Systems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects.

Genetic variants are the primary driver of congenital heart disease (CHD) pathogenesis. However, our ability to identify causative variants is limited. To identify causal CHD genes that are associated with specific molecular functions, the study used prior knowledge to filter de novo variants from 2,881 probands with sporadic severe CHD. This approach enabled the authors to identify an association between left ventricular outflow tract obstruction lesions and genes associated with the WAVE2 complex and regulation of small GTPase-mediated signal transduction. Using CRISPR zebrafish knockdowns, the study confirmed that WAVE2 complex proteins brk1, nckap1, and wasf2 and the regulators of small GTPase signaling cul3a and racgap1 are critical to cardiac development

Air temperature and inflammatory and coagulation responses in men with coronary or pulmonary disease during the winter season

Background and Objective Air temperature changes are associated with increased cardiovascular and respiratory risk, but the roles of inflammatory and coagulation markers are not well understood. We investigated the associations between temperature and several blood markers in patients with coronary heart disease (CHD) and pulmonary disease (PD). Methods Two studies were conducted in Erfurt, Germany, over two successive winters. 578 and 381 repeated blood measurements were collected from 57 CHD and 38 PD patients, respectively. Data on patient characteristics and disease history were gathered at baseline. Meteorological data were collected from existing networks. Associations were analysed using additive mixed models with random patient effects. Effect modification by diabetes status was investigated only in CHD patients, as only two PD patients had diabetes. Results Mean daily air temperature varied between -13 degrees C and 16 degrees C in both study periods. A 10 degrees C decrease in the 5-day temperature average before blood withdrawal led to an increase in platelet counts (% change from the mean: 3.0%, 95% CI 0.6% to 5.5%) and fibrinogen (5.5%, 1.3% to 9.7%), no change in C-reactive protein in PD patients, and a decrease in C-reactive protein in CHD patients. A 2-day delayed increase in factor VII associated with temperature decrease was seen in CHD patients (4.9%; 0.7% to 9.2%), while PD patients showed no effect. `Effects in CHD patients without diabetes' into `Effects on factor VII in CHD patients without diabetes'. Conclusions This study suggests that temperature decrease is associated with change in several blood parameters. The complex interplay of blood markers at low temperature may contribute to the observed association between cold and cardiovascular mortality and morbidity

Convex hulls of spheres and convex hulls of convex polytopes lying on parallel hyperplanes

Given a set $\Sigma$ of spheres in $\mathbb{E}^d$, with $d\ge{}3$ and $d$ odd, having a fixed number of $m$ distinct radii $\rho_1,\rho_2,...,\rho_m$, we show that the worst-case combinatorial complexity of the convex hull $CH_d(\Sigma)$ of $\Sigma$ is $\Theta(\sum_{1\le{}i\ne{}j\le{}m}n_in_j^{\lfloor\frac{d}{2}\rfloor})$, where $n_i$ is the number of spheres in $\Sigma$ with radius $\rho_i$. To prove the lower bound, we construct a set of $\Theta(n_1+n_2)$ spheres in $\mathbb{E}^d$, with $d\ge{}3$ odd, where $n_i$ spheres have radius $\rho_i$, $i=1,2$, and $\rho_2\ne\rho_1$, such that their convex hull has combinatorial complexity $\Omega(n_1n_2^{\lfloor\frac{d}{2}\rfloor}+n_2n_1^{\lfloor\frac{d}{2}\rfloor})$. Our construction is then generalized to the case where the spheres have $m\ge{}3$ distinct radii. For the upper bound, we reduce the sphere convex hull problem to the problem of computing the worst-case combinatorial complexity of the convex hull of a set of $m$ $d$-dimensional convex polytopes lying on $m$ parallel hyperplanes in $\mathbb{E}^{d+1}$, where $d\ge{}3$ odd, a problem which is of independent interest. More precisely, we show that the worst-case combinatorial complexity of the convex hull of a set $\{\mathcal{P}_1,\mathcal{P}_2,...,\mathcal{P}_m\}$ of $m$ $d$-dimensional convex polytopes lying on $m$ parallel hyperplanes of $\mathbb{E}^{d+1}$ is $O(\sum_{1\le{}i\ne{}j\le{}m}n_in_j^{\lfloor\frac{d}{2}\rfloor})$, where $n_i$ is the number of vertices of $\mathcal{P}_i$. We end with algorithmic considerations, and we show how our tight bounds for the parallel polytope convex hull problem, yield tight bounds on the combinatorial complexity of the Minkowski sum of two convex polytopes in $\mathbb{E}^d$.Comment: 22 pages, 5 figures, new proof of upper bound for the complexity of the convex hull of parallel polytopes (the new proof gives upper bounds for all face numbers of the convex hull of the parallel polytopes

3D printing is a transformative technology in congenital heart disease

Survival in congenital heart disease has steadily improved since 1938, when Dr. Robert Gross successfully ligated for the first time a patent ductus arteriosus in a 7-year-old child. To continue the gains made over the past 80 years, transformative changes with broad impact are needed in management of congenital heart disease. Three-dimensional printing is an emerging technology that is fundamentally affecting patient care, research, trainee education, and interactions among medical teams, patients, and caregivers. This paper first reviews key clinical cases where the technology has affected patient care. It then discusses 3-dimensional printing in trainee education. Thereafter, the role of this technology in communication with multidisciplinary teams, patients, and caregivers is described. Finally, the paper reviews translational technologies on the horizon that promise to take this nascent field even further

