Moving average filtering with deconvolution (MAD) for hidden Markov model with filtering and correlated noise.

Ion channel data recorded using the patch clamp technique are low-pass filtered to remove high-frequency noise. Almanjahie et al. (Eur Biophys J 44:545-556, 2015) based statistical analysis of such data on a hidden Markov model (HMM) with a moving average adjustment for the filter but without correlated noise, and used the EM algorithm for parameter estimation. In this paper, we extend their model to include correlated noise, using signal processing methods and deconvolution to pre-whiten the noise. The resulting data can be modelled as a standard HMM and parameter estimates are again obtained using the EM algorithm. We evaluate this approach using simulated data and also apply it to real data obtained from the mechanosensitive channel of large conductance (MscL) in Escherichia coli. Estimates of mean conductances are comparable to literature values. The key advantages of this method are that it is much simpler and computationally considerably more efficient than currently used HMM methods that include filtering and correlated noise.

Accuracy of tablet splitting and liquid measurements: an examination of who, what and how.

OBJECTIVE: To examine factors that might affect the ability of patients to accurately halve tablets or measure a 5-ml liquid dose. METHODS: Eighty-eight participants split four different placebo tablets by hand and using a tablet splitter, while 85 participants measured 5 ml of water, 0.5% methylcellulose (MC) and 1% MC using a syringe and dosing cup. Accuracy of manipulation was determined by mass measurements. KEY FINDINGS: The general population was less able than pharmacy students to break tablets into equal parts, although age, gender and prior experience were insignificant factors. Greater accuracy of tablet halving was observed with tablet splitter, with scored tablets split more equally than unscored tablets. Tablet size did not affect the accuracy of splitting. However, >25% of small scored tablets failed to be split by hand, and 41% of large unscored tablets were split into >2 portions in the tablet splitter. In liquid measurement, the syringe provided more accurate volume measurements than the dosing cup, with higher accuracy observed for the more viscous MC solutions than water. CONCLUSION: Formulation characteristics and manipulation technique have greater influences on the accuracy of medication modification and should be considered in off-label drug use in vulnerable populations.