Novel high-efficiency 2D position-sensitive ZnS:Ag/6LiF scintillator detector for neutron diffraction.

Scintillator-based ZnS:Ag/6LiF neutron detectors have been under development at ISIS for more than three decades. Continuous research and development aim to improve detector capabilities, achieve better performance and meet the increasingly demanding requirements set by neutron instruments. As part of this program, a high-efficiency 2D position-sensitive scintillator detector with wavelength-shifting fibres has been developed for neutron-diffraction applications. The detector consists of a double scintillator-fibre layer to improve detection efficiency. Each layer is made up of two orthogonal fibre planes placed between two ZnS:Ag/6LiF scintillator screens. Thin reflective foils are attached to the front and back scintillators of each layer to minimize light cross-talk between layers. The detector has an active area of 192 × 192 mm with a square pixel size of 3 × 3 mm. As part of the development process of the double-layer detector, a single-layer detector was built, together with a prototype detector in which the two layers of the detector could be read out separately. Efficiency calculations and measurements of all three detectors are discussed. The novel double-layer detector has been installed and tested on the SXD diffractometer at ISIS. The detector performance is compared with the current scintillator detectors employed on SXD by studying reference crystal samples. More than a factor of 3 improvement in efficiency is achieved with the double-layer wavelength-shifting-fibre detector. Software routines for further optimizations in spatial resolution and uniformity of response have been implemented and tested for 2D detectors. The methods and results are discussed in this manuscript.

Lawsonella clevelandensis causing spinal subdural empyema.

Lawsonella clevelandensis is a recently described species and genus of bacterium in the Corynebacterineae suborder which is Gram-stain positive, partially acid-fast and anaerobic. Very few cases of human infection due to this organism are described and here we seek to add to the limited medical literature. We report the case of a 2-year-old girl who presented with an infected spinal dermoid cyst secondary to Lawsonella clevelandensis which required surgical drainage and a long course of antibiotics. We encountered diagnostic and therapeutic difficulties because this is a fastidious organism which was difficult to culture and ultimately required molecular detection and identification. To the best of our knowledge, this is only the seventh reported case of Lawsonella clevelandensis causing human infection worldwide and the first in the UK. This is the first reported case of Lawsonella clevelandensis infection in a child and the second reported case of this organism causing spinal infection.

Does dermatoneuro syndrome have a viral aetiology?

Scleromyxoedema is a rare disease characterized by a generalized papular and sclerodermoid cutaneous eruption. It is associated with fibroblast proliferation and mucin deposition in the dermis. Most patients have a monoclonal gammopathy, defined by the presence of IgG. Treatment of scleromyxoedema is challenging, but there is mounting evidence to support the use of intravenous immunoglobulin (IVIg). Individual reports of systemic complications have been described. Dermatoneuro syndrome (DNS) is a rare but sometimes fatal manifestation, which consists of a triad of fever, coma and seizures preceded by a flu-like illness. We describe a patient with scleromyxoedema who developed DNS. Our case highlights interesting findings suggesting that DNS may have a viral aetiology. In addition, this case demonstrates a favourable response of the cutaneous features of scleromyxoedema to IVIg.

Experimental measurement of the mechanical properties of carotid atherothrombotic plaque fibrous cap.

Eleven carotid atherothrombotic plaque samples were harvested from patients. Three samples that were highly calcified were discarded, while eight yielded results. The elastic properties of the material were estimated by fitting the measured indentation response to finite element simulations. The methodology was refined and its accuracy quantified using a synthetic rubber. The neo-Hookean form of the material model gave a good fit to the measured response of the tissue. The inferred shear modulus mu was found to be in the range 7-100 kPa, with a median value of 11 kPa. A review of published materials data showed a wide range of material properties for human atherothrombotic tissue. The effects of anisotropy and time dependency in these published results were highlighted. The present measurements were comparable to the static radial compression tests of Lee et al, 1991 [Structure-dependent dynamic behaviour of fibrous caps from human atherosclerotic plaques. Circulation 83, 1764-1770].

Association between white matter ischaemia and carotid plaque morphology as defined by high-resolution in vivo MRI.

