Whole lung morphometry with 3D multiple b-value hyperpolarized gas MRI and compressed sensing.

PURPOSE: To demonstrate three-dimensional (3D) multiple b-value diffusion-weighted (DW) MRI of hyperpolarized (3) He gas for whole lung morphometry with compressed sensing (CS). METHODS: A fully-sampled, two b-value, 3D hyperpolarized (3) He DW-MRI dataset was acquired from the lungs of a healthy volunteer and retrospectively undersampled in the ky and kz phase-encoding directions for CS simulations. Optimal k-space undersampling patterns were determined by minimizing the mean absolute error between reconstructed and fully-sampled (3) He apparent diffusion coefficient (ADC) maps. Prospective three-fold, undersampled, 3D multiple b-value (3) He DW-MRI datasets were acquired from five healthy volunteers and one chronic obstructive pulmonary disease (COPD) patient, and the mean values of maps of ADC and mean alveolar dimension (LmD ) were validated against two-dimensional (2D) and 3D fully-sampled (3) He DW-MRI experiments. RESULTS: Reconstructed undersampled datasets showed no visual artifacts and good preservation of the main image features and quantitative information. A good agreement between fully-sampled and prospective undersampled datasets was found, with a mean difference of +3.4% and +5.1% observed in mean global ADC and LmD values, respectively. These differences were within the standard deviation range and consistent with values reported from healthy and COPD lungs. CONCLUSIONS: Accelerated CS acquisition has facilitated 3D multiple b-value (3) He DW-MRI scans in a single breath-hold, enabling whole lung morphometry mapping. Magn Reson Med, 2016. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Het Deltaplan Hoge Zandgronden

In de loop van 2014 worden de Deltabeslissingen genomen. Hoewel deze nog niet definitief zijn, zijn de hoofdlijnen van de opgave duidelijk. Voor het Deltaplan Hoge Zandgronden (DHZ) van het Delta(deel)programma Zoetwater liggen de opgaven op het gebied van watertekorten en -overlast met consequenties voor diverse functies (landbouw, natuur, drinkwater, scheepvaart, industrie, recreatie, stedelijk gebied, bodemdaling en waterveiligheid). Een uitvoeringsprogramma voor deze opgaven is opgesteld, waarbij verschillende partijen betrokken zijn als stakeholders, maar ook als kostendragers. Het huidige Deltaprogramma biedt de kaders voor de nationale inbedding van dit regionale uitvoe-ringsprogramma, maar na de Deltabeslissingen is het nog niet duidelijk hoe de uitvoeringsorganisatie er uit ziet. Het advies van Teisman en Van Buuren (2014) benadrukt het belang van instandhouding van regionale fora voor afstemming, met name ook op het snijvlak van water en ruimte, en als bouw-steen voor een vitaal multilevel governance arrangement. Ook benadrukken zij het belang om uit-voering en strategievorming hand in hand te laten gaan

Comparison of 3He and129Xe MRI for evaluation of lung microstructure and ventilation at 1.5T

