A confident source of hard X-rays: radiation from a tokamak applicable for runaway electrons diagnosis.

In a tokamak with a toroidal electric field, electrons that exceed the critical velocity are freely accelerated and can reach very high energies. These so-called `runaway electrons' can cause severe damage to the vacuum vessel and are a dangerous source of hard X-rays. Here the effect of toroidal electric and magnetic field changes on the characteristics of runaway electrons is reported. A possible technique for runaways diagnosis is the detection of hard X-ray radiation; for this purpose, a scintillator (NaI) was used. Because of the high loop voltage at the beginning of a plasma, this investigation was carried out on toroidal electric field changes in the first 5 ms interval from the beginning of the plasma. In addition, the toroidal magnetic field was monitored for the whole discharge time. The results indicate that with increasing toroidal electric field the mean energy of runaway electrons rises, and also an increase in the toroidal magnetic field can result in a decrease in intensity of magnetohydrodynamic oscillations which means that for both conditions more of these high-energy electrons will be generated.

Gene and Protein Expression of Chemokine (C-C-Motif) Ligand 19 is Upregulated in Unstable Carotid Atherosclerotic Plaques.

OBJECTIVE/BACKGROUND: The aim was to investigate the expression of genes associated with carotid plaque instability and their protein products at a local and systemic level. METHODS: Carotid plaques from 24 patients undergoing carotid endarterectomy (CEA) were classified as stable or unstable using clinical, histological, ultrasound, and transcranial Doppler criteria, and compared using whole genome microarray chips. Initial results of differentially expressed genes were validated by quantitative reverse transcriptase polymerase chain reaction in an independent group of 96 patients undergoing CEA. The protein product of genes significantly differentially expressed between patients with stable and unstable plaques were analysed by plaque immunohistochemistry and serum protein quantification by enzyme-linked immunosorbent assay on a further independent cohort. RESULTS: Expression of chemokine (c-c-motif) ligand 19 (CCL19) was significantly upregulated in plaques from patients with clinically unstable disease (p < .001). Cathepsin G expression was upregulated in histologically unstable plaques (p = .04). Serum concentration of CCL19 was significantly higher in patients with clinically unstable plaques (p = .02). Immunohistochemical staining for CCL19 demonstrated positive staining in histologically and clinically unstable plaques (p = .03). CCL19 also co-localised with CD3+ T-cell lymphocytes in the core region, around where CCL19 was expressed. CONCLUSIONS: CCL19 is significantly overexpressed in patients with unstable carotid atherosclerotic plaques and may be a possible novel biomarker for identifying high-risk patients in whom more urgent intervention may be indicated.

Microarray-based Gene Expression Profiling of Abdominal Aortic Aneurysm.

OBJECTIVE/BACKGROUND: Microarray-based gene expression profiling studies may detect transcriptional signatures carrying prognostic value in abdominal aortic aneurysms (AAA). A gene expression profiling study was conducted to compare individuals with AAA with screened controls. METHODS: The peripheral blood transcriptome was compared between 12 individuals with AAA and 12 age- and sex-matched controls using microarray. Validation by Taqman real-time quantitative (qPCR) was performed in an independent group as described. Peripheral blood RNA was hybridized to Illumina microarrays, each representing 37,846 genes, allowing comparison of gene expression between cases and controls. Eleven differentially expressed genes were re-quantified by qPCR in the independent group with AAA (n = 95), controls (n = 92), pre- and postendovascular AAA repair (EVAR, n = 31); or open AAA repair (n = 13), AAA wall biopsies (n = 11), and in matched smooth muscle cultures (n = 7). RESULTS: Microarray detected 47 significantly differentially expressed genes in AAA after correction for multiple testing (p < .05). These genes conferred roles in regulation of apoptosis, proteolysis, the electron transport chain, leukocyte migration, and the humoral immune response. Gene quantification in the independent group demonstrated three genes to be downregulated in AAA compared with controls: MSN, PSMB10, and STIM1; however, their expression remained unchanged post-AAA repair. PSMB10 was the only gene conferring a consistent direction of effect in both the discovery and validation analyses (downregulated). EIF3G, SIVA, PUF60, CYC1, FIBP, and CARD8 were downregulated post-EVAR. Expression of all 11 genes of interest was detected in aortic biopsies and matched smooth muscle cultures. CONCLUSION: This study demonstrates differential expression of transcripts in peripheral blood of individuals with AAA, with functional roles in proteolysis, inflammation, and apoptotic processes. These were modulated by aneurysm exclusion from the circulation and expressed in matched aortic biopsies and smooth muscle cultures. These observations further support the key roles for these pathways in the pathogenesis of AAA.

