Potential types of bias when estimating causal effects in environmental research and how to interpret them.

To inform environmental policy and practice, researchers estimate effects of interventions/exposures by conducting primary research (e.g., impact evaluations) or secondary research (e.g., evidence reviews). If these estimates are derived from poorly conducted/reported research, then they could misinform policy and practice by providing biased estimates. Many types of bias have been described, especially in health and medical sciences. We aimed to map all types of bias from the literature that are relevant to estimating causal effects in the environmental sector. All the types of bias were initially identified by using the Catalogue of Bias (catalogofbias.org) and reviewing key publications (n = 11) that previously collated and described biases. We identified 121 (out of 206) types of bias that were relevant to estimating causal effects in the environmental sector. We provide a general interpretation of every relevant type of bias covered by seven risk-of-bias domains for primary research: risk of confounding biases; risk of post-intervention/exposure selection biases; risk of misclassified/mismeasured comparison biases; risk of performance biases; risk of detection biases; risk of outcome reporting biases; risk of outcome assessment biases, and four domains for secondary research: risk of searching biases; risk of screening biases; risk of study appraisal and data coding/extraction biases; risk of data synthesis biases. Our collation should help scientists and decision makers in the environmental sector be better aware of the nature of bias in estimation of causal effects. Future research is needed to formalise the definitions of the collated types of bias such as through decomposition using mathematical formulae.

Cattle production strategies to deliver protein with less land and lower environmental impact.

Global land resources are over-exploited and natural habitats are declining, often driven by expanding livestock production. In Ireland, pastureland for grazing cattle and sheep account for circa 60% of terrestrial land use. The agriculture, forestry and other land use sector (AFOLU) is responsible for 44% of national greenhouse gas (GHG) emissions. A new Grassland Animal response Model (GLAM) was developed to relate livestock-cohort grass and feed requirements to farm-grassland system areas, enhancing environmental assessment of prospective AFOLU configurations. Although land conversion targets are often well-defined, they tend to lack a clear definition of where land sparing can occur. Through analyses of 10 scenarios of milk and beef production and management strategies, we found that displacing beef cows with dairy cows can increase national protein output while sparing up to 0.75 million ha (18%) of grassland (albeit with a minor increase in overseas land requirement for additional concentrate feed). Reducing slaughter age, increasing exports of male dairy calves and increasing grassland use efficiency on beef farms each achieved between 0.19 and 0.32 million ha of land sparing. Sexed semen to achieve more favourable male-female birth ratios had a minor impact. GHG emissions, ammonia emissions and nutrient leaching were only reduced substantially when overall cattle numbers declined, confirming the need for cattle reductions to achieve environmental objectives. Nonetheless, application of GLAM shows potential for improved grass and cattle management to spare good quality land suitable for productive forestry and wetland restoration. This change is urgently needed to generate scalable carbon dioxide removals from the land sector in Ireland, and globally.

Unravelling the respiratory health path across the lifespan for survivors of preterm birth.

Many survivors of preterm birth will have abnormal lung development, reduced peak lung function and, potentially, an increased rate of physiological lung function decline, each of which places them at increased risk of chronic obstructive pulmonary disease across the lifespan. Current rates of preterm birth indicate that by the year 2040, around 50 years since the introduction of surfactant therapy, more than 700 million individuals will have been born prematurely-a number that will continue to increase by about 15 million annually. In this Personal View, we describe current understanding of the impact of preterm birth on lung function through the life course, with the aim of putting this emerging health crisis on the radar for the respiratory community. We detail the potential underlying mechanisms of prematurity-associated lung disease and review current approaches to prevention and management. Furthermore, we propose a novel way of considering lung disease after preterm birth, using a multidimensional model to determine individual phenotypes of lung disease-a first step towards optimising management approaches for prematurity-associated lung disease.

