Tumor architecture exerts no bias on nuclear grading in breast cancer diagnosis

We recently reported that nuclear grading in prostate cancer is subject to a strong confirmation bias induced by the tumor architecture. We now wondered whether a similar bias governs nuclear grading in breast carcinoma. An unannounced test was performed at a pathology conference. Pathologists were asked to grade nuclei in a PowerPoint presentation. Circular high power fields of 27 invasive ductal carcinomas were shown, superimposed over low power background images of either tubule-rich or tubule-poor carcinomas. We found (a) that diagnostic reproducibility of nuclear grades was poor to moderate (weighed kappa values between 0.07 and 0.54, 27 cases, 44 graders), but (b) that nuclear grades were not affected by the tumor architecture. We speculate that the categorized grading in breast cancer, separating tubule formation, nuclear pleomorphism, and mitotic figure counts in a combined three tier score, prevents the bias that architecture exerts on nuclear grades in less well-controlled situations.

What was I thinking? Eye-tracking experiments underscore the bias that architecture exerts on nuclear grading in prostate cancer

We previously reported that nuclear grade assignment of prostate carcinomas is subject to a cognitive bias induced by the tumor architecture. Here, we asked whether this bias is mediated by the non-conscious selection of nuclei that "match the expectation" induced by the inadvertent glance at the tumor architecture. 20 pathologists were asked to grade nuclei in high power fields of 20 prostate carcinomas displayed on a computer screen. Unknown to the pathologists, each carcinoma was shown twice, once before a background of a low grade, tubule-rich carcinoma and once before the background of a high grade, solid carcinoma. Eye tracking allowed to identify which nuclei the pathologists fixated during the 8 second projection period. For all 20 pathologists, nuclear grade assignment was significantly biased by tumor architecture. Pathologists tended to fixate on bigger, darker, and more irregular nuclei when those were projected before kigh grade, solid carcinomas than before low grade, tubule-rich carcinomas (and vice versa). However, the morphometric differences of the selected nuclei accounted for only 11% of the architecture-induced bias, suggesting that it can only to a small part be explained by the unconscious fixation on nuclei that "match the expectation". In conclusion, selection of « matching nuclei » represents an unconscious effort to vindicate the gravitation of nuclear grades towards the tumor architecture.

Avoiding misclassification bias with the traditional Charnley classification: rationale for a fourth Charnley class BB

Long-term follow up of patients with total hip arthroplasty (THA) revealed a marked deterioration of walking capacities in Charnley class B after postoperative year 4. We hypothesized that a specific group of patients, namely those with unilateral hip arthroplasty and an untreated but affected contralateral hip was responsible for this observation. Therefore, we conducted a study taking into consideration the two subclasses that make up Charnley class B: patients with unilateral THA and contralateral hip disease and patients with bilateral THA. A sample of 15,160 patients with 35,773 follow ups that were prospectively collected over 10 years was evaluated. The sample was categorized into four classes according to a new modified Charnley classification. Annual analyses of the proportion of patients with ambulation longer than 60 min were conducted. The traditionally labeled Charnley class B consists of two very different patient groups with respect to their walking capacities. Those with unilateral THA and contralateral hip disease have underaverage walking capacities and a deterioration of ambulation beginning 3 to 4 years after surgery. Those with bilateral THA have stable overaverage walking capacities similar to Charnley class A. An extension of the traditional Charnley classification is proposed, taking into account the two different patient groups in Charnley class B. The new fourth Charnley class consists of patients with bilateral THA and was labeled BB in order to express the presence of two artificial hip joints and to preserve the traditional classification A through C.

Association between reported exposure to road traffic and respiratory symptoms in children: evidence of bias

BACKGROUND: Many studies showing effects of traffic-related air pollution on health rely on self-reported exposure, which may be inaccurate. We estimated the association between self-reported exposure to road traffic and respiratory symptoms in preschool children, and investigated whether the effect could have been caused by reporting bias. METHODS: In a random sample of 8700 preschool children in Leicestershire, UK, exposure to road traffic and respiratory symptoms were assessed by a postal questionnaire (response rate 80%). The association between traffic exposure and respiratory outcomes was assessed using unconditional logistic regression and conditional regression models (matching by postcode). RESULTS: Prevalence odds ratios (95% confidence intervals) for self-reported road traffic exposure, comparing the categories 'moderate' and 'dense', respectively, with 'little or no' were for current wheezing: 1.26 (1.13-1.42) and 1.30 (1.09-1.55); chronic rhinitis: 1.18 (1.05-1.31) and 1.31 (1.11-1.56); night cough: 1.17 (1.04-1.32) and 1.36 (1.14-1.62); and bronchodilator use: 1.20 (1.04-1.38) and 1.18 (0.95-1.46). Matched analysis only comparing symptomatic and asymptomatic children living at the same postcode (thus exposed to similar road traffic) showed similar ORs, suggesting that parents of children with respiratory symptoms reported more road traffic than parents of asymptomatic children. CONCLUSIONS: Our study suggests that reporting bias could explain some or even all the association between reported exposure to road traffic and disease. Over-reporting of exposure by only 10% of parents of symptomatic children would be sufficient to produce the effect sizes shown in this study. Future research should be based only on objective measurements of traffic exposure.

A non-spatial bias favouring fixated stimuli revealed in patients with spatial neglect

The cardinal feature of spatial neglect is severely impaired exploration of the contralesional space, a failure resulting in unawareness of many contralesional stimuli. This deficit is exacerbated by a reflexive attentional bias toward ipsilesional items. Here we show that, in addition to these spatially lateralized failures, neglect patients also exhibit a severe bias favouring stimuli presented at fixation. We tested neglect patients and matched healthy and right-hemisphere damaged patients without neglect in a task requiring saccade execution to targets in the left or right hemifield. Targets were presented alone or simultaneously with a distracter that appeared in the same hemifield, in the opposite hemifield, or at fixation. We found two fundamental biases in saccade initiation of neglect patients: irrelevant distracters presented in the preserved hemifield tended to capture gaze reflexively, resulting in a large number of saccades erroneously directed toward the distracter. Additionally, distracters presented at fixation severely disrupted saccade initiation irrespective of saccade direction, leading to disproportionately increased latencies of left and right saccades. This latency increase was specific to oculomotor responses of neglect patients and was not observed when a manual response was required. These results show that, in addition to their failure to inhibit reflexive glances toward ipsilesional items neglect patients exhibit a strong oculomotor bias favouring fixated stimuli. We conclude that impaired initiation of saccades in any direction contributes to the deficits of spatial exploration that characterize spatial neglect.