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New ice cores retrieved from the Taylor Glacier (Antarctica) blue ice area contain ice and air spanning the Marine Isotope Stage (MIS) 5–4 transition, a period of global cooling and ice sheet expansion. We determine chronologies for the ice and air bubbles in the new ice cores by visually matching variations in gas- and ice-phase tracers to preexisting ice core records. The chronologies reveal an ice age–gas age difference (Δage) approaching 10 ka during MIS 4, implying very low snow accumulation in the Taylor Glacier accumulation zone. A revised chronology for the analogous section of the Taylor Dome ice core (84 to 55 ka), located to the south of the Taylor Glacier accumulation zone, shows that Δage did not exceed 3 ka. The difference in Δage between the two records during MIS 4 is similar in magnitude but opposite in direction to what is observed at the Last Glacial Maximum. This relationship implies that a spatial gradient in snow accumulation existed across the Taylor Dome region during MIS 4 that was oriented in the opposite direction of the accumulation gradient during the Last Glacial Maximum.

Global temperature is a fundamental climate metric highly correlated with sea level, which implies that keeping shorelines near their present location requires keeping global temperature within or close to its preindustrial Holocene range. However, global temperature excluding short-term variability now exceeds +1 °C relative to the 1880–1920 mean and annual 2016 global temperature was almost +1.3 °C. We show that global temperature has risen well out of the Holocene range and Earth is now as warm as it was during the prior (Eemian) interglacial period, when sea level reached 6–9 m higher than today. Further, Earth is out of energy balance with present atmospheric composition, implying that more warming is in the pipeline, and we show that the growth rate of greenhouse gas climate forcing has accelerated markedly in the past decade. The rapidity of ice sheet and sea level response to global temperature is difficult to predict, but is dependent on the magnitude of warming. Targets for limiting global warming thus, at minimum, should aim to avoid leaving global temperature at Eemian or higher levels for centuries. Such targets now require negative emissions, i.e., extraction of CO2 from the air. If phasedown of fossil fuel emissions begins soon, improved agricultural and forestry practices, including reforestation and steps to improve soil fertility and increase its carbon content, may provide much of the necessary CO2 extraction. In that case, the magnitude and duration of global temperature excursion above the natural range of the current interglacial (Holocene) could be limited and irreversible climate impacts could be minimized. In contrast, continued high fossil fuel emissions today place a burden on young people to undertake massive technological CO2 extraction if they are to limit climate change and its consequences. Proposed methods of extraction such as bioenergy with carbon capture and storage (BECCS) or air capture of CO2 have minimal estimated costs of USD 89–535 trillion this century and also have large risks and uncertain feasibility. Continued high fossil fuel emissions unarguably sentences young people to either a massive, implausible cleanup or growing deleterious climate impacts or both.

Background: Three-dimensional (3D) printing has emerged as a promising new technology for the development of surgical prosthetics. Research in orthopedic surgery has demonstrated that using 3D printed customized prosthetics results in more precise implant placements and better patient outcomes. However, there has been little research on implementing customized 3D printed prosthetics in otolaryngology. The program sought to determine whether computed tomography (CT) serves as feasible templates to construct 3D printed palatal obturator prosthetics for defects in patients who have been treated for head and neck cancers., Observations: A retrospective review of patients with palatal defects was conducted and identified 1 patient with high quality CTs compatible with 3D modeling. CTs of the patient's craniofacial anatomy were used to develop a 3D model and a Formlabs 3B+ printer printed the palatal prosthetic. We successfully developed and produced an individualized prosthetic using CTs from a veteran with head and neck deformities caused by cancer treatment who was previously treated at the Veterans Affairs Palo Alto Health Care System. This project was successful in printing patient-specific implants using CT reproductions of the patient's craniofacial anatomy, particularly of the palate. The program was a proof of concept and the implant we created was not used on the patient., Conclusions: Customized 3D printed implants may allow otolaryngologists to enhance the performance and efficiency of surgeries and better rehabilitate and reconstruct craniofacial deformities to restore appearance and function to patients. Additional research will strive to enhance the therapeutic potential of these prosthetics to serve as low-cost, patient-specific implants., Competing Interests: Author disclosures: Sandy Napel receives honoraria from Fovia, Inc. The other authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article., (Copyright © 2024 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

