Mathematical Medicine and Biology-A Journal of the Ima最新文献_第6页

A mathematical model of HIV dynamics treated with a population of gene-edited haematopoietic progenitor cells exhibiting threshold phenomenon. 具有阈值现象的基因编辑的造血祖细胞群体处理HIV动力学的数学模型。

IF 1.1 4区数学

Mathematical Medicine and Biology-A Journal of the Ima Pub Date : 2020-05-29 DOI: 10.1093/imammb/dqz011

Vardayani Ratti, Seema Nanda, Susan K Eszterhas, Alexandra L Howell, Dorothy I Wallace

{"title":"A mathematical model of HIV dynamics treated with a population of gene-edited haematopoietic progenitor cells exhibiting threshold phenomenon.","authors":"Vardayani Ratti, Seema Nanda, Susan K Eszterhas, Alexandra L Howell, Dorothy I Wallace","doi":"10.1093/imammb/dqz011","DOIUrl":"https://doi.org/10.1093/imammb/dqz011","url":null,"abstract":"The use of gene-editing technology has the potential to excise the CCR5 gene from haematopoietic progenitor cells, rendering their differentiated CD4-positive (CD4+) T cell descendants HIV resistant. In this manuscript, we describe the development of a mathematical model to mimic the therapeutic potential of gene editing of haematopoietic progenitor cells to produce a class of HIV-resistant CD4+ T cells. We define the requirements for the permanent suppression of viral infection using gene editing as a novel therapeutic approach. We develop non-linear ordinary differential equation models to replicate HIV production in an infected host, incorporating the most appropriate aspects found in the many existing clinical models of HIV infection, and extend this model to include compartments representing HIV-resistant immune cells. Through an analysis of model equilibria and stability and computation of $R_0$ for both treated and untreated infections, we show that the proposed therapy has the potential to suppress HIV infection indefinitely and return CD4+ T cell counts to normal levels. A computational study for this treatment shows the potential for a successful 'functional cure' of HIV. A sensitivity analysis illustrates the consistency of numerical results with theoretical results and highlights the parameters requiring better biological justification. Simulations of varying level production of HIV-resistant CD4+ T cells and varying immune enhancements as the result of these indicate a clear threshold response of the model and a range of treatment parameters resulting in a return to normal CD4+ T cell counts.","PeriodicalId":49863,"journal":{"name":"Mathematical Medicine and Biology-A Journal of the Ima","volume":"37 2","pages":"212-242"},"PeriodicalIF":1.1,"publicationDate":"2020-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqz011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37383420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Impact of ART-induced viral suppression on the HIV epidemic in Italy. art诱导的病毒抑制对意大利艾滋病毒流行的影响。

IF 1.1 4区数学

Mathematical Medicine and Biology-A Journal of the Ima Pub Date : 2020-05-29 DOI: 10.1093/imammb/dqz010

Federico Papa, Giovanni Felici, Marco Franzetti, Alberto Gandolfi, Carmela Sinisgalli

{"title":"Impact of ART-induced viral suppression on the HIV epidemic in Italy.","authors":"Federico Papa, Giovanni Felici, Marco Franzetti, Alberto Gandolfi, Carmela Sinisgalli","doi":"10.1093/imammb/dqz010","DOIUrl":"https://doi.org/10.1093/imammb/dqz010","url":null,"abstract":"The present study aims to clarify the role of the fraction of patients under antiretroviral therapy (ART) achieving viral suppression (VS) (i.e. having plasma viral load below the detectability threshold) on the human immunodeficiency virus (HIV) epidemic in Italy. Based on the hypothesis that VS makes the virus untransmittable, we extend a previous model and we develop a time-varying ordinary differential equation model with immigration and treatment, where the naive and non-naive populations of infected are distinguished, and different compartments account for treated subjects virally suppressed and not suppressed. Moreover, naive and non-naive individuals with acquired immune deficiency syndrome (AIDS) are considered separately. Clinical data stored in the nationwide database Antiviral Response Cohort Analysis are used to reconstruct the history of the fraction of virally suppressed patients since highly active ART introduction, as well as to assess some model parameters. Other parameters are set according to the literature and the final model calibration is obtained by fitting epidemic data over the years 2003-2015. Predictions on the evolution of the HIV epidemic up to the end of 2035 are made assuming different future trends of the fraction of virally suppressed patients and different eligibility criteria for treatment. Increasing the VS fraction is found to reduce the incidence, the new cases of AIDS and the deaths from AIDS per year, especially in combination with early ART initiation. The asymptotic properties of a time-invariant formulation of the model are studied, and the existence and global asymptotic stability of a unique positive equilibrium are proved.","PeriodicalId":49863,"journal":{"name":"Mathematical Medicine and Biology-A Journal of the Ima","volume":"37 2","pages":"183-211"},"PeriodicalIF":1.1,"publicationDate":"2020-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqz010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37303377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

