Histopathology laboratory operations analysis and improvement

Histopathology laboratories aim to deliver high quality diagnoses based on patient tissue samples. Indicators for quality are the accuracy of the diagnoses and the diagnostic turnaround times. However, challenges exist regarding employee workload and turnaround times in the histopathology laboratory. This paper proposes a decomposed planning and scheduling method for the histopathology laboratory using (mixed) integer linear programming ((M)ILP) to improve the spread of workload and reduce the diagnostic turnaround times. First, the batching problem is considered, in which batch completion times are equally divided over the day to spread the workload. This reduces the peaks of physical work available in the laboratory. Thereafter, the remaining processes are scheduled to minimize the tardiness of orders. Preliminary results show that using this decomposition method, the peaks in histopathology workload in UMC Utrecht, a large university medical center in the Netherlands, are potentially reduced with up to 50% by better spreading the workload over the day. Furthermore, turnaround times are potentially reduced with up to 20% compared to current practices

Automatic nuclei segmentation in H&E stained breast cancer histopathology images

The introduction of fast digital slide scanners that provide whole slide images has led to a revival of interest in image analysis applications in pathology. Segmentation of cells and nuclei is an important first step towards automatic analysis of digitized microscopy images. We therefore developed an automated nuclei segmentation method that works with hematoxylin and eosin (H&E) stained breast cancer histopathology images, which represent regions of whole digital slides. The procedure can be divided into four main steps: 1) pre-processing with color unmixing and morphological operators, 2) marker-controlled watershed segmentation at multiple scales and with different markers, 3) post-processing for rejection of false regions and 4) merging of the results from multiple scales. The procedure was developed on a set of 21 breast cancer cases (subset A) and tested on a separate validation set of 18 cases (subset B). The evaluation was done in terms of both detection accuracy (sensitivity and positive predictive value) and segmentation accuracy (Dice coefficient). The mean estimated sensitivity for subset A was 0.875 (±0.092) and for subset B 0.853 (±0.077). The mean estimated positive predictive value was 0.904 (±0.075) and 0.886 (±0.069) for subsets A and B, respectively. For both subsets, the distribution of the Dice coefficients had a high peak around 0.9, with the vast majority of segmentations having values larger than 0.8. © 2013 Veta et al

Procedural fairness in judicial review of migration decisions: The evolution of a fundamental common law principle

Procedural fairness has undergone significant evolution from a moral limit on the exercise of power to a fundamental principle of the common law. The thesis explains and reconciles this evolution of procedural fairness in Australia in the context of judicial review of decisions made under the Migration Act 1958 (Cth). By historical analysis of the origins and development of the principles of procedural fairness, the thesis identifies values and concepts underlying those principles. The High Court’s current conception of fairness, as protecting individual rights and interests in the exercise of power, evolved from the idea that there is a morally correct and just way to decide things. The thesis explains how by judicial development the implication of the obligation to observe procedural fairness in Australia, in the context of migration decisions, was shaped and informed, expressly and implicitly, by these values and concepts. The thesis explains the basis for the current restatement of procedural fairness as a fundamental principle of the common law, the relationship between procedural fairness and the principle of legality, and the positioning of procedural fairness as a principle or presumption of statutory construction. The thesis suggests that the explanation rests in legal coherence, in particular defining the obligation to observe procedural fairness in terms of an implied limit on the exercise of statutory power. The thesis also suggests that the dual presumptions created by recognising procedural fairness as a fundamental principle buttressed by the principle of legality, practically deny the exclusion of the principles in all but a limited number of cases

Predicting turnaround time reductions of the diagnostic track in the histopathology laboratory using mathematical modelling

Background \ud Pathology departments face a growing volume of more and more complex testing in an era where healthcare costs tend to explode and short turnaround times (TATs) are expected. In contrast, the histopathology workforce tends to shrink, so histopathology employees experience high workload during their shifts. This points to the need for efficient planning of activities in the histopathology laboratory, to ensure an equal division of workload and low TATs, at minimum costs. \ud \ud Methods \ud The histopathology laboratory of a large academic hospital in The Netherlands was analysed using mathematical modelling. Data were collected from the Laboratory Management System to determine laboratory TATs and workload performance during regular working hours. A mixed integer linear programme (MILP) was developed to model the histopathology processes and to measure the expected performance of possible interventions in terms of TATs and spread of workload. \ud \ud Results \ud The MILP model predicted that tissue processing at specific moments during the day, combined with earlier starting shifts, can result in up to 25% decrease of TATs, and a more equally spread workload over the day. \ud \ud Conclusions \ud Mathematical modelling can help to optimally organise the workload in the histopathology laboratory by predicting the performance of possible interventions before actual implementation. The interventions that were predicted by the model to have the highest performance have been implemented in the histopathology laboratory of University Medical Center Utrecht. Further research should be executed to collect empirical evidence and evaluate the actual impact on TAT, quality of work and employee stress levels

A novel method to quantify IRDye800CW fluorescent antibody probes ex vivo in tissue distribution studies

BACKGROUND: We describe a new method for biodistribution studies with IRDye800CW fluorescent antibody probes. This method allows the quantification of the IRDye800CW fluorescent tracer in percentage of injected dose per gram of tissue (% ID/g), and it is herein compared to the generally used reference method that makes use of radioactivity. METHODS: Cetuximab was conjugated to both the near-infrared fluorophore IRDye800CW and/or the positron emitter 89-zirconium, which was injected in nude mice bearing A431 human tumor xenografts. Positron emission tomography (PET) and optical imaging were performed 24 h post-injection (p.i.). For the biodistribution study, organs and tumors were collected 24 h p.i., and each of these was halved. One half was used for the determination of probe uptake by radioactivity measurement. The other half was homogenized, and the content of the fluorescent probe was determined by extrapolation from a calibration curve made with the injected probe. RESULTS: Tumors were clearly visualized with both modalities, and the calculated tumor-to-normal tissue ratios were very similar for optical and PET imaging: 3.31 ± 1.09 and 3.15 ± 0.99, respectively. Although some variations were observed in ex vivo analyses, tumor uptake was within the same range for IRDye800CW and gamma ray quantification: 15.07 ± 3.66% ID/g and 13.92 ± 2.59% ID/g, respectively. CONCLUSIONS: The novel method for quantification of the optical tracer IRDye800CW gives similar results as the reference method of gamma ray quantification. This new method is considered very useful in the context of the preclinical development of IRDye800CW fluorescent probes for optical molecular imaging, likely contributing to the selection of lead compounds that are the most promising for clinical translation