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1.
Circ Res ; 128(4): e63-e83, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33375811

RESUMO

RATIONALE: Ca2+ alternans plays an essential role in cardiac alternans that can lead to ventricular fibrillation, but the mechanism underlying Ca2+ alternans remains undefined. Increasing evidence suggests that Ca2+ alternans results from alternations in the inactivation of cardiac RyR2 (ryanodine receptor 2). However, what inactivates RyR2 and how RyR2 inactivation leads to Ca2+ alternans are unknown. OBJECTIVE: To determine the role of CaM (calmodulin) on Ca2+ alternans in intact working mouse hearts. METHODS AND RESULTS: We used an in vivo local gene delivery approach to alter CaM function by directly injecting adenoviruses expressing CaM-wild type, a loss-of-function CaM mutation, CaM (1-4), and a gain-of-function mutation, CaM-M37Q, into the anterior wall of the left ventricle of RyR2 wild type or mutant mouse hearts. We monitored Ca2+ transients in ventricular myocytes near the adenovirus-injection sites in Langendorff-perfused intact working hearts using confocal Ca2+ imaging. We found that CaM-wild type and CaM-M37Q promoted Ca2+ alternans and prolonged Ca2+ transient recovery in intact RyR2 wild type and mutant hearts, whereas CaM (1-4) exerted opposite effects. Altered CaM function also affected the recovery from inactivation of the L-type Ca2+ current but had no significant impact on sarcoplasmic reticulum Ca2+ content. Furthermore, we developed a novel numerical myocyte model of Ca2+ alternans that incorporates Ca2+-CaM-dependent regulation of RyR2 and the L-type Ca2+ channel. Remarkably, the new model recapitulates the impact on Ca2+ alternans of altered CaM and RyR2 functions under 9 different experimental conditions. Our simulations reveal that diastolic cytosolic Ca2+ elevation as a result of rapid pacing triggers Ca2+-CaM dependent inactivation of RyR2. The resultant RyR2 inactivation diminishes sarcoplasmic reticulum Ca2+ release, which, in turn, reduces diastolic cytosolic Ca2+, leading to alternations in diastolic cytosolic Ca2+, RyR2 inactivation, and sarcoplasmic reticulum Ca2+ release (ie, Ca2+ alternans). CONCLUSIONS: Our results demonstrate that inactivation of RyR2 by Ca2+-CaM is a major determinant of Ca2+ alternans, making Ca2+-CaM dependent regulation of RyR2 an important therapeutic target for cardiac alternans.


Assuntos
Sinalização do Cálcio , Coração/fisiologia , Miócitos Cardíacos/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Potenciais de Ação , Animais , Canais de Cálcio Tipo L/metabolismo , Calmodulina/metabolismo , Células Cultivadas , Frequência Cardíaca , Camundongos , Camundongos Endogâmicos C57BL , Contração Miocárdica , Miócitos Cardíacos/fisiologia
2.
Eur J Pediatr ; 182(5): 2421-2432, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36914778

