Telemetric Blood Pressure Assessment in Angiotensin II-Infused ApoE\u3csup\u3e-/-\u3c/sup\u3e Mice: 28 Day Natural History and Comparison to Tail-Cuff Measurements

Abdominal aortic aneurysm (AAA) is a disease of the aortic wall, which can progress to catastrophic rupture. Assessment of mechanical characteristics of AAA, such as aortic distensibility, may provide important insights to help identify at-risk patients and understand disease progression. While the majority of studies on this topic have focused on retrospective patient data, recent studies have used mouse models of AAA to prospectively evaluate the evolution of aortic mechanics. Quantification of aortic distensibility requires accurate measurement of arterial blood pressure, particularly pulse pressure, which is challenging to perform accurately in murine models. We hypothesized that volume/pressure tail-cuff measurements of arterial pulse pressure in anesthetized mice would have sufficient accuracy to enable calculations of aortic distensibility with minimal error. Telemetry devices and osmotic mini-pumps filled with saline or angiotensin-II were surgically implanted in male apolipoprotein-E deficient (ApoE-/-) mice. Blood pressure in the aortic arch was measured continuously via telemetry. In addition, simultaneous blood pressure measurements with a volume/pressure tail-cuff system were performed under anesthesia at specific intervals to assess agreement between techniques. Compared to controls, mice infused with angiotensin-II had an overall statistically significant increase in systolic pressure, with no overall difference in pulse pressure; however, pulse pressure did increase significantly with time. Systolic measurements agreed well between telemetry and tail-cuff (coefficient of variation = 10%), but agreement of pulse pressure was weak (20%). In fact, group-averaged pulse pressure from telemetry was a better predictor of a subject\u27s pulse pressure on a given day than a simultaneous tail-cuff measurement. Furthermore, these approximations introduced acceptable errors (15.1 ± 12.8%) into the calculation of aortic distensibility. Contrary to our hypothesis, we conclude that tail-cuff measures of arterial pulse pressure have limited accuracy. Future studies of aneurysm mechanics using the ApoE-/-/angiotensin-II model would be better in assuming pulse pressure profiles consistent with our telemetry findings instead of attempting to measure pulse pressure in individual mice

Modified Dispersion Relations from the Renormalization Group of Gravity

We show that the running of gravitational couplings, together with a suitable identification of the renormalization group scale can give rise to modified dispersion relations for massive particles. This result seems to be compatible with both the frameworks of effective field theory with Lorentz invariance violation and deformed special relativity. The phenomenological consequences depend on which of the frameworks is assumed. We discuss the nature and strength of the available constraints for both cases and show that in the case of Lorentz invariance violation, the theory would be strongly constrained.Comment: revtex4, 9 pages, updated to match published versio

The construction of identities in narratives about serious leisure occupations

Engagement in occupation contributes to the shaping of identity throughout the human life. The act of telling about such engagement involves interaction based on symbolic meaning; the speaker constructing an identity by conveying how the occupation is personally meaningful. This study explored meaning in narratives told by people who engage in serious leisure occupations. A total of 78 narratives were extracted from interviews with 17 people who invest considerable time and other resources into their leisure. Analysis focused on the content, structure and performance of each narrative in order to explore meaning. The meanings were organised into a framework based around three dimensions: the located self, the active self and the changing self. Each dimension has facets that the individual might emphasise, constructing a unique identity. The framework offers a structured basis for conceptualising how occupation contributes to the shaping of the internalised self and the socially situated identity

Asymptotic analysis for the generalized langevin equation

Various qualitative properties of solutions to the generalized Langevin equation (GLE) in a periodic or a confining potential are studied in this paper. We consider a class of quasi-Markovian GLEs, similar to the model that was introduced in \cite{EPR99}. Geometric ergodicity, a homogenization theorem (invariance principle), short time asymptotics and the white noise limit are studied. Our proofs are based on a careful analysis of a hypoelliptic operator which is the generator of an auxiliary Markov process. Systematic use of the recently developed theory of hypocoercivity \cite{Vil04HPI} is made.Comment: 27 pages, no figures. Submitted to Nonlinearity

Characterizing the Temporal Evolution of Altered Cardiac Mechanics in Diet-Induced Obese Mice Using Cine DENSE CMR

