A multivariate data analysis approach for the investigation of in vitro derived metabolites of ACP-105 in comparison with human in vivo metabolites.

Selective androgen receptor modulators (SARMs) such as ACP-105 are prohibited in sports due to their anabolic properties. ACP-105 has in previous equine studies shown to undergo extensive metabolism, which makes its metabolite profile important to investigate in humans, since the metabolism is unknown in this species. The aims of the study were to systematically optimize in vitro microsome incubations for improved metabolite yield and to utilize a multivariate data analysis (MVDA) approach to aid the metabolite discovery. Microsomes together with S9 fractions were used at optimal conditions, both with and without phase II additives. Furthermore, the relevance of the in vitro derived metabolites was evaluated as analytical targets in doping control by comparison with results from a human post-administration urine sample collected after a single dose of 100 µg ACP-105. All samples were analyzed with liquid chromatography - Orbitrap mass spectrometry. The use of the systematical optimization and MVDA greatly simplified the search and a total of 18 in vitro metabolites were tentatively identified. The yield of the two main monohydroxylated isomers increased by 24 and 10 times, respectively. In the human urine sample, a total of seven metabolites of ACP-105, formed by a combination of hydroxylations and glucuronic acid conjugations, were tentatively identified. The main metabolites were two monohydroxylated forms that are suggested as analytical targets for human doping control after hydrolysis. All the in vivo metabolites could be detected with the MVDA approach on the in vitro models, demonstrating its usefulness for prediction of the in vivo metabolite profile.

Following children with severe or profound intellectual and multiple disabilities and their mothers through a communication intervention: single-case mixed-methods findings.

There is limited research targeting communication interventions for children with severe/profound intellectual and multiple disabilities. This study addressed outcomes from a communication course for parents of children with severe/profound intellectual and multiple disabilities and follows up on a previous publication by Rensfeldt Flink et al. (2020). Potential observable changes in the children's and parents' communicative behavior were studied as well as the parents' experiences of the intervention process and the effect of the course on parent-child communication. A mixed-methods design with a case-study framework was used. Two mother-child dyads participated. Data were collected before, during, and after the course. Video-recorded repeated play interactions by the dyads were coded and analyzed for the mothers' responsivity and use of augmentative and alternative communication and the children's interactive engagement. Longitudinal interview data from the mothers were analyzed thematically. No clear signs of behavioral change were observed in the coded video data. However, thematic analyses showed that the mothers experienced changes to communicative behaviors. Moreover, the course affected both mothers' reasoning about communication with their child and their child's communicative needs. The mothers' narratives contributed insights into how reflective processes might guide action in parent-mediated communication interventions. The implications for research and clinical practice are discussed.

Equine in vivo metabolite profiling of the selective androgen receptor modulator LGD-3303 for doping control.

LGD-3303 is a Selective Androgen Receptor Modulator (SARM) that is prohibited in both equine and human sports due to its anabolic properties. The aim of this study was to investigate the equine in vivo metabolite profile of LGD-3303 and identify drug metabolites that can be suitable as new and improved analytical targets for equine doping control. This was performed by an oral administration of 0.05 mg·kg-1 LGD-3303 to horses, where blood and urine samples were collected up to 96 h after administration. The in vivo samples consisting of plasma, urine and hydrolyzed urine were analyzed utilizing ultra-high performance liquid chromatography hyphenated to a Q Exactive™ Orbitrap™ high resolution mass spectrometer with a heated electrospray ionization source. A total of eight metabolites of LGD-3303 were tentatively identified, including one carboxylated and several hydroxylated metabolites in combination with glucuronic acid conjugates. A monohydroxylated metabolite is suggested as an analytical target for doping control analysis of plasma and urine after hydrolysis with ß-glucuronidase, due to the high intensity and prolonged detection time in comparison to parent LGD-3303.

Behavioural strengths and difficulties in relation to intellectual functions and age in Swedish boys with Duchenne muscular dystrophy.