A structured model for COVID-19 spread: modelling age and healthcare inequities 新冠肺炎传播的结构化模型：年龄和医疗不平等模型

IF 1.1 4区数学

Mathematical Medicine and Biology-A Journal of the Ima Pub Date : 2020-05-21 DOI: 10.1101/2020.05.17.20104976

A. James, M. Plank, Rachelle N. Binny, K. Hannah, S. Hendy, Audrey Lustig, N. Steyn

{"title":"A structured model for COVID-19 spread: modelling age and healthcare inequities","authors":"A. James, M. Plank, Rachelle N. Binny, K. Hannah, S. Hendy, Audrey Lustig, N. Steyn","doi":"10.1101/2020.05.17.20104976","DOIUrl":"https://doi.org/10.1101/2020.05.17.20104976","url":null,"abstract":"We use stochastic branching process model, structured by age and level of healthcare access, to look at the heterogeneous spread of COVID-19 within a population. We examine the effect of control scenarios targeted at particular groups, such as school closures or social distancing by older people. Although we currently lack detailed empirical data about contact and infection rates between different age groups and groups with different levels of healthcare access within New Zealand, these scenarios illustrate how such evidence could be used to inform specific interventions. We find that an increase in the transmission rates amongst children as a result of reopening schools is, on its own, unlikely to significantly increase the number of cases. However, if this is accompanied by a change in adult behaviour, for example increased contact rates among parents, it could have a much bigger effect. We also find that there is a risk of undetected outbreaks occurring in communities that have low access to healthcare and that are socially isolated from more privileged communities. The greater the inequity and the greater the degree of social segregation, the longer it will take before any outbreaks are detected. Well-established evidence for health inequities, particularly in accessing primary healthcare and testing, indicates that M[a]ori and Pacific peoples are at higher risk of undetected outbreaks in Aotearoa New Zealand. This highlights the importance of ensuring that community needs for access to healthcare, including early proactive testing, rapid contact tracing, and the ability to isolate, are being met equitably. Finally, these scenarios illustrate how information concerning contact and infection rates across different demographic groups may be useful in informing specific policy interventions.","PeriodicalId":49863,"journal":{"name":"Mathematical Medicine and Biology-A Journal of the Ima","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2020-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49033124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 16

OUP accepted manuscript OUP接受稿件

IF 1.1 4区数学

Mathematical Medicine and Biology-A Journal of the Ima Pub Date : 2020-01-01 DOI: 10.1093/imammb/dqaa004

引用次数: 0

An implicit discontinuous Galerkin method for modeling acute edema and resuscitation in the small intestine. 一种模拟小肠急性水肿和复苏的隐式间断伽辽金方法。

IF 1.1 4区数学

Mathematical Medicine and Biology-A Journal of the Ima Pub Date : 2019-12-04 DOI: 10.1093/imammb/dqz001

Travis B Thompson, Beatrice M Riviere, Matthew G Knepley

{"title":"An implicit discontinuous Galerkin method for modeling acute edema and resuscitation in the small intestine.","authors":"Travis B Thompson, Beatrice M Riviere, Matthew G Knepley","doi":"10.1093/imammb/dqz001","DOIUrl":"https://doi.org/10.1093/imammb/dqz001","url":null,"abstract":"Edema, also termed oedema, is a generalized medical condition associated with an abnormal aggregation of fluid in a tissue matrix. In the intestine, excessive edema can lead to serious health complications associated with reduced motility. A $7.5%$ solution of hypertonic saline (HS) has been hypothesized as an effective means to reduce the effects of edema following surgery or injury. However, detailed clinical edema experiments can be difficult to implement, or costly, in practice. In this manuscript we introduce an implicit in time discontinuous Galerkin method with novel adaptations for modeling edema in the 3D layered physiology of the intestine. The model improves over early work via inclusion of the tissue intrinsic storage coefficient, and the effects of Starling overestimation for high venous pressures. Validation against a recent clinical experiment in HS resuscitation of acute edema is presented; the results support the clinical hypothesis that 7.5% HS solution may be effective in the resuscitation of acute edema formation. New results include an improved view into the effects of resuscitation on the hydrostatic pressure profile of edematous rats, effects on lumenal volume attenuation, relative fluid gain and an estimation of the impacts of both acute edema and resuscitation on intestinal motility.","PeriodicalId":49863,"journal":{"name":"Mathematical Medicine and Biology-A Journal of the Ima","volume":"36 4","pages":"513-548"},"PeriodicalIF":1.1,"publicationDate":"2019-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqz001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36979057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Analytic solutions for calcium ion fertilisation waves on the surface of eggs. 卵表面钙离子受精波的解析解。

