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Tumor growth inhibition (TGI) modeling attempts to describe the time course changes in tumor size for patients undergoing cancer therapy. TGI models present several advantages over traditional exposure–response models that are based explicitly on clinical end points and have become a popular tool in the pharmacometrics community. Unfortunately, the data required to fit TGI models, namely longitudinal tumor measurements, are sparse or often not available in literature or publicly accessible databases. On the contrary, common end points such as progression‐free survival (PFS) and objective response rate (ORR) are directly derived from longitudinal tumor measurements and are routinely published. To this end, a Bayesian generative model relating underlying tumor dynamics to summary PFS and ORR data is introduced to learn TGI model parameters using only published summary data. The parameterized model can describe the tumor dynamics, quantify treatment effect, and account for differences in the study population. The utility of this model is shown by applying it to several published studies, and learned parameters are combined to simulate an in silico trial of a novel combination therapy in a novel setting. [ABSTRACT FROM AUTHOR]

We introduce an approach based on the Givens representation for posterior inference in statistical models with orthogonal matrix parameters, such as factor models and probabilistic principal component analysis (PPCA). We show how the Givens representation can be used to develop practical methods for transforming densities over the Stiefel manifold into densities over subsets of Euclidean space. We show how to deal with issues arising from the topology of the Stiefel manifold and how to inexpensively compute the change-of-measure terms. We introduce an auxiliary parameter approach that limits the impact of topological issues. We provide both analysis of our methods and numerical examples demonstrating the effectiveness of the approach. We also discuss how our Givens representation can be used to define general classes of distributions over the space of orthogonal matrices. We then give demonstrations on several examples showing how the Givens approach performs in practice in comparison with other methods. [ABSTRACT FROM AUTHOR]

We study the association between weight fluctuation and activity tracking in an on-line population of thousands of individuals using digital health trackers (1,749 ≤ N ≤ 14,411, depending on the activity tracker considered) with millions of recorded activities (119,292 ≤ N ≤ 2,221,382) over the years 2013–2015. In a first between-subject analysis, we found a positive association between activity tracking frequency and weight loss. Users who log food with moderate frequency lost an additional 0.63% (CI [0.55, 0.72]; p < .001) of their body weight per month relative to low frequency loggers. Frequent workout loggers lost an additional 0.38% (CI [0.20, 0.56]; p < .001) and frequent weight loggers lost an additional 0.40% (CI [0.33, 0.47]; p < .001) as compared to infrequent loggers. In a subsequent within-subject analysis on a subset of the population (799 ≤ N ≤ 6,052) with sufficient longitudinal data, we used fixed effect models to explore the temporal relationship between a change in tracking adherence and weight change. We found that for the same individual, weight loss is significantly higher during periods of high adherence to tracking vs. periods of low adherence: +2.74% of body weight lost per month (CI [2.68, 2.81]; p < .001) during adherent weight tracking, +1.35% per month (CI [1.26, 1.43]; p < .001) during adherent food tracking, and +0.60% per month (CI [0.44, 0.76]; p < .001) during adherent workout tracking. The findings suggest that adherence to activity tracking can be utilized as a convenient real-time predictor of weight fluctuations, enabling large-scale, personalized intervention strategies. [ABSTRACT FROM AUTHOR]

Being able to infer one way direct connections in an oscillatory network such as the suprachiastmatic nucleus (SCN) of the mammalian brain using time series data is difficult but crucial to understanding network dynamics. Although techniques have been developed for inferring networks from time series data, there have been no attempts to adapt these techniques to infer directional connections in oscillatory time series, while accurately distinguishing between direct and indirect connections. In this paper an adaptation of Granger Causality is proposed that allows for inference of circadian networks and oscillatory networks in general called Adaptive Frequency Granger Causality (AFGC). Additionally, an extension of this method is proposed to infer networks with large numbers of cells called LASSO AFGC. The method was validated using simulated data from several different networks. For the smaller networks the method was able to identify all one way direct connections without identifying connections that were not present. For larger networks of up to twenty cells the method shows excellent performance in identifying true and false connections; this is quantified by an area-under-the-curve (AUC) 96.88%. We note that this method like other Granger Causality-based methods, is based on the detection of high frequency signals propagating between cell traces. Thus it requires a relatively high sampling rate and a network that can propagate high frequency signals. [ABSTRACT FROM AUTHOR]