Abstract: We describe two approaches to detecting anomalies in time series of multi-parameter clinical data: (1) metric and model-based indicators and (2) information surprise. (1) Metric and model-based indicators are commonly used as early warning signals to detect transitions between alternate states based on individual time series. Here we explore the applicability of existing indicators to distinguish critical (anomalies) from non-critical conditions in patients undergoing cardiac surgery, based on a small anonymized clinical trial dataset. We find that a combination of time-varying autoregressive model, kurtosis, and skewness indicators correctly distinguished critical from non-critical patients in 5 out of 36 blood parameters at a window size of 0.3 (average of 37 hours) or higher. (2) Information surprise quantifies how the progression of one patient's condition differs from that of rest of the population based on the cross-section of time series. With the maximum surprise and slope features we detect all critical patients at the 0.05 significance level. Moreover we show that a naive outlier detection does not work, demonstrating the need for the more sophisticated approaches explored here. Our preliminary results suggest that future developments in early warning systems for patient condition monitoring may predict the onset of critical transition and allow medical intervention preventing patient death. Further method development is needed to avoid overfitting and spurious results, and verification on large clinical datasets.

Abstract: A clinical trial is a study designed to demonstrate the ecacy and safety of a drug, procedure, medical device, or diagnostic test. Since clinical trials involve research in humans, they must be carefully designed and must comply strictly with a set of ethical conditions. Logistical disadvantages, ethical constraints, costs and high execution times could have a negative impact on the execution of the clinical trial. This article proposes the use of a simulation tool, the MRSA-T-Simulator, to design and perform "virtual clinical trials" for the purpose of studying MRSA contact transmission among hospitalized patients. The main advantage of the simulator is its flexibility when it comes to configuring the patient population, healthcare staff and the simulation environment.

Abstract: What does the informational complexity of dynamical networked systems tell us about intrinsic mechanisms and functions of these complex systems? Recent complexity measures such as integrated information have sought to operationalize this problem taking a whole-versus-parts perspective, wherein one explicitly computes the amount of information generated by a network as a whole over and above that generated by the sum of its parts during state transitions. While several numerical schemes for estimating network integrated information exist, it is instructive to pursue an analytic approach that computes integrated information as a function of network weights. Our formulation of integrated information uses a Kullback-Leibler divergence between the multi-variate distribution on the set of network states versus the corresponding factorized distribution over its parts. Implementing stochastic Gaussian dynamics, we perform computations for several prototypical network topologies. Our findings show increased informational complexity near criticality, which remains consistent across network topologies. Spectral decomposition of the system's dynamics reveals how informational complexity is governed by eigenmodes of both, the network's covariance and adjacency matrices. We find that as the dynamics of the system approach criticality, high integrated information is exclusively driven by the eigenmode corresponding to the leading eigenvalue of the covariance matrix, while sub-leading modes get suppressed. The implication of this result is that it might be favorable for complex dynamical networked systems such as the human brain or communication systems to operate near criticality so that efficient information integration might be achieved.

Abstract: Simulation has become an important tool for studying plant physiology. An important aspect of this is discovering the processes that influence leaf growth at a cellular level. To this end, we have extended an existing, morphogen-based model for the growth of Arabidopsis leaves. We have fitted parameters to match important leaf growth properties reported in experimental data. A sensitivity analysis was performed, which allowed us to estimate the effect of these different parameters on leaf growth, and identify viable strategies for increasing leaf size.