Identification of patients with a histologically unstable carotid plaque using ultrasonic plaque image analysis.

OBJECTIVES: In patients with carotid stenosis the risk of stroke is highest in the first few days after onset of symptoms and it is low in asymptomatic patients. The ability to identify patients with a high (or low) probability of having a histologically unstable plaque might become a complimentary method that can refine the indications for surgical intervention. METHODS: Two histopathologists, using validated American Heart Association criteria, independently graded plaques harvested during carotid endarterectomy. Preoperative Duplex images were independently assessed for juxtaluminal black area, plaque type, plaque area, and grey-scale median (GSM) following image normalization. Logistic regression analysis was then performed to create a model for predicting predominantly histologically unstable or stable plaques. RESULTS: A total of 126 patients were included in the study. Based on the presence and extent of histological features including haemorrhage, thrombus, fibrous tissue, lipid core, inflammation, neovascularity, foam cells, and cap rupture, 39 plaques were graded as predominantly stable, while 87 were predominantly unstable. Unstable plaques were associated with a plaque area >95 mm(2) (OR 4.15; 95% CI 1.34-12.8 p = .009), a juxtaluminal black area >6 mm(2) (OR 2.77; 95% CI 1.24 to 6.17 p = .01) and a GSM <25 (OR 3.76; 95% CI 1.14-12.39). Logistic regression indicated that patients with the first two features had a 90% probability of having a histologically unstable plaque. The model was used to calculate the probability of having an unstable plaque in each patient. The receiver operating characteristic curve using the p value was 0.68 (95% CI 0.59-0.78). CONCLUSIONS: Computerized plaque analysis has the potential to identify patients with histologically unstable carotid plaques. This model requires validation, but offers the potential to influence patient selection for emergency interventions and the monitoring of medical therapy.

Histologically unstable asymptomatic carotid plaques have altered expression of genes involved in chemokine signalling leading to localised plaque inflammation and rupture.

BACKGROUND: Many studies have evaluated histological and gene expression profiles in TIA/stroke patients after onset of symptoms, but there is limited understanding as to how these plaque related features interact before symptom onset. In particular, no studies have evaluated differential gene expression in histologically unstable (vs stable plaques) in neurologically asymptomatic patients. METHODS: Nine asymptomatic patients had their plaques scored blindly by two independent Histopathologists using the AHA plaque scoring system. RNA extracted from the plaques was hybridised onto a whole genome microarray. Analysis was performed using GenomeStudio (v1.0) and the DAVID bioinformatics resource (v6.7). RESULTS: Three plaques were histologically unstable (Grade 2/3), while six were stable (Grade 0/1). 346 differentially expressed genes (>1.3 fold, P < 0.05) were identified (293 down-regulated and 53 up-regulated) between stable and unstable plaques. Genes related to chemokine and protein signalling (pro-inflammatory/pro-apoptotic) were identified to have high enrichment scores (>1.3) and were significantly up-regulated in unstable (asymptomatic) plaques. CONCLUSION: The findings confirm the intuitively held belief that changes in chemokine and protein signalling may be associated with acute plaque disruption and precede the onset of symptoms. Once validated, these genes could therefore become targets for innovative medical treatments in the future or could help identify asymptomatic patients with histologically unstable plaques that would benefit from surgical intervention.