The aim of this study was to describe behavioral strengths and difficulties in relation to intellectual function and age in boys with DMD. In a cross-sectional design, 70 boys with DMD were tested at 5, 8, 11, and 14 years of age (mean age 10y 5 m). Parental ratings of behavioral strengths and difficulties were studied in relation to age, intellectual function, motor function, and family socioeconomic status (SES). Results show a significant relation between behavioral strengths and difficulties and age with parents rating increasingly more difficulties (slightly higher, higher and very high) from 5 years (11.1%) to 9 years (30.8%) and 11 years (78.9%) of age and then fewer difficulties at 14 years (50%) of age. Working Memory Index (WMI) explained significant variance in SDQ-Total-Score (17.5%) and SDQ-Impact-Score (11.2%). WMI together with upper motor function explained 19.5% variance in SDQ-Hyperactivity and 19.7% in SDQ-Peer-Problems. Age and SES explained an 18.9% variance in SDQ-Emotional-Problems. Age is an important factor when analyzing behavioral strengths and difficulties for boys with DMD. The development of boys with DMD needs to be understood in the context of expected developmental trajectory as well as in the decline of psychical functioning. Our study supports that age, cognition, motor function, and family SES all contribute to how behavioral strengths and difficulties evolves in boys with DMD.

Augmentative and alternative communication with children with severe/profound intellectual and multiple disabilities: speech language pathologists' clinical practices and reasoning.

PURPOSE: Augmentative and alternative communication (AAC) is recommended to be included in communication interventions directed at children/youth with severe/profound intellectual and multiple disabilities (S/PIMD). Even so, the evidence base for AAC practices with children with S/PIMD is limited. Also, little is known about how frequently AAC is implemented with this target group, which AAC tools and methods are applied, and the related clinical reasoning of speech-language pathologists (SLPs). This study aimed to explore SLPs' beliefs, clinical reasoning and practices in relation to AAC implementation with children/youth with S/PIMD. MATERIALS AND METHODS: In this sequential, mixed-methods study, 90 SLPs working with children with disabilities within habilitation services in Sweden participated in an online survey. The survey answers were statistically analysed. Subsequently, focus group data were collected from seven SLPs and analysed using thematic analysis. RESULTS AND CONCLUSIONS: Despite AAC being highly prioritized, SLPs found it challenging and complex to implement with this target group. A wide variety of AAC methods and tools were considered and implemented. Clinical decision-making was a balancing act between competing considerations and was mainly guided by the SLPs' individual, clinical experiences. The resources, engagement and wishes of the social network surrounding the child were considered crucial for clinical decision-making on AAC. Implications for research and practice are discussed.Implications for rehabilitationSpeech-language pathologists (SLPs) seemingly find a wide variety of Augmentative and Alternative Communication (AAC), ranging from unaided methods to assistive technology of various complexity, to be potentially suitable for children/youth with severe/profound intellectual and multiple disabilities (S/PIMD).The motivation and preferences of the social network surrounding the child with S/PIMD seem to influence SLPs' clinical decision-making on AAC to a high degree. Sometimes this may be considered an even more important factor than the abilities of the child.SLPs' clinical decision-making on AAC for children/youth is guided by their individual, clinical experience to a high degree.An increase in family oriented AAC intervention research targeting individuals with S/PIMD could potentially strengthen the association between research and the current, experience-based clinical practice.

Examining perceptions of a communication course for parents of children with profound intellectual and multiple disabilities.

The overall aim was to examine participants' perceptions of a communication course as held for parents of children with profound intellectual and multiple disabilities. The course curriculum included responsive strategies and augmentative and alternative communication. The research questions addressed the favourability, changes in parents' or children's communication and appreciated or unappreciated course features. Twenty-two written course evaluations were analysed. The mean scores for ratings were compared with ratings in a previous study, including those of parents of children with generally milder disabilities. Comments and answers to open-ended questions were analysed using thematic analysis. Participants were slightly more satisfied with the course as compared with parents who had children with milder disabilities. The thematic analysis suggested increased parental responsiveness after the course. Perceptions of augmentative and alternative communication varied. It was unclear whether the course altered the children's communication or not. The supportive social milieu offered by the course was highly appreciated. Although generalisation beyond this course and setting is to be determined, the results suggest that parents of children with profound intellectual and multiple disabilities can appreciate a communication course and find it useful. An individual approach within the group setting and practical learning opportunities seem important.

Investigation of Equine In Vivo and In Vitro Derived Metabolites of the Selective Androgen Receptor Modulator (SARM) ACP-105 for Improved Doping Control.

