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Sökning: WFRF:(Gavin Anna)

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1.
  • Ebersole, Charles R., et al. (författare)
  • Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
  • 2020
  • Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
  • Tidskriftsartikel (refereegranskat)abstract
    • Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
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2.
  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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3.
  • Su, Zhan, et al. (författare)
  • Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
  • 2012
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
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4.
  • Bellenguez, Celine, et al. (författare)
  • Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke
  • 2012
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:3, s. 141-328
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 x 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.
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5.
  • Dawson, Michael N., et al. (författare)
  • A second horizon scan of biogeography: Golden ages, Midas touches, and the Red Queen
  • 2016
  • Ingår i: Frontiers of Biogeography. - : University of California. - 1948-6596. ; 8:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Are we entering a new 'Golden Age' of biogeography, with continued development of infrastructure and ideas? We highlight recent developments, and the challenges and opportunities they bring, in light of the snapshot provided by the 7th biennial meeting of the International Biogeography Society (IBS 2015). We summarize themes in and across 15 symposia using narrative analysis and word clouds, which we complement with recent publication trends and 'research fronts'. We find that biogeography is still strongly defined by core sub-disciplines that reflect its origins in botanical, zoological (particularly bird and mammal), and geographic (e.g., island, montane) studies of the 1800s. That core is being enriched by large datasets (e.g. of environmental variables, 'omics', species' occurrences, traits) and new techniques (e.g., advances in genetics, remote sensing, modeling) that promote studies with increasing detail and at increasing scales; disciplinary breadth is being diversified (e.g., by developments in paleobiogeography and microbiology) and integrated through the transfer of approaches and sharing of theory (e.g., spatial modeling and phylogenetics in evolutionary-ecological contexts). Yet some subdisciplines remain on the fringe (e.g., marine biogeography, deep-time paleobiogeography), new horizons and new theory may be overshadowed by popular techniques (e.g., species distribution modelling), and hypotheses, data, and analyses may each be wanting. Trends in publication suggest a shift away from traditional biogeography journals to multidisciplinary or open access journals. Thus, there are currently many opportunities and challenges as biogeography increasingly addresses human impacts on, and stewardship of, the planet (e.g., Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services). As in the past, biogeographers doubtless will continue to be engaged by new data and methods in exploring the nexus between biology and geography for decades into the future. But golden ages come and go, and they need not touch every domain in a discipline nor affect subdisciplines at the same time; moreover, what appears to be a Golden Age may sometimes have an undesirable 'Midas touch'. Contexts within and outwith biogeography-e.g., methods, knowledge, climate, biodiversity, politics-are continually changing, and at times it can be challenging to establish or maintain relevance. In so many races with the Red Queen, we suggest that biogeography will enjoy greatest success if we also increasingly engage with the epistemology of our discipline.
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6.
  • Karyotaki, Eirini, et al. (författare)
  • Do guided internet-based interventions result in clinically relevant changes for patients with depression? : An individual participant data meta-analysis
  • 2018
  • Ingår i: Clinical Psychology Review. - : Elsevier. - 0272-7358 .- 1873-7811. ; 63, s. 80-92
  • Forskningsöversikt (refereegranskat)abstract
    • Little is known about clinically relevant changes in guided Internet-based interventions for depression. Moreover, methodological and power limitations preclude the identification of patients' groups that may benefit more from these interventions. This study aimed to investigate response rates, remission rates, and their moderators in randomized controlled trials (RCTs) comparing the effect of guided Internet-based interventions for adult depression to control groups using an individual patient data meta-analysis approach. Literature searches in PubMed, Embase, PsycINFO and Cochrane Library resulted in 13,384 abstracts from database inception to January 1, 2016. Twenty-four RCTs (4889 participants) comparing a guided Internet-based intervention with a control group contributed data to the analysis. Missing data were multiply imputed. To examine treatment outcome on response and remission, mixed-effects models with participants nested within studies were used. Response and remission rates were calculated using the Reliable Change Index. The intervention group obtained significantly higher response rates (OR = 2.49, 95% CI 2.17-2.85) and remission rates compared to controls (OR = 2.41, 95% CI 2.07-2.79). The moderator analysis indicated that older participants (OR = 1.01) and native-born participants (1.66) were more likely to respond to treatment compared to younger participants and ethnic minorities respectively. Age (OR = 1.01) and ethnicity (1.73) also moderated the effects of treatment on remission.Moreover, adults with more severe depressive symptoms at baseline were more likely to remit after receiving intemet-based treatment (OR = 1.19). Guided Internet-based interventions lead to substantial positive treatment effects on treatment response and remission at post-treatment. Thus, such interventions may complement existing services for depression and potentially reduce the gap between the need and provision of evidence-based treatments.
