude their routine clinical use. The MR modality on combined PET and MR (PET/MR) scanners can be used to correct motion with almost no additional setup time but currently must replace other MR acquisitions that may be required for clinic use. To overcome these problems, principal component analysis (PCA) and other data-driven techniques have been demonstrated to be able to reliably provide a signal related to patient motion based on raw PET data. Typically, these signals are used to split the PET acquisition into a discrete set of approximately motionfree time segments. This work introduces an approach where the PCA-signals are used as direct surrogates for the motion and regressed against rigid head motion parameters, enabling continuous pose estimation. A proof-of-concept is presented in which the approach is applied to upsample a low temporal resolution MR motion estimate. This proof-of-concept uses rapid echo planar imaging (EPI) data together with PET-derived motion signals. In a comparison of four techniques, nearest neighbour (NN) and linear temporal interpolation and linear and radial basis function (RBF) regression of pose against the PCA surrogate, we demonstrate that the model can be used to accurately interpolate pose continuously throughout the scan.

SIRF is a powerful PET/MR image reconstruction research tool for processing data and developing new algorithms. In this research, new developments to SIRF are presented, with focus on motion estimation and correction. SIRF’s recent inclusion of the adjoint of the resampling operator allows gradient propagation through resampling, enabling the MCIR technique. Another enhancement enabled registering and resampling of complex images, suitable for MRI. Furthermore, SIRF’s integration with the optimization library CIL enables the use of novel algorithms. Finally, SPM is now supported, in addition to NiftyReg, for registration. Results of MR and PET MCIR reconstructions are presented, using FISTA and PDHG, respectively. These demonstrate the advantages of incorporating motion correction and variational and structural priors. This article is part of the theme issue ‘Synergistic tomographic image reconstruction: part 2’.

Idiopathic environmental intolerance refers to a group of poorly understood health conditions characterized by heterogeneous somatic symptoms that occur in response to environmental triggers, but for which no physiological causes can be found. We focus on three varieties, namely symptoms attributed to (a) chemical substances, (b) electromagnetic fields, and (c) infrasound and vibroacoustic sources. As no clear link with organ pathology or dysfunction has been established so far, we review critical evidence about alternative causal mechanisms as a platform for a novel unifying model of these conditions. There is consistent evidence that expectancy and nocebo mechanisms are critically involved. Using recent predictive coding models of brain functioning, we describe a comprehensive new model to explain how symptoms come about and become linked to specific environmental cues. This new model integrates phenomenally different pathologies, suggests testable new hypotheses, and specifies implications for treatment.

Using the Internet to obtain health information (“online health research”, OHR) is commonplace. This paper provides a systematic narrative review of evidence concerning the relationship between OHR and health anxiety. We conclude that health anxiety is associated with more frequent self-reported OHR, heightened distress after OHR, and increased doctor visits post-OHR. Evidence suggests that OHR often has a reassurance seeking function and can relieve anxiety, but that it can also cause alarm and become a distressing, compulsive behaviour. We present a novel model that integrates these perspectives and existing research within a single explanatory framework that distinguishes between problematic OHR and compulsive OHR and describes the role of positive and negative metacognitions in their respective development.

Aims/Objectives Impulse control behaviors (ICBs) affect 15%–35% of Parkinson’s Disease patients. There is evidence of increased carer strain due to these behaviours; however, little is known about clinical variables mediating this effect. This study aims to investigate the factors predictive of carer burden within a cohort of Parkinson’s Disease patients with ICBs. Identification of such factors may allow for targeted therapeutic intervention. Method Data was collected from 45 patients with clinically significant ICBs and their carers including levodopa equivalent daily dosage, assessments of motor and neuropsychiatric symptoms, cognitive function and ICBs. Carer burden was assessed using the Zarit Burden Interview (ZBI). Univariate analyses were performed using Spearman’s Rank Correlation Coefficient. A backward model was used to remove variables to create a final multivariate model using ZBI score as the dependent variable. Results Univariate analysis identified significant correlations between ZBI and total NPI (rs=0.50, p Conclusions This is the largest study to date, looking at associations between carer burden and ICBs. Our findings indicate low mood, poor motivation, social disinhibition and neuropsychiatric symptom burden to be significant factors in carer burden. We also observe that carers reporting poorer health had increased carer strain. Further work should explore methods of physical and psychosocial support and coping strategies for carers.

Motion correction has been added to a PET-MR reconstruction tool, SIRF, by incorporating a registration package, NiftyReg. New functionality has been demonstrated in the context of estimating kinetic parameters in the left temporal lobe, comparing direct and indirect reconstructions and evaluating the impact of using motion correction.Principal component analysis was used to detect motion and to determine time frames, while STIR’s parametric-OSEM was used to perform the motion-corrected direct parametric reconstruction.It was found that the variance in the left temporal lobe decreased when motion correction was performed, and the same was true of direct reconstructions compared to indirect.With SIRF, the entirety of the demonstrated functionality can be performed from a single Matlab or Python script.