Selective Androgen Receptor Modulators (SARMs) have anabolic properties but less adverse effects than anabolic androgenic steroids. They are prohibited in both equine and human sports and there have been several cases of SARMs findings reported over the last few years. The aim of this study was to investigate the metabolite profile of the SARM ACP-105 (2-chloro-4-[(3-endo)-3-hydroxy-3-methyl-8-azabicyclo[3.2.1]oct-8-yl]-3-methylbenzonitrile) in order to find analytical targets for doping control. Oral administration of ACP-105 was performed in horses, where blood and urine samples were collected over a time period of 96 h. The in vivo samples were compared with five in vitro incubation models encompassing Cunninghamella elegans, microsomes and S9 fractions of both human and equine origin. The analyses were performed using ultra-high performance liquid chromatography coupled to high resolution Q ExactiveTM OrbitrapTM mass spectrometry (UHPLC-HRMS). A total of 21 metabolites were tentatively identified from the in vivo experiments, of which several novel glucuronides were detected in plasma and urine. In hydrolyzed urine, hydroxylated metabolites dominated. The in vitro models yielded several biotransformation products, including a number of monohydroxylated metabolites matching the in vivo results. The suggested analytical target for equine doping control in plasma is a dihydroxylated metabolite with a net loss of two hydrogens. In urine, the suggested targets are two monohydroxylated metabolites after hydrolysis with ß-glucuronidase, selected both due to prolongation of the detection time and the availability of reference material from the in vitro models.

Opportunity to participate in planning and evaluation of support for children with disabilities: Parents' and professionals' perspectives.

A random sample of parents of children with disabilities (n = 144) from three Swedish municipalities participated in a structured telephone interview including seven questions on child participation and 156 professionals from the same municipalities completed a web-based survey including six questions on child participation. The aim of the study was to explore parents' and professionals' (1) ratings of the opportunities available to children with disabilities to participate in planning, decision-making and evaluation of support and (2) satisfaction with the children's current level of such participation. The results indicated that opportunities for children with disability to participate directly in decision-making processes were limited. Parents and professionals rated older children's opportunities to participate as better compared to younger. Most professionals relied more on parents' descriptions of the child's needs and opinions of support services than on direct communication with the child.

Ozone impact on wheat in Europe, Asia and North America - A comparison.

Data from experiments where field-grown wheat was exposed to ozone were collated in order to compare the effects in Europe, Asia and North America using dose-response regression. In addition to grain yield, average grain mass and harvest index were included to reflect the influence of ozone on the crop growth pattern. In order to include as many experiments as possible, daytime average ozone concentration was used as the ozone exposure index, but AOT40, estimated from average ozone concentrations, was also used to compare the performance of the two exposure metrics. The response to ozone differed significantly between the continents only for grain yield when using AOT40 as the exposure index. North American wheat was less sensitive than European and Asian that responded similarly. The variation in responses across all three continents was smallest for harvest index, followed by grain mass and grain yield. The highly consistent effect on harvest index shows that not only effects on biomass accumulation, but also on the partitioning of biomass, are important for the ozone-induced grain yield loss in wheat. The average duration of daily ozone exposure was longer in European experiments compared to North American and Asian. It cannot be excluded that this contributed to the indicated higher ozone sensitivity in European wheat in relation to North American. The main conclusions from this study are that on the average the response of wheat to ozone was lower for the older North American experiments and that the ozone response of the growth pattern reflected by grain mass and harvest index did not differ between continents.

Nitrogen application is required to realize wheat yield stimulation by elevated CO2 but will not remove the CO2 -induced reduction in grain protein concentration.

Elevated CO2 (eCO2 ) generally promotes increased grain yield (GY) and decreased grain protein concentration (GPC), but the extent to which these effects depend on the magnitude of fertilization remains unclear. We collected data on the eCO2 responses of GY, GPC and grain protein yield and their relationships with nitrogen (N) application rates across experimental data covering 11 field grown wheat (Triticum aestivum) cultivars studied in eight countries on four continents. The eCO2 -induced stimulation of GY increased with N application rates up to ~200 kg/ha. At higher N application, stimulation of GY by eCO2 stagnated or even declined. This was valid both when the yield stimulation was expressed as the total effect and using per ppm CO2 scaling. GPC was decreased by on average 7% under eCO2 and the magnitude of this effect did not depend on N application rate. The net effect of responses on GY and protein concentration was that eCO2 typically increased and decreased grain protein yield at N application rates below and above ~100 kg/ha respectively. We conclude that a negative effect on wheat GPC seems inevitable under eCO2 and that substantial N application rates may be required to sustain wheat protein yields in a world with rising CO2 .

