Detecting the fingerprints of observed climate change on surface ozone variability

At the surface, tropospheric ozone is an air pollutant that adversely impacts human health, natural vegetation and crop yield and quality. This important trace gas also plays key roles as a greenhouse gas, and as the primary source of the hydroxyl (OH) radical, which determines the lifetime of many other trace gases in the atmosphere. Tropospheric ozone has a variety of sources including photochemical production from anthropogenic and naturally occurring precursor gases, and transport from the stratosphere. As a result of its high reactivity and its wide range of sources, ozone&rsquo;s lifetime can vary from minutes in the polluted boundary layer to several weeks in the mid- and upper troposphere.</p

Tropospheric Ozone Assessment Report: Tropospheric ozone from 1877 to 2016, observed levels, trends and uncertainties

From the earliest observations of ozone in the lower atmosphere in the 19th century, both measurement methods and the portion of the globe observed have evolved and changed. These methods have different uncertainties and biases, and the data records differ with respect to coverage (space and time), information content, and representativeness. In this study, various ozone measurement methods and ozone datasets are reviewed and selected for inclusion in the historical record of background ozone levels, based on relationship of the measurement technique to the modern UV absorption standard, absence of interfering pollutants, representativeness of the well-mixed boundary layer and expert judgement of their credibility. There are significant uncertainties with the 19th and early 20th-century measurements related to interference of other gases. Spectroscopic methods applied before 1960 have likely underestimated ozone by as much as 11% at the surface and by about 24% in the free troposphere, due to the use of differing ozone absorption coefficients. There is no unambiguous evidence in the measurement record back to 1896 that typical mid-latitude background surface ozone values were below about 20 nmol mol&ndash;1, but there is robust evidence for increases in the temperate and polar regions of the northern hemisphere of 30&ndash;70%, with large uncertainty, between the period of historic observations, 1896&ndash;1975, and the modern period (1990&ndash;2014). Independent historical observations from balloons and aircraft indicate similar changes in the free troposphere. Changes in the southern hemisphere are much less. Regional representativeness of the available observations remains a potential source of large errors, which are difficult to quantify. The great majority of validation and intercomparison studies of free tropospheric ozone measurement methods use ECC ozonesondes as reference. Compared to UV-absorption measurements they show a modest (~1&ndash;5% &plusmn;5%) high bias in the troposphere, but no evidence of a change with time. Umkehr, lidar, and FTIR methods all show modest low biases relative to ECCs, and so, using ECC sondes as a transfer standard, all appear to agree to within one standard deviation with the modern UV-absorption standard. Other sonde types show an increase of 5&ndash;20% in sensitivity to tropospheric ozone from 1970&ndash;1995. Biases and standard deviations of satellite retrieval comparisons are often 2&ndash;3 times larger than those of other free tropospheric measurements. The lack of information on temporal changes of bias for satellite measurements of tropospheric ozone is an area of concern for long-term trend studies.</p

A study of psychiatrists’ concepts of mental illness

Background: There are multiple models of mental illness that inform professional and lay understanding. Few studies have formally investigated psychiatrists' attitudes. We aimed to measure how a group of trainee psychiatrists understand familiar mental illnesses in terms of propositions drawn from different models. Method: We used a questionnaire study of a sample of trainees from South London and Maudsley National Health Service (NHS) Foundation Trust designed to assess attitudes across eight models of mental illness (e.g. biological, psychodynamic) and four psychiatric disorders. Methods for analysing repeated measures and a principal components analysis (PCA) were used. Results: No one model was endorsed by all respondents. Model endorsement varied with disorder. Attitudes to schizophrenia were expressed with the greatest conviction across models. Overall, the ‘biological’ model was the most strongly endorsed. The first three components of the PCA (interpreted as dimensions around which psychiatrists, as a group, understand mental illness) accounted for 56% of the variance. Each main component was classified in terms of its distinctive combination of statements from different models: PC1 33% biological versus non-biological; PC2 12% ‘eclectic’ (combining biological, behavioural, cognitive and spiritual models); and PC3 10% psychodynamic versus sociological. Conclusions: Trainee psychiatrists are most committed to the biological model for schizophrenia, but in general are not exclusively committed to any one model. As a group, they organize their attitudes towards mental illness in terms of a biological/non-biological contrast, an ‘eclectic’ view and a psychodynamic/sociological contrast. Better understanding of how professional group membership influences attitudes may facilitate better multidisciplinary working

Inhibition of Ral GTPases Using a Stapled Peptide Approach.