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7.
  • Newton-Cheh, Christopher, et al. (författare)
  • Genome-wide association study identifies eight loci associated with blood pressure
  • 2009
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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9.
  • Padmanabhan, Sandosh, et al. (författare)
  • Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension
  • 2010
  • Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 59 region of Uromodulin (UMOD; rs13333226, combined P value of 3.6x10(-11)). The minor G allele is associated with a lower risk of hypertension (OR [95% CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.
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10.
  • Sawcer, Stephen, et al. (författare)
  • Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
  • 2011
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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11.
  • Wang, Gang, et al. (författare)
  • Spirometric phenotypes from early childhood to young adulthood : a Chronic Airway Disease Early Stratification study
  • 2021
  • Ingår i: ERJ Open Research. - : ERS Publications. - 2312-0541. ; 7:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The prevalences of obstructive and restrictive spirometric phenotypes, and their relation to early-life risk factors from childhood to young adulthood remain poorly understood. The aim was to explore these phenotypes and associations with well-known respiratory risk factors across ages and populations in European cohorts.Methods: We studied 49334 participants from 14 population-based cohorts in different age groups (⩽10, >10–15, >15–20, >20–25 years, and overall, 5–25 years). The obstructive phenotype was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) z-score less than the lower limit of normal (LLN), whereas the restrictive phenotype was defined as FEV1/FVC z-score ⩾LLN, and FVC z-score Results: The prevalence of obstructive and restrictive phenotypes varied from 3.2–10.9% and 1.8–7.7%, respectively, without clear age trends. A diagnosis of asthma (adjusted odds ratio (aOR=2.55, 95% CI 2.14–3.04), preterm birth (aOR=1.84, 1.27–2.66), maternal smoking during pregnancy (aOR=1.16, 95% CI 1.01–1.35) and family history of asthma (aOR=1.44, 95% CI 1.25–1.66) were associated with a higher prevalence of obstructive, but not restrictive, phenotype across ages (5–25 years). A higher current body mass index (BMI was more often observed in those with the obstructive phenotype but less in those with the restrictive phenotype (aOR=1.05, 95% CI 1.03–1.06 and aOR=0.81, 95% CI 0.78–0.85, per kg·m−2 increase in BMI, respectively). Current smoking was associated with the obstructive phenotype in participants older than 10 years (aOR=1.24, 95% CI 1.05–1.46).Conclusion: Obstructive and restrictive phenotypes were found to be relatively prevalent during childhood, which supports the early origins concept. Several well-known respiratory risk factors were associated with the obstructive phenotype, whereas only low BMI was associated with the restrictive phenotype, suggesting different underlying pathobiology of these two phenotypes.
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12.
  • Adrian, Juliane, et al. (författare)
  • A Glossary for Research on Human Crowd Dynamics
  • 2019
  • Ingår i: Collective Dynamics. - 2366-8539. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • This article presents a glossary of terms that are frequently used in research onhuman crowds. This topic is inherently multidisciplinary as it includes work in and across computer science, engineering, mathematics, physics, psychology and social science, for example. We do not view the glossary presented here as a collection of finalised and formal definitions. Instead, we suggest it is a snapshot of current views and the starting point of an ongoing process that we hope will be useful in providing some guidance on the use of terminology to develop a mutual understanding across disciplines. The glossary was developed collaboratively during a multidisciplinary meeting. We deliberately allowseveral definitions of terms, to reflect the confluence of disciplines in the field. This also reflects the fact not all contributors necessarily agree with all definitions in this glossary.
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13.
  • Aktaa, Suleman, et al. (författare)
  • Data standards for transcatheter aortic valve implantation : the European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart).
  • 2023
  • Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - : Oxford University Press. - 2058-5225 .- 2058-1742. ; 9:5, s. 529-536
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: Standardized data definitions are necessary for the quantification of quality of care and patient outcomes in observational studies and randomised controlled trials (RCTs). The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) project of the European Society of Cardiology (ESC) aims to create pan-European data standards for cardiovascular diseases and interventions, including transcatheter aortic valve implantation (TAVI).METHODS AND RESULTS: We followed the EuroHeart methodology for cardiovascular data standard development. A Working Group of 29 members representing 12 countries was established and included a patient representative, as well as experts in the management of valvular heart disease from the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Association of Cardiovascular Imaging (EACVI) and the Working Group on Cardiovascular Surgery. We conducted a systematic review of the literature and used a modified Delphi method to reach consensus on a final set of variables. For each variable, the Working Group provided a definition, permissible values and categorized the variable as mandatory (Level 1) or additional (Level 2) based on its clinical importance and feasibility. In total, 93 Level 1 and 113 Level 2 variables were selected, with the level 1 variables providing the dataset for registration of patients undergoing TAVI on the EuroHeart IT platform.CONCLUSION: This document provides details of the EuroHeart data standards for TAVI processes of care and in-hospital outcomes. In the context of EuroHeart, this will facilitate quality improvement, observational research, registry-based RCTs and post-marketing surveillance of devices and pharmacotherapies.
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14.
  • Anderson, Christopher J., et al. (författare)
  • Response to Comment on "Estimating the reproducibility of psychological science"
  • 2016
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 351:6277
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Gilbert et al. conclude that evidence from the Open Science Collaboration's Reproducibility Project: Psychology indicates high reproducibility, given the study methodology. Their very optimistic assessment is limited by statistical misconceptions and by causal inferences from selectively interpreted, correlational data. Using the Reproducibility Project: Psychology data, both optimistic and pessimistic conclusions about reproducibility are possible, and neither are yet warranted.
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15.
  • Bansal, Sheel, et al. (författare)
  • Practical Guide to Measuring Wetland Carbon Pools and Fluxes
  • 2023
  • Ingår i: Wetlands (Wilmington, N.C.). - : SPRINGER. - 0277-5212 .- 1943-6246. ; 43:8
  • Forskningsöversikt (refereegranskat)abstract
    • Wetlands cover a small portion of the world, but have disproportionate influence on global carbon (C) sequestration, carbon dioxide and methane emissions, and aquatic C fluxes. However, the underlying biogeochemical processes that affect wetland C pools and fluxes are complex and dynamic, making measurements of wetland C challenging. Over decades of research, many observational, experimental, and analytical approaches have been developed to understand and quantify pools and fluxes of wetland C. Sampling approaches range in their representation of wetland C from short to long timeframes and local to landscape spatial scales. This review summarizes common and cutting-edge methodological approaches for quantifying wetland C pools and fluxes. We first define each of the major C pools and fluxes and provide rationale for their importance to wetland C dynamics. For each approach, we clarify what component of wetland C is measured and its spatial and temporal representativeness and constraints. We describe practical considerations for each approach, such as where and when an approach is typically used, who can conduct the measurements (expertise, training requirements), and how approaches are conducted, including considerations on equipment complexity and costs. Finally, we review key covariates and ancillary measurements that enhance the interpretation of findings and facilitate model development. The protocols that we describe to measure soil, water, vegetation, and gases are also relevant for related disciplines such as ecology. Improved quality and consistency of data collection and reporting across studies will help reduce global uncertainties and develop management strategies to use wetlands as nature-based climate solutions.
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16.
  • Beck, Anna Severine, et al. (författare)
  • Will there be a next Nordic TAG? Reflections on theoretical archaeology in the Nordic countries today
  • 2019
  • Ingår i: Arkæologisk Forum. - 1399-5545. ; :41, s. 17-19
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The first meeting in Nordic Theoretical Archaeology Group (Nordic TAG) was held in 1985. The – so far – last meeting in Nordic TAG was held in Copenhagen in 2015. At this meeting, the theme was “the Next 30 years in Theoretical Archaeology” – or in other words the aim wasto discussin which direction theories in the archaeological discipline will develop and especially what new theories, methodologies and perspectives might influence the field in the future. Tragicomically – or prophetically – no meetings have been organized since then. Now almost five years later we must ask: what is the future of Nordic TAG, and what does the lack of it tell us about the development of theoretical archaeology in the Nordic countries today?
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17.
  • Beecham, Ashley H, et al. (författare)
  • Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
  • 2013
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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18.
  • Bohman, Björn, et al. (författare)
  • Identification of (Z)-8-Heptadecene and n-Pentadecane as Electrophysiologically Active Compounds in Ophrys insectifera and Its Argogorytes Pollinator
  • 2020
  • Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Sexually deceptive orchids typically depend on specific insect species for pollination, which are lured by sex pheromone mimicry. European Ophrys orchids often exploit specific species of wasps or bees with carboxylic acid derivatives. Here, we identify the specific semiochemicals present in O. insectifera, and in females of one of its pollinator species, Argogorytes fargeii. Headspace volatile samples and solvent extracts were analysed by GC-MS and semiochemicals were structurally elucidated by microderivatisation experiments and synthesis. (Z)-8-Heptadecene and n-pentadecane were confirmed as present in both O. insectifera and A. fargeii female extracts, with both compounds being found to be electrophysiologically active to pollinators. The identified semiochemicals were compared with previously identified Ophrys pollinator attractants, such as (Z)-9 and (Z)-12-C-27-C-29 alkenes in O. sphegodes and (Z)-9-octadecenal, octadecanal, ethyl linoleate and ethyl oleate in O. speculum, to provide further insights into the biosynthesis of semiochemicals in this genus. We propose that all these currently identified Ophrys semiochemicals can be formed biosynthetically from the same activated carboxylic acid precursors, after a sequence of elongation and decarbonylation reactions in O. sphegodes and O. speculum, while in O. insectifera, possibly by decarbonylation without preceding elongation.
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19.
  • Byskov, Jens, et al. (författare)
  • Accountable priority setting for trust in health systems : the need for research into a new approach for strengthening sustainable health action in developing countries
  • 2009
  • Ingår i: Health Research Policy and Systems. - : BioMed Central. - 1478-4505. ; 7, s. 23-
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite multiple efforts to strengthen health systems in low and middle income countries, intended sustainable improvements in health outcomes have not been shown. To date most priority setting initiatives in health systems have mainly focused on technical approaches involving information derived from burden of disease statistics, cost effectiveness analysis, and published clinical trials. However, priority setting involves value-laden choices and these technical approaches do not equip decision-makers to address a broader range of relevant values - such as trust, equity, accountability and fairness - that are of concern to other partners and, not least, the populations concerned. A new focus for priority setting is needed. Accountability for Reasonableness (AFR) is an explicit ethical framework for legitimate and fair priority setting that provides guidance for decision-makers who must identify and consider the full range of relevant values. AFR consists of four conditions: i) relevance to the local setting, decided by agreed criteria; ii) publicizing priority-setting decisions and the reasons behind them; iii) the establishment of revisions/appeal mechanisms for challenging and revising decisions; iv) the provision of leadership to ensure that the first three conditions are met. REACT - "REsponse to ACcountable priority setting for Trust in health systems" is an EU-funded five-year intervention study started in 2006, which is testing the application and effects of the AFR approach in one district each in Kenya, Tanzania and Zambia. The objectives of REACT are to describe and evaluate district-level priority setting, to develop and implement improvement strategies guided by AFR and to measure their effect on quality, equity and trust indicators. Effects are monitored within selected disease and programme interventions and services and within human resources and health systems management. Qualitative and quantitative methods are being applied in an action research framework to examine the potential of AFR to support sustainable improvements to health systems performance. This paper reports on the project design and progress and argues that there is a high need for research into legitimate and fair priority setting to improve the knowledge base for achieving sustainable improvements in health outcomes.
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21.
