How Reliable Is Ki-67 Immunohistochemistry in Grade 2 Breast Carcinomas? A QA Study of the Swiss Working Group of Breast- and Gynecopathologists

Adjuvant chemotherapy decisions in breast cancer are increasingly based on the pathologist's assessment of tumor proliferation. The Swiss Working Group of Gyneco- and Breast Pathologists has surveyed inter- and intraobserver consistency of Ki-67-based proliferative fraction in breast carcinomas. Methods Five pathologists evaluated MIB-1-labeling index (LI) in ten breast carcinomas (G1, G2, G3) by counting and eyeballing. In the same way, 15 pathologists all over Switzerland then assessed MIB-1-LI on three G2 carcinomas, in self-selected or pre-defined areas of the tumors, comparing centrally immunostained slides with slides immunostained in the different laboratoires. To study intra-observer variability, the same tumors were re-examined 4 months later. Results The Kappa values for the first series of ten carcinomas of various degrees of differentiation showed good to very good agreement for MIB-1-LI (Kappa 0.56–0.72). However, we found very high inter-observer variabilities (Kappa 0.04–0.14) in the read-outs of the G2 carcinomas. It was not possible to explain the inconsistencies exclusively by any of the following factors: (i) pathologists' divergent definitions of what counts as a positive nucleus (ii) the mode of assessment (counting vs. eyeballing), (iii) immunostaining technique, and (iv) the selection of the tumor area in which to count. Despite intensive confrontation of all participating pathologists with the problem, inter-observer agreement did not improve when the same slides were re-examined 4 months later (Kappa 0.01–0.04) and intra-observer agreement was likewise poor (Kappa 0.00–0.35). Conclusion Assessment of mid-range Ki-67-LI suffers from high inter- and intra-observer variability. Oncologists should be aware of this caveat when using Ki-67-LI as a basis for treatment decisions in moderately differentiated breast carcinomas

How do German bilingual schoolchildren process German prepositions? - A study on language-motor interactions

<div><p>While much support is found for embodied language processing in a first language (L1), evidence for embodiment in second language (L2) processing is rather sparse. In a recent study, we found support for L2 embodiment, but also an influence of L1 on L2 processing in adult learners. In the present study, we compared bilingual schoolchildren who speak German as one of their languages with monolingual German schoolchildren. We presented the German prepositions <i>auf</i> (<i>on</i>), <i>über</i> (<i>above</i>), and <i>unter</i> (<i>under</i>) in a Stroop-like task. Upward or downward responses were made depending on the font colour, resulting in compatible and incompatible trials. We found compatibility effects for all children, but in contrast to the adult sample, there were no processing differences between the children depending on the nature of their other language, suggesting that the processing of German prepositions of bilingual children is embodied in a similar way as in monolingual German children.</p></div

Mean response times for correct responses as a function of response direction and stimulus for the different language groups separately.

<p>Error bars represent 95% confidence intervals [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193349#pone.0193349.ref067" target="_blank">67</a>].</p

Example item from the used adaptation of the TRPS [45].

<p>The child is expected to fill in the preposition <i>über</i> (<i>Der Wecker steht über dem Bett / The alarm clock is standing above the bed)</i>.</p

Mean response times of the high-proficiency and the low-proficiency group for correct responses as a function of response direction and stimulus.

<p>Error bars represent 95% confidence intervals [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193349#pone.0193349.ref067" target="_blank">67</a>].</p

Single comparisons of the RTs for compatible and incompatible trials per proficiency group.

<p>Single comparisons of the RTs for compatible and incompatible trials per proficiency group.</p

Single comparisons of the error rates for compatible and incompatible trials per proficiency group.

<p>Single comparisons of the error rates for compatible and incompatible trials per proficiency group.</p

Descriptive information about class level, school type, and bilingualism [57] of our participants.

<p>Descriptive information about class level, school type, and bilingualism [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193349#pone.0193349.ref057" target="_blank">57</a>] of our participants.</p