The use of a formal sensitivity analysis on epidemic models with immune protection from maternally acquired antibodies

This paper considers the outcome of a formal sensitivity analysis on a series of epidemic model structures developed to study the population level effects of maternal antibodies. The analysis is used to compare the potential influence of maternally acquired immunity on various age and time domain observations of infection and serology, with and without seasonality. The results of the analysis indicate that time series observations are largely insensitive to variations in the average duration of this protection, and that age related empirical data are likely to be most appropriate for estimating these characteristics

A multispecies model for the transmission and control of mastitis in dairy cows

Mastitis in dairy cows is a significant economic and animal welfare issue in the dairy industry. The bacterial pathogens responsible for infection of the mammary gland may be split into two main categories: major and minor pathogens. Infection with major pathogens generally results in clinical illness or strong inflammatory responses and reduced milk yields, whereas minor pathogen infection is usually subclinical. Previous investigations have considered the transmission of these pathogens independently. Experimental evidence has shown cross-protection between species of pathogens. In this study a mathematical model for the coupled transmission of major and minor pathogens along with their interaction via the host was developed in order to consider various methods for controlling the incidence of major pathogen infection. A stability analysis of the model equilibria provides explanations for observed phenomena and previous decoupled modelling results. This multispecies model structure has provided a basis for quantifying the extent of cross-protection between species and assessing possible control strategies against the disease

Modelling the dynamics of intramammary E. coli infections in dairy cows: understanding mechanisms that distinguish transient from persistent infections

The majority of intramammary infections with Escherichia coli in dairy cows result in transient infections with duration of about 10 days or less, although more persistent infections (2 months or longer) have been identified. We apply a mathematical model to explore the role of an intracellular mammary epithelial cell reservoir in the dynamics of infection. We included biological knowledge of the bovine immune response and known characteristics of the bacterial population in both transient and persistent infections. The results indicate that varying the survival duration of the intracellular reservoir reproduces the data for both transient and persistent infections. Survival in an intracellular reservoir is the most likely mechanism that ensures persistence of E. coli infections in mammary glands. Knowledge of the pathogenesis of persistent infections is essential to develop preventive and treatment programmes for these important infections in dairy cows

A coupled drug kinetics-cell cycle model to analyse the response of human cells to intervention by topotecan

A model describing the response of the growth of single human cells in the absence and presence of the anti-cancer agent topotecan (TPT) is presented. The model includes a novel coupling of both the kinetics of TPT and cell cycle responses to the agent. By linking the models in this way, rather than using separate (disjoint) approaches, it is possible to illustrate how the drug perturbs the cell cycle. The model is compared to experimental in vitro cell cycle response data (comprising single cell descriptors for molecular and behavioural events), showing good qualitative agreement for a range of TPT dose levels

Multidispensor cartesian robotic printer

Disclosed are systems, compositions, and methods for three-dimensional (3D) printing. An example system includes a plurality dispensers configured to deposit materials from their tips and a printing surface for receiving the materials. The system includes a position sensing detector configured to detect positions of the tips of the dispensers and the location and dimensions of the printing surface. The system includes a robotic positioning device configured to drive the dispensers. The system also includes a control unit configured to receive and map in a 3D space the positions of the tips of the dispensers and the position and dimensions of the printing surface. The control unit is further configured to control the robotic positioning device to drive the dispensers relative to the printing surface in the 3D space, and to independently deposit materials on the printing surface, or on material deposited on the printing surface

Reprint of “Pharmacokinetic modelling of the anti-malarial drug artesunate and its active metabolite dihydroartemisinin”

A four compartment mechanistic mathematical model is developed for the pharmacokinetics of the commonly used anti-malarial drug artesunate and its principle metabolite dihydroartemisinin following oral administration of artesunate. The model is structurally unidentifiable unless additional constraints are imposed. Combinations of mechanistically derived constraints are considered to assess their effects on structural identifiability and on model fits. Certain combinations of the constraints give rise to locally or globally identifiable model structures. Initial validation of the model under various combinations of the constraints leading to identifiable model structures was performed against a dataset of artesunate and dihydroartemisinin concentration–time profiles of 19 malaria patients. When all the discussed constraints were imposed on the model, the resulting globally identifiable model structure was found to fit reasonably well to those patients with normal drug absorption profiles. However, there is wide variability in the fitted parameters and further investigation is warranted

Kinerja Pengawas SMA/SMK Ditinjau dari Lingkungan Kerja dan Motivasi Kerja di Wilayah Kaili