  • Dare, Anna J., et al. (författare)
  • Prioritizing Surgical Care on National Health Agendas : A Qualitative Case Study of Papua New Guinea, Uganda, and Sierra Leone
  • 2016
  • Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 13:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Little is known about the social and political factors that influence priority setting for different health services in low- and middle-income countries (LMICs), yet these factors are integral to understanding how national health agendas are established. We investigated factors that facilitate or prevent surgical care from being prioritized in LMICs. Methods and Findings: We undertook country case studies in Papua New Guinea, Uganda, and Sierra Leone, using a qualitative process-tracing method. We conducted 74 semi-structured interviews with stakeholders involved in health agenda setting and surgical care in these countries. Interviews were triangulated with published academic literature, country reports, national health plans, and policies. Data were analyzed using a conceptual framework based on four components (actor power, ideas, political contexts, issue characteristics) to assess national factors influencing priority for surgery. Political priority for surgical care in the three countries varies. Priority was highest in Papua New Guinea, where surgical care is firmly embedded within national health plans and receives significant domestic and international resources, and much lower in Uganda and Sierra Leone. Factors influencing whether surgical care was prioritized were the degree of sustained and effective domestic advocacy by the local surgical community, the national political and economic environment in which health policy setting occurs, and the influence of international actors, particularly donors, on national agenda setting. The results from Papua New Guinea show that a strong surgical community can generate priority from the ground up, even where other factors are unfavorable. Conclusions: National health agenda setting is a complex social and political process. To embed surgical care within national health policy, sustained advocacy efforts, effective framing of the problem and solutions, and country-specific data are required. Political, technical, and financial support from regional and international partners is also important.
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22.
  • Forouzanfar, Mohammad H, et al. (författare)
  • Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
  • 2015
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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23.
  • Friedlander, Michael, et al. (författare)
  • Clinical trials in recurrent ovarian cancer.
  • 2011
  • Ingår i: International Journal of Gynecological Cancer. - : Lippincott Williams & Wilkins. - 1048-891X .- 1525-1438. ; 21:4, s. 771-775
  • Forskningsöversikt (refereegranskat)abstract
    • The 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup was held in Vancouver, Canada, in June 2010. Representatives of 23 cooperative research groups studying gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. Group C, 1 of the 3 discussion groups, examined recurrent ovarian cancer, and we report the consensus reached regarding 4 questions. These included the following: (1) What is the role of cytoreductive surgery for recurrent ovarian cancer? (2) How do we define distinct patient populations in need of specific therapeutic approaches? (3) Should end points for trials with recurrent disease vary from those of first-line trials? (4) Is CA-125 progression alone sufficient for entry/eligibility into clinical trials?
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24.
  • Gerber, Evgeny, et al. (författare)
  • The missing pieces of the PuO2 nanoparticle puzzle
  • 2020
  • Ingår i: Nanoscale. - : ROYAL SOC CHEMISTRY. - 2040-3364 .- 2040-3372. ; 12:35, s. 18039-18048
  • Tidskriftsartikel (refereegranskat)abstract
    • The nanoscience field often produces results more mystifying than any other discipline. It has been argued that changes in the plutonium dioxide (PuO2) particle size from bulk to nano can have a drastic effect on PuO2 properties. Here we report a full characterization of PuO2 nanoparticles (NPs) at the atomic level and probe their local and electronic structures by a variety of methods available at the synchrotron, including extended X-ray absorption fine structure (EXAFS) at the Pu L-3 edge, X-ray absorption near edge structure (XANES) in high energy resolution fluorescence detection (HERFD) mode at the Pu L-3 and M-4 edges, high energy X-ray scattering (HEXS) and X-ray diffraction (XRD). The particles were synthesized from precursors with different oxidation states of plutonium (III, IV, and V) under various environmentally and waste storage relevant conditions (pH 8 and pH > 10). Our experimental results analyzed with state-of-the-art theoretical approaches demonstrate that well dispersed, crystalline NPs with a size of similar to 2.5 nm in diameter are always formed in spite of diverse chemical conditions. Identical crystal structures and the presence of only the Pu(IV) oxidation state in all NPs, reported here for the first time, indicate that the structure of PuO2 NPs is very similar to that of the bulk PuO2. All methods give complementary information and show that investigated fundamental properties of PuO2 NPs, rather than being exotic, are very similar to those of the bulk PuO2.
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25.
