Nitrogen budgeting for water quality improvement in pineapple production systems of south eastern Queensland, Australia.

The Glass House Mountains area was identified as a source of elevated nitrogen (N) which flows into the Pumicestone Passage and Moreton Bay. Elevated N causes decline in water quality and ecological function of these internationally important Ramsar wetlands, fisheries habitat, and recreational tourism natural amenities. Investigations into the origin of elevated aquatic N levels identified intensive horticultural activities were likely key contributors. A review of horticulture in the catchment was undertaken. The review determined that pineapple production systems in this area presented the largest opportunity for addressing aquatic N levels. Using a systems agronomy approach a partial N budget and review of nutrient management practices investigated nitrogen use efficiency (NUE). Findings identified N loading in waterways was impact by rainfall volume and frequency. Agronomic timing of N application to meet plant demand was imbalanced. Deep drainage is the predominant N loss pathway in major soil types of the catchment

Effectiveness of Denitrifying Bioreactors on Water Pollutant Reduction from Agricultural Areas

HighlightsDenitrifying woodchip bioreactors treat nitrate-N in a variety of applications and geographies.This review focuses on subsurface drainage bioreactors and bed-style designs (including in-ditch).Monitoring and reporting recommendations are provided to advance bioreactor science and engineering. Denitrifying bioreactors enhance the natural process of denitrification in a practical way to treat nitrate-nitrogen (N) in a variety of N-laden water matrices. The design and construction of bioreactors for treatment of subsurface drainage in the U.S. is guided by USDA-NRCS Conservation Practice Standard 605. This review consolidates the state of the science for denitrifying bioreactors using case studies from across the globe with an emphasis on full-size bioreactor nitrate-N removal and cost-effectiveness. The focus is on bed-style bioreactors (including in-ditch modifications), although there is mention of denitrifying walls, which broaden the applicability of bioreactor technology in some areas. Subsurface drainage denitrifying bioreactors have been assessed as removing 20% to 40% of annual nitrate-N loss in the Midwest, and an evaluation across the peer-reviewed literature published over the past three years showed that bioreactors around the world have been generally consistent with that (N load reduction median: 46%; mean ±SD: 40% ±26%; n = 15). Reported N removal rates were on the order of 5.1 g N m-3 d-1 (median; mean ±SD: 7.2 ±9.6 g N m-3 d-1; n = 27). Subsurface drainage bioreactor installation costs have ranged from less than $5,000 to$27,000, with estimated cost efficiencies ranging from less than $2.50 kg-1 N year-1 to roughly$20 kg-1 N year-1 (although they can be as high as $48 kg-1 N year-1). A suggested monitoring setup is described primarily for the context of conservation practitioners and watershed groups for assessing annual nitrate-N load removal performance of subsurface drainage denitrifying bioreactors. Recommended minimum reporting measures for assessing and comparing annual N removal performance include: bioreactor dimensions and installation date; fill media size, porosity, and type; nitrate-N concentrations and water temperatures; bioreactor flow treatment details; basic drainage system and bioreactor design characteristics; and N removal rate and efficiency

Progress in adolescent health and wellbeing: tracking 12 headline indicators for 195 countries and territories, 1990–2016

