Global and mitosis-specific interobserver variation in mitotic count scoring and implications for malignant melanoma staging

AIMS Staging is the gold standard for predicting malignant melanoma outcome but changes in its criteria over time indicate ongoing evolution. One notable recent change from the 8 edition of the AJCC staging manual was removal of mitotic count. We explore the extent that this feature is limited by interobserver error in order to find ways to improve its fitness for use should it be revisited in future staging versions. METHODS AND RESULTS In a cohort of 476 patients with melanoma ≤ 1.0 mm, a mitotic count of 0 vs 1 was significant for metastasis-free survival, but not melanoma-specific or overall survival. In 10 melanomas that were 0.9 to 1.0 mm thick, the mitotic count intra-class correlation coefficient for histopathologists was 0.58 (moderate agreement). Uniquely, we also assessed agreement for specific putative mitotic figures, identifying precise reasons why specific mitotic figures qualified for scoring or elimination. A kappa score was 0.54 (moderate agreement). We also gathered data on other staging features. Breslow thickness had an intraclass correlation coefficient of 0.41 (moderate agreement) and there was a systematic difference between histopathologists across cases (p = 0.04). Every case had a range that crossed the AJCC8 0.8 mm pT1a/pT1b staging boundary. Ulceration was only identified in 2 out the 10 cases. For ulceration, kappa agreement score was 0.31 (fair). CONCLUSION This study supports the removal of mitotic count from staging but shows that its scoring is substantially affected by interobserver variation, suggesting that more prescriptive guidelines might have a beneficial impact on its prognostic value

Comunicaciones presentadas al I Congreso Internacional "La Administración de justicia en España y en América"

Congreso homenaje al profesor José Martín Ostos, con motivo de su jubilació

Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, $\alpha=2$ as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed $>$600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that $\alpha = 1.63 \pm 0.03$. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating.Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 7