Water use of sorghum (Sorghum bicolor L. Moench) in response to varying planting dates evaluated under rainfed conditions

It is vital to understand how rainfall onset, amount and distribution between planting dates affect sorghum yield and water use, in order to aid planting date and cultivar selection. This study investigated morphological, physiological, phenological, yield and water use characteristics of different sorghum genotypes in response to different planting dates under rainfed conditions. Four genotypes (PAN8816 [hybrid], Macia [open-pollinated variety, OPV], Ujiba and IsiZulu [both landraces]) were planted on 3 planting dates (early, optimal, and late) in a split-plot design, with planting dates as the main factor. Low soil water at the optimal planting date was associated with delayed crop establishment and low final emergence. Sorghum genotypes adapted to low and irregular rainfall at the late planting date through low leaf number, canopy cover, chlorophyll content index and stomatal conductance, and hastened phenological development. This resulted in low biomass and grain yields. Landraces exhibited grain yield stability across planting dates, whilst OPV and hybrid genotypes significantly reduced grain yield in response to low water availability when planted late. Biomass and grain yield water use efficiency (WUE) were highest at optimal planting date (30.5 and 9.2 kg∙ha-1·mm-1), relative to late (23.1 and 8.7 kg·ha-1·mm-1), and early planting dates (25.2 and 8.3 kg·ha-1·mm-1). For PAN8816 and Macia, biomass and grain WUE decreased in response to low soil water content, and irregular and disproportionate rainfall experienced during the late planting date. By contrast, biomass and grain WUE for Ujiba and IsiZulu improved with decreasing rainfall. PAN8816 is recommended when planting under low soil water availability to maximize crop stand. Cultivation of Macia is recommended under optimal conditions. Ujiba and IsiZulu landraces are recommended for low rainfall areas with highly variable rainfall. Repetition or modelling of genotype responses across environments different from Ukulinga is required for thorough water use characterisation of these genotypes.Keywords: planting dates, water use efficiency, rainfall variability, cultivar selection, landraces and improved sorghum varietie

The vulnerabilities of agricultural land and food production to future water scarcity

Rapidly increasing populations coupled with increased food demand requires either an expansion of agriculturalland or sufficient production gains from current resources. However, in a changing world, reduced wateravailability might undermine improvements in crop and grass productivity and may disproportionately affectdifferent parts of the world. Using multi-model studies, the potential trends, risks and uncertainties to land useand land availability that may arise from reductions in water availability are examined here. In addition, theimpacts of different policy interventions on pressures from emerging risks are examined.Results indicate that globally, approximately 11% and 10% of current crop- and grass-lands could be vul-nerable to reduction in water availability and may lose some productive capacity, with Africa and the MiddleEast, China, Europe and Asia particularly at risk. While uncertainties remain, reduction in agricultural land areaassociated with dietary changes (reduction of food waste and decreased meat consumption) offers the greatestbuffer against land loss and food insecurity

Characterisation of Innate Fungal Recognition in the Lung

The innate recognition of fungi by leukocytes is mediated by pattern recognition receptors (PRR), such as Dectin-1, and is thought to occur at the cell surface triggering intracellular signalling cascades which lead to the induction of protective host responses. In the lung, this recognition is aided by surfactant which also serves to maintain the balance between inflammation and pulmonary function, although the underlying mechanisms are unknown. Here we have explored pulmonary innate recognition of a variety of fungal particles, including zymosan, Candida albicans and Aspergillus fumigatus, and demonstrate that opsonisation with surfactant components can limit inflammation by reducing host-cell fungal interactions. However, we found that this opsonisation does not contribute directly to innate fungal recognition and that this process is mediated through non-opsonic PRRs, including Dectin-1. Moreover, we found that pulmonary inflammatory responses to resting Aspergillus conidia were initiated by these PRRs in acidified phagolysosomes, following the uptake of fungal particles by leukocytes. Our data therefore provides crucial new insights into the mechanisms by which surfactant can maintain pulmonary function in the face of microbial challenge, and defines the phagolysosome as a novel intracellular compartment involved in the innate sensing of extracellular pathogens in the lung

European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.</p

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

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)

OPTIMAX 2017 : radiation dose, image quality optimisation,the use of new technology in medical imaging

This year OPTIMAX settled in Oslo. After the successof previous years, we are proud to present the fourthEbook. As in previous years, the group was madeup of PhD-, MSc- and BSc students as well astutors from the seven European partner universities.Professional mix was drawn from medical physics/physics and radiography. OPTIMAX 2017 was partlyfunded by the partner universities and partly by theparticipants. Two students from South Africa and twofrom Brazil were invited by Hanze UAS (Groningen)and ESTeSL (Lisbon) summer school includedlectures and group projects in which experimentalresearch was conducted in four teams. Four research projects were performed with a focuson radiation dose optimization and image quality,namely: Possible dose reduction for pediatric patientsfor conventional radiology; Can the tube voltage belowered with the use of direct-conversion flat paneldetector system?; Impact of body size and kV in chestradiography; Quantity assessment on Image quality ofCBCT images of head phantom with implants of metaland ceramic objects.The last day of OPTIMAX 2017there was a poster session and a conference, in whichthe research teams presented their posters and oralpresentations. This book comprises of two sections, the first twochapters concern generic background informationabout international teamwork during the OPTIMAXsummerschool. The next chapters with theory on which the researchprojects were built. The second section containsthe research papers of the four research projects.Two research papers, Can the tube voltage belowered with the use of direct-conversion flat-paneldetector system? And Impact of body size and kV inchest radiography: Experimental receiver operatingcharacteristic analysis using a Multipurpose ChestPhantom “Lungman” have been accepted for the ECRconference, Vienna, 2018 as oral presentations

European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation.

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities