Application of distillery effluents to agricultural land: is it a win-win option for soils and environment

Molasses based distilleries in India generate approximately 40 billion litres of effluents annually characterised by high organic load and salts posing a major disposal problem. The post methanation distillery effluent (PME) also being rich in plant nutrients (K, N), its use as ferti-irrigation source in agriculture is an attractive disposal option. The paper discusses the experimental results of effects of PME application (treatments: 0, 10, 20, 30 and 40 per cent of PME (5000 mg/l)) in agricultural field on the soil microbial population and chloride levels; thereby know whether soil is a good sink for recycling this nutrient rich effluent. Microbial enumeration studies revealed a beneficial effect of PME irrigation up to 30 per cent concentration due to the presence of carbon and nutrients that enhanced the soil microbial activity. Soil chloride levels and effluent colour were highest in the 0-30 cm soil depth, and beyond 45 cm their concentration decreased significantly suggesting soil acted as a good medium. Crop growth and soil health were negatively affected at higher PME concentrations or when applied without dilution. Therefore, monitoring and integrated approaches are needed to effectively utilize PME as valuable resource in agriculture and reduce its negative effects on the environment

Building a community-based open harmonised reference data repository for global crop mapping

Reference data is key to produce reliable crop type and cropland maps. Although research projects, national and international programs as well as local initiatives constantly gather crop related reference data, finding, collecting, and harmonizing data from different sources is a challenging task. Furthermore, ethical, legal, and consent-related restrictions associated with data sharing represent a common dilemma faced by international research projects. We address these dilemmas by building a community-based, open, harmonised reference data repository at global extent, ready for model training or product validation. Our repository contains data from different sources such as the Group on Earth Observations Global Agricultural Monitoring Initiative (GEOGLAM) Joint Experiment for Crop Assessment and Monitoring (JECAM) sites, the Radiant MLHub, the Future Harvest (CGIAR) centers, the National Aeronautics and Space Administration Food Security and Agriculture Program (NASA Harvest), the International Institute for Applied Systems Analysis (IIASA) citizen science platforms (LACO-Wiki and Geo-Wiki), as well as from individual project contributions. Data of 2016 onwards were collected, harmonised, and annotated. The data sets spatial, temporal, and thematic quality were assessed applying rules developed in this research. Currently, the repository holds around 75 million harmonised observations with standardized metadata of which a large share is available to the public. The repository, funded by ESA through the WorldCereal project, can be used for either the calibration of image classification deep learning algorithms or the validation of Earth Observation generated products, such as global cropland extent and maize and wheat maps. We recommend continuing and institutionalizing this reference data initiative e.g. through GEOGLAM, and encouraging the community to publish land cover and crop type data following the open science and open data principles

Global gene expression analysis of human erythroid progenitors

This article is available open access through the publisher’s website. Copyright @ 2011 American Society of Hematology. This article has an erratum: http://bloodjournal.hematologylibrary.org/content/118/26/6993.3.Understanding the pattern of gene expression during erythropoiesis is crucial for a synthesis of erythroid developmental biology. Here, we isolated 4 distinct populations at successive erythropoietin-dependent stages of erythropoiesis, including the terminal, pyknotic stage. The transcriptome was determined using Affymetrix arrays. First, we demonstrated the importance of using defined cell populations to identify lineage and temporally specific patterns of gene expression. Cells sorted by surface expression profile not only express significantly fewer genes than unsorted cells but also demonstrate significantly greater differences in the expression levels of particular genes between stages than unsorted cells. Second, using standard software, we identified more than 1000 transcripts not previously observed to be differentially expressed during erythroid maturation, 13 of which are highly significantly terminally regulated, including RFXAP and SMARCA4. Third, using matched filtering, we identified 12 transcripts not previously reported to be continuously up-regulated in maturing human primary erythroblasts. Finally, using transcription factor binding site analysis, we identified potential transcription factors that may regulate gene expression during terminal erythropoiesis. Our stringent lists of differentially regulated and continuously expressed transcripts containing many genes with undiscovered functions in erythroblasts are a resource for future functional studies of erythropoiesis. Our Human Erythroid Maturation database is available at https://cellline.molbiol.ox.ac.uk/eryth/index.html.National Health Service Blood and Transplant, National Institute for Health Research Biomedical Research Center Program, and National Institute for Health Research

Treatment of chronic or relapsing COVID-19 in immunodeficiency

BACKGROUND: Patients with some types of immunodeficiency can suffer chronic or relapsing infection with SARS-CoV-2. This leads to morbidity and mortality, infection control challenges and the risk of evolution of novel viral variants. Optimal treatment for chronic COVID-19 is unknown. OBJECTIVE: To characterise a cohort of patients with chronic or relapsing COVID-19 disease and to record treatment response. METHODS: We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features and treatment response of immune deficient patients with chronic (at least 21 days) or relapsing (at least two episodes) of COVID-19. RESULTS: We identified 31 cases with a median age of 49 years. Underlying immune deficiency was characterised by antibody deficiency with absent or profoundly reduced peripheral B cells; prior anti-CD20 therapy and X-linked agammaglobulinemia were most common. Clinical features of COVID-19 were similar to the general population, but the median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to five episodes of illness. Remdesivir monotherapy (including when given for prolonged courses up to 20 days) was associated with sustained viral clearance in 7/23 (30.4%) clinical episodes whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 monoclonal antibodies resulted in viral clearance in 13/14 (92.8%) episodes. Patients receiving no therapy did not clear SARS-CoV-2. CONCLUSIONS: COVID-19 can present as a chronic or relapsing disease in patients with antibody deficiency. Remdesivir monotherapy is frequently associated with treatment failure, but the combination of remdesivir with antibody-based therapeutics holds promise

Cross-platform expression profiling demonstrates that SV40 small tumor antigen activates Notch, Hedgehog, and Wnt signaling in human cells

BACKGROUND: We previously analyzed human embryonic kidney (HEK) cell lines for the effects that simian virus 40 (SV40) small tumor antigen (ST) has on gene expression using Affymetrix U133 GeneChips. To cross-validate and extend our initial findings, we sought to compare the expression profiles of these cell lines using an alternative microarray platform. METHODS: We have analyzed matched cell lines with and without expression of SV40 ST using an Applied Biosystems (AB) microarray platform that uses single 60-mer oligonucleotides and single-color quantitative chemiluminescence for detection. RESULTS: While we were able to previously identify only 456 genes affected by ST with the Affymetrix platform, we identified 1927 individual genes with the AB platform. Additional technical replicates increased the number of identified genes to 3478 genes and confirmed the changes in 278 (61%) of our original set of 456 genes. Among the 3200 genes newly identified as affected by SV40 ST, we confirmed 20 by QRTPCR including several components of the Wnt, Notch, and Hedgehog signaling pathways, consistent with SV40 ST activation of these developmental pathways. While inhibitors of Notch activation had no effect on cell survival, cyclopamine had a potent killing effect on cells expressing SV40 ST. CONCLUSIONS: These data show that SV40 ST expression alters cell survival pathways to sensitize cells to the killing effect of Hedgehog pathway inhibitors

Community-Based Service Providers’ Experiences With Activities for Persons With Dementia

Persons with dementia (PWD) benefit from participating in meaningful activities. This study’s objective was to learn the characteristics of successful meaningful activities from community-based service providers who work with PWD. Six group interviews were performed with 15 unique professionals from an adult day service or community-based coordinated care program. These were supplemented by 100 hr of researcher immersion through weekly volunteering. Data were analyzed by a team, using qualitative content analysis. Participants reported successful activity content incorporated personalization; continuity and incremental challenges; and social engagement. Successful delivery of activities required managing necessary resources; involving informal (family/friend) caregivers; having a backup plan; monitoring time of day and energy levels; facilitating a domino effect; and ensuring safety. Outcomes of successful activities were experiencing fulfillment and purpose; overcoming challenges; and unexpected triggers. Research and practice recommendations include testing innovative, dynamic, and technology-enabled approaches to providing such activities

