Vascular ultrasound and cardiovascular risk assessment

Vascular ultrasound is able to detect endothelial dysfunction, arterial structural remodeling and increased arterial stiffness. These alterations have been shown to be associated with established and emerging cardiovascular risk factors and with incident cardiovascular events. Therefore, vascular ultrasound has been proposed to evaluate the role of different risk factors in the initiation and progression of atherosclerotic process, to study vascular aging and the relationship between arterial stiffness and atherosclerosis, to assess the efficacy of life-style and therapeutic interventions, and to improve the estimation of individual cardiovascular risk. The present paper provides a critical overview of the clinical evidence appraising the association of flow-mediated dilation, carotid and femoral intima-media thickness and plaque presence as well as local arterial stiffness with cardiovascular risk factors and cardiovascular events

Lipids and Cardiovascular Organ Damage in Type 2 Diabetes Mellitus

One of the mechanisms underlying increased cardiovascular (CV) risk in patients with type 2 diabetes mellitus is atherogenic dyslipidemia, that is characterized by elevated triglycerides and free fatty acids (FFAs) levels, low levels of high-density lipoprotein cholesterol (HDL) and an excess of small dense low-density lipoprotein particles (sdLDLs). Each component of atherogenic dyslipidemia is associated with CV events and triggers alterations at different levels of CV system through different pathways. FFAs and sdLDLs induce endothelial dysfunction, intima-media thickening, plaque formation and arterial stiffening through increase in oxidative stress and inflammation and promoting lipid accumulation and smooth muscle cells (SMCs) proliferation in vascular wall. In contrast, HDL exerts protective effect on arterial wall by increasing nitric oxide availability, by reverse cholesterol transport and by suppression of SMCs proliferation and migration. FFAs overload results in a switch in myocardial substrate utilization, causing changes in myocardial energy metabolism and an increase in baseline oxygen consumption. Accumulation of toxic lipid intermediates in myocardium provokes damage of cellular membrane integrity, organelle dysfunction and apoptosis with consequent decrease in myocardial performance. The structural and functional changes in myocardium can be reversed by therapy with reconstructed HDL. Therefore, the impact of atherogenic dyslipidemia on CV system is not limited on accelerated atherosclerosis, but causes different organ damages that must be considered in their complexity

Finding a reflexive voice : -- researching the problems of implementing new learning practices within a New Zealand manufacturing organisation : a 100pt thesis presented in partial fulfilment of the requirements for the degree of Master of Management in Human Resources Management at Massey University

This study explored the social forces mediating manager's participation in a new reflexive participative learning practice designed to improve profitability within a New Zealand manufacturing organisation. Despite a large theoretical and managerial body of literature on organisational learning there has been little empirical investigation of how people experience and engage their reflexivity towards challenging the status-quo to create high level learning and new knowledge. Power was identified as a potential moderator of the reflexive learning experience and the variable relations of power and learning were constructed from a review of literature and these relationships were explored and investigated within the case study. Two prevailing discourses were identified as powerful moderators of public reflexivity, the traditionalist discourse which constructed managers actions and conversations towards insularism and survivalist concerns and the productionist discourse in which institutionalised production practices encircled and mediated managers actions and what constituted legitimacy in conversations. This study used a critical action research method to place the reflexive experience of managers and the researcher at the centre of the study and provide data representative of the social discourses that constructed variable freedoms and constraints upon the reflexive voice

Inferring the diet of extinct elephants: The case study of straight-tusked elephants from Neumark Nord 1 (Northeastern Germany)

Inferring the diet of fossil mammals is a major approach to mammalian palaeobiology and palaeoecology. Compared to other mammals, proboscideans pose significant problems because elephants eat different kinds of food and may change it frequently. Results obtained by analysing the last molars of Palaeoloxodon antiquus from Neumark Nord, highlight the effectiveness of a multidisciplinary approach in inferring the dietary adaptation of elephants. The microwear pattern and stable isotope data obtained for the straight-tusked elephants from Neumark Nord 1, suggest they were mainly grazers in a wooded grassland and moderately humid environment

SPHERIOUSLY? The challenges of estimating sphere radius non-invasively in the human brain from diffusion MRI

The Soma and Neurite Density Imaging (SANDI) three-compartment model was recently proposed to disentangle cylindrical and spherical geometries, attributed to neurite and soma compartments, respectively, in brain tissue. There are some recent advances in diffusion-weighted MRI signal encoding and analysis (including the use of multiple so-called ’b-tensor’ encodings and analysing the signal in the frequency-domain) that have not yet been applied in the context of SANDI. In this work, using: (i) ultra-strong gradients; (ii) a combination of linear, planar, and spherical b-tensor encodings; and (iii) analysing the signal in the frequency domain, three main challenges to robust estimation of sphere size were identified: First, the Rician noise floor in magnitude-reconstructed data biases estimates of sphere properties in a non-uniform fashion. It may cause overestimation or underestimation of the spherical compartment size and density. This can be partly ameliorated by accounting for the noise floor in the estimation routine. Second, even when using the strongest diffusion-encoding gradient strengths available for human MRI, there is an empirical lower bound on the spherical signal fraction and radius that can be detected and estimated robustly. For the experimental setup used here, the lower bound on the sphere signal fraction was approximately 10%. We employed two different ways of establishing the lower bound for spherical radius estimates in white matter. The first, examining power-law relationships between the DW-signal and diffusion weighting in empirical data, yielded a lower bound of , while the second, pure Monte Carlo simulations, yielded a lower limit of and in this low radii domain, there is little differentiation in signal attenuation. Third, if there is sensitivity to the transverse intra-cellular diffusivity in cylindrical structures, e.g., axons and cellular projections, then trying to disentangle two diffusion-time-dependencies using one experimental parameter (i.e., change in frequency-content of the encoding waveform) makes spherical radii estimates particularly challenging. We conclude that due to the aforementioned challenges spherical radii estimates may be biased when the corresponding sphere signal fraction is low, which must be considered

Increased carotid IMT in patients with type 2 diabetes free of cardiovascular complications appears to be an adaptive mechanism to an increased wall stress more than atheromasic degeneration

Type 2 diabetes (DM2) and poor glycemic control adversely affect common carotid intima media thickness (IMT), considered marker of preclinical atherosclerosis. However, studies evaluating the effect of DM2 and glucose levels on IMT did not consider carotid diameter, known to affect IMT. A certain IMT increase could reflect a mutual adjustment between diameter and wall thickness aimed to maintain constant wall tensile stress (WTS). Aim: To compare carotid IMT, luminal diameter, WTS and local wave speed (WS) between patients with uncomplicated DM2 and healthy controls. Methods: Eighty-four patients with well controlled DM2 (HbA1c <7.8%) and 84 controls matched for sex, age and BMI. were studied by radiofrequencybased carotid ultrasound (QIMT and QAS, Esaote). Results: DM2 against controls had higher (p<0.0001) IMT (720131 vs. 62076 mm), luminal diameter (6.60.6 vs. 6.00.7 mm), WS (8.3.61.7 vs. 6.51.2 m/s) and pulse pressure (5813 vs. 478 mmHg), but comparable WTS (498 vs. 5014 kPa; pZ0.82). In the entire population, fasting glucose was not independently related to IMT, but was related to carotid diameter (together with male sex and waist), pulse pressure and local WS (together with age and antihypertensive treatment). In DM2, HbA1c was independently related to carotid diameter, pulse pressure and WS. Conclusions: Chronically increased plasma glucose levels may induce intrinsic stiffening of large artery and widening of pulse pressure. Increased pulsatile load in stiff arteries causes luminal dilatation and increases WTS, triggering an increase in arterial wall thickness. Hyperglycaemia affects arterial wall, but through a “sclerotic” more than “atherogenic” mechanism

Carotid-femoral pulse wave velocity estimated by an ultrasound system

To date, regional aortic stiffness can be evaluated by the reference tonometric technique via the pulse wave velocity (PWV) measured in two points: the carotid and the femoral arteries. Based on a similar intersecting tangent algorithm, we have developed a new method for the determination of carotid-femoral PWV using a high-resolution echo tracking ultrasound system. Herein, PWV can be computed from the measurement of the transit time between the foot of the carotid diameter waveform and the foot of the femoral diameter waveform. The study was carried out on 50 consecutive patients at rest (29 men, mean age 30 ± 18 yrs) recruited on the occasion of a vascular screening for atherosclerosis. Carotid-femoral PWV was determined by a trained operator using a tonometric technique, (PWVpp, PulsePen, Italy), and an echotracking ultrasound system, (PWVus, e-tracking Alpha 10, Aloka, Japan). Relationship between PWVpp and PWVus was evaluated by linear regression. A Pearson’s correlation coefficient of r=0.95 was found between both variables (95% confidence interval 0.90-0.99; P&lt;0.0001; PWVus= 0,91*PWVpp+0.44). The Bland–Altman plot comparing PWVpp and PWVus showed a systematic offset of -0.07 m.s-1 with a limit of agreement from -1,33 to 1,19 m.s-1. Our results show an excellent and significant correlation between both techniques which confirms that ultrasound system can provide a reliable estimate of the regional aortic stiffness like the tonometric technique does. Additional studies are now needed to show the simplicity of the measurement using ultrasound system while maintaining reliability even in overweight patients

Mapping complex cell morphology in the grey matter with double diffusion encoding MR: A simulation study

This paper investigates the impact of cell body (namely soma) size and branching of cellular projections on diffusion MR imaging (dMRI) and spectroscopy (dMRS) signals for both standard single diffusion encoding (SDE) and more advanced double diffusion encoding (DDE) measurements using numerical simulations. The aim is to investigate the ability of dMRI/dMRS to characterize the complex morphology of brain cells focusing on these two distinctive features of brain grey matter. To this end, we employ a recently developed computational framework to create three dimensional meshes of neuron-like structures for Monte Carlo simulations, using diffusion coefficients typical of water and brain metabolites. Modelling the cellular structure as realistically connected spherical soma and cylindrical cellular projections, we cover a wide range of combinations of sphere radii and branching order of cellular projections, characteristic of various grey matter cells. We assess the impact of spherical soma size and branching order on the b-value dependence of the SDE signal as well as the time dependence of the mean diffusivity (MD) and mean kurtosis (MK). Moreover, we also assess the impact of spherical soma size and branching order on the angular modulation of DDE signal at different mixing times, together with the mixing time dependence of the apparent microscopic anisotropy (μA), a promising contrast derived from DDE measurements. The SDE results show that spherical soma size has a measurable impact on both the b-value dependence of the SDE signal and the MD and MK diffusion time dependence for both water and metabolites. On the other hand, we show that branching order has little impact on either, especially for water. In contrast, the DDE results show that spherical soma size has a measurable impact on the DDE signal's angular modulation at short mixing times and the branching order of cellular projections significantly impacts the mixing time dependence of the DDE signal's angular modulation as well as of the derived μA, for both water and metabolites. Our results confirm that SDE based techniques may be sensitive to spherical soma size, and most importantly, show for the first time that DDE measurements may be more sensitive to the dendritic tree complexity (as parametrized by the branching order of cellular projections), paving the way for new ways of characterizing grey matter morphology, non-invasively using dMRS and potentially dMRI