Ion Microbeam Analyses of Dust Particles and Codeposits from JET with the ITER-Like Wall

Generation of metal dust in the JET tokamak with the ITER-like wall (ILW) is a topic of vital interest to next-step fusion devices because of safety issues with plasma operation. Simultaneous Nuclear Reaction Analysis (NRA) and Particle-Induced X-ray Emission (PIXE) with a focused four MeV 3He microbeam was used to determine the composition of dust particles related to the JET operation with the ILW. The focus was on “Be-rich particles” collected from the deposition zone on the inner divertor tile. The particles found are composed of a mix of codeposited species up to 120 μm in size with a thickness of 30–40 μm. The main constituents are D from the fusion fuel, Be and W from the main plasma-facing components, and Ni and Cr from the Inconel grills of the antennas for auxiliary plasma heating. Elemental concentrations were estimated by iterative NRA-PIXE analysis. Two types of dust particles were found: (i) larger Be-rich particles with Be concentrations above 90 at% with a deuterium presence of up to 3.4 at% and containing Ni (1–3 at%), Cr (0.4–0.8 at%), W (0.2–0.9 at%), Fe (0.3–0.6 at%), and Cu and Ti in lower concentrations and (ii) small particles rich in Al and/or Si that were in some cases accompanied by other elements, such as Fe, Cu, or Ti or W and Mo

Data on erosion and hydrogen fuel retention in Beryllium plasma-facing materials

ITER will use beryllium as a plasma-facing material in the main chamber, covering a total surface area of about 620 m(2). Given the importance of beryllium erosion and co-deposition for tritium retention in ITER, significant efforts have been made to understand the behaviour of beryllium under fusion-relevant conditions with high particle and heat loads. This paper provides a comprehensive report on the state of knowledge of beryllium behaviour under fusion-relevant conditions: the erosion mechanisms and their consequences, beryllium migration in JET, fuel retention and dust generation. The paper reviews basic laboratory studies, advanced computer simulations and experience from laboratory plasma experiments in linear simulators of plasma-wall interactions and in controlled fusion devices using beryllium plasma-facing components. A critical assessment of analytical methods and simulation codes used in beryllium studies is given. The overall objective is to review the existing set of data with a broad literature survey and to identify gaps and research needs to broaden the database for ITER.Peer reviewe

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Brain Natriuretic Peptides in Atherosclerotic Renal Artery Stenosis and Effects of Renal Angioplasty

Background: We hypothesized that plasma levels of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) would be elevated, and adiponectin concentrations reduced, in patients with atherosclerotic renal artery stenosis (ARAS) and that BNPs might be used to identify patients who would benefit from percutaneous transluminal renal angioplasty (PTRA). Methods: Data were collected before renal angiography in 91 patients with hypertension and suspected ARAS (significant ARAS; n=47, and non-RAS; n=44) and in 20 healthy controls (C). In ARAS patients analyses were repeated four weeks after PTRA. Results: Ambulatory systolic blood pressure (ASBP) was significantly elevated in the ARAS group vs. both C and non-RAS groups. Baseline plasma BNP and NT-proBNP levels were significantly elevated, and adiponectin concentrations reduced, in the ARAS group vs. C but not vs. the non-RAS group. One month after PTRA, ASBP was reduced vs. baseline (149±16 to 139±15 mm pConclusions: Patients with ARAS showed elevated of BNP and NT-proBNP concentrations, and reduced levels of adiponectin, compared to healthy controls but not vs. hypertensive individuals without RAS. Our data do no support the use of BNP analyses in the identification of ARAS patients who will have a beneficial blood pressure response to PTRA

Renal hemodynamics in renal artery stenosis and angiotensin II-dependent hypertension. Pathophysiological and diagnostic aspects.

