Clinical determinants of the PR interval duration in Swiss middle-aged adults: The CoLaus/PsyCoLaus study.

Prolonged PR interval (PRi) is associated with adverse outcomes. However, PRi determinants are poorly known. We aimed to identify the clinical determinants of the PRi duration in the general population. Some clinical data are associated with prolonged PRi. Cross-sectional study conducted between 2014 and 2017. Electrocardiogram-derived PRi duration was categorized into normal or prolonged (>200 ms). Determinants were identified using stepwise logistic regression, and results were expressed as multivariable-adjusted odds ratio (OR) (95% confidence interval). A further analysis was performed adjusting for antiarrhythmic drugs, P-wave contribution to PRi duration, electrolytes (kalemia, calcemia, and magnesemia), and history of cardiovascular disease. Overall, 3655 participants with measurable PRi duration were included (55.6% females; mean age 62 ± 10 years), and 330 (9.0%) had prolonged PRi. Stepwise logistic regression identified male sex (OR 1.41 [1.02-1.97]); aging (65-74 years: OR 2.29 [1.61-3.24], and ≥ 75 years: OR 4.21 [2.81-6.31]); increased height (per 5 cm, OR 1.15 [1.06-1.25]); hypertension (OR 1.37 [1.06-1.77]); and hs troponin T (OR 1.67 [1.15-2.43]) as significantly and positively associated, and high resting heart rate (≥70 beats/min, OR 0.43 [0.29-0.62]) as negatively associated with prolonged PRi. After further adjustment, male sex, aging and increased height remained positively, and high resting heart rate negatively associated with prolonged PRi. Hypertension and hs troponin T were no longer associated. In a sample of the Swiss middle-aged population, male sex, aging and increased height significantly increased the likelihood of a prolonged PRi duration, whereas a high resting heart rate decreased it

Measuring degree-degree association in networks

The Pearson correlation coefficient is commonly used for quantifying the global level of degree-degree association in complex networks. Here, we use a probabilistic representation of the underlying network structure for assessing the applicability of different association measures to heavy-tailed degree distributions. Theoretical arguments together with our numerical study indicate that Pearson's coefficient often depends on the size of networks with equal association structure, impeding a systematic comparison of real-world networks. In contrast, Kendall-Gibbons' $\tau_{b}$ is a considerably more robust measure of the degree-degree association

Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization disorder hypotheses in the Brugada syndrome

Aims Brugada syndrome (BrS) is characterized by arrhythmias leading to sudden cardiac death. BrS is caused, in part, by mutations in the SCN5A gene, which encodes the sodium channel alpha-subunit Nav1.5. Here, we aimed to characterize the biophysical properties and consequences of a novel BrS SCN5A mutation. Methods and results SCN5A was screened for mutations in a male patient with type-1 BrS pattern ECG. Wild-type (WT) and mutant Nav1.5 channels were expressed in HEK293 cells. Sodium currents (INa) were analysed using the whole-cell patch-clamp technique at 37°C. The electrophysiological effects of the mutation were simulated using the Luo-Rudy model, into which the transient outward current (Ito) was incorporated. A new mutation (C1850S) was identified in the Nav1.5 C-terminal domain. In HEK293 cells, mutant INa density was decreased by 62% at −20 mV. Inactivation of mutant INa was accelerated in a voltage-dependent manner and the steady-state inactivation curve was shifted by 11.6 mV towards negative potentials. No change was observed regarding activation characteristics. Altogether, these biophysical alterations decreased the availability of INa. In the simulations, the Ito density necessary to precipitate repolarization differed minimally between the two genotypes. In contrast, the mutation greatly affected conduction across a structural heterogeneity and precipitated conduction block. Conclusion Our data confirm that mutations of the C-terminal domain of Nav1.5 alter the inactivation of the channel and support the notion that conduction alterations may play a significant role in the pathogenesis of Br

Magnitude of urban heat islands largely explained by climate and population

Urban heat islands (UHIs) exacerbate the risk of heat-related mortality associated with global climate change. The intensity of UHIs varies with population size and mean annual precipitation, but a unifying explanation for this variation is lacking, and there are no geographically targeted guidelines for heat mitigation. Here we analyse summertime differences between urban and rural surface temperatures (ΔTs) worldwide and find a nonlinear increase in ΔTs with precipitation that is controlled by water or energy limitations on evapotranspiration and that modulates the scaling of ΔTs with city size. We introduce a coarse-grained model that links population, background climate, and UHI intensity, and show that urban–rural differences in evapotranspiration and convection efficiency are the main determinants of warming. The direct implication of these nonlinearities is that mitigation strategies aimed at increasing green cover and albedo are more efficient in dry regions, whereas the challenge of cooling tropical cities will require innovative solutions

Brugada syndrome and fever: Genetic and molecular characterization of patients carrying SCN5A mutations

