66 research outputs found
The impact of snow nitrate photolysis on boundary layer chemistry and the recycling and redistribution of reactive nitrogen across Antarctica and Greenland in a global chemical transport model
The formation and recycling of reactive nitrogen (NO, NO2, HONO) at the air–snow interface has implications for air quality and the oxidation capacity of the atmosphere in snow-covered regions. Nitrate (NO3−) photolysis in snow provides a source of oxidants (e.g., hydroxyl radical) and oxidant precursors (e.g., nitrogen oxides) to the overlying boundary layer, and alters the concentration and isotopic (e.g., δ15N) signature of NO3− preserved in ice cores. We have incorporated an idealized snowpack with a NO3− photolysis parameterization into a global chemical transport model (Goddard Earth Observing System (GEOS) Chemistry model, GEOS-Chem) to examine the implications of snow NO3− photolysis for boundary layer chemistry, the recycling and redistribution of reactive nitrogen, and the preservation of ice-core NO3− in ice cores across Antarctica and Greenland, where observations of these parameters over large spatial scales are difficult to obtain. A major goal of this study is to examine the influence of meteorological parameters and chemical, optical, and physical snow properties on the magnitudes and spatial patterns of snow-sourced NOx fluxes and the recycling and redistribution of reactive nitrogen across Antarctica and Greenland. Snow-sourced NOx fluxes are most influenced by temperature-dependent quantum yields of NO3− photolysis, photolabile NO3− concentrations in snow, and concentrations of light-absorbing impurities (LAIs) in snow. Despite very different assumptions about snowpack properties, the range of model-calculated snow-sourced NOx fluxes are similar in Greenland (0.5–11 × 108 molec cm−2 s−1) and Antarctica (0.01–6.4 × 108 molec cm−2 s−1) due to the opposing effects of higher concentrations of both photolabile NO3− and LAIs in Greenland compared to Antarctica. Despite the similarity in snow-sourced NOx fluxes, these fluxes lead to smaller factor increases in mean austral summer boundary layer mixing ratios of total nitrate (HNO3+ NO3−), NOx, OH, and O3 in Greenland compared to Antarctica because of Greenland's proximity to pollution sources. The degree of nitrogen recycling in the snow is dependent on the relative magnitudes of snow-sourced NOx fluxes versus primary NO3− deposition. Recycling of snow NO3− in Greenland is much less than in Antarctica Photolysis-driven loss of snow NO3− is largely dependent on the time that NO3− remains in the snow photic zone (up to 6.5 years in Antarctica and 7 months in Greenland), and wind patterns that redistribute snow-sourced reactive nitrogen across Antarctica and Greenland. The loss of snow NO3− is higher in Antarctica (up to 99 %) than in Greenland (up to 83 %) due to deeper snow photic zones and lower snow accumulation rates in Antarctica. Modeled enrichments in ice-core δ15N(NO3−) due to photolysis-driven loss of snow NO3− ranges from 0 to 363 ‰ in Antarctica and 0 to 90 ‰ in Greenland, with the highest fraction of NO3− loss and largest enrichments in ice-core δ15N(NO3−) at high elevations where snow accumulation rates are lowest. There is a strong relationship between the degree of photolysis-driven loss of snow NO3− and the degree of nitrogen recycling between the air and snow throughout all of Greenland and in Antarctica where snow accumulation rates are greater than 130 kg m−2 a−1 in the present day
Factors controlling variability in the oxidative capacity of the troposphere since the Last Glacial Maximum
The oxidative capacity of past atmospheres is highly uncertain. We present
here a new climate–biosphere–chemistry modeling framework to determine
oxidant levels in the present and past troposphere. We use the
GEOS-Chem chemical transport model driven by meteorological fields
from the NASA Goddard Institute of Space Studies (GISS) ModelE, with land
cover and fire emissions from dynamic global vegetation models. We present
time-slice simulations for the present day, late preindustrial era (AD 1770),
and the Last Glacial Maximum (LGM, 19–23 ka), and we test the sensitivity
of model results to uncertainty in lightning and fire emissions. We find that
most preindustrial and paleo climate simulations yield reduced oxidant levels
relative to the present day. Contrary to prior studies, tropospheric mean OH
in our ensemble shows little change at the LGM relative to the preindustrial
era (0.5 ± 12 %), despite large reductions in methane concentrations.
We find a simple linear relationship between tropospheric mean ozone
photolysis rates, water vapor, and total emissions of NO<sub>x</sub> and
reactive carbon that explains 72 % of the variability in global mean OH in
11 different simulations across the last glacial–interglacial time interval
and the industrial era. Key parameters controlling the tropospheric oxidative
capacity over glacial–interglacial periods include overhead stratospheric
ozone, tropospheric water vapor, and lightning NO<sub>x</sub> emissions.
Variability in global mean OH since the LGM is insensitive to fire emissions.