  • Hajdarevic, Senada, 1970-, et al. (författare)
  • Awareness of sunburn in childhood, use of sunbeds and change of moles in Denmark, Northern Ireland, Norway and Sweden
  • 2016
  • Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 26:1, s. 29-35
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Malignant melanoma (MM) is increasing rapidly in Northern Europe. To reduce incidence and mortality through earlier diagnosis, public awareness of MM is important. Thus, we aim to examine awareness of risk factors and a symptom of MM, and how awareness varies by country and socio-demographic factors in Denmark, Northern Ireland (NI), Norway and Sweden.METHODS: Population-based telephone interviews using the 'Awareness and Beliefs about Cancer' measure were conducted in 2011 among 8355 adults ≥50 years as part of the International Cancer Benchmarking Partnership Module 2. Prevalence ratios (PRs) with 95% confidence intervals were calculated.RESULTS: In these four countries, lowest awareness was found for 'sunburn in childhood' (63%), whereas awareness was high for 'use of sunbeds' (91%) and 'mole change' (97%). Lack of awareness of 'sunburn in childhood' was more prevalent among respondents from Norway [PR = 1.38 (1.28-1.48)] but less prevalent among respondents from Northern Ireland (NI) [PR = 0.78 (0.72-0.85)] and Sweden [PR = 0.86 (0.79-0.93)] compared with respondents from Denmark. Lack of awareness of 'use of sunbeds' was more prevalent among respondents from Norway [PR = 2.99 (2.39-3.74)], Sweden [PR = 1.57 (1.22-2.00)], and NI [PR = 1.65 (1.30-2.10)] compared with respondents form Denmark. Being a man, age ≥70, living alone, and having lower education, were each independently associated with lack of MM-awareness.CONCLUSIONS: The results indicate relatively low awareness of 'sunburn in childhood' as a risk factor for MM, and important disparities in MM-awareness across countries and socio-demographic groups. Improved and more directed initiatives to enhance public MM-awareness, particularly about 'sunburn in childhood', are needed.
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26.
  • Hayashi, Makoto, et al. (författare)
  • VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation
  • 2013
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4, s. 1672-
  • Tidskriftsartikel (refereegranskat)abstract
    • Vascular endothelial growth factor (VEGF) guides the path of new vessel sprouts by inducing VEGF receptor-2 activity in the sprout tip. In the stalk cells of the sprout, VEGF receptor-2 activity is downregulated. Here, we show that VEGF receptor-2 in stalk cells is dephosphorylated by the endothelium-specific vascular endothelial-phosphotyrosine phosphatase (VE-PTP). VE-PTP acts on VEGF receptor-2 located in endothelial junctions indirectly, via the Angiopoietin-1 receptor Tie2. VE-PTP inactivation in mouse embryoid bodies leads to excess VEGF receptor-2 activity in stalk cells, increased tyrosine phosphorylation of VE-cadherin and loss of cell polarity and lumen formation. Vessels in ve-ptp(-/-) teratomas also show increased VEGF receptor-2 activity and loss of endothelial polarization. Moreover, the zebrafish VE-PTP orthologue ptp-rb is essential for polarization and lumen formation in intersomitic vessels. We conclude that the role of Tie2 in maintenance of vascular quiescence involves VE-PTP-dependent dephosphorylation of VEGF receptor-2, and that VEGF receptor-2 activity regulates VE-cadherin tyrosine phosphorylation, endothelial cell polarity and lumen formation.
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27.
  • Holmér, Andreas, et al. (författare)
  • Short leucine-rich glycoproteins of the extracellular matrix display diverse patterns of complement interaction and activation.
