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Abstract The Permo-Triassic mass extinction was linked to catastrophic environmental changes and large igneous province (LIP) volcanism. In addition to the widespread marine losses, the Permo–Triassic event was the most severe terrestrial ecological crisis in Earth’s history and the only known mass extinction among insects, but the cause of extinction on land remains unclear. In this study, high-resolution Hg concentration records and multiple-archive S-isotope analyses of sediments from the Junggar Basin (China) provide evidence of repeated pulses of volcanic-S (acid rain) and increased Hg loading culminating in a crisis of terrestrial biota in the Junggar Basin coeval with the interval of LIP emplacement. Minor S-isotope analyses are, however, inconsistent with total ozone layer collapse. Our data suggest that LIP volcanism repeatedly stressed end-Permian terrestrial environments in the ~300 kyr preceding the marine extinction locally via S-driven acidification and deposition of Hg, and globally via pulsed addition of CO2.

Abstract Background Effective transitions of patients from Secondary Care Services (SCSs) to primary care are necessary for optimization of resources and care. Factors that enable or restrict smooth transitions of individuals with Serious Mental Illness (SMI) to primary care from SCSs have not been comprehensively synthesized. Methods A scoping review was conducted to answer the questions (1) “What are the barriers and facilitators to discharge from SCSs to primary care for adults with SMI?” and (2) “What programs have been developed to support these transitions?”. Results Barriers and facilitators of discharge included patient-, primary care capacity-, and transition Process/Support-related factors. Patient-related barriers and facilitators were most frequently reported. 11 discharge programs were reported across the evidence sources. The most frequently reported program components were the provision of additional mental health supports for the transition and development of care plans with relapse signatures and intervention plans. Conclusions Established discharge programs should be comprehensively evaluated to determine their relative benefits. Furthermore, research should be expanded to evaluate barriers and facilitators to discharge and discharge programs in different national contexts and models of care. Trial Registration The protocol for this scoping review is registered with the Open Science Framework ( https://doi.org/10.17605/OSF.IO/NBTMZ ).

Purpose: To describe the visual acuity (VA) outcomes from a telemedicine-enabled pathway allowing for rapid diagnosis and administration of intravenous (IV) thrombolytic treatment for non-arteritic central retinal artery occlusion (naCRAO) within 4.5 hours (4.5 h) of visual loss. Design: Retrospective observational case series. Methods: Setting: A large managed healthcare consortium.Patient Population: Eighty-five patients with naCRAO and vision loss for less than 4.5 h presenting between 2021 and 2023. Thirty-five patients received IV thrombolytic therapy and 50 patients were closely observed.Intervention: A collaborative telemedicine-enabled pathway employing fundus photography was previously established by Ophthalmology, Emergency Medicine, and Stroke services to rapidly evaluate and manage patients presenting with acute painless monocular vision loss and allow for administration of IV tenecteplase (0.25 mg/kg) for eligible consenting patients diagnosed with naCRAO within 4.5 h. Retrospective chart review was conducted to collect data on demographics, vascular risk factors, clinical features, VA outcomes, and adverse events. Comparison was made between patients who received intravenous thrombolysis and those who were observed.Main Outcome Measures: Improvement in VA of at least 0.3 logarithm of the minimum angle of resolution (logMAR) and/or from 20/200 or worse to 20/100 or better. Results: A greater percentage of patients in the treated group had VA improvement of ≥0.3 logMAR (54.3 % vs 28 %, p = .014), and a greater percentage of patients in the untreated group had VA worsening of ≥0.3 logMAR (30 % vs 5.7 %, p = .006). Twice the percentage of treated versus untreated patients had improved VA from 20/200 or worse to 20/100 or better, but this difference was not statistically significant (20 % vs 10 %, p = .192). There was a significantly shorter mean time to treatment for those patients who had VA improvement from 20/200 or worse to 20/100 or better compared to those who did not (118 versus 171 min, p = .031). Two patients experienced intracranial bleeding after IV thrombolysis. Conclusions: The evaluation and treatment of hyperacute naCRAO is possible on a large scale via an integrated telemedicine-enabled approach utilizing fundus photography. The use of IV thrombolytic was associated with better VA outcomes compared to observation alone. Prospective randomized controlled trials are needed to confirm these findings and determine optimal management.