Background Obesity and metabolic syndrome are associated with increased risk of cardiovascular disease. Research suggests that altered cardiac mechanics (i.e., reduced strains, torsion, and synchrony of contraction) are present in obesity; yet, the causes of this mechanical dysfunction and its relationship to other sequelae of obesity (e.g., hypertension and elevated blood glucose) are not well understood. We hypothesize that diet-induced obesity in mice leads to reductions in measures of left ventricular (LV) mechanics, which develop in acute response to the onset of hyperglycemia, hypertension, and ventricular remodeling. Methods Twenty 4-week-old C57BL/6J mice were randomized (n = 10 per group) to either a high-fat (60% kcal from fat) or sucrose-matched low-fat (10% kcal from fat) diet for 28 weeks. After 4 weeks and every 6 weeks thereafter, LV mechanics were quantified using cine displacement encoding with stimulated echoes (DENSE) on a 7T ClinScan MRI (Bruker, Ettlingen, Germany) with a 4-element phased array cardiac coil. Three short-axis and two long-axis slices were acquired with 13-20 frames per cardiac cycle. Semi-automated post-processing was performed using custom software in MATLAB (Mathworks, Natick, MA). Additionally, systolic blood pressure (via tail cuff measurement) and fasting blood glucose were assessed every 4 weeks on staggered schedules. Results Mice on the high-fat diet became obese relative to the low-fat controls (49.9 vs. 29.2 g, respectively, by week 28;). Fasting blood glucose was elevated in the high-fat group (202 vs. 112 mg/dL; p \u3c 0.05) starting from the earliest measurement (week 7 on diet), whereas significant differences in LV mass (88 vs. 79 mg) and systolic blood pressure (172 vs. 162 mmHg) developed much later (weeks 22 and 25 on diet, respectively). Significant reductions in peak LV radial (15%) and circumferential (8%) strains and reduced contractile synchrony were detected in the high-fat group for the first time in week 28. A 10% reduction in peak torsion was also observed at that time, but did not reach statistical significance (p = 0.075). There were no differences in LV cavity volumes or ejection fraction. Conclusions Diet-induced obesity in mice is associated with reduced left ventricular mechanics. This dysfunction develops long after the manifestation of hyperglycemia in this model, which suggests that chronic alterations in glucose/insulin levels and/or signaling may contribute more to cardiac contractile dysfunction than acute elevations. Late development of concentric ventricular hypertrophy and hypertension prior to suppressed cardiac mechanics also suggests an important role of these processes in the reduced ventricular function

Reproducibility of cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance for measuring left ventricular strains, torsion, and synchrony in mice

BACKGROUND: Advanced measures of cardiac function are increasingly important to clinical assessment due to their superior diagnostic and predictive capabilities. Cine DENSE cardiovascular magnetic resonance (CMR) is ideal for quantifying advanced measures of cardiac function based on its high spatial resolution and streamlined post-processing. While many studies have utilized cine DENSE in both humans and small-animal models, the inter-test and inter-observer reproducibility for quantification of advanced cardiac function in mice has not been evaluated. This represents a critical knowledge gap for both understanding the capabilities of this technique and for the design of future experiments. We hypothesized that cine DENSE CMR would show excellent inter-test and inter-observer reproducibility for advanced measures of left ventricular (LV) function in mice. METHODS: Five normal mice (C57BL/6) and four mice with depressed cardiac function (diet-induced obesity) were imaged twice, two days apart, on a 7T ClinScan MR system. Images were acquired with 15-20 frames per cardiac cycle in three short-axis (basal, mid, apical) and two long-axis orientations (4-chamber and 2-chamber). LV strain, twist, torsion, and measures of synchrony were quantified. Images from both days were analyzed by one observer to quantify inter-test reproducibility, while inter-observer reproducibility was assessed by a second observer\u27s analysis of day-1 images. The coefficient of variation (CoV) was used to quantify reproducibility. RESULTS: LV strains and torsion were highly reproducible on both inter-observer and inter-test bases with CoVs ≤ 15%, and inter-observer reproducibility was generally better than inter-test reproducibility. However, end-systolic twist angles showed much higher variance, likely due to the sensitivity of slice location within the sharp longitudinal gradient in twist angle. Measures of synchrony including the circumferential (CURE) and radial (RURE) uniformity of strain indices, showed excellent reproducibility with CoVs of 1% and 3%, respectively. Finally, peak measures (e.g., strains) were generally more reproducible than the corresponding rates of change (e.g., strain rate). CONCLUSIONS: Cine DENSE CMR is a highly reproducible technique for quantification of advanced measures of left ventricular cardiac function in mice including strains, torsion and measures of synchrony. However, myocardial twist angles are not reproducible and future studies should instead report torsion

