The inflammatory response aims to restore homeostasis by means of removing a biological stress, such as an invading bacterial pathogen. In cases of acute systemic inflammation, the possibility of collateral tissue damage arises, which leads to a necessary down-regulation of the response. A reduced ordinary differential equations (ODE) model of acute inflammation was presented and investigated in [10]. That system contains multiple positive and negative feedback loops and is a highly coupled and nonlinear ODE. The implementation of nonlinear model predictive control (NMPC) as a methodology for determining proper therapeutic intervention for in silico patients displaying complex inflammatory states was initially explored in [5]. Since direct measurements of the bacterial population and the magnitude of tissue damage/dysfunction are not readily available or biologically feasible, the need for robust state estimation was evident. In this present work, we present results on the nonlinear reachability of the underlying model, and then focus our attention on improving the predictability of the underlying model by coupling the NMPC with a particle filter. The results, though comparable to the initial exploratory study, show that robust state estimation of this highly nonlinear model can provide an alternative to prior updating strategies used when only partial access to the unmeasurable states of the system are available.

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We prove the existence of joint limiting spectral distributions for families of random sample covariance matrices modeled on fluctuations of discretized Lévy processes. These models were first considered in applications of random matrix theory to financial data, where datasets exhibit both strong multicollinearity and non-normality. When the underlying Lévy process is non-Gaussian, we show that the limiting spectral distributions are distinct from Marčenko–Pastur. In the context of operator-valued free probability, it is shown that the algebras generated by these families are asymptotically free with amalgamation over the diagonal subalgebra. This framework is used to construct operator-valued $$^*$$ ∗ -probability spaces, where the limits of sample covariance matrices play the role of non-commutative Lévy processes whose increments are free with amalgamation.