RESUMO

Most studies, aimed at determining the incidence and transmission of SARS-CoV-2 in children and teenagers, have been developed in school settings. Our study conducted surveillance and inferred attack rates focusing on the practice of sports. Prospective and observational study of those attending the sports facilities of Fútbol Club Barcelona (FCB), in Barcelona, Spain, throughout the 2020-2021 season. Participants were young players (from five different sports) and adult workers, who belonged to stable teams (shared routines and were involved in same quarantine rules). Biweekly health questionnaires and SARS-CoV-2 screening were conducted. From the 234 participants included, 70 (30%) both lived and trained in the FCB facilities (Recruitment Pathway 1;RP1) and 164 (70%) lived at their own household and just came to the facilities to train (RP2). During the study, 38 positive cases were identified; none had severe symptoms or needed hospitalization. The overall weekly incidence in the cohorts did not differ compared to the one expected in the community, except for 2 weeks when an outbreak occurred. The attack rate (AR) was three times higher for the participants from RP1, in comparison to those from RP2 (p < 0.01). A Basketball team showed a significant higher AR.  Conclusion: Physical activities in stable teams are not related to an increased risk of transmission of SARS-CoV-2, since there were the same observed cases than expected in the community. The risk is higher in indoor sports (Basketball vs. Football), and in closed cohort living settings (RP1 vs. RP2). The fulfilment of preventive measures is essential. What is Known: • Despite the low numerical impact caused in paediatric hospitalizations during COVID-19 pandemic, the social impact has been maximum. • The transmission potential in children and teenagers is limited, and it had been widely demonstrated in school settings. What is New: • Group physical activities in children and teenagers are not also related to an increased risk of transmission of SARS-CoV-2, when preventive measures, such as washing hands, and screening protocols are applied. • Routine and semi-professional sports activities seem safe environments to promote during this pandemic.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Adolescente , Adulto Jovem , Criança , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Estudos Prospectivos , Quarentena
3.
PLoS Comput Biol ; 16(9): e1007728, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32970668

RESUMO

Calcium oscillations and waves induce depolarization in cardiac cells which are believed to cause life-threathening arrhythimas. In this work, we study the conditions for the appearance of calcium oscillations in both a detailed subcellular model of calcium dynamics and a minimal model that takes into account just the minimal ingredients of the calcium toolkit. To avoid the effects of homeostatic changes and the interaction with the action potential we consider the somewhat artificial condition of a cell without pacing and with no calcium exchange with the extracellular medium. Both the full subcellular model and the minimal model present the same scenarios depending on the calcium load: two stationary states, one with closed ryanodine receptors (RyR) and most calcium in the cell stored in the sarcoplasmic reticulum (SR), and another, with open RyRs and a depleted SR. In between, calcium oscillations may appear. The robustness of these oscillations is determined by the amount of calsequestrin (CSQ). The lack of this buffer in the SR enhances the appearance of oscillations. The minimal model allows us to relate the stability of the oscillating state to the nullcline structure of the system, and find that its range of existence is bounded by a homoclinic and a Hopf bifurcation, resulting in a sudden transition to the oscillatory regime as the cell calcium load is increased. Adding a small amount of noise to the RyR behavior increases the parameter region where oscillations appear and provides a gradual transition from the resting state to the oscillatory regime, as observed in the subcellular model and experimentally.


Assuntos
Cálcio/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Calsequestrina/metabolismo , Modelos Biológicos , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Retículo Sarcoplasmático/metabolismo , Processos Estocásticos , Frações Subcelulares/metabolismo
4.
PLoS Comput Biol ; 16(12): e1008431, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33296373

RESUMO

The appearance and fast spreading of Covid-19 took the international community by surprise. Collaboration between researchers, public health workers, and politicians has been established to deal with the epidemic. One important contribution from researchers in epidemiology is the analysis of trends so that both the current state and short-term future trends can be carefully evaluated. Gompertz model has been shown to correctly describe the dynamics of cumulative confirmed cases, since it is characterized by a decrease in growth rate showing the effect of control measures. Thus, it provides a way to systematically quantify the Covid-19 spreading velocity and it allows short-term predictions and longer-term estimations. This model has been employed to fit the cumulative cases of Covid-19 from several European countries. Results show that there are systematic differences in spreading velocity among countries. The model predictions provide a reliable picture of the short-term evolution in countries that are in the initial stages of the Covid-19 outbreak, and may permit researchers to uncover some characteristics of the long-term evolution. These predictions can also be generalized to calculate short-term hospital and intensive care units (ICU) requirements.