The use of stable isotopes, specifically δ18OPO4 ratios, in differentiating potential sources of inorganic phosphorus (e.g., wastewater, septic, wild animals, domesticated animals, livestock, substrates, or commercial fertilizers) to watersheds is a growing field. This method produces data that, used in conjunction with statistical mixing models, enables a better understanding of contributing sources of runoff. However, given the recent development of this research area there are obvious limitations that have arisen, due in large part to the limited available reference data to compare water samples. Here, we attempt to expand the availability of reference samples by applying stable isotope methods to three types of common agricultural manures: poultry, dairy, and swine. We also aim to concatenate the organic waste literature on this topic, creating a more robust comparison database for future study and application in phosphorus source partitioning research. Among our samples, δ18OPO4 ratios for poultry were considerably elevated compared to dairy and swine manures (values of 18.5‰, 16.5‰, and 17.9‰, respectively). Extending this to other published ratios of δ18OPO4 from various types of waste products (e.g., septic, wastewater, livestock, other animals), a total range from 8.7‰ to 23.1‰ emerged (with existing poultry manure samples also ranking among the highest overall). Variation among samples in the larger dataset demonstrates the need for a further compilation of δ18OPO4 ratios for various types of waste, especially specific to geographic regions and watershed scales. With an increased sample size, the statistical strength associated with these methods would greatly improve.

Known as “forever chemicals”, per- and polyfluoroalkyl substances (PFAS) are synthetic compounds used in consumer goods but pose significant public health concerns, including disruption of the thyroid system. As thyroid hormones (THs) are required for normal brain development, PFAS may also be developmental neurotoxicants. However, this is not well understood. Here we examine the endocrine and neurodevelopmental consequences of perfluorohexane sulfonate (PFHxS) exposure in pregnant, lactating, and developing rats, and compare its effects to an anti-thyroid pharmaceutical (propylthiouracil, PTU) that induces thyroid-mediated developmental neurotoxicity. We show that PFHxS dramatically reduces maternal serum thyroxine (T4), nearly equivalently to PTU (–55 and –51%, respectively). However, only PTU increases thyroid stimulating hormone. The lactational transfer of PFHxS is significant and reduces pup serum T4 across the postnatal period. Surprisingly, brain THs are only minimally decreased by PFHxS, whereas PTU drastically diminishes them. Evaluation of brain TH action by phenotyping, RNA-Sequencing, and quantification of radial glia cell morphology supports that PTU interrupts TH signaling while PFHxS has limited to no effect. These data show that PFHxS induces abnormal serum TH profiles; however, there were no indications of hypothyroidism in the postnatal brain. We suggest the stark differences between the neurodevelopmental effects of PFHxS and a typical antithyroid agent may be due to its interaction with TH distributing proteins like transthyretin.

For decades, fear of crime researchers have disagreed about how to best measure fear of crime. One approach proposed that measuring frequency of fear of crime within the past year has the highest validity. We argue that a frequency approach is vulnerable to the anchoring effect, in which participants base their numerical estimate on an available anchor. We conducted a survey experiment to test the effect of question wording on reported frequency of fear of crime. Participants were randomly assigned to report the number of times they felt fearful of crime within either a year, a month, or a week. There was also a fourth condition that asked a forced-choice question with many response options. They also reported the intensity of their most recent instance. We hypothesized that the year condition would yield lower frequency and higher intensity reports, followed by the month condition, and then the week condition. We did not find differences in intensity between conditions, but we found stark differences in frequencies between the year, month, and week conditions in the hypothesized direction. This is consistent with the anchoring effect: the word “year,” “month,” or “week” signaled an anchor to participants, and they adjusted their estimates from those anchors. These findings have important implications for measuring fear of crime and for survey methodology generally. We advise against asking about the frequency of fear of crime because such questions will lead participants to anchor and adjust. We also strongly caution researchers who wish to measure the frequency of other emotions, feelings, or behaviors.