Footprints of Statistical Anisotropies

We propose and develop a formalism to describe and constrain statistically anisotropic primordial perturbations. Starting from a decomposition of the primordial power spectrum in spherical harmonics, we find how the temperature fluctuations observed in the CMB sky are directly related to the coefficients in this harmonic expansion. Although the angular power spectrum does not discriminate between statistically isotropic and anisotropic perturbations, it is possible to define analogous quadratic estimators that are direct measures of statistical anisotropy. As a simple illustration of our formalism we test for the existence of a preferred direction in the primordial perturbations using full-sky CMB maps. We do not find significant evidence supporting the existence of a dipole component in the primordial spectrum.Comment: 26 pages, 5 double figures. Uses RevTeX

Obesity Reduces Left Ventricular Strains, Torsion, and Synchrony in Mouse Models: A Cine Displacement Encoding with Stimulated Echoes (DENSE) Cardiovascular Magnetic Resonance Study

BACKGROUND: Obesity affects a third of adults in the US and results in an increased risk of cardiovascular mortality. While the mechanisms underlying this increased risk are not well understood, animal models of obesity have shown direct effects on the heart such as steatosis and fibrosis, which may affect cardiac function. However, the effect of obesity on cardiac function in animal models is not well-defined. We hypothesized that diet-induced obesity in mice reduces strain, torsion, and synchrony in the left ventricle (LV). METHODS: Ten 12-week-old C57BL/6 J mice were randomized to a high-fat or low-fat diet. After 5 months on the diet, mice were imaged with a 7 T ClinScan using a cine DENSE protocol. Three short-axis and two long-axis slices were acquired for quantification of strains, torsion and synchrony in the left ventricle. RESULTS: Left ventricular mass was increased by 15% (p = 0.032) with no change in volumes or ejection fraction. Subepicardial strain was lower in the obese mice with a 40% reduction in circumferential strain (p = 0.008) a 53% reduction in radial strain (p = 0.032) and a trend towards a 19% reduction in longitudinal strain (p = 0.056). By contrast, subendocardial strain was modestly reduced in the obese mice in the circumferential direction by 12% (p = 0.028), and no different in the radial (p = 0.690) or longitudinal (p = 0.602) directions. Peak torsion was reduced by 34% (p = 0.028). Synchrony of contraction was also reduced (p = 0.032) with a time delay in the septal-to-lateral direction. CONCLUSIONS: Diet-induced obesity reduces left ventricular strains and torsion in mice. Reductions in cardiac strain are mostly limited to the subepicardium, with relative preservation of function in the subendocardium. Diet-induced obesity also leads to reduced synchrony of contraction and hypertrophy in mouse models

More about Birkhoff's Invariant and Thorne's Hoop Conjecture for Horizons

A recent precise formulation of the hoop conjecture in four spacetime dimensions is that the Birkhoff invariant $\beta$ (the least maximal length of any sweepout or foliation by circles) of an apparent horizon of energy $E$ and area $A$ should satisfy $\beta \le 4 \pi E$. This conjecture together with the Cosmic Censorship or Isoperimetric inequality implies that the length $\ell$ of the shortest non-trivial closed geodesic satisfies $\ell^2 \le \pi A$. We have tested these conjectures on the horizons of all four-charged rotating black hole solutions of ungauged supergravity theories and find that they always hold. They continue to hold in the the presence of a negative cosmological constant, and for multi-charged rotating solutions in gauged supergravity. Surprisingly, they also hold for the Ernst-Wild static black holes immersed in a magnetic field, which are asymptotic to the Melvin solution. In five spacetime dimensions we define $\beta$ as the least maximal area of all sweepouts of the horizon by two-dimensional tori, and find in all cases examined that $\beta(g) \le \frac{16 \pi}{3} E$, which we conjecture holds quiet generally for apparent horizons. In even spacetime dimensions $D=2N+2$, we find that for sweepouts by the product $S^1 \times S^{D-4}$, $\beta$ is bounded from above by a certain dimension-dependent multiple of the energy $E$. We also find that $\ell^{D-2}$ is bounded from above by a certain dimension-dependent multiple of the horizon area $A$. Finally, we show that $\ell^{D-3}$ is bounded from above by a certain dimension-dependent multiple of the energy, for all Kerr-AdS black holes.Comment: 25 page

Nontrivial, Asymptotically Non-free Gauge Theories and Dynamical Unification of Couplings

An evidence for nontriviality of asymptotically non-free (ANF) Yang-Mills theories is found on the basis of optimized perturbation theory. It is argued that these theories with matter couplings can be made nontrivial by means of the reduction of couplings, leading to the idea of dynamical unification of couplings (DUC) The second-order reduction of couplings in the ANF $SU(3)$-gauged Higgs-Yukawa theory, which is assumed to be nontrivial here, is carried out to motivate independent investigations on its nontriviality and DUC