Word reading, vocabulary, and mental health problems in adolescent girls and boys with intellectual and developmental disabilities.

Reading difficulties are linked to several disadvantages in the general population. Less is known about correlates of reading difficulties in individuals with intellectual and severe developmental disabilities (IDD). Vocabulary and word reading were assessed in 112 adolescents with IDD, recruited from Special needs comprehensive schools in Sweden (grundsärskolor in Swedish). Proxy-ratings of mental health were collected from teachers and parents for a subset of the participants. Relationships between all measures were investigated. Reading and vocabulary were poorly developed in both groups and significantly associated. While mental health problems were common, there were no significant associations with word reading or with vocabulary knowledge. Thus, the study did not confirm an association between reading difficulties and mental health problems in adolescents with IDD. Still, the frequency of mental health problems and the low reading abilities point to the need for further intervention for adolescents with IDD.

Exploring the insulin secretory properties of the PGD2-GPR44/DP2 axis in vitro and in a randomized phase-1 trial of type 2 diabetes patients.

AIMS/HYPOTHESIS: GPR44 (DP2, PTGDR2, CRTh2) is the receptor for the pro-inflammatory mediator prostaglandin D2 (PGD2) and it is enriched in human islets. In rodent islets, PGD2 is produced in response to glucose, suggesting that the PGD2-GPR44/DP2 axis may play a role in human islet function during hyperglycemia. Consequently, the aim of this work was to elucidate the insulinotropic role of GPR44 antagonism in vitro in human beta-cells and in type 2 diabetes (T2DM) patients. METHODS: We determined the drive on PGD2 secretion by glucose and IL-1beta, as well as, the impact on insulin secretion by pharmacological GPR44/DP2 antagonism (AZD1981) in human islets and beta-cells in vitro. To test if metabolic control would be improved by antagonizing a hyperglycemia-driven increased PGD2 tone, we performed a proof-of-mechanism study in 20 T2DM patients (average 54 years, HbA1c 9.4%, BMI 31.6 kg/m2). The randomized, double-blind, placebo-controlled cross-over study consisted of two three-day treatment periods (AZD1981 or placebo) separated by a three-day wash-out period. Mixed meal tolerance test (MMTT) and intravenous graded glucose infusion (GGI) was performed at start and end of each treatment period. Assessment of AZD1981 pharmacokinetics, glucose, insulin, C-peptide, glucagon, GLP-1, and PGD2 pathway biomarkers were performed. RESULTS: We found (1) that PGD2 is produced in human islet in response to high glucose or IL-1beta, but likely by stellate cells rather than endocrine cells; (2) that PGD2 suppresses both glucose and GLP-1 induced insulin secretion in vitro; and (3) that the GPR44/DP2 antagonist (AZD1981) in human beta-cells normalizes insulin secretion. However, AZD1981 had no impact on neither glucose nor incretin dependent insulin secretion in humans (GGI AUC C-peptide 1-2h and MMTT AUC Glucose 0-4h LS mean ratios vs placebo of 0.94 (80% CI of 0.90-0.98, p = 0.12) and 0.99 (90% CI of 0.94-1.05, p = 0.45), despite reaching the expected antagonist exposure. CONCLUSION/INTERPRETATION: Pharmacological inhibition of the PGD2-GPR44/DP2 axis has no major impact on the modulation of acute insulin secretion in T2DM patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02367066.

Closing the global ozone yield gap: Quantification and cobenefits for multistress tolerance.

Increasing both crop productivity and the tolerance of crops to abiotic and biotic stresses is a major challenge for global food security in our rapidly changing climate. For the first time, we show how the spatial variation and severity of tropospheric ozone effects on yield compare with effects of other stresses on a global scale, and discuss mitigating actions against the negative effects of ozone. We show that the sensitivity to ozone declines in the order soybean > wheat > maize > rice, with genotypic variation in response being most pronounced for soybean and rice. Based on stomatal uptake, we estimate that ozone (mean of 2010-2012) reduces global yield annually by 12.4%, 7.1%, 4.4% and 6.1% for soybean, wheat, rice and maize, respectively (the "ozone yield gaps"), adding up to 227 Tg of lost yield. Our modelling shows that the highest ozone-induced production losses for soybean are in North and South America whilst for wheat they are in India and China, for rice in parts of India, Bangladesh, China and Indonesia, and for maize in China and the United States. Crucially, we also show that the same areas are often also at risk of high losses from pests and diseases, heat stress and to a lesser extent aridity and nutrient stress. In a solution-focussed analysis of these results, we provide a crop ideotype with tolerance of multiple stresses (including ozone) and describe how ozone effects could be included in crop breeding programmes. We also discuss altered crop management approaches that could be applied to reduce ozone impacts in the shorter term. Given the severity of ozone effects on staple food crops in areas of the world that are also challenged by other stresses, we recommend increased attention to the benefits that could be gained from addressing the ozone yield gap.