Background: Xerostomia, the subjective sensation of dry mouth, contributes to dysarthria, dysphagia, and diminished quality of life. Polypharmacy is a known and modifiable risk factor for xerostomia. The objective of this study was to evaluate the prevalence of dry mouth, the relationship between dry mouth and other oral conditions, and the impact of polypharmacy on dry mouth., Methods: This study was a retrospective cross-sectional study of all patients seen in fiscal year (FY) 2015 (October 1, 2014 to September 30, 2015) at the VA Palo Alto Health Care System (VAPAHCS), a tertiary care US Department of Veterans Affairs (VA) hospital. Patients diagnosed with xerostomia were identified using ICD-9 codes (527.7, 527.8, R68.2) and Systemized Nomenclature of Medicine Clinical Terms (SNOMED CT) codes (87715008, 78948009)., Results: Of all the patients seen at VAPAHCS during FY 2015, 138 had a diagnostic code for xerostomia; of those patients, 84 had at least 1 documented speech, dentition, or swallowing (SDS) problem, and 55 (39.9%) were taking ≥ 12 medications, more than twice as many patients as in any one of the other groups studied (0-2, 3-5, 6-8, and 9-11 medications taken). Although 4,971 total patients seen at VAPAHCS had documented SDS problems during FY 2015, of those patients only 77 (1.5%) had an additional recorded diagnosis of xerostomia., Conclusions: Heightened physician awareness regarding the signs and symptoms of and risk factors for xerostomia is needed to improve health care providers' ability to diagnose dry mouth. Polypharmacy also must be considered when developing new strategies for preventing and treating xerostomia., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to this article., (Copyright © 2020 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

While ductal carcinoma in situ (DCIS) is known as a precursor lesion to most invasive breast carcinomas, the mechanisms underlying this transition remain enigmatic. DCIS is typically diagnosed by the mammographic detection of microcalcifications (MC). MCs consisting of non-stoichiometric hydroxyapatite (HA) mineral are frequently associated with malignant disease, yet it is unclear whether HA can actively promote malignancy. To investigate this outstanding question, we compared phenotypic outcomes of breast cancer cells cultured in control or HA-containing poly(lactide-co-glycolide) (PLG) scaffolds. Exposure to HA mineral in scaffolds increased the expression of pro-tumorigenic interleukin-8 (IL-8) among transformed but not benign cells. Notably, MCF10DCIS.com cells cultured in HA scaffolds adopted morphological changes associated with increased invasiveness and exhibited increased motility that were dependent on IL-8 signaling. Moreover, MCF10DCIS.com xenografts in HA scaffolds displayed evidence of enhanced malignant progression relative to xenografts in control scaffolds. These experimental findings were supported by a pathological analysis of clinical DCIS specimens, which correlated the presence of MCs with increased IL-8 staining and ductal proliferation. Collectively, our work suggests that HA mineral may stimulate malignancy in preinvasive DCIS cells and validate PLG scaffolds as useful tools to study cell-mineral interactions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose To analyze differences in esophageal cancer survival by geographic region of the U.S. from the 1970s to the 2000s, and attribute the causes of these discrepancies. Methods Raw data were obtained from the Surveillance Epidemiology and End Results (SEER) program of the National Cancer Institute. Patients were stratified by decade of diagnosis and by geographic region (East, Hawaii/Alaska, Midwest, Southwest, and West), containing SEER registries. The Kaplan-Meier method with the log-rank test was used to compare the overall survival (OS) among these geographic groups. A multivariate Cox Proportional Hazard analysis was conducted to evaluate the impact of the following factors on differences in survival: patient age, gender, race, tumor stage, site, histology, treatment method, and metropolitan size. Results A total of 87,834 patients were identified. OS has increased significantly since 1973, with five-year OS improving from 4.9% (the 1970s) to 15.3% (2000s) ( P <0.001). Residence in the East was prognostic for higher OS compared to all the other regions, with a median OS of six months in the 1970s and 12 months in the 2000s ( P <0.001). The multivariate analysis revealed increased age, African American race, distant disease, non-distal tumor location, squamous cell histology, and no radiation therapy were associated with worse OS. The West and East had the highest amount of cancer centers (12 and seven, respectively). And the East had the highest number of cancer centers per person (5.7E-07) while the South had the lowest (1.6E-07). Conclusions There are disparities in esophageal cancer survival and quality of care through different geographic regions of the U.S., which may be attributed to a combination of the unbalanced distribution of medical resources, the regional differences in cancer biology, and other lifestyle and socioeconomic factors. More research should be conducted to further characterize regional differences and guide the implementation of improvements in survival., Competing Interests: The authors have declared that no competing interests exist.