Inhaled corticosteroids to improve lung function in children (aged 6-12 years) who were born very preterm (PICSI): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Despite the substantial burden of lung disease throughout childhood in children who were born very preterm, there are no evidence-based interventions to improve lung health beyond the neonatal period. We tested the hypothesis that inhaled corticosteroid improves lung function in this population. METHODS: PICSI was a randomised, double-blind, placebo-controlled trial at Perth Children's Hospital (Perth, WA, Australia) to assess whether fluticasone propionate, an inhaled corticosteroid, improves lung function in children who had been born very preterm (<32 weeks of gestation). Eligible children were aged 6-12 years and did not have severe congenital abnormalities, cardiopulmonary defects, neurodevelopmental impairment, diabetes, or any glucocorticoid use within the preceding 3 months. Participants were randomly assigned (1:1) to receive 125 µg fluticasone propionate or placebo twice daily for 12 weeks. Participants were stratified for sex, age, bronchopulmonary dysplasia diagnosis, and recent respiratory symptoms using the biased-coin minimisation technique. The primary outcome was change in pre-bronchodilator forced expiratory volume in 1 s (FEV1) after 12 weeks of treatment. Data were analysed by intention-to-treat (ie, all participants who were randomly assigned and took at least the tolerance dose of the drug). All participants were included in the safety analyses. This trial is registered at the Australian and New Zealand Clinical Trials Registry, number 12618000781246. FINDINGS: Between Oct 23, 2018, and Feb 4, 2022, 170 participants were randomly assigned and received at least the tolerance dose (83 received placebo and 87 received inhaled corticosteroid). 92 (54%) participants were male and 78 (46%) were female. 31 participants discontinued treatment before 12 weeks (14 in the placebo group and 17 in the inhaled corticosteroid group), mostly due to the impact of the COVID-19 pandemic. When analysed by intention-to-treat, the change in pre-bronchodilator FEV1 Z score over 12 weeks was -0·11 (95% CI -0·21 to 0·00) in the placebo group and 0·20 (0·11 to 0·30) in the inhaled corticosteroid group (imputed mean difference 0·30, 0·15-0·45). Three of 83 participants in the inhaled corticosteroid group had adverse events requiring treatment discontinuation (exacerbation of asthma-like symptoms). One of 87 participants in the placebo group had an adverse event requiring treatment discontinuation (inability to tolerate the treatment with dizziness, headaches, stomach pains, and worsening of a skin condition). INTERPRETATION: As a group, children born very preterm have only modestly improved lung function when treated with inhaled corticosteroid for 12 weeks. Future studies should consider individual phenotypes of lung disease after preterm birth and other agents to improve management of prematurity-associated lung disease. FUNDING: Australian National Health and Medical Research Council, Telethon Kids Institute, and Curtin University.

Increasing airway obstruction through life following bronchopulmonary dysplasia: a meta-analysis.

Background: Few studies exist investigating lung function trajectories of those born preterm; however growing evidence suggests some individuals experience increasing airway obstruction throughout life. Here we use the studies identified in a recent systematic review to provide the first meta-analysis investigating the impact of preterm birth on airway obstruction measured by the forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio. Methods: Cohorts were included for analysis if they reported FEV1/FVC in survivors of preterm birth (<37 weeks' gestation) and control populations born at term. Meta-analysis was performed using a random effect model, expressed as standardised mean difference (SMD). Meta-regression was conducted using age and birth year as moderators. Results: 55 cohorts were eligible, 35 of which defined groups with bronchopulmonary dysplasia (BPD). Compared to control populations born at term, lower values of FEV1/FVC were seen in all individuals born preterm (SMD -0.56), with greater differences seen in those with BPD (SMD -0.87) than those without BPD (SMD -0.45). Meta-regression identified age as a significant predictor of FEV1/FVC in those with BPD with the FEV1/FVC ratio moving -0.04 sds away from the term control population for every year of increased age. Conclusions: Survivors of preterm birth have significantly increased airway obstruction compared to those born at term with larger differences in those with BPD. Increased age is associated with a decline in FEV1/FVC values suggesting increased airway obstruction over the life course.

A Scoping Review of Non-Structural Airway Disease as a Cause of Poor Performance in Racehorses.

The association between poor performance and respiratory disease in Thoroughbred racehorses that do not have a structural abnormality of the respiratory tract, is often based on anecdotal evidence. The objective of this scoping review was to examine the scientific evidence for such associations. Publications were selected based on a search of three databases (PubMed, Scopus, and CAB Direct), in English and without date restriction, followed by a screening process to exclude non-relevant papers, duplicates, and reviews. This process identified 996 publications of which 20 were analysed using the Quality in Prognosis Studies (QUIPS) tool. The results indicated that the evidence supporting the relationship between proposed diagnostic indicators and poor performance is variable. There is a need for better quality evidence. In particular, there are conflicting reports relating to the impact of equine asthma and EIPH on athletic performance. Furthermore, a lack of standardisation in the measurement of racehorse performance makes it difficult to compare findings from different studies. The industry would benefit from high-level guidance concerning the design of controlled performance studies in Thoroughbred racehorses to collect comprehensive data and facilitate targeted interventions.

International Spread of Multidrug-Resistant Rhodococcus equi.

A multidrug-resistant clone of the animal and human pathogen Rhodococcus equi, MDR-RE 2287, has been circulating among equine farms in the United States since the 2000s. We report the detection of MDR-RE 2287 outside the United States. Our finding highlights the risk for MDR-RE spreading internationally with horse movements.

Geographical Differences and Temporal Improvements in Forced Expiratory Volume in 1 Second of Preterm-Born Children: A Systematic Review and Meta-analysis.

