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.

Does the Use of Different Indicators to Benchmark Antimicrobial Use Affect Farm Ranking?

The need to reduce antimicrobial use (AMU) in livestock production has led to the establishment of national AMU data collection systems in several countries. However, there is currently no consensus on which AMU indicator should be used and many of the systems have defined their own indicators. This study sought to explore the effect of using different internationally recognized indicators on AMU data collected from Irish pig farms and to determine if they influenced the ranking of farms in a benchmarking system. AMU data for 2016 was collected from 67 pig farms (c. 35% of Irish pig production). Benchmarks were defined using seven AMU indicators: two based on weight of active ingredient; four based on the defined daily doses (DDD) used by the European Medicines Agency and the national monitoring systems of Denmark and the Netherlands; and one based on the treatment incidence (TI200) used in several published studies. An arbitrary "action zone," characterized by farms above an acceptable level of AMU, was set to the upper quartile (i.e., the top 25% of users, n = 17). Each pair of indicators was compared by calculating the Spearman rank correlation and assessing if farms above the threshold for one indicator were also above it for the comparison indicator. The action zone was broadly conserved across all indicators; even when using weight-based indicators. The lowest correlation between indicators was 0.94. Fifteen farms were above the action threshold for at least 6 of the 7 indicators while 10 farms were above the threshold for all indicators. However, there were important differences noted for individual farms between most pairs of indicators. The biggest discrepancies were seen when comparing the TI200 to the weight-based indicators and the TI200 to the DDDANED (as used by Dutch AMU monitoring system). Indicators using the same numerator were the most similar. All indicators used in this study identified the majority of high users. However, the discrepancies noted highlight the fact that different methods of measuring AMU can affect a benchmarking system. Therefore, careful consideration should be given to the limitations of any indicator chosen for use in an AMU monitoring system.

Quantification, description and international comparison of antimicrobial use on Irish pig farms.

BACKGROUND: There is concern that the use of antimicrobials in livestock production has a role in the emergence and dissemination of antimicrobial resistance in animals and humans. Consequently, there are increasing efforts to reduce antimicrobial use (AMU) in agriculture. As the largest consumer of veterinary antimicrobials in several countries, the pig sector is a particular focus of these efforts. Data on AMU in pig production in Ireland are lacking. This study aimed to quantify AMU on Irish pig farms, to identify the major patterns of use employed and to compare the results obtained to those from other published reports and studies. RESULTS: Antimicrobial use data for 2016 was collected from 67 Irish pig farms which represented c. 35% of national production. The combined sample population consumed 14.5 t of antimicrobial by weight of active ingredient suggesting that the pig sector accounted for approximately 40% of veterinary AMU in Ireland in 2016. At farm level, median AMU measured in milligram per population correction unit (mg/PCU) was 93.9 (range: 1.0-1196.0). When measured in terms of treatment incidence (TI200), median AMU was 15.4 (range: 0.2-169.2). Oral treatments accounted for 97.5% of all AMU by weight of active ingredient and were primarily administered via medicated feed to pigs in the post weaning stages of production. AMU in Irish pig production in 2016 was higher than results obtained from the national reports of Sweden, Denmark, the Netherlands and France but lower than the United Kingdom. CONCLUSIONS: Pig production in Ireland is an important consumer of veterinary antimicrobials. The quantities and patterns of AMU on Irish pig farms are comparable to pig production in other European countries but higher than some countries with more advanced AMU reduction strategies. This AMU is characterised by a high proportion of prophylactic use and is primarily administered to pigs post weaning via medicated feed. Further studies to better understand the reasons for AMU on Irish pig farms and strategies to improve health among weaner pigs will be of benefit in the effort to reduce AMU.

Maintaining production while reducing local and global environmental emissions in dairy farming.

While milk is a major agricultural commodity, dairy farming also supports a large share of global beef production. In Life Cycle Assessment (LCA) studies of dairy farming systems, dairy-beef production is often ignored or 'allocated off', which may give a distorted view of production efficiencies. This study combines LCA with Data Envelopment Analysis (DEA) to develop an indicator of eco-efficiency for each of 738 UK dairy farms (3624 data points in 15 years) that aggregates multiple burdens and expresses them per unit of milk and dairy-beef produced. Within the DEA framework, the importance (weight) of dairy-beef relative to milk is iteratively increased to quantify the environmental losses from heavily focussing on milk-production, via e.g. higher yields per cow, with consequent lower burdens per unit of milk, yet with lower dairy-beef production levels, where burdens for beef production are externalized. Then, the relationship between DEA eco-efficiency and a series of indicators of dairy farming intensity at animal- and farm-levels was studied with Generalized Additive Models (GAM). For all sets of DEA weights (proportion of deviance explained ranged between 68% and 82%) indicate that milk yield per cow and forage area, and larger dairy herds all have a positive effect on eco-efficiency, while concentrate fed per unit of milk and the forage area both have a negative effect (p < 0.05 for all modelled relationships). These findings suggest that more intensive and consolidated dairy farms can positively impact on eco-efficiency. However, as the DEA weight for dairy-beef relative to milk increases, the relationship between environmental efficiency and farming specialization (expressed as L milk per kg dairy-beef produced) reverses from positive to negative. In conclusion, dairy-beef production is pivotal in determining the wider environmental efficiency of dairy (and ruminant food) systems, and its under-representation in efficiency studies has generated a misleading approach to meeting emission targets.

Predicting Lung Health Trajectories for Survivors of Preterm Birth.

Rates of preterm birth (<37 weeks of gestation) are increasing worldwide. Improved perinatal care has markedly increased survival of very (<32 weeks gestation) and extremely (<28 weeks gestation) preterm infants, however, long term respiratory sequalae are common among survivors. Importantly, individual's lung function trajectories are determined early in life and tend to track over the life course. Preterm infants are impacted by antenatal, postnatal and early life perturbations to normal lung growth and development, potentially resulting in significant shifts from the "normal" lung function trajectory. This review summarizes what is currently known about the long-term lung function trajectories in survivors of preterm birth. Further, this review highlights how antenatal, perinatal and early life factors are likely to contribute to individual lung health trajectories across the life course.

Mechanisms and impacts of an incentive-based conservation program with evidence from a randomized control trial.

Conservation science needs more high-quality impact evaluations, especially ones that explore mechanisms of success or failure. Randomized control trials (RCTs) provide particularly robust evidence of the effectiveness of interventions (although they have been criticized as reductionist and unable to provide insights into mechanisms), but there have been few such experiments investigating conservation at the landscape scale. We explored the impact of Watershared, an incentive-based conservation program in the Bolivian Andes, with one of the few RCTs of landscape-scale conservation in existence. There is strong interest in such incentive-based conservation approaches as some argue they can avoid negative social impacts sometimes associated with protected areas. We focused on social and environmental outcomes based on responses from a household survey in 129 communities randomly allocated to control or treatment (conducted both at the baseline in 2010 and repeated in 2015-2016). We controlled for incomplete program uptake by combining standard RCT analysis with matching methods and investigated mechanisms by exploring intermediate and ultimate outcomes according to the underlying theory of change. Previous analyses, focused on single biophysical outcomes, showed that over its first 5 years Watershared did not slow deforestation or improve water quality at the landscape scale. We found that Watershared influenced some outcomes measured using the survey, but the effects were complex, and some were unexpected. We thus demonstrated how RCTs can provide insights into the pathways of impact, as well as whether an intervention has impact. This paper, one of the first registered reports in conservation science, demonstrates how preregistration can help make complex research designs more transparent, avoid cherry picking, and reduce publication bias.