IF 1.1 4区数学

Mathematical Medicine and Biology-A Journal of the Ima Pub Date : 2019-12-04 DOI: 10.1093/imammb/dqz002

Bronwyn H Bradshaw-Hajek, Philip Broadbridge

引用次数: 7

Stability and Hopf bifurcation analysis of lac Operon model with distributed delay and nonlinear degradation rate. 具有分布延迟和非线性退化率的lac操纵子模型的稳定性和Hopf分岔分析。

IF 1.1 4区数学

Mathematical Medicine and Biology-A Journal of the Ima Pub Date : 2019-12-04 DOI: 10.1093/imammb/dqy018

Zenab Alrikaby

引用次数: 3

Emergent three-dimensional sperm motility: coupling calcium dynamics and preferred curvature in a Kirchhoff rod model. 涌现的三维精子运动:耦合钙动力学和Kirchhoff棒模型中的首选曲率。

IF 1.1 4区数学

Mathematical Medicine and Biology-A Journal of the Ima Pub Date : 2019-12-04 DOI: 10.1093/imammb/dqy015

Lucia Carichino, Sarah D Olson

{"title":"Emergent three-dimensional sperm motility: coupling calcium dynamics and preferred curvature in a Kirchhoff rod model.","authors":"Lucia Carichino, Sarah D Olson","doi":"10.1093/imammb/dqy015","DOIUrl":"https://doi.org/10.1093/imammb/dqy015","url":null,"abstract":"Changes in calcium concentration along the sperm flagellum regulate sperm motility and hyperactivation, characterized by an increased flagellar bend amplitude and beat asymmetry, enabling the sperm to reach and penetrate the ovum (egg). The signalling pathways by which calcium increases within the flagellum are well established. However, the exact mechanisms of how calcium regulates flagellar bending are still under investigation. We extend our previous model of planar flagellar bending by developing a fluid-structure interaction model that couples the 3D motion of the flagellum in a viscous Newtonian fluid with the evolving calcium concentration. The flagellum is modelled as a Kirchhoff rod: an elastic rod with preferred curvature and twist. The calcium dynamics are represented as a 1D reaction-diffusion model on a moving domain, the flagellum. The two models are coupled assuming that the preferred curvature and twist of the sperm flagellum depend on the local calcium concentration. To investigate the effect of calcium on sperm motility, we compare model results of flagellar bend amplitude and swimming speed for three cases: planar, helical (spiral with equal amplitude in both directions), and quasi-planar (spiral with small amplitude in one direction). We observe that for the same parameters, the planar swimmer is faster and a turning motion is more clearly observed when calcium coupling is accounted for in the model. In the case of flagellar bending coupled to the calcium concentration, we observe emergent trajectories that can be characterized as a hypotrochoid for both quasi-planar and helical bending.","PeriodicalId":49863,"journal":{"name":"Mathematical Medicine and Biology-A Journal of the Ima","volume":"36 4","pages":"439-469"},"PeriodicalIF":1.1,"publicationDate":"2019-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqy015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36588681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

A mathematical model of white blood cell dynamics during maintenance therapy of childhood acute lymphoblastic leukemia. 儿童急性淋巴细胞白血病维持治疗期间白细胞动力学的数学模型。

IF 1.1 4区数学

Mathematical Medicine and Biology-A Journal of the Ima Pub Date : 2019-12-04 DOI: 10.1093/imammb/dqy017

Thuy T T Le, Felix Jost, Thomas Raupach, Jakob Zierk, Manfred Rauh, Meinolf Suttorp, Martin Stanulla, Markus Metzler, Sebastian Sager

引用次数: 7

A simple mathematical model to describe antibody-dependent enhancement in heterologous secondary infection in dengue. 描述登革热异源继发感染中抗体依赖性增强的简单数学模型。

IF 1.1 4区数学

Mathematical Medicine and Biology-A Journal of the Ima Pub Date : 2019-12-04 DOI: 10.1093/imammb/dqy016

Miller Cerón Gómez, Hyun Mo Yang

引用次数: 21