Prevalence of pemphigus and pemphigoid autoantibodies in the general population

Background: Mucocutaneous blistering is characteristic of autoimmune bullous dermatoses (AIBD). Blisters are caused by autoantibodies directed against structural components of the skin. Hence, detection of specific autoantibodies has become a hallmark for AIBD diagnosis. Studies on prevalence of AIBD autoantibodies in healthy individuals yielded contradictory results. Methods: To clarify this, samples from 7063 blood donors were tested for presence of anti-BP180-NC16A, anti-BP230 and anti-Dsg1/3 IgG by indirect immunofluorescence (IF) microscopy using a biochip. Results: Cumulative prevalence of these autoantibodies was 0.9 % (CI: 0.7-1.1 %), with anti-BP180-NC16A IgG being most prevalent. Validation of IF findings using ELISA confirmed presence of autoantibodies in 7/15 (anti-Dsg1), 6/7 (anti-Dsg3), 35/37 (anti-BP180-NC16A) and 2/3 (anti-BP230) cases. Moreover, in 16 samples, anti-BP180-NC16A autoantibody concentrations exceeded the cut-off for the diagnosis of bullous pemphigoid. Interestingly, these anti-BP180-NC16A autoantibodies from healthy individuals formed immune complexes with recombinant antigen and dose-dependently activated neutrophils in vitro. However, fine-epitope mapping within NC16A showed a different binding pattern of anti-BP180-NC16A autoantibodies from healthy individuals compared to bullous pemphigoid patients, while IgG subclasses were identical. Conclusions: Collectively, we here report a low prevalence of AIBD autoantibodies in a large cohort of healthy individuals. Furthermore, functional analysis shows differences between autoantibodies from healthy donors and AIBD patients

Regional Fluid-Attenuated Inversion Recovery (FLAIR) at 7 Tesla correlates with amyloid beta in hippocampus and brainstem of cognitively normal elderly subjects

Background: Accumulation of amyloid beta (Aβ) may occur during healthy aging and is a risk factor for Alzheimer Disease (AD). While individual Aβ-accumulation can be measured non-invasively using Pittsburgh Compund-B positron emission tomography (PiB-PET), Fluid-attenuated inversion recovery (FLAIR) is a Magnetic Resonance Imaging (MRI) sequence, capable of indicating heterogeneous age-related brain pathologies associated with tissue-edema. In the current study cognitively normal elderly subjects were investigated for regional correlation of PiB- and FLAIR intensity. Methods: Fourteen healthy elderly subjects without known history of cognitive impairment received 11C-PiB-PET for estimation of regional Aβ-load. In addition, whole brain T1-MPRAGE and FLAIR-MRI sequences were acquired at high field strength of 7 Tesla (7T). Volume-normalized intensities of brain regions were assessed by applying an automated subcortical segmentation algorithm for spatial definition of brain structures. Statistical dependence between FLAIR- and PiB-PET intensities was tested using Spearman's rank correlation coefficient (rho), followed by Holm–Bonferroni correction for multiple testing. Results: Neuropsychological testing revealed normal cognitive performance levels in all participants. Mean regional PiB-PET and FLAIR intensities were normally distributed and independent. Significant correlation between volume-normalized PiB-PET signals and FLAIR intensities resulted for Hippocampus (right: rho = 0.86; left: rho = 0.84), Brainstem (rho = 0.85) and left Basal Ganglia vessel region (rho = 0.82). Conclusions: Our finding of a significant relationship between PiB- and FLAIR intensity mainly observable in the Hippocampus and Brainstem, indicates regional Aβ associated tissue-edema in cognitively normal elderly subjects. Further studies including clinical populations are necessary to clarify the relevance of our findings for estimating individual risk for age-related neurodegenerative processes such as AD

Comparative U, Np and Pu M edge high energy resolution X-ray absorption spectroscopy (HR-XANES) investigations of model and genuine active waste glass