The use of conventional chemical disinfectants is a common practice in built environments and has drastically increased in response to the COVID-19 pandemic. While effective for instantaneous disinfection, the application of chemical disinfectants to indoor surfaces is associated with recontamination and is prone to select for antimicrobial-resistant pathogens. In contrast, probiotic-based sanitation (PBS) relies on the premise that probiotic bacteria, namely apathogenic Bacillus spp., when combined with eco-friendly detergents and applied to indoor surfaces can outcompete and exclude pathogens. Recent in situ studies assessing PBS in healthcare settings have demonstrated overwhelmingly positive results, including significant reductions in pathogen burden, antimicrobial-resistant genes and nosocomial infections, yet these studies are limited in duration and scope. Here, we review results of Bacillus-based PBS in practice, identify knowledge gaps and discuss the considerations for the widespread use of PBS in built environments. In a time when indoor cleaning and disinfection has come to the forefront, PBS may offer an attractive, effective and sustainable alternative to conventional chemical disinfectants.

The production and consumer use of disinfectants has substantially increased during the COVID-19 pandemic. Benzalkonium chloride (BAC) is a mixture of alkyl benzyl dimethyl ammonium chloride compounds and is the most common active ingredient in surface cleaning and disinfecting products. Accordingly, BAC compounds are routinely in contact with microorganisms in indoor environments, which may contribute to the development of antimicrobial tolerance and cross-resistance. To investigate the impact of BAC exposure on commensal and opportunistic bacteria of public health importance, we exposed Staphylococcus epidermidis, Corynebacterium xerosis, Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa to a standard BAC mixture (BAC12–14), as well as purified BAC16. Minimum inhibitory concentrations (MICs) and antibiotic susceptibilities were determined before and after repeated exposure to sublethal BAC concentrations. MICs for Gram-negative bacteria were significantly higher than Gram-positive bacteria. Additionally, BAC12–14 MICs were significantly higher for opportunistic pathogens and BAC-tolerance was associated with antibiotic cross-resistance. These results suggest that common Gram-negative opportunistic pathogens are less sensitive to BAC-inhibition than commensal species and may preferentially develop antimicrobial tolerance upon repeated or prolonged exposure to BAC12–14. Reevaluating the formulation and concentration of BAC-containing products in efforts to limit the development of antimicrobial tolerance and antibiotic co-resistance is warranted.

Introduction: Nutrition and physical activity are key components for the prevention of cardiovascular disease. There remains a paucity of trial data on the effect of specific nutritional interventions on physical activity and sedentary time. One question is how a common nutrient-dense food such as avocado may impact physical activity and sedentary time in Hispanic/Latino families, a group that reports the lowest levels of physical activity. Design: This is a 6-month clustered RCT. Setting/participants: Seventy-two families (235 individuals) who identified as Hispanic/Latino were enrolled through the San Ysidro Health Center (San Diego, CA) between April 2017 and June 2018. Intervention: After a 2-week run-in period, 35 families were randomized to the intervention arm (14 avocados/family/week), and 37 families were assigned to the control arm (3 avocados/family/week). Main outcome measures: Linear mixed-effects models were used to assess changes in physical activity (MET minutes per week) between the groups during the 6-month trial. Secondary outcomes included sedentary time (minutes/week), BMI, and systolic and diastolic blood pressures. Results: An adherence goal of >80% was achieved for both arms. Total mean physical activity increased by 2,197 MET minutes per week more in the intervention group (p

Abstract Rainfall is a key abiotic factor of ecosystems that can both provide benefits and contribute to negative environmental impacts. Due to spring precipitation levels increasing in the Midwest, there has been increased interest in developing and evaluating practices that can mitigate the effects of heavy rainfall. As this is an area of interest for both agriculture and environmental sciences, demonstrating the actions of severe rainfall can be a powerful tool in the natural sciences classroom as well as in the field. Rainfall simulators are ideal for this demonstration as they can create repeated, uniform rainfall events while introducing limited variability between events. Building on previous literature, we constructed a cost‐effective, easily transportable design that can be utilized in the classroom, the lab, and the field. Here, tests were conducted to measure flow rate, rain droplet size, and uniformity of water dispersion on the cost‐effective and easily obtained solid cone‐style herbicide nozzle. We found no statistically significant differences among rainfall dispersion metrics or in raindrop uniformity analyses. This demonstrates the capability of constructing this type of teaching and research equipment at little cost while producing highly consistent and size‐relevant artificial rainfall.