Objective: Brugada syndrome (BrS) is characterized by ventricular tachyarrhythmias leading to sudden cardiac death and is caused, in part, by mutations in the SCN5A gene encoding the sodium channel Nav1.5. Fever can trigger or exacerbate the clinical manifestations of BrS. The aim of this work was to characterize the genetic and molecular determinants of fever-dependent BrS. Methods: Four male patients with typical BrS ST-segment elevation in V1-V3 or ventricular arrhythmias during fever were screened for mutations in the SCN5A gene. Wild-type (WT) and mutant Nav1.5 channels were expressed in HEK293 cells. The sodium currents (INa) were analysed using the whole-cell patch clamp technique at various temperatures. Protein expression of WT and mutant channels was studied by Western blot experiments. Results: Two mutations in SCN5A, L325R and R535X, were identified. Expression of the two mutant Nav1.5 channels in HEK293 cells revealed in each case a severe loss-of-function. Upon the increase of temperature up to 42 °C, we observed a pronounced acceleration of Nav1.5 activation and fast inactivation kinetics. Cardiac action potential modelling experiments suggest that in patients with reduced INa, fever could prematurely shorten the action potential by virtue of its effect on WT channels. Further experiments revealed that L325R channels are likely misfolded, since their function could be partially rescued by mexiletine or curcumin. In co-expression experiments, L325R channels interfered with the proper function of WT channels, suggesting that a dominant negative phenomenon may underlie BrS triggered by fever. Conclusions: The genetic background of BrS patients sensitive to fever is heterogeneous. Our experimental data suggest that the clinical manifestations of fever-exacerbated BrS may not be mutation specifi

Role of Network Topology in the Synchronization of Power Systems

We study synchronization dynamics in networks of coupled oscillators with bimodal distribution of natural frequencies. This setup can be interpreted as a simple model of frequency synchronization dynamics among generators and loads working in a power network. We derive the minimum coupling strength required to ensure global frequency synchronization. This threshold value can be efficiently found by solving a binary optimization problem, even for large networks. In order to validate our procedure, we compare its results with numerical simulations on a realistic network describing the European interconnected high-voltage electricity system, finding a very good agreement. Our synchronization threshold can be used to test the stability of frequency synchronization to link removals. As the threshold value changes only in very few cases when aplied to the European realistic network, we conclude that network is resilient in this regard. Since the threshold calculation depends on the local connectivity, it can also be used to identify critical network partitions acting as synchronization bottlenecks. In our stability experiments we observe that when a link removal triggers a change in the critical partition, its limits tend to converge to national borders. This phenomenon, which can have important consequences to synchronization dynamics in case of cascading failure, signals the influence of the uncomplete topological integration of national power grids at the European scale.Comment: The final publication is available at http://www.epj.org (see http://www.springerlink.com/content/l22k574x25u6q61m/

Prospective Assessment of Sex-Related Differences in Symptom Status and Health Perception Among Patients With Atrial Fibrillation.

We prospectively assessed sex-specific differences in health perception, overall symptom status, and specific symptoms in a large cohort of patients with atrial fibrillation. We performed a prospective multicenter observational cohort study of 1553 patients with atrial fibrillation. Patients completed questionnaires about personal characteristics, comorbidities, and symptoms on a yearly basis. Mean age was 70±11 years among women and 67±12 years among men. Health perception on a visual analogue scale ranging from 0 to 100 (with higher scores indicating better health perception) was significantly lower in women than in men (70 [interquartile range: 50-80] versus 75 [interquartile range: 60-85]; javax.xml.bind.JAXBElement@29592a5d <0.0001). More women than men had any symptoms (85.0% versus 68.3%; javax.xml.bind.JAXBElement@7ac0b4e4 <0.0001), palpitations (65.2% versus 44.4%; javax.xml.bind.JAXBElement@41229466 <0.0001), dizziness (25.6% versus 13.5%; javax.xml.bind.JAXBElement@61871784 <0.0001), dyspnea (35.7% versus 21.8%; javax.xml.bind.JAXBElement@16cc22b <0.0001), and fatigue (25.3% versus 19.1%; javax.xml.bind.JAXBElement@7ef43176 =0.006). At 1-year follow-up, symptoms decreased in both sexes but remained more frequent in women (49.1% versus 32.6%, javax.xml.bind.JAXBElement@2b200b6a <0.0001). In multivariable adjusted longitudinal regression models, female sex remained an independent predictor for lower health perception (ß=-4.8; 95% CI, -6.5 to -3.1; javax.xml.bind.JAXBElement@72c212bd <0.0001), any symptoms (odds ratio [OR]: 2.6; 95% CI, 2.1-3.4; javax.xml.bind.JAXBElement@15d8fb54 <0.0001), palpitations (OR: 2.6; 95% CI, 2.1-3.2; javax.xml.bind.JAXBElement@4af80718 <0.0001), dizziness (OR: 2.9; 95% CI, 2.1-3.9; javax.xml.bind.JAXBElement@61282e76 <0.0001), dyspnea (OR: 2.1; 95% CI, 1.6-2.8; javax.xml.bind.JAXBElement@31d9f14 <0.0001), fatigue (OR: 1.6; 95% CI, 1.2-2.2; javax.xml.bind.JAXBElement@51cdd678 =0.0008), and chest pain (OR: 1.8; 95% CI, 1.3-2.6; javax.xml.bind.JAXBElement@5b87db9e =0.001). Women with atrial fibrillation have a substantially higher symptom burden and lower health perception than men. These relationships persisted after multivariable adjustment and during prospective follow-up