Repeatability of fractional flow reserve despite variations in systemic and coronary hemodynamics

Objectives This study classified and quantified the variation in fractional flow reserve (FFR) due to fluctuations in systemic and coronary hemodynamics during intravenous adenosine infusion. Background Although FFR has become a key invasive tool to guide treatment, questions remain regarding its repeatability and stability during intravenous adenosine infusion because of systemic effects that can alter driving pressure and heart rate. Methods We reanalyzed data from the VERIFY (VERification of Instantaneous Wave-Free Ratio and Fractional Flow Reserve for the Assessment of Coronary Artery Stenosis Severity in EverydaY Practice) study, which enrolled consecutive patients who were infused with intravenous adenosine at 140 μg/kg/min and measured FFR twice. Raw phasic pressure tracings from the aorta (Pa) and distal coronary artery (Pd) were transformed into moving averages of Pd/Pa. Visual analysis grouped Pd/Pa curves into patterns of similar response. Quantitative analysis of the Pd/Pa curves identified the “smart minimum” FFR using a novel algorithm, which was compared with human core laboratory analysis. Results A total of 190 complete pairs came from 206 patients after exclusions. Visual analysis revealed 3 Pd/Pa patterns: “classic” (sigmoid) in 57%, “humped” (sigmoid with superimposed bumps of varying height) in 39%, and “unusual” (no pattern) in 4%. The Pd/Pa pattern repeated itself in 67% of patient pairs. Despite variability of Pd/Pa during the hyperemic period, the “smart minimum” FFR demonstrated excellent repeatability (bias −0.001, SD 0.018, paired p = 0.93, r2 = 98.2%, coefficient of variation = 2.5%). Our algorithm produced FFR values not significantly different from human core laboratory analysis (paired p = 0.43 vs. VERIFY; p = 0.34 vs. RESOLVE). Conclusions Intravenous adenosine produced 3 general patterns of Pd/Pa response, with associated variability in aortic and coronary pressure and heart rate during the hyperemic period. Nevertheless, FFR – when chosen appropriately – proved to be a highly reproducible value. Therefore, operators can confidently select the “smart minimum” FFR for patient care. Our results suggest that this selection process can be automated, yet comparable to human core laboratory analysis

Phasic pressure measurements for coronary and valvular interventions using fluid-filled catheters: Errors, automated correction, and clinical implications.

We sought to develop an automatic method for correcting common errors in phasic pressure tracings for physiology-guided interventions on coronary and valvular stenosis. Effective coronary and valvular interventions rely on accurate hemodynamic assessment. Phasic (subcycle) indexes remain intrinsic to valvular stenosis and are emerging for coronary stenosis. Errors, corrections, and clinical implications of fluid-filled catheter phasic pressure assessments have not been assessed in the current era of ubiquitous, high-fidelity pressure wire sensors. We recruited patients undergoing invasive coronary physiology assessment. Phasic aortic pressure signals were recorded simultaneously using a fluid-filled guide catheter and 0.014″ pressure wire before and after standard calibration as well as after pullback. We included additional subjects undergoing hemodynamic assessment before and after transcatheter aortic valve implantation. Using the pressure wire as reference standard, we developed an automatic algorithm to match phasic pressures. Removing pressure offset and temporal shift produced the largest improvements in root mean square (RMS) error between catheter and pressure wire signals. However, further optimization <1 mmHg RMS error was possible by accounting for differential gain and the oscillatory behavior of the fluid-filled guide. The impact of correction was larger for subcycle (like systole or diastole) versus whole-cycle metrics, indicating a key role for valvular stenosis and emerging coronary pressure ratios. When calibrating phasic aortic pressure signals using a pressure wire, correction requires these parameters: offset, timing, gain, and oscillations (frequency and damping factor). Automatically eliminating common errors may improve some clinical decisions regarding physiology-based intervention

Deciphering the Link between Doubly Uniparental Inheritance of mtDNA and Sex Determination in Bivalves: Clues from Comparative Transcriptomics