OBJECTIVES AND DESIGN: Both carotid plaque morphology and severity of white matter ischaemia (WMI) have been shown to be independent predictors of stroke risk. This study tests the hypothesis that there is an association between carotid plaque morphology as determined by high-resolution carotid MRI and WMI. MATERIALS AND METHODS: Forty patients (80 arteries) with at least 40% stenosis on screening Doppler ultrasound were recruited and underwent high-resolution axial carotid MRI at 1.5 T. In a blinded manner, plaque characteristics such as lipid core, fibrous cap, intraplaque haemorrhage, lumen area, plaque area, and American Heart Association (AHA) classification were qualitatively and quantitatively evaluated. The severity of WMI was independently quantified using a modified Scheltens score based on standard brain Fluid-Attenuated Inversion Recovery. Linear mixed effect models were used to test if carotid plaque characteristics could independently predict severity of WMI. RESULTS: Hypertension (p=0.005) and previous a history of transient ischaemic attack or stroke (p=0.038) were found to be significant predictors of severity of WMI. After accounting for confounding variables, no significant association was found between the modified Scheltens score and lipid core size (p=0.122), fibrous cap status (p=0.991), intraplaque haemorrhage (p=0.708), plaque area (0.835), lumen area (0.371) or an AHA Type VI complex plaque (p=0.195). CONCLUSIONS: Carotid plaque morphology as defined by MRI does not independently predict severity of WMI.

Temporal dependence of in vivo USPIO-enhanced MRI signal changes in human carotid atheromatous plaques.

INTRODUCTION: Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced MRI has been shown to be a useful modality to image activated macrophages in vivo, which are principally responsible for plaque inflammation. This study determined the optimum imaging time-window to detect maximal signal change post-USPIO infusion using T1-weighted (T1w), T2*-weighted (T2*w) and quantitative T2* (qT2*) imaging. METHODS: Six patients with an asymptomatic carotid stenosis underwent high resolution T1w, T2*w and qT2* MR imaging of their carotid arteries at 1.5 T. Imaging was performed before and at 24, 36, 48, 72 and 96 h after USPIO (Sinerem, Guerbet, France) infusion. Each slice showing atherosclerotic plaque was manually segmented into quadrants and signal changes in each quadrant were fitted to an exponential power function to model the optimum time for post-infusion imaging. RESULTS: The power function determining the mean time to convergence for all patients was 46, 41 and 39 h for the T1w, T2*w and qT2* sequences, respectively. When modelling each patient individually, 90% of the maximum signal intensity change was observed at 36 h for three, four and six patients on T1w, T2*w and qT2*, respectively. The rates of signal change decrease after this period but signal change was still evident up to 96 h. CONCLUSION: This study showed that a suitable imaging window for T1w, T2*w and qT2* signal changes post-USPIO infusion was between 36 and 48 h. Logistically, this would be convenient in bringing patients back for one post-contrast MRI, but validation is required in a larger cohort of patients.

Social gaze cueing to auditory locations.

Spatial attention is oriented by social visual cues: targets appearing at cued (gazed-at) locations are detected more rapidly than those appearing at uncued locations. The current studies provide evidence that social gaze directs attention to auditory as well as visual targets at cued locations. For auditory target detection the effect lasted from 300 to 1,005 ms while for discrimination the effect was restricted to 600 ms. Improved performance at 600-ms stimulus onset asynchrony was observed across all experiments and may reflect an optimal processing window for social stimuli. In addition, the orienting of attention by gaze was impaired by the presentation of negative faces. These experiments further demonstrate the unique and cross-modal nature of social gaze cueing.

Utility of USPIO-enhanced MR imaging to identify inflammation and the fibrous cap: a comparison of symptomatic and asymptomatic individuals.

BACKGROUND AND PURPOSE: Inflammation is a risk factor the vulnerable atheromatous plaque. This can be detected in vivo on high-resolution magnetic resonance (MR) imaging using a contrast agent, Sinerem, an ultra-small super-paramagnetic iron oxide (USPIO). The aim of this study was to explore whether there is a difference in the degree of MR defined inflammation using USPIO particles, between symptomatic and asymptomatic carotid plaques. We report further on its T(1) effect of enhancing the fibrous cap, which may allow dual contrast resolution of carotid atheroma. METHODS: Twenty patients with carotid stenosis (10 symptomatic and 10 asymptomatic) underwent multi-sequence MR imaging before and 36 h post-USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant was calculated following USPIO administration. Mean signal change across all quadrants were compared between the two groups. RESULTS: Symptomatic patients had significantly more quadrants with a signal drop than asymptomatic individuals (75% vs. 32%, p<0.01). Asymptomatic plaques had more quadrants with signal enhancement than symptomatic ones (68% vs. 25%, p<0.05); their mean signal change was also higher (46% vs. 15%, p<0.01) and this appeared to correlate with a thicker fibrous cap on histology. CONCLUSIONS: Symptomatic patients had more quadrants with signal drop suggesting larger inflammatory infiltrates. Asymptomatic individuals showed significantly more enhancement possibly suggesting greater stability as a result of thicker fibrous caps. However, some asymptomatic plaques also had focal areas of signal drop, suggesting an occult macrophage burden. If validated by larger studies, USPIO may be a useful dual contrast agent able to improve risk stratification of patients with carotid stenosis and inform selection for intervention.