Thyroid hormone (TH) action controls brain development in a spatiotemporal manner. Previously, we demonstrated that perinatal hypothyroidism led to formation of a periventricular heterotopia in developing rats. This heterotopia occurs in the posterior telencephalon, and its formation was preceded by loss of radial glia cell polarity. As radial glia mediate cell migration and originate in a progenitor cell niche called the ventricular zone (VZ), we hypothesized that TH action may control cell signaling in this region. Here we addressed this hypothesis by employing laser capture microdissection and RNA-Seq to evaluate the VZ during a known period of TH sensitivity. Pregnant rats were exposed to a low dose of propylthiouracil (PTU, 0.0003%) through the drinking water during pregnancy and lactation. Dam and pup THs were quantified postnatally and RNA-Seq of the VZ performed in neonates. The PTU exposure resulted in a modest increase in maternal thyroid stimulating hormone and reduced thyroxine (T4). Exposed neonates exhibited hypothyroidism and T4 and triiodothyronine (T3) were also reduced in the telencephalon. RNA-Seq identified 358 differentially expressed genes in microdissected VZ cells of hypothyroid neonates as compared to controls (q-values ≤0.05). Pathway analyses showed processes like maintenance of the extracellular matrix and cytoskeleton, cell adhesion, and cell migration were significantly affected by hypothyroidism. Immunofluorescence also demonstrated that collagen IV, F-actin, radial glia, and adhesion proteins were reduced in the VZ. Immunohistochemistry of integrin αvβ3 and isoforms of both thyroid receptors (TRα/TRβ) showed highly overlapping expression patterns, including enrichment in the VZ. Taken together, our results show that TH action targets multiple components of cell junctions in the VZ, and this may be mediated by both genomic and nongenomic mechanisms. Surprisingly, this work also suggests that the blood-brain and blood-cerebrospinal fluid barriers may also be affected in hypothyroid newborns.

Background: Cervical cancer, a preventable cancer of disparities, is the primary cause of cancer death for women in Nicaragua. Clinics and personnel in rural and remote Nicaragua may not be accessible to perform recommended screening or follow-up services. Objective: To assess acceptability and feasibility of integrating innovations for high-quality screening and treatment follow-up (tele-colposcopy) into existing pathways on Nicaragua's Caribbean Coast within the context of the National Cervical Cancer Control Program. Methods: Provider focus groups, key informant interviews, and environmental scans were conducted for 13 clinics on the Caribbean Coast of Nicaragua. Topics discussed included a smartphone-based mobile colposcope (MobileODT hardware and mobile platform), mobile connectivity capacity, clinic resources, provider acceptability, and current diagnostic and clinical protocols. We tested device connectivity through image upload availability and real-time video connection and simulated clinical encounters utilizing MobileODT and a low-cost cervical simulator. We developed a database of colposcopic images to establish feasibility of integrating this database and clinical characteristics into the cervical cancer registry. Results: Provider acceptability of integrating tele-colposcopy into existing cancer control efforts was high. Image upload connectivity varied by location (mean?=?1?h 9?min). Most clinics had running water (84.6%) and consistent electricity (92.3%), but some did not have access to landline telephones (53.8%). Conclusions: As faster connectivity becomes available in remote settings, Mobile Health tools such as tele-colposcopy will be increasingly feasible to provide access to high-quality cervical cancer follow-up. World Health Organization guidance on integrating technology into existing programs will remain important to ensure programmatic efficacy, local relevance, and sustainability.

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality.Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children

Multiciliated cells (MCCs) are terminally differentiated epithelia that assemble multiple motile cilia used to promote fluid flow. To template these cilia, MCCs dramatically expand their centriole content during a process known as centriole amplification. In cycling cells, the master regulator of centriole assembly Polo-like kinase 4 (PLK4) is essential for centriole duplication; however recent work has questioned the role of PLK4 in centriole assembly in MCCs. To address this discrepancy, we created genetically engineered mouse models and demonstrated that both PLK4 protein and kinase activity are critical for centriole amplification in MCCs. Tracheal epithelial cells that fail centriole amplification accumulate large assemblies of centriole proteins and do not undergo apical surface area expansion. These results show that the initial stages of centriole assembly are conserved between cycling cells and MCCs and suggest that centriole amplification and surface area expansion are coordinated events.

Abstract Drought has long been suspected as playing an important role in the abandonment of pre-Columbian Native American settlements across the midcontinental United States between 1350 and 1450 CE. However, high-resolution paleoclimatic reconstructions reflecting local effective moisture (the ratio of precipitation to evaporation) that are located in proximity to Mississippi period (1050–1450 CE) population centers are lacking. Here, we present a 1600-year-long decadally resolved oxygen isotope (δ18O) record from Horseshoe Lake (Collinsville, IL), an evaporatively influenced oxbow lake that is centrally located within the largest and mostly densely populated series of Mississippian settlements known as Greater Cahokia. A shift to higher δ18O in the Horseshoe Lake sediment record from 1200 to 1400 CE indicates that strongly evaporative conditions (i.e., low effective moisture) were persistent during the leadup to Cahokia’s abandonment. These results support the hypothesis that climate, and drought specifically, strongly impacted agriculturally based pre-Columbian Native American cultures in the midcontinental US and highlights the susceptibility of this region, presently a global food production center, to hydroclimate extremes.

The proposed article seeks to provide a case study of a doctoral program aspiring to create change through student progress and provide an overview of how they have structured program curricula to promote academic and professional growth and empower students to become global leaders. Further, this proposed article is focused on providing a focus on the importance of learning technologies and how doctoral students develop the skill sets and expertise needed to employ technology into educational and organizational contexts to enhance academic outcomes, instructional approaches, and employee productivity. Particularly, information will be provided on the importance of providing students access to cutting edge technologies that are transforming the landscape of educational and organizational learning.

We reported previously that the BET inhibitor (BETi) JQ1 decreases levels of the DNA repair protein RAD51 and that this decrease is concomitant with increased levels of DNA damage. Based on these findings, we hypothesized that a BETi would augment DNA damage produced by radiation and function as a radiosensitizer. We used clonogenic assays to evaluate the effect of JQ1 ± ionizing radiation (IR) on three pancreatic cancer cell lines in vitro. We performed immunofluorescence assays to assess the impact of JQ1 ± IR on DNA damage as reflected by levels of the DNA damage marker γH2AX, and immunoblots to assess levels of the DNA repair protein RAD51. We also compared the effect of these agents on the clonogenic potential of transfectants that expressed contrasting levels of the principle molecular targets of JQ1 (BRD2, BRD4) to determine whether levels of these BET proteins affected sensitivity to JQ1 ± IR. The data show that JQ1 + IR decreased the clonogenic potential of pancreatic cancer cells more than either modality alone. This anticlonogenic effect was associated with increased DNA damage and decreased levels of RAD51. Further, lower levels of BRD2 or BRD4 increased sensitivity to JQ1 and JQ1 + IR, suggesting that pre-treatment levels of BRD2 or BRD4 may predict sensitivity to a BETi or to a BETi + IR. We suggest that a BETi + IR merits evaluation as therapy prior to surgery for pancreatic cancer patients with borderline resectable disease.

Earth’s surface underwent a dramatic transition ~2.3 billion years ago when atmospheric oxygen first accumulated during the Great Oxidation Event. Here, the authors find that biogenic methane and volcanic emissions played a vital role in the reduced Late Archean atmosphere.

Objectives Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs.Design A multicentre, international, collaborative cohort study.Setting 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020.Participants Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, Hodgkin lymphoma, Wilms’ tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer.Main outcome measure All-cause mortality at 30 days and 90 days.Results 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p

Serving in dual caregiving roles presents challenges and has consequences for caregivers’ physical and mental health. Forty-six dual caregivers in rural southwest Virginia participated in one semi-structured telephone interview pre-pandemic. Of these caregivers, nine dual caregivers of multiple older adults (MOA) and six caregivers of multiple generations (MG) participated in two telephone interviews during the COVID-19 pandemic. Pre-pandemic health, stress, and support data were used to compare dual caregivers of MOA and MG; differences were minimal. Responses to interviews conducted during the pandemic highlighted the effects of social restrictions on MOA and MG caregivers, revealing five themes (1) Increased isolation, (2) Increased need for vigilance, (3) Negative impact on mental health, (4) Tendency to “do it all,” and (5) Increased informal help. MOA and MG caregivers differed on managing care responsibilities and ensuring the health of care recipients. In general, dual caregivers experienced decreased mental health, increased social isolation, and increased caregiving responsibilities. Antecedents of the pandemic experiences differentiated MOA and MG caregiver. Findings suggest that programs and services should target dual caregivers’ unique needs.

