A revised lower estimate of ozone columns during Earth's oxygenated history.

The history of molecular oxygen (O2) in Earth's atmosphere is still debated; however, geological evidence supports at least two major episodes where O2 increased by an order of magnitude or more: the Great Oxidation Event (GOE) and the Neoproterozoic Oxidation Event. O2 concentrations have likely fluctuated (between 10-3 and 1.5 times the present atmospheric level) since the GOE ∼2.4 Gyr ago, resulting in a time-varying ozone (O3) layer. Using a three-dimensional chemistry-climate model, we simulate changes in O3 in Earth's atmosphere since the GOE and consider the implications for surface habitability, and glaciation during the Mesoproterozoic. We find lower O3 columns (reduced by up to 4.68 times for a given O2 level) compared to previous work; hence, higher fluxes of biologically harmful UV radiation would have reached the surface. Reduced O3 leads to enhanced tropospheric production of the hydroxyl radical (OH) which then substantially reduces the lifetime of methane (CH4). We show that a CH4 supported greenhouse effect during the Mesoproterozoic is highly unlikely. The reduced O3 columns we simulate have important implications for astrobiological and terrestrial habitability, demonstrating the relevance of three-dimensional chemistry-climate simulations when assessing paleoclimates and the habitability of faraway worlds.

Airway events in obese vs. non-obese elective surgical patients: a cross-sectional observational study.

Obesity is an increasingly prevalent comorbidity within the UK population. The aim of this study was to determine the proportion of obese patients in an elective surgical population. The second aim was to determine the choice of airway equipment and incidence of airway events in obese vs. non-obese patients. We conducted a cross-sectional observational study over two 24-h periods in March 2018 across 39 hospitals in the greater London area. Data were collected regarding 1874 patients. The incidence of obesity was 32% in the study population compared with 26% in the general UK population (p < 0.0001). Minor airway events were defined as: desaturation to Sp O2 < 90%; failed mask ventilation; supraglottic airway device problem; aspiration; airway trauma and difficult intubation; or recognised oesophageal intubation. Major airway events were defined as: unrecognised oesophageal intubation; a 'cannot intubate cannot oxygenate' emergency; the need for unplanned front-of-neck airway; cardiac arrest; or unplanned intensive care unit admission due to an airway event. In total, 89 minor and two major airway events were recorded. Obese patients were more likely to experience a minor airway event (RR 2.39, 95%CI 1.60-3.57), the most common being desaturation (Sp O2 < 90%). The use of a supraglottic airway device in obese vs. non-obese patients was associated with increased airway events (RR 3.46 [1.88-6.40]). Tracheal intubation vs. supraglottic airway device use increased with obesity class but was not associated with a decrease in airway events (RR 0.90 [0.53-1.55]). Our data suggest that obesity is more common in the elective surgical vs. general population and minor airway events are more common in obese vs. non-obese elective patients.

Using bivalve chronologies for quantifying environmental drivers in a semi-enclosed temperate sea.

Annual growth increments formed in bivalve shells are increasingly used as proxies of environmental variability and change in marine ecosystems, especially at higher latitudes. Here, we document that well-replicated and exactly dated chronologies can also be developed to capture oceanographic processes in temperate and semi-enclosed seas, such as the Mediterranean. A chronology is constructed for Glycymeris pilosa from a shallow embayment of the northern Adriatic and extends from 1979 to 2016. The chronology significantly (p < 0.05) and positively correlates to winter sea surface temperatures, but negatively correlates to summer temperatures, which suggests that extreme winter lows and extreme summer highs may be limiting to growth. However, the strongest and most consistent relationships are negative correlations with an index of the Adriatic-Ionian Bimodal Oscillating System (BiOS) for which positive values indicate the inflow of the ultraoligotrophic Eastern Mediterranean waters to the Adriatic. In contrast, the substantial freshwater flows that discharge into the Adriatic do not correlate to the bivalve chronology, emphasizing the importance of remote oceanographic processes to growth at this highly coastal site. Overall, this study underscores the potential of bivalve chronologies to capture biologically relevant, local- to regional-scale patterns of ocean circulation in mid-latitude, temperate systems.