Background: Rapid demographic, epidemiological, and nutritional transitons have brought a pressing need to track progress in adolescent health. Here, we present country-level estimates of 12 headline indicators from the Lancet Commission on adolescent health and wellbeing, from 1990 to 2016. Methods: Indicators included those of health outcomes (disability-adjusted life-years [DALYs] due to communicable, maternal, and nutritional diseases; injuries; and non-communicable diseases); health risks (tobacco smoking, binge drinking, overweight, and anaemia); and social determinants of health (adolescent fertility; completion of secondary education; not in education, employment, or training [NEET]; child marriage; and demand for contraception satisfied with modern methods). We drew data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016, International Labour Organisation, household surveys, and the Barro-Lee education dataset. Findings: From 1990 to 2016, remarkable shifts in adolescent health occurred. A decrease in disease burden in many countries has been offset by population growth in countries with the poorest adolescent health profiles. Compared with 1990, an additional 250 million adolescents were living in multi-burden countries in 2016, where they face a heavy and complex burden of disease. The rapidity of nutritional transition is evident from the 324·1 million (18%) of 1·8 billion adolescents globally who were overweight or obese in 2016, an increase of 176·9 million compared with 1990, and the 430·7 million (24%) who had anaemia in 2016, an increase of 74·2 million compared with 1990. Child marriage remains common, with an estimated 66 million women aged 20–24 years married before age 18 years. Although gender-parity in secondary school completion exists globally, prevalence of NEET remains high for young women in multi-burden countries, suggesting few opportunities to enter the workforce in these settings. Interpretation: Although disease burden has fallen in many settings, demographic shifts have heightened global inequalities. Global disease burden has changed little since 1990 and the prevalence of many adolescent health risks have increased. Health, education, and legal systems have not kept pace with shifting adolescent needs and demographic changes. Gender inequity remains a powerful driver of poor adolescent health in many countries. Funding: Australian National Health and Medical Research Council, and the Bill & Melinda Gates Foundatio

Alcohol Consumption in Diabetic Patients with Nonalcoholic Fatty Liver Disease

Aim. To examine the association between lifetime alcohol consumption and significant liver disease in type 2 diabetic patients with NAFLD. Methods. A cross-sectional study assessing 151 patients with NAFLD at risk of clinically significant liver disease. NAFLD fibrosis severity was classified by transient elastography; liver stiffness measurements ≥8.2 kPa defined significant fibrosis. Lifetime drinking history classified patients into nondrinkers, light drinkers (always ≤20 g/day), and moderate drinkers (any period with intake >20 g/day). Result. Compared with lifetime nondrinkers, light and moderate drinkers were more likely to be male (p=0.008) and to be Caucasian (p=0.007) and to have a history of cigarette smoking (p=0.000), obstructive sleep apnea (p=0.003), and self-reported depression (p=0.003). Moderate drinkers required ≥3 hypoglycemic agents to maintain diabetic control (p=0.041) and fibrate medication to lower blood triglyceride levels (p=0.044). Compared to lifetime nondrinkers, light drinkers had 1.79 (95% CI: 0.67–4.82; p=0.247) and moderate drinkers had 0.91 (95% CI: 0.27–3.10; p=0.881) times the odds of having liver stiffness measurements ≥8.2 kPa (adjusted for age, gender, and body mass index). Conclusions. In diabetic patients with NAFLD, light or moderate lifetime alcohol consumption was not significantly associated with liver fibrosis. The impact of lifetime alcohol intake on fibrosis progression and diabetic comorbidities, in particular obstructive sleep apnea and hypertriglyceridemia, requires further investigation

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

Changes in meltwater chemistry over a 20-year period following a thermal regime switch from polythermal to cold-based glaciation at Austre Broggerbreen, Svalbard

Our long-term study gives a rare insight into meltwater hydrochemistry following the transition of Austre Brøggerbreen from polythermal to cold-based glaciation and its continued retreat. We find that the processes responsible for ion acquisition did not change throughout the period of records but became more productive. Two regimes before and after July/August 2000 were identified from changes in solute concentrations and pH. They resulted from increased chemical weathering occurring in ice-marginal and proglacial environments that have become progressively exposed by glacier retreat. Carbonate carbonation nearly doubled between 2000 and 2010, whilst increases in the weathering of silicate minerals were also marked. In addition, the end of ablation season chemistry was characterized by reactions in long residence time flow paths like those in subglacial environments, in spite of their absence in the watershed. Furthermore, the retreat of the glacier caused the sudden re-routing of meltwaters through its immediate forefield during 2009, which more than doubled crustal ion yields in this particular year and influenced chemical weathering in 2010 regardless of a low water flux. Such a “flush” of crustally derived ions can be meaningful for downstream terrestrial and marine ecosystems. We therefore find that, during glacier retreat, the recently exposed forefield is the most chemically active part of the watershed, making high rates of weathering possible, even when ice losses have caused a switch to cold-based conditions with no delayed subglacial drainage flowpaths. In addition, the drainage system reorganization events result in significant pCO2 depletion in an otherwise high pCO2 system

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)