Prevalence and correlates of coronary microvascular dysfunction in heart failure with preserved ejection fraction: PROMIS-HFpEF.

Aims: To date, clinical evidence of microvascular dysfunction in patients with heart failure (HF) with preserved ejection fraction (HFpEF) has been limited. We aimed to investigate the prevalence of coronary microvascular dysfunction (CMD) and its association with systemic endothelial dysfunction, HF severity, and myocardial dysfunction in a well defined, multi-centre HFpEF population. Methods and results: This prospective multinational multi-centre observational study enrolled patients fulfilling strict criteria for HFpEF according to current guidelines. Those with known unrevascularized macrovascular coronary artery disease (CAD) were excluded. Coronary flow reserve (CFR) was measured with adenosine stress transthoracic Doppler echocardiography. Systemic endothelial function [reactive hyperaemia index (RHI)] was measured by peripheral arterial tonometry. Among 202 patients with HFpEF, 151 [75% (95% confidence interval 69-81%)] had CMD (defined as CFR <2.5). Patients with CMD had a higher prevalence of current or prior smoking (70% vs. 43%; P = 0.0006) and atrial fibrillation (58% vs. 25%; P = 0.004) compared with those without CMD. Worse CFR was associated with higher urinary albumin-to-creatinine ratio (UACR) and NTproBNP, and lower RHI, tricuspid annular plane systolic excursion, and right ventricular (RV) free wall strain after adjustment for age, sex, body mass index, atrial fibrillation, diabetes, revascularized CAD, smoking, left ventricular mass, and study site (P < 0.05 for all associations). Conclusions: PROMIS-HFpEF is the first prospective multi-centre, multinational study to demonstrate a high prevalence of CMD in HFpEF in the absence of unrevascularized macrovascular CAD, and to show its association with systemic endothelial dysfunction (RHI, UACR) as well as markers of HF severity (NTproBNP and RV dysfunction). Microvascular dysfunction may be a promising therapeutic target in HFpEF.

Crop quality under rising atmospheric CO2.

Crops grown under elevated CO2 (eCO2) typically exhibit enhanced yields but at the same time decreased nutritional quality. The latter effect has often been explained as a growth dilution phenomenon, but this cannot be the only process involved since crop nutrient concentrations are decreased also when production is unaffected by eCO2. We review the current knowledge on eCO2 effects on crop nutritional quality with focus on the current understanding of the possible mechanisms and processes causing these effects. Emphasis is on crop nitrogen (N) and protein concentrations but effects on other nutrients and how they compare with those on N are also covered.

Ozone pollution will compromise efforts to increase global wheat production.

Introduction of high-performing crop cultivars and crop/soil water management practices that increase the stomatal uptake of carbon dioxide and photosynthesis will be instrumental in realizing the United Nations Sustainable Development Goal (SDG) of achieving food security. To date, however, global assessments of how to increase crop yield have failed to consider the negative effects of tropospheric ozone, a gaseous pollutant that enters the leaf stomatal pores of plants along with carbon dioxide, and is increasing in concentration globally, particularly in rapidly developing countries. Earlier studies have simply estimated that the largest effects are in the areas with the highest ozone concentrations. Using a modelling method that accounts for the effects of soil moisture deficit and meteorological factors on the stomatal uptake of ozone, we show for the first time that ozone impacts on wheat yield are particularly large in humid rain-fed and irrigated areas of major wheat-producing countries (e.g. United States, France, India, China and Russia). Averaged over 2010-2012, we estimate that ozone reduces wheat yields by a mean 9.9% in the northern hemisphere and 6.2% in the southern hemisphere, corresponding to some 85 Tg (million tonnes) of lost grain. Total production losses in developing countries receiving Official Development Assistance are 50% higher than those in developed countries, potentially reducing the possibility of achieving UN SDG2. Crucially, our analysis shows that ozone could reduce the potential yield benefits of increasing irrigation usage in response to climate change because added irrigation increases the uptake and subsequent negative effects of the pollutant. We show that mitigation of air pollution in a changing climate could play a vital role in achieving the above-mentioned UN SDG, while also contributing to other SDGs related to human health and well-being, ecosystems and climate change.