Genuine radioactive glass sampled from the vitrification plant Karlsruhe and actinide doped model 2 glasses  are  investigated  by  U/Pu/Np  M4/M5  high  energy  resolution  X‐ray  absorption near edge structure (HR‐XANES), U L3 EXAFS and XPS spectroscopy techniques to characterize and compare the U, Pu and Np oxidation states and their local atomic environments. The importance of the results will be discussed in terms of the strategy of using simplified simulated waste glasses to understand more complex industrial glass samples. The final goal of these studies is to predict the long term behavior of vitrified nuclear waste stored in a nuclear waste repository. Highly active waste concentrate (HAWC) from nuclear fuel reprocessing is immobilized in borosilicate glass matrices to generate a disposable waste form [1]. Between 2009 and 2010, the vitrification plant Karlsruhe (VEK) was operated for vitrification of liquid process residues left over from operation of the former reprocessing plant Karlsruhe (WAK). About 56 m3 HAWC were processed, resulting in 50 t of waste  glass  [2].  The  long  term  radiotoxicity  of  U,  Np,  Pu  and  other  actinide  elements  (An),  minor constitute of the reprocessed waste, is of great concern in safety assessment studies of nuclear waste repositories. For example, in case of water intrusion and interaction with the glass matrix, corrosion processes will take place which might facilitate the release of radionuclides into the geosphere. The An redox state and bonding characteristics in the glass matrix determine their release mechanisms and retention processes taking place in near and far field of the repository [3]. Understanding the long term behavior of vitrified nuclear waste requires full and detailed characterization of the materials including their characteristics as synthesized and after exposure to  groundwater. Genuine radioactive waste glass has a complex chemical composition. Therefore we take a simplified approach by investigating and comparing the oxidation states of U, Pu and Np in high level waste (HLW) glass sampled from the VEK vitrification process (VEK glass) and in model glasses. The model glasses doped with U and Pu have the same borosilicate glass frit composition as the VEK glass, whereas  the  model  glass  doped  with  Np  has  a  base  glass  composition  (R7T7)  typically  used  for  vitrification of HLW in France. U/Pu/Np  M4/M5  edge  high  energy  resolution  X‐ray  absorption  near  edge  structure  (HR‐XANES)  spectroscopy technique [4] is applied to characterize the An oxidation states

Comparative U, Np and Pu M edge high energy resolution X-ray absorption spectroscopy (HR-XANES) investigations of model and genuine active waste glass

Understanding the long term behavior of vitrified nuclear waste requires a full and detailed characterization of the materials including their characteristics as synthesized and after exposure to groundwater. Genuine radioactive waste glass has a complex chemical composition. Therefore we take a simplified approach by investigating and comparing the oxidation states of U, Pu and Np in high level waste (HLW) glass sampled from the VEK vitrification process (VEK glass) and in model glasses. The model glasses doped with U and Pu have the same borosilicate glass frit composition as the VEK glass, whereas the model glass doped with Np has a base glass composition (R7T7) typically used for vitrification of HLW in France. U/Pu/Np M4/M5 edge high energy resolution X-ray absorption near edge structure (HR-XANES) spectroscopy technique [1] is applied to characterize the An oxidation states in model and genuine VEK HLW glass. The HR-XANES analyses suggest predominant existence of U(VI) and Pu(IV) in the HLW and the model glasses as expected from the oxidative vitrification conditions. Weak changes in U oxidation state as a function of the U loading (1.2 – 5 wt% UO2) are discussed on the basis of U M4 edge HR-XANES and X-ray photoelectron spectroscopy (XPS) results. One significant difference found between the model and the genuine HLW glasses is the strong radiation damage induced in the HLW glass by the soft X-ray beam (position of the U M4 edge: 3.73 keV) which was not observed for the U doped model glasses and the previous L3 edge investigations of the HLW glass sample. The dominant U(VI) oxidation state is reduced almost by 50% to U(IV) within 5 h of measurement. The complex chemical composition of the HLW glass leads to different local U atomic environments compared to the model glass as found by EXAFS investigations. EXAFS results confirm that U in the HLW glass is coordinated by Al/Si neighbors in the second coordination sphere, whereas no neighboring atoms are observed at this distance for the model glass. Differences in results obtained for the Np oxidation state for Np doped asprepared and leached R7T7 borosilicate model glasses and the HLW glass will be presented and discussed