Preparation of Recombinant Centromeric Nucleosomes and Formation of Complexes with Nonhistone Centromere Proteins.

Centromeres are present on each chromosome to direct proper segregation during cell division. The understanding of how the histone H3 variant, CENP-A, epigenetically marks the location of the centromere on the chromosome has been advanced, in part, through the study of histone complexes, nucleosomes, and nucleosomal complexes with nonhistone centromere proteins. In this chapter, we describe the preparation of recombinant versions of these complexes. The methodology is firmly rooted in classic nucleosome reconstitution methods, but we highlight the aspects of the preparations that diverge from those used for the methods established with canonical histones. We also provide a method for producing PCR-amplified nucleosomal DNA sequences in milligram quantities that is particularly useful for studies where multiple sequences and/or chemical modifications are desired. Lastly, we describe our approach to assemble and analyze a complex between the recombinant human CENP-A nucleosome and one of its binding partners, CENP-C.

Equine allogeneic umbilical cord blood derived mesenchymal stromal cells reduce synovial fluid nucleated cell count and induce mild self-limiting inflammation when evaluated in an lipopolysaccharide induced synovitis model.

REASONS FOR PERFORMING STUDY: Improvement has been reported following intra-articular (i.a.) injection of mesenchymal stromal cells (MSCs) in several species. These observations have led to the use of i.a. MSCs in equine practice with little understanding of the mechanisms by which perceived improvement occurs. OBJECTIVES: To evaluate the effect of i.a. allogeneic umbilical cord blood (CB-) derived MSCs using a lipopolysaccharide (LPS) induced synovitis model. We hypothesised that i.a. CB-MSCs would reduce the inflammatory response associated with LPS injection. STUDY DESIGN: Randomised, blinded experimental study. METHODS: Feasibility studies evaluated i.a. LPS or CB-MSCs alone into the tarsocrural joint. In the principal study, middle carpal joint synovitis was induced bilaterally with LPS and then CB-MSCs were injected into one middle carpal joint. Lameness, routine synovial fluid analysis, and synovial fluid biomarkers were evaluated at 0, 8, 24, 48 and 72 h. RESULTS: LPS injection alone resulted in transient lameness and signs of inflammation. In joints untreated with LPS, injection of 30 million CB-MSCs resulted in mild synovitis that resolved without treatment. Mild (grade 1-2) lameness in the CB-MSC-treated limb was observed in 2 horses and severe lameness (grade 4) in the 3rd, 24 h post injection. Lameness did not correlate with synovitis induced by CB-MSC injection. Simultaneous injection of LPS and CB-MSCs resulted in significant reduction in synovial fluid total nucleated, neutrophil and mononuclear cell numbers compared with contralateral LPS-only joints. No difference was detected in other parameters associated with synovial fluid analysis or in synovial fluid biomarkers. The incidence of lameness was only different from baseline at 8 h, where horses were lame in CB-MSC limbs. CONCLUSIONS: Allogeneic CB-MSCs reduced synovial fluid cell populations and stimulated mild self-limiting inflammation in the synovitis model. Continued evaluation of the effects of i.a. CB-MSC therapy on synovitis in horses is needed to evaluate anti- and proinflammatory properties of CB-MSCs. Immediate interests are dose, timing of treatment, and treatment frequency.

Describing readmissions to an Ebola case management centre (CMC), Sierra Leone, 2014.

Case management centres (CMCs) are part of the outbreak control plan for Ebola virus disease (EVD). A CMC in Sierra Leone had 33% (138/419) of primary admissions discharged as EVD negative (not a case). Fifteen of these were readmitted within 21 days, nine of which were EVD positive. All readmissions had contact with an Ebola case in the community in the previous 21 days indicating that the infection was likely acquired outside the CMC.

Climate change. Climate change and wind intensification in coastal upwelling ecosystems.

In 1990, Andrew Bakun proposed that increasing greenhouse gas concentrations would force intensification of upwelling-favorable winds in eastern boundary current systems that contribute substantial services to society. Because there is considerable disagreement about whether contemporary wind trends support Bakun's hypothesis, we performed a meta-analysis of the literature on upwelling-favorable wind intensification. The preponderance of published analyses suggests that winds have intensified in the California, Benguela, and Humboldt upwelling systems and weakened in the Iberian system over time scales ranging up to 60 years; wind change is equivocal in the Canary system. Stronger intensification signals are observed at higher latitudes, consistent with the warming pattern associated with climate change. Overall, reported changes in coastal winds, although subtle and spatially variable, support Bakun's hypothesis of upwelling intensification in eastern boundary current systems.

Vaccination with tumor cells expressing IL-15 and IL-15Rα inhibits murine breast and prostate cancer.

A number of antitumor vaccines have recently shown promise in upregulating immune responses against tumor antigens and improving patient survival. In this study, we examine the effectiveness of vaccination using interleukin (IL)-15-expressing tumor cells and also examine their ability to upregulate immune responses to tumor antigens. We demonstrated that the coexpression of IL-15 with its receptor, IL-15Rα, increased the cell-surface expression and secretion of IL-15. We show that a gene transfer approach using recombinant adenovirus to express IL-15 and IL-15Rα in murine TRAMP-C2 prostate or TS/A breast tumors induced antitumor immune responses. From this, we developed a vaccine platform, consisting of TRAMP-C2 prostate cancer cells or TS/A breast cancer cells coexpressing IL-15 and IL-15Rα that inhibited tumor formation when mice were challenged with tumor. Inhibition of tumor growth led to improved survival when compared with animals receiving cells expressing IL-15 alone or unmodified tumor cells. Animals vaccinated with tumor cells coexpressing IL-15 and IL-15Rα showed greater tumor infiltration with CD8(+) T and natural killer (NK) cells, as well as increased antitumor CD8(+) T-cell responses. Vaccination with IL-15/IL-15Rα-modified TS/A breast cancer cells provided a survival advantage to mice challenged with unrelated murine TUBO breast cancer cells, indicating the potential for allogeneic IL-15/IL-15Rα-expressing vaccines.

Neuronal beacon.

The controlled navigation of the axonal growth cone of a neuron toward the dendrite of its synaptic partner neuron is the fundamental process in forming neuronal circuitry. While a number of technologies have been pursued for axonal guidance over the past decades, they are either invasive or not controllable with high spatial and temporal resolution and are often limited by low guidance efficacy. Here, we report a neuronal beacon based on light for highly efficient and controlled guidance of cortical primary neurons.

Fiber-optic two-photon optogenetic stimulation.

Optogenetic stimulation of genetically targeted cells is proving to be a powerful tool in the study of cellular systems, both in vitro and in vivo. However, most opsins are activated in the visible spectrum, where significant absorption and scattering of stimulating light occurs, leading to low penetration depth and less precise stimulation. Since we first (to the best of our knowledge) demonstrated two-photon optogenetic stimulation (TPOS), it has gained considerable interest in the probing of cellular circuitry by precise spatial modulation. However, all existing methods use microscope objectives and complex scanning beam geometries. Here, we report a nonscanning method based on multimode fiber to accomplish fiber-optic TPOS of cells.

Esperanto for histones: CENP-A, not CenH3, is the centromeric histone H3 variant.

The first centromeric protein identified in any species was CENP-A, a divergent member of the histone H3 family that was recognised by autoantibodies from patients with scleroderma-spectrum disease. It has recently been suggested to rename this protein CenH3. Here, we argue that the original name should be maintained both because it is the basis of a long established nomenclature for centromere proteins and because it avoids confusion due to the presence of canonical histone H3 at centromeres.

The effects of perineural and intrasynovial anaesthesia of the equine foot on subsequent magnetic resonance images.

REASONS FOR PERFORMING STUDY: Artefacts caused by regional anaesthesia can influence image interpretation of ultrasonography and nuclear scintigraphy. Perineural and intrasynovial anaesthesia are commonly performed prior to magnetic resonance imaging (MRI); and the effects on MR images, if any, are unknown. OBJECTIVES: To determine if perineural and intrasynovial anaesthesia of structures in the equine foot cause iatrogenic changes detectable with MRI. METHODS: A baseline MRI examination of both front feet was performed on 15 horses, 2-6 days prior to mepivacaine injection adjacent to the lateral and medial palmar digital nerves, and into the podotrochlear bursa, digital flexor tendon sheath and distal interphalangeal joint of one randomly assigned forelimb. Magnetic resonance imaging was repeated at 24 and 72 h post injection; then qualitative and quantitative assessments of MRI findings were performed. RESULTS: Magnetic resonance imaging findings associated with the palmar digital nerves, podotrochlear bursa and distal interphalangeal joint at 24 and 72 h after mepivacaine injection did not alter significantly from those at baseline. Compared with baseline, a significant increase in synovial fluid volume of the digital flexor tendon sheath was detected with MRI at 24 and 72 h post injection. CONCLUSIONS: Perineural anaesthesia of the palmar digital nerves and intrasynovial anaesthesia of the podotrochlear or distal interphalangeal joint did not interfere with the interpretation of MR images acquired at 24 or 72 h after injection. However, intrasynovial anaesthesia of the digital flexor tendon sheath caused an iatrogenic increase in synovial fluid, detectable on MR images for at least 72 h. POTENTIAL RELEVANCE: Although a definite time frame for resolution of digital flexor tendon sheath distension was not determined, we recommend waiting more than 3 days between intrasynovial anaesthesia of the digital flexor tendon sheath and evaluation with MRI.

SU-E-J-37: Radiation Dose during Chemoembolization: A Predictive Model.

PURPOSE: To identify variables correlated with radiation dose during hepatic chemoembolization, quantify their individual impact, and apply these findings to build a dose prediction model. METHODS: A retrospective review of 77 patients undergoing hepatic chemoembolization between 1/2010-10/2010 was performed. Variables included: Radiation dose metrics[DAP, CD, number of cone beam CT and fluoroscopy time] and clinical parameters(BMI, session number, extrahepatic embolization, lesion number, chemoembolization regimen and lobe(s) treated). CD was the primary outcome measurement used for the dose model. Univariate and multivariate linear regression models were used to assess the association between dose metrics and predictive variables and assess the relative impact of each variable on dose. Variables were considered statistically significant at the p<0.05 level. Coefficient of determination(R2)and root mean square error(RMSE) were calculated for CD. R2 was used to evaluate goodness of fit and RMSE was used to establish a measurement of the typical size of the error in predicting the cumulative dose. RESULTS: Based on the multivariate analysis: higher BMI, regimen, single lesions, 1° tumor and initial session were statistically significant and incorporated into the following dose prediction model: Predicted Dose(mGy)= -672+BMI(56.3)+558(session #1)+1789(extrahepatic a. embolized)+232(1°tumor)+[-667(2-4 lesions)or - 12(>5 lesions)]+[370(dox-bead regimen)or 1618(ethiodol based regimen)]. Plots of the predicted vs actual CD were performed and the adjusted R2 for CD is 52.9%(RMSE = 697). The model is accurate at predicting 52% of the variation. When the model predicts a dosage of 1000 or 2000 mGy the actual dose interval ranges from 519-2519 mGy or 384-3616 mGy, respectively. CONCLUSIONS: Creating a radiation dose prediction model is feasible. This is the first known attempt at creating a dose model for image guided intervention and refinements to the model will be required to improve its accuracy. Prospective dose modeling will become more relevant as the cost benefit analysis of radiation exposure enters the decision making process in patient care. Alda Tam: Angiodynamics Inc., research funding Joseph Steele: MedicaSafe, Inc ownership Intelliject medical ownership INTIO medical consultant/ownership Caymus Medical ownership Cayenne Medical ownership.

Identification of community-residing individuals with dementia and their unmet needs for care.

BACKGROUND: Innovative approaches to the widespread delivery of evidence-based dementia care are needed. The aims of this study were to determine whether a telephone screening method could efficiently identify individuals in the community in need of care for dementia and to develop a multidimensional needs assessment tool for identifying the type and frequency of unmet needs related to memory disorders in the home setting. METHODS: This was a cross-sectional evaluation of 292 community-residing individuals aged 70 and older in Maryland. Participants were given a brief cognitive telephone screen. A subsample (n=43) received a comprehensive in-home assessment for dementia and dementia-related needs. Cognitive, functional, behavioral, and clinical factors were assessed. The Johns Hopkins Dementia Care Needs Assessment (JHDCNA) was used to identify unmet needs related to dementia. RESULTS: Telephone screening for the sample took 350 h, and 27% screened positive for dementia. Virtually all participants with dementia who received an in-home assessment had at least one unmet need, with the most frequent unmet needs being for a dementia workup, general medical care, environmental safety, assistance with ADL impairments, and access to meaningful activities. Caregivers, when present, also had a number of unmet needs, with the most common being caregiver education about dementia, knowledge of community resources, and caregiver mental health care. CONCLUSIONS: Effective and efficient means for identifying community-residing individuals with dementia are needed so that dementia care interventions can be provided to address unmet care needs of patients and their caregivers.