Bivalves exhibit an astonishing diversity of sexual systems and sex-determining mechanisms. They can be gonochoric, hermaphroditic or androgenetic, with both genetic and environmental factors known to determine or influence sex. One unique sex-determining system involving the mitochondrial genome has also been hypothesized to exist in bivalves with doubly uniparental inheritance (DUI) of mtDNA. However, the link between DUI and sex determination remains obscure. In this study, we performed a comparative gonad transcriptomics analysis for two DUI-possessing freshwater mussel species to better understand the mechanisms underlying sex determination and DUI in these bivalves. We used a BLAST reciprocal analysis to identify orthologs between Venustaconcha ellipsiformis and Utterbackia peninsularis and compared our results with previously published sex-specific bivalve transcriptomes to identify conserved sex-determining genes. We also compared our data with other DUI species to identify candidate genes possibly involved in the regulation of DUI. A total of 3c12,000 orthologous relationships were found, with 2,583 genes differentially expressed in both species. Among these genes, key sex-determining factors previously reported in vertebrates and in bivalves (e.g., Sry, Dmrt1, Foxl2) were identified, suggesting that some steps of the sex-determination pathway may be deeply conserved in metazoans. Our results also support the hypothesis that a modified ubiquitination mechanism could be responsible for the retention of the paternal mtDNA in male bivalves, and revealed that DNA methylation could also be involved in the regulation of DUI. Globally, our results suggest that sets of genes associated with sex determination and DUI are similar in distantly-related DUI species

Higher order contributions to the effective action of N=2 super Yang-Mills

We apply heat kernel techniques in N=1 superspace to compute the one-loop effective action to order $F^5$ for chiral superfields coupled to a non-Abelian super Yang-Mills background. The results, when combined with those of hep-th/0210146, yield the one-loop effective action to order $F^5$ for any N=2 super Yang-Mills theory coupled to matter hypermultiplets.Comment: 23 pages, references adde

The effect of two-temperature post-shock accretion flow on the linear polarization pulse in magnetic cataclysmic variables

The temperatures of electrons and ions in the post-shock accretion region of a magnetic cataclysmic variable (mCV) will be equal at sufficiently high mass flow rates or for sufficiently weak magnetic fields. At lower mass flow rates or in stronger magnetic fields, efficient cyclotron cooling will cool the electrons faster than the electrons can cool the ions and a two-temperature flow will result. Here we investigate the differences in polarized radiation expected from mCV post-shock accretion columns modeled with one- and two-temperature hydrodynamics. In an mCV model with one accretion region, a magnetic field >~30 MG and a specific mass flow rate of ~0.5 g/cm/cm/s, along with a relatively generic geometric orientation of the system, we find that in the ultraviolet either a single linear polarization pulse per binary orbit or two pulses per binary orbit can be expected, depending on the accretion column hydrodynamic structure (one- or two-temperature) modeled. Under conditions where the physical flow is two-temperature, one pulse per orbit is predicted from a single accretion region where a one-temperature model predicts two pulses. The intensity light curves show similar pulse behavior but there is very little difference between the circular polarization predictions of one- and two-temperature models. Such discrepancies indicate that it is important to model some aspect of two-temperature flow in indirect imaging procedures, like Stokes imaging, especially at the edges of extended accretion regions, were the specific mass flow is low, and especially for ultraviolet data.Comment: Accepted for publication in Astrophysics & Space Scienc

The effect of chirality phenotype and genotype on the fecundity and viability of Partula suturalis and Lymnaea stagnalis: Implications for the evolution of sinistral snails

Why are sinistral snails so rare? Two main hypotheses are that selection acts against the establishment of new coiling morphs, because dextral and sinistral snails have trouble mating, or else a developmental constraint prevents the establishment of sinistrals. We therefore used an isolate of the snail Lymnaea stagnalis, in which sinistrals are rare, and populations of Partula suturalis, in which sinistrals are common, as well as a mathematical model, to understand the circumstances by which new morphs evolve. The main finding is that the sinistral genotype is associated with reduced egg viability in L. stagnalis, but in P. suturalis individuals of sinistral and dextral genotype appear equally fecund, implying a lack of a constraint. As positive frequency-dependent selection against the rare chiral morph in P. suturalis also operates over a narrow range (< 3%), the results suggest a model for chiral evolution in snails in which weak positive frequency-dependent selection may be overcome by a negative frequency-dependent selection, such as reproductive character displacement. In snails, there is not always a developmental constraint. As the direction of cleavage, and thus the directional asymmetry of the entire body, does not generally vary in other Spiralia (annelids, echiurans, vestimentiferans, sipunculids and nemerteans), it remains an open question as to whether this is because of a constraint and/or because most taxa do not have a conspicuous external asymmetry (like a shell) upon which selection can act

