Hypoalbuminaemia predicts outcome in adult patients with congenital heart disease

Background In patients with acquired heart failure, hypoalbuminaemia is associated with increased risk of death. The prevalence of hypoproteinaemia and hypoalbuminaemia and their relation to outcome in adult patients with congenital heart disease (ACHD) remains, however, unknown. Methods Data on patients with ACHD who underwent blood testing in our centre within the last 14 years were collected. The relation between laboratory, clinical or demographic parameters at baseline and mortality was assessed using Cox proportional hazards regression analysis. Results A total of 2886 patients with ACHD were included. Mean age was 33.3 years (23.6–44.7) and 50.1% patients were men. Median plasma albumin concentration was 41.0 g/L (38.0–44.0), whereas hypoalbuminaemia (<35 g/L) was present in 13.9% of patients. The prevalence of hypoalbuminaemia was significantly higher in patients with great complexity ACHD (18.2%) compared with patients with moderate (11.3%) or simple ACHD lesions (12.1%, p<0.001). During a median follow-up of 5.7 years (3.3–9.6), 327 (11.3%) patients died. On univariable Cox regression analysis, hypoalbuminaemia was a strong predictor of outcome (HR 3.37, 95% CI 2.67 to 4.25, p<0.0001). On multivariable Cox regression, after adjusting for age, sodium and creatinine concentration, liver dysfunction, functional class and disease complexity, hypoalbuminaemia remained a significant predictor of death. Conclusions Hypoalbuminaemia is common in patients with ACHD and is associated with a threefold increased risk of risk of death. Hypoalbuminaemia, therefore, should be included in risk-stratification algorithms as it may assist management decisions and timing of interventions in the growing ACHD population

Signals in solid-state photochemically induced dynamic nuclear polarization recover faster than signals obtained with the longitudinal relaxation time

Biological and Soft Matter PhysicsSolid state NMR/Biophysical Organic Chemistr

Right atrial area and right ventricular outflow tract akinetic length predict sustained tachyarrhythmia in repaired tetralogy of Fallot

AIMS: Repaired tetralogy of Fallot (rtoF) patients are at risk of atrial or ventricular tachyarrhythmia and sudden cardiac death. Risk stratification for arrhythmia remains difficult. We investigated whether cardiac anatomy and function predict arrhythmia. METHODS: One-hundred-and-fifty-four adults with rtoF, median age 30.8 (21.9–40.2) years, were studied with a standardised protocol including cardiovascular magnetic resonance (CMR) and prospectively followed up over median 5.6 (4.6–7.0) years for the pre-specified endpoints of new-onset atrial or ventricular tachyarrhythmia (sustained ventricular tachycardia/ventricular fibrillation). RESULTS: Atrial tachyarrhythmia (n = 11) was predicted by maximal right atrial area indexed to body surface area (RAAi) on four-chamber cine-CMR (Hazard ratio 1.17, 95% Confidence Interval 1.07–1.28 per cm(2)/m(2); p = 0.0005, survival receiver operating curve; ROC analysis, area under curve; AUC 0.74 [0.66–0.81]; cut-off value 16 cm(2)/m(2)). Atrial arrhythmia-free survival was reduced in patients with RAAi ≥ 16 cm(2)/m(2) (logrank p = 0.0001). Right ventricular (RV) restrictive physiology on echocardiography (n = 38) related to higher RAAi (p = 0.02) and had similar RV dilatation compared with remaining patients. Ventricular arrhythmia (n = 9) was predicted by CMR RV outflow tract (RVOT) akinetic area length (Hazard ratio 1.05, 95% Confidence Interval 1.01–1.09 per mm; p = 0.003, survival ROC analysis, AUC 0.77 [0.83–0.61]; cut-off value 30 mm) and decreased RV ejection fraction (Hazard ratio 0.93, 95% Confidence Interval 0.87–0.99 per %; p = 0.03). Ventricular arrhythmia-free survival was reduced in patients with RVOT akinetic region length > 30 mm (logrank p = 0.02). CONCLUSION: RAAi predicts atrial arrhythmia and RVOT akinetic region length predicts ventricular arrhythmia in late follow-up of rtoF. These are simple, feasible measurements for inclusion in serial surveillance and risk stratification of rtoF patients

