Measurement of Wall Shear Stress Exerted by Flowing Blood in the Human Carotid Artery: Ultrasound Doppler Velocimetry and Echo Particle Image Velocimetry

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordVascular endothelial cells lining the arteries are sensitive to wall shear stress (WSS) exerted by flowing blood. An important component of the pathophysiology of vascular diseases, WSS is commonly estimated by centerline ultrasound Doppler velocimetry (UDV). However, the accuracy of this method is uncertain. We have previously validated the use of a novel, ultrasound-based, particle image velocimetry technique (echo PIV) to compute 2-D velocity vector fields, which can easily be converted into WSS data. We compared WSS data derived from UDV and echo PIV in the common carotid artery of 27 healthy participants. Compared with echo PIV, time-averaged WSS was lower using UDV (28 ± 35%). Echo PIV revealed that this was due to considerable spatiotemporal variation in the flow velocity profile, contrary to the assumption that flow is steady and the velocity profile is parabolic throughout the cardiac cycle. The largest WSS underestimation by UDV was found during peak systole (118 ± 16%) and the smallest during mid-diastole (4.3± 46%). The UDV method underestimated WSS for the accelerating and decelerating systolic measurements (68 ± 30% and 24 ± 51%), whereas WSS was overestimated for end-diastolic measurements (−44 ± 55%). Our data indicate that UDV estimates of WSS provided limited and largely inaccurate information about WSS and that the complex spatiotemporal flow patterns do not fit well with traditional assumptions about blood flow in arteries. Echo PIV-derived WSS provides detailed information about this important but poorly understood stimulus that influences vascular endothelial pathophysiology.National Institute of HealthNational Institute for Health Research (NIHR

Reservoir-Excess Pressure Parameters Independently Predicts Cardiovascular Events in Individuals With Type 2 Diabetes.

The parameters derived from reservoir-excess pressure analysis have prognostic utility in several populations. However, evidence in type 2 diabetes (T2DM) remains scarce. We determined if these parameters were associated with T2DM and whether they would predict cardiovascular events in individuals with T2DM. We studied 306 people with T2DM with cardiovascular disease (CVD; DMCVD, 70.4±7.8 years), 348 people with T2DM but without CVD (diabetes mellitus, 67.7±8.4 years), and 178 people without T2DM or CVD (control group [CTRL], 67.2±8.9 years). Reservoir-excess pressure analysis-derived parameters, including reservoir pressure integral, peak reservoir pressure, excess pressure integral, systolic rate constant, and diastolic rate constant, were obtained by radial artery tonometry. Reservoir pressure integral was lower in DMCVD diabetes mellitus and than CTRL. Peak reservoir pressure was lower, and excess pressure integral was greater in DMCVD diabetes mellitus than and CTRL. Systolic rate constant was lower in a stepwise manner among groups (DMCVD< diabetes mellitus <CTRL). Diastolic rate constant was greater in DMCVD than CTRL. In the subgroup of individuals with T2DM (n=642), 14 deaths (6 cardiovascular and 9 noncardiovascular causes), and 108 cardiovascular events occurred during a 3-year follow-up period. Logistic regression analysis revealed that reservoir pressure integral (odds ratio, 0.59 [95% CI, 0.45-0.79]) and diastolic rate constant (odds ratio, 1.60 [95% CI, 1.25-2.06]) were independent predictors of cardiovascular events during follow-up after adjusting for conventional risk factors (both P<0.001). Further adjustments for potential confounders had no influence on associations. These findings demonstrate that altered reservoir-excess pressure analysis-derived parameters are associated with T2DM. Furthermore, baseline values of reservoir pressure integral and diastolic rate constant independently predict cardiovascular events in individuals with T2DM, indicating the potential clinical utility of these parameters for risk stratification in T2DM

