Permafrost degradation and nitrogen cycling in Arctic rivers: Insights from stable nitrogen isotope studies

Abstract. Across the Arctic, vast areas of permafrost are being degraded by climate change, which has the potential to release substantial quantities of nutrients, including nitrogen into large Arctic rivers. These rivers heavily influence the biogeochemistry of the Arctic Ocean, so it is important to understand the potential changes to rivers from permafrost degradation. This study utilized dissolved nitrogen species (nitrate and dissolved organic nitrogen (DON)) along with nitrogen isotope values (δ15N-NO3- and δ15N-DON) of samples collected from permafrost sites in the Kolyma River and the six largest Arctic rivers. Large inputs of DON and nitrate with a unique isotopically heavy δ15N signature were documented in the Kolyma, suggesting the occurrence of denitrification and highly invigorated nitrogen cycling in the Yedoma permafrost thaw zones along the Kolyma. We show evidence for permafrost-derived DON being recycled to nitrate as it passes through the river, transferring the high 15N signature to nitrate. However, the potential to observe these thaw signals at the mouths of rivers depends on the spatial scale of thaw sites, permafrost degradation, and recycling mechanisms. In contrast with the Kolyma, with near 100 % continuous permafrost extent, the Ob River, draining large areas of discontinuous and sporadic permafrost, shows large seasonal changes in both nitrate and DON isotopic signatures. During winter months, water percolating through peat soils records isotopically heavy denitrification signals in contrast with the lighter summer values when surface flow dominates. This early year denitrification signal was present to a degree in the Kolyma, but the ability to relate seasonal nitrogen signals across Arctic Rivers to permafrost degradation could not be shown with this study. Other large rivers in the Arctic show different seasonal nitrogen trends. Based on nitrogen isotope values, the vast majority of nitrogen fluxes in the Arctic rivers is from fresh DON sourced from surface runoff through organic-rich topsoil and not from permafrost degradation. However, with future permafrost thaw, other Arctic rivers may begin to show nitrogen trends similar to the Ob. Our study demonstrates that nitrogen inputs from permafrost thaw can be identified through nitrogen isotopes, but only on small spatial scales. Overall, nitrogen isotopes show potential for revealing integrated catchment wide nitrogen cycling processes. </jats:p

Report of the ACBS Task Force on the Strategies and Tactics of Contextual Behavioral Science Research

Throughout its history the strategy and tactics of contextual behavioral science (CBS) research have had distinctive features as compared to traditional behavioral science approaches. Continued progress in CBS research can be facilitated by greater clarity about how its strategy and tactics can be brought to bear on current challenges. The present white paper is the result of a 2 1/2-year long process designed to foster consensus among representative producers and consumers of CBS research about the best strategic pathway forward. The Task Force agreed that CBS research should be multilevel, process-based, multidimensional, prosocial, and pragmatic, and provided 33 recommendations to the CBS community arranged across these characteristics. In effect, this report provides a detailed research agenda designed to maximize the impact of CBS as a field. Scientists and practitioners are encouraged to mount this ambitious agenda

Understanding the consequences of education inequality on cardiovascular disease: mendelian randomisation study.

OBJECTIVES: To investigate the role of body mass index (BMI), systolic blood pressure, and smoking behaviour in explaining the effect of education on the risk of cardiovascular disease outcomes. DESIGN: Mendelian randomisation study. SETTING: UK Biobank and international genome-wide association study data. PARTICIPANTS: Predominantly participants of European ancestry. EXPOSURE: Educational attainment, BMI, systolic blood pressure, and smoking behaviour in observational analysis, and randomly allocated genetic variants to instrument these traits in mendelian randomisation. MAIN OUTCOMES MEASURE: The risk of coronary heart disease, stroke, myocardial infarction, and cardiovascular disease (all subtypes; all measured in odds ratio), and the degree to which this is mediated through BMI, systolic blood pressure, and smoking behaviour respectively. RESULTS: Each additional standard deviation of education (3.6 years) was associated with a 13% lower risk of coronary heart disease (odds ratio 0.86, 95% confidence interval 0.84 to 0.89) in observational analysis and a 37% lower risk (0.63, 0.60 to 0.67) in mendelian randomisation analysis. As a proportion of the total risk reduction, BMI was estimated to mediate 15% (95% confidence interval 13% to 17%) and 18% (14% to 23%) in the observational and mendelian randomisation estimates, respectively. Corresponding estimates were 11% (9% to 13%) and 21% (15% to 27%) for systolic blood pressure and 19% (15% to 22%) and 34% (17% to 50%) for smoking behaviour. All three risk factors combined were estimated to mediate 42% (36% to 48%) and 36% (5% to 68%) of the effect of education on coronary heart disease in observational and mendelian randomisation analyses, respectively. Similar results were obtained when investigating the risk of stroke, myocardial infarction, and cardiovascular disease. CONCLUSIONS: BMI, systolic blood pressure, and smoking behaviour mediate a substantial proportion of the protective effect of education on the risk of cardiovascular outcomes and intervening on these would lead to reductions in cases of cardiovascular disease attributable to lower levels of education. However, more than half of the protective effect of education remains unexplained and requires further investigation.Includes MRC, ESRC, Wellcome Trust and NIHR

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

SJS/TEN 2019: From science to translation.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs

Whole-genome sequencing of acral melanoma reveals genomic complexity and diversity

To increase understanding of the genomic landscape of acral melanoma, a rare form of melanoma occurring on palms, soles or nail beds, whole genome sequencing of 87 tumors with matching transcriptome sequencing for 63 tumors was performed. Here we report that mutational signature analysis reveals a subset of tumors, mostly subungual, with an ultraviolet radiation signature. Significantly mutated genes are BRAF, NRAS, NF1, NOTCH2, PTEN and TYRP1. Mutations and amplification of KIT are also common. Structural rearrangement and copy number signatures show that whole genome duplication, aneuploidy and complex rearrangements are common. Complex rearrangements occur recurrently and are associated with amplification of TERT, CDK4, MDM2, CCND1, PAK1 and GAB2, indicating potential therapeutic options.This work was supported by a National Health and Medical Research Council of Australia (NHMRC) Program Grant (1093017, G.J.M., R.A.S., N.H., G.V.L., J.F.T.), an NHMRC project grant (APP1123217) and NHMRC Fellowship grants (R.A.S., N.K.H. - APP1139071, G.VL.). G.V.L is supported by an NHMRC Practitioner Fellowship and the University of Sydney Medical Foundation. R.A.S is supported by an NHMRC Practitioner Fellowship. J.S.W. is supported by a NHMRC early career fellowship (1111678). N.W. is supported by an NHMRC Senior Research Fellowship (1139071). N.K.H. is supported by an NHMRC Senior Principal Research Fellowship (1117663). P.M.F. was supported by the Deborah and John McMurtrie MIA Pathology Fellowship. T.J.D. was supported by the Jani Haenke Melanoma Pathology Fellowship. Support from Melanoma Institute Australia, the Royal Prince Alfred Hospital and New South Wales Health Pathology is also gratefully acknowledged

Procalcitonin Is Not a Reliable Biomarker of Bacterial Coinfection in People With Coronavirus Disease 2019 Undergoing Microbiological Investigation at the Time of Hospital Admission

Abstract Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.11–1.70] ng/mL vs 0.24 [0.10–0.90] ng/mL) nor diagnostically useful (area under the receiver operating characteristic curve, 0.56 [95% confidence interval, .51–.60]).</jats:p

Exploring the impact of public health teams on alcohol premises licensing in England and Scotland (ExILEnS): procotol for a mixed methods natural experiment evaluation.

Background: Recent regulatory changes in the system by which premises are licensed to sell alcohol, have given health representatives a formal role in the process in England and Scotland. The degree to which local public health teams engage with this process varies by locality in both nations, which have different licensing regimes. This study aims to critically assess the impact on alcohol-related harms - and mechanisms - of public health stakeholders’ engagement in alcohol premises licensing from 2012 to 2018, comparing local areas with differing types and intensities of engagement, and examining practice in Scotland and England. Methods: The study will recruit 20 local authority areas where public health stakeholders have actively engaged with the alcohol premises licensing system (the 'intervention’) and match them to a group of 20 lower activity areas using genetic matching. Four work packages are included: (1) Structured interviews and documentary analysis will examine the type and level of intervention activity from 2012 to 2018, creating a novel composite measure of the intensity of such activity and will assess the local licensing system and potential confounding activities over the same period. In-depth interviews with public health, licensing, police and others will explore perceived mechanisms of change, acceptability, and impact. (2) Using longitudinal growth models and time series analyses, the study will evaluate the impact of high and low levels of activity on alcohol-related harms using routine data from baseline 2009 to 2018. (3) Intervention costs, estimated National Health Service cost savings and health gains will be evaluated using the Sheffield Alcohol Policy Model to estimate impact on alcohol consumption and health inequalities. (4) The study will engage public health teams to create a new theory of change for public health involvement in the licensing process using our data. We will share findings with local, national and international stakeholders. Discussion: This interdisciplinary study examines, for the first time, whether and how public health stakeholders involvement in alcohol licensing impacts on alcohol harms. Using mixed methods and drawing on complex systems thinking, it will make an important contribution to an expanding literature evaluating interventions not suited to traditional epidemiological research

Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council