{"title":"Which airways should we treat? Structure-function relationships and estimation of the singular input modes from the forward model alone.","authors":"Graham M Donovan","doi":"10.1093/imammb/dqad006","DOIUrl":"10.1093/imammb/dqad006","url":null,"abstract":"<p><p>Structure-function relationships occur throughout the sciences. Motivated by optimization of such systems, we develop a framework for estimating the input modes from the singular value decomposition from the action of the forward operator alone. These can then be used to determine the input (structure) changes, which induce the largest output (function) changes. The accuracy of the estimate is determined by reference to the method of snapshots. The proposed method is demonstrated on several example problems, and finally used to approximate the optimal airway treatment set for a problem in respiratory physiology.</p>","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":" ","pages":"291-307"},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41167354","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}
Jacob M Jepson, Reuben D O'Dea, John Billingham, Nabil T Fadai
{"title":"Pattern formation and travelling waves in a multiphase moving boundary model of tumour growth.","authors":"Jacob M Jepson, Reuben D O'Dea, John Billingham, Nabil T Fadai","doi":"10.1093/imammb/dqad008","DOIUrl":"10.1093/imammb/dqad008","url":null,"abstract":"<p><p>We employ the multiphase, moving boundary model of Byrne et al. (2003, Appl. Math. Lett., 16, 567-573) that describes the evolution of a motile, viscous tumour cell phase and an inviscid extracellular liquid phase. This model comprises two partial differential equations that govern the cell volume fraction and the cell velocity, together with a moving boundary condition for the tumour edge, and here we characterize and analyse its travelling-wave and pattern-forming behaviour. Numerical simulations of the model indicate that patterned solutions can be obtained, which correspond to multiple regions of high cell density separated by regions of low cell density. In other parameter regimes, solutions of the model can develop into a forward- or backward-moving travelling wave, corresponding to tumour growth or extinction, respectively. A travelling-wave analysis allows us to find the corresponding wave speed, as well as criteria for the growth or extinction of the tumour. Furthermore, a stability analysis of these travelling-wave solutions provides us with criteria for the occurrence of patterned solutions. Finally, we discuss how the initial cell distribution, as well as parameters related to cellular motion and cell-liquid drag, control the qualitative features of patterned solutions.</p>","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":" ","pages":"327-347"},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138300845","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}
Matthew G Doyle;Marina Chugunova;S Lucy Roche;James P Keener
{"title":"Lumped parameter models for two-ventricle and healthy and failing extracardiac Fontan circulations","authors":"Matthew G Doyle;Marina Chugunova;S Lucy Roche;James P Keener","doi":"10.1093/imammb/dqab012","DOIUrl":"10.1093/imammb/dqab012","url":null,"abstract":"Fontan circulations are surgical strategies to treat infants born with single ventricle physiology. Clinical and mathematical definitions of Fontan failure are lacking, and understanding is needed of parameters indicative of declining physiologies. Our objective is to develop lumped parameter models of two-ventricle and single-ventricle circulations. These models, their mathematical formulations and a proof of existence of periodic solutions are presented. Sensitivity analyses are performed to identify key parameters. Systemic venous and systolic left ventricular compliances and systemic capillary and pulmonary venous resistances are identified as key parameters. Our models serve as a framework to study the differences between two-ventricle and single-ventricle physiologies and healthy and failing Fontan circulations.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 4","pages":"442-466"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39426912","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":"Synchronization in epidemic growth and the impossibility of selective containment","authors":"Jan C Budich;Emil J Bergholtz","doi":"10.1093/imammb/dqab013","DOIUrl":"10.1093/imammb/dqab013","url":null,"abstract":"Containment, aiming to prevent the epidemic stage of community-spreading altogether, and mitigation, aiming to merely ‘flatten the curve’ of a wide-ranged outbreak, constitute two qualitatively different approaches to combating an epidemic through non-pharmaceutical interventions. Here, we study a simple model of epidemic dynamics separating the population into two groups, namely a low-risk group and a high-risk group, for which different strategies are pursued. Due to synchronization effects, we find that maintaining a slower epidemic growth behaviour for the high-risk group is unstable against any finite coupling between the two groups. More precisely, the density of infected individuals in the two groups qualitatively evolves very similarly, apart from a small time delay and an overall scaling factor quantifying the coupling between the groups. Hence, selective containment of the epidemic in a targeted (high-risk) group is practically impossible whenever the surrounding society implements a mitigated community-spreading. We relate our general findings to the ongoing COVID-19 pandemic.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 4","pages":"467-473"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=9686632","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39555501","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}
