Studies in the nitrogen heterocyclic series

PART I. SYNTHESES IN THE QUINOXALINE SERIES: Several α-hydroxy nitrogen heterocyclic bases have been treated with an equimolecular mixture of phosphorus oxychloride and water. Simple α-hydroxyquinoxalines, acridone, and phenanthridone are converted to the corresponding chloro derivatives by this mixture. The mixture is a less efficient chlorinating agent than phosphorus oxychloride itself. Derivatives of methin-(2'-(3'-keto) tetrahydroquinoxaline) I are converted to the corresponding methin-(2'-dihydroquinoxaline) bases II in good yield by this mixture. Methin-(2- pyrazinyl)-(2'-dihydroquinoxaline) (II - R = 2-pyrazinyl) and a yellow base, C₁₃H₈N₄, for which the structure 10H- pyrazino (2',3':3,4)cyclopenta(b) quinoxaline III has been suggested, are obtained when methin-(2-quinoxalinyl)-(2' -(3' -keto) piperazine) IV is treated with the mixture. Two bases are also obtained when methin-(2-pyrazinyl)- (2' -(3'-keto)piperazine) is treated with the mixture. Structures have been proposed for these bases. Attempts to synthesise 1'-ketocyclopenta (4',5':2,3) quinoxaline, the starting material for a proposed synthesis of 10H-pyrazino (2', 3':3,4)cyclopenta(b)quinoxaline III, have been made. PART II STUDIES ON CERTAIN QUINOXALINE DERIVATIVES. This research has been directed toward the elucidation of the structure of a red base, C₂₀₁H₄N₄, obtained from the reaction of 2-acetyl-3-methylquinoxaline with 2-methylquinoxaline in dilute acid. A structure, quinoxalo(2',3':8,9)benzo(2,3)-7-methyl-tropazine V, had been proposed for this base. An attempt to prepare quinoxalo (2',3':8,9)benzo(2,3)tropazine by the cyclisation of α-(3-methylquinoxaliny1-2)-ß-(quinoxalinyl- 2')-ethylene was unsuccessful. Attempts to brominate the C-methyl group with bromine directly and with N-bromosuccinimide failed. Attempted oxidations of the C-methyl group with selenium dioxide, and of the base with hydrogen peroxide, ozone and osmium tetroxide failed to give identifiable products. Chromic acid oxidation, however, gave a ketone, C₁₁H₈ or ₉N₂0, for which a structure has been tentatively advanced. Investigations into the method of formation of the base have ruled out the previously proposed method of formation. Doubt has been cast on the proposed structure of the base and preliminary investigations of a similar bromo-substituted red base have been made

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

A multi-country analysis of COVID-19 hospitalizations by vaccination status

Background: Individuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), when infected, can still develop disease that requires hospitalization. It remains unclear whether these patients differ from hospitalized unvaccinated patients with regard to presentation, coexisting comorbidities, and outcomes. Methods: Here, we use data from an international consortium to study this question and assess whether differences between these groups are context specific. Data from 83,163 hospitalized COVID-19 patients (34,843 vaccinated, 48,320 unvaccinated) from 38 countries were analyzed. Findings: While typical symptoms were more often reported in unvaccinated patients, comorbidities, including some associated with worse prognosis in previous studies, were more common in vaccinated patients. Considerable between-country variation in both in-hospital fatality risk and vaccinated-versus-unvaccinated difference in this outcome was observed. Conclusions: These findings will inform allocation of healthcare resources in future surges as well as design of longer-term international studies to characterize changes in clinical profile of hospitalized COVID-19 patients related to vaccination history. Funding: This work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome (215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z, and 220757/Z/20/Z); the Bill & Melinda Gates Foundation (OPP1209135); and the philanthropic support of the donors to the University of Oxford's COVID-19 Research Response Fund (0009109). Additional funders are listed in the "acknowledgments" section

An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients

Background: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings. Methods: Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. Results: Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61-0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population. Conclusions: Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome