Objectives To estimate the marginal effectiveness of a fourth versus third dose and the vaccine effectiveness of mRNA covid-19 vaccines BNT162b2 and mRNA-1273 against any infection, symptomatic infection, and severe outcomes (hospital admission or death) related to the omicron variant. Design Test negative design. Setting Long term care facilities in Ontario, Canada, 30 December 2021 to 27 April 2022. Participants After exclusions, 61 344 residents aged 60 years or older across 626 long term care facilities in Ontario, Canada who were tested for SARS-CoV-2 were included. Main outcome measures Laboratory confirmed omicron SARS-CoV-2 infection (any and symptomatic) by reverse transcription polymerase chain reaction (RT-PCR), and hospital admission or death. Multivariable logistic regression was used to estimate marginal effectiveness (four versus three doses) and vaccine effectiveness (two, three, or four doses versus no doses) while adjusting for personal characteristics, comorbidities, week of test, and previous positive SARS-CoV-2 test result more than 90 days previously. Results 13 654 residents who tested positive for omicron SARS-CoV-2 infection and 205 862 test negative controls were included. The marginal effectiveness of a fourth dose (95% of vaccine recipients received mRNA-1273 as the fourth dose) seven days or more after vaccination versus a third dose received 84 or more days previously was 19% (95% confidence interval 12% to 26%) against infection, 31% (20% to 41%) against symptomatic infection, and 40% (24% to 52%) against severe outcomes. Vaccine effectiveness in vaccine recipients (compared with unvaccinated) increased with each additional dose, and for a fourth dose was 49% (95% confidence interval 43% to 54%) against infection, 69% (61% to 76%) against symptomatic infection, and 86% (81% to 90%) against severe outcomes. Conclusions The findings suggest that compared with a third dose of mRNA covid-19 vaccine, a fourth dose improved protection against infection, symptomatic infection, and severe outcomes among long term care residents during an omicron dominant period. A fourth vaccine dose was associated with strong protection against severe outcomes in vaccinated residents compared with unvaccinated residents, although the duration of protection remains unknown.
The fragmentation of protonated tripeptides under metastable ion conditions and collision-induced conditions are reported. The majority of protonated tripeptides cleave at the C-terminal amide bond to form b2 and y1 ions, with the relative amounts depending on the proton affinities of the amino acids derived from the C-terminal amino acid residue. Protonated tripeptides that have a proline residue at the C-terminal position fragment almost exclusively by cleavage of the amide bond adjacent to the proline and give mainly y1 ions; where there is a proline residue in the central position, fragmentation of the protonated tripeptide occurs at both the N-terminal and the C-terminal amide bonds to form y2 and b2 ions; finally, two of the tripeptides with proline at the N-terminal position, Pro-Pro-Pro and Pro-Gly-Gly, fragment largely by cleavage at the N-terminal, the former by cleavage of the amide bond and the latter by direct formation of the a1 ion. Protonated Pro-Val-Gly fragments to give predominantly b2 and a2 ions at low energy, but the a1 ion becomes the dominant product at higher energies. In the fragmentation of protonated peptides, the lack of b ions formed by cleavage at the amide bond C-terminal to proline (i.e., with the proline residue in the oxazolone ring) has conventionally been attributed to ring strain in a bicyclic oxazolone. Here we show, however, that the bicyclic oxazolone structure containing proline derived from protonated Gly-Pro-Gly is only 2.7 kcal/mol higher in free energy, at the B3LYP/6-31++G(d,p) level of theory, than the isomeric nonbicyclic oxazolone derived from protonated Pro−Gly−Gly; that is, strain appears to be a small or negligible factor. Formation of the y2 ion in protonated Gly-Pro-Gly has a barrier of 3 kcal/mol higher free energy than that of the b2 ion. In comparison, the difference increases to 10 kcal/mol in protonated Gly-Phe-Gly. The neutral products that are formed along with the y2 ion are CO and methanimine, not aziridinone as once proposed.
BackgroundThe re-emergence of syphilis among HIV-positive gay and other men who have sex with men (MSM) requires vigilance. We estimated incidence of and risk factors for first and subsequent syphilis diagnoses among MSM in HIV care in Ontario, Canada.MethodsWe analyzed data from 2,280 MSM under follow-up from 2006 to 2010 in the Ontario HIV Treatment Network Cohort Study (OCS), a multi-site clinical cohort. We obtained syphilis serology results via record linkage with the provincial public health laboratory. Rates were calculated using Poisson regression.ResultsFirst syphilis diagnoses occurred at a rate of 2.0 per 100 person-years (95 % CI 1.7, 2.4; 121 cases) whereas the re-diagnosis rate was 7.5 per 100 person-years (95 % CI 6.3, 8.8; 136 cases). We observed higher rates over time and among men who were aged <30 years, receiving care in the two largest urban centers, or had a previous syphilis diagnosis. Syphilis diagnosis was less common among Indigenous men, men with higher CD4 cell counts, and, for first diagnoses only, among men with less than high school education.ConclusionsCompared to reported cases in the general male population, incidence of a new syphilis diagnosis was over 300 times greater among HIV-positive MSM but year-to-year changes reflected provincial trends. Re-diagnosis was common, suggesting treatment failure or re-infection. Novel syphilis control efforts are needed among HIV-positive MSM.
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