Assessment of synthetic cannabinoid FUB-AMB and its ester hydrolysis metabolite in human liver microsomes and human blood samples using UHPLC–MS/MS

FUB-AMB, an indazole carboxamide synthetic cannabinoid recreational drug, was one of the compounds most frequently reported to governmental agencies worldwide between 2016 and 2019. It has been implicated in intoxications and fatalities, posing a risk to public health. In the current study, FUB-AMB was incubated with human liver microsomes (HLM) to assess its metabolic fate and stability and to determine if its major ester hydrolysis metabolite (M1) was present in 12 authentic forensic human blood samples from driving under the influence of drug cases and postmortem investigations using UHPLC–MS/MS. FUB-AMB was rapidly metabolized in HLM, generating M1 that was stable through a 120-min incubation period, a finding that indicates a potential long detection window in human biological samples. M1 was identified in all blood samples, and no parent drug was detected. The authors propose that M1 is a reliable marker for inclusion in laboratory blood screens for FUB-AMB; this metabolite may be pharmacologically active like its precursor FUB-AMB. M1 frequently appears in samples in which the parent drug is undetectable and can point to the causative agent. The results suggest that it is imperative that synthetic cannabinoid laboratory assay panels include metabolites, especially known or potential pharmacologically active metabolites, particularly for compounds with short half-lives.     

The Essential Spectrum of Schrödinger, Jacobi, and CMV Operators

We provide a very general result which identifies the essential spectrum of broad classes of operators as exactly equal to the closure of the union of the spectra of suitable limits at infinity. Included is a new result on the essential spectra when potentials are asymptotic to isospectral tori. We also recover within a unified framework the HVZ Theorem and Krein's results on orthogonal polynomials with finite essential spectra. Supported in part by The Israel Science Foundation (grant No. 188/02). Supported in part by NSF grant DMS-01 40592. Research supported in part by grant No. 2002068 from the United States-Israel Binational Science Foundation (BSF), Jerusalem, Israel.     

Spray flame dynamics with oscillating flow and droplet grouping

The co-flow laminar spray diffusion flame in an oscillating flow field is investigated. Mild slip is permitted between the droplets and their host surroundings and droplet grouping resulting from the host flow oscillations is accounted for. The spray is modelled using the sectional approach and a perturbation analysis using a small sectional Stokes number is utilised for solving the liquid phase governing equations. The effect of droplet grouping is described through a specially constructed model for the vaporisation Damkohler number. The large chemical Damkohler number assumption is adopted and a formal analytical solution is developed for Schwab-Zeldovitch parameters through which the dynamics of the spray flame front shapes and thermal fields are deduced. Computed results based on the solutions demonstrate how the phenomenon of droplet grouping can lead to the existence of multiple flame sheets as a result of the dynamic change in the type of the main homogeneous flame from under- to over-ventilated as the flow field oscillates. Concomitant fluctuating thermal fields are also shown to be present indicating a potential impact on undesirable pollutants production.     

Children’s use of realistic considerations in problem solving: some English evidence

This is the second of two papers exploring children’s responses to an extended version of a division-with-remainder problem intended to elicit general rather than particular realistic considerations during mathematical problem solving. Responses to two problems are analyzed. The first is a ‘realistically’ contextualised item drawn from national tests in England whose ambiguities have been previously discussed (Cooper, 1992); the second is a version of this problem revised to encourage a wider range of realistic responses. In Cooper and Harries (2002), the responses of children at the end of their first year of secondary schooling were analyzed. Here the responses of children at the end of their primary schooling are analyzed and compared with the previous results. It is shown that many children, given suitable encouragement, are willing and able to enter into an extended form of realistic thinking during problem solving, although the original test item renders this invisible.     

Non-Uniformity and Generalised Sacks Splitting

We show that there do not exist computable functions f ₁(e, i), f ₂(e, i), g ₁(e, i), g ₂(e, i) such that for all e, i ∈ ω, (1) $ {\left( {W_{{f_{1} {\left( {e,i} \right)}}} - W_{{f_{2} {\left( {e,i} \right)}}} } \right)} \leqslant _{{\rm T}} {\left( {W_{e} - W_{i} } \right)}; $ (2) $ {\left( {W_{{g_{1} {\left( {e,i} \right)}}} - W_{{g_{2} {\left( {e,i} \right)}}} } \right)} \leqslant _{{\rm T}} {\left( {W_{e} - W_{i} } \right)}; $ (3) $ {\left( {W_{e} - W_{i} } \right)} \not\leqslant _{{\rm T}} {\left( {W_{{f_{1} {\left( {e,i} \right)}}} - W_{{f_{2} {\left( {e,i} \right)}}} } \right)} \oplus {\left( {W_{{g_{1} {\left( {e,i} \right)}}} - W_{{g_{2} {\left( {e,i} \right)}}} } \right)}; $ (4) $ {\left( {W_{e} - W_{i} } \right)} \not\leqslant _{{\rm T}} {\left( {W_{{f_{1} {\left( {e,i} \right)}}} - W_{{f_{2} {\left( {e,i} \right)}}} } \right)}{\text{unless}}{\left( {W_{e} - W_{i} } \right)} \leqslant _{{\rm T}} {\emptyset};{\text{and}} $ (5) $ {\left( {W_{e} - W_{i} } \right)} \leqslant _{{\rm T}} {\left( {W_{{g_{1} {\left( {e,i} \right)}}} - W_{{g_{2} {\left( {e,i} \right)}}} } \right)}{\text{unless}}{\left( {W_{e} - W_{i} } \right)} \leqslant _{{\rm T}} {\emptyset}. $ It follows that the splitting theorems of Sacks and Cooper cannot be combined uniformly.     

On a Conjecture of Kleene and Post

A proof is given that 0 ′ (the argest Turing degree containing a computably enumerable set) is definable in the structure of the degrees of unsolvability. This answers a long‐standing question of Kleene and Post, and has a number of corollaries including the definability of the jump operator.     

In situ device for salinity measurements (chloride detection) of ocean surface

Microbend sodium chloride sensors based on polymer swelling are the latest approach to fiberoptic sodium chloride sensors. We have designed, constructed, and tested a compact microbend fiberoptic sodium chloride sensor that utilizes microbend and polymer swelling effects through the use of modified polymer beads. The design of this sensor is an improvement over previously reported microbend sensors. This sodium chloride sensor has shown feasibility as a practical, stable, inexpensive device with excellent performance and most of the desirable sensor properties including reversibility. Further optimization of the sensor is possible for the various applications we envision.     

Spectral-domain optical coherence phase microscopy for quantitative phase-contrast imaging

We describe a novel microscopy technique for quantitative phase-contrast imaging of a transparent specimen. The technique is based on depth-resolved phase information provided by common path spectral-domain optical coherence tomography and can measure minute phase variations caused by changes in refractive index and thickness inside the specimen. We demonstrate subnanometer level path-length sensitivity and present images obtained on reflection from a known phase object and human epithelial cheek cells.     

Nano-LC: An updated review

Low-flow chromatography has a rich history of innovation but has yet to reach widespread implementation in bioanalytical applications. Improvements in pump technology, microfluidic connections, and nano-electrospray sources for MS have laid the groundwork for broader application, and innovation in this space has accelerated in recent years. This article reviews the instrumentation used for nano-flow LC, the types of columns employed, and strategies for multidimensionality of separations, which are key to the future state of the technique to the high-throughput needs of modern bioanalysis. An update of the current applications where nano-LC is widely used, such as proteomics and metabolomics, is discussed. But the trend toward biopharmaceutical development of increasingly complex, targeted, and potent therapeutics for the safe treatment of disease drives the need for ultimate selectivity and sensitivity of our analytical platforms for targeted quantitation in a regulated space. The selectivity needs are best addressed by mass spectrometric detection, especially at high resolutions, and exquisite sensitivity is provided by nano-electrospray ionization as the technology continues to evolve into an accessible, robust, and easy-to-use platform.