Statistics at square zero: a survival guide

In order to understand or conduct research, it is important that all clinicians have at least a basic grasp of the commonly encountered statistical tests. Each has its limitations but there is usually a best or more appropriate test to use for a given set of data. This is a key skill for all clinicians and is one of the curriculum competencies identified by the Royal College of Paediatrics of Child Health. Much to the chagrin of many trainees it is also tested in the RCPCH examinations. A basic understanding of some of the more commonly encountered tests is helpful: it allows a more thorough appreciation of the data that are being presented in published studies and for those undertaking the RCPCH Theory and Science examination offers ‘marks for free’. This short article provides simple guidance on how to pick the best test to use for different types of data. It is aimed at a novice who might consider themselves to be at step zero rather than step one.     

Acute encephalopathy with biphasic seizures and late reduced diffusion in a Spanish girl

We report a case of a 22-month-old Spanish girl who presented acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). Serum procalcitonin (PCT) reached a maximum of 50.5 ng/mL on the first day whereas C-reactive protein (CRP) peaked at 1.21 mg/dL on the second. At the time of discharge, right spastic hemiparesis persisted. MR spectroscopy on day 23 revealed a decrease in N-acetylaspartate and an increase in choline. To our knowledge, we report the first case of AESD in Europe. These findings support the role of PCT and PCT/CRP ratio in the early diagnosis of AESD and correlation of MR spectroscopy findings with neurological outcome.     

Numerical Integrators for Dispersion-Managed KdV Equation

In this paper, we consider the numerics of the dispersion-managed Korteweg-de Vries (DM-KdV) equation for describing wave propagations in inhomogeneous media. The DM-KdV equation contains a variable dispersion map with discontinuity, which makes the solution non-smooth in time. We formally analyze the convergence order reduction problems of some popular numerical methods including finite difference and time-splitting for solving the DM-KdV equation, where a necessary constraint on the time step has been identified. Then, two exponential-type dispersion-map integrators up to second order accuracy are derived, which are efficiently incorporated with the Fourier pseudospectral discretization in space, and they can converge regardless of the discontinuity and the step size. Numerical comparisons show the advantage of the proposed methods with the application to solitary wave dynamics and extension to the fast & strong dispersion-management regime.     

Numerical Investigation of Analytical Models of Drug Flux Through Microporated Skin

In this study, drug flux through microporated skin was modeled using detailed numerical solution of the diffusion equation. The results of the modeling were compared to previously published simplified and easy to use analytical equations. Limitations and accuracy of these equations were investigated. Appropriate modifications of the equations were identified to expand them to wider practical applications when pore shape is not circular. Numerical simulations have shown a good accuracy of the new simple equations when these are used within their limits of application.     

Impact of sampling rate on statistical significance for single subject fMRI connectivity analysis

A typical time series in functional magnetic resonance imaging (fMRI) exhibits autocorrelation, that is, the samples of the time series are dependent. In addition, temporal filtering, one of the crucial steps in preprocessing of functional magnetic resonance images, induces its own autocorrelation. While performing connectivity analysis in fMRI, the impact of the autocorrelation is largely ignored. Recently, autocorrelation has been addressed by variance correction approaches, which are sensitive to the sampling rate. In this article, we aim to investigate the impact of the sampling rate on the variance correction approaches. Toward this end, we first derived a generalized expression for the variance of the sample Pearson correlation coefficient (SPCC) in terms of the sampling rate and the filter cutoff frequency, in addition to the autocorrelation and cross‐covariance functions of the time series. Through simulations, we illustrated the importance of the variance correction for a fixed sampling rate. Using the real resting state fMRI data sets, we demonstrated that the data sets with higher sampling rates were more prone to false positives, in agreement with the existing empirical reports. We further demonstrated with single subject results that for the data sets with higher sampling rates, the variance correction strategy restored the integrity of true connectivity.     

Carboxylesterase catalyzed 18O-labeling of carboxylic acid and its potential application in LC-MS/MS based quantification of drug metabolites

LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel ¹⁸O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H₂¹⁸O in the presence of the enzyme, generating singly- and doubly-¹⁸O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery.     

Do regions of interest location and type influence liver stiffness measurement using magnetic resonance elastography?

PurposeTo assess the variability of liver stiffness measurements using magnetic resonance elastography (MRE) at 1.5 T, depending on different approaches of regions of interest (ROIs) drawing.Material and methodsFifty consecutive patients with successful liver MRE were included. There were 32 men and 18 women with a mean age of 52 ± 14 (SD) years (range: 20–85 years). MRE was acquired using a gradient recalled-echo MRE sequence. At the level of the portal bifurcation, one observer drawn in the right liver first 3 elliptical ROI and then one free-hand ROI, as large as possible based on the confidence map and the anatomy. Three additional elliptical ROIs were further drawn on the slice above and 3 other on the slice below, for a total of 9 elliptical ROIs. The average value of liver stiffness in the 3 elliptical ROIs of the central slice and the one from the 9 elliptical ROIs were computed. Three liver stiffness values were obtained for each patient from the 3 measurement methods (one free-hand ROI, 3 elliptical ROIs and 9 elliptical ROIs). Inter-method variability was assessed using the intra-class correlation coefficient (ICC) and Bland-Altman analysis.ResultsThe variability between the 3 methods was excellent with ICC > 0.978 (P < 0.0001). The Bland-Altman analysis revealed high agreement between the 3 methods with bias < 0.45 kPa and limits of agreement < ±1.13 kPa. The variability was lower when comparing a large free-hand ROI and the 3-elliptical ROIs, than when comparing the 9-elliptical ROIs to one of the other methods.ConclusionOur results show that the variability between the 3 methods of ROI drawing and placement is very low.