Features of unstable carotid plaque during and after the hyperacute period following TIA/stroke.

BACKGROUND: The aim was to test the hypothesis that histologically unstable carotid plaque features were more prevalent in patients undergoing carotid endarterectomy (CEA) in the acute period after onset of symptoms and that the plaque would assume more stable histological characteristics as the delay from the most recent event increased. METHODS: Seven histological features of plaque instability (haemorrhage, large lipid core, chronic plaque inflammation, chronic cap inflammation, marked vascularity, cap rupture and many foam cells) were independently quantified and then correlated with recency of symptoms in patients undergoing CEA. RESULTS: In patients undergoing CEA ≤14 days of their last event, 87/119 (73%) exhibited ≥5/7 unstable histological plaque features, compared with 22/40 (55%) of patients undergoing delayed surgery (P = 0.048). As expected, there was a sustained decline in the prevalence of unstable plaque features in 61 patients undergoing surgery between days 7-28. However, there was then a marked increase in the prevalence of plaque haemorrhage (59% up to 65%), large lipid core (41% up to 78%), chronic plaque inflammation (71% up to 91%), cap rupture (35% up to 39%), many foam cells (24% up to 43%) and marked vascularity (71% up to 91%) in 23 patients undergoing CEA after 29 days had elapsed. CONCLUSION: Patients undergoing surgery ≤14 days had a significantly higher overall burden of high risk plaque features compared with those undergoing delayed CEA. However, the secondary upsurge across a range of unstable plaque features in patients undergoing CEA after ≥29 days had elapsed suggests that the relationship between recency of symptoms and plaque histology is more complex than had been anticipated in previous studies.

Patients with recurrent ischaemic events from carotid artery disease have a large lipid core and low GSM.

OBJECTIVES: The aim of the current study was to determine whether computerised ultrasound plaque analysis could identify features predictive of an increased risk of early recurrent events after symptom onset. METHODS: Between August 2008 and December 2010, 158 consecutive symptomatic patients undergoing carotid endarterectomy (CEA) had their plaques harvested at CEA and then independently scored for markers of histological plaque instability. Duplex ultrasound images recorded prior to CEA were independently assessed using the Iconsoft software. RESULTS: One hundred and fifty eight recently symptomatic patients underwent CEA with 118 (75%) undergoing their operation within 14 days of their most recent clinical event. Twenty (12.7%) suffered a recurrent cerebral ischaemic event following admission to the vascular unit and before undergoing CEA. Using multivariate stepwise analysis; lipid core (OR 4.00, 95% CI 1.07 to 14.83, P = 0.042) and a low GSM (OR 6.21, 95% CI 1.86 to 20.4, P = 0.003) were independently associated with recurrent cerebrovascular events. CONCLUSION: Within a cohort of patients presenting with recent onset cerebral ischaemic events undergoing CEA, the plaques of patients with recurrent events following admission to hospital had evidence a large lipid core and a low GSM.

Spontaneous cerebral embolisation in asymptomatic and recently symptomatic patients with TIA/Minor stroke.

OBJECTIVES: Spontaneous embolisation (SE) detected using Transcranial Doppler (TCD) after a Transient Ischaemic Attack (TIA)/Minor stroke is an independent predictor of recurrent stroke. There are, however limited data on the differential prevalence of SE in the first few days/weeks after onset of symptoms. METHOD: 156 consecutive patients (symptomatic n = 123, asymptomatic n = 33) underwent Carotid Endarterectomy (CEA) during an 18 month period and had an accessible window permitting 30 min of pre-operative TCD monitoring. A prospective study was conducted with assessors blinded to clinical status. RESULTS: Spontaneous embolisation was detected in 31 symptomatic patients (25%) of which 1/1 (100%), 14/35 (40%), 8/37 (22%) and in 8/50 (16%) patients presented within 48 h, 3-7 days, 8-14 days and >14 days respectively from the index clinical event. SE occurred in only 6% of asymptomatic patients. Out of 31 symptomatic patients with SE, seven (22.6%) suffered recurrent cerebrovascular events following admission as opposed to 11/92 patients (11.9%) who had no evidence of spontaneous embolisation after admission (OR 2.2 (95% CI 0.8-6.1))(P = 0.2) CONCLUSION: Patients presenting for CEA in the hyperacute period after onset of TIA/Minor stroke have a high incidence of SE. Patients with SE had a 23% risk of recurrent cerebrovascular events. These data support the current drive towards expedited CEA in recently symptomatic patients.

