A rapid computational filter for predicting the rate of human renal clearance

In silico models that predict the rate of human renal clearance for a diverse set of drugs, that exhibit both active secretion and net re-absorption, have been produced using three statistical approaches. Partial Least Squares (PLS) and Random Forests (RF) have been used to produce continuous models whereas Classification And Regression Trees (CART) has only been used for a classification model. The best models generated from either PLS or RF produce significant models that can predict acids/zwitterions, bases and neutrals with approximate average fold errors of 3, 3 and 4, respectively, for an independent test set that covers oral drug-like property space. These models contain additional information on top of any influence arising from plasma protein binding on the rate of renal clearance. Classification And Regression Trees (CART) has been used to generate a classification tree leading to a simple set of Renal Clearance Rules (RCR) that can be applied to man. The rules are influenced by lipophilicity and ion class and can correctly predict 60% of an independent test set. These percentages increase to 71% and 79% for drugs with renal clearances of < 0.1 ml/min/kg and > 1 ml/min/kg, respectively. As far as the authors are aware these are the first set of models to appear in the literature that predict the rate of human renal clearance and can be used to manipulate molecular properties leading to new drugs that are less likely to fail due to renal clearance.     

Fundamental dynamics of flow through carbon nanotube membranes

The flow of a model non-polar liquid through small carbon nanotubes is studied using non-equilibrium molecular dynamics simulation. We explain how a membrane of small-diameter nanotubes can transport this liquid faster than a membrane consisting of larger-diameter nanotubes. This effect is shown to be back-pressure dependent, and the reasons for this are explored. The flow through the very smallest nanotubes is shown to depend strongly on the depth of the potential inside, suggesting atomic separation can be based on carbon interaction strength as well as physical size. Finally, we demonstrate how increasing the back-pressure can counter-intuitively result in lower exit velocities from a nanotube. Such studies are crucial for optimisation of nanotube membranes.     

An improved approximation to the precision of fixed effects from restricted maximum likelihood

An approximate small sample variance estimator for fixed effects from the multivariate normal linear model, together with appropriate inference tools based on a scaled F pivot, is now well established in practice and there is a growing literature on its properties in a variety of settings. Although effective under linear covariance structures, there are examples of nonlinear structures for which it does not perform as well. The cause of this problem is shown to be a missing term in the underlying Taylor series expansion which accommodates the bias in the estimators of the parameters of the covariance structure. The form of this missing term is derived, and then used to adjust the small sample variance estimator. The behaviour of the resulting estimator is explored in terms of invariance under transformation of the covariance parameters and also using a simulation study. It is seen to perform successfully in the way predicted from its derivation.     

Distribution-preserving statistical disclosure limitation

One approach to limiting disclosure risk in public-use microdata is to release multiply-imputed, partially synthetic data sets. These are data on actual respondents, but with confidential data replaced by multiply-imputed synthetic values. A mis-specified imputation model can invalidate inferences based on the partially synthetic data, because the imputation model determines the distribution of synthetic values. We present a practical method to generate synthetic values when the imputer has only limited information about the true data generating process. We combine a simple imputation model (such as regression) with density-based transformations that preserve the distribution of the confidential data, up to sampling error, on specified subdomains. We demonstrate through simulations and a large scale application that our approach preserves important statistical properties of the confidential data, including higher moments, with low disclosure risk.     

Sentinel-1-based flood mapping: a fully automated processing chain

This article presents an automated Sentinel-1-based processing chain designed for flood detection and monitoring in near-real-time (NRT). Since no user intervention is required at any stage of the flood mapping procedure, the processing chain allows deriving time-critical disaster information in less than 45 min after a new data set is available on the Sentinel Data Hub of the European Space Agency (ESA). Due to the systematic acquisition strategy and high repetition rate of Sentinel-1, the processing chain can be set up as a web-based service that regularly informs users about the current flood conditions in a given area of interest. The thematic accuracy of the thematic processor has been assessed for two test sites of a flood situation at the border between Greece and Turkey with encouraging overall accuracies between 94.0% and 96.1% and Cohen’s kappa coefficients (κ) ranging from 0.879 to 0.910. The accuracy assessment, which was performed separately for the standard polarizations (VV/VH) of the interferometric wide swath (IW) mode of Sentinel-1, further indicates that under calm wind conditions, slightly higher thematic accuracies can be achieved by using VV instead of VH polarization data.