Ada J Ellingsrud;Nicolas Boullé;Patrick E Farrell;Marie E Rognes
{"title":"Accurate numerical simulation of electrodiffusion and water movement in brain tissue","authors":"Ada J Ellingsrud;Nicolas Boullé;Patrick E Farrell;Marie E Rognes","doi":"10.1093/imammb/dqab016","DOIUrl":"10.1093/imammb/dqab016","url":null,"abstract":"Mathematical modelling of ionic electrodiffusion and water movement is emerging as a powerful avenue of investigation to provide a new physiological insight into brain homeostasis. However, in order to provide solid answers and resolve controversies, the accuracy of the predictions is essential. Ionic electrodiffusion models typically comprise non-trivial systems of non-linear and highly coupled partial and ordinary differential equations that govern phenomena on disparate time scales. Here, we study numerical challenges related to approximating these systems. We consider a homogenized model for electrodiffusion and osmosis in brain tissue and present and evaluate different associated finite element-based splitting schemes in terms of their numerical properties, including accuracy, convergence and computational efficiency for both idealized scenarios and for the physiologically relevant setting of cortical spreading depression (CSD). We find that the schemes display optimal convergence rates in space for problems with smooth manufactured solutions. However, the physiological CSD setting is challenging: we find that the accurate computation of CSD wave characteristics (wave speed and wave width) requires a very fine spatial and fine temporal resolution.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 4","pages":"516-551"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ieeexplore.ieee.org/iel7/8016811/9686629/09686655.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39743841","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":"Diffusion of dermatological irritant in drying laundered cloth","authors":"P Broadbridge;B S Tilley","doi":"10.1093/imammb/dqab014","DOIUrl":"10.1093/imammb/dqab014","url":null,"abstract":"Sodium dodecyl sulphate (SDS), a commonly used laundry surfactant, has been known to cause some damage to epithelial cells in skin. Further, independent experiments have shown that a single laundry wash with rinsing leaves a residue of around 10% of the chemicals used in a wash cycle. A realistic nonlinear system of partial differential equations is developed for coupled water and solute transport through a drying porous medium when the solute has a mobile state (monomers) as well as an immobile state (micelles). An accurate finite difference scheme is developed and tested against known exact solutions of the nonlinear porous medium equation for transport of water and against known conservation laws. It shows that at the end of atmosphere-controlled stage 1 of drying when little water remains, the concentration of SDS near the drying surface, where it may contact skin, is commonly an order of magnitude higher than its initial value. The problem is exacerbated by successive regular wash cycles and by higher evaporation rates in electronic dryers. The numerical solutions show the partitioning between the two phases of SDS.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 4","pages":"474-489"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39569600","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}
D E Andreev;P V Baranov;A Milogorodskii;D Rachinskii
{"title":"A deterministic model for non-monotone relationship between translation of upstream and downstream open reading frames","authors":"D E Andreev;P V Baranov;A Milogorodskii;D Rachinskii","doi":"10.1093/imammb/dqab015","DOIUrl":"10.1093/imammb/dqab015","url":null,"abstract":"Totally asymmetric simple exclusion process (TASEP) modelling was shown to offer a parsimonious explanation for the experimentally confirmed ability of a single upstream open reading frames (uORFs) to upregulate downstream translation during the integrated stress response. As revealed by numerical simulations, the model predicts that reducing the density of scanning ribosomes upstream of certain uORFs increases the flow of ribosomes downstream. To gain a better insight into the mechanism which ensures the non-monotone relation between the upstream and downstream flows, in this work, we propose a phenomenological deterministic model approximating the TASEP model of the translation process. We establish the existence of a stationary solution featuring the decreasing density along the uORF for the deterministic model. Further, we find an explicit non-monotone relation between the upstream ribosome density and the downstream flow for the stationary solution in the limit of increasing uORF length and increasingly leaky initiation. The stationary distribution of the TASEP model, the stationary solution of the deterministic model and the explicit limit are compared numerically.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 4","pages":"490-515"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39576651","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}
Laura D'Orsi;Luciano Curcio;Fabio Cibella;Alessandro Borri;Lilach Gavish;Arik Eisenkraft;Andrea De Gaetano