Assuntos
COVID-19 , Modelos Estatísticos , COVID-19/epidemiologia , COVID-19/transmissão , Biologia Computacional , Europa (Continente) , Humanos , Saúde Pública , SARS-CoV-2
5.
PLoS Comput Biol ; 16(6): e1007572, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32502205

RESUMO

Ventricular contraction is roughly proportional to the amount of calcium released from the Sarcoplasmic Reticulum (SR) during systole. While it is rather straightforward to measure calcium levels and contractibility under different physiological conditions, the complexity of calcium handling during systole and diastole has made the prediction of its release at steady state impossible. Here we approach the problem analyzing the evolution of intracellular and extracellular calcium fluxes during a single beat which is away from homeostatic balance. Using an in-silico subcellular model of rabbit ventricular myocyte, we show that the high dimensional nonlinear problem of finding the steady state can be reduced to a two-variable general equilibrium condition where pre-systolic calcium level in the cytosol and in the SR must fulfill simultaneously two different equalities. This renders calcium homeostasis as a problem that can be studied in terms of its equilibrium structure, leading to precise predictions of steady state from single-beat measurements. We show how changes in ion channels modify the general equilibrium, as shocks would do in general equilibrium macroeconomic models. This allows us to predict when an enhanced entrance of calcium in the cell reduces its contractibility and explain why SERCA gene therapy, a change in calcium handling to treat heart failure, might fail to improve contraction even when it successfully increases SERCA expression.


Assuntos
Cálcio/metabolismo , Ventrículos do Coração/metabolismo , Íons , Células Musculares/metabolismo , Animais , Simulação por Computador , Citosol/metabolismo , Homeostase , Contração Miocárdica , Miócitos Cardíacos/metabolismo , Coelhos , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Retículo Sarcoplasmático/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Sístole
6.
Chaos ; 27(9): 093928, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28964152

RESUMO

In the heart, rapid pacing rates may induce alternations in the strength of cardiac contraction, termed pulsus alternans. Often, this is due to an instability in the dynamics of the intracellular calcium concentration, whose transients become larger and smaller at consecutive beats. This alternation has been linked experimentally and theoretically to two different mechanisms: an instability due to (1) a strong dependence of calcium release on sarcoplasmic reticulum (SR) load, together with a slow calcium reuptake into the SR or (2) to SR release refractoriness, due to a slow recovery of the ryanodine receptors (RyR2) from inactivation. The relationship between calcium alternans and refractoriness of the RyR2 has been more elusive than the corresponding SR Ca load mechanism. To study the former, we reduce a general calcium model, which mimics the deterministic evolution of a calcium release unit, to its most basic elements. We show that calcium alternans can be understood using a simple nonlinear equation for calcium concentration at the dyadic space, coupled to a relaxation equation for the number of recovered RyR2s. Depending on the number of RyR2s that are recovered at the beginning of a stimulation, the increase in calcium concentration may pass, or not, over an excitability threshold that limits the occurrence of a large calcium transient. When the recovery of the RyR2 is slow, this produces naturally a period doubling bifurcation, resulting in calcium alternans. We then study the effects of inactivation, calcium diffusion, and release conductance for the onset of alternans. We find that the development of alternans requires a well-defined value of diffusion while it is less sensitive to the values of inactivation or release conductance.


Assuntos
Sinalização do Cálcio , Modelos Biológicos , Retículo Sarcoplasmático/metabolismo , Potenciais de Ação/fisiologia , Fatores de Tempo
7.
Phys Rev Lett ; 114(10): 108101, 2015 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-25815968

RESUMO

Electromechanical alternans is a beat-to-beat alternation in the strength of contraction of a cardiac cell, which can be caused by an instability of calcium cycling. Using a distributed model of subcellular calcium we show that alternans occurs via an order-disorder phase transition which exhibits critical slowing down and a diverging correlation length. We apply finite size scaling along with a mapping to a stochastic coupled map model, to show that this transition in two dimensions is characterized by critical exponents consistent with the Ising universality class. These findings highlight the important role of cooperativity in biological cells, and suggest novel approaches to investigate the onset of the alternans instability in the heart.