Thermal variation in gradient response: measurement and modeling

Purpose Many aspects and imperfections of gradient dynamics in MRI have been successfully captured by linear time-invariant (LTI) models. Changes in gradient behavior due to heating, however, violate time invariance. The goal of this work is to study such changes at the level of transfer functions and model them by thermal extension of the LTI framework. Methods To study the impact of gradient heating on transfer functions, a clinical MR system was heated using a range of high-amplitude DC and AC waveforms, each followed by measuring transfer functions in rapid succession while the system cooled down. Simultaneously, gradient temperature was monitored with an array of temperature sensors positioned according to initial infrared recordings of the gradient tube. The relation between temperatures and transfer functions is cast into local and global linear models. The models are analysed in terms of self-consistency, conditioning, and prediction performance. Results Pronounced thermal effects are observed in the time resolved transfer functions, largely attributable to in-coil eddy currents and mechanical resonances. Thermal modeling is found to capture these effects well. The keys to good model performance are well-placed temperature sensors and suitable training data. Conclusion Heating changes gradient response, violating time invariance. The utility of LTI modeling can nevertheless be recovered by a linear thermal extension, relying on temperature sensing and adequate one-time training.ISSN:0740-3194ISSN:1522-259

On the signal-to-noise ratio benefit of spiral acquisition in diffusion MRI

Purpose Spiral readouts combine several favorable properties that promise superior net sensitivity for diffusion imaging. The purpose of this study is to verify the signal‐to‐noise ratio (SNR) benefit of spiral acquisition in comparison with current echo‐planar imaging (EPI) schemes. Methods Diffusion‐weighted in vivo brain data from three subjects were acquired with a single‐shot spiral sequence and several variants of single‐shot EPI, including full‐Fourier and partial‐Fourier readouts as well as different diffusion‐encoding schemes. Image reconstruction was based on an expanded signal model including field dynamics obtained by concurrent field monitoring. The effective resolution of each sequence was matched to that of full‐Fourier EPI with 1 mm nominal resolution. SNR maps were generated by determining the noise statistics of the raw data and analyzing the propagation of equivalent synthetic noise through image reconstruction. Using the same approach, maps of noise amplification due to parallel imaging (g‐factor) were calculated for different acceleration factors. Results Relative to full‐Fourier EPI at b = 0 s/mm2, spiral acquisition yielded SNR gains of 42‐88% and 40‐89% in white and gray matter, respectively, depending on the diffusion‐encoding scheme. Relative to partial‐Fourier EPI, the gains were 36‐44% and 34‐42%. Spiral g‐factor maps exhibited less spatial variation and lower maxima than their EPI counterparts. Conclusion Spiral readouts achieve significant SNR gains in the order of 40‐80% over EPI in diffusion imaging at 3T. Combining systematic effects of shorter echo time, readout efficiency, and favorable g‐factor behavior, similar benefits are expected across clinical and neurosciences uses of diffusion imaging.ISSN:0740-3194ISSN:1522-259

A comprehensive approach for correcting voxel-wise b-value errors in diffusion MRI

Purpose In diffusion MRI, the actual b‐value played out on the scanner may deviate from the nominal value due to magnetic field imperfections. A simple image‐based correction method for this problem is presented. Methods The apparent diffusion constant (ADC) of a water phantom was measured voxel‐wise along 64 diffusion directions at b = 1000 s/mm2. The true diffusion constant of water was estimated, considering the phantom temperature. A voxel‐wise correction factor, providing an effective b‐value including any magnetic field deviations, was determined for each diffusion direction by relating the measured ADC to the true diffusion constant. To test the method, the measured b‐value map was used to calculate the corrected voxel‐wise ADC for additionally acquired diffusion data sets on the same water phantom and data sets acquired on a small water phantom at three different positions. Diffusion tensor was estimated by applying the measured b‐value map to phantom and in vivo data sets. Results The b‐value‐corrected ADC maps of the phantom showed the expected spatial uniformity as well as a marked improvement in consistency across diffusion directions. The b‐value correction for the brain data resulted in a 5.8% and 5.5% decrease in mean diffusivity and angular differences of the primary diffusion direction of 2.71° and 0.73° inside gray and white matter, respectively. Conclusion The actual b‐value deviates significantly from its nominal setting, leading to a spatially variable error in the common diffusion outcome measures. The suggested method measures and corrects these artifacts.ISSN:0740-3194ISSN:1522-259