Centromere identity, function, and epigenetic propagation across cell divisions.

The key to understanding centromere identity is likely to lie in the chromatin containing the histone H3 variant CENP-A. CENP-A is the prime candidate to carry the epigenetic information that specifies the chromosomal location of the centromere in nearly all eukaryotic species, raising questions fundamental to understanding chromosome inheritance: How is the epigenetic centromere mark propagated? What physical properties of CENP-A-containing complexes are important for epigenetically marking centromeres? What are the molecules that recognize centromeric chromatin and serve as the foundation for the mitotic kinetochore? We discuss recent advances from our research groups that have yielded substantial insight into these questions and present our current understanding of the centromere. Future work promises an understanding of the molecular processes that confer fidelity to genome transmission at cell division.

The hemodynamic and neurohumoral phenotype of postural tachycardia syndrome.

BACKGROUND: Previous studies of patients with postural tachycardia syndrome (POTS) have been hampered by relatively small cohorts, failure to control medications and diet, and inconsistent testing procedures. METHODS: The Vanderbilt Autonomic Dysfunction Center Database provided results of posture studies performed in 165 patients and 66 normal controls after dietary and medication restrictions. All posture studies were performed after an overnight fast and > or =30 minutes of supine rest. RESULTS: In both the supine and standing positions, heart rate (HR) and plasma concentrations of norepinephrine (NE), epinephrine, and dopamine were higher in patients with POTS compared with the healthy controls. Supine diastolic blood pressure (BP) was also elevated in POTS, whereas supine plasma l-3,4-dihydroxyphenyalanine was reduced. In an analysis of patient subgroups with either an upright plasma NE > or = 3.54 nM (high NE) or an upright plasma NE < 3.54 nM (normal NE), HR and BP were greater in the patient subgroup with high NE. In addition to these significant differences in hemodynamic and catechol measurements, we demonstrated that supine and standing plasma aldosterone and the aldosterone/renin ratio were decreased in patients with POTS. Plasma renin activity (PRA) tended to be higher in patients, and standing HR for those in the highest PRA quartile was significantly greater than for those in the lowest PRA quartile. CONCLUSIONS: Our results from larger cohorts of patients and controls than previously studied confirm published findings and contribute additional evidence of sympathetic activation in postural tachycardia syndrome (POTS). Abnormalities in the renin-angiotensin-aldosterone system may also contribute to the POTS phenotype.

Response of turkey poults to soybean lectin levels typically encountered in commercial diets. 2. Effect on intestinal development and lymphoid organs.

Lectins are capable of altering intestinal morphology by binding to and disrupting the intestinal brush border membrane. They are also known to alter the weight of lymphoid organs. Therefore, we evaluated the effect of soybean lectin (SBL) on intestinal morphology and lymphoid organ weights of poults fed diets containing SBL. Dietary treatments evaluated in this study included a cornstarch and casein-based control (lectin-free) semipurified diet (PD) and semipurified diets containing 0.024 or 0.048% SBL (PDL and PDH, respectively). Experimental diets were fed from hatch to 14 d. Morphological evaluation of the intestine involved measurement of the villi height and perimeter, crypt depth, villus:crypt, and thickness of the muscle layer in the jejunum. Intestinal physical characteristics were also determined by measuring intestinal weight, length, and volume. Results indicated that 0.048% SBL in PDH increased villus:crypt and reduced total intestinal length in turkey poults. In addition, both the 0.024 and 0.048% dietary SBL levels reduced thymus weights. It was concluded that dietary SBL up to 0.048% enhanced intestinal development by increasing villus:crypt, but might alter the structural integrity of lymphoid organs.