Mecanismos e Impactos de un Programa de Conservación Basada en Incentivos con Evidencias de un Ensayo Aleatorio de Control Resumen Las ciencias de la conservación necesitan evaluaciones de impacto de mayor calidad, especialmente aquellas que exploran los mecanismos del éxito o del fracaso. Los ensayos aleatorios de control (RCTs) proporcionan evidencias particularmente sólidas de la efectividad de las intervenciones (aunque han recibido críticas por considerarlas reduccionistas e incapaces de proporcionar conocimiento sobre los mecanismos) pero ha habido pocos experimentos de ese tipo que investiguen los efectos de la conservación a escala del paisaje. Exploramos el impacto de Watershared, un programa de conservación basada en incentivos en marcha en los Andes bolivianos, con uno de los pocos RCTs existentes de conservación a escala de paisaje. Existe un gran interés por dichas estrategias de conservación basada en incentivos pues hay quienes argumentan que pueden evitar los impactos sociales negativos que a veces se asocian con las áreas protegidas. Nos enfocamos en los resultados sociales y ambientales con base en las respuestas de una encuesta a hogares en 129 comunidades asignadas al azar para controlar o tratar (ambas encuestas realizadas en la línea base en 2010 y repetidas en 2015/16). Impusimos un control para la aceptación incompleta del programa al combinar el análisis estandarizado de RCTs con métodos de emparejamiento e investigamos los mecanismos mediante la exploración de resultados intermedios y finales de acuerdo con la teoría subyacente del cambio. Los análisis previos, enfocados en resultados biofísicos únicos, mostraron que durante los primeros cinco años del programa Watershared, la deforestación no experimentó una desaceleración y tampoco hubo mejoras en la calidad del agua a escala de paisaje. Descubrimos que Watershared influyó sobre algunos resultados medidos con la encuesta, pero sus efectos fueron complejos y algunos fueron inesperados. De este modo demostramos como los RCTs pueden proporcionar conocimiento sobre las vías de impacto, así como también si una intervención genera un impacto. Este artículo, uno de los primeros reportes registrados en las ciencias de la conservación, demuestra cómo el prerregistro puede ayudar a hacer más transparentes los diseños complejos de investigación, evitar la selección subjetiva de datos y reducir el sesgo de publicación.

Diversification not specialization reduces global and local environmental burdens from livestock production.

Milk and beef production generates environmental burdens globally and locally. Across many regions a typical dairy intensification pathway is for dairy farms to specialize on milk production and reduce the co-production of beef (i.e. 'dairy-beef'). Dairy-beef thus reduces and beef needs to be produced elsewhere if beef production is to be maintained. Life Cycle Assessment (LCA) studies quantifying the environmental implications of dairy and beef production have largely focused on the farm level and not captured system connections. Further LCA work has generally represented the 'average' farm of a region, consequently ignoring the range in farm management observed in practice and few studies consider a range of LCA environmental footprints other than carbon footprints. For the first time, we present comprehensive LCA results for multiple environmental burdens based on a large panel dataset for commercial dairy and suckler-beef farms. We present a 15-year LCA assessment of a total of 738 dairy (3624 data points in 15 years) and 1887 suckler-beef (10,340 data points in 15 years) UK farms for five major LCA footprints. We also explore the footprint implications of compensating for reduced dairy-beef through producing this 'displaced' beef on suckler-beef farms. We found a substantial variation in farm footprints not captured in 'average farm' studies. Dairy-beef was much more efficient than beef produced on suckler-beef farms in terms of footprints per unit of beef output. Reducing dairy-beef and replacing it on a suckler-beef farm generally significantly increased environmental burdens. A reduction in carbon footprint was also associated with a reduction in other burdens suggesting no trade-off between local and global emissions. Increasing dairy farm diversification via higher dairy-beef output per unit of milk reduced burdens by up to 11-56%, on average, depending on burden and sensitivity run. We conclude that overspecialization of dairy farms in milk production increases the combined burdens from beef and milk, and that more intensive beef systems that make more efficient use of forage land play a crucial role in mitigating these burdens.

Preference classes in society for coastal marine protected areas.

Marine protected areas (MPAs) are increasingly being used as conservation tools in the marine environment. Success of MPAs depends upon sound scientific design and societal support. Studies that have assessed societal preferences for temperate MPAs have generally done it without considering the existence of discrete groups of opinion within society and have largely considered offshore and deep-sea areas. This study quantifies societal preferences and economic support for coastal MPAs in Wales (UK) and assesses the presence of distinct groups of preference for MPA management, through a latent class choice experiment approach. Results show a general support for the protection of the marine environment in the form of MPAs and that society is willing to bear the costs derived from conservation. Despite a general opposition toward MPAs where human activities are completely excluded, there is some indication that three classes of preferences within society can be established regarding the management of potentially sea-floor damaging activities. This type of approach allows for the distinction between those respondents with positive preferences for particular types of management from those who experience disutility. We conclude that insights from these types of analyses can be used by policy-makers to identify those MPA designs and management combinations most likely to be supported by particular sectors of society.

