The Common Representative Intermediates Mechanism Version 2 in the United Kingdom Chemistry and Aerosols Model

Funder: Met Office and the Natural Environment Research CouncilFunder: ESA Climate Change InitiativeAbstract: We document the implementation of the Common Representative Intermediates Mechanism version 2, reduction 5 into the United Kingdom Chemistry and Aerosol model (UKCA) version 10.9. The mechanism is merged with the stratospheric chemistry already used by the StratTrop mechanism, as used in UKCA and the UK Earth System Model, to create a new CRI‐Strat mechanism. CRI‐Strat simulates a more comprehensive treatment of non‐methane volatile organic compounds (NMVOCs) and provides traceability with the Master Chemical Mechanism. In total, CRI‐Strat simulates the chemistry of 233 species competing in 613 reactions (compared to 87 species and 305 reactions in the existing StratTrop mechanism). However, while more than twice as complex than StratTrop, the new mechanism is only 75% more computationally expensive. CRI‐Strat is evaluated against an array of in situ and remote sensing observations and simulations using the StratTrop mechanism in the UKCA model. It is found to increase production of ozone near the surface, leading to higher ozone concentrations compared to surface observations. However, ozone loss is also greater in CRI‐Strat, leading to less ozone away from emission sources and a similar tropospheric ozone burden compared to StratTrop. CRI‐Strat also produces more carbon monoxide than StratTrop, particularly downwind of biogenic VOC emission sources, but has lower burdens of nitrogen oxides as more is converted into reservoir species. The changes to tropospheric ozone and nitrogen budgets are sensitive to the treatment of NMVOC emissions, highlighting the need to reduce uncertainty in these emissions to improve representation of tropospheric chemical composition

Controlling behavior, power relations within intimate relationships and intimate partner physical and sexual violence against women in Nigeria

<p>Abstract</p> <p>Background</p> <p>Controlling behavior is more common and can be equally or more threatening than physical or sexual violence. This study sought to determine the role of husband/partner controlling behavior and power relations within intimate relationships in the lifetime risk of physical and sexual violence in Nigeria.</p> <p>Methods</p> <p>This study used secondary data from a cross-sectional nationally-representative survey collected by face-to-face interviews from women aged 15 - 49 years in the 2008 Nigeria Demographic and Health Survey. Utilizing a stratified two-stage cluster sample design, data was collected frrm 19 216 eligible with the DHS domestic violence module, which is based on the Conflict Tactics Scale (CTS). Multivariate logistic regression analysis was used to determine the role of husband/partner controlling behavior in the risk of ever experiencing physical and sexual violence among 2877 women aged 15 - 49 years who were currently or formerly married or cohabiting with a male partner.</p> <p>Results</p> <p>Women who reported controlling behavior by husband/partner had a higher likelihood of experiencing physical violence (RR = 3.04; 95% CI: 2.50 - 3.69), and women resident in rural areas and working in low status occupations had increased likelihood of experiencing physical IPV. Controlling behavior by husband/partner was associated with higher likelihood of experiencing physical violence (RR = 4.01; 95% CI: 2.54 - 6.34). In addition, women who justified wife beating and earned more than their husband/partner were at higher likelihood of experiencing physical and sexual violence. In contrast, women who had decision-making autonomy had lower likelihood of experiencing physical and sexual violence.</p> <p>Conclusion</p> <p>Controlling behavior by husband/partner significantly increases the likelihood of physical and sexual IPV, thus acting as a precursor to violence. Findings emphasize the need to adopt a proactive integrated approach to controlling behavior and intimate partner violence within the society.</p

Telomere Shortening Impairs Regeneration of the Olfactory Epithelium in Response to Injury but Not Under Homeostatic Conditions

