Deterministic and stochastic cooperation transitions in evolutionary games on networks.

Although the cooperative dynamics emerging from a network of interacting players has been exhaustively investigated, it is not yet fully understood when and how network reciprocity drives cooperation transitions. In this work, we investigate the critical behavior of evolutionary social dilemmas on structured populations by using the framework of master equations and Monte Carlo simulations. The developed theory describes the existence of absorbing, quasiabsorbing, and mixed strategy states and the transition nature, continuous or discontinuous, between the states as the parameters of the system change. In particular, when the decision-making process is deterministic, in the limit of zero effective temperature of the Fermi function, we find that the copying probabilities are discontinuous functions of the system's parameters and of the network degrees sequence. This may induce abrupt changes in the final state for any system size, in excellent agreement with the Monte Carlo simulation results. Our analysis also reveals the existence of continuous and discontinuous phase transitions for large systems as the temperature increases, which is explained in the mean-field approximation. Interestingly, for some game parameters, we find optimal "social temperatures" maximizing or minimizing the cooperation frequency or density.

PREvention of recurrent arrhythmias with Mediterranean diet (PREDIMAR) study in patients with atrial fibrillation: Rationale, design and methods.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Catheter ablation aims to restore sinus rhythm. However, relapses occur in up to 30% of patients. A Mediterranean diet (MedDiet) enriched with extra-virgin olive oil (EVOO) substantially reduced the incidence of AF in the PREDIMED trial. The PREDIMAR will test a similar intervention in secondary prevention. Methods: PREDIMAR is a multicenter, randomized, single-blind trial testing the effect of a MedDiet enriched with EVOO to reduce tachyarrhythmia relapses after AF ablation. The primary outcome is the recurrence of any sustained atrial tachyarrhythmia after ablation (excluding those occurring only during the first 3 months after ablation). The target final sample size is 720 patients (360 per group) recruited from 4 Spanish hospitals. A remote intervention, maintained for 2 years, is delivered to the active intervention group including periodic phone calls by a dietitian and free provision of EVOO. The control group will receive delayed intervention after trial completion. Routine electrocardiogram (ECG) and Holter ECG are performed, and a portable cardiac rhythm monitoring device is provided to be worn by participants during 15 months. Results: Recruitment started in March 2017. Up to July 2019, 609 patients were randomized (average inclusion rate: 5.3 patients/wk). Retention rates after 18 months are >94%. Conclusions: If our hypothesis is confirmed, the utility of the MedDiet enriched with EVOO in slowing the progression of AF will be proven, preventing recurrences and potentially reducing complications.

Bupivacaine Toxicity Increases Transmural Dispersion of Repolarization, Developing of a Brugada-like Pattern and Ventricular Arrhythmias, Which is Reversed by Lipid Emulsion Administration. Study in an Experimental Porcine Model.

Unintentional administration of bupivacaine may be associated with electrocardiogram changes that promote the development cardiac arrhythmias. Ventricular repolarization markers (corrected QT, QT dispersion, Tpeak-Tend and Tpeak-Tend dispersion) are useful to predict cardiac arrhythmias. We aim to investigate the effects of bupivacaine on the transmural dispersion of repolarization and their reversion following intravenous lipid emulsion (ILE) administration. Fourteen pigs were anaesthetized with thiopental and sevoflurane and underwent tracheal intubation. After instrumentation, a 4 mg kg-bolus of bupivacaine was administrated followed by an infusion of 100 µg kg-1 min-1. QT interval, QTc:QT corrected by heart rate, Tpeak-to-Tend interval and QT and Tpeak-to-Tend dispersion were determined in a sequential fashion: after bupivacaine (at 1 min, 5 min and 10 min) and after ILE (1.5 mL kg-1 over 1 min followed by an infusion of 0.25 mL kg-1 min-1). Three additional animals received only ILE (control group). Bupivacaine significantly prolonged QT interval (∆:36%), QT dispersion (∆:68%), Tpeak-to-Tend (∆:163%) and Tpeak-to-Tend dispersion (∆:98%), from baseline to 10 min. Dispersion of repolarization was related to lethal arrhythmias [three events, including asystole, sustained ventricular tachycardia (VT)] and repeated non-sustained VT (4/14, 28%). A Brugada-like-ECG pattern was visualized at V1-4 leads in 5/14 pigs (35%). ILE significantly decreased the alterations induced by bupivacaine, with the termination of VT within 10 min. No ECG changes were observed in control group. Bupivacaine toxicity is associated with an increase of transmural dispersion of repolarization, the occurrence of a Brugada-like pattern and malignant VA. ILE reverses the changes in dispersion of repolarization, favouring the disappearance of the Brugada-like pattern and VT.

