350 research outputs found

    Population-Level Effects of Human Papillomavirus Vaccination Programs on Infections with Nonvaccine Genotypes

    Get PDF
    We analyzed human papillomavirus (HPV) prevalences during prevaccination and postvaccination periods to consider possible changes in nonvaccine HPV genotypes after introduction of vaccines that confer protection against 2 high-risk types, HPV16 and HPV18. Our meta-analysis included 9 studies with data for 13,886 girls and women ≤19 years of age and 23,340 women 20–24 years of age. We found evidence of cross-protection for HPV31 among the younger age group after vaccine introduction but little evidence for reductions of HPV33 and HPV45. For the group this same age group, we also found slight increases in 2 nonvaccine high-risk HPV types (HPV39 and HPV52) and in 2 possible high-risk types (HPV53 and HPV73). However, results between age groups and vaccines used were inconsistent, and the increases had possible alternative explanations; consequently, these data provided no clear evidence for type replacement. Continued monitoring of these HPV genotypes is important

    Receptor modelling of both particle composition and size distribution from a background site in London, UK

    Get PDF
    Positive Matrix Factorisation (PMF) analysis was applied to PM10 chemical composition and particle Number Size Distribution (NSD) data measured at an urban background site (North Kensington) in London, UK for the whole of 2011 and 2012. The PMF analyses revealed six and four factors respectively which described seven sources or aerosol types. These included Nucleation, Traffic, Diffuse Urban, Secondary, Fuel Oil, Marine and Non-Exhaust/Crustal sources. Diffuse Urban, Secondary and Traffic sources were identified by both the chemical composition and particle number size distribution analysis, but a Nucleation source was identified only from the particle Number Size Distribution dataset. Analysis of the PM10 chemical composition dataset revealed Fuel Oil, Marine, Non-Exhaust Traffic/Crustal sources which were not identified from the number size distribution data. The two methods appear to be complementary, as the analysis of the PM10 chemical composition data is able to distinguish components contributing largely to particle mass whereas the number particle size distribution dataset is more effective for identifying components making an appreciable contribution to particle number. Analysis was also conducted on the combined chemical composition and number size distribution dataset revealing five factors representing Diffuse Urban, Nucleation, Secondary, Aged Marine and Traffic sources. However, the combined analysis appears not to offer any additional power to discriminate sources above that of the aggregate of the two separate PMF analyses. Day-of-the-week and month-of-the-year associations of the factors proved consistent with their assignment to source categories, and bivariate polar plots which examined the wind directional and wind speed association of the different factors also proved highly consistent with their inferred sources

    Emulation and Sensitivity Analysis of the Community Multiscale Air Quality Model for a UK Ozone Pollution Episode

    Get PDF
    Gaussian process emulation techniques have been used with the Community Multiscale Air Quality model, simulating the effects of input uncertainties on ozone and NO2 output, to allow robust global sensitivity analysis (SA). A screening process ranked the effect of perturbations in 223 inputs, isolating the 30 most influential from emissions, boundary conditions (BCs), and reaction rates. Community Multiscale Air Quality (CMAQ) simulations of a July 2006 ozone pollution episode in the UK were made with input values for these variables plus ozone dry deposition velocity chosen according to a 576 point Latin hypercube design. Emulators trained on the output of these runs were used in variance-based SA of the model output to input uncertainties. Performing these analyses for every hour of a 21 day period spanning the episode and several days on either side allowed the results to be presented as a time series of sensitivity coefficients, showing how the influence of different input uncertainties changed during the episode. This is one of the most complex models to which these methods have been applied, and here, they reveal detailed spatiotemporal patterns of model sensitivities, with NO and isoprene emissions, NO2 photolysis, ozone BCs, and deposition velocity being among the most influential input uncertainties

    Recombinant HIV Envelope Proteins Fail to Engage Germline Versions of Anti-CD4bs bNAbs

    Get PDF
    Vaccine candidates for HIV-1 so far have not been able to elicit broadly neutralizing antibodies (bNAbs) although they express the epitopes recognized by bNAbs to the HIV envelope glycoprotein (Env). To understand whether and how Env immunogens interact with the predicted germline versions of known bNAbs, we screened a large panel (N:56) of recombinant Envs (from clades A, B and C) for binding to the germline predecessors of the broadly neutralizing anti-CD4 binding site antibodies b12, NIH45-46 and 3BNC60. Although the mature antibodies reacted with diverse Envs, the corresponding germline antibodies did not display Env-reactivity. Experiments conducted with engineered chimeric antibodies combining the mature and germline heavy and light chains, respectively and vice-versa, revealed that both antibody chains are important for the known cross-reactivity of these antibodies. Our results also indicate that in order for b12 to display its broad cross-reactivity, multiple somatic mutations within its VH region are required. A consequence of the failure of the germline b12 to bind recombinant soluble Env is that Env-induced B-cell activation through the germline b12 BCR does not take place. Our study provides a new explanation for the difficulties in eliciting bNAbs with recombinant soluble Env immunogens. Our study also highlights the need for intense efforts to identify rare naturally occurring or engineered Envs that may engage the germline BCR versions of bNAbs
    corecore