The Spectrum of Goldstini and Modulini

When supersymmetry is broken in multiple sectors via independent dynamics, the theory furnishes a corresponding multiplicity of "goldstini" degrees of freedom which may play a substantial role in collider phenomenology and cosmology. In this paper, we explore the tree-level mass spectrum of goldstini arising from a general admixture of F-term, D-term, and almost no-scale supersymmetry breaking, employing non-linear superfields and a novel gauge fixing for supergravity discussed in a companion paper. In theories of F-term and D-term breaking, goldstini acquire a mass which is precisely twice the gravitino mass, while the inclusion of no-scale breaking renders one of these modes, the modulino, massless. We argue that the vanishing modulino mass can be explained in terms of an accidental and spontaneously broken "global" supersymmetry.Comment: 10 pages, 2 figures; v2: typo corrected, references updated; v3: version to appear in JHE

The impact of cardiovascular co-morbidities and duration of diabetes on the association between microvascular function and glycaemic control

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Good glycaemic control in type 2 diabetes (T2DM) protects the microcirculation. Current guidelines suggest glycaemic targets be relaxed in advanced diabetes. We explored whether disease duration or pre-existing macrovascular complications attenuated the association between hyperglycaemia and microvascular function. METHODS: 743 participants with T2DM (n = 222), cardiovascular disease (CVD = 183), both (n = 177) or neither (controls = 161) from two centres in the UK, underwent standard clinical measures and endothelial dependent (ACh) and independent (SNP) microvascular function assessment using laser Doppler imaging. RESULTS: People with T2DM and CVD had attenuated ACh and SNP responses compared to controls. This was additive in those with both (ANOVA p < 0.001). In regression models, cardiovascular risk factors accounted for attenuated ACh and SNP responses in CVD, whereas HbA1c accounted for the effects of T2DM. HbA1c was associated with ACh and SNP response after adjustment for cardiovascular risk factors (adjusted standardised beta (β) -0.096, p = <0.008 and -0.135, p < 0.001, respectively). Pre-existing CVD did not modify this association (β -0.099; p = 0.006 and -0.138; p < 0.001, respectively). Duration of diabetes accounted for the association between HbA1c and ACh (β -0.043; p = 0.3), but not between HbA1c and SNP (β -0.105; p = 0.02). CONCLUSIONS: In those with T2DM and CVD, good glycaemic control is still associated with better microvascular function, whereas in those with prolonged disease this association is lost. This suggests duration of diabetes may be a better surrogate for "advanced disease" than concomitant CVD, although this requires prospective validation.This received support from the Innovative Medicines Initiative Joint Undertaking under the Grant Agreement No. 115006; http://www.imi-summit.eu

Six-dimensional Supergravity and Projective Superfields

We propose a superspace formulation of N=(1,0) conformal supergravity in six dimensions. The corresponding superspace constraints are invariant under super-Weyl transformations generated by a real scalar parameter. The known variant Weyl super-multiplet is recovered by coupling the geometry to a super-3-form tensor multiplet. Isotwistor variables are introduced and used to define projective superfields. We formulate a locally supersymmetric and super-Weyl invariant action principle in projective superspace. Some families of dynamical supergravity-matter systems are presented.Comment: 39 pages; v3: some modifications in section 2; equations (2.3), (2.14b), (2.16) and (2.17) correcte

The Two Faces of Anomaly Mediation

Anomaly mediation is a ubiquitous source of supersymmetry (SUSY) breaking which appears in almost every theory of supergravity. In this paper, we show that anomaly mediation really consists of two physically distinct phenomena, which we dub "gravitino mediation" and "Kahler mediation". Gravitino mediation arises from minimally uplifting SUSY anti-de Sitter (AdS) space to Minkowski space, generating soft masses proportional to the gravitino mass. Kahler mediation arises when visible sector fields have linear couplings to SUSY breaking in the Kahler potential, generating soft masses proportional to beta function coefficients. In the literature, these two phenomena are lumped together under the name "anomaly mediation", but here we demonstrate that they can be physically disentangled by measuring associated couplings to the goldstino. In particular, we use the example of gaugino soft masses to show that gravitino mediation generates soft masses without corresponding goldstino couplings. This result naively violates the goldstino equivalence theorem but is in fact necessary for supercurrent conservation in AdS space. Since gravitino mediation persists even when the visible sector is sequestered from SUSY breaking, we can use the absence of goldstino couplings as an unambiguous definition of sequestering.Comment: 21 pages, 1 table; v2, references added, extended discussion in introduction and appendix; v3, JHEP versio