Análisis de la regresión temporal en el ensanchamiento del intervalo QRS inducido por bupivacaína con la administración de Intralipid. Estudio en un modelo experimental porcino / Analysis of the temporal regression of the QRS widening induced by bupivacaine after Intralipid administration. Study in an experimental porcine model

Objetivo: La toxicidad cardiaca inducida por la bupivacaína (B) se relaciona con el bloqueo de los canales de sodio, que se traduce por un ensanchamiento del intervalo QRS. Estudios experimentales recientes, sugieren que el Intralipid (IL) es eficaz en revertir la toxicidad cardiaca de la B. Nuestro objetivo fue analizar la evolución temporal del ensanchamiento del QRS inducido por la B con la administración de IL. Material y método: Doce cerdos fueron anestesiados con tiopental sódico, 5 mg kg−1, y sevoflurano a concentración alveolar mínima de 2,6%. Tras la instrumentalización se administró un bolo de B de 4-6 mg kg−1 con el objetivo de inducir un aumento de 150% en la duración del QRS. El grupo IL recibió 1,5 mL kg−1 de IL seguido de 0,25 mL kg min−1; el grupo control (C) recibió salino. Se registraron los parámetros electrocardiográficos tras la infusión de B y a 1, 5,10 y 30 min de la administración de Intralipid/salino. Resultados: La administración de B (4,33°æ 0,81 mg/kg en el grupo IL y 4,66°æ 1,15 mg/kg en el grupo C) indujo cambios electrocardiográficos similares en ambos grupos; el porcentaje medio de incremento máximo en el QRS fue de 184°æ 62% en el grupo IL, y de 230°æ 56% en el grupo C. El IL revirtió el ensanchamiento del QRS inducido por la B, a los 10 min de su administración el intervalo QRS disminuyó 132°æ 56% vs. 15°æ 76%, en relación al máximo incremento inducido por la B, en el grupo IL y grupo C respectivamente. Conclusión: El IL revirtió eficazmente el ensanchamiento del intervalo QRS inducido por la B. El tiempo hasta la normalización de los parámetros electrocardiográficos puede prolongarse más de 10 min. Mientras persistan los fenómenos de toxicidad cardíaca, las medidas de resucitación y monitorización deben continuarse hasta que los parámetros de conducción cardíaca se hayan restaurado de forma adecuada (AU)

Objective: The principal mechanism of cardiac toxicity of bupivacaine relates to the blockade of myocardial sodium channels, which leads to an increase in the QRS duration. Recently, experimental studies suggest that lipid emulsion is effective in reversing bupivacaine cardiac toxicity. We aimed to evaluate the temporal evolution of the QRS widening induced by bupivacaine with the administration of Intralipid. Material and methods: Twelve pigs were anesthetized with intravenous sodium thiopental 5 mg kg−1 and sevoflurane 1 MAC (2.6%). Femoral artery and vein were canalized for invasive monitoring, analysis of blood gases and determination of bupivacaine levels. After instrumentation and monitoring, a bupivacaine bolus of 4-6 mg kg−1 was administered in order to induce a 150% increase in QRS duration (defined as the toxic point). The pigs were randomized into two groups of six individuals. Intralipid group (IL) received 1.5 mL kg−1of IL over one minute, followed by an infusion of 0.25 mL kg min−1. Control group (C) received the same volume of a saline solution. The electrocardiographic parameters were recorded, and blood samples were taken after bupivacaine and 1, 5, 10 and 30 minutes after Intralipid/saline administration. Results: Bupivacaine (4.33°æ 0.81 mg/kg in IL group and 4.66°æ 1.15 mg/kg in C group) induced similar electrocardiographic changes in both groups; mean maximal percent increase in QRS interval was 184°æ 62% in IL group, and 230°æ 56% in control group (NS). Lipid administration reversed the QRS widening previously impaired by bupivacaine. After ten minutes of the administration of IL, the mean QRS interval decreased to 132°æ 56% vs. 15°æ 76% relative to the maximum widening induced by bupivacaine, in IL and C group, respectively. Conclusion: Intralipid reversed the lengthening of QRS interval induced by the injection of bupivacaine. Time to normalization of electrocardiographic parameters can last more than 10 minutes. While the phenomena of cardiac toxicity persist, resuscitation measures and adequate monitoring should be continued until adequate heart conduction parameters are restored (AU)