{"title":"A mathematical model of cardiovascular dynamics for the diagnosis and prognosis of hemorrhagic shock","authors":"Laura D'Orsi;Luciano Curcio;Fabio Cibella;Alessandro Borri;Lilach Gavish;Arik Eisenkraft;Andrea De Gaetano","doi":"10.1093/imammb/dqab011","DOIUrl":"10.1093/imammb/dqab011","url":null,"abstract":"A variety of mathematical models of the cardiovascular system have been suggested over several years in order to describe the time-course of a series of physiological variables (i.e. heart rate, cardiac output, arterial pressure) relevant for the compensation mechanisms to perturbations, such as severe haemorrhage. The current study provides a simple but realistic mathematical description of cardiovascular dynamics that may be useful in the assessment and prognosis of hemorrhagic shock. The present work proposes a first version of a differential-algebraic equations model, the model dynamical ODE model for haemorrhage (dODEg). The model consists of 10 differential and 14 algebraic equations, incorporating 61 model parameters. This model is capable of replicating the changes in heart rate, mean arterial pressure and cardiac output after the onset of bleeding observed in four experimental animal preparations and fits well to the experimental data. By predicting the time-course of the physiological response after haemorrhage, the dODEg model presented here may be of significant value for the quantitative assessment of conventional or novel therapeutic regimens. The model may be applied to the prediction of survivability and to the determination of the urgency of evacuation towards definitive surgical treatment in the operational setting.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 4","pages":"417-441"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39416172","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":"Classification under uncertainty: data analysis for diagnostic antibody testing","authors":"Paul N Patrone;Anthony J Kearsley","doi":"10.1093/imammb/dqab007","DOIUrl":"10.1093/imammb/dqab007","url":null,"abstract":"Formulating accurate and robust classification strategies is a key challenge of developing diagnostic and antibody tests. Methods that do not explicitly account for disease prevalence and uncertainty therein can lead to significant classification errors. We present a novel method that leverages optimal decision theory to address this problem. As a preliminary step, we develop an analysis that uses an assumed prevalence and conditional probability models of diagnostic measurement outcomes to define optimal (in the sense of minimizing rates of false positives and false negatives) classification domains. Critically, we demonstrate how this strategy can be generalized to a setting in which the prevalence is unknown by either (i) defining a third class of hold-out samples that require further testing or (ii) using an adaptive algorithm to estimate prevalence prior to defining classification domains. We also provide examples for a recently published SARS-CoV-2 serology test and discuss how measurement uncertainty (e.g. associated with instrumentation) can be incorporated into the analysis. We find that our new strategy decreases classification error by up to a decade relative to more traditional methods based on confidence intervals. Moreover, it establishes a theoretical foundation for generalizing techniques such as receiver operating characteristics by connecting them to the broader field of optimization.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 3","pages":"396-416"},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ieeexplore.ieee.org/iel7/8016811/9579095/09579102.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39307448","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":"Mathematical modelling of ageing acceleration of the human follicle due to oxidative stress and other factors","authors":"A M Portillo;C Peláez","doi":"10.1093/imammb/dqab004","DOIUrl":"10.1093/imammb/dqab004","url":null,"abstract":"There is a gradual telomere shortening due to the inability of the replication machinery to copy the very ends of chromosomes. Additionally, other factors such as high levels of oxidation (free radicals or reactive oxygen species (ROS)), e.g. due to cumulated stress, inflammation or tobacco smoke, accelerate telomere shortening. In humans, the average telomere length is about 10–15 kb at birth and telomeres shorten at a pace of 70 bp per year. However, when cells are exposed to ROS, telomere attrition happens at a faster pace, generating a wide variety of telomere size distribution in different length percentiles, which are different to what is expected just by age. In this work, the generational age of a cell is associated with its telomere length (TL), from certain maximum to the minimal TL that allows replication. In order to study the accumulation of aged granulosa cells in human follicles, from preantral to preovulatory size, a mathematical model is proposed, regarding different degrees of accelerated telomere shortening, which reflect the action of ROS in addition to the telomere shortening that happens after cell division. In cases of cells with TL shorter than cells with average TL, with low telomerase activity and accelerated telomere shortening, the mathematical model predicts an aged outcome in preovulatory follicles. The model provides a plausible explanation for what has been observed in oocytes from older women, which have been exposed to ROS for a longer period of time and have bad outcomes after in vitro fertilization.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 3","pages":"273-291"},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqab004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25532334","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}