Oral Immunoglobulin Levels are Not a Good Surrogate for Cervical Immunoglobulin Levels

Background: We sought to determine whether oral secretions could be used as a surrogate for cervical secretions for monitoring cervical immunoglobulin (Ig) levels. To do so, we examined (1) whether oral IgG and IgA levels correlated with those observed at the cervix, and (2) whether time of menstrual cycle and other factors previously reported to influence cervical Ig levels were associated with oral IgG and IgA levels. Methods: We obtained oral samples from a group of 85 Costa Rican woman 25–35 years of age measured at three time points during one menstrual cycle. Total IgG and IgA levels were measured by ELISA. Generalized estimating equations methods that account for repeated measures were used to evaluate the association between oral and cervical Ig levels and to evaluate the association between various covariates and oral IgA and IgG levels. Results: We did not observe an association between oral and cervical IgG [linear regression coefficient (LRC) 0.01; 95% CI, −0.05 to 0.07] and IgA levels (LRC 0.02; 95% CI, −0.04 to 0.08). Oral IgG and IgA levels were not influenced by phase of menstrual cycle, in contrast to what has previously been observed for cervical Ig levels. Conclusion: Our data suggest that oral IgG and IgA measures are not a good surrogate for cervical IgG and IgA levels. Future studies should examine whether antigen-specific antibody responses induced by vaccination correlate across mucosal sites

Relative sea-level change in Connecticut (USA) during the last 2200 yrs

We produced a relative sea-level (RSL) reconstruction from Connecticut (USA) spanning the last ∼2200 yrs that is free from the influence of sediment compaction. The reconstruction used a suite of vertically- and laterally-ordered sediment samples ≤2 cm above bedrock that were collected by excavating a trench along an evenly-sloped bedrock surface. Paleomarsh elevation was reconstructed using a regional-scale transfer function trained on the modern distribution of foraminifera on Long Island Sound salt marshes and supported by bulk-sediment δ13C measurements. The history of sediment accumulation was estimated using an age-elevation model constrained by radiocarbon dates and recognition of pollution horizons of known age. The RSL reconstruction was combined with regional tide-gauge measurements spanning the last ∼150 yrs before being quantitatively analyzed using an error-in-variables integrated Gaussian process model to identify sea-level trends with formal and appropriate treatment of uncertainty and the temporal distribution of data. RSL rise was stable (∼1 mm/yr) from ∼200 BCE to ∼1000 CE, slowed to a minimum rate of rise (0.41 mm/yr) at ∼1400 CE, and then accelerated continuously to reach a current rate of 3.2 mm/yr, which is the fastest, century-scale rate of the last 2200 yrs. Change point analysis identified that modern rates of rise in Connecticut began at 1850–1886 CE. This timing is synchronous with changes recorded at other sites on the U.S. Atlantic coast and is likely the local expression of a global sea-level change. Earlier sea-level trends show coherence north of Cape Hatteras that are contrasted with southern sites. This pattern may represent centennial-scale variability in the position and/or strength of the Gulf Stream. Comparison of the new record to three existing and reanalyzed RSL reconstructions from the same site developed using sediment cores indicates that compaction is unlikely to significantly distort RSL reconstructions produced from shallow (∼2–3 m thick) sequences of salt-marsh peat