Normal subgroups in the Cremona group (long version)

Let k be an algebraically closed field. We show that the Cremona group of all birational transformations of the projective plane P^2 over k is not a simple group. The strategy makes use of hyperbolic geometry, geometric group theory, and algebraic geometry to produce elements in the Cremona group that generate non trivial normal subgroups.Comment: With an appendix by Yves de Cornulier. Numerous but minors corrections were made, regarding proofs, references and terminology. This long version contains detailled proofs of several technical lemmas about hyperbolic space

Quantification of biventricular myocardial function using cardiac magnetic resonance feature tracking, endocardial border delineation and echocardiographic speckle tracking in patients with repaired tetralogy of fallot and healthy controls

Background: Parameters of myocardial deformation have been suggested to be superior to conventional measures of ventricular function in patients with tetralogy of Fallot (ToF), but have required non-routine, tagged cardiovascular magnetic resonance (CMR) techniques. We assessed biventricular myocardial function using CMR cine-based feature racking (FT) and compared it to speckle tracking echocardiography (STE) and to simple endocardial border delineation (EBD). In addition, the relation between parameters of myocardial deformation and clinical parameters was assessed. Methods: Overall, 28 consecutive adult patients with repaired ToF (age 40.4 ± 13.3 years) underwent standard steadystate- free precession sequence CMR, echocardiography, and cardiopulmonary exercise testing. In addition, 25 healthy subjects served as controls. Myocardial deformation was assessed by CMR based FT (TomTec Diogenes software), CMR based EBD (using custom written software) and STE (TomTec Cardiac Performance Analysis software). Results: Feature tracking was feasible in all subjects. A close agreement was found between measures of global left (LV) and right ventricular (RV) global strain. Interobserver agreement for FT and STE was similar for longitudinal LV global strain, but FT showed better inter-observer reproducibility than STE for circumferential or radial LV and longitudinal RV global strain. Reproducibility of regional strain on FT was, however, poor. The relative systolic length change of the endocardial border measured by EBD yielded similar results to FT global strain. Clinically, biventricular longitudinal strain on FT was reduced compared to controls (P<0.0001) and was related to the number of previous cardiac operations. In addition, FT derived RV strain was related to exercise capacity and VE/VCO2-slope. Conclusions: Although neither the inter-study reproducibility nor accuracy of FT software were investigated, and its interobserver reproducibility for regional strain calculation was poor, its calculations of global systolic strain showed similar or better inter-oberver reproducibility than those by STE, and could be applied across RV image regions inaccessible to echo. ‘Global strain’ calculated by EBD gave similar results to FT. Measurements made using FT related to exercise tolerance in ToF patients suggesting that the approach could have clinical relevance and deserves further study

The solid-state photo-CIDNP effect

The solid-state photo-CIDNP effect is the occurrence of a non-Boltzmann nuclear spin polarization in rigid samples upon illumination. For solid-state NMR, which can detect this enhanced nuclear polarization as a strong modification of signal intensity, the effect allows for new classes of experiments. Currently, the photo- and spin-chemical machinery of various RCs is studied by photo-CIDNP MAS NMR in detail. Until now, the effect has only been observed at high magnetic fields with 13C and 15N MAS NMR and in natural photosynthetic RC preparations in which blocking of the acceptor leads to cyclic electron transfer. In terms of irreversible thermodynamics, the high-order spin structure of the initial radical pair can be considered as a transient order phenomenon emerging under non-equilibrium conditions and as a first manifestation of order in the photosynthetic process. The solid-state photo-CIDNP effect appears to be an intrinsic property of natural RCs. The conditions of its occurrence seem to be conserved in evolution. The effect may be based on the same fundamental principles as the highly optimized electron transfer. Hence, the effect may allow for guiding artificial photosynthesis

Substantiating a political public sphere in the Scottish press : a comparative analysis

