Heterogeneity of human adipose blood flow

BACKGROUND: The long time pharmacokinetics of highly lipid soluble compounds is dominated by blood-adipose tissue exchange and depends on the magnitude and heterogeneity of adipose blood flow. Because the adipose tissue is an infinite sink at short times (hours), the kinetics must be followed for days in order to determine if the adipose perfusion is heterogeneous. The purpose of this paper is to quantitate human adipose blood flow heterogeneity and determine its importance for human pharmacokinetics. METHODS: The heterogeneity was determined using a physiologically based pharmacokinetic model (PBPK) to describe the 6 day volatile anesthetic data previously published by Yasuda et. al. The analysis uses the freely available software PKQuest and incorporates perfusion-ventilation mismatch and time dependent parameters that varied from the anesthetized to the ambulatory period. This heterogeneous adipose perfusion PBPK model was then tested by applying it to the previously published cannabidiol data of Ohlsson et. al. and the cannabinol data of Johansson et. al. RESULTS: The volatile anesthetic kinetics at early times have only a weak dependence on adipose blood flow while at long times the pharmacokinetics are dominated by the adipose flow and are independent of muscle blood flow. At least 2 adipose compartments with different perfusion rates (0.074 and 0.014 l/kg/min) were needed to describe the anesthetic data. This heterogeneous adipose PBPK model also provided a good fit to the cannabinol data. CONCLUSION: Human adipose blood flow is markedly heterogeneous, varying by at least 5 fold. This heterogeneity significantly influences the long time pharmacokinetics of the volatile anesthetics and tetrahydrocannabinol. In contrast, using this same PBPK model it can be shown that the long time pharmacokinetics of the persistent lipophilic compounds (dioxins, PCBs) do not depend on adipose blood flow. The ability of the same PBPK model to describe both the anesthetic and cannabinol kinetics provides direct qualitative evidence that their kinetics are flow limited and that there is no significant adipose tissue diffusion limitation

Search for resonant and nonresonant production of pairs of dijet resonances in proton-proton collisions at s \sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2206.09997v2 [hep-ex], https://arxiv.org/abs/2206.09997v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at this http URL (CMS Public Pages). Report number: CMS-EXO-21-010, CERN-EP-2022-103,A search for pairs of dijet resonances with the same mass is conducted in final states with at least four jets. Results are presented separately for the case where the four jet production proceeds via an intermediate resonant state and for nonresonant production. The search uses a data sample corresponding to an integrated luminosity of 138 fb^{−1} collected by the CMS detector in proton-proton collisions at √s = 13 TeV. Model-independent limits, at 95% confidence level, are reported on the production cross section of four-jet and dijet resonances. These first LHC limits on resonant pair production of dijet resonances via high mass intermediate states are applied to a signal model of diquarks that decay into pairs of vector-like quarks, excluding diquark masses below 7.6 TeV for a particular model scenario. There are two events in the tails of the distributions, each with a four-jet mass of 8 TeV and an average dijet mass of 2 TeV, resulting in local and global significances of 3.9 and 1.6 standard deviations, respectively, if interpreted as a signal. The nonresonant search excludes pair production of top squarks with masses between 0.50 TeV to 0.77 TeV, with the exception of a small interval between 0.52 and 0.58 TeV, for supersymmetric R-parity-violating decays to quark pairs, significantly extending previous limits. Here, the most significant excess above the predicted background occurs at an average dijet mass of 0.95 TeV, for which the local and global significances are 3.6 and 2.5 standard deviations, respectively.SCOAP3

Development and application of an off-line SPE-LC-UV methodology for the determination of penoxsulam in aquatic systems adjacent to rice fields

An accurate, simple, reproducible and sensitive off-line SPE–LC–UV method was developed and validated for the determination of penoxsulam, a new triazolopyrimidine sulphonamide herbicide widely used in rice culture. The method was validated in terms of precision, linearity, detection limit, quantification limit and accuracy. The repeatability and intermediate precision of LC–UV conditions chosen were evaluated, with an RSD always bellow 10%. A limit of detection of 0.07 lgL -1 was achieved after SPE concentration. Recovery studies, performed in two different matrixes (run-off water from rice fields and brackish water), ranged from 93 to 105%. The methodology was successfully used to detect penoxsulam in aquatic systems, during an application period in rice fields.publishe