Stable coronary syndromes: pathophysiology, diagnostic advances and therapeutic need

The diagnostic management of patients with angina pectoris typically centres on the detection of obstructive epicardial CAD, which aligns with evidence-based treatment options that include medical therapy and myocardial revascularisation. This clinical paradigm fails to account for the considerable proportion (approximately one-third) of patients with angina in whom obstructive CAD is excluded. This common scenario presents a diagnostic conundrum whereby angina occurs but there is no obstructive CAD (ischaemia and no obstructive coronary artery disease—INOCA). We review new insights into the pathophysiology of angina whereby myocardial ischaemia results from a deficient supply of oxygenated blood to the myocardium, due to various combinations of focal or diffuse epicardial disease (macrovascular), microvascular dysfunction or both. Macrovascular disease may be due to the presence of obstructive CAD secondary to atherosclerosis, or may be dynamic due to a functional disorder (eg, coronary artery spasm, myocardial bridging). Pathophysiology of coronary microvascular disease may involve anatomical abnormalities resulting in increased coronary resistance, or functional abnormalities resulting in abnormal vasomotor tone. We consider novel clinical diagnostic techniques enabling new insights into the causes of angina and appraise the need for improved therapeutic options for patients with INOCA. We conclude that the taxonomy of stable CAD could improve to better reflect the heterogeneous pathophysiology of the coronary circulation. We propose the term ‘stable coronary syndromes’ (SCS), which aligns with the well-established terminology for ‘acute coronary syndromes’. SCS subtends a clinically relevant classification that more fully encompasses the different diseases of the epicardial and microvascular coronary circulation

What Brown saw and you can too

A discussion is given of Robert Brown's original observations of particles ejected by pollen of the plant \textit{Clarkia pulchella} undergoing what is now called Brownian motion. We consider the nature of those particles, and how he misinterpreted the Airy disc of the smallest particles to be universal organic building blocks. Relevant qualitative and quantitative investigations with a modern microscope and with a "homemade" single lens microscope similar to Brown's, are presented.Comment: 14.1 pages, 11 figures, to be published in the American Journal of Physics. This differs from the previous version only in the web site referred to in reference 3. Today, this Brownian motion web site was launched, and http://physerver.hamilton.edu/Research/Brownian/index.html, is now correc

Integral D-Finite Functions

We propose a differential analog of the notion of integral closure of algebraic function fields. We present an algorithm for computing the integral closure of the algebra defined by a linear differential operator. Our algorithm is a direct analog of van Hoeij's algorithm for computing integral bases of algebraic function fields

Single versus two-stent strategies for coronary bifurcation lesions: a systematic review and meta-analysis of randomized trials with long-term follow-up

Background: The majority of coronary bifurcation lesions are treated with a provisional single‐stent strategy rather than an up‐front 2‐stent strategy. This approach is supported by multiple randomized controlled clinical trials with short‐ to medium‐term follow‐up; however, long‐term follow‐up data is evolving from many data sets. Methods and Results: Meta‐analysis of randomized controlled trials evaluating long‐term outcomes (≥1 year) according to treatment strategy for coronary bifurcation lesions. Nine randomized controlled trials with 3265 patients reported long‐term clinical outcomes at mean weighted follow‐up of 3.1±1.8 years. Provisional single stenting was associated with lower all‐cause mortality (2.94% versus 4.23%; risk ratio: 0.69; 95% confidence interval, 0.48–1.00; P=0.049; I2=0). There was no difference in major adverse cardiac events (15.8% versus 15.4%; P=0.79), myocardial infarction (4.8% versus 5.5%; P=0.51), target lesion revascularization (9.3% versus 7.6%; P=0.19), or stent thrombosis (1.8% versus 1.6%; P=0.28) between the groups. Prespecified sensitivity analysis of long‐term mortality at a mean of 4.7 years of follow‐up showed that the provisional single‐stent strategy was associated with reduced all‐cause mortality (3.9% versus 6.2%; risk ratio: 0.63; 95% confidence interval, 0.42–0.97; P=0.036; I2=0). Conclusions: Coronary bifurcation percutaneous coronary intervention using a provisional single‐stent strategy is associated with a reduction in all‐cause mortality at long‐term follow‐up