Assuntos
Cálcio/metabolismo , Modelos Cardiovasculares , Miócitos Cardíacos/metabolismo , Contração Miocárdica , Frações Subcelulares/metabolismo
8.
Front Public Health ; 12: 1288531, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38528860

RESUMO

Introduction: We use Spanish data from August 2020 to March 2021 as a natural experiment to analyze how a standardized measure of COVID-19 growth correlates with asymmetric meteorological and mobility situations in 48 Spanish provinces. The period of time is selected prior to vaccination so that the level of susceptibility was high, and during geographically asymmetric implementation of non-pharmacological interventions. Methods: We develop reliable aggregated mobility data from different public sources and also compute the average meteorological time series of temperature, dew point, and UV radiance in each Spanish province from satellite data. We perform a dimensionality reduction of the data using principal component analysis and investigate univariate and multivariate correlations of mobility and meteorological data with COVID-19 growth. Results: We find significant, but generally weak, univariate correlations for weekday aggregated mobility in some, but not all, provinces. On the other hand, principal component analysis shows that the different mobility time series can be properly reduced to three time series. A multivariate time-lagged canonical correlation analysis of the COVID-19 growth rate with these three time series reveals a highly significant correlation, with a median R-squared of 0.65. The univariate correlation between meteorological data and COVID-19 growth is generally not significant, but adding its two main principal components to the mobility multivariate analysis increases correlations significantly, reaching correlation coefficients between 0.6 and 0.98 in all provinces with a median R-squared of 0.85. This result is robust to different approaches in the reduction of dimensionality of the data series. Discussion: Our results suggest an important effect of mobility on COVID-19 cases growth rate. This effect is generally not observed for meteorological variables, although in some Spanish provinces it can become relevant. The correlation between mobility and growth rate is maximal at a time delay of 2-3 weeks, which agrees well with the expected 5?10 day delays between infection, development of symptoms, and the detection/report of the case.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Temperatura , Análise Multivariada
9.
Front Public Health ; 12: 1339267, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855458

RESUMO

Background: Countries across Europe have faced similar evolutions of SARS-CoV-2 variants of concern, including the Alpha, Delta, and Omicron variants. Materials and methods: We used data from GISAID and applied a robust, automated mathematical substitution model to study the dynamics of COVID-19 variants in Europe over a period of more than 2 years, from late 2020 to early 2023. This model identifies variant substitution patterns and distinguishes between residual and dominant behavior. We used weekly sequencing data from 19 European countries to estimate the increase in transmissibility ( Δ ß ) between consecutive SARS-CoV-2 variants. In addition, we focused on large countries with separate regional outbreaks and complex scenarios of multiple competing variants. Results: Our model accurately reproduced the observed substitution patterns between the Alpha, Delta, and Omicron major variants. We estimated the daily variant prevalence and calculated Δ ß between variants, revealing that: ( i ) Δ ß increased progressively from the Alpha to the Omicron variant; ( i i ) Δ ß showed a high degree of variability within Omicron variants; ( i i i ) a higher Δ ß was associated with a later emergence of the variant within a country; ( i v ) a higher degree of immunization of the population against previous variants was associated with a higher Δ ß for the Delta variant; ( v ) larger countries exhibited smaller Δ ß , suggesting regionally diverse outbreaks within the same country; and finally ( v i ) the model reliably captures the dynamics of competing variants, even in complex scenarios. Conclusion: The use of mathematical models allows for precise and reliable estimation of daily cases of each variant. By quantifying Δ ß , we have tracked the spread of the different variants across Europe, highlighting a robust increase in transmissibility trend from Alpha to Omicron. Additionally, we have shown that the geographical characteristics of a country, as well as the timing of new variant entrances, can explain some of the observed differences in variant substitution dynamics across countries.