Rapid access carotid endarterectomy can be performed in the hyperacute period without a significant increase in procedural risks.

OBJECTIVES: The highest risk of recurrent stroke after suffering a transient ischaemic attack (TIA) or minor stroke is during the first 7-14 days. Contemporary guidelines recommend that carotid endarterectomy (CEA) should be performed within this time period, but there are concerns regarding (1) how this can be achieved logistically and (2) whether this policy is associated with a significant increase in procedural risks. DESIGN: This is a prospective, consecutive study of delays to surgery and 30-day outcomes in recently symptomatic patients who underwent CEA between 1 October 2008 and 15 June 2010 after the creation of a rapid access TIA service. RESULTS: A total of 109 symptomatic patients underwent CEA, 78% within 14 days of the index event and 90% within 14 days of referral. The median delay to surgery was 9 days from the index event and 4 days from referral. There were no perioperative deaths. Two strokes occurred (one intra-operative and one post-operative) to give a 30-day death/stroke rate of 1.83%. Patients undergoing CEA within 14 days of the index event incurred a death/stroke rate of 2.4% (2/84), increasing to 4.3% in patients undergoing surgery within 7 days (2/47). CONCLUSION: Service reconfigurations can lead to significant reductions in delays to treatment in patients with symptomatic carotid disease. CEA can be performed in the hyperacute period without significantly increasing the operative risk.

Should Asian men be included in abdominal aortic aneurysm screening programmes?

INTRODUCTION: A national AAA screening programme for men aged 65 is shortly to be implemented in England. Trials that have provided evidence for this screening programme have not included information on ethnicity. Hence their findings may not be applicable to ethnically diverse populations. REPORT: This study retrospectively looked at the prevalence of AAA in men aged 65, from different ethnic backgrounds in our city's current screening programme.19014 men (Caucasians n=18,431, Asian n=446, others n=137) were screened. Prevalence was 4.69% (4.39-5% 95% CI), and 0.45% (0.054-1.161% 95% CI) in Caucasians and Asians respectively (Fisher's exact test: P<0.0001). DISCUSSION: Prevalence of AAAs in men aged 65 of Asian origin appears to be low and so increases uncertainty about cost-effectiveness of screening Asian men.

Autosomal recessive ataxia, slow eye movements, dementia and extrapyramidal disturbances.

An Arab family with an autosomal recessive form of spinocerebellar degeneration with slow eye movements is reported. Hitherto all the reported cases were either sporadic or of autosomal dominant inheritance. Associated are progressive intellectual impairment and extrapyramidal dysfunction as well as peripheral neuropathy and skeletal abnormalities. Muscle biopsy revealed non-specific mitochondrial abnormalities. The spectrum of eye movement abnormalities is discussed and the literature is reviewed. It is concluded that the hallmark of this syndrome (slow or even absent saccades) is one of a group of oculomotor abnormalities, all being characterized by delayed initiation and slow velocity. The syndrome seems to be related to the olivopontocerebellar degenerations, but differs in that there is in addition selective degeneration of certain tracts and nuclei in the mesencephalon and probably more rostral structures.

Late onset cerebello-pontomesencephalic degeneration.

Two siblings are presented with late onset, rapidly progressive truncal ataxia, paralysis of down-gaze and loss of up-gaze saccades in association with other oculomotor dysfunctions as well as dementia. Electron microscopic muscle studies revealed abnormal distribution and form of the mitochondria, probably being the ultrastructural basis of the pathologic changes. A neurological syndrome as that described here has not been reported before.