AI-based automation of enrollment criteria and endpoint assessment in clinical trials in liver diseases

\ua9 The Author(s) 2024.Clinical trials in metabolic dysfunction-associated steatohepatitis (MASH, formerly known as nonalcoholic steatohepatitis) require histologic scoring for assessment of inclusion criteria and endpoints. However, variability in interpretation has impacted clinical trial outcomes. We developed an artificial intelligence-based measurement (AIM) tool for scoring MASH histology (AIM-MASH). AIM-MASH predictions for MASH Clinical Research Network necroinflammation grades and fibrosis stages were reproducible (κ = 1) and aligned with expert pathologist consensus scores (κ = 0.62–0.74). The AIM-MASH versus consensus agreements were comparable to average pathologists for MASH Clinical Research Network scores (82% versus 81%) and fibrosis (97% versus 96%). Continuous scores produced by AIM-MASH for key histological features of MASH correlated with mean pathologist scores and noninvasive biomarkers and strongly predicted progression-free survival in patients with stage 3 (P < 0.0001) and stage 4 (P = 0.03) fibrosis. In a retrospective analysis of the ATLAS trial (NCT03449446), responders receiving study treatment showed a greater continuous change in fibrosis compared with placebo (P = 0.02). Overall, these results suggest that AIM-MASH may assist pathologists in histologic review of MASH clinical trials, reducing inter-rater variability on trial outcomes and offering a more sensitive and reproducible measure of patient responses

Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review

Classifying chimpanzee (Pan troglodytes) landscapes across large scale environmental gradients in Africa

Primates are sometimes categorized in terms of their habitat. Although such categorization can be over-simplistic, there are scientific benefits from the clarity and consistency that habitat categorization can bring. Chimpanzees (Pan troglodytes) inhabit various environments, but researchers often refer to ‘forest’ or ‘savanna’ chimpanzees. Despite the wide use of this forest-savanna distinction, clear definitions of these landscapes for chimpanzees, based on environmental variables at study sites or determined in relation to existing bioclimatic classifications, are lacking. The robustness of the forest-savanna distinction thus remains to be assessed. We review 43 chimpanzee study sites to assess how the landscape classifications of researchers fit with the environmental characteristics of study sites and with three bioclimatic classifications. We use scatterplots and Principal Components 15 Analysis to assess the distribution of chimpanzee field sites along gradients of environmental 16 variables (temperature, rainfall, precipitation seasonality, forest cover and satellite-derived 17 Hansen tree cover). This revealed an environmental continuum of chimpanzee study sites 18 from savanna to dense forest, with a rarely acknowledged forest mosaic category in between, 19 but with no natural separation into these three classes and inconsistencies with the bioclimatic 20 classifications assessed. The current forest–savanna dichotomy therefore masks a progression 21 of environmental adaptation for chimpanzees, and we propose that recognizing an additional, 22 intermediate ‘forest mosaic’ category is more meaningful than focusing on the ends of this 23 environmental gradient only. Future studies should acknowledge this habitat continuum, place their study sites on the forest–savanna gradient, and include detailed environmental data to support further attempts at quantification

Kiloton-scale xenon detectors for neutrinoless double beta decay and other new physics searches

Large detectors employing xenon are a leading technology in existing and planned searches for new physics, including searches for neutrinoless double beta decay (0νββ) and dark matter. While upcoming detectors will employ target masses of a ton or more, further extending gas- or liquid-phase Xe detectors to the kton scale would enable extremely sensitive next-generation searches for rare phenomena. The key challenge to extending this technology to detectors well beyond the ton scale is the acquisition of the Xe itself. We describe the motivation for extending Xe time-projection chambers to the kton scale and possible avenues for Xe acquisition that avoid existing supply chains. If acquisition of Xe in the required quantities is successful, kton-scale detectors of this type could enable a new generation of experiments, including searches for 0νββ at half-life sensitivities as long as 1030 yr

Kiloton-scale xenon detectors for neutrinoless double beta decay and other new physics searches

Large detectors employing xenon are a leading technology in existing and planned searches for new physics, including searches for neutrinoless double beta decay (0νββ) and dark matter. While upcoming detectors will employ target masses of a ton or more, further extending gas- or liquid-phase Xe detectors to the kton scale would enable extremely sensitive next-generation searches for rare phenomena. The key challenge to extending this technology to detectors well beyond the ton scale is the acquisition of the Xe itself. We describe the motivation for extending Xe time-projection chambers to the kton scale and possible avenues for Xe acquisition that avoid existing supply chains. If acquisition of Xe in the required quantities is successful, kton-scale detectors of this type could enable a new generation of experiments, including searches for 0νββ at half-life sensitivities as long as 1030 yr