Combined PET-FDG and USPIO-enhanced MR imaging in patients with symptomatic moderate carotid artery stenosis.

INTRODUCTION: PET-FDG and USPIO-enhanced MRI are increasingly being used in depicting carotid atheroma inflammation--a risk factor for the high risk plaque. Their combined use has not been previously reported. REPORT: Two patients presenting with stroke and identified with 50% carotid stenosis on duplex ultrasonography, underwent PET FDG and USPIO-enhanced MR imaging. Results were concordant and complementary suggesting that both techniques reflect similar metabolic processes. DISCUSSION: The selection of patients for carotid revascularisation has largely been based on the severity of luminal stenosis alone. The two imaging modalities, which identify inflammatory activity, may be potential surrogate risk markers in the selection of patients eligible for carotid surgery, if plaque inflammation can be correlated with risk of developing clinical symptoms.

Comparison of the inflammatory burden of truly asymptomatic carotid atheroma with atherosclerotic plaques in patients with asymptomatic carotid stenosis undergoing coronary artery bypass grafting: an ultrasmall superparamagnetic iron oxide enhanced magnetic resonance study.

INTRODUCTION: Inflammation is a recognized risk factor for the vulnerable atherosclerotic plaque. The aim of this study was to explore whether there is a difference in the degree of Magnetic Resonance (MR) defined inflammation using Ultra Small Super-Paramagnetic Iron Oxide (USPIO) particles, within carotid atheroma in completely asymptomatic individuals and the asymptomatic carotid stenosis in a cohort of patients undergoing coronary artery bypass grafting (CABG). METHODS: 10 patients awaiting CABG with asymptomatic carotid disease and 10 completely asymptomatic individuals with no documented coronary artery disease underwent multi-sequence MR imaging before and 36 hours post USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant, normalised to adjacent muscle signal, was calculated following USPIO administration. RESULTS: The mean percentage of quadrants showing signal loss was 94% in the CABG group, compared to 24% in the completely asymptomatic individuals (p<0.001). The carotid plaques from the CABG patients showed a significant mean signal intensity decrease of 16.4% after USPIO infusion (95% CI 10.6% to 22.2%; p<0.001). The truly asymptomatic plaques showed a mean signal intensity increase (i.e. enhancement) after USPIO infusion of 8.4% (95% CI 2.6% to 14.2%; p=0.007). The mean signal difference between the two groups was 24.9% (95% CI 16.7% to 33.0%; p<0.001). CONCLUSIONS: These findings are consistent with the hypothesis that inflammatory atheroma is a systemic disease. The carotid territory is more likely to take up USPIO if another vascular territory is symptomatic.

Characterisation of carotid atheroma in symptomatic and asymptomatic patients using high resolution MRI.

BACKGROUND AND PURPOSE: To prospectively evaluate differences in carotid plaque characteristics in symptomatic and asymptomatic patients using high resolution MRI. METHODS: 20 symptomatic and 20 asymptomatic patients, with at least 50% carotid stenosis as determined by Doppler ultrasound, underwent preoperative in vivo multispectral MRI of the carotid arteries. Studies were analysed both qualitatively and quantitatively in a randomised manner by two experienced readers in consensus, blinded to clinical status, and plaques were classified according to the modified American Heart Association (AHA) criteria. RESULTS: After exclusion of poor quality images, 109 MRI sections in 18 symptomatic and 19 asymptomatic patients were available for analysis. There were no significant differences in mean luminal stenosis severity (72.9% vs 67.6%; p = 0.09) or plaque burden (median plaque areas 50 mm(2) vs 50 mm(2); p = 0.858) between the symptomatic and asymptomatic groups. However, symptomatic lesions had a higher incidence of ruptured fibrous caps (36.5% vs 8.7%; p = 0.004), haemorrhage or thrombus (46.5% vs 14.0%; p<0.001), large necrotic lipid cores (63.8% vs 28.0%; p = 0.002) and complicated type VI AHA lesions (61.5% vs 28.1%; p = 0.001) compared with asymptomatic lesions. The MRI findings of plaque haemorrhage or thrombus had an odds ratio of 5.25 (95% CI 2.08 to 13.24) while thin or ruptured fibrous cap (as opposed to a thick fibrous cap) had an odds ratio of 7.94 (95% CI 2.93 to 21.51) for prediction of symptomatic clinical status. CONCLUSIONS: There are significant differences in plaque characteristics between symptomatic and asymptomatic carotid atheroma and these can be detected in vivo by high resolution MRI.

