@article{wright_fayad_selgrade_olufsen_2020, title={Mechanistic model of hormonal contraception}, volume={16}, ISSN={["1553-7358"]}, DOI={10.1371/journal.pcbi.1007848}, abstractNote={Contraceptive drugs intended for family planning are used by the majority of married or in-union women in almost all regions of the world. The two most prevalent types of hormones associated with contraception are synthetic estrogens and progestins. Hormonal based contraceptives contain a dose of a synthetic progesterone (progestin) or a combination of a progestin and a synthetic estrogen. In this study we use mathematical modeling to understand better how these contraceptive paradigms prevent ovulation, special focus is on understanding how changes in dose impact hormonal cycling. To explain this phenomenon, we added two autocrine mechanisms essential to achieve contraception within our previous menstrual cycle models. This new model predicts mean daily blood concentrations of key hormones during a contraceptive state achieved by administering progestins, synthetic estrogens, or a combined treatment. Model outputs are compared with data from two clinical trials: one for a progestin only treatment and one for a combined hormonal treatment. Results show that contraception can be achieved with synthetic estrogen, with progestin, and by combining the two hormones. An advantage of the combined treatment is that a contraceptive state can be obtained at a lower dose of each hormone. The model studied here is qualitative in nature, but can be coupled with a pharmacokinetic/pharamacodynamic (PKPD) model providing the ability to fit exogenous inputs to specific bioavailability and affinity. A model of this type may allow insight into a specific drug’s effects, which has potential to be useful in the pre-clinical trial stage identifying the lowest dose required to achieve contraception.}, number={6}, journal={PLOS COMPUTATIONAL BIOLOGY}, author={Wright, A. Armean and Fayad, Ghassan N. and Selgrade, James F. and Olufsen, Mette S.}, year={2020}, month={Jun} }
 @article{panza_wright_selgrade_2016, title={A delay differential equation model of follicle waves in women}, volume={10}, ISSN={["1751-3766"]}, DOI={10.1080/17513758.2015.1115564}, abstractNote={ABSTRACT This article presents a mathematical model for hormonal regulation of the menstrual cycle which predicts the occurrence of follicle waves in normally cycling women. Several follicles of ovulatory size that develop sequentially during one menstrual cycle are referred to as follicle waves. The model consists of 13 nonlinear, delay differential equations with 51 parameters. Model simulations exhibit a unique stable periodic cycle and this menstrual cycle accurately approximates blood levels of ovarian and pituitary hormones found in the biological literature. Numerical experiments illustrate that the number of follicle waves corresponds to the number of rises in pituitary follicle stimulating hormone. Modifications of the model equations result in simulations which predict the possibility of two ovulations at different times during the same menstrual cycle and, hence, the occurrence of dizygotic twins via a phenomenon referred to as superfecundation. Sensitive parameters are identified and bifurcations in model behaviour with respect to parameter changes are discussed. Studying follicle waves may be helpful for improving female fertility and for understanding some aspects of female reproductive ageing.}, number={1}, journal={JOURNAL OF BIOLOGICAL DYNAMICS}, author={Panza, Nicole M. and Wright, Andrew A. and Selgrade, James F.}, year={2016}, pages={200–221} }
 @article{williams_wind-willassen_wright_program_mehlsen_ottesen_olufsen_2014, title={Patient-specific modelling of head-up tilt}, volume={31}, ISSN={["1477-8602"]}, DOI={10.1093/imammb/dqt004}, abstractNote={Short-term cardiovascular responses to head-up tilt (HUT) involve complex cardiovascular regulation in order to maintain blood pressure at homoeostatic levels. This manuscript presents a patient-specific model that uses heart rate as an input to fit the dynamic changes in arterial blood pressure data during HUT. The model contains five compartments representing arteries and veins in the upper and lower body of the systemic circulation, as well as the left ventricle facilitating pumping of the heart. A physiologically based submodel describes gravitational pooling of the blood into the lower extremities during HUT, and a cardiovascular regulation model adjusts cardiac contractility and vascular resistance to the blood pressure changes. Nominal parameter values are computed from patient-specific data and literature estimates. The model is rendered patient specific via the use of parameter estimation techniques. This process involves sensitivity analysis, prediction of a subset of identifiable parameters, and non-linear optimization. The approach proposed here was applied to the analysis of aortic and carotid HUT data from five healthy young subjects. Results showed that it is possible to identify a subset of model parameters that can be estimated allowing the model to fit changes in arterial blood pressure observed at the level of the carotid bifurcation. Moreover, the model estimates physiologically reasonable values for arterial and venous blood pressures, blood volumes and cardiac output for which data are not available.}, number={4}, journal={MATHEMATICAL MEDICINE AND BIOLOGY-A JOURNAL OF THE IMA}, author={Williams, Nakeya D. and Wind-Willassen, Oistein and Wright, Andrew A. and Program, Reu and Mehlsen, Jesper and Ottesen, Johnny T. and Olufsen, Mette S.}, year={2014}, month={Dec}, pages={365–392} }