The effectiveness of Payments for Ecosystem Services at delivering improvements in water quality: lessons for experiments at the landscape scale.

BACKGROUND: Randomised Control Trials (RCTs) are used in impact evaluation in a range of fields. However, despite calls for their greater use in environmental management, their use to evaluate landscape scale interventions remains rare. Payments for Ecosystem Services (PES) incentivise land users to manage land to provide environmental benefits. We present the first RCT evaluation of a PES program aiming to improve water quality. Watershared is a program which incentivises landowners to avoid deforestation and exclude cattle from riparian forests. Using this unusual landscape-scale experiment we explore the efficacy of Watershared at improving water quality, and draw lessons for future RCT evaluations of landscape-scale environmental management interventions. METHODS: One hundred and twenty-nine communities in the Bolivian Andes were randomly allocated to treatment (offered Watershared agreements) or control (not offered agreements) following baseline data collection (including Escherichia coli contamination in most communities) in 2010. We collected end-line data in 2015. Using our end-line data, we explored the extent to which variables associated with the intervention (e.g. cattle exclusion, absence of faeces) predict water quality locally. We then investigated the efficacy of the intervention at improving water quality at the landscape scale using the RCT. This analysis was done in two ways; for the subset of communities for which we have both baseline and end-line data from identical locations we used difference-in-differences (matching on baseline water quality), for all sites we compared control and treatment at end-line controlling for selected predictors of water quality. RESULTS: The presence of cattle faeces in water adversely affected water quality suggesting excluding cattle has a positive impact on water quality locally. However, both the matched difference-in-differences analysis and the comparison between treatment and control communities at end-line suggested Watershared was not effective at reducing E. coli contamination at the landscape scale. Uptake of Watershared agreements was very low and the most important land from a water quality perspective (land around water intakes) was seldom enrolled. DISCUSSION: Although excluding cattle may have a positive local impact on water quality, higher uptake and better targeting would be required to achieve a significant impact on the quality of water consumed in the communities. Although RCTs potentially have an important role to play in building the evidence base for approaches such as PES, they are far from straightforward to implement. In this case, the randomised trial was not central to concluding that Watershared had not produced a landscape scale impact. We suggest that this RCT provides valuable lessons for future use of randomised experiments to evaluate landscape-scale environmental management interventions.

Who bears the cost of forest conservation?

BACKGROUND: While the importance of conserving ecosystems for sustainable development is widely recognized, it is increasingly evident that despite delivering global benefits, conservation often comes at local cost. Protected areas funded by multilateral lenders have explicit commitments to ensure that those negatively affected are adequately compensated. We make the first comparison of the magnitude and distribution of the local costs of a protected area with the magnitude and distribution of the compensation provided under the World Bank social safeguard policies (Performance Standard 5). METHODS: In the Ankeniheny-Zahamena Corridor (a new protected area and REDD+ pilot project in eastern Madagascar), we used choice experiments to estimate local opportunity costs (n = 453) which we annualized using a range of conservative assumptions concerning discount rates. Detailed surveys covering farm inputs and outputs as well as off-farm income (n = 102) allowed us to explore these opportunity costs as a proportion of local incomes. Intensive review of publically available documents provided estimates of the number of households that received safeguard compensation and the amount spent per household. We carried out a contingent valuation exercise with beneficiaries of this compensation two years after the micro-development projects were implemented (n = 62) to estimate their value as perceived by beneficiaries. RESULTS: Conservation restrictions result in very significant costs to forest communities. The median net present value of the opportunity cost across households in all sites was US$2,375. When annualized, these costs represent 27-84% of total annual income for median-income households; significantly higher proportionally for poorer households. Although some households have received compensation, we conservatively estimate that more than 50% of eligible households (3,020 households) have not. Given the magnitude of compensation (based both on amount spent and valuation by recipients two years after the compensation was distributed) relative to costs, we argue that no one was fully compensated. Achieving full compensation will require an order of magnitude more than was spent but we suggest that this should be affordable given the global value of forest conservation. DISCUSSION: By analyzing in unprecedented depth both the local costs of conservation, and the compensation distributed under donor policies, we demonstrate that despite well-intentioned policies, some of the poorest people on the planet are still bearing the cost of forest conservation. Unless significant extra funding is provided by the global beneficiaries of conservation, donors' social safeguarding requirements will not be met, and forest conservation in developing countries will jeopardize, rather than contribute to, sustainable development goals.

Metrics and methods for characterizing dairy farm intensification using farm survey data.

Evaluation of agricultural intensification requires comprehensive analysis of trends in farm performance across physical and socio-economic aspects, which may diverge across farm types. Typical reporting of economic indicators at sectorial or the "average farm" level does not represent farm diversity and provides limited insight into the sustainability of specific intensification pathways. Using farm business data from a total of 7281 farm survey observations of English and Welsh dairy farms over a 14-year period we calculate a time series of 16 key performance indicators (KPIs) pertinent to farm structure, environmental and socio-economic aspects of sustainability. We then apply principle component analysis and model-based clustering analysis to identify statistically the number of distinct dairy farm typologies for each year of study, and link these clusters through time using multidimensional scaling. Between 2001 and 2014, dairy farms have largely consolidated and specialized into two distinct clusters: more extensive farms relying predominantly on grass, with lower milk yields but higher labour intensity, and more intensive farms producing more milk per cow with more concentrate and more maize, but lower labour intensity. There is some indication that these clusters are converging as the extensive cluster is intensifying slightly faster than the intensive cluster, in terms of milk yield per cow and use of concentrate feed. In 2014, annual milk yields were 6,835 and 7,500 l/cow for extensive and intensive farm types, respectively, whilst annual concentrate feed use was 1.3 and 1.5 tonnes per cow. For several KPIs such as milk yield the mean trend across all farms differed substantially from the extensive and intensive typologies mean. The indicators and analysis methodology developed allows identification of distinct farm types and industry trends using readily available survey data. The identified groups allow the accurate evaluation of the consequences of the reduction in dairy farm numbers and intensification at national and international scales.

Ensartinib (X-396) in ALK-Positive Non-Small Cell Lung Cancer: Results from a First-in-Human Phase I/II, Multicenter Study.

Purpose: Evaluate safety and determine the recommended phase II dose (RP2D) of ensartinib (X-396), a potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), and evaluate preliminary pharmacokinetics and antitumor activity in a first-in-human, phase I/II clinical trial primarily in patients with non-small cell lung cancer (NSCLC).Patients and Methods: In dose escalation, ensartinib was administered at doses of 25 to 250 mg once daily in patients with advanced solid tumors; in dose expansion, patients with advanced ALK-positive NSCLC were administered 225 mg once daily. Patients who had received prior ALK TKI(s) and patients with brain metastases were eligible.Results: Thirty-seven patients enrolled in dose escalation, and 60 enrolled in dose expansion. The most common treatment-related toxicities were rash (56%), nausea (36%), pruritus (28%), vomiting (26%), and fatigue (22%); 23% of patients experienced a treatment-related grade 3 to 4 toxicity (primarily rash and pruritus). The maximum tolerated dose was not reached, but the RP2D was chosen as 225 mg based on the frequency of rash observed at 250 mg without improvement in activity. Among the ALK-positive efficacy evaluable patients treated at ≥200 mg, the response rate (RR) was 60%, and median progression-free survival (PFS) was 9.2 months. RR in ALK TKI-naïve patients was 80%, and median PFS was 26.2 months. In patients with prior crizotinib only, the RR was 69% and median PFS was 9.0 months. Responses were also observed in the central nervous system, with an intracranial RR of 64%.Conclusions: Ensartinib was active and generally well tolerated in patients with ALK-positive NSCLC. Clin Cancer Res; 24(12); 2771-9. ©2018 AACR.