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Abstract Earth’s obliquity and eccentricity cycles are strongly imprinted on Earth’s climate and widely used to measure geological time. However, the record of these imprints on the oxygen isotope record in deep-sea benthic foraminifera (δ18Ob) shows contradictory signals that violate isotopic principles and cause controversy over climate-ice sheet interactions. Here, we present a δ18Ob record of high fidelity from International Ocean Drilling Program (IODP) Site U1406 in the northwest Atlantic Ocean. We compare our record to other records for the time interval between 28 and 20 million years ago, when Earth was warmer than today, and only Antarctic ice sheets existed. The imprint of eccentricity on δ18Ob is remarkably consistent globally whereas the obliquity signal is inconsistent between sites, indicating that eccentricity was the primary pacemaker of land ice volume. The larger eccentricity-paced early Antarctic ice ages were vulnerable to rapid termination. These findings imply that the self-stabilizing hysteresis effects of large land-based early Antarctic ice sheets were strong enough to maintain ice growth despite consecutive insolation-induced polar warming episodes. However, rapid ice age terminations indicate that resistance to melting was weaker than simulated by numerical models and regularly overpowered, sometimes abruptly.

Abstract Denosumab is a monoclonal anti-RANKL antibody that inhibits bone resorption, increases bone mass, and reduces fracture risk. Denosumab discontinuation causes an extensive wave of rebound resorption, but the cellular mechanisms remain poorly characterized. We utilized in situ hybridization (ISH) as a direct approach to identify the cells that activate osteoclastogenesis through the RANKL/OPG pathway. ISH was performed across species, skeletal sites, and following recombinant OPG (OPG:Fc) and parathyroid hormone 1–34 (PTH) treatment of mice. OPG:Fc treatment in mice induced an increased expression of RANKL mRNA mainly in trabecular, but not endocortical bone surface cells. Additionally, a decreased expression of OPG mRNA was detected in bone surface cells and osteocytes of both compartments. A similar but more pronounced effect on RANKL and OPG expression was seen one hour after PTH treatment. These findings suggest that bone surface cells and osteocytes conjointly regulate the activation of osteoclastogenesis, and that OPG:Fc treatment induces a local accumulation of osteoclastogenic activation sites, ready to recruit and activate osteoclasts upon treatment discontinuation. Analysis of publicly available single-cell RNA sequencing (scRNAseq) data from murine bone marrow stromal cells revealed that Tnfsf11 + cells expressed high levels of Mmp13, Limch1, and Wif1, confirming their osteoprogenitor status. ISH confirmed co-expression of Mmp13 and Tnfsf11 in bone surface cells of both vehicle- and OPG:Fc-treated mice. Under physiological conditions of human/mouse bone, RANKL is expressed mainly by osteoprogenitors proximate to the osteoclasts, while OPG is expressed mainly by osteocytes and bone-forming osteoblasts.

Abstract Background Human Papillomavirus (HPV) vaccine uptake is low among East African adolescents in the US. Adolescents’ preferences influence HPV vaccine decisions, yet few interventions exist that address East African adolescents’ beliefs about HPV vaccines. We describe a multi-step process on how to create a theory-based comic book by integrating empirical findings, theory and focus group data from East African parents in the US. Methods Our multi-methods process included conducting focus groups with Somali, Ethiopian, and Eritrean mothers (n = 30) to understand mothers and adolescents socio-cultural beliefs and information needs about the HPV vaccine, creating comic book messages integrating the focus group findings, and assessing the acceptability of the finalized comic book among Somali, Ethiopian, and Eritrean adolescents (n = 134). Results We identified categories around socio-cultural beliefs (such ethnic representation and concerns about pork gelatin in vaccines), HPV vaccine information needs, and diffusion of information. We then mapped the categories to theoretical constructs and operationalized them into the comic book. Finally, we describe the overall acceptability of the comic book and specifics on comic book structure, appeal of characters, and message relevance. Conclusions A rigorous multi-step process that integrates theory and focus group data can help create culturally appropriate health messages that can educate and appeal to the community.

Background: HPV vaccine studies in East African communities are few and focus mainly on Somali women and girls. We examined how HPV vaccine perceptions and uptake are shaped among Somali, Ethiopian, and Eritrean mothers. Methods: We convened three focus groups in Somali, Amharic, and Tigrinya with mothers of 11–17 year old children. The Socio-Context Framework (social, cultural, and religious factors) and Andersen's Behavioral Model (predisposing, enabling, and need for care factors) informed question development. Results: Negative vaccine perceptions, lack of HPV vaccine knowledge, and concerns about side effects emerged as predisposing factors. Having a provider who engages parents on HPV vaccination and takes responsibility for vaccine-related risks emerged as enabling factors. Availability of vaccine information resources (e.g., person-to-person, word of mouth education for parents) were also enabling factors. Need for care factors included having comprehensive vaccine information, strong recommendation from a doctor, and validation from a co-ethnic medical professional. Women exerted strong social influence on vaccine uptake (social), had concerns about pork gelatin in vaccines (religious), and felt discussions about sex with children were culturally unacceptable (cultural). Conclusion: Strategies for vaccine uptake among East African immigrants need to address factors that shape HPV vaccine perceptions for adolescents, caregivers, and providers.