Importance: Although preterm birth is associated with later deficits in lung function, there is a paucity of information on geographical differences and whether improvements occur over time, especially after surfactant was introduced. Objective: To determine deficits in percentage predicted forced expiratory volume in 1 second (%FEV1) in preterm-born study participants, including those with bronchopulmonary dysplasia (BPD) in infancy, when compared with term-born control groups. Data Sources: Eight databases searched up to December 2021. Study Selection: Studies reporting spirometry for preterm-born participants with or without a term-born control group were identified. Data Extraction and Synthesis: Data were extracted and quality assessed by 1 reviewer and checked by another. Data were pooled using random-effects models and analyzed using Review Manager and the R metafor package. Main Outcomes and Measures: Deficits in %FEV1 between preterm-born and term groups. Associations between deficits in %FEV1 and year of birth, age, introduction of surfactant therapy, and geographical region of birth and residence were also assessed. Results: From 16 856 titles, 685 full articles were screened: 86 with and without term-born control groups were included. Fifty studies with term controls were combined with the 36 studies from our previous systematic review, including 7094 preterm-born and 17 700 term-born participants. Of these studies, 45 included preterm-born children without BPD, 29 reported on BPD28 (supplemental oxygen dependency at 28 days), 26 reported on BPD36 (supplemental oxygen dependency at 36 weeks' postmenstrual age), and 86 included preterm-born participants. Compared with the term-born group, the group of all preterm-born participants (all preterm) had deficits of %FEV1 of -9.2%; those without BPD had deficits of -5.8%, and those with BPD had deficits of approximately -16% regardless of whether they had BPD28 or BPD36. As year of birth increased, there was a statistically significant narrowing of the difference in mean %FEV1 between the preterm- and term-born groups for the all preterm group and the 3 BPD groups but not for the preterm-born group without BPD. For the all BPD group, when compared with Scandinavia, North America and western Europe had deficits of -5.5% (95% CI, -10.7 to -0.3; P = .04) and -4.1% (95% CI, -8.8 to 0.5; P = .08), respectively. Conclusions and Relevance: Values for the measure %FEV1 were reduced in preterm-born survivors. There were improvements in %FEV1 over recent years, but geographical region had an association with later %FEV1 for the BPD groups.

Elevated serum antibody responses to synthetic mycobacterial lipid antigens among UK farmers: an indication of exposure to environmental mycobacteria?

Background: mycobacterial cells contain complex mixtures of mycolic acid esters. These can be used as antigens recognised by antibodies in the serum of individuals with active tuberculosis, caused by Mycobacterium tuberculosis. In high burden populations, a significant number of false positives are observed; possibly these antigens are also recognised by antibodies generated by other mycobacterial infections, particularly ubiquitous 'environmental mycobacteria'. This suggests similar responses may be observed in a low burden TB population, particularly in groups regularly exposed to mycobacteria. Methods: ELISA using single synthetic trehalose mycolates corresponding to major classes in many mycobacteria was used to detect antibodies in serum of individuals with no known mycobacterial infection, comprising farmers, abattoir workers, and rural and urban populations. Results: serum from four Welsh or Scottish cohorts showed lower (with some antigens significantly lower) median responses than those reported for TB negatives from high-burden TB populations, and significantly lower responses than those with active TB. A small fraction, particularly older farmers, showed strong responses. A second study examined BCG vaccinated and non-vaccinated farmers and non-farmers. Farmers gave significantly higher median responses than non-farmers with three of five antigens, while there was no significant difference between vaccinated or non-vaccinated for either farmer or non-farmer groups. Conclusions: this initial study shows that serodiagnosis with mycobacterial lipid antigens can detect antibodies in a population sub-group that is significantly exposed to mycobacteria, in an assay that is not interfered with by vaccination. Given the links between mycobacterial exposure and a range of immune system diseases, further understanding such responses may provide a new opportunity for monitoring public health and directing treatment.

Key traits for ruminant livestock across diverse production systems in the context of climate change: perspectives from a global platform of research farms.

Ruminant livestock are raised under diverse cultural and environmental production systems around the globe. Ruminant livestock can play a critical role in food security by supplying high-quality, nutrient-dense food with little or no competition for arable land while simultaneously improving soil health through vital returns of organic matter. However, in the context of climate change and limited land resources, the role of ruminant-based systems is uncertain because of their reputed low efficiency of feed conversion (kilogram of feed required per kilogram of product) and the production of methane as a by-product of enteric fermentation. A growing human population will demand more animal protein, which will put greater pressure on the Earth's planetary boundaries and contribute further to climate change. Therefore, livestock production globally faces the dual challenges of mitigating emissions and adapting to a changing climate. This requires research-led animal and plant breeding and feeding strategies to optimise ruminant systems. This study collated information from a global network of research farms reflecting a variety of ruminant production systems in diverse regions of the globe. Using this information, key changes in the genetic and nutritional approaches relevant to each system were drawn that, if implemented, would help shape more sustainable future ruminant livestock systems.