Analysis of the temporal regression of the QRS widening induced by bupivacaine after Intralipid administration. Study in an experimental porcine model.

OBJECTIVE: The principal mechanism of cardiac toxicity of bupivacaine relates to the blockade of myocardial sodium channels, which leads to an increase in the QRS duration. Recently, experimental studies suggest that lipid emulsion is effective in reversing bupivacaine cardiac toxicity. We aimed to evaluate the temporal evolution of the QRS widening induced by bupivacaine with the administration of Intralipid. MATERIAL AND METHODS: Twelve pigs were anesthetized with intravenous sodium thiopental 5mg kg(-1) and sevoflurane 1 MAC (2.6%). Femoral artery and vein were canalized for invasive monitoring, analysis of blood gases and determination of bupivacaine levels. After instrumentation and monitoring, a bupivacaine bolus of 4-6 mg kg(-1) was administered in order to induce a 150% increase in QRS duration (defined as the toxic point). The pigs were randomized into two groups of six individuals. Intralipid group (IL) received 1.5 mL kg(-1)of IL over one minute, followed by an infusion of 0.25 mL kg min(-1). Control group (C) received the same volume of a saline solution. The electrocardiographic parameters were recorded, and blood samples were taken after bupivacaine and 1, 5, 10 and 30 minutes after Intralipid/saline administration. RESULTS: Bupivacaine (4.33±0.81 mg/kg in IL group and 4.66±1.15 mg/kg in C group) induced similar electrocardiographic changes in both groups; mean maximal percent increase in QRS interval was 184±62% in IL group, and 230±56% in control group (NS). Lipid administration reversed the QRS widening previously impaired by bupivacaine. After ten minutes of the administration of IL, the mean QRS interval decreased to 132±56% vs. 15±76% relative to the maximum widening induced by bupivacaine, in IL and C group, respectively. CONCLUSION: Intralipid reversed the lengthening of QRS interval induced by the injection of bupivacaine. Time to normalization of electrocardiographic parameters can last more than 10 minutes. While the phenomena of cardiac toxicity persist, resuscitation measures and adequate monitoring should be continued until adequate heart conduction parameters are restored.

Effects of degree correlations on the explosive synchronization of scale-free networks.

We study the organization of finite-size, large ensembles of phase oscillators networking via scale-free topologies in the presence of a positive correlation between the oscillators' natural frequencies and the network's degrees. Under those circumstances, abrupt transitions to synchronization are known to occur in growing scale-free networks, while the transition has a completely different nature for static random configurations preserving the same structure-dynamics correlation. We show that the further presence of degree-degree correlations in the network structure has important consequences on the nature of the phase transition characterizing the passage from the phase-incoherent to the phase-coherent network state. While high levels of positive and negative mixing consistently induce a second-order phase transition, moderate values of assortative mixing, such as those ubiquitously characterizing social networks in the real world, greatly enhance the irreversible nature of explosive synchronization in scale-free networks. The latter effect corresponds to a maximization of the area and of the width of the hysteretic loop that differentiates the forward and backward transitions to synchronization.

Effective centrality and explosive synchronization in complex networks.

Synchronization of networked oscillators is known to depend fundamentally on the interplay between the dynamics of the graph's units and the microscopic arrangement of the network's structure. We here propose an effective network whose topological properties reflect the interplay between the topology and dynamics of the original network. On that basis, we are able to introduce the effective centrality, a measure that quantifies the role and importance of each network's node in the synchronization process. In particular, in the context of explosive synchronization, we use such a measure to assess the propensity of a graph to sustain an irreversible transition to synchronization. We furthermore discuss a strategy to induce the explosive behavior in a generic network, by acting only upon a fraction of its nodes.

Explosive synchronization in weighted complex networks.