Aberrant Ras signaling drives numerous cancers, and drugs to inhibit this are urgently required. This compelling clinical need combined with recent innovations in drug discovery including the advent of biologic therapeutic agents, has propelled Ras back to the forefront of targeting efforts. Activated Ras has proved extremely difficult to target directly, and the focus has moved to the main downstream Ras-signaling pathways. In particular, the Ras-Raf and Ras-PI3K pathways have provided conspicuous enzyme therapeutic targets that were more accessible to conventional drug-discovery strategies. The Ras-RalGEF-Ral pathway is a more difficult challenge for traditional medicinal development, and there have, therefore, been few inhibitors reported that disrupt this axis. We have used our structure of a Ral-effector complex as a basis for the design and characterization of α-helical-stapled peptides that bind selectively to active, GTP-bound Ral proteins and that compete with downstream effector proteins. The peptides have been thoroughly characterized biophysically. Crucially, the lead peptide enters cells and is biologically active, inhibiting isoform-specific RalB-driven cellular processes. This, therefore, provides a starting point for therapeutic inhibition of the Ras-RalGEF-Ral pathway.This work was supported by a Cambridge Cancer Centre Pump Priming award to CA, DO and HRM, a BBSRC Studentship to NSC, and a National Institutes for Health grant (CA71443) and the Welch Foundation (grant number I-1414) to MAW.This is the final version of the article. It first appeared from the American Society for Biochemistry and Molecular Biology via https://doi.org/10.1074/jbc.M116.72024

Impacts of global NOx inversions on NO2 and ozone simulations

Tropospheric NO2 and ozone simulations have large uncertainties, but their biases, seasonality, and trends can be improved with NO2 assimilations. We perform global top-down estimates of monthly NOx emissions using two Ozone Monitoring Instrument (OMI) NO2 retrievals (NASAv3 and DOMINOv2) from 2005 to 2016 through a hybrid 4D-Var/mass balance inversion. Discrepancy in NO2 retrieval products is a major source of uncertainties in the top-down NOx emission estimates. The different vertical sensitivities in the two NO2 retrievals affect both magnitude and seasonal variations of top-down NOx emissions. The 12-year averages of regional NOx budgets from the NASA posterior emissions are 37&thinsp;% to 53&thinsp;% smaller than the DOMINO posterior emissions. Consequently, the DOMINO posterior surface NO2 simulations greatly reduced the negative biases in China (by 15&thinsp;%) and the US (by 22&thinsp;%) compared to surface NO2 measurements. Posterior NOx emissions show consistent trends over China, the US, India, and Mexico constrained by the two retrievals. Emission trends are less robust over South America, Australia, western Europe, and Africa, where the two retrievals show less consistency. NO2 trends have more consistent decreases (by 26&thinsp;%) with the measurements (by 32&thinsp;%) in the US from 2006 to 2016 when using the NASA posterior emissions. The performance of posterior ozone simulations has spatial heterogeneities from region to region. On a global scale, ozone simulations using NASA-based emissions alleviate the double peak in the prior simulation of global ozone seasonality. The higher abundances of NO2 from the DOMINO posterior simulations increase the global background ozone concentrations and therefore reduce the negative biases more than the NASA posterior simulations using GEOS-Chem v12 at remote sites. Compared to surface ozone measurements, posterior simulations have more consistent magnitude and interannual variations than the prior estimates, but the performance from the NASA-based and DOMINO-based emissions varies across ozone metrics. The limited availability of remote-sensing data and the use of prior NOx diurnal variations hinder improvement of ozone diurnal variations from the assimilation, and therefore have mixed performance on improving different ozone metrics. Additional improvements in posterior NO2 and ozone simulations require more precise and consistent NO2 retrieval products, more accurate diurnal variations of NOx and VOC emissions, and improved simulations of ozone chemistry and depositions. </div

The CU mobile Solar Occultation Flux instrument: structure functions and emission rates of NH₃, NO₂ and C₂H₆

We describe the University of Colorado mobile Solar Occultation Flux instrument (CU mobile SOF). The instrument consists of a digital mobile solar tracker that is coupled to a Fourier transform spectrometer (FTS) of 0.5 cm−1 resolution and a UV–visible spectrometer (UV–vis) of 0.55 nm resolution. The instrument is used to simultaneously measure the absorption of ammonia (NH3), ethane (C2H6) and nitrogen dioxide (NO2) along the direct solar beam from a moving laboratory. These direct-sun observations provide high photon flux and enable measurements of vertical column densities (VCDs) with geometric air mass factors, high temporal resolution of 2 s and spatial resolution of 5–19 m. It is shown that the instrument line shape (ILS) of the FTS is independent of the azimuth and elevation angle pointing of the solar tracker. Further, collocated measurements next to a high-resolution FTS at the National Center for Atmospheric Research (HR-NCAR-FTS) show that the CU mobile SOF measurements of NH3 and C2H6 are precise and accurate; the VCD error at high signal to noise ratio is 2–7 %. During the Front Range Air Pollution and Photochemistry Experiment (FRAPPE) from 21 July to 3 September 2014 in Colorado, the CU mobile SOF instrument measured median (minimum, maximum) VCDs of 4.3 (0.5, 45)  ×  1016 molecules cm−2 NH3, 0.30 (0.06, 2.23)  ×  1016 molecules cm−2 NO2 and 3.5 (1.5, 7.7)  ×  1016 molecules cm−2 C2H6. All gases were detected in larger 95 % of the spectra recorded in urban, semi-polluted rural and remote rural areas of the Colorado Front Range. We calculate structure functions based on VCDs, which describe the variability of a gas column over distance, and find the largest variability for NH3. The structure functions suggest that currently available satellites resolve about 10 % of the observed NH3 and NO2 VCD variability in the study area. We further quantify the trace gas emission fluxes of NH3 and C2H6 and production rates of NO2 from concentrated animal feeding operations (CAFO) using the mass balance method, i.e., the closed-loop vector integral of the VCD times wind speed along the drive track. Excellent reproducibility is found for NH3 fluxes and also, to a lesser extent, NO2 production rates on 2 consecutive days; for C2H6 the fluxes are affected by variable upwind conditions. Average emission factors were 12.0 and 11.4 gNH3 h−1 head−1 at 30 °C for feedlots with a combined capacity for  ∼  54 000 cattle and a dairy farm of  ∼  7400 cattle; the pooled rate of 11.8 ± 2.0 gNH3 h−1 head−1 is compatible with the upper range of literature values. At this emission rate the NH3 source from cattle in Weld County, CO (535 766 cattle), could be underestimated by a factor of 2–10. CAFO soils are found to be a significant source of NOx. The NOx source accounts for  ∼  1.2 % of the N flux in NH3 and has the potential to add  ∼  10 % to the overall NOx emissions in Weld County and double the NOx source in remote areas. This potential of CAFO to influence ambient NOx concentrations on the regional scale is relevant because O3 formation is NOx sensitive in the Colorado Front Range. Emissions of NH3 and NOx are relevant for the photochemical O3 and secondary aerosol formation

Springtime high surface ozone events over the western United States: Quantifying the role of stratospheric intrusions

The published literature debates the extent to which naturally occurring stratospheric ozone intrusions reach the surface and contribute to exceedances of the U.S. National Ambient Air Quality Standard (NAAQS) for ground-level ozone (75 ppbv implemented in 2008). Analysis of ozonesondes, lidar, and surface measurements over the western U.S. from April to June 2010 show that a global high-resolution (∼50 × 50 km2) chemistry-climate model (GFDL AM3) captures the observed layered features and sharp ozone gradients of deep stratospheric intrusions, representing a major improvement over previous chemical transport models. Thirteen intrusions enhanced total daily maximum 8-h average (MDA8) ozone to ∼70–86 ppbv at surface sites. With a stratospheric ozone tracer defined relative to a dynamically varying tropopause, we find that stratospheric intrusions can episodically increase surface MDA8 ozone by 20–40 ppbv (all model estimates are bias corrected), including on days when observed ozone exceeds the NAAQS threshold. These stratospheric intrusions elevated background ozone concentrations (estimated by turning off North American anthropogenic emissions in the model) to MDA8 values of 60–75 ppbv. At high-elevation western U.S. sites, the 25th–75th percentile of the stratospheric contribution is 15–25 ppbv when observed MDA8 ozone is 60–70 ppbv, and increases to ∼17–40 ppbv for the 70–85 ppbv range. These estimates, up to 2–3 times greater than previously reported, indicate a major role for stratospheric intrusions in contributing to springtime high-O3events over the high-altitude western U.S., posing a challenge for staying below the ozone NAAQS threshold, particularly if a value in the 60–70 ppbv range were to be adopted

Circulating markers of arterial thrombosis and late-stage age-related macular degeneration: a case-control study.