Assuntos
COVID-19 , Modelos Teóricos , SARS-CoV-2 , Humanos , COVID-19/transmissão , COVID-19/epidemiologia , Europa (Continente)/epidemiologia , SARS-CoV-2/genética
10.
Front Public Health ; 11: 1307425, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38259774

RESUMO

Introduction: Bronchiolitis, mostly caused by Respiratory Syncytial Virus (RSV), and influenza among other respiratory infections, lead to seasonal saturation at healthcare centers in temperate areas. There is no gold standard to characterize the stages of epidemics, nor the risk of respiratory infections growing. We aimed to define a set of indicators to assess the risk level of respiratory viral epidemics, based on both incidence and their short-term dynamics, and considering epidemical thresholds. Methods: We used publicly available data on daily cases of influenza for the whole population and bronchiolitis in children <2 years from the Information System for Infection Surveillance in Catalonia (SIVIC). We included a Moving Epidemic Method (MEM) variation to define epidemic threshold and levels. We pre-processed the data with two different nowcasting approaches and performed a 7-day moving average. Weekly incidences (cases per 105 population) were computed and the 5-day growth rate was defined to create the effective potential growth (EPG) indicator. We performed a correlation analysis to define the forecasting ability of this index. Results: Our adaptation of the MEM method allowed us to define epidemic weekly incidence levels and epidemic thresholds for bronchiolitis and influenza. EPG was able to anticipate daily 7-day cumulative incidence by 4-5 (bronchiolitis) or 6-7 (influenza) days. Discussion: We developed a semi-empirical risk panel incorporating the EPG index, which effectively anticipates surpassing epidemic thresholds for bronchiolitis and influenza. This panel could serve as a robust surveillance tool, applicable to respiratory infectious diseases characterized by seasonal epidemics, easy to handle for individuals lacking a mathematical background.


Assuntos
Bronquiolite , Influenza Humana , Infecções Respiratórias , Criança , Humanos , Influenza Humana/epidemiologia , Saúde Pública , Atenção à Saúde
11.
Phys Rev Lett ; 109(14): 144502, 2012 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-23083248

RESUMO

Conventional viscous fingering flow in radial Hele-Shaw cells employs a constant injection rate, resulting in the emergence of branched interfacial shapes. The search for mechanisms to prevent the development of these bifurcated morphologies is relevant to a number of areas in science and technology. A challenging problem is how best to choose the pumping rate in order to restrain the growth of interfacial amplitudes. We use an analytical variational scheme to look for the precise functional form of such an optimal flow rate. We find it increases linearly with time in a specific manner so that interface disturbances are minimized. Experiments and nonlinear numerical simulations support the effectiveness of this particularly simple, but nontrivial, pattern controlling process.

12.
Front Physiol ; 13: 836622, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370783

RESUMO

Regulation of intracellular calcium is a critical component of cardiac electrophysiology and excitation-contraction coupling. The calcium spark, the fundamental element of the intracellular calcium transient, is initiated in specialized nanodomains which co-locate the ryanodine receptors and L-type calcium channels. However, calcium homeostasis is ultimately regulated at the cellular scale, by the interaction of spatially separated but diffusively coupled nanodomains with other sub-cellular and surface-membrane calcium transport channels with strong non-linear interactions; and cardiac electrophysiology and arrhythmia mechanisms are ultimately tissue-scale phenomena, regulated by the interaction of a heterogeneous population of coupled myocytes. Recent advances in imaging modalities and image-analysis are enabling the super-resolution reconstruction of the structures responsible for regulating calcium homeostasis, including the internal structure of nanodomains themselves. Extrapolating functional and imaging data from the nanodomain to the whole-heart is non-trivial, yet essential for translational insight into disease mechanisms. Computational modeling has important roles to play in relating structural and functional data at the sub-cellular scale and translating data across the scales. This review covers recent methodological advances that enable image-based modeling of the single nanodomain and whole cardiomyocyte, as well as the development of multi-scale simulation approaches to integrate data from nanometer to whole-heart. Firstly, methods to overcome the computational challenges of simulating spatial calcium dynamics in the nanodomain are discussed, including image-based modeling at this scale. Then, recent whole-cell models, capable of capturing a range of different structures (such as the T-system and mitochondria) and cellular heterogeneity/variability are discussed at two different levels of discretization. Novel methods to integrate the models and data across the scales and simulate stochastic dynamics in tissue-scale models are then discussed, enabling elucidation of the mechanisms by which nanodomain remodeling underlies arrhythmia and contractile dysfunction. Perspectives on model differences and future directions are provided throughout.