Bayesian Methods for Analysis and Adaptive Scheduling of Exoplanet Observations

We describe work in progress by a collaboration of astronomers and statisticians developing a suite of Bayesian data analysis tools for extrasolar planet (exoplanet) detection, planetary orbit estimation, and adaptive scheduling of observations. Our work addresses analysis of stellar reflex motion data, where a planet is detected by observing the "wobble" of its host star as it responds to the gravitational tug of the orbiting planet. Newtonian mechanics specifies an analytical model for the resulting time series, but it is strongly nonlinear, yielding complex, multimodal likelihood functions; it is even more complex when multiple planets are present. The parameter spaces range in size from few-dimensional to dozens of dimensions, depending on the number of planets in the system, and the type of motion measured (line-of-sight velocity, or position on the sky). Since orbits are periodic, Bayesian generalizations of periodogram methods facilitate the analysis. This relies on the model being linearly separable, enabling partial analytical marginalization, reducing the dimension of the parameter space. Subsequent analysis uses adaptive Markov chain Monte Carlo methods and adaptive importance sampling to perform the integrals required for both inference (planet detection and orbit measurement), and information-maximizing sequential design (for adaptive scheduling of observations). We present an overview of our current techniques and highlight directions being explored by ongoing research.Comment: 29 pages, 11 figures. An abridged version is accepted for publication in Statistical Methodology for a special issue on astrostatistics, with selected (refereed) papers presented at the Astronomical Data Analysis Conference (ADA VI) held in Monastir, Tunisia, in May 2010. Update corrects equation (3

Random tree growth by vertex splitting

We study a model of growing planar tree graphs where in each time step we separate the tree into two components by splitting a vertex and then connect the two pieces by inserting a new link between the daughter vertices. This model generalises the preferential attachment model and Ford's $\alpha$-model for phylogenetic trees. We develop a mean field theory for the vertex degree distribution, prove that the mean field theory is exact in some special cases and check that it agrees with numerical simulations in general. We calculate various correlation functions and show that the intrinsic Hausdorff dimension can vary from one to infinity, depending on the parameters of the model.Comment: 47 page

GHOSTS I: A New Faint very Isolated Dwarf Galaxy at D = 12 +/- 2 Mpc

We report the discovery of a new faint dwarf galaxy, GHOSTS I, using HST/ACS data from one of our GHOSTS (Galaxy Halos, Outer disks, Substructure, Thick disk, and Star clusters) fields. Its detected individual stars populate an approximately one magnitude range of its luminosity function (LF). Using synthetic color-magnitude diagrams (CMDs) to compare with the galaxy's CMD, we find that the colors and magnitudes of GHOSTS I's individual stars are most consistent with being young helium-burning and asymptotic giant branch stars at a distance of 12 +/- 2 Mpc. Morphologically, GHOSTS I appears to be actively forming stars, so we tentatively classify it as a dwarf irregular (dIrr) galaxy, although future HST observations deep enough to resolve a larger magnitude range in its LF are required to make a more secure classification. GHOSTS I's absolute magnitude is $M_V = -9.85^{+ 0.40}_{- 0.33}$, making it one of the least luminous dIrr galaxies known, and its metallicity is lower than [Fe/H] =-1.5 dex. The half-light radius of GHOSTS I is 226 +/- 38 pc and its ellipticity is 0.47 +/- 0.07, similar to Milky Way and M31 dwarf satellites at comparable luminosity. There are no luminous massive galaxies or galaxy clusters within ~ 4 Mpc from GHOSTS I that could be considered as its host, making it a very isolated dwarf galaxy in the Local Universe.Comment: 8 pages, 7 figures. Accepted for publication in Ap