The current study aimed to explore the phenomenon of disease-related ‘query escalation’ in high/low health anxious Internet users ( N = 40). During a 15-minute health-related Internet search, participants rated their anxiety and the perceived seriousness of information on each page. Post-search interviews determined the reasons for, and effects of, escalating queries to consider serious diseases. Both groups were found to be significantly more anxious after escalating queries. The high group was significantly more likely to escalate queries. Evaluating personal relevance of material was the main reason for escalations and moderated anxiety post-escalation. We conclude that searching for online disease information can increase anxiety, particularly for people worried about their health.

This paper presents a simulation framework for dynamic PET-MR. The main focus of this framework is to provide motion-resolved MR and PET data and ground truth motion information. This can be used in the optimisation and quantitative evaluation of image registration and in assessing the error propagation due to inaccuracies in motion estimation in complex motion-compensated reconstruction algorithms. Contrast and tracer kinetics can also be simulated and are available as ground truth information. To closely emulate medical examination, input and output of the simulation are files in standardised open-source raw data formats. This enables the use of existing raw data as a template input and ensures seamless integration of the output into existing reconstruction pipelines. The proposed framework was validated in PET-MR and image registration applications. It was used to simulate a FDG-PET-MR scan with cardiac and respiratory motion. Ground truth motion information could be utilised to optimise parameters for PET and synergistic PET-MR image registration. In addition, a free-breathing dynamic contrast enhancement (DCE) abdominal scan of a patient with hepatic lesions was simulated. In order to correct for breathing motion, a motion-corrected image reconstruction scheme was used and a Toft's model was fit to the DCE data to obtain quantitative DCE-MRI parameters. Utilising the ground truth motion information, the dependency of quantitative DCE-MR images on the accuracy of the motion estimation was evaluated. We demonstrated that respiratory motion had to be available with an average accuracy of at least the spatial resolution of the DCE-MR images in order to ensure an improvement in lesions visualisation and quantification compared to no motion correction. The proposed framework provides a valuable tool with a wide range of scientific PET and MR applications and will be available as part of the open-source project Synergistic Image Reconstruction Framework (SIRF).

The combination of positron emission tomography (PET) with magnetic resonance (MR) imaging opens the way to more accurate diagnosis and improved patient management. At present, the data acquired by PET-MR scanners are essentially processed separately, but the opportunity to improve accuracy of the tomographic reconstruction via synergy of the two imaging techniques is an active area of research. In this paper, we present Release 2.1.0 of the CCP-PETMR Synergistic Image Reconstruction Framework (SIRF) software suite, providing an open-source software platform for efficient implementation and validation of novel reconstruction algorithms. SIRF provides user-friendly Python and MATLAB interfaces built on top of C++ libraries. SIRF uses advanced PET and MR reconstruction software packages and tools. Currently, for PET this is Software for Tomographic Image Reconstruction (STIR); for MR, Gadgetron and ISMRMRD; and for image registration tools, NiftyReg. The software aims to be capable of reconstructing images from acquired scanner data, whilst being simple enough to be used for educational purposes. The most recent version of the software can be downloaded from http://www.ccppetmr.ac.uk/downloads and https://github.com/CCPPETMR/ . Program summary Program Title: Synergistic Image Reconstruction Framework (SIRF) Program Files DOI: http://dx.doi.org/10.17632/s45f5jh55j.1 Licensing provisions: GPLv3 and Apache-2.0 Programming languages: C++, C, Python, MATLAB Nature of problem: In current practice, data acquired by PET-MR scanners are processed separately. Methods for improving the accuracy of the tomographic reconstruction using the synergy of the two imaging techniques are actively being investigated by the PET-MR research and development community, however, practical application is heavily reliant on software. Open-source software available to the PET-MR community – such as the PET package (STIR) (Thielemans et al., 2012) and the MR package Gadgetron (Hansen and Sorensen, 2013) – provide a basis for new synergistic PET-MR software. However, these two software packages are independent and have very different software architectures. They are mostly written in C++ but many researchers in the PET-MR community are more familiar with script-style languages, such as Python and MATLAB, which enable rapid prototyping of novel reconstruction algorithms. In the current situation it is difficult for researchers to exploit any synergy between PET and MR data. Furthermore, techniques from one field cannot easily be applied in the other. Solution method: In SIRF, the bulk of computation is performed by available advanced open-source reconstruction and registration software (currently STIR, Gadgetron and NiftyReg) that can use multithreading and GPUs. The SIRF C++ code provides a thin layer on top of these existing libraries. The SIRF layer has unified data-containers and access mechanisms. This C++ layer provides the basis for a simple and intuitive Python and MATLAB interface, enabling users to quickly develop and test their reconstruction algorithms using these scripting languages only. At the same time, advanced users proficient in C++ can directly utilise wider SIRF functionality via the SIRF C++ libraries that we provide.