Atrophy of the olfactory epithelium (OE) associated with impaired olfaction and dry nose represents one of the most common phenotypes of human aging. Impairment in regeneration of a functional olfactory epithelium can also occur in response to injury due to infection or nasal surgery. These complications occur more frequently in aged patients. Although age is the most unifying risk factor for atrophic changes and functional decline of the olfactory epithelium, little is known about molecular mechanisms that could influence maintenance and repair of the olfactory epithelium. Here, we analyzed the influence of telomere shortening (a basic mechanism of cellular aging) on homeostasis and regenerative reserve in response to chemical induced injury of the OE in late generation telomere knockout mice (G3 mTerc−/−) with short telomeres compared to wild type mice (mTerc+/+) with long telomeres. The study revealed no significant influence of telomere shortening on homeostatic maintenance of the OE during mouse aging. In contrast, the regenerative response to chemical induced injury of the OE was significantly impaired in G3 mTerc−/− mice compared to mTerc+/+ mice. Seven days after chemical induced damage, G3 mTerc−/− mice exhibited significantly enlarged areas of persisting atrophy compared to mTerc+/+ mice (p = 0.031). Telomere dysfunction was associated with impairments in cell proliferation in the regenerating epithelium. Deletion of the cell cycle inhibitor, Cdkn1a (p21) rescued defects in OE regeneration in telomere dysfunctional mice. Together, these data indicate that telomere shortening impairs the regenerative capacity of the OE by impairing cell cycle progression in a p21-dependent manner. These findings could be relevant for the impairment in OE function in elderly people

Traumatic physical health consequences of intimate partner violence against women: what is the role of community-level factors?

<p>Abstract</p> <p>Background</p> <p>Intimate partner violence (IPV) against women is a serious public health issue with recognizable direct health consequences. This study assessed the association between IPV and traumatic physical health consequences on women in Nigeria, given that communities exert significant influence on the individuals that are embedded within them, with the nature of influence varying between communities.</p> <p>Methods</p> <p>Cross-sectional nationally-representative data of women aged 15 - 49 years in the 2008 Nigeria Demographic and Health Survey was used in this study. Multilevel logistic regression analysis was used to assess the association between IPV and several forms of physical health consequences.</p> <p>Results</p> <p>Bruises were the most common form of traumatic physical health consequences. In the adjusted models, the likelihood of sustaining bruises (OR = 1.91, 95% CI = 1.05 - 3.46), wounds (OR = 2.54, 95% CI = 1.31 - 4.95), and severe burns (OR = 3.20, 95% CI = 1.63 - 6.28) was significantly higher for women exposed to IPV compared to those not exposed to IPV. However, after adjusting for individual- and community-level factors, women with husbands/partners with controlling behavior, those with primary or no education, and those resident in communities with high tolerance for wife beating had a higher likelihood of experiencing IPV, whilst mean community-level education and women 24 years or younger were at lower likelihood of experiencing IPV.</p> <p>Conclusions</p> <p>Evidence from this study shows that exposure to IPV is associated with increased likelihood of traumatic physical consequences for women in Nigeria. Education and justification of wife beating were significant community-level factors associated with traumatic physical consequences, suggesting the importance of increasing women's levels of education and changing community norms that justify controlling behavior and IPV.</p

SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

On 24th November 2021, the sequence of a new SARS-CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titers of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic Alpha, Beta, Gamma, or Delta are substantially reduced, or the sera failed to neutralize. Titers against Omicron are boosted by third vaccine doses and are high in both vaccinated individuals and those infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of the large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses and uses mutations that confer tight binding to ACE2 to unleash evolution driven by immune escape. This leads to a large number of mutations in the ACE2 binding site and rebalances receptor affinity to that of earlier pandemic viruses

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.

BACKGROUND: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. METHODS: We present data from three single-blind randomised controlled trials-one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)-and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 1010 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). FINDINGS: Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4-74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3-85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59-0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3-91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0-69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18-55 years (GMR 2·32 [2·01-2·68]). INTERPRETATION: The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose. FUNDING: UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca