Noise-Induced Desynchronization and Stochastic Escape from Equilibrium in Complex Networks

Complex physical systems are unavoidably subjected to external environments not accounted for in the set of differential equations that models them. The resulting perturbations are standardly represented by noise terms. We derive conditions under which such noise terms perturb the dynamics strongly enough that they lead to stochastic escape from the initial basin of attraction of an initial stable equilibrium state of the unperturbed system. Focusing on Kuramoto-like models we find in particular that, quite counterintuitively, systems with inertia leave their initial basin faster than or at the same time as systems without inertia, except for strong white-noise perturbations.Comment: Main text: 5 pages, 4 figures. Supplemental material: 6 pages, 7 figure

Host Genetics of Response to Hepatitis B Vaccine: A Systematic Review

Background. Hepatitis B virus (HBV) is an important cause of chronic viral disease worldwide and can be life threatening. While a safe and effective vaccine is widely available, 5 to 10% of healthy vaccinees fail to achieve a protective anti-hepatitis B surface antigen antibody (anti-HBs) titer (>10mIU/ml). A limited number of studies investigated host genetics of the response to HBV vaccine. To our knowledge, no comprehensive overview of genetic polymorphisms both within and outside the HLA system has been done so far. Aim. The aim of this study was to perform a systematic review of the literature of human genetics influencing immune response after hepatitis B vaccination. Methods. Literature searches using keywords were conducted in the electronic databases Medline, Embase and ISI Web of Science the cut-off date being March 2014. After selection of papers according to stringent inclusion criteria, relevant information was systematically collected from the remaining articles, including demographic data, number of patients, schedule and type of vaccine, phenotypes, genes and single nucleotide polymorphisms (SNPs) genotyping results and their association with immune response to hepatitis B vaccine. Results. The literature search produced a total of 1968 articles from which 46 studies were kept for further analyses. From these studies, data was extracted for 19 alleles from the human leukocyte antigen (HLA) region that were reported as significant at least twice. Among those alleles, 9 were firmly associated with vaccine response outcome (DQ2 [DQB1*02 and DQB1*0201], DR3 [DRB1*03 and DRB1*0301], DR7 [DRB1*07 and DRB1*0701], C4AQ0, DPB1*0401, DQ3, DQB1*06, DRB1*01 and DRB1*13 [DRB1*1301]). In addition, data was extracted for 55 different genes from which 13 extra-HLA genes had polymorphisms that were studied by different group of investigators or by the same group with a replication study. Among the 13 genes allowing comparison, 4 genes (IL-1B, IL-2, IL-4R and IL- 6) revealed no significant data, 6 genes (IL-4, IL-10, IL-12B, IL-13, TNFA, IFNG and TLR2) were explored with inconsistent results and 2 genes (CD3Z and ITGAL) yielded promising results as their association with vaccine response was confirmed by a replication approach. Furthermore, this review produced a list of 46 SNPs from 26 genes that were associated with immune response to vaccine only once, providing novel candidates to be tested in datasets from existing genome-wide association studies (GWAS). Conclusion. To the best of our knowledge, this is the first systematic review of immunogenetic studies of response to hepatitis B vaccine. While this work reassesses the role of several HLA alleles on vaccine response outcome, the associations with polymorphisms in genes outside the HLA region were rather inconsistent. Moreover, this work produced a list of 46 significant SNPs that were reported by a single group of investigators, opening up some interesting possibilities for further research

Topologically Protected Loop Flows in High Voltage AC Power Grids

Geographical features such as mountain ranges or big lakes and inland seas often result in large closed loops in high voltage AC power grids. Sizable circulating power flows have been recorded around such loops, which take up transmission line capacity and dissipate but do not deliver electric power. Power flows in high voltage AC transmission grids are dominantly governed by voltage angle differences between connected buses, much in the same way as Josephson currents depend on phase differences between tunnel-coupled superconductors. From this previously overlooked similarity we argue here that circulating power flows in AC power grids are analogous to supercurrents flowing in superconducting rings and in rings of Josephson junctions. We investigate how circulating power flows can be created and how they behave in the presence of ohmic dissipation. We show how changing operating conditions may generate them, how significantly more power is ohmically dissipated in their presence and how they are topologically protected, even in the presence of dissipation, so that they persist when operating conditions are returned to their original values. We identify three mechanisms for creating circulating power flows, (i) by loss of stability of the equilibrium state carrying no circulating loop flow, (ii) by tripping of a line traversing a large loop in the network and (iii) by reclosing a loop that tripped or was open earlier. Because voltage angles are uniquely defined, circulating power flows can take on only discrete values, much in the same way as circulation around vortices is quantized in superfluids.Comment: 12 pages 6 figures + Supplementary Material, Accepted for publication in New Journal of Physic

Cardiovascular risk assessment in people living with HIV compared to the general population

La prévention et le traitement des maladies cardiovasculaires (MCV) repose en partie sur la stratification des individus au moyen de scores de risque cardiovasculaire. Dans la pratique clinique, il est débattu de savoir quel score utiliser chez les personnes vivant avec le VIH (PVVIH), particulièrement exposés aux maladies chroniques sous l’ère des traitements antiviraux hautement efficaces. Nous avons évalué et comparé de manière prospective la performance des scores de risque cardiovasculaire chez les PVVIH et les personnes de la population générale. Nous avons également testé si l’ajout de variables spécifiques au VIH pouvait améliorer la performance des scores de risque développés pour la population générale. Le score européen Systematic COronary Risk Evaluation 2 (SCORE2), le score nord-américain Pooled Cohort Equations (PCE) et le score spécifique au HIV Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) ont été calculés chez des participants exempts de MCV entre 2003 et 2009. Au total, 6373 (âge moyen, 40,6 ans (déviation standard (DS), 9,9)) PVVIH de l’étude de cohorte suisse sur le VIH (SHCS) et 5403 (52,8 ans (DS, 10,7)) personnes de la cohorte CoLaus|PsyCoLaus ont été inclus dans l’analyse. Nous avons testé la discrimination et l’étalonnage, et calculé le Net Reclassification Improvement (NRI) après ajout de facteurs spécifiques au VIH aux scores développés pour la population générale. Respectivement 533 (8,4%) et 374 (6,9%) personnes ont développé une MCV durant des suivis moyens de 13,5 (DS, 4,1) ans dans la SHCS et de 9,9 (DS, 2,3) ans dans CoLaus|PsyCoLaus. Cela correspondait à des taux d’incidence ajustés selon l’âge de respectivement 12,9 et 7,5 pour 1000 personnes-année. Dans la SHCS, SCORE2, PCE et D:A:D présentaient des capacités discriminatives comparables (aire sous la courbe ROC (receiver operating characteristic) de 0,745 (intervalle de confiance (IC) à 95 %, IC, 0,723–0,767), 0,757 (IC à 95 %, 0,736–0,777) et 0,763 (IC à 95 %, 0,743–0,783)). L’ajout de variables spécifiques au VIH (nadir CD4 et exposition à l’abacavir) à SCORE2 et PCE a donné un NRI de respectivement -0,1 % (IC à 95 %, -1,24 à 1, P = 0,83) et de 2,7 % (IC à 95 %, 0,3 à 5,1, P = 0,03). En conclusion, les PVVIH présentent un taux deux fois plus élevé de MCV que les individus de la population générale. SCORE2 et PCE sont valides pour prédire les MCV chez les PVVIH, notamment en raison de leur ensemble de variables plus faciles à utiliser par rapport à des scores plus complexes intégrant des données spécifiques au VIH. L'ajout de facteurs spécifiques au VIH aux scores développés pour la population générale n'a pas entraîné d'amélioration cliniquement significative de leur performance

Embolic stroke of unknown source (ESUS) in patients with atrial septum defect and patent foramen ovale: difference and similarities

Introduction Paradoxical embolism from right-to-left shunt through a patent foramen ovale (PFO) is a well-characterized cause of embolic strokes of undetermined source (ESUS). In order to better understand the pathogenic role of atrial septum defects (ASD), we compared them with ESUS of high and low likelihood of being related to PFO. Methods In the Acute STroke Registry and Analysis of Lausanne (ASTRAL), we calculated prevalence of PFO and ASD in ESUS patient undergoing echocardiography, and odds ratios (OR) when to compared to non-cryptogenic strokes. Using the Risk of Paradoxical Embolism (RoPE) score, we divided cryptogenic PFO patients in high (HL-PFO, RoPE 8- 10) and low-likelihood (LL-PFO, RoPE 0-4) PFO-related stroke. We then performed univariate comparison of epidemiological, clinical and radiological variables of both group with ESUS ASD patients. Results Among all ESUS, prevalence for ASD and PFO were 1.3% and 36.8% respectively. When compared to non-cryptogenic stroke, ASD and PFO were associated with ESUS (OR of 5.2, CI= 1.6-16.6, and 2.8, CI= 2.1-3.8). Compared with HL-PFO, ASD were older, more often female, had more cardiovascular risk factors (CVRF) and silent strokes. Compared with LL-PFO, ASD group was significantly younger, more often female, and had less CVRF. No differences were found for clinical and radiological characteristics and outcome. Conclusion In ESUS, ASD seems to be a rare but significant stroke risk factor. Given that characteristics of such patients lie in-between high and low-likelihood paradoxical PFO- stroke, a thorough workup for other stroke mechanisms is warranted in ASD patients before routine ASD closure

Network Inference using Sinusoidal Probing

The aim of this manuscript is to present a non-invasive method to recover the network structure of a dynamical system. We propose to use a controlled probing input and to measure the response of the network, in the spirit of what is done to determine oscillation modes in large electrical networks. For a large class of dynamical systems, we show that this approach is analytically tractable and we confirm our findings by numerical simulations of networks of Kuramoto oscillators. Our approach also allows us to determine the number of agents in the network by probing and measuring a single one of them.Comment: 5 pages, 4 figure