18 research outputs found
Contextuality and nonlocality in 'no signaling' theories
We define a family of 'no signaling' bipartite boxes with arbitrary inputs
and binary outputs, and with a range of marginal probabilities. The defining
correlations are motivated by the Klyachko version of the Kochen-Specker
theorem, so we call these boxes Kochen-Specker-Klyachko boxes or, briefly,
KS-boxes. The marginals cover a variety of cases, from those that can be
simulated classically to the superquantum correlations that saturate the
Clauser-Horne-Shimony-Holt inequality, when the KS-box is a generalized PR-box
(hence a vertex of the `no signaling' polytope). We show that for certain
marginal probabilities a KS-box is classical with respect to nonlocality as
measured by the Clauser-Horne-Shimony-Holt correlation, i.e., no better than
shared randomness as a resource in simulating a PR-box, even though such
KS-boxes cannot be perfectly simulated by classical or quantum resources for
all inputs. We comment on the significance of these results for contextuality
and nonlocality in 'no signaling' theories.Comment: 22 pages. Changes to Introduction and final Commentary section. Added
two tables, one to Section 5, and some new reference
Higher Midazolam Clearance in Obese Adolescents Compared with Morbidly Obese Adults
Background
The clearance of cytochrome P450 (CYP) 3A substrates is reported to be reduced with lower age, inflammation and obesity. As it is unknown what the overall influence is of these factors in the case of obese adolescents vs. morbidly obese adults, we studied covariates influencing the clearance of the CYP3A substrate midazolam in a combined analysis of data from obese adolescents and morbidly obese adults.
Methods
Data from 19 obese adolescents [102.7 kg (62â149.5 kg)] and 20 morbidly obese adults [144 kg (112â186 kg)] receiving intravenous midazolam were analysed, using population pharmacokinetic modelling (NONMEM 7.2). In the covariate analysis, the influence of study group, age, total body weight (TBW), developmental weight (WTfor age and length) and excess body weight (WTexcess = TBW â WTfor age and length) was evaluated.
Results
The population mean midazolam clearance was significantly higher in obese adolescents than in morbidly obese adults [0.71 (7%) vs. 0.44 (11%) L/min; p < 0.01]. Moreover, clearance in obese adolescents increased with TBW (p < 0.01), which seemed mainly explained by WTexcess, and for which a so-called âexcess weightâ model scaling WTfor age and length to the power of 0.75 and a separate function for WTexcess was proposed.
Discussion
We hypothesise that higher midazolam clearance in obese adolescents is explained by less obesity-induced suppression of CYP3A activity, while the increase with WTexcess is explained by increased liver blood flow. The approach characterising the influence of obesity in the paediatric population we propose here may be of value for use in future studies in obese adolescents
Population pharmacokinetics of midazolam and its metabolites in overweight and obese adolescents
Aim In view of the increasing prevalence of obesity in adolescents, the aim of this study was to determine the pharmacokinetics of the CYP3A substrate midazolam and its metabolites in overweight and obese adolescents. Methods Overweight (BMI for age â„ 85th percentile) and ob
Saliva microbiome in relation to SARS-CoV-2 infection in a prospective cohort of healthy US adultsResearch in context
Summary: Background: The clinical outcomes of SARS-CoV-2 infection vary in severity, potentially influenced by the resident human microbiota. There is limited consensus on conserved microbiome changes in response to SARS-CoV-2 infection, with many studies focusing on severely ill individuals. This study aimed to assess the variation in the upper respiratory tract microbiome using saliva specimens in a cohort of individuals with primarily mild to moderate disease. Methods: In early 2020, a cohort of 831 adults without known SARS-CoV-2 infection was followed over a six-month period to assess the occurrence and natural history of SARS-CoV-2 infection. From this cohort, 81 participants with a SARS-CoV-2 infection, along with 57 unexposed counterparts were selected with a total of 748 serial saliva samples were collected for analysis. Total bacterial abundance, composition, population structure, and gene function of the salivary microbiome were measured using 16S rRNA gene and shotgun metagenomic sequencing. Findings: The salivary microbiome remained stable in unexposed individuals over the six-month study period, as evidenced by all measured metrics. Similarly, participants with mild to moderate SARS-CoV-2 infection showed microbiome stability throughout and after their infection. However, there were significant reductions in microbiome diversity among SARS-CoV-2-positive participants with severe symptoms early after infection. Over time, the microbiome diversity in these participants showed signs of recovery. Interpretation: These findings demonstrate the resilience of the salivary microbiome in relation to SARS-CoV-2 infection. Mild to moderate infections did not significantly disrupt the stability of the salivary microbiome, suggesting its ability to maintain its composition and function. However, severe SARS-CoV-2 infection was associated with temporary reductions in microbiome diversity, indicating the limits of microbiome resilience in the face of severe infection. Funding: This project was supported in part by Danone North America and grants from the National Institutes of Health, United States