Objective High symptom reporting (HSR) and medically unexplained symptoms (MUS) are associated with considerable distress, disability, healthcare utilization and costs, but are poorly understood, and current treatments are of limited benefit. Most models of HSR and MUS implicate cognitive-perceptual factors, such as increased body-focused attention, reduced perceptual thresholds and a tendency to experience somatic misperception, but little is known about the causal role of these variables. We investigated this issue by studying whether there is a longitudinal relationship between perceptual-attentional variables and later clinical outcomes in primary care patients. Method Primary care patients (N = 102) completed clinical (physical symptom reporting, health anxiety and healthcare utilization) and perceptual-attentional (body-focused attention, perceptual threshold, somatic misperception) measures at baseline and then again six months later (N = 72). Hierarchical regression was used to examine cross-lagged relationships between baseline and follow-up scores. Results Contrary to expectation, attending away from the body at baseline predicted increased not decreased symptom reporting six months later. Neither perceptual threshold nor somatic misperception predicted clinical outcomes at six months. Conclusions These findings suggest that body avoidance, rather than increased body focus, contribute to the development of HSR. Future studies should consider the potential clinical benefits of reducing bodily avoidance, via techniques that promote adaptive engagement with bodily sensations.

Chronic pain is exacerbated by maladaptive cognition such as pain catastrophizing (PC). Biomarkers of PC mechanisms may aid precision medicine for chronic pain. Here, we investigate EEG biomarkers using mass univariate and multivariate (machine learning) approaches. We test theoretical notions that PC results from a combination of augmented aversive-value encoding (“magnification”) and persistent expectations of pain (“rumination”). Healthy individuals with high or low levels of PC underwent an experimental pain model involving nociceptive laser stimuli preceded by cues predicting forthcoming pain intensity. Analysis of EEG acquired during the cue and laser stimulation provided event-related potentials (ERPs) identifying spatially and temporally-extended neural representations associated with pain catastrophizing. Specifically, differential neural responses to cues predicting high vs. low intensity pain (i.e. aversive value encoding) were larger in the high PC group, largely originating from mid-cingulate and superior parietal cortex. Multivariate spatiotemporal EEG patterns evoked from cues with high aversive value selectively and significantly differentiated the high PC from low PC group (64.6% classification accuracy). Regression analyses revealed that neural patterns classifying groups could be partially predicted (R2 = 28%) from those neural patterns classifying the aversive value of cues. In contrast, behavioural and EEG analyses did not provide evidence that PC modifies more persistent effects of prior expectation on pain perception and nociceptive responses. These findings support the hypothesis of magnification of aversive value encoding but not persistent expression of expectation in pain catastrophizers. Multivariate patterns of aversive value encoding provide promising biomarkers of maladaptive cognitive responses to chronic pain that have future potential for psychological treatment development and clinical stratification.

Aims and methodTo develop and pilot a clinician-rated outcome scale to evaluate symptomatic outcomes in liaison psychiatry services. Three hundred and sixty patient contacts with 207 separate individuals were rated using six subscales (mood, psychosis, cognition, substance misuse, mind–body problems and behavioural disturbance) plus two additional items (side-effects of medication and capacity to consent for medical treatment). Each item was rated on a five-point scale from 0 to 5 (nil, mild, moderate, severe and very severe).ResultsThe liaison outcome measure was acceptable and easy to use. All subscales showed acceptable interrater reliability, with the exception of the mind–body subscale. Overall, the measure appears to show stability and sensitivity to change.Clinical implicationsThe measure provides a useful and robust way to determine symptomatic change in a liaison mental health setting, although the mind–body subscale requires modification.Declaration of interestNone.

The current study aimed to obtain health anxious students’ perspectives on their reasons for using the Internet to obtain health information, and the nature and effects of such usage. Data were gathered using semi-structured interviews with 20 postgraduate and undergraduate students identified as highly health anxious, and were examined using thematic analysis. Results suggested that themes were organized by different stages of the search process. Reasons for searching included curiosity, anxiety/worry about undiagnosed symptoms, and remedy-seeking. Both positive (e.g. reassurance) and negative (e.g. uncertainty) outcomes were reported. Findings from the current study suggest that the Internet constitutes an important resource for obtaining health information by health anxious individuals, with the potential to both reduce and exacerbate health anxiety.

Reason for withdrawal from publication Protocol withdrawn. Cochrane Oral Health was unable to maintain contact with the contact author. The co-authors are unable to take over this protocol.

This paper describes an algorithm for 3D reconstruction of a smooth surface with a relatively dense set of self-similar point features from two calibrated views. We bypass the usual correspondence problem by triangulating a point in space from all pairs of features satisfying the epipolar constraint. The surface is then extracted from the resulting point cloud by taking advantage of the statistical and geometric properties of the point distribution on the surface. Results are presented for computer simulations and for a laboratory experiment on a silicon gel phantom used in a breast cancer screening project.