Relative Sea-Level Trends in New York City During the Past 1500 Years

New York City (NYC) is threatened by 21st-century relative sea-level (RSL) rise because it will experience a trend that exceeds the global mean and has high concentrations of low-lying infrastructure and socioeconomic activity. To provide a long-term context for anticipated trends, we reconstructed RSL change during the past ~1500 years using a core of salt-marsh sediment from Pelham Bay in The Bronx. Foraminifera and bulk-sediment δ13C values were used as sea-level indicators. The history of sediment accumulation was established by radiocarbon dating and recognition of pollution and land-use trends of known age in down-core elemental, isotopic, and pollen profiles. The reconstruction was generated within a Bayesian hierarchical model to accommodate multiple proxies and to provide a unified statistical framework for quantifying uncertainty. We show that RSL in NYC rose by ~1.70 m since ~575 CE (including ~0.38 m since 1850 CE). The rate of RSL rise increased markedly at 1812–1913 CE from ~1.0 to ~2.5 mm/yr, which coincides with other reconstructions along the US Atlantic coast. We investigated the possible influence of tidal-range change in Long Island Sound on our reconstruction using a regional tidal model, and we demonstrate that this effect was likely small. However, future tidal-range change could exacerbate the impacts of RSL rise in communities bordering Long Island Sound. The current rate of RSL rise is the fastest that NYC has experienced for \u3e1500 years, and its ongoing acceleration suggests that projections of 21st-century local RSL rise will be realized

Managing for climate change on federal lands of the western United States: perceived usefulness of climate science, effectiveness of adaptation strategies, and barriers to implementation

Recent mandates in the United States require federal agencies to incorporate climate change science into land management planning efforts. These mandates target possible adaptation and mitigation strategies. However, the degree to which climate change is actively being considered in agency planning and management decisions is largely unknown. We explored the usefulness of climate change science for federal resource managers, focusing on the efficacy of potential adaptation strategies and barriers limiting the use of climate change science in adaptation efforts. Our study was conducted in the northern Rocky Mountains region of the western United States, where we interacted with 77 U.S. Forest Service and Bureau of Land Management personnel through surveys, semistructured interviews, and four collaborative workshops at locations across Idaho and Montana. We used a mixed-methods approach to evaluate managers' perceptions about adapting to and mitigating for climate change. Although resource managers incorporate general language about climate change in regional and landscape-level planning documents, they are currently not planning on-the-ground adaptation or mitigation projects. However, managers felt that their organizations were most likely to adapt to climate change through use of existing management strategies that are already widely implemented for other non climate-related management goals. These existing strategies, (e.g., thinning and prescribed burning) are perceived as more feasible than new climate-specific methods (e.g., assisted migration) because they already have public and agency support, accomplish multiple goals, and require less anticipation of the future timing and probability of climate change impacts. Participants reported that the most common barriers to using climate change information included a lack of management-relevant climate change science, inconsistent agency guidance, and insufficient time and resources to access, interpret, and apply current climate science information to management plans.Key words: adaptation; Bureau of Land Management; climate change; decision making; Forest Service; land management; public landsThis is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Resilience Alliance. The published article can be found at: http://www.ecologyandsociety.org

HPV16 Seropositivity and Subsequent HPV16 Infection Risk in a Naturally Infected Population: Comparison of Serological Assays

Background: Several serological assays have been developed to detect antibodies elicited against infections with oncogenic human papillomavirus (HPV) type 16. The association between antibody levels measured by various assays and subsequent HPV infection risk may differ. We compared HPV16-specific antibody levels previously measured by a virus-like particle (VLP)-based direct enzyme-linked immunoassay (ELISA) with levels measured by additional assays and evaluated the protection against HPV16 infection conferred at different levels of the assays. Methodology/Principal Findings Replicate enrollment serum aliquots from 388 unvaccinated women in the control arm of the Costa Rica HPV vaccine trial were measured for HPV16 seropositivity using three serological assays: a VLP-based direct ELISA; a VLP-based competitive Luminex immunoassay (cLIA); and a secreted alkaline phosphatase protein neutralization assay (SEAP-NA). We assessed the association of assay seropositivity and risk of subsequent HPV16 infection over four years of follow-up by calculating sampling-adjusted odds ratios (OR) and HPV16 seropositivity based on standard cutoff from the cLIA was significantly associated with protection from subsequent HPV16 infection (OR = 0.48, CI = 0.27–0.86, compared with seronegatives). Compared with seronegatives, the highest seropositive tertile antibody levels from the direct ELISA (OR = 0.53, CI = 0.28–0.90) as well as the SEAP-NA (OR = 0.20, CI = 0.06, 0.64) were also significantly associated with protection from HPV16 infection. Conclusions/Significance: Enrollment HPV16 seropositivity by any of the three serological assays evaluated was associated with protection from subsequent infection, although cutoffs for immune protection were different. We defined the assays and seropositivity levels after natural infection that better measure and translate to protective immunity