Our simulations are broadly consistent with ice-core records of
Δ<sup>17</sup>O in sulfate and nitrate at the LGM, and CO, HCHO, and
H<sub>2</sub>O<sub>2</sub> in the preindustrial era. Our results imply that the
glacial–interglacial changes in atmospheric methane observed in ice cores
are predominantly driven by changes in its sources as opposed to its sink
with OH
Atmospheric Input and Seasonal Inventory of Dissolved Iron in the Sargasso Sea: Implications for Iron Dynamics in Surface Waters of the Subtropical Ocean
Constraining the role of dust deposition in regulating the concentration of the essential micronutrient iron in surface ocean waters requires knowledge of the flux of seawater-soluble iron in aerosols and the replacement time of dissolved iron (DFe) in the euphotic zone. Here we estimate these quantities using seasonally resolved DFe data from the Bermuda Atlantic Time-series Study region and weekly-scale measurements of iron in aerosols and rain from Bermuda during 2019. In response to seasonal changes in vertical mixing, primary production and dust deposition, surface DFe concentrations vary from ∼0.2 nM in early spring to \u3e1 nM in late summer, with DFe inventories ranging from ∼30 to ∼80 μmol/m2, respectively, over the upper 200 m. Assuming the upper ocean approximates steady state for DFe on an annual basis, our aerosol and rainwater data require a mean euphotic-zone residence time of ∼0.8–1.9 years for DFe with respect to aeolian input
Three‐year efficacy and safety of certolizumab pegol for the treatment of plaque psoriasis: results from the randomized phase 3 CIMPACT trial
From Wiley via Jisc Publications RouterHistory: received 2021-02-23, rev-recd 2021-05-21, accepted 2021-06-22, pub-electronic 2021-08-17Article version: VoRPublication status: PublishedFunder: Dermira, IncFunder: UCB PharmaAbstract: Background: Certolizumab pegol (CZP) is an Fc‐free, PEGylated anti‐tumor necrosis factor biologic. Objectives: To report 3‐year outcomes from the CIMPACT (NCT02346240) phase 3, CZP in moderate to severe plaque psoriasis, randomized controlled trial. Methods: Adults were randomized 3:3:3:1 to CZP 200 mg every other week (Q2W), CZP 400 mg Q2W, etanercept biweekly or placebo. At Week 16, CZP‐ and etanercept‐treated PASI 75 responders were re‐randomized to CZP 200 mg Q2W, CZP 400 mg Q4W, CZP 400 mg Q2W or placebo for maintenance treatment; PASI 75 non‐responders entered an open‐label escape CZP 400 mg Q2W arm. Patients entering the open‐label extension (OLE; Weeks 48–144) from blinded treatment received CZP 200 mg Q2W. Results: Double‐blinded results have been reported previously. 261 patients received 200 mg Q2W upon OLE entry. PASI 75 response was maintained in patients continuing 200 mg Q2W treatment through Weeks 16–144 (Week 144: 96.2%). In patients dosed down at Week 48 (double‐blinded 400 mg to 200 mg Q2W), PASI 75 decreased (Week 48: 98.7%; Week 144: 85.9%). In patients who received placebo through Weeks 16–48, PASI 75 response decreased (Week 48: 60.4%), then increased following Week 48 switch to 200 mg Q2W (Week 144: 95.1%). 48 and 36 patients initially randomized to 200 and 400 mg Q2W, respectively, were Week 16 PASI 75 non‐responders and entered the escape arm; at Week 144, 71.8% and 78.2% achieved PASI 75. No new safety signals were identified. Conclusions: Response to CZP was durable over three years; no new safety signals were identified
Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial
Objective: Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents.
Methods: In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients.
Results: More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60.
Conclusions: The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients
Nitrogen isotopes in ice core nitrate linked to anthropogenic atmospheric acidity change
A new proprietary gel containing glabridin, andrographolide, and apolactoferrin improves the appearance of epidermal melasma in adult women: A 6‐month pilot, uncontrolled open‐label study
Gradients in intact polar diacylglycerolipids across the Mediterranean Sea are related to phosphate availability
International audienceIntact polar membrane lipids compose a significant fraction of cellular material in plankton and their synthesis imposes a substantial constraint on planktonic nutrient requirements. As a part of the Biogeochemistry from the Oligotrophic to the Ultraoligotrophic Mediterranean (BOUM) cruise we examined the distribution of several classes of intact polar diacylglycerolipids (IP-DAGs) across the Mediterranean, and found that phospholipid concentration as a percent of total lipids correlated with phosphate concentration. In addition, the ratios of non-phosphorus lipids to phospholipids – sulfoquinovosyldiacylglycerol (SQDG) to phosphatidylglycerol (PG), and betaine lipids to phosphatidylcholine (PC) – were also found to increase from west to east across the Mediterranean. Additionally, microcosm incubations from across the Mediterranean were amended with phosphate and ammonium, and in the course of several days nutrient amendments elicited a shift in the ratios of IP-DAGs. These experiments were used to assess the relative contribution of community shifts and physiological response to the observed change in IP-DAGs across the Mediterranean. The ratio of SQDG to chlorophyll-a was also explored as an indicator of phytoplankton response to nitrogen availability. This study is the first to demonstrate the dynamic response of membrane lipid composition to changes in nutrients in a natural, mixed planktonic community
Efficacy and safety of apremilast in patients with moderate to severe plaque psoriasis of the scalp: results up to 32 weeks from a randomised, phase 3 study
Scalp psoriasis is common and is often severe enough to negatively impact quality of life (QOL).(1,2) In STYLE (NCT03123471), oral apremilast 30 mg twice daily (BID) demonstrated significantly greater improvements in moderate to severe plaque psoriasis of the scalp, scalp itch, whole body itch, and QOL versus placebo(3) during the 16-week, placebo-controlled phase; safety and tolerability were consistent with the known safety profile of apremilast.(3,4) We report the efficacy and safety of apremilast during the apremilast extension phase of STYLE (Weeks 16 to 32). During the extension phase, patients initially randomised to placebo were switched to apremilast (placebo/apremilast group; with titration during Week 16) and patients initially randomised to apremilast continued active treatment (apremilast/apremilast group; with dummy titration during Week 16) through Week 32. We also present efficacy of apremilast at Week 16 in patient subgroups based on baseline demographics and treatment characteristics
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