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We conducted simulations, a preference judgment task for novel contour shapes, and applied computational model analyses to the behavioral data. The results showed that the CBL model with both the chosen and rejected value’s updated were a good fit for the IDM behavioral data compared to the other candidate models. Although previous studies using subjective preference ratings had repeatedly reported changes only in one of the values of either the chosen or rejected items, we demonstrated for the first time both items’ value changes were based solely on IDM choice behavioral data with computational model analyses.Characterizing the gut microbiota in terms of their capacity to interfere with drug metabolism is necessary to achieve drug efficacy and safety. Although examples of drug-microbiome interactions are well-documented, little has been reported about a computational pipeline for systematically identifying and characterizing bacterial enzymes that process particular classes of drugs. The goal of our study is to develop a computational approach that compiles drugs whose metabolism may be influenced by a particular class of microbial enzymes and that quantifies the variability in the collective level of those enzymes among individuals. The present paper describes this approach, with microbial β-glucuronidases as an example, which break down drug-glucuronide conjugates and reactivate the drugs or their metabolites. We identified 100 medications that may be metabolized by β-glucuronidases from the gut microbiome. These medications included morphine, estrogen, ibuprofen, midazolam, and their structural analogues. The analysis of metagenomic data available through the Sequence Read Archive (SRA) showed that the level of β-glucuronidase in the gut metagenomes was higher in males than in females, which provides a potential explanation for the sex-based differences in efficacy and toxicity for several drugs, reported in previous studies. Our analysis also showed that infant gut metagenomes at birth and 12 months of age have higher levels of β-glucuronidase than the metagenomes of their mothers and the implication of this observed variability was discussed in the context of breastfeeding as well as infant hyperbilirubinemia. Overall, despite important limitations discussed in this paper, our analysis provided useful insights on the role of the human gut metagenome in the variability in drug response among individuals. Importantly, this approach exploits drug and metagenome data available in public databases as well as open-source cheminformatics and bioinformatics tools to predict drug-metagenome interactions.

Histopathologic factors predictive of nintedanib efficacy in idiopathic pulmonary fibrosis have not been studied. We aimed to describe the characteristics, focusing on histopathology, of idiopathic pulmonary fibrosis patients who did and did not respond to nintedanib.

This study retrospectively examined the clinicoradiopathologic features of 40 consecutive patients with surgical lung biopsy-confirmed idiopathic pulmonary fibrosis treated with nintedanib. Additionally, we compared the histopathologic scoring of 21 microscopic features between patients with functional or radiological progression and those with non-progression during 12 months of treatment.

The histopathologic evaluation showed edematous changes in the interlobular septum as the only histologic finding observed more frequently in patients with both functional and radiological progression than in those without (58% vs. 14%, P = 0.007 and 50% vs. 0%, P = 0.003, respectively). Regarding per-year change, patients with edematous changes in the interlobular septum showed greater progression in median changes in spared area (-12%, interquartile range [-25%–5%], vs. -3% [-7%-0%], P = 0.004) and reticular shadow (7% [3%-13%], vs. 0% [0%-5%], P = 0.041) on computed tomography. Functional and radiological progression-free survival were shorter in patients with edematous changes in the interlobular septum than in those without (6.6 months, 95% confidence interval [5.9-25.3], vs. event <50%, [12.1-Not available], P = 0.0009, and 6.1 months, [5.2-6.6] vs. 14.5 months [7.8-not available], P<0.0001).

Edematous changes in the interlobular septum may indicate poor nintedanib efficacy in idiopathic pulmonary fibrosis. Further studies are needed to validate these findings and address the mechanism behind ECIS.

Edematous changes in the interlobular septum may indicate poor nintedanib efficacy in idiopathic pulmonary fibrosis. Further studies are needed to validate these findings and address the mechanism behind ECIS.

Reducing potentially preventable hospitalisations (PPH) is a priority for health services. This paper describes the factors that clinicians perceived contributed to preventable admissions for angina, diabetes, congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD), and what they considered might have been done in the three months leading up to an admission to prevent it.

The study was conducted in a rural and a metropolitan health district in NSW, Australia. Expert Panels reviewed detailed case reports to assess preventability. For those admissions identified as preventable, comments from clinicians indicating what they perceived could have made a difference and/or been done differently to prevent each of the preventable admissions were analysed qualitatively.

148 (46%) of 323 admissions were assessed as preventable. Across the two districts, the most commonly identified groups of contributing factors to preventable admissions were ‘Systems issues Community based services missinor comprehensiveness may explain why many programs seeking to reduce PPH have been unsuccessful.

These findings suggest preventability of individual admissions is complex and context specific. There is no single, simple solution likely to reduce PPH. Rather, an approach addressing multiple factors is required. This need for comprehensiveness may explain why many programs seeking to reduce PPH have been unsuccessful.Facial expressions are complex and subtle signals, central for communication and emotion in social mammals. Traditionally, facial expressions have been classified as a whole, disregarding small but relevant differences in displays. Even with the same morphological configuration different information can be conveyed depending on the species. Due to a hardwired processing of faces in the human brain, humans are quick to attribute emotion, but have difficulty in registering facial movement units. The well-known human FACS (Facial Action Coding System) is the gold standard for objectively measuring facial expressions, and can be adapted through anatomical investigation and functional homologies for cross-species systematic comparisons. GW4064 agonist Here we aimed at developing a FACS for Japanese macaques, following established FACS methodology first, we considered the species’ muscular facial plan; second, we ascertained functional homologies with other primate species; and finally, we categorised each independent facial movement into Action Units (AUs).