BACKGROUND: To support translational lung MRI research with hyperpolarized129Xe gas, comprehensive evaluation of derived quantitative lung function measures against established measures from3He MRI is required. Few comparative studies have been performed to date, only at 3T, and multisession repeatability of129Xe functional metrics have not been reported. PURPOSE/HYPOTHESIS: To compare hyperpolarized129Xe and3He MRI-derived quantitative metrics of lung ventilation and microstructure, and their repeatability, at 1.5T. STUDY TYPE: Retrospective. POPULATION: Fourteen healthy nonsmokers (HN), five exsmokers (ES), five patients with chronic obstructive pulmonary disease (COPD), and 16 patients with nonsmall-cell lung cancer (NSCLC). FIELD STRENGTH/SEQUENCE: 1.5T. NSCLC, COPD patients and selected HN subjects underwent 3D balanced steady-state free-precession lung ventilation MRI using both3He and129Xe. Selected HN, all ES, and COPD patients underwent 2D multislice spoiled gradient-echo diffusion-weighted lung MRI using both hyperpolarized gas nuclei. ASSESSMENT: Ventilated volume percentages (VV%) and mean apparent diffusion coefficients (ADC) were derived from imaging. COPD patients performed the whole MR protocol in four separate scan sessions to assess repeatability. Same-day pulmonary function tests were performed. STATISTICAL TESTS: Intermetric correlations: Spearman's coefficient. Intergroup/internuclei differences: analysis of variance / Wilcoxon's signed rank. Repeatability: coefficient of variation (CV), intraclass correlation (ICC) coefficient. RESULTS: A significant positive correlation between3He and129Xe VV% was observed (r = 0.860, P < 0.001). VV% was larger for3He than129Xe (P = 0.001); average bias, 8.79%. A strong correlation between mean3He and129Xe ADC was obtained (r = 0.922, P < 0.001). MR parameters exhibited good correlations with pulmonary function tests. In COPD patients, mean CV of3He and129Xe VV% was 4.08% and 13.01%, respectively, with ICC coefficients of 0.541 (P = 0.061) and 0.458 (P = 0.095). Mean3He and129Xe ADC values were highly repeatable (mean CV: 2.98%, 2.77%, respectively; ICC: 0.995, P < 0.001; 0.936, P < 0.001). DATA CONCLUSION:129Xe lung MRI provides near-equivalent information to3He for quantitative lung ventilation and microstructural MRI at 1.5T. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage

Selection-free predictions in global games with endogenous information and multiple equilibria

Global games with endogenous information often exhibit multiple equilibria. In this paper, we show how one can nevertheless identify useful predictions that are robust across all equilibria and that cannot be delivered in the common-knowledge counterparts of these games. Our analysis is conducted within a flexible family of games of regime change, which have been used to model, inter alia, speculative currency attacks, debt crises, and political change. The endogeneity of information originates in the signaling role of policy choices. A novel procedure of iterated elimination of nonequilibrium strategies is used to deliver probabilistic predictions that an outside observer—an econometrician—can form under arbitrary equilibrium selections. The sharpness of these predictions improves as the noise gets smaller, but disappears in the complete-information version of the model

Overcoming bortezomib resistance in human B cells by anti-CD20/rituximab-mediated complement-dependent cytotoxicity and epoxyketone-based irreversible proteasome inhibitors

UNLABELLED: BACKGROUND: In clinical and experimental settings, antibody-based anti-CD20/rituximab and small molecule proteasome inhibitor (PI) bortezomib (BTZ) treatment proved effective modalities for B cell depletion in lymphoproliferative disorders as well as autoimmune diseases. However, the chronic nature of these diseases requires either prolonged or re-treatment, often with acquired resistance as a consequence. METHODS: Here we studied the molecular basis of acquired resistance to BTZ in JY human B lymphoblastic cells following prolonged exposure to this drug and examined possibilities to overcome resistance by next generation PIs and anti-CD20/rituximab-mediated complement-dependent cytotoxicity (CDC). RESULTS: Characterization of BTZ-resistant JY/BTZ cells compared to parental JY/WT cells revealed the following features: (a) 10-12 fold resistance to BTZ associated with the acquisition of a mutation in the PSMB5 gene (encoding the constitutive $β$5 proteasome subunit) introducing an amino acid substitution (Met45Ile) in the BTZ-binding pocket, (b) a significant 2-4 fold increase in the mRNA and protein levels of the constitutive $β$5 proteasome subunit along with unaltered immunoproteasome expression, (c) full sensitivity to the irreversible epoxyketone-based PIs carfilzomib and (to a lesser extent) the immunoproteasome inhibitor ONX 0914. Finally, in association with impaired ubiquitination and attenuated breakdown of CD20, JY/BTZ cells harbored a net 3-fold increase in CD20 cell surface expression, which was functionally implicated in conferring a significantly increased anti-CD20/rituximab-mediated CDC. CONCLUSIONS: These results demonstrate that acquired resistance to BTZ in B cells can be overcome by next generation PIs and by anti-CD20/rituximab-induced CDC, thereby paving the way for salvage therapy in BTZ-resistant disease