Tujuan penelitian ini adalah untuk mengetahui besar hubungan kinerja pengawas SMA/SMK di tinjau dari lingkungan kerja dan motivasi kerja pengawas sekolah di Wilayah Kaili. (1) Lingkungan kerja dengan kinerja pengawas SMA/SMK di Wilayah Kaili, (2) Motivasi kerja dengan kinerja pengawas SMA/SMK di Wilayah Kaili, (3) Lingkungan kerja dan motivasi kerja dengan Kinerja pengawas SMA/SMK di Wilayah Kaili, (4) Lingkungan kerja dengan kinerja pengawas SMA/SMK di Wilayah Kaili apabila motivasi kerja dikontrol, (5) Motivasi kerja dengan kinerja pengawas SMA/SMK di Wilayah Kaili apabila lingkungan kerja pengawas dikontrol. Penelitian ini adalah penelitian survey yang bersifat korelasional. Populasi dalam penelitian ini adalah seluruh pengawas SMA / SMK di Wilayah Kaili yaitu Kota Palu, Kabupaten Donggala, Kabupaten Parigi, dan Kabupaten Sigi dengan jumlah pengawas sekolah 48 orang. Pengambilan sampel dilakukan secara rambang sederhana. Ukuran sampel dalam penelitian ini sebanyak 43 pengawas sekolah sebagai responden. Mengidentifikasi data sebagai outlier dari sekumpulan data yang menyimpang, terdapat 7 data pencilan sehingga data yang diinferensi sebanyak 37 orang. Instrumen yang digunakan berupa kuesioner. Pengembangan instrumen dilakukan mulai dari menyusun indikator, kisi-kisi instrumen, kemudian butir-butir instrumen yang di validasi isi, analisis butir secara kualitatif sehingga instrumen siap digunakan. Data dianalisis dengan menggunakan analisis deskriptif dan analisis inferensial. Hasil analisis deskriptif menunjukkan bahwa lingkungan kerja, motivasi kerja dan kinerja pengawas sekolah berada pada kategori baik. Hasil analisis inferensial menunjukkan bahwa: (1) Lingkungan kerja tidak mempunyai hubungan yang positif dan signifikan dengan kinerja pengawas SMA/SMK, (2) Motivasi kerja mempunyai hubungan yang positif dan signifikan dengan kinerja pengawas SMA/SMK, (3) Lingkungan kerja dan motivasi kerja mempunyai hubungan yang positif dan signifikan dengan Kinerja pengawas SMA/SMK, (4) Lingkungan kerja tidak mempunyai hubungan yang positif dan signifikan dengan kinerja pengawas SMA/SMK apabila motivasi kerja dikontrol, (5) Motivasi kerja mempunyai hubungan yang positif dan signifikan dengan kinerja pengawas SMA/SMK apabila lingkungan kerja pengawas dikontrol

Lyapunov exponents for certain stochastic flows

This thesis examines the asymptotic behaviour of solution flows of certain stochastic differential equations utilising the theory of Lyapunov exponents. The approach is taken on two fronts. Initially flows are considered on compact manifolds that arise from embedding the manifold in some Euclidean space - the Gradient Brownian flow. In this case the existence of the Lyapunov exponents is known. Results are obtained for the sum of the exponents - which has the geometrical interpretation as the exponential rate of change of volume under the action of the flow - and for the largest exponent on generalised Clifford Tori and convex hypersurfaces. The situation on non-compact manifolds is then considered - where the existence of the exponents is uncertain due to the fact that the existence of a finite invariant measure is not guaranteed. However, by considering a stochastic mechanical system this problem is overcome and conditions for existence are obtained for both the Lyapunov spectrum and the sum' of the exponents. Some examples are then considered in the noncompact case. Finally in the Appendix a computational method for calculating the largest Lyapunov exponent on a hypersurface is considered

Input-dependent structural identifiability of nonlinear systems

A dynamic model is structurally identifiable if it is possible to infer its unknown parameters by observing its output. Structural identifiability depends on the system dynamics, output, and input, as well as on the specific values of initial conditions and parameters. Here we present a symbolic method that characterizes the input that a model requires to be structurally identifiable. It determines which derivatives must be non-zero in order to have a sufficiently exciting input. Our approach considers structural identifiability as a generalization of nonlinear observability and incorporates extended Lie derivatives. The methodology assesses structural identifiability for time-varying inputs and, additionally, it can be used to determine the input profile that is required to make the parameters structurally locally identifiable. Furthermore, it is sometimes possible to replace an experiment with time-varying input with multiple experiments with constant inputs. We implement the resulting method as a MATLAB toolbox named STRIKE-GOLDD2. This tool can assist in the design of new experiments for the purpose of parameter estimation

Model-based Bayesian inference of brain oxygenation using quantitative BOLD

© 2019 The Authors Streamlined Quantitative BOLD (sqBOLD) is an MR technique that can non-invasively measure physiological parameters including Oxygen Extraction Fraction (OEF) and deoxygenated blood volume (DBV) in the brain. Current sqBOLD methodology rely on fitting a linear model to log-transformed data acquired using an Asymmetric Spin Echo (ASE) pulse sequence. In this paper, a non-linear model implemented in a Bayesian framework was used to fit physiological parameters to ASE data. This model makes use of the full range of available ASE data, and incorporates the signal contribution from venous blood, which was ignored in previous analyses. Simulated data are used to demonstrate the intrinsic difficulty in estimating OEF and DBV simultaneously, and the benefits of the proposed non-linear model are shown. In vivo data are used to show that this model improves parameter estimation when compared with literature values. The model and analysis framework can be extended in a number of ways, and can incorporate prior information from external sources, so it has the potential to further improve OEF estimation using sqBOLD