Mathematical medicine and biology : a journal of the IMA最新文献

{"title":"A coupled non-Fickian model of a cardiovascular drug delivery system","authors":"J. A. Ferreira;J. Naghipoor;Paula de Oliveira","doi":"10.1093/imammb/dqv023","DOIUrl":"10.1093/imammb/dqv023","url":null,"abstract":"A coupled non-Fickian model of a cardiovascular drug delivery system using a biodegradable drug-eluting stent is proposed. The numerical results are obtained using an implicit–explicit finite-element method. The influence of vessel stiffness on the transport of drug eluted from the stent is analysed. The results presented in this paper suggest new perspectives to adapt the drug delivery profile to the needs of the patient.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"33 3","pages":"329-357"},"PeriodicalIF":0.0,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqv023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33877873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extreme protraction for low-grade gliomas: theoretical proof of concept of a novel therapeutical strategy","authors":"Victor M. Pérez-García;Luis A. Pérez-Romasanta","doi":"10.1093/imammb/dqv017","DOIUrl":"10.1093/imammb/dqv017","url":null,"abstract":"Grade II gliomas are slowly growing primary brain tumours that affect mostly young patients and become fatal after a variable time period. Current clinical handling includes surgery as first-line treatment. Cytotoxic therapies (radiotherapy RT or chemotherapy QT) are used initially only for patients having a bad prognosis. Therapies are administered following the ‘maximum dose in minimum time’ principle, which is the same schedule used for high-grade brain tumours. Using mathematical models describing the growth of these tumours in response to radiotherapy, we find that an extreme protraction therapeutical strategy, i.e. enlarging substantially the time interval between RT fractions, may lead to better tumour control. Explicit formulas are found providing the optimal spacing between doses in a very good agreement with the simulations of the full 3D mathematical model approximating the tumour spatiotemporal dynamics. This idea, although breaking the well-established paradigm, has biological meaning since, in these slowly growing tumours, it may be more favourable to treat the tumour as the tumour cells leave the quiescent compartment and move into the cell cycle.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"33 3","pages":"253-271"},"PeriodicalIF":0.0,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqv017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33301568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paradox of enrichment and system order reduction: bacteriophages dynamics as case study","authors":"Andrei Korobeinikov;Elena Shchepakina;Vladimir Sobolev","doi":"10.1093/imammb/dqv025","DOIUrl":"10.1093/imammb/dqv025","url":null,"abstract":"The paradox of enrichment in a 3D model for bacteriophage dynamics, with a free infection stage of the phage and a bilinear incident rate, is considered. An application of the technique of singular perturbation theory allows us to demonstrate why the paradox arises in this 3D model despite the fact that it has a bilinear incident rate (while in 2D predator–prey models it is usually associated with the concavity of the attack rate). Our analysis demonstrates that the commonly applied approach of the model order reduction using the so-called quasi-steady-state approximation can lead to a loss of important properties of an original system.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"33 3","pages":"359-369"},"PeriodicalIF":0.0,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqv025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34290366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aggregation and asymptotic analysis of an SI-epidemic model for heterogeneous populations","authors":"V. M. Veliov;A. Widder","doi":"10.1093/imammb/dqv018","DOIUrl":"10.1093/imammb/dqv018","url":null,"abstract":"The paper investigates a version of a simple epidemiological model involving only susceptible and infected individuals, where the heterogeneity of the population with respect to susceptibility/infectiousness is taken into account. A comprehensive analysis of the asymptotic behaviour of the disease is given, based on an explicit aggregation of the model. The results are compared with those of a homogeneous version of the model to highlight the influence of the heterogeneity on the asymptotics. Moreover, the performed analysis reveals in which cases incomplete information about the heterogeneity of the population is sufficient in order to determine the long-run outcome of the disease. Numerical simulation is used to emphasize that, for a given level of prevalence, the evolution of the disease under the influence of heterogeneity may in the long run qualitatively differ from the one ‘predicted’ by the homogeneous model. Furthermore, it is shown that, in a closed population, the indicator for the survival of the population is in the presence of heterogeneity distinct from the basic reproduction number.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"33 3","pages":"295-318"},"PeriodicalIF":0.0,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqv018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33333819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computed tear film and osmolarity dynamics on an eye-shaped domain","authors":"Longfei Li;Richard J. Braun;Tobin A. Driscoll;William D. Henshaw;Jeffrey W. Banks;P. Ewen King-Smith","doi":"10.1093/imammb/dqv013","DOIUrl":"10.1093/imammb/dqv013","url":null,"abstract":"The concentration of ions, or osmolarity, in the tear film is a key variable in understanding dry eye symptoms and disease. In this manuscript, we derive a mathematical model that couples osmolarity (treated as a single solute) and fluid dynamics within the tear film on a 2D eye-shaped domain. The model includes the physical effects of evaporation, surface tension, viscosity, ocular surface wettability, osmolarity, osmosis and tear fluid supply and drainage. The governing system of coupled non-linear partial differential equations is solved using the Overture computational framework, together with a hybrid time-stepping scheme, using a variable step backward differentiation formula and a Runge–Kutta–Chebyshev method that were added to the framework. The results of our numerical simulations provide new insight into the osmolarity distribution over the ocular surface during the interblink.