Diabet. Med. 28, 1028–1033 (2011) Abstract Aim Maturity-onset diabetes of the young is a monogenic form of familial, young-onset diabetes. It is rare (∼1% diabetes) and may be misdiagnosed as Type 1 diabetes and inappropriately treated with insulin. Type 1 diabetes is characterized by the presence of islet autoantibodies, including glutamate decarboxylase (GAD) and islet antigen-2 (IA-2) antibodies. The prevalence of islet autoantibodies is unknown in maturity-onset diabetes of the young and may have the potential to differentiate this form of diabetes from Type 1 diabetes. The aim of this study was to determine the prevalence of GAD and IA-2 antibodies in patients with maturity-onset diabetes of the young and Type 1 diabetes. Methods We measured plasma GAD and IA-2 antibodies in 508 patients with the most common forms of maturity-onset diabetes of the young (GCK: n = 227; HNF1A: n = 229; HNF4A: n = 52) and 98 patients with newly diagnosed Type 1 diabetes (diagnosed

Digital image-based elasto-tomography technology relies on obtaining high-resolution images of a breasts surface under high-frequency actuation, typically in the range of 50-100 Hz. Off-the-shelf digital cameras and imaging elements are unable to capture images directly at these speeds. A method based on strobe imaging is presented for obtaining the required high-speed image capture at a resolution of 1280 times 1024 pixels and actuation frequency of 100 Hz. The final working system produced images that enabled effective 3-D motion tracking of the surface of a silicon phantom. The motion is tracked accurately using a novel Euclidean Invariant signature method.

The effects of ultraviolet light exposure on scar pigmentation are well documented. There is a commonly held belief among physicians that sun exposure may also worsen the appearance of fresh scars and result in excess collagen deposition. However, few studies have documented a relationship between ultraviolet light exposure and hypertrophic scarring. This study sought to evaluate the effect of ultraviolet light exposure on scar hypertrophy in an established rabbit model of cutaneous scarring.Four 7-mm ulcers were created on the ventral ears of eight rabbits. Starting on postoperative day 15, half of the wounds were exposed to ultraviolet-B radiation daily for either 7 or 14 days. Ultraviolet-B-exposed (n = 16) and control (n = 16) scars were harvested on postoperative day 32 for histologic and reverse-transcriptase polymerase chain reaction analysis.Exposure to ultraviolet-B radiation for 7 or 14 days was associated with a 52 percent (p0.01) or 74 percent (p0.05) reduction in scar volume, respectively, compared with controls. In wounds subjected to ultraviolet-B radiation for 14 days, collagen type I-alpha2 mRNA expression was 29 percent lower than in controls (p0.05). There was no difference in the mRNA expression of transforming growth factor-beta1.: These short-term observations demonstrate that ultraviolet-B radiation exposure reduces scar hypertrophy in this clinically relevant animal model. A reduction in collagen production or increase in collagen breakdown may account for this result. However, sunscreen should still be used as primary protection when skin is exposed to direct sunlight.

This paper outlines a method for accurately tracking surface motion on an actuated breast as part of a Digital Image-based Elasto-Tomography (DIET) breast cancer screening project. The tracking method is validated in both simulation and experiment on a silicon breast phantom which has similar elasticity characteristics to human breast tissue. Given mean reprojection error ranges between 0.3 and 0.5 pixels for 2M pixel cameras the end result is sub-millimetre surface tracking of a silicon phantom actuated at 100 Hz. This highly accurate, fast and low cost method of tracking is thus well suited to a DIET system.

Blood flow through a vessel depends upon compliance and resistance. Resistance changes dynamically due to vasoconstriction and vasodilation as a result of metabolic activity, thus allowing for more or less flow to a particular area. The structure responsible for directing blood to the different areas of the brain and supplying the increase flow is the cerebral arterial circle (CAC). A series of 1D equations were utilized to model propagating flow and pressure waves from the left ventricle of the heart to the CAC. The focus of the current research was to understand the collateral capability of the circle. This was done by decreasing the peripheral resistance in each of the efferent arteries, up to 10% both unilaterally and bilaterally. The collateral patterns were then analyzed. After the initial 60 simulations, it became apparent that flow could increase beyond the scope of a 10% reduction and still be within in vivo conditions. Simulations with higher percentage decreases were performed such that the same amount of flow increase would be induced through each of the efferent arteries separately, same flow tests (SFTs), as well as those that were found to allow for the maximum flow increase through the stimulated artery, maximum flow tests (MFTs). The collateral pattern depended upon which efferent artery was stimulation and if the stimulation was unilaterally or bilaterally induced. With the same amount of flow increase through each of the efferent arteries, the MCAs (middle cerebral arteries) had the largest impact on the collateral capability of the circle, both unilaterally and bilaterally.

Background Agitation is a common experience for people living with dementia, particularly as day-to-day function and cognition start to decline more. At the present time there are limited pharmacological options for relieving agitation and little is known about the safety and efficacy of opioid drugs in this setting. Objectives To determine the clinical efficacy and safety of opioids for agitation in people with dementia. Search methods We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, on 13 June 2014 using the terms: narcotic OR opioid OR opium OR morphine OR buprenorphine OR codeine OR dextromoramide OR diphenoxylate OR dipipanone OR dextropropoxyphene OR propoxyphene OR diamorphine OR dihydrocodeine OR alfentanil OR fentanyl OR remifentanil OR meptazinol OR methadone OR nalbuphine OR oxycodone OR papaveretum OR pentazocine OR meperidine OR pethidine OR phenazocine OR hydrocodone OR hydromorphone OR levorphanol OR oxymorphone OR butorphanol OR dezocine OR sufentanil OR ketobemidone. ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases such as MEDLINE, EMBASE and PscyINFO, as well as numerous trial registries and grey literature sources. Selection criteria Randomised, controlled trials of opioids compared to placebo for agitation in people with dementia. Data collection and analysis Two authors independently assessed the studies identified by the search against the inclusion criteria. Main results There are currently no completed randomised, placebo controlled trials of opioids for agitation in dementia. There are two potentially relevant trials still in progress. Authors' conclusions We found insufficient evidence to establish the clinical efficacy and safety of opioids for agitation in people with dementia. There remains a lack of data to determine if or when opioids either relieve or exacerbate agitation. More evidence is needed to guide the effective, appropriate and safe use of opioids in dementia.