Is pre-implantation genetic diagnosis (PGD) more of a strain regarding satisfaction with marital quality for male or female partners? A three-year follow-up study.

INTRODUCTION: Men and women with a hereditary genetic disease are faced with different options when they plan to become parents. One is pre-implantation genetic diagnosis (PGD) which is a combination of in vitro fertilization (IVF) and genetic analysis of the embryo before implantation. The present study focuses on how men and women planning for PGD experience the quality of marital satisfaction when they apply for treatment and again, three years later. METHODS: The study was a prospective cohort study where all couples (n = 22) applying for PGD during 2010 and 2011 were eligible. Nineteen women and 17 men (i.e. 17 couples and two women) participated. Participants answered several questionnaires (Dyadic Adjustment Scale, Hospital Anxiety and Depression Scale and Parental Stress Questionnaire) before PGD treatment, and again three years later. RESULTS: Women who underwent PGD rated the quality of their marital relationship similarly to that of first-time parents and IVF couples, whereas men rated the marital quality somewhat lower than the contrasts groups. Satisfaction with marital quality was stable over the three-year period although men were less satisfied than women on both occasions. At year three, there was a significant correlation between martial satisfaction and parental stress in men, and between martial satisfaction and anxiety and depression in women. DISCUSSION: Men are equally, or more, affected by their situation than their female partners, with consequences for satisfaction with marital quality. For this reason they should be included in any counselling offered.

Protection and restriction: A mixed-methods study of self-reported well-being among youth with intellectual disabilities.

BACKGROUND: As most mental health studies of school-aged children with intellectual and developmental disabilities (IDD) are based on proxy ratings, the subjective views of these young persons are rarely explored. The present study explores experiences of well-being, mental ill-health, family, school, and peer relations in students in special education. METHODS: Ten students in special education, aged 13-16 years, answered the Wellbeing in Special Education Questionnaire (WellSEQ) and participated in semi-structured interviews. Data were analyzed using a mixed methods phenomenological research approach. RESULTS: The general agreement between questionnaire responses and interview accounts appears to be good, and the students emphasized mainly positive emotions and good mental health. Students described their school environment and family relations as inclusive contexts experienced as both protective and restrictive. CONCLUSION: Using well-adapted research instruments enables students with IDD to communicate subjective experiences of well-being and how it relates to aspects of their everyday environment.

Current surface ozone concentrations significantly decrease wheat growth, yield and quality.

Tropospheric ozone is known to adversely affect crops and other vegetation. Most studies have focussed on the effects of elevated ozone levels vs. present ambient. We investigated the effect of present ambient surface ozone (O3) concentrations vs. preindustrial on a range of agronomically important response variables in field-grown wheat, using results from 33 experiments (representing 9 countries, 3 continents, 17 cultivars plus one set of 4 cultivars) having both charcoal filtered (CF) and non-filtered (NF) air treatments. Average filtration efficiency was 62%, reducing the O3 concentration from 35.6±10.6SDppb in NF to 13.7±8.8SDppb in CF. Average CF concentrations were in the range of levels believed to represent pre-industrial conditions, while NF concentrations were 7% lower than in the ambient air at plant height on the experimental sites. NF had significant (p<0.05) negative effects compared to CF on grain yield (-8.4%), grain mass (-3.7%), harvest index (-2.4%), total above-ground biomass (-5.4%), starch concentration (-3.0%), starch yield (-10.9%), and protein yield (-6.2%). No significant effect was found for grain number and protein concentration. There was a significant relationship between the effect of filtration on grain yield and the difference in O3 concentration between NF and CF treatments. The average yield loss per ppb O3 removed was 0.38% and did not systematically vary with year of experiment (ranging from 1982 to 2010) or with the average O3 level in the experiments. Although there are many differences among the field experiments included in this meta-analysis (e.g. genotype, degree of O3 pollution of the site and year, nutrient and soil condition, filtration efficiency), our study clearly shows that there is a consistent and significant effect of present ambient O3 exposure on a range of important response variables in wheat, the most strongly affected being starch yield.