Airspace Dimension Assessment (AiDA) by inhaled nanoparticles: benchmarking with hyperpolarised 129Xe diffusion-weighted lung MRI

Enlargements of distal airspaces can indicate pathological changes in the lung, but accessible and precise techniques able to measure these regions are lacking. Airspace Dimension Assessment with inhaled nanoparticles (AiDA) is a new method developed for in vivo measurement of distal airspace dimensions. The aim of this study was to benchmark the AiDA method against quantitative measurements of distal airspaces from hyperpolarised 129Xe diffusion-weighted (DW)-lung magnetic resonance imaging (MRI). AiDA and 129Xe DW-MRI measurements were performed in 23 healthy volunteers who spanned an age range of 23–70 years. The relationship between the 129Xe DW-MRI and AiDA metrics was tested using Spearman’s rank correlation coefficient. Significant correlations were observed between AiDA distal airspace radius (rAiDA) and mean 129Xe apparent diffusion coefficient (ADC) (p < 0.005), distributed diffusivity coefficient (DDC) (p < 0.001) and distal airspace dimension (LmD) (p < 0.001). A mean bias of − 1.2 µm towards rAiDA was observed between 129Xe LmD and rAiDA, indicating that rAiDA is a measure of distal airspace dimension. The AiDA R0 intercept correlated with MRI 129Xe α (p = 0.02), a marker of distal airspace heterogeneity. This study demonstrates that AiDA has potential to characterize the distal airspace microstructures and may serve as an alternative method for clinical examination of the lungs

Static quantities of the W boson in the SU_L(3) X U_X(1) model with right-handed neutrinos

The static electromagnetic properties of the $W$ boson, $\Delta \kappa$ and $\Delta Q$, are calculated in the SU_L(3)} \times U_X(1) model with right-handed neutrinos. The new contributions from this model arise from the gauge and scalar sectors. In the gauge sector there is a new contribution from a complex neutral gauge boson $Y^0$ and a singly-charged gauge boson $Y^\pm$. The mass of these gauge bosons, called bileptons, is expected to be in the range of a few hundreds of GeV according to the current bounds from experimental data. If the bilepton masses are of the order of 200 GeV, the size of their contribution is similar to that obtained in other weakly coupled theories. However the contributions to both $\Delta Q$ and $\Delta \kappa$ are negligible for very heavy or degenerate bileptons. As for the scalar sector, an scenario is examined in which the contribution to the $W$ form factors is identical to that of a two-Higgs-doublet model. It is found that this sector would not give large corrections to $\Delta \kappa$ and $\Delta Q$.Comment: New material included. Final version to apppear in Physical Review

Normal and Lateral Casimir Forces between Deformed Plates

The Casimir force between macroscopic bodies depends strongly on their shape and orientation. To study this geometry dependence in the case of two deformed metal plates, we use a path integral quantization of the electromagnetic field which properly treats the many-body nature of the interaction, going beyond the commonly used pairwise summation (PWS) of van der Waals forces. For arbitrary deformations we provide an analytical result for the deformation induced change in Casimir energy, which is exact to second order in the deformation amplitude. For the specific case of sinusoidally corrugated plates, we calculate both the normal and the lateral Casimir forces. The deformation induced change in the Casimir interaction of a flat and a corrugated plate shows an interesting crossover as a function of the ratio of the mean platedistance H to the corrugation length \lambda: For \lambda \ll H we find a slower decay \sim H^{-4}, compared to the H^{-5} behavior predicted by PWS which we show to be valid only for \lambda \gg H. The amplitude of the lateral force between two corrugated plates which are out of registry is shown to have a maximum at an optimal wavelength of \lambda \approx 2.5 H. With increasing H/\lambda \gtrsim 0.3 the PWS approach becomes a progressively worse description of the lateral force due to many-body effects. These results may be of relevance for the design and operation of novel microelectromechanical systems (MEMS) and other nanoscale devices.Comment: 20 pages, 5 figure