The emergence of dynamical abrupt transitions in the macroscopic state of a system is currently a subject of the utmost interest. Given a set of phase oscillators networking with a generic wiring of connections and displaying a generic frequency distribution, we show how combining dynamical local information on frequency mismatches and global information on the graph topology suggests a judicious and yet practical weighting procedure which is able to induce and enhance explosive, irreversible, transitions to synchronization. We report extensive numerical and analytical evidence of the validity and scalability of such a procedure for different initial frequency distributions, for both homogeneous and heterogeneous networks, as well as for both linear and nonlinear weighting functions. We furthermore report on the possibility of parametrically controlling the width and extent of the hysteretic region of coexistence of the unsynchronized and synchronized states.

Explosive transitions to synchronization in networks of phase oscillators.

The emergence of dynamical abrupt transitions in the macroscopic state of a system is currently a subject of the utmost interest. The occurrence of a first-order phase transition to synchronization of an ensemble of networked phase oscillators was reported, so far, for very particular network architectures. Here, we show how a sharp, discontinuous transition can occur, instead, as a generic feature of networks of phase oscillators. Precisely, we set conditions for the transition from unsynchronized to synchronized states to be first-order, and demonstrate how these conditions can be attained in a very wide spectrum of situations. We then show how the occurrence of such transitions is always accompanied by the spontaneous setting of frequency-degree correlation features. Third, we show that the conditions for abrupt transitions can be even softened in several cases. Finally, we discuss, as a possible application, the use of this phenomenon to express magnetic-like states of synchronization.

Reappraisal of classical electrocardiographic criteria in detecting accessory pathways with a strict para-Hisian location.

BACKGROUND: Identification of electrocardiographic (ECG) criteria for para-Hisian accessory pathways (APs) is based on a small series of patients. The presence of a negative delta wave in leads V(1) and V(2) has been suggested as an ECG marker of this AP location. OBJECTIVE: To validate these ECG findings in a large series of patients with strict invasive criteria for that location. METHODS: We included 105 patients (39 women, 66 men; mean age 26 ± 12 years, range 5-82 years) with an ECG pattern compatible with preexcitation through an anteroseptal or midseptal AP following established ECG criteria. A para-Hisian AP was defined when the location of its successful catheter ablation coincided with either the largest recordable His bundle electrogram or a His bundle potential of>0.1 mV. Patients without that definition were included in the control group. RESULTS: A para-Hisian location of the AP was found in 52 patients. AP locations of the remaining 53 patients (control group) were anteroseptal (n = 39), midseptal (n = 9), and fasciculoventricular (n = 5). A negative delta wave in leads V(1) and V(2) was observed in 13 patients with para-Hisian APs (sensitivity 25%; specificity 92%). However, the sum of initial r-wave amplitudes in those leads was<0.5 mV in 44 of the patients with para-Hisian APs and in 13 patients of the control group (sensitivity 85%; specificity 75.5%; area under receiver-operator characteristic curve 0.85). CONCLUSIONS: The presence of negative delta waves in leads V(1) and V(2) indicates a poor sensitivity and high specificity to detect APs with a strict definition of para-Hisian location. The sum of initial r-wave amplitudes in those ECG leads could be a useful, adjunctive marker in the noninvasive identification of these challenging APs.

Integration versus segregation in functional brain networks.

We propose a new methodology to evaluate the balance between segregation and integration in functional brain networks by using singular value decomposition techniques. By means of magnetoencephalography, we obtain the brain activity of a control group of 19 individuals during a memory task. Next, we project the node-to-node correlations into a complex network that is analyzed from the perspective of its modular structure encoded in the contribution matrix. In this way, we are able to study the role that nodes play I/O its community and to identify connector and local hubs. At the mesoscale level, the analysis of the contribution matrix allows us to measure the degree of overlapping between communities and quantify how far the functional networks are from the configuration that better balances the integrated and segregated activity.

Synchronization waves in geometric networks.

We report synchronization of networked excitable nodes embedded in a metric space, where the connectivity properties are mostly determined by the distance between units. Such a high clustered structure, combined with the lack of long-range connections, prevents full synchronization and yields instead the emergence of synchronization waves. We show that this regime is optimal for information transmission through the system, as it enhances the options of reconstructing the topology from the dynamics. Measurements of topological and functional centralities reveal that the wave-synchronization state allows detection of the most structurally relevant nodes from a single observation of the dynamics, without any a priori information on the model equations ruling the evolution of the ensemble.