13.
PLoS One ; 17(4): e0266233, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35381041

RESUMO

The development of modeling structures at the channel level that can integrate subcellular and cell models and properly reproduce different experimental data is of utmost importance in cardiac electrophysiology. In contrast to gate-based models, Markov Chain models are well suited to promote the integration of the subcellular level of the cardiomyocyte to the whole cell. In this paper, we develop Markov Chain models for the L-type Calcium current that can reproduce the electrophysiology of two established human models for the ventricular and Purkinje cells. In addition, instead of presenting a single set of parameters, we present a collection of set of parameters employing Differential Evolution algorithms that can properly reproduce very different protocol data. We show the importance of using an ensemble of a set of parameter values to obtain proper results when considering a second protocol that suppresses calcium inactivation and mimics a pathological condition. We discuss how model discrepancy, data availability, and parameter identifiability can influence the choice of the size of the collection. In summary, we have modified two cardiac models by proposing new Markov Chain models for the L-type Calcium. We keep the original whole-cell dynamics by reproducing the same characteristic action potential and calcium dynamics, whereas the Markov chain-based description of the L-type Calcium channels allows novel small spatial scale simulations of subcellular processes. Finally, the use of collections of parameters was crucial for addressing model discrepancy, identifiability issues, and avoiding fitting parameters overly precisely, i.e., overfitting.


Assuntos
Canais de Cálcio Tipo L , Cálcio , Miócitos Cardíacos , Potenciais de Ação , Cálcio/metabolismo , Canais de Cálcio Tipo L/fisiologia , Humanos , Cadeias de Markov , Miócitos Cardíacos/metabolismo
15.
Front Public Health ; 10: 961030, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36033822

RESUMO

Purpose: We aim to compare the severity of infections between omicron and delta variants in 609,352 SARS-CoV-2 positive cases using local hospitalization, vaccination, and variants data from the Catalan Health Care System (which covers around 7. 8 million people). Methods: We performed a substitution model to establish the increase in transmissibility of omicron using variant screening data from primary care practices (PCP) and hospital admissions. In addition, we used this data from PCP to establish the two periods when delta and omicron were, respectively, dominant (above 95% of cases). After that, we performed a population-based cohort analysis to calculate the rates of hospital and intensive care unit (ICU) admissions for both periods and to estimate reduction in severity. Rate ratios (RR) and 95% confidence intervals (95% CI) were calculated and stratified by age and vaccination status. In a second analysis, the differential substitution model in primary care vs. hospitals allowed us to obtain a population-level average change in severity. Results: We have included 48,874 cases during the delta period and 560,658 during the omicron period. During the delta period, on average, 3.8% of the detected cases required hospitalization for COVID-19. This percentage dropped to 0.9% with omicron [RR of 0.46 (95% CI: 0.43 to 0.49)]. For ICU admissions, it dropped from 0.8 to 0.1% [RR 0.25 (95% CI: 0.21 to 0.28)]. The proportion of cases hospitalized or admitted to ICU was lower in the vaccinated groups, independently of the variant. Omicron was associated with a reduction in risk of admission to hospital and ICU in all age and vaccination status strata. The differential substitution models showed an average RR between 0.19 and 0.50. Conclusion: Both independent methods consistently show an important decrease in severity for omicron relative to delta. The systematic reduction happens regardless of age. The severity is also reduced for non-vaccinated and vaccinated groups, but it remains always higher in the non-vaccinated population. This suggests an overall reduction in severity, which could be intrinsic to the omicron variant. The fact is that the RR in ICU admission is systematically smaller than in hospitalization points in the same direction.


