A mathematical model of tumor-immune interactions

A mathematical model of the interactions between a growing tumor and the immune system is presented. The equations and parameters of the model are based on experimental and clinical results from published studies. The model includes the primary cell populations involved in effector T cell mediated tumor killing: regulatory T cells, helper T cells, and dendritic cells. A key feature is the inclusion of multiple mechanisms of immunosuppression through the main cytokines and growth factors mediating the interactions between the cell populations. Decreased access of effector cells to the tumor interior with increasing tumor size is accounted for. The model is applied to tumors with different growth rates and antigenicities to gauge the relative importance of various immunosuppressive mechanisms. The most important factors leading to tumor escape are TGF-induced immunosuppression, conversion of helper T cells into regulatory T cells, and the limitation of immune cell access to the full tumor at large tumor sizes. The results suggest that for a given tumor growth rate, there is an optimal antigenicity maximizing the response of the immune system. Further increases in antigenicity result in increased immunosuppression, and therefore a decrease in tumor killing rate

A Mathematical Model for Cisplatin Cellular Pharmacodynamics

AbstractA simple theoretical model for the cellular pharmacodynamics of cisplatin is presented. The model, which takes into account the kinetics of cisplatin uptake by cells and the intracellular binding of the drug, can be used to predict the dependence of survival (relative to controls) on the time course of extracellular exposure. Cellular pharmacokinetic parameters are derived from uptake data for human ovarian and head and neck cancer cell lines. Survival relative to controls is assumed to depend on the peak concentration of DNA-bound intracellular platinum. Model predictions agree well with published data on cisplatin cytotoxicity for three different cancer cell lines, over a wide range of exposure times. In comparison with previously published mathematical models for anticancer drug pharmacodynamics, the present model provides a better fit to experimental data sets including long exposure times (∼100 hours). The model provides a possible explanation for the fact that cell kill correlates well with area under the extracellular concentration-time curve in some data sets, but not in others. The model may be useful for optimizing delivery schedules and for the dosing of cisplatin for cancer therapy

Two-Mechanism Peak Concentration Model for Cellular Pharmacodynamics of Doxorubicin

AbstractA mathematical model is presented for the cellular uptake and cytotoxicity of the anticancer drug doxorubicin. The model assumes sigmoidal, Hill-type dependence of cell survival on drug-induced damage. Experimental evidence indicates distinct intracellular and extracellular mechanisms of doxorubicin cytotoxicity. Drug-induced damage is therefore expressed as the sum of two terms, representing the peak values over time of concentrations of intracellular and extracellular drugs. Dependence of cell kill on peak values of concentration rather than on an integral over time is consistent with observations that dose-response curves for doxorubicin converge to a single curve as exposure time is increased. Drug uptake by cells is assumed to include both saturable and unsaturable components, consistent with experimental data. Overall, the model provides better fits to in vitro cytotoxicity data than previous models. It shows how saturation of cellular uptake or binding with concentration can result in plateaus in the dose-response curve at high concentrations and short exposure, as observed experimentally in some cases. The model provides a unified framework for analyzing doxorubicin cellular pharmacokinetic and pharmacodynamic data, can be applied in mathematical models for tumor response and treatment optimization

Discriminative and Distinct Phenotyping by Constrained Tensor Factorization

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Acute flaccid paralysis incidence rate and epidemiology in children in Lebanon: a rise in numbers in the post-vaccination and refugee crisis era

Background: Acute flaccid paralysis (AFP) is a clinical syndrome characterized by the acute onset of weakness and paralysis with reduced muscle tone. This study explored the incidence and different aspects of AFP in Lebanese children between 2009 and 2019. Methods: AFP data were collected from the Lebanese Ministry of Public Health. Incidence rate according to year, age groups, clinical data, follow-up, diagnosis, and vaccination status was analyzed in the 11-years period. Results: AFP incidence rates increased importantly from 0.63 per 100,000 in 2009 till 4.96 per 100,000 in 2019. Most of the patients were children under ten years of age, 40.6% of all cases were under five years old, and 37.9% were between 5 and 9 years old. Follow-up revealed that approximately two out of five patients experienced residual weakness. As for the final diagnosis, around 30% of cases were diagnosed as Guillain-Barre Syndrome (GBS). Most cases were children having received between 3 and 5 doses of polio vaccine. Conclusions: The rise in cases coincided with the Syrian refugee crisis in Lebanon and the progressively deteriorating economy in the country; yet, incidence rates were in the lower margin compared with other countries. Keywords: Acute flaccid paralysis; Epidemiology; Guillain-Barré Syndrome; Lebanon; Pediatrics

Multi-element cylindrical electrostatic lens systems for focusing and controlling charged particles

This paper describes theoretical modelling of electrostatic lenses based on 3, 4 and 5 closely spaced cylindrical electrodes, respectively. In each case, modelling is carried out numerically using commercial packages SIMION and LENSYS, and a variety of performance parameters are obtained. These include the magnification, the 3rd order spherical and chromatic aberration coefficients. Special cases such as zoom lens (i.e., lenses whose magnification may be changed without losing focus) are considered. Results are obtained as a function of the ratios of the electrode lengths and gaps, and as a function of ratios of the controlling voltages. As a result, it is shown that how a multi-element lens system can be operated with the whole focal properties in a useful mode for using in experimental studies.Comment: 20 pages, 15 figure

Losing weights: Failure to recognize and act on weight loss documented in an electronic health record

Background: Involuntary weight loss is associated with higher mortality.  When this weight loss is unrecognized, opportunities for timely diagnosis of significant conditions may be missed.  Objective:To use electronic health record (EHR) data to estimate the frequency of unrecognized involuntary weight loss and its implications. Methods: We performed a retrospective analysis of the weights recorded in an EHR of 100,000 adult patients seen in outpatient clinics over a five-year period using a novel data visualization and review tool.  We reviewed charts of a random sample of 170 patients experiencing weight loss periods.   Our outcomes included determinations of whether weight loss 1) was voluntary vs. involuntary; 2) was recognized and documented; and 3) possible explanations identifiable at the index visit or within the subsequent two years.  Results: Of 170 randomly-selected weight loss periods reviewed, 22 (13%) were involuntary, 36 (21%) were voluntary and 112 (66%) were indeterminate.  Sixty-six (39%) weight loss periods were recognized by clinician at the index visits and an additional 3 (1%) at the next PCP visits.  Possible explanations for weight loss emerged in the subsequent two years including medical conditions in 60 (45%), psycho-social conditions in 19 (14%), erroneous data entry in 9 (7%), voluntary weight loss in 8 (6%),  and postpartum weight loss in 6 (4%).   No possible explanations were found in 32 (24%).   Conclusions:Periods of weight loss were common, often involuntary and frequently not recognized or documented.  Many patients with involuntary weight loss had potential explanations that emerged within the subsequent two years