An empirical investigation into the role of subjective prior probability in searching for potentially missing items.

There are many examples from the scientific literature of visual search tasks in which the length, scope and success rate of the search have been shown to vary according to the searcher's expectations of whether the search target is likely to be present. This phenomenon has major practical implications, for instance in cancer screening, when the prevalence of the condition is low and the consequences of a missed disease diagnosis are severe. We consider this problem from an empirical Bayesian perspective to explain how the effect of a low prior probability, subjectively assessed by the searcher, might impact on the extent of the search. We show how the searcher's posterior probability that the target is present depends on the prior probability and the proportion of possible target locations already searched, and also consider the implications of imperfect search, when the probability of false-positive and false-negative decisions is non-zero. The theoretical results are applied to two studies of radiologists' visual assessment of pulmonary lesions on chest radiographs. Further application areas in diagnostic medicine and airport security are also discussed.

Towards a framework for analysis of eye-tracking studies in the three dimensional environment: a study of visual search by experienced readers of endoluminal CT colonography.

OBJECTIVE: Eye tracking in three dimensions is novel, but established descriptors derived from two-dimensional (2D) studies are not transferable. We aimed to develop metrics suitable for statistical comparison of eye-tracking data obtained from readers of three-dimensional (3D) "virtual" medical imaging, using CT colonography (CTC) as a typical example. METHODS: Ten experienced radiologists were eye tracked while observing eight 3D endoluminal CTC videos. Subsequently, we developed metrics that described their visual search patterns based on concepts derived from 2D gaze studies. Statistical methods were developed to allow analysis of the metrics. RESULTS: Eye tracking was possible for all readers. Visual dwell on the moving region of interest (ROI) was defined as pursuit of the moving object across multiple frames. Using this concept of pursuit, five categories of metrics were defined that allowed characterization of reader gaze behaviour. These were time to first pursuit, identification and assessment time, pursuit duration, ROI size and pursuit frequency. Additional subcategories allowed us to further characterize visual search between readers in the test population. CONCLUSION: We propose metrics for the characterization of visual search of 3D moving medical images. These metrics can be used to compare readers' visual search patterns and provide a reproducible framework for the analysis of gaze tracking in the 3D environment. ADVANCES IN KNOWLEDGE: This article describes a novel set of metrics that can be used to describe gaze behaviour when eye tracking readers during interpretation of 3D medical images. These metrics build on those established for 2D eye tracking and are applicable to increasingly common 3D medical image displays.

Comparison of risk-scoring methods in predicting the immediate outcome after elective open abdominal aortic aneurysm surgery.

BACKGROUND & OBJECTIVES: The aim of this study was to apply three simple risk - scoring systems to prospectively collected data on all elective open Abdominal Aortic Aneurysm (AAA) operations in the Cambridge Academic Vascular Unit over a 6 - year period (January 1998 to January 2004), to compare their predictive values and to evaluate their validity with respect to prediction of mortality and post-operative complications. METHODS: 204 patients underwent elective open infra-renal AAA repair. Data were prospectively collected and risk assessment scores were calculated for mortality and morbidity according to the Glasgow Aneurysm Score (GAS), VBHOM (Vascular Biochemistry and Haematology Outcome Models) and Estimation of Physiologic Ability and Surgical Stress (E-PASS). RESULTS: The mortality rate was 6.3% (13/204) and 59% (121/204) experienced a post-operative complication (30-day outcome). For GAS, VBHOM and E-PASS the receiver operating characteristics (ROC) curve analysis for prediction of in-hospital mortality showed area under the curve (AUC) of 0.84 (95% confidence interval [CI], 0.76 to 0.92; p<0.0001), 0.82 (95% CI, 0.68 to 0.95; p=0.0001) and 0.92 (95% CI, 0.87 to 0.97; p<0.0001) respectively. There were also significant correlations between post-operative complications and length of hospital stay and each of the three scores, but the correlation was substantially higher in the case of E-PASS. CONCLUSIONS: All three scoring systems accurately predicted the risk of mortality and morbidity in patients undergoing elective open AAA repair. Among these, E-PASS seemed to be the most accurate predictor in this patient population.