This article uses content analysis to characterize the performance of the media in a national public sphere, by setting apart those qualities that typify internal press coverage of a political event. The article looks at the coverage of the 1999 devolved Scottish election from the day before the election until the day after. It uses a word count to measure the election material in Scottish newspapers the Herald, the Press and Journal and the Scotsman, and United Kingdom newspapers the Guardian, the Independent and The Times, and categorizes that material according to discourse type, day and page selection. The article finds a number of qualities that typify the Scottish sample in particular, and might be broadly indicative of a political public sphere in action. Firstly, and not unexpectedly, it finds that the Scottish newspapers carry significantly more election coverage. Just as tellingly, though, the article finds that the Scottish papers offer a greater proportion of advice and background information, in the form of opinion columns and feature articles. It also finds that the Scottish papers place a greater concentration of both informative and evaluative material in the period before the vote, consistent with their making a contribution to informed political action. Lastly, the article finds that the Scottish sample situates coverage nearer the front of the paper and places a greater proportion on recto pages. The article therefore argues that the Scottish papers display features that distinguish them from the UK papers, and are broadly consistent with their forming part of a deliberative public sphere, and suggests that these qualities might be explored as a means of judging future media performance

Variation in inbreeding rates across the range of Northern Spotted Owls (\u3ci\u3eStrix occidentalis caurina\u3c/i\u3e): Insights from over 30 years of monitoring data

Inbreeding has been difficult to quantify in wild populations because of incomplete parentage information. We applied and extended a recently developed framework for addressing this problem to infer inbreeding rates in Northern Spotted Owls (Strix occidentalis caurina) across the Pacific Northwest, USA. Using pedigrees from 14,187 Northern Spotted Owls, we inferred inbreeding rates for 14 types of matings among relatives that produce pedigree inbreeding coefficients of F=0.25 or F=0.125. Inbreeding was most common in the Washington Cascades, where an estimated 15% of individuals are inbred. Inbreeding was lowest in western Oregon (3.5%) and northern California (2.7%), and intermediate for the Olympic Peninsula of Washington (6.1%). Estimates from the Olympic Peninsula were likely underestimates because of small sample sizes and the presence of few pedigrees capable of resolving inbreeding events. Most inbreeding resulted from matings between full siblings or half siblings, although a high rate of inbreeding from mother–son pairs was identified in the Olympic Peninsula. Geographic variation in inbreeding rates may reflect population declines and bottlenecks that have been detected in prior investigations. We show that there is strong selection against inbred birds. Only 3 of 44 inbred birds were later identified as parents (6.8%), whereas 2,823 of 10,380 birds that represented a comparable cross section of the data were later seen as reproducing parents (27.2%). Habitat loss and competition with Barred Owls (S. varia) remain primary threats to Northern Spotted Owls. However, given the negative consequences of inbreeding, Spotted Owl populations in Washington with suitable habitat and manageable numbers of Barred Owls may benefit from translocations of individuals from Oregon and California to introduce new genetic variation and reduce future inbreeding events. La endogamia ha sido dif´ıcil de cuantificar en las poblaciones silvestres debido a la falta de informaci ´on sobre los parentescos. Aplicamos y extendimos un marco conceptual recientemente desarrollado para encarar el problema de inferir las tasas de endogamia en Strix occidentalis caurina a trav´es del noroeste del Pac´ıfico, EEUU. Usando los pedigr´ıes provenientes de 14187 individuos, inferimos las tasas de endogamia para 14 tipos de apareamiento entre parientes que producen coeficientes de endogamia de pedigr´ı de F=0.25 o F=0.125. La endogamia fue ma´s com´un en las Cascadas de Washington, donde se estima que 15% de los individuos son endoga´micos. La endogamia fue menor en el oeste de Oreg´on (3.5%) y el norte de California (2.7%), e intermedia en la Pen´ınsula Ol´ımpica de Washington (6.1%). Las estimaciones de la Pen´ınsula Ol´ımpica fueron probablemente subestimadas debido a los peque ˜nos tama ˜nos de muestreo y a la presencia de pocos pedigr´ıes capaces de resolver los eventos de endogamia. La mayor´ıa de la endogamia result ´o de los apareamientos entre hermanos completos o medios hermanos, aunque se identific ´o una alta tasa de endogamia en parejas madre/hijo en la Pen´ınsula Ol´ımpica. La variaci ´on geogra´ fica en las tasas de endogamia puede reflejar disminuciones poblacionales y cuellos de botella que han sido detectados en investigaciones previas. Mostramos que hay una fuerte selecci ´on contra las aves endoga´micas. Solo tres de 44 aves endoga´micas fueron ma´s tarde identificadas como progenitores (6.8%), mientras que 2823 de 10380 aves que representaron una secci ´on transversal comparable de datos fueron vistas ma´s tarde como progenitores reproductivos (27.2%). La p´erdida de ha´bitat y la competencia con Strix varia sigue siendo la principal amenaza para S. o. caurina. Sin embargo, dadas las consecuencias negativas de la endogamia, las poblaciones de S. occidentalis en Washington con ha´bitat adecuado y n´umeros manejables de Strix varia pueden beneficiarse de traslocaciones de individuos de Oreg´on y California para introducir nueva variaci ´on gen´etica y reducir futuros eventos de endogamia

