Temporal representation and reasoning in medicine: research directions and challenges

Objective: The main aim of this paper is to propose and discuss promising directions of research in the field of temporal representation and reasoning in medicine, taking into account the recent scientific literature and challenging issues of current interest as viewed from the different research perspectives of the authors of the paper. Background: Temporal representation and reasoning in medicine is a well-known field of research in the medical as well as computer science community. It encompasses several topics, such as summarizing data from temporal clinical databases, reasoning on temporal clinical data for therapeutic assessments, and modeling uncertainty in clinical knowledge and data. It is also related to several medical tasks, such as monitoring intensive care patients, providing treatments for chronic patients, as well as planning and scheduling clinical routine activities within complex healthcare organizations. Methodology: The authors jointly identified significant research areas based on their importance as for temporal representation and reasoning issues; the subjects were considered to be promising topics of future activity. Every subject was addressed in detail by one or two authors and then discussed with the entire team to achieve a consensus about future fields of research. Results: We identified and focused on four research areas, namely (i) fuzzy logic, time, and medicine, (ii) temporal reasoning and data mining, (iii) health information systems, business processes, and time, and (iv) temporal clinical databases. For every area, we first highlighted a few basic notions that would permit any reader-including those who are unfamiliar with the topic-to understand the main goals. We then discuss interesting and promising directions of research, taking into account the recent literature and underlining the yet unresolved medical/clinical issues that deserve further scientific investigation. The considered research areas are by no means disjointed, because they share common theoretical and methodological features. Moreover, subjects of imminent interest in medicine are represented in many of the fields considered. Conclusions: We propose and discuss promising subjects of future research that deserve investigation to develop software systems that will properly manage the multifaceted temporal aspects of information and knowledge encountered by physicians during their clinical work. As the subjects of research have resulted from merging the different perspectives of the authors involved in this study, we hope the paper will succeed in stimulating discussion and multidisciplinary work in the described fields of researc

Effects of perfusion and vascular architecture on contrast dispersion: validation in ex-vivo porcine liver under machine perfusion

Dynamic contrast enhanced ultrasound (DCE-US) enables imaging of cancer angiogenesis by quantification of perfusion and dispersion. Although increased perfusion may be found in areas of active angiogenesis due to increased demands for blood supply, decreased perfusion may be caused by the decreased efficiency and functionality, typical of cancer angiogenic microvasculature. Contrast dispersion, mainly determined by the flow profile in large vessels and by the multipath trajectories in the microvasculature, may thus represent a suitable alternative to characterize cancer angiogenesis. Based on a model of the contrast transport kinetics as a convective-dispersion process, several DCE-US methods have been proposed estimating dispersion for characterization of cancer angiogenic vasculature. Although dispersion imaging has shown promising in a clinical context, its physical link with variations in flow and vascular architecture has never been shown. The objective of this work is thus to investigate the influence of flow and underlying vascular architecture on the estimation of dispersion in an ex-vivo machine-perfused pig liver

Finding and explaining optimal treatments

Contains fulltext : 112472.pdf (publisher's version ) (Closed access

Abstracting Steady Qualitative Descriptions over Time from Noisy, High-Frequency Data

On-line monitoring at neonatal intensive care units produces high volumes of data. Numerous devices generate data at high frequency (one data set every second). Both, the high volume and the quite high error-rate of the data make it essential to reach at higher levels of description from suchraw data. These abstractions should improve the medical decision making. We will present a time-oriented data-abstraction method to derive steady qualitative descriptions from ..

MeDIP real-time qPCR of maternal peripheral blood reliably identifies trisomy 21

Objective: To reevaluate the efficiency of the 12 differentially methylated regions (DMRs) used in the methylated DNA immunoprecipitation (MeDIP) real-time quantitative polymerase chain reaction (real-time qPCR) based approach, develop an improved version of the diagnostic formula and perform a larger validation study. Methods: Twelve selected DMRs were checked for copy number variants in the Database of Genomic Variants. The DMRs located within copy number variants were excluded from the analysis. One hundred and seventy-five maternal peripheral blood samples were used to reconstruct and evaluate the new diagnostic formula and for a larger-scale blinded validation study using MeDIP real-time qPCR. Results: Seven DMRs entered the final model of the prediction equation and a larger blinded validation study demonstrated 100% sensitivity and 99.2% specificity. No significant evidence for association was observed between cell free fetal DNA concentration and D value. Conclusion: The MeDIP real-time qPCR method for noninvasive prenatal diagnosis of trisomy 21 was confirmed and revalidated in 175 samples with satisfactory results demonstrating that it is accurate and reproducible. We are currently working towards simplification of the method to make it more robust and therefore easily, accurately, and rapidly reproduced and adopted by other laboratories. Nevertheless, larger scale validation studies are necessary before the MeDIP real-time qPCR-based method could be applied in clinical practice. © 2012 John Wiley & Sons, Ltd

Targeted capture enrichment assay for non-invasive prenatal testing of large and small size sub-chromosomal deletions and duplications

<div><p>Noninvasive prenatal testing (NIPT) using whole genome and targeted sequencing has become increasingly accepted for clinical detection of Trisomy 21 and sex chromosome aneuploidies. Few studies have shown that sub-chromosomal deletions or duplications associated with genetic syndromes can also be detected in the fetus noninvasively. There are still limitations on these methodologies such as the detection of variants of unknown clinical significance, high number of false positives, and difficulties to detect small aberrations. We utilized a recently developed targeted sequencing approach for the development of a NIPT assay, for large and small size deletions/duplications, which overcomes these existing limitations. Artificial pregnancies with microdeletion/microduplication syndromes were created by spiking DNA from affected samples into cell free DNA (cfDNA) from non-pregnant samples. Unaffected spiked samples and normal pregnancies were used as controls. Target Capture Sequences (TACS) for seven syndromes were designed and utilized for targeted capture enrichment followed by sequencing. Data was analyzed using a statistical pipeline to identify deletions or duplications on targeted regions. Following the assay development a proof of concept study using 33 normal pregnancies, 21 artificial affected and 17 artificial unaffected pregnancies was carried out to test the sensitivity and specificity of the assay. All 21 abnormal spiked-in samples were correctly classified as subchromosomal aneuploidies while the 33 normal pregnancies or 17 normal spiked-in samples resulted in a false positive result. We have developed an NIPT assay for the detection of sub-chromosomal deletions and duplications using the targeted capture enrichment technology. This assay demonstrates high accuracy, high read depth of the genomic region of interest, and can identify deletions/duplications as small as 0.5 Mb. NIPT of fetal microdeletion/microduplication syndromes can be of enormous benefit in the management of pregnancies at risk both for prospective parents and health care providers.</p></div

Affected samples used to create artificial plasma pregnancies with deletion or duplication syndromes.

<p>Affected samples used to create artificial plasma pregnancies with deletion or duplication syndromes.</p