PURPOSE: The aim of this study was to examine the relation of late-stage age-related macular degeneration (AMD) with markers of systemic atherothrombosis. METHODS: A hospital-based case-control study of AMD was undertaken in London, UK. Cases of AMD (n=81) and controls (n=77) were group matched for age and sex. Standard protocols were used for colour fundus photography and to classify AMD; physical examination included height, weight, history of or treatment for vascular-related diseases and smoking status. Blood samples were taken for measurement of fibrinogen, factor VIIc (FVIIc), factor VIIIc, prothrombin fragment F1.2 (F1.2), tissue plasminogen activator, and von Willebrand factor. Odds ratios from logistic regression analyses of each atherothrombotic marker with AMD were adjusted for age, sex, and established cardiovascular disease risk factors, including smoking, blood pressure, body mass index, and total cholesterol. RESULTS: After adjustment FVIIc and possibly F1.2 were inversely associated with the risk of AMD; per 1 standard deviation increase in these markers the odds ratio were, respectively, 0.62 (95% confidence interval 0.40, 0.95) and 0.71 (0.46, 1.09). None of the other atherothrombotic risk factors appeared to be related to AMD status. There was weak evidence that aspirin is associated with a lower risk of AMD. CONCLUSIONS: This study does not provide strong evidence of associations between AMD and systematic markers of arterial thrombosis, but the potential effects of FVIIc, and F1.2 are worthy of further investigation

Language matters. Addressing the use of language in the care of people with diabetes: position statement of the English Advisory Group

The language used by healthcare professionals can have a profound impact on how people living with diabetes, and those who care for them, experience their condition and feel about living with it day-to-day. At its best, good use of language, both verbal and written, can lower anxiety, build confidence, educate and help to improve self-care. Conversely, poor communication can be stigmatizing, hurtful and undermining of self-care and can have a detrimental effect on clinical outcomes. The language used in the care of those with diabetes has the power to reinforce negative stereotypes, but it also has the power to promote positive ones. The use of language is controversial and has many perspectives. The development of this position statement aimed to take account of these as well as the current evidence base. A working group, representing people with diabetes and key organizations with an interest in the care of people with diabetes, was established to review the use of language. The work of this group has culminated in this position statement for England. It follows the contribution of Australia and the USA to this important international debate. The group has set out practical examples of language that will encourage positive interactions with those living with diabetes and subsequently promote positive outcomes. These examples are based on a review of the evidence and are supported by a simple set of principles

Differential responses of myoblasts and myotubes to photobiomodulation are associated with mitochondrial number

Objective Photobiomodulation (PBM) is the application of light to promote tissue healing. Current indications suggest PBM induces its beneficial effects in vivo through upregulation of mitochondrial activity. However, how mitochondrial content influences such PBM responses have yet to be evaluated. Hence, the current study assessed the biological response of cells to PBM with varying mitochondrial contents. Methods DNA was isolated from myoblasts and myotubes (differentiated myoblasts), and mitochondrial DNA (mtDNA) was amplified and quantified using a microplate assay. Cells were seeded in 96‐wellplates, incubated overnight and subsequently irradiated using a light‐emitting diode array (400, 450, 525, 660, 740, 810, 830 and white light, 24 mW/cm2, 30‐240 seconds, 0.72‐5.76J/cm2). The effects of PBM on markers of mitochondrial activity including reactive‐oxygen‐species and real‐time mitochondrial respiration (Seahorse XFe96) assays were assessed 8 hours post‐irradiation. Datasets were analysed using general linear model followed by one‐way analysis of variance (and post hoc‐Tukey tests); P = 0.05). Results Myotubes exhibited mtDNA levels 86% greater than myoblasts (P < 0.001). Irradiation of myotubes at 400, 450 or 810 nm induced 53%, 29% and 47% increases (relative to non‐irradiated control) in maximal respiratory rates, respectively (P < 0.001). Conversely, irradiation of myoblasts at 400 or 450 nm had no significant effect on maximal respiratory rates. Conclusion This study suggests that mitochondrial content may influence cellular responses to PBM and as such explain the variability of PBM responses seen in the literature