Patients with renovascular hypertension have a poor renal and cardiovascular prognosis. To improve the care of these patients, we need to increase knowledge about the pathophysiological mechanisms involved. Thus, the aims of these studies were to examine: (1) renal hemodynamics and renal blood flow autoregulation (RBFA) in an experimental model of chronic angiotensin (Ang) II-dependent hypertension and the role of superoxide and endothelin (ET)-1; (2) the diagnostic value of intrarenal velocimetric color duplex sonography (CDS) indices in patients with suspected renal artery stenosis (RAS); and (3) biomarkers of oxidative stress (oxs), and ET-1, in hypertensive patients with atherosclerotic RAS (ARAS) and the effect of renal angioplasty. In chronically Ang II-infused rats, high-NaCl intake (AngII-HNa) resulted in a marked impairment in the myogenic response (MR) of dynamic RBFA. This abnormality was not seen in sham rats on a high-NaCl diet and was significantly more pronounced than in Ang II-infused rats on a normal-NaCl diet. Chronic treatment with tempol, a superoxide dismutase mimetic, attenuated the abnormality in dynamic RBFA in AngII-HNa, whereas acute treatment with ETA and/or ETB receptor antagonists had no effect on this abnormality. In AngII-HNa, ETA antagonism reduced arterial pressure (AP) and specifically increased outer medullary perfusion. These effects were attenuated or abolished by co-administration of ETB receptor antagonist. In a retrospective cohort of patients undergoing renal angiography for suspected RAS, acceleration indices of CDS; maximal systolic acceleration (ACCmax) and maximal acceleration index (AImax= ACCmax/peak systolic velocity) provided comparable, good diagnostic accuracy in detecting a hemodynamically significant RAS even in patients with markedly reduced kidney function, in contrast to pulsatility index which correlated significantly to age, renal function and pulse pressure, but not the degree of RAS. In a prospective cohort of patients undergoing renal angiography for suspected ARAS (significant ARAS; n=83, and non-RAS; n=59) baseline (prior to angiography) inflammatory, but not oxs, biomarkers were significantly elevated in group ARAS vs. both group non-RAS and healthy matched controls (n=20). Plasma ET-1 at baseline was significantly increased in group ARAS vs. healthy controls and was significantly reduced compared to baseline 4 weeks after angioplasty. Angioplasty had no significant effects on AP, biomarkers of oxs, inflammation or serum creatinine. In conclusion, in a rat model of AngII-dependent hypertension, high-NaCl intake produced a marked impairment in the MR of dynamic RBFA. Tempol attenuated this abnormality, whereas ET-1 receptor antagonists did not, indicating a role for superoxide in the impaired autoregulatory response. In the same animal model, acute ETA antagonism reduced AP and selectively increased outer medullary perfusion. Our results suggest that selective ETA antagonists are more effective than combined ETA+B antagonists in this model. Acceleration indices ACCmax and AImax are superior to pulsatility index, and provide a similar, good, diagnostic accuracy in detecting a hemodynamically significant RAS, even in patients with markedly reduced kidney function. Biomarkers of inflammation, but not oxs, are elevated in patients with ARAS. Angioplasty did not decrease inflammatory biomarkers but reduced plasma levels of ET-1 4 weeks after intervention

Dust Monitors in JET with ITER-like Wall for Diagnosis of Mobilized Particles and Co-Deposited Layers

Silicon plates were installed above the inner and outer divertor of the JET with the ITER-like wall (ILW) after the second and third ILW campaigns to monitor dust generation and deposition with the aim to determine the morphology and content of individual particles and co-deposits, including deuterium content. Particular interest was in metal-based particles: Be, W, steel, Cu. Ex-situ examination after two ILW campaigns was performed by a set of microscopy and ion beam methods including micro-beam nuclear reaction analysis and particle-induced X-ray emission. Different categories of Be-rich particles were found: co-deposits peeled-off from plasma-facing components (PFC), complex multi-element spherical objects, and solid metal splashes and regular spherical droplets. The fuel content on the two latter categories was at the level of 1 × 1016 at/cm−2 indicating that Be melting and splashing occurred in the very last phase of the second experimental campaign. The splashes adhere firmly to the substrate thus not posing risk of Be dust mobilisation. No tungsten droplets were detected. The only W-containing particles were fragments of tungsten coatings from the divertor tiles

Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study

Background: People with Huntington's disease (HD) have been observed to have lower rates of cancers. Objective: To investigate the relationship between age of onset of HD, CAG repeat length, and cancer diagnosis. Methods: Data were obtained from the European Huntington's disease network REGISTRY study for 6540 subjects. Population cancer incidence was ascertained from the GLOBOCAN database to obtain standardised incidence ratios of cancers in the REGISTRY subjects. Results: 173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22-0.30). Individual cancers showed a lower age-standardised incidence rate compared with the control population with prostate and colorectal cancers showing the lowest rates. There was no effect of CAG length on the likelihood of cancer, but a cancer diagnosis within the last year was associated with a greatly increased rate of HD onset (Hazard Ratio 18.94, p < 0.001). Conclusions: Cancer is less common than expected in the HD population, confirming previous reports. However, this does not appear to be related to CAG length in HTT. A recent diagnosis of cancer increases the risk of HD onset at any age, likely due to increased investigation following a cancer diagnosis