Dynamics of overlapping structures in modular networks.

Modularity is a fundamental feature of real networks, being intimately bounded to their functionality, i.e., to their capability of performing parallel tasks in a coordinated way. Although the modular structure of real graphs has been intensively studied, very little is known on the interactions between functional modules of a graph. Here, we present a general method based on synchronization of networking oscillators, that is able to detect overlapping structures in multimodular environments. We furthermore report the full analytical and theoretical description on the relationship between the overlapping dynamics and the underlying network topology. The method is illustrated by means of a series of applications.

Entraining the topology and the dynamics of a network of phase oscillators.

We show that the topology and dynamics of a network of unsynchronized Kuramoto oscillators can be simultaneously controlled by means of a forcing mechanism which yields a phase locking of the oscillators to that of an external pacemaker in connection with the reshaping of the network's degree distribution. The entrainment mechanism is based on the addition, at regular time intervals, of unidirectional links from oscillators that follow the dynamics of a pacemaker to oscillators in the pristine graph whose phases hold a prescribed phase relationship. Such a dynamically based rule in the attachment process leads to the emergence of a power-law shape in the final degree distribution of the graph whenever the network is entrained to the dynamics of the pacemaker. We show that the arousal of a scale-free distribution in connection with the success of the entrainment process is a robust feature, characterizing different networks' initial configurations and parameters.

Cardiac electrophysiological effects of remifentanil: study in a closed-chest porcine model.

BACKGROUND: Remifentanil has been implicated as causing intraoperative bradyarrhythmias, but little information is available regarding its cardiac electrophysiological effects. Thus, we evaluated the cardiac electrophysiological properties before and after remifentanil in a closed-chest porcine model. METHODS: Eighteen Landrace-Large pigs were premedicated with ketamine and anaesthetized with propofol (4.5 mg kg(-1) bolus followed by 13 mg kg(-1) h(-1)). After instrumentation, an electrophysiological evaluation was performed under propofol and repeated after remifentanil (bolus of 1 microg kg(-1), followed by an infusion of 0.5 microg kg(-1) min(-1)). We evaluated sinus node function [sinus node recovery time (SNRT) and sinoatrial conduction time (SACT)], atrioventricular (AV) nodal function [AH intervals during sinus rhythm (SR) and atrial pacing, Wenckebach cycle length (WCL), and effective refractory periods (ERP)], atrial, His-Purkinje, and ventricular conduction and refractoriness. Significant changes between 'propofol protocol' and 'propofol+remifentanil protocol' were evaluated. RESULTS: Remifentanil caused a significant increase in sinus cycle length (21%, P=0.001) and a significant prolongation of SNRT (43%, P=0.001), corrected SNRT (136%, P=0.003), SACT (40%, P=0.005), AH interval during SR (17%, P=0.02), AH interval during atrial pacing (25%, P=0.01), and ventricular ERP (12%, P=0.004). There was a tendency towards a prolongation of WCL and AV nodal refractoriness. Similar significant changes were observed in a reference group of seven animals in which sevoflurane was used instead of propofol. No significant changes were observed in atrial parameters, His-Purkinje function, parameters of intraventricular conduction, and QT intervals. CONCLUSIONS: Remifentanil depresses sinus node function and most parameters of AV nodal function. This contributes to an explanation for clinical observations of remifentanil-related severe bradyarrhythmias.

Regulating synchronous states of complex networks by pinning interaction with an external node.

To shed light on how biological and technological systems can establish or maintain a synchronous functioning, we address the problem of how to engineer an external pinning action on a network of dynamical units. In particular, we study the regulation of a network toward a synchronized behavior by means of a bidirectional interaction with an external node that leaves unchanged its inner parameters and architecture. We demonstrate that there are two classes of networks susceptible of being regulated into a synchronous motion and provide a simple method, for each one of them, to properly design a pinning sequence to achieve regulation. We also discuss how the obtained sequence can be compared with a topological ranking of the network nodes.

Synchronization interfaces and overlapping communities in complex networks.