Introduction The biologic anti-tumour necrosis factor alpha (anti-TNFα) agents infliximab and adalimumab are monoclonal antibodies with binding specificity to TNFα, which are used for the treatment of Crohn’s disease. Clinical response is varied from complete with mucosal healing, to primary non-response, loss of response and adverse drug reactions. Measuring trough blood levels of infliximab and adalimumab may guide clinical management. The sample handling requirements for infliximab and adalimumab were previously unknown. Aim The aim of this study was to determine the in vitro stability of infliximab and adalimumab in samples stored for up to seven days at room temperature. Methods Samples were stored as clotted whole blood or serum at room temperature for up to seven days, before being frozen (−20℃) and analysed as a batch for either infliximab or adalimumab. Results No significant difference between the concentration of infliximab and adalimumab measured in samples stored as serum or whole blood for seven days at room temperature, as compared to baseline was found ( t-test; infliximab: P = .35 [serum], P = .38 [whole blood]; adalimumab: P = .12 [serum], P = .49 [whole blood]). Conclusion The stability of infliximab and adalimumab at room temperature for seven days allows samples to be posted direct from clinics and research centres to the analysing laboratory.

Background: Nevus sebaceus (NS) of Jadassohn is a common congenital lesion associated with numerous benign and malignant tumors. However, mucoepidermoid carcinoma (MEC) has not been described in association with NS. Methods: We describe an unusual case of MEC arising within NS. Results: A 72-year-old man presented with an enlarging plaque on his forehead, along the hairline. Physical examination revealed a mounded, erythematous lesion that was completely excised. Histological evaluation revealed a typical MEC with areas of squamous and adenomatous differentiation with foci of typical intermediate cells. Conclusion: The diagnosis of MEC is an important one, because it portends a poor prognosis, requiring long follow-up. This is, to our knowledge, the first report of MEC arising within NS.

Health-related Internet use has grown rapidly, yet little research has considered how health anxious individuals use the Internet for this purpose. Our aim was to examine the relationships between health anxiety and the extent of, reasons for, and consequences of health-related Internet usage in university students (n = 255). Responses on a purpose-made Internet use questionnaire were correlated with health anxiety scores; multiple regression analyses controlling for depression and anxiety were also conducted. Health anxiety positively correlated with (all ps < .01): frequency of health-related searching (r(s) = .163), proportion of health-related information sought (r(s) = .200), time spent online for health purposes (r(s) = .166), and number of searches for both illness (r(s) = .453) and wellness (r(s) = .208) information. Health anxiety further positively correlated with advantages perceived in health-related Internet use (r(s) = .183), heightened tension (r(s) = .364) and relief (r(s) = .174) post-search, and perceived doctor disadvantages (r(s) = .306), yet a greater likelihood to visit a doctor post-search (r(s) = .217). Health anxiety also correlated with six measures of possible addiction to using the Internet for health purposes (r(s) range = .171 to .366, all ps < .01). Some (including several potentially dysfunctional) aspects of health-related Internet use correlate with health anxiety. Research evaluating the possible role of Internet use in the development and maintenance of health anxiety is warranted.

Purpose The occurrence of psychiatric symptoms after temporal lobectomy is well documented. The aim of the present study was to identify preoperative factors that predict postoperative psychiatric outcome. Methods We studied the case notes of 121 patients (from an initial sample of 167) who underwent temporal lobectomy at the National Hospital of Neurology and Neurosurgery, Queen Square, London, between 1988 and 1997. Data concerning gender, laterality of lesion, pathology, seizure outcome, psychiatric history, psychiatric outcome, resection volume, telemetry, and MRI scans were systematically collected. Factors that predict the occurrence of postoperative psychiatric symptomatology were investigated using correlational, chi(2), and logistic regression techniques. Results Poor postoperative psychiatric outcome in general was positively associated with preoperative bilateral independent spike discharges at telemetry. The size of surgical resection was positively correlated with the occurrence of postoperative emotional lability. The laterality of the epileptogenic lesion was not associated with a poor psychiatric outcome. Developmental lesions were associated with a good psychiatric outcome at a marginally significant level. Patients with a preoperative psychiatric history and de novo psychiatric symptomatology had a poorer surgical outcome in terms of seizure frequency, also at a marginally significant level. A significant correlation was found between a past psychiatric history and seizure outcome. Conclusions We identified a high frequency of psychiatric symptoms both before and after temporal lobectomy, demonstrating that it is not a benign procedure from the point of view of psychopathology. Our results show that there are certain predictive factors that may help identify patients most at risk for postoperative psychiatric disorders.

