Visualizing the 3D collagen structure of human atherosclerotic plaques using Diffusion Tensor Imaging

Introduction Ischemic strokes and heart attacks are mainly caused by rupture of the fibrous cap of an atherosclerotic plaque. Reliable prediction of the fibrous cap rupture is, therefore, crucial to prevent these potentially lethal cardiovascular events. Since cap rupture occurs when the stresses in the cap exceed the strength of the cap, biomechanical modeling may help to improve cap rupture prediction. Biomechanical models depend strongly on the material parameters used as input. Previous studies focused on the anisotropic mechanical behaviour of atherosclerotic plaques and produced stiffness values for the collagen fibers in plaques [1]. However, for a more complete characterization knowledge of the global 3D collagen architecture in atherosclerotic plaques is required. Therefore, for the first time diffusion tensor imaging (DTI) was used to investigate the 3D collagen structure of human atherosclerotic plaques. Methods Until now five human carotid atherosclerotic plaques were obtained from endarterectomy patients and embedded in 4 % type VII agarose. The samples were placed in a 9.4 T horizontal-bore MRI scanner to conduct DTI. DTI enabled the tracking of the fiber directions and visualisation of the collagen fibers [2]. Results The consistent results of five different plaques suggest that collagen fibers are deposited in a new layer in a different direction during the development of atherosclerosis (see figure for one representative result). Two distinct layers of collagen fibers were found; an outer layer, where the collagen is aligned in the circumferential direction (14.5°±28.0°), similar to healthy arteries [2], and an inner layer where the collagen follows a longitudinal direction (77.4°±22.4°). Conclusions DTI allowed the visualization of the global 3D collagen architecture of atherosclerotic plaques. The inner collagen layer showed a surprising result and implies a change of strain distribution in the artery during the later stage of atherosclerosis, possibly due to the thickening and stiffening of the diseased intimal tissue. These data, combined with collagen stiffness data found in previous studies [1], will be used as input for biomechanical models including the anisotropic mechanical behaviour of plaque tissue. Models using general over-simplified assumptions like isotropic behaviour can be replaced by models including the anisotopic behavior and thereby improve the stress analysis of plaques. Improved models might help in the diagnosis and treatment of plaque rupture preventing heart attacks and ischemic strokes. References [1] Chai C-K, Akyildiz AC, Speelman L, Gijsen FJH, Oomens CWJ, Sambeek MRHM, van der Lugt A, Baaijens FTP, Anisotropic mechanical behaviour of carotid atherosclerotic plaques at large strain, The 8th international symposium on Biomechanics in Vascular Biology and Cardiovascular Disease, Rotterdam, 2013. [2] Ghazanfari S, Driessen-Mol A, Strijkers GJ, Kanters FMW, Baaijens FPT, Bouten CVC, A comparative analysis of the collagen architecture in the carotid artery: Second harmonic generation versus diffusion tensor imaging, Biochemical and Biophysical Research Communications, 426(1): 54-58, 2012

Cost-benefit analysis of introducing next-generation sequencing (metagenomic) pathogen testing in the setting of pyrexia of unknown origin

Pyrexia of unknown origin (PUO) is defined as a temperature of >38.3°C that lasts for >3 weeks, where no cause can be found despite appropriate investigation. Existing protocols for the work-up of PUO can be extensive and costly, motivating the application of recent advances in molecular diagnostics to pathogen testing. There have been many reports describing various analytical methods and performance of metagenomic pathogen testing in clinical samples but the economics of it has been less well studied. This study pragmatically evaluates the feasibility of introducing metagenomic testing in this setting by assessing the relative cost of clinically-relevant strategies employing this investigative tool under various cost and performance scenarios using Singapore as a demonstration case, and assessing the price and performance benchmarks, which would need to be achieved for metagenomic testing to be potentially considered financially viable relative to the current diagnostic standard. This study has some important limitations: we examined only impact of introducing the metagenomic test to the overall diagnostic cost and excluded costs associated with hospitalization and makes assumptions about the performance of the routine diagnostic tests, limiting the cost of metagenomic test, and the lack of further work-up after positive pathogen detection by the metagenomic test. However, these assumptions were necessary to keep the model within reasonable limits. In spite of these, the simplified presentation lends itself to the illustration of the key insights of our paper. In general, we find the use of metagenomic testing as second-line investigation is effectively dominated, and that use of metagenomic testing at first-line would typically require higher rates of detection or lower cost than currently available in order to be justifiable purely as a cost-saving measure. We conclude that current conditions do not warrant a widespread rush to deploy metagenomic testing to resolve any and all uncertainty, but rather as a front-line technology that should be used in specific contexts, as a supplement to rather than a replacement for careful clinical judgement

Generation of two-mode nonclassical states and a quantum phase gate operation in trapped ion cavity QED

We propose a scheme to generate nonclassical states of a quantum system, which is composed of the one-dimensional trapped ion motion and a single cavity field mode. We show that two-mode SU(2) Schr\"odinger-cat states, entangled coherent states, two-mode squeezed vacuum states and their superposition can be generated. If the vibration mode and the cavity mode are used to represent separately a qubit, a quantum phase gate can be implemented.Comment: to appear in PR

Generation of arbitrary two dimensional motional state of a trapped ion

We present a scheme to generate an arbitrary two-dimensional quantum state of motion of a trapped ion. This proposal is based on a sequence of laser pulses, which are tuned appropriately to control transitions on the sidebands of two modes of vibration. Not more than $(M+1)(N+1)$ laser pulses are needed to generate a pure state with upper phonon number $M$ and $N$ in the $x$ and $y$ direction respectively.Comment: to appear in PR

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

Strategic heuristic and valuation of defence R&amp;D investments: A real options approach

10.1109/ICMIT.2010.54929045th IEEE International Conference on Management of Innovation and Technology, ICMIT20101147-115

High thermal stability of zero-field ferromagnetic resonance above 5 GHz in ferrite-doped CoFe thin films

10.1063/1.4816754Applied Physics Letters1034-APPL

Temperature-dependent dynamic magnetization of FeCoHf thin films fabricated by oblique deposition

10.1063/1.4763361Journal of Applied Physics1128-JAPI