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1.
  • Wain, Louise V., et al. (author)
  • Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
  • 2017
  • In: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
  • Journal article (peer-reviewed)abstract
    • Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
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2.
  • Albrecht, Matthias, et al. (author)
  • The effectiveness of flower strips and hedgerows on pest control, pollination services and crop yield : a quantitative synthesis
  • 2020
  • In: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 23:10, s. 1488-1498
  • Journal article (peer-reviewed)abstract
    • Floral plantings are promoted to foster ecological intensification of agriculture through provisioning of ecosystem services. However, a comprehensive assessment of the effectiveness of different floral plantings, their characteristics and consequences for crop yield is lacking. Here we quantified the impacts of flower strips and hedgerows on pest control (18 studies) and pollination services (17 studies) in adjacent crops in North America, Europe and New Zealand. Flower strips, but not hedgerows, enhanced pest control services in adjacent fields by 16% on average. However, effects on crop pollination and yield were more variable. Our synthesis identifies several important drivers of variability in effectiveness of plantings: pollination services declined exponentially with distance from plantings, and perennial and older flower strips with higher flowering plant diversity enhanced pollination more effectively. These findings provide promising pathways to optimise floral plantings to more effectively contribute to ecosystem service delivery and ecological intensification of agriculture in the future.
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3.
  • Axfors, Cathrine, et al. (author)
  • Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
  • 2021
  • In: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
  • Research review (peer-reviewed)abstract
    • Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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4.
  • Berndt, Sonja I., et al. (author)
  • Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
  • 2013
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
  • Journal article (peer-reviewed)abstract
    • Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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5.
  • Chiang, Michael F., et al. (author)
  • International Classification of Retinopathy of Prematurity, Third Edition
  • 2021
  • In: Ophthalmology. - : Elsevier. - 0161-6420 .- 1549-4713. ; 128:10, s. 51-68
  • Journal article (peer-reviewed)abstract
    • Purpose: The International Classification of Retinopathy of Prematurity is a consensus statement that creates a standard nomenclature for classification of retinopathy of prematurity (ROP). It was initially published in 1984, expanded in 1987, and revisited in 2005. This article presents a third revision, the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), which is now required because of challenges such as: (1) concerns about subjectivity in critical elements of disease classification; (2) innovations in ophthalmic imaging; (3) novel pharmacologic therapies (e.g., antievascular endothelial growth factor agents) with unique regression and reactivation features after treatment compared with ablative therapies; and (4) recognition that patterns of ROP in some regions of the world do not fit neatly into the current classification system.Design: Review of evidence-based literature, along with expert consensus opinion. Participants: International ROP expert committee assembled in March 2019 representing 17 countries and comprising 14 pediatric ophthalmologists and 20 retinal specialists, as well as 12 women and 22 men.Methods: The committee was initially divided into 3 subcommittees-acute phase, regression or reactivation, and imaging-each of which used iterative videoconferences and an online message board to identify key challenges and approaches. Subsequently, the entire committee used iterative videoconferences, 2 in-person multiday meetings, and an online message board to develop consensus on classification.Main Outcome Measures: Consensus statement.Results: The ICROP3 retains current definitions such as zone (location of disease), stage (appearance of disease at the avascular-vascular junction), and circumferential extent of disease. Major updates in the ICROP3 include refined classification metrics (e.g., posterior zone II, notch, subcategorization of stage 5, and recognition that a continuous spectrum of vascular abnormality exists from normal to plus disease). Updates also include the definition of aggressive ROP to replace aggressive-posterior ROP because of increasing recognition that aggressive disease may occur in larger preterm infants and beyond the posterior retina, particularly in regions of the world with limited resources. ROP regression and reactivation are described in detail, with additional description of long-term sequelae.Conclusions: These principles may improve the quality and standardization of ROP care worldwide and may provide a foundation to improve research and clinical care.
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6.
  • Gardner, Emma, et al. (author)
  • Field boundary features can stabilise bee populations and the pollination of mass-flowering crops in rotational systems
  • 2021
  • In: Journal of Applied Ecology. - : Wiley. - 0021-8901 .- 1365-2664. ; 58:10, s. 2287-2304
  • Journal article (peer-reviewed)abstract
    • Pollinators experience large spatiotemporal fluctuations in resource availability when mass-flowering crops are rotated with resource-poor cereal crops. Yet, few studies have considered the effect this has on pollinator population stability, nor how this might be mitigated to maintain consistent crop pollination services. We assess the potential of boundary features (standard narrow 1 m grassy margins, hedgerows and wide 4 m agri-environment margins) to support and stabilise pollinator populations and pollination service in agricultural landscapes under crop rotation. Assuming a 6-year rotation, we use a process-based pollinator model to predict yearly pollinator population size and in-crop visitation rates to oilseed rape and field bean across 117 study landscapes in England with varying amounts of boundary features. We model both ground-nesting bumblebees and solitary bees and compare the predictions including and excluding boundary features from the landscapes. Ground-nesting bumblebee populations, whose longer-lifetime colonies benefit from continuity of resources, were larger and more stable (relative to the no-features scenario) in landscapes with more boundary features. Ground-nesting solitary bee populations were also larger but not significantly more stable, except with the introduction of wide permanent agri-environment margins, due to their shorter lifetimes and shorter foraging/dispersal ranges. Crop visitation by ground-nesting bumblebees was greater and more stable in landscapes with more boundary features, partly due to increased colony growth prior to crop flowering. Time averaged crop visitation by ground-nesting solitary bees was slightly lower, due to females dividing their foraging time between boundary features and the crop. However, despite this, the minimum pollination service delivered was higher, due to the more stable delivery. Synthesis and applications. Field boundary features have an important role in stabilising pollinator populations and pollination service in rotational systems, although maintenance of larger semi-natural habitat patches may be more effective for stabilising less mobile solitary bee populations. We recommend using combinations of boundary features, accounting for pollinator range when spacing features/rotating crops, and synchronising boundary feature management with crop rotation to maximise their stabilising benefits.
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7.
  • Gardner, Emma, et al. (author)
  • Reliably predicting pollinator abundance : Challenges of calibrating process-based ecological models
  • 2020
  • In: Methods in Ecology and Evolution. - 2041-210X. ; 11:12, s. 1673-1689
  • Journal article (peer-reviewed)abstract
    • Pollination is a key ecosystem service for global agriculture but evidence of pollinator population declines is growing. Reliable spatial modelling of pollinator abundance is essential if we are to identify areas at risk of pollination service deficit and effectively target resources to support pollinator populations. Many models exist which predict pollinator abundance but few have been calibrated against observational data from multiple habitats to ensure their predictions are accurate. We selected the most advanced process-based pollinator abundance model available and calibrated it for bumblebees and solitary bees using survey data collected at 239 sites across Great Britain. We compared three versions of the model: one parameterised using estimates based on expert opinion, one where the parameters are calibrated using a purely data-driven approach and one where we allow the expert opinion estimates to inform the calibration process. All three model versions showed significant agreement with the survey data, demonstrating this model's potential to reliably map pollinator abundance. However, there were significant differences between the nesting/floral attractiveness scores obtained by the two calibration methods and from the original expert opinion scores. Our results highlight a key universal challenge of calibrating spatially explicit, process-based ecological models. Notably, the desire to reliably represent complex ecological processes in finely mapped landscapes necessarily generates a large number of parameters, which are challenging to calibrate with ecological and geographical data that are often noisy, biased, asynchronous and sometimes inaccurate. Purely data-driven calibration can therefore result in unrealistic parameter values, despite appearing to improve model-data agreement over initial expert opinion estimates. We therefore advocate a combined approach where data-driven calibration and expert opinion are integrated into an iterative Delphi-like process, which simultaneously combines model calibration and credibility assessment. This may provide the best opportunity to obtain realistic parameter estimates and reliable model predictions for ecological systems with expert knowledge gaps and patchy ecological data.
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8.
  • Garratt, Michael P D, et al. (author)
  • Opportunities to reduce pollination deficits and address production shortfalls in an important insect pollinated crop
  • 2021
  • In: Ecological Applications. - : Wiley. - 1051-0761 .- 1939-5582.
  • Journal article (peer-reviewed)abstract
    • Pollinators face multiple pressures and there is evidence of populations in decline. As demand for insect-pollinated crops increases, crop production is threatened by shortfalls in pollination services. Understanding the extent of current yield deficits due to pollination and identifying opportunities to protect or improve crop yield and quality through pollination management is therefore of international importance. To explore the extent of 'pollination deficits', where maximum yield is not being achieved due to insufficient pollination, we use an extensive dataset on a globally important crop, apples. We quantified how these deficits vary between orchards and countries as well as compare 'pollinator dependence' across different apple varieties. We found evidence of pollination deficits and in some cases, risks of over-pollination were even apparent where fruit quality could be reduced by too much pollination. In almost all regions studied we found some orchards performing significantly better than others, in terms of avoiding a pollination deficit and crop yield shortfalls due to sub-optimal pollination. This represents an opportunity to improve production through better pollinator and crop management. Our findings also demonstrate that pollinator dependence varies considerably between apple varieties in terms of fruit number and fruit quality. We propose that assessments of pollination service and deficits in crops can be used to quantify supply and demand for pollinators and help target local management to address deficits although crop variety has a strong influence on the role of pollinators.
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9.
  • Hutchinson, Louise A., et al. (author)
  • Using ecological and field survey data to establish a national list of the wild bee pollinators of crops
  • 2021
  • In: Agriculture, Ecosystems and Environment. - : Elsevier BV. - 0167-8809 .- 1873-2305. ; 315
  • Journal article (peer-reviewed)abstract
    • The importance of wild bees for crop pollination is well established, but less is known about which species contribute to service delivery to inform agricultural management, monitoring and conservation. Using sites in Great Britain as a case study, we use a novel qualitative approach combining ecological information and field survey data to establish a national list of crop pollinating bees for four economically important crops (apple, field bean, oilseed rape and strawberry). A traits data base was used to establish potential pollinators, and combined with field data to identify both dominant crop flower visiting bee species and other species that could be important crop pollinators, but which are not presently sampled in large numbers on crops flowers. Whilst we found evidence that a small number of common, generalist species make a disproportionate contribution to flower visits, many more species were identified as potential pollinators, including rare and specialist species. Furthermore, we found evidence of substantial variation in the bee communities of different crops. Establishing a national list of crop pollinators is important for practitioners and policy makers, allowing targeted management approaches for improved ecosystem services, conservation and species monitoring. Data can be used to make recommendations about how pollinator diversity could be promoted in agricultural landscapes. Our results suggest agri-environment schemes need to support a higher diversity of species than at present, notably of solitary bees. Management would also benefit from targeting specific species to enhance crop pollination services to particular crops. Whilst our study is focused upon Great Britain, our methodology can easily be applied to other countries, crops and groups of pollinating insects.
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10.
  • Image, Mike, et al. (author)
  • Does agri-environment scheme participation in England increase pollinator populations and crop pollination services?
  • 2022
  • In: Agriculture, Ecosystems and Environment. - : Elsevier BV. - 0167-8809. ; 325
  • Journal article (peer-reviewed)abstract
    • Agri-environment schemes are programmes where landholders enter into voluntary agreements (typically with governments) to manage agricultural land for environmental protection and nature conservation objectives. Previous work at local scale has shown that these features can provide additional floral and nesting resources to support wild pollinators, which may indirectly increase floral visitation to nearby crops. However, the effect of entire schemes on this important ecosystem service has never previously been studied at national scale. Focusing on four wild pollinator guilds (ground-nesting bumblebees, tree-nesting bumblebees, ground-nesting solitary bees, and cavity-nesting solitary bees), we used a state-of-the-art, process-based spatial model to examine the relationship between participation in agri-environment schemes across England during 2016 and the predicted abundances of these guilds and their visitation rates to four pollinator dependent crops (oilseed rape, field beans, orchard fruit and strawberries). Our modelling predicts that significant increases in national populations of ground-nesting bumblebees and ground-nesting solitary bees have occurred in response to the schemes. Lack of significant population increases for other guilds likely reflects specialist nesting resource requirements not well-catered for in schemes. We do not predict statistically significant increases in visitation to pollinator-dependent crops at national level as a result of scheme interventions but do predict some localised areas of significant increase in bumblebee visitation to crops flowering in late spring. Lack of any significant change in visitation to crops which flower outside this season is likely due to a combination of low provision of nesting resource relative to floral resource by scheme interventions and low overall participation in more intensively farmed landscapes. We recommend future schemes place greater importance on nesting resource provision alongside floral resource provision, better cater for the needs of specialised species and promote more contiguous patches of semi-natural habitat to better support solitary bee visitation.
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