Electromagnetic transitions of the helium atom in superstrong magnetic fields

We investigate the electromagnetic transition probabilities for the helium atom embedded in a superstrong magnetic field taking into account the finite nuclear mass. We address the regime \gamma=100-10000 a.u. studying several excited states for each symmetry, i.e. for the magnetic quantum numbers 0,-1,-2,-3, positive and negative z parity and singlet and triplet symmetry. The oscillator strengths as a function of the magnetic field, and in particular the influence of the finite nuclear mass on the oscillator strengths are shown and analyzed.Comment: 10 pages, 8 figure

Hawaii energy strategy project 2: Fossil energy review. Task 1: World and regional fossil energy dynamics

This report in the Hawaii Energy Strategy Project examines world and regional fossil energy dynamics. The topics of the report include fossil energy characteristics, the world oil industry including reserves, production, consumption, exporters, importers, refining, products and their uses, history and trends in the global oil market and the Asia-Pacific market; world gas industry including reserves, production, consumption, exporters, importers, processing, gas-based products, international gas market and the emerging Asia-Pacific gas market; the world coal industry including reserves, classification and quality, utilization, transportation, pricing, world coal market, Asia-Pacific coal outlook, trends in Europe and the Americas; and environmental trends affecting fossil fuels. 132 figs., 46 tabs

Helium in superstrong magnetic fields

We investigate the helium atom embedded in a superstrong magnetic field gamma=100-10000 au. All effects due to the finite nuclear mass for vanishing pseudomomentum are taken into account. The influence and the magnitude of the different finite mass effects are analyzed and discussed. Within our full configuration interaction approach calculations are performed for the magnetic quantum numbers M=0,-1,-2,-3, singlet and triplet states, as well as positive and negative z parities. Up to six excited states for each symmetry are studied. With increasing field strength the number of bound states decreases rapidly and we remain with a comparatively small number of bound states for gamma=10^4 au within the symmetries investigated here.Comment: 16 pages, including 14 eps figures, submitted to Phys. Rev.

The association of dietary choline and betaine with the risk of type 2 diabetes: The atherosclerosis risk in communities (aric) study

OBJECTIVE To examine the association between dietary intake of choline and betaine and the risk of type 2 diabetes. RESEARCH DESIGN AND METHODS Among 13,440 Atherosclerosis Risk in Communities (ARIC) study participants, the prospective longitudinal association between dietary choline and betaine intake and the risk of type 2 diabetes was assessed using interval-censored Cox pro-portional hazards and logistic regression models adjusted for baseline potential confounding variables. RESULTS Among 13,440 participants (55% women, mean age 54 [SD 7.4] years), 1,396 developed incident type 2 diabetes during median follow-up of 9 years from 1987 to 1998. There was no statistically significant association between every 1-SD increase in dietary choline and risk of type 2 diabetes (hazard ratio [HR] 1.01 [95% CI 0.87, 1.16]) nor between dietary betaine intake and the risk of type 2 diabetes (HR 1.01 [0.94, 1.10]). Those in the highest quartile of dietary choline intake did not have a statistically significant higher risk of type 2 diabetes than those in the lowest choline quartile (HR 1.09 [0.84, 1.42]); similarly, dietary betaine intake was not associated with the risk of type 2 diabetes comparing the highest quartile to the lowest (HR 1.06 [0.87, 1.29]). Among women, there was a higher risk of type 2 diabetes, comparing the highest to lowest dietary choline quartile (HR 1.54 [1.06, 2.25]), while in men, the association was null (HR 0.82 [0.57, 1.17]). Nevertheless, there was a nonsignificant interaction between high choline intake and sex on the risk of type 2 diabetes (P 5 0.07). The results from logistic regression were similar. CONCLUSIONS Overall and among male participants, dietary choline or betaine intakes were not associated with the risk of type 2 diabetes. Among female participants, there was a trend for a modestly higher risk of type 2 diabetes among those with the highest as compared with the lowest quartile of dietary choline intake. Our study should inform clinical trials on dietary choline and betaine supplementation in relationship with the risk of type 2 diabetes