Assuntos
COVID-19 , SARS-CoV-2 , Estudos de Coortes , Cuidados Críticos , Hospitalização , Humanos , Espanha
16.
Front Public Health ; 9: 633123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307270

RESUMO

The current worldwide pandemic produced by coronavirus disease 2019 (COVID-19) has changed the paradigm of mathematical epidemiology due to the high number of unknowns of this new disease. Thus, the empirical approach has emerged as a robust tool to analyze the actual situation carried by the countries and also allows us to predict the incoming scenarios. In this paper, we propose three empirical indexes to estimate the state of the pandemic. These indexes quantify both the propagation and the number of estimated cases, allowing us to accurately determine the real risk of a country. We have calculated these indexes' evolution for several European countries. Risk diagrams are introduced as a tool to visualize the evolution of a country and evaluate its current risk as a function of the number of contagious individuals and the empiric reproduction number. Risk diagrams at the regional level are useful to observe heterogeneity on COVID-19 penetration and spreading in some countries, which is essential during deconfinement processes. During the pandemic, there have been significant differences seen in countries reporting case criterion and detection capacity. Therefore, we have introduced estimations about the real number of infectious cases that allows us to have a broader view and to better estimate the risk. These diagrams and indexes have been successfully used for the monitoring of European countries and regions during the COVID-19 pandemic.


Assuntos
COVID-19 , Pandemias , Europa (Continente) , Humanos , SARS-CoV-2
17.
Front Public Health ; 9: 693956, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34291033

RESUMO

Monitoring transmission is a prerequisite for containing COVID-19. We report on effective potential growth (EPG) as a novel measure for the early identification of local outbreaks based on primary care electronic medical records (EMR) and PCR-confirmed cases. Secondly, we studied whether increasing EPG precedes local hospital and intensive care (ICU) admissions and mortality. Population-based cohort including all Catalan citizens' PCR tests, hospitalization, intensive care (ICU) and mortality between 1/07/2020 and 13/09/2020; linked EMR covering 88.6% of the Catalan population was obtained. Nursing home residents were excluded. COVID-19 counts were ascertained based on EMR and PCRs separately. Weekly empirical propagation (ρ7) and 14-day cumulative incidence (A14) and 95% confidence intervals were estimated at care management area (CMA) level, and combined as EPG = ρ7 × A14. Overall, 7,607,201 and 6,798,994 people in 43 CMAs were included for PCR and EMR measures, respectively. A14, ρ7, and EPG increased in numerous CMAs during summer 2020. EMR identified 2.70-fold more cases than PCRs, with similar trends, a median (interquartile range) 2 (1) days earlier, and better precision. Upticks in EPG preceded increases in local hospital admissions, ICU occupancy, and mortality. Increasing EPG identified localized outbreaks in Catalonia, and preceded local hospital and ICU admissions and subsequent mortality. EMRs provided similar estimates to PCR, but some days earlier and with better precision. EPG is a useful tool for the monitoring of community transmission and for the early identification of COVID-19 local outbreaks.


Assuntos
COVID-19 , Surtos de Doenças , Registros Eletrônicos de Saúde , Humanos , Atenção Primária à Saúde , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2 , Espanha/epidemiologia
18.
PLoS One ; 16(1): e0243701, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33411737