Purpose We have previously reported that one in six patients stops experiencing psychogenic nonepileptic seizures (PNES) following our communication protocol. This prospective multicentre study describes a psycho-educational intervention for PNES building on the initial communication of the diagnosis and examines the feasibility of its delivery by healthcare professionals with minimal experience in psychological therapies. Method Three healthcare professionals with minimal training in psychological therapies took part in a one-day training course. 20 participants attended for a four-session manualised psycho-educational intervention delivered at three different clinical neuroscience centres. Participants completed self-report measures prior to the intervention at baseline ( n =29) and seven months after diagnosis ( n =13) measures included seizure frequency, health related quality of life, healthcare utilisation, activity levels, symptom attributions and levels of functioning. Therapy sessions were audiorecorded and manual adherence assessed. Results Of 29 patients enrolled into the study, 20 started and 13 completed the intervention and provided follow-up information. At follow-up, 4/13 of patients had achieved complete seizure control and a further 3/13 reported a greater than 50% improvement in seizure frequency. After training, epilepsy nurses and assistant psychologists demonstrated sufficient adherence to the manualised psycho-educational intervention in 80% of sessions. Conclusion The delivery of our brief manualised psycho-educational intervention for PNES by health professionals with minimal training in psychological treatment was feasible. The intervention was associated with higher rates of PNES cessation than those observed in our previous studies describing the short-term outcome of the communication of the diagnosis alone. An RCT of the intervention is justified but a significant proportion of drop-outs will have to be anticipated.

BACKGROUND: Non-motor symptoms are present in Parkinson's disease (PD) and a key determinant of quality of life. The Non-motor Symptoms Scale (NMSS) is a validated scale that allows quantifying frequency and severity (burden) of NMS. We report a proposal for using NMSS scores to determine levels of NMS burden (NMSB) and to complete PD patient classification.METHODS: This was an observational, cross-sectional international study of 935 consecutive patients. Using a distribution of NMSS scores by quartiles, a classification based on levels from 0 (no NMSB at all) to 4 (very severe NMSB) was obtained and its relation with Hoehn and Yahr (HY) staging, motor and health-related quality of life scales was analyzed. Concordance between NMSB levels and grouping based on clinician's global impression of severity, using categorical regression, was determined. Disability and HRQoL predictors were identified by multiple regression models.RESULTS: The distribution of motor and QoL scales scores by HY and NMSB levels was significantly discriminative. The difference in the classification of cases for both methods, HY and NMSB, was significant (gamma = 0.45; ASE = 0.032). Concordance between NMSB and global severity-based levels from categorical regression was 91.8%, (kappaw = 0.97). NMS score was predictor of disability and QoL.CONCLUSIONS: Current clinical practice does not address a need for inclusion of non-motor scores in routine assessment of PD in spite of the overwhelming influence of NMS on disability and quality of life. Our data overcome the problems of "pure motor assessment" and we propose a combined approach with addition of NMSB levels to standard motor assessments.

We previously described a communication strategy for the delivery of the diagnosis of psychogenic non-epileptic seizures (PNES) that was acceptable and effective at communicating the psychological cause of PNES. This prospective multicenter study describes the short-term seizure and psychosocial outcomes after the communication of the diagnosis and with no additional treatment. Participants completed self-report measures at baseline, two and six months after the diagnosis (seizure frequency, HRQoL, health care utilization, activity levels, symptom attributions and levels of functioning). Thirty-six participants completed the self-report questionnaires. A further eight provided seizure frequency data. After six months, the median seizure frequency had dropped from 10 to 7.5 per month (p = 0.9), 7/44 participants (16%) were seizure-free, and an additional 10/44 (23%) showed greater than 50% improvement in seizure frequency. Baseline questionnaire measures demonstrated high levels of impairment, which had not improved at follow-up. The lack of change in self-report measures illustrates the need for further interventions in this patient group.

When attempting to detect a near-threshold signal, participants often incorrectly report the presence of a signal, particularly when a stimulus in a different modality is presented. Here we investigated the effect of prior experience of bimodal visuotactile stimuli on the rate of falsely reported touches in the presence of a light. In Experiment 1, participants made more false alarms in light-present than light-absent trials, despite having no experience of the experimental visuotactile pairing. This suggests that light-evoked false alarms are a consequence of an existing association, rather than one learned during the experiment. In Experiment 2, we sought to manipulate the strength of the association through prior training, using supra-threshold tactile stimuli that were given a high or low association with the light. Both groups still exhibited an increased number of false alarms during light-present trials, however, the low association group made significantly fewer false alarms across conditions, and there was no corresponding group difference in the number of tactile stimuli correctly identified. Thus, while training did not affect the boosting of the tactile signal by the visual stimulus, the low association training affected perceptual decision-making more generally, leading to a lower number of illusory touch reports, independent of the light. © 2011 Elsevier B.V.

It is well known that stimuli grab attention to their location, but do they also grab attention to their sensory modality? The modality shift effect (MSE), the observation that responding to a stimulus leads to reaction time benefits for subsequent stimuli in the same modality, suggests that this may be the case. If noninformative cue stimuli, which do not require a response, also lead to benefits for their modality, this would suggest that the effect is automatic. We investigated the time-course of the visuotactile MSE and the difference between the effects of cues and targets. In Experiment 1, when visual and tactile tasks and stimulus locations were matched, uninformative cues did not lead to reaction time benefits for targets in the same modality. However, the modality of the previous target led to a significant MSE. Only stimuli that require a response, therefore, appear to lead to reaction time benefits for their modality. In Experiment 2, increasing attention to the cue stimuli attenuated the effect of the previous target, but the cues still did not lead to a MSE. In Experiment 3, a MSE was demonstrated between successive targets, and this effect decreased with increasing intertrial intervals. Overall, these studies demonstrate how cue- and target-induced effects interact and suggest that modalities do not automatically capture attention as locations do; rather, the MSE is more similar to other task repetition effects.

The performance of AlGaN/GaN high electron mobility transistors (HEMTs) with an Al x Si y N z passivation is reported for the first time. Thin films (30 nm) of Al x Si y N z and Si y N z were used to passivate devices (fabricated side-by-side) and their performance was compared in both small signal and large signal measurement environments. Examination of MIS structures with each dielectric by capacitance-voltage measurements revealed the Al x Si y N z provides a net negative fixed charge density allowing controlled depletion of the two dimensional electron gas (2DEG) in ungated regions of the channel. This is in contrast to Si y N z passivation where the surface depletion of the 2DEG is almost completely removed [1], which results in the full channel charge existing in the ungated portions of the channel. Reducing the charge in the ungated portions of the channel can be used to reduce the electric field at high drain bias with small increases in source and drain access resistance. Reduction of channel charge using a MIS gate extension (field plate) is now commonly used to increase the device performance at large drain bias. The charged dielectric approach described in this study allows for the elimination of the field plate (and its associated parasitic capacitances) while maintaining state-of-the-art performance at drain biases up to 55 V for a device with a 0.2 micron gate length.

Breast cancer is one of the most prevalent forms of cancer in the world today. The search for effective treatment and screening methods is a highly active area of research. The Digital Image-based Elasto-Tomography (DIET) project is a new breast cancer screening system under development, where surface motion from the mechanically actuated breast is measured in 3D, and used as input to an inverse problem solving for breast elasticity. Cancerous lesions appear as high contrast features, being an order of magnitude stiffer than healthy tissue. The 3D motion capture is measured by an array of digital cameras using computer vision techniques. This paper presents a computer vision imaging system for the capture of 3D breast surface motion for the DIET system, including the image acquisition system, camera calibration, and 3D surface and motion reconstruction. Results are presented for experiments performed with silicone gel phantoms, with conditions designed to replicate the clinical procedure. Full 3D surface motion is successfully captured using an array of five cameras. Some successful results from the DIET inverse problem are also presented to demonstrate the viability of the system in practice.

Peripheral cues are thought to facilitate responses to stimuli presented at the same location because they lead to exogenous attention shifts. Facilitation has been observed in numerous studies of visual and auditory attention, but there have been only four demonstrations of tactile facilitation, all in studies with potential confounds. Three studies used a spatial (finger versus thumb) discrimination task, where the cue could have provided a spatial framework that might have assisted the discrimination of subsequent targets presented on the same side as the cue. The final study circumvented this problem by using a non-spatial discrimination; however, the cues were informative and interspersed with visual cues which may have affected the attentional effects observed. In the current study, therefore, we used a non-spatial tactile frequency discrimination task following a non-informative tactile white noise cue. When the target was presented 150 ms after the cue, we observed faster discrimination responses to targets presented on the same side compared to the opposite side as the cue; by 1000 ms, responses were significantly faster to targets presented on the opposite side to the cue. Thus, we demonstrated that tactile attentional facilitation can be observed in a non-spatial discrimination task, under unimodal conditions and with entirely non-predictive cues. Furthermore, we provide the first demonstration of significant tactile facilitation and tactile inhibition of return within a single experiment.

A Digital Image-based Elasto-Tomography (DIET) system for breast cancer screening has been proposed in which the elastic properties of breast tissue are recovered by solving an inverse problem on the surface motion of a breast under low frequency (50-100 Hz) mechanical actuation. The proposed means for capturing the surface motion of the breast in 3D is to use a stroboscope to capture images from multiple digital cameras at preselected phase angles. Photogrammetric techniques are then used to reconstruct matched point features in 3D. Since human skin lacks high contrast visual features, it is necessary to introduce artificial fiducials which can be easily extracted from digital images. The chosen fiducials are points in three different colours in differing proportions randomly applied to the skin surface. A three-dimensional signature which is invariant to locally Euclidean transformations between images is defined on the points of the lowest proportion colour. The approximate local Euclidean invariance between adjacent frames enables these points to be matched using this signature. The remaining points are matched by interpolating the transformation of the matched points. This algorithm has significant performance gains over conventional gradient-based tracking algorithms because it utilises the intrinsic problem geometry. Successful results are presented for simulated image sequences and for images of a mechanically actuated viscoelastic gel phantom with tracking errors within 3 pixels. The errors in the phantom sequence correspond to less than 0.3 mm error in space, which is more than sufficient accuracy for the DIET system.

Digital Image-based Elasto-Tomography (DIET) is an emerging technology for non-invasive breast cancer screening. This technology actuates breast tissue and measures the surface motion using digital imaging technology. The internal distribution of stiffness is then reconstructed using Boundary Element or Finite Element Methods (FEM or BEM). However, obtaining accurate imaging at high frequency and high resolution in terms of numbers of pixels is challenging if enough accuracy is to be obtained in the motion sensing to deliver a useful result. The overall focus of such mechatronic and digitally centred systems is on providing a low-cost, radiation dose-free and portable screening system capable of screening numerous patients per day — in direct contrast to current low throughput, non-portable and high cost x-ray and MRI based approaches. Thus, DIET technology relies on obtaining high resolution images of a breasts surface under high frequency actuation, typically in the range of 50–100Hz. Off-the-shelf digital cameras and imaging elements are unable to capture images directly at these speeds. A method is presented for obtaining the required high speed image capture at a resolution of 1280×1024 pixels and actuation frequency of 100Hz. The prototype apparatus presented uses two imaging sensors in combination with frame grabbers and a dSpace™ control system, to produce an automated image capture system. The system integrates a precision controlled strobe lighting system to selectively capture sinusoids at different points in the sinusoidal cycle of response. The final working system produced images that enabled effective 3D motion tracking of the surface of a silicon phantom actuated at 100Hz. The surface of the phantom was strobed at pre-selected phases from 0 to 360 degrees, and an image was captured for each phase. The times at which image capture occurred were calculated for a phase lag increment of 10 degrees resulting in an image effectively every 0.00028s for the actuator cycle of 0.01s. The comparison of the actual trigger times and pre-selected ideal trigger times gave a mean absolute error of 1.4%, thus demonstrating the accuracy of the final system. Final validation is performed using this system to track motion in a silicon gel phantom. The motion is tracked accurately using a novel Euclidean Invariant signature method. Both cameras delivered similar results with over 90% of points tracked to within 1–2%. This level of accuracy confirms the ability to effectively accurately reconstruct the stiffness as validated in other related studies.

Airflow over mountainous terrain can produce atmospheric waves in the lee of the mountains that have large vertical air velocities. These waves are used as sources of lift by sailplane pilots. Methods are developed for inverting flight data of airspeed and GPS-derived position to obtain estimates of the vector windspeed in mountain waves. Data from flight path segments with significantly different ground velocities within a region of constant windspeed give a well-determined solution for the windspeed. The methods are applied to flight data from a Perlan Project flight in lee waves of the Sierra Nevada Mountains in California.© (2004) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Background: Patients with neurologically unexplained symptoms (NUS) often have a previous history of other medically unexplained symptoms. A past history of such symptoms can help make a positive diagnosis of a somatoform or affective disorder, and enable appropriate management strategies. However, information on past medical diagnoses is primarily obtained from patient interviews and may be inaccurate, particularly in patients with NUS. Objective: To assess the reliability of past medical diagnoses reported by patients with NUS compared with patients with confirmed neurological disease (ND) without suspicion of somatoform illness. Methods: 21 patients with NUS and 16 patients with ND were interviewed about their current and past medical problems and diagnoses. The accuracy of the reported diagnoses was assessed through examination of their complete general practice notes. Results: The median number of previous diagnoses reported by patients with NUS was significantly higher than in controls (7 v 3, p = 0.001). There was no difference in the median number of confirmed diagnoses between the two groups (2 v 2.5); however, the median percentage of reported diagnoses confirmed by investigations was significantly smaller in the NUS group (22% v 80%, p = 0.001). The additional diagnoses reported by patients with NUS not only comprised functional syndromes such as irritable bowel syndrome or non-cardiac chest pain (6% v 0%, p = 0.01), but also organic diagnoses which had either been unequivocally excluded (5% v 0%, p = 0.006), were based on equivocal findings often found after multiple investigations (9% v 0%, p = 0.01), or had not been investigated before a clinical diagnosis was made (50% v 18%, p = 0.04). Conclusion: Reported previous diagnoses should not be taken at face value when the current differential diagnosis includes a functional/somatoform neurological syndrome, particularly if the list of past medical diagnoses is long. Confirmation of previous diagnoses from alternative sources may contribute to a diagnosis of somatoform disorder, allowing appropriate management strategies for the current (and past) complaints to be initiated.

One of the UK Government's key commitments is to develop an integrated transport policy and its intention is to produce a White paper during 1998. The purpose of this paper is to discuss how intelligent transport systems (ITS) might contribute to delivering that policy and identify what actions are required if we are to fully exploit its potential. The paper covers the following areas: background to the current policy position; contribution of ITS to Government policy aims; potential benefits of ITS facilities; and national action plan.