Niveau and coniveau filtrations on cohomology groups and Chow groups

The Bloch-Beilinson-Murre conjectures predict the existence of a descending filtration on Chow groups of smooth projective varieties which is functorial with respect to the action of correspondences and whose graded parts depend solely on the topology -- i.e. the cohomology -- of $X$. In this paper, we wish to explore, at the cost of having to assume general conjectures about algebraic cycles, how the coniveau filtration on the cohomology of $X$ has an incidence on the Chow groups of $X$. However, by keeping such assumptions minimal, we are able to prove some of these conjectures either in low-dimensional cases or when a variety is known to have small Chow groups. For instance, we give a new example of a fourfold of general type with trivial Chow group of zero-cycles and we prove Murre's conjectures for threefolds dominated by a product of curves, for threefolds rationally dominated by the product of three curves, for rationally connected fourfolds and for complete intersections of low degree. The BBM conjectures are closely related to Kimura-O'Sullivan's notion of finite-dimensionality. Assuming the standard conjectures on algebraic cycles the former is known to imply the latter. We show that the missing ingredient for finite-dimensionality to imply the BBM conjectures is the coincidence of a certain niveau filtration with the coniveau filtration on Chow groups.Comment: Final versio

Cyclic cohomology for graded C∗,rC^{*,r}-algebras and its pairings with van Daele KK-theory

We consider cycles for graded $C^{*,r}$-algebras (Real $C^{*}$-algebras) which are compatible with the $*$-structure and the real structure. Their characters are cyclic cocycles. We define a Connes type pairing between such characters and elements of the van Daele $K$-groups of the $C^{*,r}$-algebra and its real subalgebra. This pairing vanishes on elements of finite order. We define a second type of pairing between characters and $K$-group elements which is derived from a unital inclusion of $C^{*}$-algebras. It is potentially non-trivial on elements of order two and torsion valued. Such torsion valued pairings yield topological invariants for insulators. The two-dimensional Kane-Mele and the three-dimensional Fu-Kane-Mele strong invariant are special cases of torsion valued pairings. We compute the pairings for a simple class of periodic models and establish structural results for two dimensional aperiodic models with odd time reversal invariance.Comment: 57 page

Hydrogen-atom Attack on Phenol and Toluene is \u3cem\u3eortho\u3c/em\u3e-directed

The reaction of H + phenol and H/D + toluene has been studied in a supersonic expansion after electric discharge. The (1 + 1′) resonance-enhanced multiphoton ionization (REMPI) spectra of the reaction products, at m/z = parent + 1, or parent + 2 amu, were measured by scanning the first (resonance) laser. The resulting spectra are highly structured. Ionization energies were measured by scanning the second (ionization) laser, while the first laser was tuned to a specific transition. Theoretical calculations, benchmarked to the well-studied H + benzene → cyclohexadienyl radical reaction, were performed. The spectrum arising from the reaction of H + phenol is attributed solely to the ortho-hydroxy-cyclohexadienyl radical, which was found in two conformers (syn and anti). Similarly, the reaction of H/D + toluene formed solely the ortho isomer. The preference for the ortho isomer at 100–200 K in the molecular beam is attributed to kinetic, not thermodynamic effects, caused by an entrance channel barrier that is ∼5 kJ mol−1 lower for ortho than for other isomers. Based on these results, we predict that the reaction of H + phenol and H + toluene should still favour the ortho isomer under elevated temperature conditions in the early stages of combustion (200–400 °C)

Exploring the equity of GP practice prescribing rates for selected coronary heart disease drugs: a multiple regression analysis with proxies of healthcare need

Background There is a small, but growing body of literature highlighting inequities in GP practice prescribing rates for many drug therapies. The aim of this paper is to further explore the equity of prescribing for five major CHD drug groups and to explain the amount of variation in GP practice prescribing rates that can be explained by a range of healthcare needs indicators (HCNIs). Methods The study involved a cross-sectional secondary analysis in four primary care trusts (PCTs 1–4) in the North West of England, including 132 GP practices. Prescribing rates (average daily quantities per registered patient aged over 35 years) and HCNIs were developed for all GP practices. Analysis was undertaken using multiple linear regression. Results Between 22–25% of the variation in prescribing rates for statins, beta-blockers and bendrofluazide was explained in the multiple regression models. Slightly more variation was explained for ACE inhibitors (31.6%) and considerably more for aspirin (51.2%). Prescribing rates were positively associated with CHD hospital diagnoses and procedures for all drug groups other than ACE inhibitors. The proportion of patients aged 55–74 years was positively related to all prescribing rates other than aspirin, where they were positively related to the proportion of patients aged >75 years. However, prescribing rates for statins and ACE inhibitors were negatively associated with the proportion of patients aged >75 years in addition to the proportion of patients from minority ethnic groups. Prescribing rates for aspirin, bendrofluazide and all CHD drugs combined were negatively associated with deprivation. Conclusion Although around 25–50% of the variation in prescribing rates was explained by HCNIs, this varied markedly between PCTs and drug groups. Prescribing rates were generally characterised by both positive and negative associations with HCNIs, suggesting possible inequities in prescribing rates on the basis of ethnicity, deprivation and the proportion of patients aged over 75 years (for statins and ACE inhibitors, but not for aspirin)