We show that a complex network of phase oscillators may display interfaces between domains (clusters) of synchronized oscillations. The emergence and dynamics of these interfaces are studied for graphs composed of either dynamical domains (influenced by different forcing processes), or structural domains (modular networks). The obtained results allow us to give a functional definition of overlapping structures in modular networks, and suggest a practical method able to give information on overlapping clusters in both artificially constructed and real world modular networks.

Parvovirus variation for disease: a difference with RNA viruses?

The Parvoviridae, a family of viruses with single-stranded DNA genomes widely spread from invertebrates to mammal and human hosts, display a remarkable evolutionary capacity uncommon in DNA genomes. Parvovirus populations show high genetic heterogeneity and large population sizes resembling the quasispecies found in RNA viruses. These viruses multiply in proliferating cells, causing acute, persistent or latent infections relying in the immunocompetence and developmental stage of the hosts. Some parvovirus populations in natural settings, such as carnivore autonomous parvoviruses or primate adeno associated virus, show a high degree of genetic heterogeneity. However, other parvoviruses such as the pathogenic B19 human erythrovirus or the porcine parvovirus, show little genetic variation, indicating different virus-host relationships. The Parvoviridae evolutionary potential in mammal infections has been modeled in the experimental system formed by the immunodeficient scid mouse infected by the minute virus of mice (MVM) under distinct immune and adaptive pressures. The sequence of viral genomes (close to 10(5) nucleotides) in emerging MVM pathogenic populations present in the organs of 26 mice showed consensus sequences not representing the complex distribution of viral clones and a high genetic heterogeneity (average mutation frequency 8.3 x 10(-4) substitutions/nt accumulated over 2-3 months). Specific amino acid changes, selected at a rate up to 1% in the capsid and in the NS2 nonstructural protein, endowed these viruses with new tropism and increased fitness. Further molecular analysis supported the notion that, in addition to immune pressures, the affinity of molecular interactions with cellular targets, as the Crml nuclear export receptor or the primary capsid receptor, as well as the adaptation to tissues enriched in proliferating cells, are major selective factors in the rapid parvovirus evolutionary dynamics.

Sparse repulsive coupling enhances synchronization in complex networks.

Through the last years, different strategies to enhance synchronization in complex networks have been proposed. In this work, we show that synchronization of nonidentical dynamical units that are attractively coupled in a small-world network is strongly improved by just making phase-repulsive a tiny fraction of the couplings. By a purely topological analysis that does not depend on the dynamical model, we link the emerging dynamical behavior with the structural properties of the sparsely coupled repulsive network.

Comparative effects of thiopental and propofol on atrial vulnerability: electrophysiological study in a porcine model including acute alcoholic intoxication.

BACKGROUND: Atrial tachyarrhythmias (AT) frequently complicate the perioperative period. Alcohol intoxication is a recognized causative factor for dysrrhythmias. We studied the effects of propofol and thiopental on atrial electrophysiology and vulnerability to AT in a closed-chest porcine model in which AT are facilitated by ethanol. METHODS: Thirty-eight pigs were randomly assigned to thiopental (T-group, n=19) or propofol (P-group n=19). All animals were assigned to undergo a right atrial electrical stimulation protocol (RASP) at baseline. Thirty pigs were assigned to undergo additional RASP during ethanol infusion, while the remaining eight were assigned to undergo additional RASP during saline infusion (control group). We analysed effective refractory period (ERP), and intra-atrial conduction interval (ICI) (between atrial sites 4 cm apart), at several cycle lengths (CL). RESULTS: There were no significant differences at baseline. During ethanol infusion, propofol produced a greater rate-dependent decrease in excitability, manifested by a longer minimum paced CL with 1:1 atrial capture: 145 (11) vs 164 (27) ms in the T- and P-group, respectively (P=0.01). Propofol was associated with a greater rate-related slowing in conduction: difference between ICI at CL of 300 ms and ICI at minimum CL: 30 ms in P-group and 22 ms in T-group (P<0.03). In the P-group we observed a longer duration of induced arrhythmias (145 (131) vs 74 (91) s, P<0.03) and a higher proportion with atrial flutter (AFl) (76 vs 19%, P<0.001). CONCLUSIONS: Propofol in this model was more arrhythmogenic than thiopental, as manifested by a longer duration of induced arrhythmias, particularly AFI.