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When strength of forensic evidence is quantified using sample data and statistical models, a concern may be raised as to whether the output of a model overestimates the strength of evidence. This is particularly the case when the amount of sample data is small, and hence sampling variability is high. This concern is related to concern about precision. This paper describes, explores, and tests three procedures which shrink the value of the likelihood ratio or Bayes factor toward the neutral value of one. The procedures are: (1) a Bayesian procedure with uninformative priors, (2) use of empirical lower and upper bounds (ELUB), and (3) a novel form of regularized logistic regression. As a benchmark, they are compared with linear discriminant analysis, and in some instances with non-regularized logistic regression. The behaviours of the procedures are explored using Monte Carlo simulated data, and tested on real data from comparisons of voice recordings, face images, and glass fragments., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

In order for clinicians to manage disease progression and make effective decisions about drug dosage, treatment regimens or scheduling follow up appointments, it is necessary to be able to identify both short and long-term trends in repeated biomedical measurements. However, this is complicated by the fact that these measurements are irregularly sampled and influenced by both genuine physiological changes and external factors. In their current forms, existing regression algorithms often do not fulfil all of a clinician's requirements for identifying short-term (acute) events while still being able to identify long-term, chronic, trends in disease progression. Therefore, in order to balance both short term interpretability and long term flexibility, an extension to broken-stick regression models is proposed in order to make them more suitable for modelling clinical time series. The proposed probabilistic broken-stick model can robustly estimate both short-term and long-term trends simultaneously, while also accommodating the unequal length and irregularly sampled nature of clinical time series. Moreover, since the model is parametric and completely generative, its first derivative provides a long-term non-linear estimate of the annual rate of change in the measurements more reliably than linear regression. The benefits of the proposed model are illustrated using estimated glomerular filtration rate as a case study used to manage patients with chronic kidney disease., (Copyright © 2017. Published by Elsevier Inc.)

Diagnosis and treatment of circadian rhythm sleep-wake disorders both require assessment of circadian phase of the brain's circadian pacemaker. The gold-standard univariate method is based on collection of a 24-hr time series of plasma melatonin, a suprachiasmatic nucleus-driven pineal hormone. We developed and validated a multivariate whole-blood mRNA-based predictor of melatonin phase which requires few samples. Transcriptome data were collected under normal, sleep-deprivation and abnormal sleep-timing conditions to assess robustness of the predictor. Partial least square regression (PLSR), applied to the transcriptome, identified a set of 100 biomarkers primarily related to glucocorticoid signaling and immune function. Validation showed that PLSR-based predictors outperform published blood-derived circadian phase predictors. When given one sample as input, the R 2 of predicted vs observed phase was 0.74, whereas for two samples taken 12 hr apart, R 2 was 0.90. This blood transcriptome-based model enables assessment of circadian phase from a few samples.

Images of the kidneys using dynamic contrast-enhanced magnetic resonance renography (DCE-MRR) contains unwanted complex organ motion due to respiration. This gives rise to motion artefacts that hinder the clinical assessment of kidney function. However, due to the rapid change in contrast agent within the DCE-MR image sequence, commonly used intensity-based image registration techniques are likely to fail. While semi-automated approaches involving human experts are a possible alternative, they pose significant drawbacks including inter-observer variability, and the bottleneck introduced through manual inspection of the multiplicity of images produced during a DCE-MRR study. To address this issue, we present a novel automated, registration-free movement correction approach based on windowed and reconstruction variants of dynamic mode decomposition (WR-DMD). Our proposed method is validated on ten different healthy volunteers' kidney DCE-MRI data sets. The results, using block-matching-block evaluation on the image sequence produced by WR-DMD, show the elimination of 99 % of mean motion magnitude when compared to the original data sets, thereby demonstrating the viability of automatic movement correction using WR-DMD., (© The Author(s) 2017.)

Introduction: Renal function is reported using the estimates of glomerular filtration rate (eGFR). However, eGFR values are recorded without reference to the particular serum creatinine (SCr) assays used to derive them, and newer assays were introduced at different time points across the laboratories in the United Kingdom. These changes may cause systematic bias in eGFR reported in routinely collected data, even though laboratory-reported eGFR values have a correction factor applied., Design: An algorithm to detect changes in SCr that in turn affect eGFR calculation method was developed. It compares the mapping of SCr values on to eGFR values across a time series of paired eGFR and SCr measurements., Setting: Routinely collected primary care data from 20,000 people with the richest renal function data from the quality improvement in chronic kidney disease trial., Results: The algorithm identified a change in eGFR calculation method in 114 (90%) of the 127 included practices. This change was identified in 4736 (23.7%) patient time series analysed. This change in calibration method was found to cause a significant step change in the reported eGFR values, producing a systematic bias. The eGFR values could not be recalibrated by applying the Modification of Diet in Renal Disease equation to the laboratory reported SCr values., Conclusions: This algorithm can identify laboratory changes in eGFR calculation methods and changes in SCr assay. Failure to account for these changes may misconstrue renal function changes over time. Researchers using routine eGFR data should account for these effects.

Background: Medical research increasingly requires the linkage of data from different sources. Conducting a requirements analysis for a new application is an established part of software engineering, but rarely reported in the biomedical literature; and no generic approaches have been published as to how to link heterogeneous health data., Methods: Literature review, followed by a consensus process to define how requirements for research, using, multiple data sources might be modeled., Results: We have developed a requirements analysis: i-ScheDULEs - The first components of the modeling process are indexing and create a rich picture of the research study. Secondly, we developed a series of reference models of progressive complexity: Data flow diagrams (DFD) to define data requirements; unified modeling language (UML) use case diagrams to capture study specific and governance requirements; and finally, business process models, using business process modeling notation (BPMN)., Discussion: These requirements and their associated models should become part of research study protocols.