Background: DNA repair deficiency accumulates DNA damage and sensitizes tumor cells to PARP inhibitors (PARPi). Based on our observation that the BET inhibitor JQ1 increases levels of DNA damage, we evaluated the efficacy of JQ1 + the PARPi olaparib in preclinical models of pancreatic ductal adenocarcinoma (PDAC). We also addressed the mechanism by which JQ1 increased DNA damage. Methods: The effect of JQ1 + olaparib on in vivo tumor growth was assessed with patient-derived xenograft (PDX) models of PDAC. Changes in protein expression were detected by immunohistochemistry and immunoblot. In vitro growth inhibition and mechanistic studies were done using alamarBlue, qRT-PCR, immunoblot, immunofluorescence, ChIP, and shRNA knockdown assays. Findings: Tumors exposed in vivo to JQ1 had higher levels of the DNA damage marker γH2AX than tumors exposed to vehicle only. Increases in γH2AX was concomitant with decreased expression of DNA repair proteins Ku80 and RAD51. JQ1 + olaparib inhibited the growth of PDX tumors greater than either drug alone. Mechanistically, ChIP assays demonstrated that JQ1 decreased the association of BRD4 and BRD2 with promoter loci of Ku80 and RAD51, and shRNA data showed that expression of Ku80 and RAD51 was BRD4- and BRD2-dependent in PDAC cell lines. Interpretation: The data are consistent with the hypothesis that JQ1 confers a repair deficient phenotype and the consequent accumulation of DNA damage sensitizes PDAC cells to PARPi. Combinations of BET inhibitors with PARPi may provide a novel strategy for treating PDAC. Fund: NIH grants R01CA208272 and R21CA205501; UAB CMB T32 predoctoral training grant. Keywords: BET bromodomain inhibitor (BETi), Pancreatic cancer, PARP inhibitor (PARPi), DNA repair and damage, Patient-derived xenograft model, DNA double-strand break repair proteins

Summary: Antibodies that target the glycan cap epitope on the ebolavirus glycoprotein (GP) are common in the adaptive response of survivors. A subset is known to be broadly neutralizing, but the details of their epitopes and basis for neutralization are not well understood. Here, we present cryoelectron microscopy (cryo-EM) structures of diverse glycan cap antibodies that variably synergize with GP base-binding antibodies. These structures describe a conserved site of vulnerability that anchors the mucin-like domains (MLDs) to the glycan cap, which we call the MLD anchor and cradle. Antibodies that bind to the MLD cradle share common features, including use of IGHV1-69 and IGHJ6 germline genes, which exploit hydrophobic residues and form β-hairpin structures to mimic the MLD anchor, disrupt MLD attachment, destabilize GP quaternary structure, and block cleavage events required for receptor binding. Our results provide a molecular basis for ebolavirus neutralization by broadly reactive glycan cap antibodies.

Both essential and non-essential elements have been associated with female reproductive function in epidemiologic investigations, including among IVF populations. To date, most investigators have used blood or urine to assess biomarkers of exposure, with few employing ovarian follicular fluid (FF). FF may offer a more direct “snapshot” of the oocyte microenvironment than blood or urine, however previous studies report follicle-to-follicle variability in FF constituents that may contribute to exposure misclassification. Our objectives were to investigate sources of trace element variability, to estimate FF biomarker reliability among women undergoing IVF (n = 34), and to determine the minimum number of follicles required to estimate subject-specific mean concentrations. We measured As, Hg, Cd, Pb, Cu, Mn, Se, and Zn in FF samples using inductively coupled plasma tandem mass spectrometry. Inter-subject (between-women) variability contributed most of the variability in FF element concentrations, with ovarian, follicular, and analytical as smaller sources of variability. The proportion of variability attributable to sources between-follicles differed by age, body mass index (BMI), race, and cigarette smoking for Cu, Se, and Zn, by BMI and cigarette smoking for As, by primary infertility diagnosis for Hg, Cu, Se, and Zn, and by ovarian stimulation protocol for Mn and Se. Four to five individual follicles were sufficient to estimate subject-specific mean Cu, Se, and Zn concentrations, while >14 were necessary for As, Hg, Cd, Pb, and Mn. Overall, our results suggest that FF is a suitable source of biomarkers of As and Hg exposure in ovarian follicles. Although limited in size, our study offers the most comprehensive exploration of biological variation in FF trace elements to date and may provide guidance for future studies of ovarian trace element exposures.