ORALLY ACTIVE INHIBITORS OF HUMAN LEUKOCYTE ELASTASE. II. DISPOSITION OF L-694,458 IN RATS AND RHESUS MONKEYS

ABSTRACT: The disposition of L-694,458, a potent monocyclic ␤-lactam inhibitor of human leukocyte elastase, was studied in male SpragueDawley rats and rhesus monkeys. After iv dosing, L-694,458 exhibited similar pharmacokinetic parameters in rats and rhesus monkeys. The mean values for its plasma clearance, terminal halflife, and volume of distribution at steady state were 27 ml/min/kg, 1.8 hr, and 4.0 liters/kg in rats and 34 ml/min/kg, 2.3 hr, and 5 liters/kg in rhesus monkeys. The bioavailability of a 10 mg/kg oral dose was higher in rats (65%) than in rhesus monkeys (39%). In both species, concentrations of L-694,458 in plasma increased more than proportionally when the oral dose was increased from 10 mg/kg to 40 mg/kg. In monkeys a protracted plasma concentration-time profile was observed at 40 mg/kg, characterized by a delayed T max (8-24 hr) and a long terminal half-life (6 hr). [ 3 H]L-694,458 was well absorbed after oral dosing to rats at 10 mg/kg, as indicated by the high recovery of radioactivity in bile (83%) and urine (6%) of bile duct-cannulated rats. Only ϳ5% or less of the radioactivity in bile, urine, and feces was a result of intact L-694,458, indicating that the compound was being eliminated by metabolism, followed by excretion of the metabolites in feces, via bile. Demethylenation of the methylenedioxyphenyl group resulting in the catechol was the primary metabolic pathway in human and rhesus monkey liver microsomes. In rat liver microsomes, the major metabolite was the N-oxide of the methyl-substituted piperazine nitrogen. In rats dosed iv and orally with [ 3 H]L-694,458, concentrations of radioactivity were highest in the lung (the primary target tissue), adrenals, and liver. L-694,458 was unstable in rat blood and plasma, degrading via a pathway believed to be catalyzed by B-esterases and to involve cleavage of the ␤-lactam ring and loss of the methylpiperazine phenoxy group. In vitro studies indicated that in human liver, L-694,458 was metabolized by CYP3A and 2C isozymes, and in both monkey and human liver microsomes the compound acted as an inhibitor of testosterone 6␤-hydroxylation. Leukocyte elastase is a serine protease capable of proteolytic degradation of a variety of substrates, including elastin and collagen, which are components of connective tissue. Specific inhibitors of leukocyte elastase are being explored as potential therapeutic agents for the treatment of inflammatory diseases, such as cystic fibrosis and rheumatoid arthritis where high amounts of extracellular elastase, either free or bound to its natural inhibitors, ␣ 1 -proteinase inhibitor and secretory leukocyte proteinase inhibitor, have been detected extracellularly (1-3). Several classes of inhibitors of elastase have been synthesized and evaluated to date (4 -19). L-694,458 Materials and Methods Chemicals. L-694,458 ( Microsomes. Fresh rat liver and frozen human and rhesus monkey liver tissue were used for the preparation of microsomes. Microsomes containing 1 Abbreviations used are: L-694,458, N-[1(R)-(1,3-benzodioxol-5-yl

BSACI guidance for the implementation of Palforzia\uae peanut oral immunotherapy in the United Kingdom: A Delphi consensus study