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"33 2","pages":"123-157"},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqv013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33225542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the benefits of antibody immune response in HIV-1 infection using a discrete model","authors":"S. P. Showa;F. Nyabadza;S. D. Hove-Musekwa;G. Magombedze","doi":"10.1093/imammb/dqv014","DOIUrl":"10.1093/imammb/dqv014","url":null,"abstract":"The role of antibodies in HIV-1 infection is investigated using a discrete-time mathematical model that considers cell-free and cell-associated transmission of the virus. Model analysis shows that the effect of each type of antibody is dependent on the stage of the infection. Neutralizing antibodies are efficient in controlling the viral levels in the early days after seroconversion and antibodies that coat HIV-1-infected cells and recruit effector cells to either kill the HIV-1-infected cells or inhibit viral replication are efficient when the infection becomes established. Model simulations show that antibodies that inhibit viral replication are more effective in controlling the infection than those that recruit Natural Killer T cells after infection establishment. The model was fitted to subjects of the Tsedimoso study conducted in Botswana and conclusions similar to elasticity analysis results were obtained. Model fitting results predicted that neutralizing antibodies are more efficient in controlling the viral levels than antibodies that coat HIV-1-infected cells and recruit effector cells to either kill the HIV-1-infected cells or inhibit viral replication in the early days after seroconversion.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"33 2","pages":"189-210"},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqv014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33240226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Back matter","authors":"","doi":"","DOIUrl":"https://doi.org/","url":null,"abstract":"","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"33 2","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ieeexplore.ieee.org/iel7/8016811/8189260/08189267.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50351792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal fractionation in radiotherapy with multiple normal tissues","authors":"Fatemeh Saberian;Archis Ghate;Minsun Kim","doi":"10.1093/imammb/dqv015","DOIUrl":"10.1093/imammb/dqv015","url":null,"abstract":"The goal in radiotherapy is to maximize the biological effect (BE) of radiation on the tumour while limiting its toxic effects on healthy anatomies. Treatment is administered over several sessions to give the normal tissue time to recover as it has better damage-repair capabilities than tumour cells. This is termed fractionation. A key problem in radiotherapy involves finding an optimal number of treatment sessions (fractions) and the corresponding dosing schedule. A major limitation of existing mathematically rigorous work on this problem is that it includes only a single normal tissue. Since essentially no anatomical region of interest includes only one normal tissue, these models may incorrectly identify the optimal number of fractions and the corresponding dosing schedule. We present a formulation of the optimal fractionation problem that includes multiple normal tissues. Our model can tackle any combination of maximum dose, mean dose and dose-volume type constraints for serial and parallel normal tissues as this is characteristic of most treatment protocols. We also allow for a spatially heterogeneous dose distribution within each normal tissue. Furthermore, we do not a priori assume that the doses are invariant across fractions. Finally, our model uses a spatially optimized treatment plan as input and hence can be seamlessly combined with any treatment planning system. Our formulation is a mixed-integer, non-convex, quadratically constrained quadratic programming problem. In order to simplify this computationally challenging problem without loss of optimality, we establish sufficient conditions under which equal-dosage or single-dosage fractionation is optimal. Based on the prevalent estimates of tumour and normal tissue model parameters, these conditions are expected to hold in many types of commonly studied tumours, such as those similar to head-and-neck and prostate cancers. This motivates a simple reformulation of our problem that leads to a closed-form formula for the dose per fraction. We then establish that the tumour-BE is quasiconcave in the number of fractions; this ultimately helps in identifying the optimal number of fractions. We perform extensive numerical experiments using 10 head-and-neck and prostate test cases to uncover several clinically relevant insights.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"33 2","pages":"211-252"},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqv015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33189257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving Bacillus Calmette-Guérin (BCG) immunotherapy for bladder cancer by adding interleukin 2 (IL-2): a mathematical model","authors":"Svetlana Bunimovich-Mendrazitsky;Sarel Halachmi;Natalie Kronik","doi":"10.1093/imammb/dqv007","DOIUrl":"10.1093/imammb/dqv007","url":null,"abstract":"One of the treatments offered to non-invasive bladder cancer patients is BCG instillations, using a well-established, time-honoured protocol. Some of the patients, however, do not respond to this protocol. To examine possible changes in the protocol, we provide a platform for in silico testing of alternative protocols for BCG instillations and combinations with IL-2, to be used by urologists in planning new treatment strategies for subpopulations of bladder cancer patients who may benefit from a personalized protocol. We use a systems biology approach to describe the BCG-tumour-immune interplay and translate it into a set of mathematical differential equations. The variables of the equation set are the number of tumour cells, bacteria cells, immune cells, and cytokines participating in the tumour-immune response. Relevant parameters that describe the system's dynamics are taken from a variety of independent literature, unrelated to the clinical trial results assessed by the model predictions. Model simulations use a clinically relevant range of initial tumour sizes (tumour volume) and tumour growth rates (tumour grade), representative of a virtual population of fifty patients. Our model successfully retrieved previous clinical results for BCG induction treatment and BCG maintenance therapy with a complete response (CR) rate of 82%. Furthermore, we designed alternative maintenance protocols, using IL-2 combinations with BCG, which improved success rates up to 86% and 100% of the patients, albeit without considering possible side effects. We have shown our simulation platform to be reliable by demonstrating its ability to retrieve published clinical trial results. We used this platform to predict the outcome of treatment combinations. Our results suggest that the subpopulation of non-responsive patients may benefit from an intensified combined BCG IL-2 maintenance treatment.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"33 2","pages":"159-188"},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqv007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33229472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Front matter","authors":"","doi":"","DOIUrl":"https://doi.org/","url":null,"abstract":"","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"33 2","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ieeexplore.ieee.org/iel7/8016811/8189260/08189265.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50425688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}