Abstract The Imperial Valley region of Southeastern California has become one of the most productive agricultural regions in the state and has the highest rates of childhood asthma in California. Lack of precipitation in the Imperial Valley has caused the water level of the Salton Sea to recede to a record low since its formation in the early 1900s. Previous studies of wind and dust deposition conducted in other regions have shown how reduced precipitation, ground heating, and the diminishing water level in an arid climate pose a risk of exposing previously sequestered toxic chemicals to open air, adversely affecting lung health. The purpose of this study is to draw historical parallels between the Aral Sea and Salton Sea in the context of geomorphology, ecology, human health, economics, and human migration, to inform an assessment of environmentally related health impacts of those living in the Imperial Valley region. Future droughts and heatwaves are expected to rise in frequency and severity, disproportionately affecting those impacted by financial and health disparities. Future research must include the implications of population health in the context of GeoHealth as a result of the most recent drought and the receding water levels of the Salton Sea.

Purpose: To present a case of glioblastoma multiforme which initially presented with only ophthalmic manifestations. Observations: A 48-year-old man presented with decreased vision and pain with eye movements of the right eye. MRI of the brain showed increased T2/FLAIR signal involving the right optic nerve with no other identified abnormalities. He was treated with intravenous steroids for presumed optic neuritis. His visual acuity then rapidly worsened to no light perception, with new orbital apex symptoms including central retinal artery and vein occlusions and inferior division third and fourth nerve palsies. Repeat MRI with contrast showed perineural enhancement surrounding the right optic nerve and markedly reduced diffusion along its entire course. After an unrevealing initial workup and then a 7 month period during which the patient refused follow up, he re-presented with left sided weakness, headache, and confusion. Repeat brain MRI revealed a large mass involving the right optic nerve, optic chiasm, basal ganglia, corpus callosum and brainstem. Biopsy led to a diagnosis of WHO grade IV glioblastoma multiforme. The disease was poorly responsive to temozolomide, bevacizumab and external beam radiation, and the patient passed away 5 months later. Conclusions and importance: Malignant optic glioma of adulthood is a challenging diagnosis with a poor prognosis. This rare case highlights the importance of maintaining neoplasm in the differential for optic neuritis masqueraders. Keywords: Optic neuritis, Central retinal artery occlusion, Central retinal vein occlusion, Third nerve palsy, Fourth nerve palsy, Glioblastoma multiforme

Purpose: Breast cancer (BCA) is the most common cancer and leading cause of cancer mortality among women in Latin America and the Caribbean (LAC), and the number of deaths from BCA is expected to continue to increase. Although barriers to care include the physical accessibility of screening resources, personal and cultural barriers must be explored to understand necessary next steps to increase access to preventive care. The purpose of this in-depth narrative literature review was to explore empiric literature that surrounds the knowledge, attitudes, and beliefs toward BCA screening practices among women in LAC. To our knowledge, this is the first literature review to include articles from all countries and national languages (Portuguese, English, and Spanish) that pertain to this topic. Methods: OVID Medline, CINAHL, and Web of Science/SciELO were used to identify articles. Thirty-five articles were included according to inclusion and exclusion criteria. Results: Themes identified in the literature included knowledge about screening procedures and cause of cancer; knowledge sources; catalysts and deterrents for screening, such as family support, family history; social support or taboo, fear, self-neglect, cost, and transportation; and the perception of the screening experience. Conclusion: In addition to physical availability of resources and health care personnel, there is a necessity for culturally competent community educational interventions across all aspects of BCA screening and prevention. In light of the barriers to preventive health care, providers such as nurses and community health workers are uniquely qualified to provide culturally appropriate and individualized health education to address cultural and psychological barriers to BCA screening.

Purpose: To examine geospatial gaps in identification and evaluation of children with special healthcare needs (CSHCN) within public child development centers (CDCs). Methods: A descriptive geospatial design was used to visually depict service gaps, proximity, and clustering of area-level sociodemographic attributes of Virginia counties, and patient-level data within each CDC. Results: Geospatial analysis shows population density of uninsured children against CDC resources. Data visualization facilitates policy advocacy based on the identification of care and screening gaps for CSHCN. Conclusion: This project illustrates the collaborative potential between researchers and Health Department members to identify gaps in access to care.