RESUMO

Policymakers need clear, fast assessment of the real spread of the COVID-19 epidemic in each of their respective countries. Standard measures of the situation provided by the governments include reported positive cases and total deaths. While total deaths indicate immediately that countries like Italy and Spain had the worst situation as of mid-April, 2020, reported cases alone do not provide a complete picture of the situation. Different countries diagnose differently and present very distinctive reported case fatality ratios. Similar levels of reported incidence and mortality might hide a very different underlying pictures. Here we present a straightforward and robust estimation of the diagnostic rate in each European country. From that estimation we obtain a uniform, unbiased incidence of the epidemic. The method to obtain the diagnostic rate is transparent and empirical. The key assumption of the method is that the infection fatality ratio of COVID-19 in Europe is not strongly country-dependent. We show that this number is not expected to be biased due to demography nor to the way total deaths are reported. The estimation protocol is dynamic, and it has been yielding converging numbers for diagnostic rates in all European countries as from mid-April, 2020. Using this diagnostic rate, policy makers can obtain Effective Potential Growth updated every day, providing an unbiased assessment of the countries at greater risk of experiencing an uncontrolled situation. The method developed has been and will be used to track possible improvements in the diagnostic rate in European countries as the epidemic evolves.


Assuntos
COVID-19/epidemiologia , Número Básico de Reprodução , COVID-19/diagnóstico , COVID-19/mortalidade , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis , Europa (Continente)/epidemiologia , União Europeia , Política de Saúde , Humanos , Incidência
19.
Phys Rev E Stat Nonlin Soft Matter Phys ; 78(2 Pt 2): 026305, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18850934

RESUMO

The development of immiscible viscous fingering patterns in a rotating Hele-Shaw cell is investigated. We focus on understanding how the time evolution and the resulting morphologies are affected by the action of the Coriolis force. The problem is approached analytically and numerically by employing a vortex sheet formalism. The vortex sheet strength and a linear dispersion relation are derived analytically, revealing that the most relevant Coriolis force contribution comes from the normal component of the averaged interfacial velocity. It is shown that this normal velocity, uniquely due to the presence of the Coriolis force, is responsible for the complex-valued nature of the linear dispersion relation making the linear phases vary with time. Fully nonlinear stages are studied through intensive numerical simulations. A suggestive interplay between inertial and viscous effects is found, which modifies the dynamics, leading to different pattern-forming structures. The inertial Coriolis contribution plays a characteristic role: it generates a phase drift by deviating the fingers in the sense opposite to the actual rotation of the cell. However, the direction and intensity of finger bending is predominantly determined by viscous effects, being sensitive to changes in the magnitude and sign of the viscosity contrast. The finger competition behavior at advanced time stages is also discussed.

20.
Phys Rev E ; 95(3-1): 032313, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28415301

RESUMO

Signal transduction within biological cells is governed by networks of interacting proteins. Communication between these proteins is mediated by signaling molecules which bind to receptors and induce stochastic transitions between different conformational states. Signaling is typically a cooperative process which requires the occurrence of multiple binding events so that reaction rates have a nonlinear dependence on the amount of signaling molecule. It is this nonlinearity that endows biological signaling networks with robust switchlike properties which are critical to their biological function. In this study we investigate how the properties of these signaling systems depend on the network architecture. Our main result is that these nonlinear networks exhibit bistability where the network activity can switch between states that correspond to a low and high activity level. We show that this bistable regime emerges at a critical coupling strength that is determined by the spectral structure of the network. In particular, the set of nodes that correspond to large components of the leading eigenvector of the adjacency matrix determines the onset of bistability. Above this transition the eigenvectors of the adjacency matrix determine a hierarchy of clusters, defined by its spectral properties, which are activated sequentially with increasing network activity. We argue further that the onset of bistability occurs either continuously or discontinuously depending upon whether the leading eigenvector is localized or delocalized. Finally, we show that at low network coupling stochastic transitions to the active branch are also driven by the set of nodes that contribute more strongly to the leading eigenvector. However, at high coupling, transitions are insensitive to network structure since the network can be activated by stochastic transitions of a few nodes. Thus this work identifies important features of biological signaling networks that may underlie their biological function.


Assuntos
Modelos Biológicos , Transdução de Sinais , Análise por Conglomerados , Dinâmica não Linear , Processos Estocásticos
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