Medicine-Based Evidence in Congenital Heart Disease: How Artificial Intelligence Can Guide Treatment Decisions for Individual Patients

Built on the foundation of the randomized controlled trial (RCT), Evidence Based Medicine (EBM) is at its best when optimizing outcomes for homogeneous cohorts of patients like those participating in an RCT. Its weakness is a failure to resolve a clinical quandary: patients appear for care individually, each may differ in important ways from an RCT cohort, and the physician will wonder each time if following EBM will provide best guidance for this unique patient. In an effort to overcome this weakness, and promote higher quality care through a more personalized approach, a new framework has been proposed: Medicine-Based Evidence (MBE). In this approach, big data and deep learning techniques are embraced to interrogate treatment responses among patients in real-world clinical practice. Such statistical models are then integrated with mechanistic disease models to construct a “digital twin,” which serves as the real-time digital counterpart of a patient. MBE is thereby capable of dynamically modeling the effects of various treatment decisions in the context of an individual's specific characteristics. In this article, we discuss how MBE could benefit patients with congenital heart disease, a field where RCTs are difficult to conduct and often fail to provide definitive solutions because of a small number of subjects, their clinical complexity, and heterogeneity. We will also highlight the challenges that must be addressed before MBE can be embraced in clinical practice and its full potential can be realized

Transport lattice models of heat transport in skin with spatially heterogeneous, temperature-dependent perfusion

BACKGROUND: Investigation of bioheat transfer problems requires the evaluation of temporal and spatial distributions of temperature. This class of problems has been traditionally addressed using the Pennes bioheat equation. Transport of heat by conduction, and by temperature-dependent, spatially heterogeneous blood perfusion is modeled here using a transport lattice approach. METHODS: We represent heat transport processes by using a lattice that represents the Pennes bioheat equation in perfused tissues, and diffusion in nonperfused regions. The three layer skin model has a nonperfused viable epidermis, and deeper regions of dermis and subcutaneous tissue with perfusion that is constant or temperature-dependent. Two cases are considered: (1) surface contact heating and (2) spatially distributed heating. The model is relevant to the prediction of the transient and steady state temperature rise for different methods of power deposition within the skin. Accumulated thermal damage is estimated by using an Arrhenius type rate equation at locations where viable tissue temperature exceeds 42°C. Prediction of spatial temperature distributions is also illustrated with a two-dimensional model of skin created from a histological image. RESULTS: The transport lattice approach was validated by comparison with an analytical solution for a slab with homogeneous thermal properties and spatially distributed uniform sink held at constant temperatures at the ends. For typical transcutaneous blood gas sensing conditions the estimated damage is small, even with prolonged skin contact to a 45°C surface. Spatial heterogeneity in skin thermal properties leads to a non-uniform temperature distribution during a 10 GHz electromagnetic field exposure. A realistic two-dimensional model of the skin shows that tissue heterogeneity does not lead to a significant local temperature increase when heated by a hot wire tip. CONCLUSIONS: The heat transport system model of the skin was solved by exploiting the mathematical analogy between local thermal models and local electrical (charge transport) models, thereby allowing robust, circuit simulation software to obtain solutions to Kirchhoff's laws for the system model. Transport lattices allow systematic introduction of realistic geometry and spatially heterogeneous heat transport mechanisms. Local representations for both simple, passive functions and more complex local models can be easily and intuitively included into the system model of a tissue