Clinical & Experimental Allergy\ua9 2024 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.Background: Palforzia\uae enables the safe and effective desensitisation of children with peanut allergy. The treatment pathway requires multiple visits for dose escalation, up-dosing, monitoring of patients taking maintenance therapy and conversion onto daily real-world peanut consumption. The demand for peanut immunotherapy outstrips current National Health Service (NHS) capacity and requires services to develop a national consensus on how best to offer Palforzia\uae in a safe and equitable manner. We undertook a Delphi consensus exercise to determine guidance statements for the implementation of Palforzia\uae-based immunotherapy in the NHS. Methods: We undertook focus groups with children and young people who had received peanut immunotherapy to assess what was important for them and their carers. Common themes from patients formed the basis of creating draft statements. A panel of 18 multi-disciplinary professionals engaged in two rounds of anonymised voting to adapt the statements and score their importance. A final consensus workshop consolidated any variation in comments and scores to develop the final guidance statements. Results: The panel achieved consensus on 91% (29/32) of guidance statements, demonstrating strong consensus around pragmatic principles for assuring the integrity of consent, safety and conversion from Palforzia\uae to real-world peanut products. The greatest amount of feedback was generated from three broad issues; (i) whether eligibility assessment should include compulsory peanut challenges and whether these should be designed to assess the threshold at which patients react to peanut, (ii) the governance processes to best ensure that patients\u27 interests are prioritised and (iii) how to safely transition young people to other services, or discharge them, while they are taking daily peanut. Conclusions: This consensus highlights the urgent need for the NHS to increase capacity for undertaking diagnostic food challenges as well as developing Palforzia\uae immunotherapy pathways. The voting panel agreed that families of peanut allergic children should be made aware of immunotherapy, that eligibility assessment should include how co-morbid conditions are managed and that services should monitor for adverse effects. The finalised statements are now published online for clinical practice in the UK. These guidance statements will be adapted in the coming years as more evidence is published and as the international experience of peanut immunotherapy evolves

Anaesthesia, surgery, and life-threatening allergic reactions: epidemiology and clinical features of perioperative anaphylaxis in the 6th National Audit Project (NAP6)

BACKGROUND: Anaphylaxis during anaesthesia is a serious complication for patients and anaesthetists. METHODS: The 6th National Audit Project (NAP6) on perioperative anaphylaxis collected and reviewed 266 reports of Grades 3-5 anaphylaxis over 1 yr from all NHS hospitals in the UK. RESULTS: The estimated incidence was ≈1:10 000 anaesthetics. Case exclusion because of reporting delays or incomplete data means true incidence might be ≈70% higher. The distribution of 199 identified culprit agents included antibiotics (94), neuromuscular blocking agents (65), chlorhexidine (18), and Patent Blue dye (9). Teicoplanin comprised 12% of antibiotic exposures, but caused 38% of antibiotic-induced anaphylaxis. Eighteen patients reacted to an antibiotic test dose. Succinylcholine-induced anaphylaxis, mainly presenting with bronchospasm, was two-fold more likely than other neuromuscular blocking agents. Atracurium-induced anaphylaxis mainly presented with hypotension. Non-depolarising neuromuscular blocking agents had similar incidences to each other. There were no reports of local anaesthetic or latex-induced anaphylaxis. The commonest presenting features were hypotension (46%), bronchospasm (18%), tachycardia (9.8%), oxygen desaturation (4.7%), bradycardia (3%), and reduced/absent capnography trace (2.3%). All patients were hypotensive during the episode. Onset was rapid for neuromuscular blocking agents and antibiotics, but delayed with chlorhexidine and Patent Blue dye. There were 10 deaths and 40 cardiac arrests. Pulseless electrical activity was the usual type of cardiac arrest, often with bradycardia. Poor outcomes were associated with increased ASA, obesity, beta blocker, and angiotensin-converting enzyme inhibitor medication. Seventy per cent of cases were reported to the hospital incident reporting system, and only 24% to Medicines and Healthcare products Regulatory Agency via the Yellow Card Scheme. CONCLUSIONS: The overall incidence of perioperative anaphylaxis was estimated to be 1 in 10 000 anaesthetics