Immunogenicity and safety of one-dose human papillomavirus vaccine compared with two or three doses in Tanzanian girls (DoRIS): an open-label, randomised, non-inferiority trial

Background An estimated 15% of girls aged 9-14 years worldwide have been vaccinated against human papillomavirus (HPV) with the recommended two-dose or three-dose schedules. A one-dose HPV vaccine schedule would be simpler and cheaper to deliver. We report immunogenicity and safety results of different doses of two different HPV vaccines in Tanzanian girls. Methods In this open-label, randomised, phase 3, non-inferiority trial, we enrolled healthy schoolgirls aged 9-14 years from Government schools in Mwanza, Tanzania. Eligible participants were randomly assigned to receive one, two, or three doses of either the 2-valent vaccine (Cervarix, GSK Biologicals, Rixensart) or the 9-valent vaccine (Gardasil-9, Sanofi Pasteur MSD, Lyon). The primary outcome was HPV 16 specific or HPV 18 specific seropositivity following one dose compared with two or three doses of the same HPV vaccine 24 months after vaccination. Safety was assessed as solicited adverse events up to 30 days after each dose and unsolicited adverse events up to 24 months after vaccination or to last study visit. The primary outcome was done in the per-protocol population, and safety was analysed in the total vaccinated population. This study was registered in ClinicalTrials.gov, NCT02834637. Findings Between Feb 23, 2017, and Jan 6, 2018, we screened 1002 girls for eligibility. 72 girls were excluded. 930 girls were enrolled and randomly assigned to receive one dose of Cervarix (155 participants), two doses of Cervarix (155 participants), three doses of Cervarix (155 participants), one dose of Gardasil-9 (155 participants), two doses of Gardasil-9 (155 participants), or three doses of Gardasil-9 (155 participants). 922 participants received all scheduled doses within the defined window (three withdrew, one was lost to follow-up, and one died before completion; two received their 6-month doses early, and one received the wrong valent vaccine in error; all 930 participants were included in the total vaccinated cohort). Retention at 24 months was 918 (99%) of 930 participants. In the accordingto-protocol cohort, at 24 months, 99% of participants who received one dose of either HPV vaccine were seropositive for HPV 16 IgG antibodies, compared with 100% of participants who received two doses, and 100% of participants who received three doses. This met the prespecified non-inferiority criteria. Anti-HPV 18 seropositivity at 24 months did not meet non-inferiority criteria for one dose compared to two doses or three doses for either vaccine, although more than 98% of girls in all groups had HPV 18 antibodies. 53 serious adverse events (SAEs) were experienced by 42 (4.5%) of 930 girls, the most common of which was hospital admission for malaria. One girl died of malaria. Number of events was similar between groups and no SAEs were considered related to vaccination. Interpretation A single dose of the 2-valent or 9-valent HPV vaccine in girls aged 9-14 years induced robust immune responses up to 24 months, suggesting that this reduced dose regimen could be suitable for prevention of HPV infection among girls in the target age group for vaccination. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

Cellular immune responses to HPV-18, -31, and -53 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles. Virology 2006

Abstract Human papillomavirus-like particles (HPV VLP) are candidate vaccines that have shown to be efficacious in reducing infection and inducing robust antiviral immunity. Neutralizing antibodies generated by vaccination are largely type-specific, but little is known about the type-specificity of cellular immune responses to VLP vaccination. To determine whether vaccination with HPV-16 L1VLP induces cellular immunity to heterologous HPV types (HPV-18, HPV-31, and HPV-53), we examined proliferative and cytokine responses in vaccine (n = 11) and placebo (n = 5) recipients. Increased proliferative and cytokine responses to heterologous types were observed postvaccination in some individuals. The proportion of women responding to heterologous types postvaccination (36%-55%) was lower than that observed in response to HPV-16 (73%). Response to HPV-16 VLP predicted response to other types. The strongest correlations in response were observed between HPV-16 and HPV-31, consistent with their phylogenetic relatedness. In summary, PBMC from HPV-16 VLP vaccine recipients can respond to L1VLP from heterologous HPV types, suggesting the presence of conserved T cell epitopes

Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment

BackgroundHuman papillomavirus vaccines prevent human papillomavirus infection and cervical precancers. The impact of vaccinating women with a current infection or after treatment for an human papillomavirus-associated lesion is not fully understood.ObjectivesTo determine whether human papillomavirus-16/18 vaccination influences the outcome of infections present at vaccination and the rate of infection and disease after treatment of lesions.Study DesignWe included 1711 women (18−25 years) with carcinogenic human papillomavirus infection and 311 women of similar age who underwent treatment for cervical precancer and who participated in a community-based trial of the AS04-adjuvanted human papillomavirus-16/18 virus-like particle vaccine. Participants were randomized (human papillomavirus or hepatitis A vaccine) and offered 3 vaccinations over 6 months. Follow-up included annual visits (more frequently if clinically indicated), referral to colposcopy of high-grade and persistent low-grade lesions, treatment by loop electrosurgical excisional procedure when clinically indicated, and cytologic and virologic follow-up after treatment. Among women with human papillomavirus infection at the time of vaccination, we considered type-specific viral clearance, and development of cytologic (squamous intraepithelial lesions) and histologic (cervical intraepithelial neoplasia) lesions. Among treated women, we considered single-time and persistent human papillomavirus infection, squamous intraepithelial lesions, and cervical intraepithelial neoplasia 2 or greater. Outcomes associated with infections absent before treatment also were evaluated. Infection-level analyses were performed and vaccine efficacy estimated.ResultsMedian follow-up was 56.7 months (women with human papillomavirus infection) and 27.3 months (treated women). There was no evidence of vaccine efficacy to increase clearance of human papillomavirus infections or decrease incidence of cytologic/histologic abnormalities associated with human papillomavirus types present at enrollment. Vaccine efficacy for human papillomavirus 16/18 clearance and against human papillomavirus 16/18 progression from infection to cervical intraepithelial neoplasia 2 or greater were −5.4% (95% confidence interval −19,10) and 0.3% (95% confidence interval −69,41), respectively. Among treated women, 34.1% had oncogenic infection and 1.6% had cervical intraepithelial neoplasia 2 or greater detected after treatment, respectively, and of these 69.8% and 20.0% were the result of new infections. We observed no significant effect of vaccination on rates of infection/lesions after treatment. Vaccine efficacy estimates for human papillomavirus 16/18 associated persistent infection and cervical intraepithelial neoplasia 2 or greater after treatment were 34.7% (95% confidence interval −131, 82) and −211% (95% confidence interval −2901, 68), respectively. We observed evidence for a partial and nonsignificant protective effect of vaccination against new infections absent before treatment. For incident human papillomavirus 16/18, human papillomavirus 31/33/45, and oncogenic human papillomavirus infections post-treatment, vaccine efficacy estimates were 57.9% (95% confidence interval −43, 88), 72.9% (95% confidence interval 29, 90), and 36.7% (95% confidence interval 1.5, 59), respectively.ConclusionWe find no evidence for a vaccine effect on the fate of detectable human papillomavirus infections. We show that vaccination does not protect against infections/lesions after treatment. Evaluation of vaccine protection against new infections after treatment and resultant lesions warrants further consideration in future studies

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts