COVID-19, nausea, and vomiting.

Exclusion of nausea (N) and vomiting (V) from detailed consideration as symptoms of COVID‐19 is surprising as N can be an early presenting symptom. We examined the incidence of NV during infection before defining potential mechanisms. We estimate that the overall incidence of nausea (median 10.5%), although variable, is comparable with diarrhea. Poor definition of N, confusion with appetite loss, and reporting of N and/or V as a single entity may contribute to reporting variability and likely underestimation. We propose that emetic mechanisms are activated by mediators released from the intestinal epithelium by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) modulate vagal afferents projecting to the brainstem and after entry into the blood, activate the area postrema (AP) also implicated in anorexia. The receptor for spike protein of SARS‐CoV‐2, angiotensin 2 converting enzyme (ACE2), and transmembrane protease serine (for viral entry) is expressed in upper gastrointestinal (GI) enterocytes, ACE2 is expressed on enteroendocrine cells (EECs), and SARS‐CoV‐2 infects enterocytes but not EECs (studies needed with native EECs). The resultant virus‐induced release of epithelial mediators due to exocytosis, inflammation, and apoptosis provides the peripheral and central emetic drives. Additionally, data from SARS‐CoV‐2 show an increase in plasma angiotensin II (consequent on SARS‐CoV‐2/ACE2 interaction), a centrally (AP) acting emetic, providing a further potential mechanism in COVID‐19. Viral invasion of the dorsal brainstem is also a possibility but more likely in delayed onset symptoms. Overall, greater attention must be given to nausea as an early symptom of COVID‐19 and for the insights provided into the GI effects of SARS‐CoV‐2

Conflict-free connection numbers of line graphs

A path in an edge-colored graph is called \emph{conflict-free} if it contains at least one color used on exactly one of its edges. An edge-colored graph $G$ is \emph{conflict-free connected} if for any two distinct vertices of $G$, there is a conflict-free path connecting them. For a connected graph $G$, the \emph{conflict-free connection number} of $G$, denoted by $cfc(G)$, is defined as the minimum number of colors that are required to make $G$ conflict-free connected. In this paper, we investigate the conflict-free connection numbers of connected claw-free graphs, especially line graphs. We first show that for an arbitrary connected graph $G$, there exists a positive integer $k$ such that $cfc(L^k(G))\leq 2$. Secondly, we get the exact value of the conflict-free connection number of a connected claw-free graph, especially a connected line graph. Thirdly, we prove that for an arbitrary connected graph $G$ and an arbitrary positive integer $k$, we always have $cfc(L^{k+1}(G))\leq cfc(L^k(G))$, with only the exception that $G$ is isomorphic to a star of order at least~$5$ and $k=1$. Finally, we obtain the exact values of $cfc(L^k(G))$, and use them as an efficient tool to get the smallest nonnegative integer $k_0$ such that $cfc(L^{k_0}(G))=2$.Comment: 11 page

Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists

PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg(−1) dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg(−1), which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5 mg kg(−1)) emesis by 68% (45–91%) during the acute phase (day 1) and by 67% (48–86%) and 53% (38–68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret

Quantile Models with Endogeneity

In this article, we review quantile models with endogeneity. We focus on models that achieve identification through the use of instrumental variables and discuss conditions under which partial and point identification are obtained. We discuss key conditions, which include monotonicity and full-rank-type conditions, in detail. In providing this review, we update the identification results of Chernozhukov & Hansen (2005). We illustrate the modeling assumptions through economically motivated examples. We also briefly review the literature on estimation and inference

Quantifying sources of methane using light alkanes in the Los Angeles basin, California

Methane (CH4), carbon dioxide (CO2), carbon monoxide (CO), and C2-C5 alkanes were measured throughout the Los Angeles (L.A.) basin in May and June 2010. We use these data to show that the emission ratios of CH4/CO and CH4/CO2 in the L.A. basin are larger than expected from population-apportioned bottom-up state inventories, consistent with previously published work. We use experimentally determined CH4/CO and CH4/CO2 emission ratios in combination with annual State of California CO and CO2 inventories to derive a yearly emission rate of CH4 to the L.A. basin. We further use the airborne measurements to directly derive CH4 emission rates from dairy operations in Chino, and from the two largest landfills in the L.A. basin, and show these sources are accurately represented in the California Air Resources Board greenhouse gas inventory for CH4. We then use measurements of C2-C5 alkanes to quantify the relative contribution of other CH4 sources in the L.A. basin, with results differing from those of previous studies. The atmospheric data are consistent with the majority of CH4 emissions in the region coming from fugitive losses from natural gas in pipelines and urban distribution systems and/or geologic seeps, as well as landfills and dairies. The local oil and gas industry also provides a significant source of CH4 in the area. The addition of CH4 emissions from natural gas pipelines and urban distribution systems and/or geologic seeps and from the local oil and gas industry is sufficient to account for the differences between the top-down and bottom-up CH4 inventories identified in previously published work. Key PointsTop-down estimates of CH4 emissions in L.A. are greater than inventory estimatesEstimates of CH4 emissions from landfills in L.A. agree with CARB inventoryPipeline natural gas and/or seeps, and landfills are main sources of CH4 in L.A. ©2013. American Geophysical Union. All Rights Reserved

<em>Micromonospora parastrephiae</em> sp. nov. and <em>Micromonospora tarensis</em> sp. nov., isolated from the rhizosphere of a <em>Parastrephia quadrangularis</em> plant growing in the Salar de Tara region of the Central Andes in Chile

\ua9 2023 The Authors. Two novel Micromonospora strains, STR1-7T and STR1S-6T, were isolated from the rhizosphere of a Parastrephia quadran-gularis plant growing in the Salar de Tara region of the Atacama Desert, Chile. Chemotaxonomic, cultural and phenotypic features confirmed that the isolates belonged to the genus Micromonospora. They grew from 20 to 37 \ub0C, from pH7 to 8 and in the presence of up to 3 %, w/v NaCl. The isolates formed distinct branches in Micromonospora gene trees based on 16S rRNA gene sequences and on a multi-locus sequence analysis of conserved house-keeping genes. A phylogenomic tree generated from the draft genomes of the isolates and their closest phylogenetic neighbours showed that isolate STR1-7T is most closely related to Micromonospora orduensis S2509T, and isolate STR1S-6T forms a distinct branch that is most closely related to 12 validly named Micromonospora species, including Micromonospora saelicesensis the earliest proposed member of the group. The isolates were separated from one another and from their closest phylogenomic neighbours using a combination of chemo-taxonomic, genomic and phenotypic features, and by low average nucleotide index and digital DNA–DNA hybridization values. Consequently, it is proposed that isolates STR1-7T and STR1S-6T be recognized as representing new species in the genus Micromonospora, namely as Micromonospora parastrephiae sp. nov. and Micromonospora tarensis sp. nov.; the type strains are STR1-7T (=CECT 9665T=LMG 30768T) and STR1S-6T (=CECT 9666T=LMG 30770T), respectively. Genome mining showed that the isolates have the capacity to produce novel specialized metabolites, notably antibiotics and compounds that promote plant growth, as well as a broad-range of stress-related genes that provide an insight into how they cope with harsh abiotic conditions that prevail in high-altitude Atacama Desert soils

Icebergs in the North Atlantic: Modelling circulation changes and glacio-marine deposition

In order to investigate meltwater events in the North Atlantic, a simple iceberg generation, drift, and melting routine was implemented in a high-resolution OGCM. Starting from the modelled last glacial state, every 25th day cylindrical model icebergs 300 meters high were released at 32 specific points along the coasts. Icebergs launched at the Barents Shelf margin spread a light meltwater lid over the Norwegian and Greenland Seas, shutting down the deep convection and the anti-clockwise circulation in this area. Due to the constraining ocean circulation, the icebergs produce a tongue of relatively cold and fresh water extending eastward from Hudson Strait that must develop at this location, regardless of iceberg origin. From the total amount of freshwater inferred by the icebergs, the thickness of the deposited IRD could be calculated in dependance of iceberg sediment concentration. In this way, typical extent and thickness of Heinrich layers could be reproduced, running the model for 250 years of steady state with constant iceberg meltwater inflow