Correlation of carotid atheromatous plaque inflammation with biomechanical stress: utility of USPIO enhanced MR imaging and finite element analysis.

OBJECTIVE: The aim of this study was to explore whether there is a relationship between the degree of MR-defined inflammation using ultra small super-paramagnetic iron oxide (USPIO) particles, and biomechanical stress using finite element analysis (FEA) techniques, in carotid atheromatous plaques. METHODS AND RESULTS: 18 patients with angiographically proven carotid stenoses underwent multi-sequence MR imaging before and 36 h after USPIO infusion. T(2)(*) weighted images were manually segmented into quadrants and the signal change in each quadrant normalised to adjacent muscle was calculated after USPIO administration. Plaque geometry was obtained from the rest of the multi-sequence dataset and used within a FEA model to predict maximal stress concentration within each slice. Subsequently, a new statistical model was developed to explicitly investigate the form of the relationship between biomechanical stress and signal change. The Spearman's rank correlation coefficient for USPIO enhanced signal change and maximal biomechanical stress was -0.60 (p=0.009). CONCLUSIONS: There is an association between biomechanical stress and USPIO enhanced MR-defined inflammation within carotid atheroma, both known risk factors for plaque vulnerability. This underlines the complex interaction between physiological processes and biomechanical mechanisms in the development of carotid atheroma. However, this is preliminary data that will need validation in a larger cohort of patients.

Is the recommended target of 4 hours from head injury to emergency craniotomy achievable?

Guidelines recommend that head-injured patients who require life-saving decompressive surgery should undergo surgery within 4 h. To assess the compliance with this recommendation 100 consecutive head-injured patients admitted to a regional neurosurgical unit (RNU) were studied. Time points from head injury to craniotomy were documented and analysed. Twenty-four patients underwent emergency craniotomy, only one being operated on within 4 h. In this cohort of patients there was no relationship between timing of surgery and outcome. In order to investigate whether it is possible to reduce delays in transportation time, theoretical models were created to determine whether direct transfer to the RNU would be faster by land or air ambulance.

On the implications of interpreting the stability index: a spine example.

Quantifying the stability of the spinal column offers a perspective on the effectiveness of the motor control strategy to ensure a stable spine--and minimize the risk of injury from experiencing an unstable event. There are essentially three energy based methods of calculating a stability index for the lumbar spine. All three methods involve mathematical manipulation of an 18 x 18 Hessian matrix. The purpose of this paper was to consider the mathematical implications for the three methods of determining a single stability index, and examine the effects of biological factors such as muscle activation in each of these methods. The first approach computes the Hessian's determinant and is thought to represent a more global or "average" perspective on stability. A second approach computes the smallest eigenvalue of the Hessian matrix to determine the weakest link of the spine. The final method determines an average critical stiffness difference for the spine and is intended to effectively determines how far a human spine is from instability, and allows comparison between tasks. This study shows that the same interpretation of stability is achieved via all three computational approaches--they agree as to whether the spine is stable or not. However they appear to differ in their sensitivity to the effect of muscle activation patterns.

Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).

Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.

Screening for major depression in Asian-Americans: a comparison of the Beck and the Chinese Depression Inventory.

OBJECTIVE: This study compares the effectiveness of the Chinese version of the Beck Depression Inventory (CBDI) and the Chinese Depression Inventory (CDI) in screening for depression among Chinese Americans. METHOD: Five hundred and three Chinese-Americans in primary care were administered the CBDI and the CDI for depression screening. The results were compared with standard semistructured interview. RESULTS: With empirically determined cutoff scores of the CBDI (> or =13) and the CDI (>/=16), both instruments have good sensitivity (0.78) and excellent specificity (0.91 and 0.93, respectively). The correlation between the total scores of the two instruments was high (0.785, P < 0.01). The areas under the Receiver Operating Characteristic (ROC) curve of the CBDI and the CDI were 0.94 and 0.95, respectively, and were not significantly different. CONCLUSION: When administered by interviewers, the CBDI and the CDI have comparable effectiveness. Low participation among Chinese-Americans with self-report measures limits both scales as efficient depression screening instruments.

The genome sequence of Schizosaccharomyces pombe.

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.