Transjugular liver biopsy in patients with diffuse liver disease: comparison of three cores with one or two cores for accurate histological interpretation.

BACKGROUND: Transjugular liver biopsy (TJLB) can be performed to obtain more than two cores safely. This advantage has not been evaluated in terms of diagnostic accuracy or grading/staging evaluation. AIM: To evaluate whether three separate cores of TJLB provide more histological information compared with two or one cores. METHODS: Twenty-three patients, who had three separate passes, with each core >/=7mm in length using a 19G Tru-cut needle, were evaluated. Each TJLB was blindly coded; the pathologist randomly assessed: (a) each core separately covering the other two, (b) two cores simultaneously covering the third and (c) the three cores together for diagnostic yield, inflammation and fibrosis. RESULTS: The mean TJLB length was 32+/-5.5mm. In 12 one-core (52%) and 18 2-core (78%) assessments, diagnosis (mainly cirrhosis) was made correctly in each core. The within-patient standard deviations for one-core vs two-core assessment were similar for grading (0.42 and 0.47, respectively), but higher for staging (0.39 and 0.15, respectively). Staging was underestimated in assessing one-core and less for two cores compared to three cores. CONCLUSION: Three non-fragmented cores (each core >/=7mm in length) of TJLB can be considered a minimum requirement for histological assessment, giving better reproducibility in diagnosis as well as for inflammation and fibrosis.

Mitogenic growth signalling, DNA replication licensing, and survival are linked in prostate cancer.

Activation of mitogen/extracellular-signal-regulated kinase kinase 5/extracellular signal-regulated kinase-5 (MEK5/ERK5) growth signalling is coupled to increased cell proliferation in prostate cancer (PCa). Dysregulation of the DNA replication licensing pathway, a critical step in growth control downstream of transduction signalling pathways, is associated with development of PCa. In this study we have investigated linkages between the MEK5/ERK5 pathway and DNA replication licensing during prostate carcinogenesis. The effects of increased MEK5/ERK5 signalling on the expression of replication licensing factors Mcm2 and geminin and the proliferation marker Ki67 were studied in an ecdysone-inducible system expressing a constitutively activated mutant of MEK5 in EcR293 cells and in stable ERK5 over-expressing PC3 clones. In parallel, expression of these biomarkers in PCa biopsy specimens (n=58) was studied and compared to clinicopathological parameters. In both in vitro systems induction of MEK5 expression resulted in increased levels of phosphorylated ERK5 and Mcm2, geminin and Ki67 proteins. In PCa specimens average Mcm2 expression was greater than Ki67 and geminin expression (median labelling index (LI) 36.7, 18.1, and 3.4% respectively), consistent with their differential expression according to growth status (P<0.0001). Mcm2, geminin and Ki67 expression were significantly associated with Gleason grade (P=0.0002, P=0.0003, P=0.004); however there was no link with T or M stage. There was a significant relationship between increasing ERK5 expression and increasing Mcm2 (P=0.003) and Ki67 (P=0.009) expression, with non-significant trends seen with increasing MEK5 expression. There were significant associations between Gleason grade and the number of cells traversing G1 phase (Ki67(LI)-geminin(LI); (P=0.001)), with high ERK5 levels associated with both an increase in replication licensed but non-cycling cells (Mcm2(LI)-Ki67(LI); (P=0.01)) and accelerated cell cycle progression (geminin(LI)/Ki67(LI); (P= 0.005)), all indicative of a shift towards increasing proliferative potential. While Mcm2 and Ki67 were both prognostic factors on univariate analysis, only Mcm2 remained an independent prognostic marker on multivariate analysis. Taken together, our data show that induction of MEK5/ERK5 signalling is linked to activation of the DNA replication licensing pathway in PCa, and that the strong prognostic value of MCM proteins may result from their function as relay stations coupling growth regulatory pathways to genome duplication.