An investigation into morphological and physiological approaches to screen maize (Zea mays L.) hybrids for drought tolerance

A pot experiment was carried out in completely randomized design (CRD) having three replications to screen out six maize (Zea mays L.) hybrids viz; FH-810, 32-F-10, FH-782, 32-B-33, YH-1898, Monsanto-6525, R-2315 and R-3304 for drought tolerance. The study was carried out with objective to screen hybrids, when exposed to drought on the early phase of their vegetative growth. The moisture treatments comprised of 100% field capacity (FC), 75% FC and 50% FC. The results exhibited that all these hybrids varied substantially in their stability against drought tolerance. However, the results pertaining to interaction of maize hybrids with three moisture levels of 100% FC, 75% FC and 50% FC revealed that 32-F-10 performed comparatively better in contrast to other maize hybrids in plant height (79.74 cm, 47.02 cm and 41.65 cm), leaf area per plant (865.10 cm2, 405.7 cm2 and 178.60 cm2), relative water contents (81.23%, 69.79% and 65.98%), at 100%, 75% and 50% FC, respectively, while YH-1898 hybrid produced lowest values of these attributes in almost all water levels. However, a better stomatal conductance (gs), photosynthetic rate (A) and transpiration rate (E) were exhibited by 32-F-10 while YH-1898 revealed least gas-exchange values among all hybrids. The experimental results revealed that under drought conditions 32-F-10 performed best than all other maize hybrids and could be used for further investigation to screen out other drought tolerant-maize hybrids for maximum production

Large-scale discovery of novel genetic causes of developmental disorders

Despite three decades of successful, predominantly phenotype-driven discovery of the genetic causes of monogenic disorders1, up to half of children with severe developmental disorders of probable genetic origin remain without a genetic diagnosis. Particularly challenging are those disorders rare enough to have eluded recognition as a discrete clinical entity, those with highly variable clinical manifestations, and those that are difficult to distinguish from other, very similar, disorders. Here we demonstrate the power of using an unbiased genotype-driven approach2 to identify subsets of patients with similar disorders. By studying 1,133 children with severe, undiagnosed developmental disorders, and their parents, using a combination of exome sequencing3,4,5,6,7,8,9,10,11 and array-based detection of chromosomal rearrangements, we discovered 12 novel genes associated with developmental disorders. These newly implicated genes increase by 10% (from 28% to 31%) the proportion of children that could be diagnosed. Clustering of missense mutations in six of these newly implicated genes suggests that normal development is being perturbed by an activating or dominant-negative mechanism. Our findings demonstrate the value of adopting a comprehensive strategy, both genome-wide and nationwide, to elucidate the underlying causes of rare genetic disorders

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions. Funding: Bill & Melinda Gates Foundation

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Methyl jasmonate-induced alteration in lipid peroxidation, antioxidative defence system and yield in soybean under drought

International audienceMethyl jasmonate (MeJA), a plant-signalling molecule, is involved in an array of plant development and the defence responses. This study was conducted to explore the role of exogenous MeJA application in alleviating the adversities of drought stress in soybean (Glycine max L. Merrill.). Soybean plants were grown under normal conditions until blooming and were then subjected to drought by withholding irrigation followed by foliar application of (50 µm) MeJA. Drought stress substantially suppressed the yield and yield-related traits, whereas it accelerated the membrane lipid peroxidation. Nonetheless, substantial increase in activities of enzymatic antioxidants (superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)), proline, relative water contents (RWC) with simultaneous decrease in membrane lipid peroxidation was observed in MeJA-treated plants under drought. These beneficial effects led to improvement in biological and grain yield, and harvest index under drought. Interestingly, MeJA application was also useful under well-watered conditions. These results suggest the involvement of MeJA in improving the drought tolerance of soybean by modulating the membrane lipid peroxidation and antioxidant activities

Causation in evidence-based medicine: In reply to Strand and Parkkinen

Strand and Parkkinen criticize our dispositional account of causation in evidence-based medicine for failing to provide a proper epistemology of causal knowledge. In particular, they claim that we do not explain how causal inferences should be drawn. In response, we point out that dispositionalism does indeed have an account of the epistemology of causation, including counterfactual dependence, intervention, prediction and clinical decision. Furthermore, we argue that this is an epistemology that fits better with the known fallibility of even our best-informed predictions. Predictions are made on the basis that causes dispose or tend towards their effects, rather than guarantee them. The ontology of causation remains a valuable study for, among other reasons, it tells us that powers do not always combine additively. This counts against the monocausality that is tested by randomized controlled trials