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A dynamical model of TGF-β activation in asthmatic airways. 哮喘气道中 TGF-β 激活的动态模型。
IF 1.1 4区 数学 Q2 Medicine Pub Date : 2023-09-15 DOI: 10.1093/imammb/dqad004
Hannah J Pybus, Reuben D O'Dea, Bindi S Brook

Excessive activation of the regulatory cytokine transforming growth factor $beta $ (TGF-$beta $) via contraction of airway smooth muscle (ASM) is associated with the development of asthma. In this study, we develop an ordinary differential equation model that describes the change in density of the key airway wall constituents, ASM and extracellular matrix (ECM), and their interplay with subcellular signalling pathways leading to the activation of TGF-$beta $. We identify bistable parameter regimes where there are two positive steady states, corresponding to either reduced or elevated TGF-$beta $ concentration, with the latter leading additionally to increased ASM and ECM density. We associate the former with a healthy homeostatic state and the latter with a diseased (asthmatic) state. We demonstrate that external stimuli, inducing TGF-$beta $ activation via ASM contraction (mimicking an asthmatic exacerbation), can perturb the system irreversibly from the healthy state to the diseased one. We show that the properties of the stimuli, such as their frequency or strength, and the clearance of surplus active TGF-$beta $, are important in determining the long-term dynamics and the development of disease. Finally, we demonstrate the utility of this model in investigating temporal responses to bronchial thermoplasty, a therapeutic intervention in which ASM is ablated by applying thermal energy to the airway wall. The model predicts the parameter-dependent threshold damage required to obtain irreversible reduction in ASM content, suggesting that certain asthma phenotypes are more likely to benefit from this intervention.

通过气道平滑肌(ASM)收缩过度激活调节细胞因子转化生长因子(TGF-$beta $)与哮喘的发生有关。在这项研究中,我们建立了一个常微分方程模型,该模型描述了气道壁主要成分 ASM 和细胞外基质(ECM)密度的变化,以及它们与导致 TGF-$beta $ 激活的亚细胞信号通路的相互作用。我们确定了双稳态参数区,其中有两种正稳态,分别对应于 TGF-$beta $ 浓度降低或升高,后者还会导致 ASM 和 ECM 密度增加。我们将前者与健康的平衡状态联系起来,将后者与疾病(哮喘)状态联系起来。我们证明,通过 ASM 收缩(模拟哮喘加重)诱导 TGF-$beta $ 激活的外部刺激,可以不可逆转地扰乱系统,使其从健康状态转变为疾病状态。我们表明,刺激的特性,如刺激的频率或强度,以及剩余活性 TGF-$beta $ 的清除,对于决定长期动态和疾病的发展非常重要。最后,我们展示了该模型在研究支气管热成形术时间反应方面的实用性,支气管热成形术是一种通过对气道壁施加热能来消融 ASM 的治疗干预措施。该模型预测了ASM含量不可逆减少所需的参数依赖性阈值损伤,这表明某些哮喘表型更有可能从这种干预措施中获益。
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引用次数: 0
A generalized order mixture model for tracing connectivity of white matter fascicles complexity in brain from diffusion MRI. 从弥散核磁共振成像追踪脑白质束复杂性连接的广义阶混合物模型。
IF 1.1 4区 数学 Q2 Medicine Pub Date : 2023-09-15 DOI: 10.1093/imammb/dqad002
Ashishi Puri, Sanjeev Kumar

This paper focuses on tracing the connectivity of white matter fascicles in the brain. In particular, a generalized order algorithm based on mixture of non-central Wishart distribution model is proposed for this purpose. The proposed algorithm utilizes the generalization of integer order based approach with the mixture of non-central Wishart distribution model. Pseudo super anomalous behavior of water diffusion inside human brain is the prime motivation of the the present study. We have shown results on multiple synthetic simulations with fibers orientations in two and three directions in each voxel as well as experiments on real data. Synthetic simulations were performed with varying noise levels and diffusion weighting gradient i.e. $b-$values. The proposed model performed outstanding especially for distinguishing closely oriented fibers.

本文的重点是追踪大脑白质分册的连通性。为此,本文特别提出了一种基于非中心 Wishart 分布模型混合物的广义阶算法。所提出的算法利用了基于整数阶次方法的广义阶次与非中心 Wishart 分布模型的混合物。人脑内部水扩散的伪超反常行为是本研究的主要动机。我们展示了在每个体素的两个和三个方向上纤维方向的多个合成模拟结果,以及真实数据的实验结果。合成模拟是在不同的噪声水平和扩散加权梯度(即 $b-$值)下进行的。所提出的模型表现出色,尤其是在区分紧密定向的纤维方面。
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引用次数: 1
Quantifying assays: inhibition of signalling pathways of cancer. 量化试验:抑制癌症信号通路。
IF 1.1 4区 数学 Q2 Medicine Pub Date : 2023-09-15 DOI: 10.1093/imammb/dqad005
Roumen Anguelov, G Manjunath, Avulundiah E Phiri, Trevor T Nyakudya, Priyesh Bipath, June C Serem, Yvette N Hlophe

Inhibiting a signalling pathway concerns controlling the cellular processes of a cancer cell's viability, cell division and death. Assay protocols created to see if the molecular structures of the drugs being tested have the desired inhibition qualities often show great variability across experiments, and it is imperative to diminish the effects of such variability while inferences are drawn. In this paper, we propose the study of experimental data through the lenses of a mathematical model depicting the inhibition mechanism and the activation-inhibition dynamics. The method is exemplified through assay data obtained from an experimental study of the inhibition of the chemokine receptor 4 (CXCR4) and chemokine ligand 12 (CXCL12) signalling pathway of melanoma cells. The quantitative analysis is conducted as a two step process: (i) deriving theoretically from the model the cell viability as a function of time depending on several parameters; (ii) estimating the values of the parameters by using the experimental data. The cell viability is obtained as a function of concentration of the inhibitor and time, thus providing a comprehensive characterization of the potential therapeutic effect of the considered inhibitor, e.g. $IC_{50}$ can be computed for any time point.

抑制信号通路涉及控制癌细胞的存活、分裂和死亡等细胞过程。为了解受试药物的分子结构是否具有理想的抑制效果而制定的检测方案往往在不同实验中表现出很大的差异性,因此在进行推断时必须减少这种差异性的影响。在本文中,我们提出通过描述抑制机制和活化-抑制动态的数学模型来研究实验数据。该方法通过对抑制黑色素瘤细胞趋化因子受体 4(CXCR4)和趋化因子配体 12(CXCL12)信号通路的实验研究中获得的检测数据进行举例说明。定量分析分两步进行:(i) 根据模型从理论上推导出细胞存活率与多个参数有关的时间函数;(ii) 利用实验数据估算参数值。细胞存活率是抑制剂浓度和时间的函数,因此可以全面描述所考虑抑制剂的潜在治疗效果,例如可以计算任何时间点的 $IC_{50}$。
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引用次数: 0
Phenomenological analysis of simple ion channel block in large populations of uncoupled cardiomyocytes. 大量未偶联心肌细胞中简单离子通道阻滞的现象学分析。
IF 1.1 4区 数学 Q2 Medicine Pub Date : 2023-06-14 DOI: 10.1093/imammb/dqad001
Radostin D Simitev, Antesar Al Dawoud, Muhamad H N Aziz, Rachel Myles, Godfrey L Smith

Current understanding of arrhythmia mechanisms and design of anti-arrhythmic drug therapies hinges on the assumption that myocytes from the same region of a single heart have similar, if not identical, action potential waveforms and drug responses. On the contrary, recent experiments reveal significant heterogeneity in uncoupled healthy myocytes both from different hearts as well as from identical regions within a single heart. In this work, a methodology is developed for quantifying the individual electrophysiological properties of large numbers of uncoupled cardiomyocytes under ion channel block in terms of the parameters values of a conceptual fast-slow model of electrical excitability. The approach is applied to a population of nearly 500 rabbit ventricular myocytes for which action potential duration (APD) before and after the application of the drug nifedipine was experimentally measured (Lachaud et al., 2022, Cardiovasc. Res.). To this end, drug action is represented by a multiplicative factor to an effective ion conductance, a closed form asymptotic expression for APD is derived and inverted to determine model parameters as functions of APD and $varDelta $APD (drug-induced change in APD) for each myocyte. Two free protocol-related quantities are calibrated to experiment using an adaptive-domain procedure based on an original assumption of optimal excitability. The explicit APD expression and the resulting set of model parameter values allow (a) direct evaluation of conditions necessary to maintain fixed APD or $varDelta $APD, (b) predictions of the proportion of cells remaining excitable after drug application, (c) predictions of stimulus period dependency and (d) predictions of dose-response curves, the latter being in agreement with additional experimental data.

目前对心律失常机制的理解和抗心律失常药物治疗的设计取决于来自单个心脏同一区域的肌细胞具有相似(如果不是相同的话)动作电位波形和药物反应的假设。相反,最近的实验显示,来自不同心脏和单个心脏内相同区域的未偶联健康肌细胞存在显著的异质性。在这项工作中,开发了一种方法,用于根据电兴奋性的概念快-慢模型的参数值来量化离子通道阻滞下大量未耦合心肌细胞的个体电生理特性。该方法应用于近500只兔心室肌细胞,实验测量了应用硝苯地平药物前后的动作电位持续时间(APD) (Lachaud et al., 2022, cardiovascular .)。>)。为此,药物作用由有效离子电导的乘法因子表示,推导出APD的封闭形式渐近表达,并倒置以确定模型参数作为每个肌细胞的APD和$varDelta $APD(药物诱导的APD变化)的函数。使用基于最优兴奋性原始假设的自适应域程序校准两个与协议相关的自由量。明确的APD表达和由此产生的模型参数值集允许(a)直接评估维持固定APD或$ varDelta $APD所需的条件,(b)预测药物应用后仍可兴奋的细胞比例,(c)预测刺激期依赖性和(d)预测剂量-反应曲线,后者与其他实验数据一致。
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引用次数: 0
Discrete and continuum models for the coevolutionary dynamics between CD8+ cytotoxic T lymphocytes and tumour cells. CD8+细胞毒性T淋巴细胞和肿瘤细胞共同进化动力学的离散和连续模型。
IF 1.1 4区 数学 Q2 Medicine Pub Date : 2023-06-14 DOI: 10.1093/imammb/dqac017
Luís Almeida, Chloe Audebert, Emma Leschiera, Tommaso Lorenzi

We present an individual-based model for the coevolutionary dynamics between CD8+ cytotoxic T lymphocytes (CTLs) and tumour cells. In this model, every cell is viewed as an individual agent whose phenotypic state is modelled by a discrete variable. For tumour cells, this variable represents a parameterization of the antigen expression profiles, while for CTLs it represents a parameterization of the target antigens of T-cell receptors (TCRs). We formally derive the deterministic continuum limit of this individual-based model, which comprises a non-local partial differential equation for the phenotype distribution of tumour cells coupled with an integro-differential equation for the phenotype distribution of CTLs. The biologically relevant homogeneous steady-state solutions of the continuum model equations are found. The linear-stability analysis of these steady-state solutions is then carried out in order to identify possible conditions on the model parameters that may lead to different outcomes of immune competition and to the emergence of patterns of phenotypic coevolution between tumour cells and CTLs. We report on computational results of the individual-based model, and show that there is a good agreement between them and analytical and numerical results of the continuum model. These results shed light on the way in which different parameters affect the coevolutionary dynamics between tumour cells and CTLs. Moreover, they support the idea that TCR-tumour antigen binding affinity may be a good intervention target for immunotherapy and offer a theoretical basis for the development of anti-cancer therapy aiming at engineering TCRs so as to shape their affinity for cancer targets.

我们提出了一个基于个体的CD8+细胞毒性T淋巴细胞(ctl)和肿瘤细胞之间共同进化动力学的模型。在这个模型中,每个细胞都被视为一个单独的因子,其表型状态由一个离散变量来建模。对于肿瘤细胞,该变量代表抗原表达谱的参数化,而对于ctl,它代表t细胞受体(TCRs)靶抗原的参数化。我们正式推导了这种基于个体的模型的确定性连续极限,该模型包括肿瘤细胞表型分布的非局部偏微分方程以及ctl表型分布的积分微分方程。找到了连续统模型方程的生物学相关齐次稳态解。然后对这些稳态溶液进行线性稳定性分析,以确定模型参数上可能导致免疫竞争不同结果的条件,以及肿瘤细胞和ctl之间表型共同进化模式的出现。我们报告了基于个体的模型的计算结果,并表明它们与连续体模型的解析和数值结果有很好的一致性。这些结果揭示了不同的参数如何影响肿瘤细胞和ctl之间的共同进化动力学。此外,他们支持了tcr -肿瘤抗原结合亲和力可能是一个很好的免疫治疗干预靶点的观点,并为开发针对工程tcr的抗癌治疗提供了理论基础,从而塑造其对癌症靶点的亲和力。
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引用次数: 4
COVID-19 immunotherapy: a mathematical model. COVID-19免疫治疗:一个数学模型
IF 1.1 4区 数学 Q2 Medicine Pub Date : 2023-06-14 DOI: 10.1093/imammb/dqad003
J N Tavares, Emilie Gomes

The pandemic caused by SARS-CoV-2 is responsible for a terrible health devastation with profoundly harmful consequences for the economic, social and political activities of communities on a global scale. Extraordinary efforts have been made by the world scientific community, who, in solidarity, shared knowledge so that effective vaccines could be produced quickly. However, it is still important to study therapies that can reduce the risk, until group immunity is reached, which, globally, will take a time that is still difficult to predict. On the other hand, the immunity time guaranteed by already approved vaccines is still uncertain. The current study proposes a therapy whose foundation lies in the important role that innate immunity may have, by preventing the disease from progressing to the acute phase that may eventually lead to the patient's death. Our focus is on natural killer (NK) cells and their relevant role. NKs are considered the primary defence lymphocytes against virus-infected cells. They play a critical role in modulating the immune system. Preliminary studies in COVID-19 patients with severe disease suggest a reduction in the number and function of NK cells, resulting in decreased clearance of infected and activated cells and unchecked elevation of inflammation markers that damage tissue. SARS-CoV-2 infection distorts the immune response towards a highly inflammatory phenotype. Restoring the effector functions of NK cells has the potential to correct the delicate immune balance needed to effectively overcome SARS-CoV-2 infection.

由SARS-CoV-2引起的大流行造成了可怕的健康破坏,对全球范围内社区的经济、社会和政治活动产生了深远的有害后果。世界科学界作出了非凡的努力,他们团结一致,分享知识,以便能够迅速生产出有效的疫苗。然而,在达到群体免疫之前,研究可以降低风险的治疗方法仍然很重要,这在全球范围内仍需要一段难以预测的时间。另一方面,已获批准的疫苗所保证的免疫时间仍不确定。目前的研究提出了一种治疗方法,其基础在于先天免疫可能发挥的重要作用,通过防止疾病进展到可能最终导致患者死亡的急性期。我们的重点是自然杀伤(NK)细胞及其相关作用。nk被认为是抵抗病毒感染细胞的初级防御淋巴细胞。它们在调节免疫系统中起着关键作用。对COVID-19重症患者的初步研究表明,NK细胞的数量和功能减少,导致感染和活化细胞的清除减少,炎症标志物不受控制地升高,从而损害组织。SARS-CoV-2感染扭曲了免疫反应,导致高度炎症表型。恢复NK细胞的效应功能有可能纠正有效克服SARS-CoV-2感染所需的微妙免疫平衡。
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引用次数: 2
Intransigent vs. volatile opinions in a kinetic epidemic model with imitation game dynamics. 带有模仿博弈动力学的流行病动力学模型中的不妥协与易变意见。
IF 1.1 4区 数学 Q2 Medicine Pub Date : 2023-06-14 DOI: 10.1093/imammb/dqac018
Rossella Della Marca, Nadia Loy, Marco Menale

In the mathematical epidemiology community, there is an increasing interest in shaping the complex interplay between human behaviour and disease spreading. We give a contribution in this direction by illustrating a method to derive behavioural change epidemic models from a stochastic particle description by the means of kinetic equations. We consider a susceptible-infected-removed-like model where contact rates depend on the behavioural patterns adopted across the population. The selection of the social behaviour happens during the interactions between individuals adopting alternative strategies and it is driven by an imitation game dynamics. Agents have a double microscopic state: a discrete label, which denotes the epidemiological compartment to which they belong, and the degree of flexibility of opinion, i.e. a measure of the personal attitude to change opinion and, hence, to switch between the alternative social contact patterns. We derive kinetic evolution equations for the distribution functions of the degree of flexibility of opinion of the individuals for each compartment, whence we obtain macroscopic equations for the densities and average flexibilities of opinion. After providing the basic properties of the macroscopic model, we numerically investigate it by focusing on the impact of the flexibility of opinion on the epidemic course and on the consequent behavioural responses.

在数学流行病学领域,人们对塑造人类行为与疾病传播之间复杂的相互作用越来越感兴趣。我们在这个方向上做出了贡献,说明了一种方法,通过动力学方程从随机粒子描述中推导出行为变化流行病模型。我们考虑一个易感-感染-移除的模型,其中接触率取决于整个人群采用的行为模式。社会行为的选择发生在个体间采取不同策略的互动过程中,它是由模仿博弈动力学驱动的。行为主体具有双重微观状态:一个离散的标签,表示他们所属的流行病学分区,以及意见的灵活性程度,即衡量个人改变意见的态度,从而在不同的社会联系模式之间切换。我们推导了每个隔间的个体意见灵活性的分布函数的动力学演化方程,由此我们得到了密度和平均意见灵活性的宏观方程。在提供宏观模型的基本属性后,我们通过关注舆论灵活性对流行病过程和随之而来的行为反应的影响来对其进行数值研究。
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引用次数: 6
Mal de Debarquement Syndrome explained by a vestibulo-cerebellar oscillator. Debarquement综合征由前庭-小脑振荡器解释。
IF 1.1 4区 数学 Q2 Medicine Pub Date : 2023-03-13 DOI: 10.1093/imammb/dqac016
Bruno Burlando, Viviana Mucci, Cherylea J Browne, Serena Losacco, Iole Indovina, Lucio Marinelli, Franco Blanchini, Giulia Giordano

Mal de Debarquement Syndrome (MdDS) is a puzzling central vestibular disorder characterized by a long-lasting perception of oscillatory postural instability that may occur after sea travels or flights. We have postulated that MdDS originates from the post-disembarking persistence of an adaptive internal oscillator consisting of a loop system, involving the right and left vestibular nuclei, and the Purkinje cells of the right and left flocculonodular cerebellar cortex, connected by GABAergic and glutamatergic fibers. We have formulated here a mathematical model of the vestibulo-cerebellar loop system and carried out a computational analysis based on a set of differential equations describing the interactions among the loop elements and containing Hill functions that model input-output firing rates relationships among neurons. The analysis indicates that the system acquires a spontaneous and permanent oscillatory behavior for a decrease of threshold and an increase of sensitivity in neuronal input-output responses. These results suggest a role for synaptic plasticity in MdDS pathophysiology, thus reinforcing our previous hypothesis that MdDS may be the result of excessive synaptic plasticity acting on the vestibulo-cerebellar network during its entraining to an oscillatory environment. Hence, our study points to neuroendocrine pathways that lead to increased synaptic response as possible new therapeutic targets for the clinical treatment of the disorder.

脱机综合症(MdDS)是一种令人困惑的中枢前庭疾病,其特征是在海上旅行或飞行后可能出现持久的振荡姿势不稳定的感觉。我们假设MdDS起源于一个由循环系统组成的自适应内部振荡器,该系统涉及左右前庭核和左右小脑小叶结节皮质的浦肯野细胞,由gaba能和谷氨酸能纤维连接。我们在此建立了前庭-小脑回路系统的数学模型,并基于一组描述回路元素之间相互作用的微分方程进行了计算分析,该微分方程包含模拟神经元之间输入-输出放电率关系的Hill函数。分析表明,由于阈值的降低和神经元输入输出响应的灵敏度的增加,系统获得了自发的永久振荡行为。这些结果表明突触可塑性在MdDS的病理生理中起作用,从而加强了我们之前的假设,即MdDS可能是前庭-小脑网络在振荡环境中受到过度突触可塑性作用的结果。因此,我们的研究指出,导致突触反应增加的神经内分泌通路可能是临床治疗该疾病的新治疗靶点。
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引用次数: 1
Solute transport with Michaelis-Menten kinetics for in vitro cell culture. 体外细胞培养中溶质运输的Michaelis-Menten动力学。
IF 1.1 4区 数学 Q2 Medicine Pub Date : 2023-03-13 DOI: 10.1093/imammb/dqac014
Lauren Hyndman, Sean McKee, Sean McGinty

A traditional method of in vitro cell culture involves a monolayer of cells at the base of a petri dish filled with culture medium. While the primary role of the culture medium is to supply nutrients to the cells, drug or other solutes may be added, depending on the purpose of the experiment. Metabolism by cells of oxygen, nutrients and drug is typically governed by Michaelis-Menten (M-M) kinetics. In this paper, a mathematical model of solute transport with M-M kinetics is developed. Upon non-dimensionalization, the reaction/diffusion system is re-characterized in terms of Volterra integral equations, where a parameter $beta $, the ratio of the initial solute concentration to the M-M constant, proves important: $beta ll 1$ is relevant to drug metabolism for the liver, whereas $beta gg 1$ is more appropriate in the case of oxygen metabolism. Regular perturbation expansions for both cases are obtained. A small-time expansion and steady-state solution are also presented. All results are compared against the numerical solution of the Volterra integral equations, and excellent agreement is found. The utility of the model and analytical solutions are discussed in the context of assisting experimental researchers to better understand the environment within in vitro cell culture experiments.

传统的体外细胞培养方法是在充满培养基的培养皿底部放置一层细胞。培养基的主要作用是为细胞提供营养,但根据实验目的,也可以添加药物或其他溶质。细胞对氧气、营养物质和药物的代谢通常受米切里斯-门腾(M-M)动力学控制。本文建立了溶质输运的M-M动力学数学模型。在非量纲化的情况下,反应/扩散系统用Volterra积分方程重新表征,其中参数$beta $,即初始溶质浓度与M-M常数的比值,证明是重要的:$beta ll 1$与肝脏的药物代谢有关,而$beta gg 1$更适合于氧代谢的情况。得到了这两种情况的正则摄动展开式。给出了小时间展开式和稳态解。所有结果都与Volterra积分方程的数值解进行了比较,结果非常吻合。在帮助实验研究人员更好地了解体外细胞培养实验环境的背景下,讨论了模型和分析解决方案的实用性。
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引用次数: 0
Mathematical modeling and investigation on the role of demography and contact patterns in social distancing measures effectiveness in COVID-19 dissemination. 人口和接触方式对社会距离措施在COVID-19传播中的作用的数学建模和调查。
IF 1.1 4区 数学 Q2 Medicine Pub Date : 2023-03-13 DOI: 10.1093/imammb/dqac015
Marco A Ridenti, Lara K Teles, Alexandre Maranhão, Vladimir K Teles

In this article, we investigate the importance of demography and contact patterns in determining the spread of COVID-19 and to the effectiveness of social distancing policies. We investigate these questions proposing an augmented epidemiological model with an age-structured model, with the population divided into susceptible (S), exposed (E), asymptomatic infectious (A), hospitalized (H), symptomatic infectious (I) and recovered individuals (R), to simulate COVID-19 dissemination. The simulations were carried out using six combinations of four types of isolation policies (work restrictions, isolation of the elderly, community distancing and school closures) and four representative fictitious countries generated over alternative demographic transition stage patterns (aged developed, developed, developing and least developed countries). We concluded that the basic reproduction number depends on the age profile and the contact patterns. The aged developed country had the lowest basic reproduction number ($R0=1.74$) due to the low contact rate among individuals, followed by the least developed country ($R0=2.00$), the developing country ($R0=2.43$) and the developed country ($R0=2.64$). Because of these differences in the basic reproduction numbers, the same intervention policies had higher efficiencies in the aged and least developed countries. Of all intervention policies, the reduction in work contacts and community distancing were the ones that produced the highest decrease in the $R0$ value, prevalence, maximum hospitalization demand and fatality rate. The isolation of the elderly was more effective in the developed and aged developed countries. The school closure was the less effective intervention policy, though its effects were not negligible in the least developed and developing countries.

在本文中,我们研究了人口统计学和接触模式在确定COVID-19传播和社会距离政策有效性方面的重要性。为了研究这些问题,我们提出了一个年龄结构模型的增强流行病学模型,将人群分为易感人群(S)、暴露人群(E)、无症状感染者(A)、住院患者(H)、有症状感染者(I)和康复个体(R),以模拟COVID-19的传播。模拟采用四种隔离政策(工作限制、隔离老年人、保持社区距离和关闭学校)的六种组合,以及根据不同的人口过渡阶段模式(老龄发达国家、发达国家、发展中国家和最不发达国家)产生的四个具有代表性的虚构国家。我们的结论是,基本繁殖数取决于年龄分布和接触方式。高龄发达国家由于个体间接触率低,基本繁殖数最低($R0=1.74$),其次是最不发达国家($R0=2.00$)、发展中国家($R0=2.43$)和发达国家($R0=2.64$)。由于基本再生产数字的这些差异,同样的干预政策在老龄国家和最不发达国家效率更高。在所有干预政策中,减少工作接触和社区距离是在R0$值、患病率、最大住院需求和死亡率方面产生最大降幅的政策。老年人隔离在发达国家和老龄发达国家更为有效。关闭学校是效果较差的干预政策,尽管其影响在最不发达国家和发展中国家不可忽视。
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引用次数: 0
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