  • 2009
  • Ingår i: Molecular Immunology. - : Elsevier BV. - 1872-9142 .- 0161-5890. ; 46, s. 830-839
  • Tidskriftsartikel (refereegranskat)abstract
    • The extracellular matrix consists of structural macromolecules and other proteins with regulatory functions. An important family of the latter class of molecules found in most tissues is the small leucine-rich repeat proteins (SLRPs). We have previously shown that the SLRP fibromodulin binds directly to C1q and activates the classical pathway of complement. In the present study we further examine the interactions between SLRPs and complement. Osteoadherin, like fibromodulin, binds C1q and activates the classical pathway strongly while moderate activation is seen in the terminal pathway. This can be explained by the interaction of fibromodulin and osteoadherin with factor H, a major soluble inhibitor of complement. Also, chondroadherin was found to bind C1q and activate complement, albeit to a lesser extent. Chondroadherin also binds factor H. We confirm published data showing that biglycan and decorin bind C1q but do not activate complement. In this study a similar pattern is seen for lumican although its affinity for C1q is lower than for biglycan and decorin. Furthermore, using electron microscopy and radiolabeled SLRPs, we demonstrate two different classes of SLRP binding sites on C1q, to head and stalk respectively, where only binding to the head appears to be activating. We propose a role for SLRPs in the regulation of complement activation in diseases involving the extracellular matrix, particularly those characterized by chronic inflammation such as rheumatoid arthritis, atherosclerosis, osteoarthritis and chronic obstructive lung disease.
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28.
  • Jordan, Anna, et al. (författare)
  • The potential of the solitary parasitoid Microctonus brassicae for the biological control of the adult cabbage stem flea beetle, Psylliodes chrysocephala
  • 2020
  • Ingår i: Entomologia Experimentalis et Applicata. - : John Wiley & Sons. - 0013-8703 .- 1570-7458. ; , s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • The cabbage stem flea beetle (CSFB), Psylliodes chrysocephala L. (Coleoptera: Chrysomelidae), is a major pest of oilseed rape, Brassica napus L. (Brassicaceae), within the UK and continental Europe. Following the withdrawal of many broad-spectrum pesticides, most importantly neonicotinoids, and with increased incidence of pyrethroid resistance, few chemical control options remain, resulting in the need for alternative pest management strategies. We identified the parasitoid wasp Microctonus brassicae (Haeselbarth) (Hymenoptera: Braconidae) within CSFB collected from three independent sites in Norfolk, UK. Parasitism of adult CSFB was confirmed, and wasp oviposition behaviour was described. Moreover, we show that within captive colonies parasitism rates are sufficient to generate significant biological control of CSFB populations. A sequence of the M. brassicae mitochondrial cytochrome oxidase 1 (MT-CO1) gene was generated for rapid future identification. Moroccan specimens of Microctonus aethiopoides (Loan), possessing 90% sequence similarity, were the closest identified sequenced species. This study represents the first description published in English of this parasitoid of the adult cabbage stem flea beetle.
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29.
  • Kappos, Ludwig, et al. (författare)
  • Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
  • 2018
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 391, s. 1263-1273
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2018 Elsevier Ltd Background: No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatme nt arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation: Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding: Novartis Pharma AG.
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30.
  • Karp, Melissa A., et al. (författare)
  • Increasing the uptake of multispecies models in fisheries management 
  • 2023
  • Ingår i: ICES Journal of Marine Science. - : Oxford University Press (OUP). - 1054-3139 .- 1095-9289. ; 80:2, s. 243-257
  • Tidskriftsartikel (refereegranskat)abstract
    • Multispecies models have existed in a fisheries context since at least the 1970s, but despite much exploration, advancement, and consideration of multispecies models, there remain limited examples of their operational use in fishery management. Given that species and fleet interactions are inherently multispecies problems and the push towards ecosystem-based fisheries management, the lack of more regular operational use is both surprising and compelling. We identify impediments hampering the regular operational use of multispecies models and provide recommendations to address those impediments. These recommendations are: (1) engage stakeholders and managers early and often; (2) improve messaging and communication about the various uses of multispecies models; (3) move forward with multispecies management under current authorities while exploring more inclusive governance structures and flexible decision-making frameworks for handling tradeoffs; (4) evaluate when a multispecies modelling approach may be more appropriate; (5) tailor the multispecies model to a clearly defined purpose; (6) develop interdisciplinary solutions to promoting multispecies model applications; (7) make guidelines available for multispecies model review and application; and (8) ensure code and models are well documented and reproducible. These recommendations draw from a global assemblage of subject matter experts who participated in a workshop entitled “Multispecies Modeling Applications in Fisheries Management”. 
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31.
  • Kim, Anna, 1989, et al. (författare)
  • Label-free millimeter-wave sensor for investigations of biological model membrane systems
  • 2015
  • Ingår i: µTAS 2015. - 9780979806483 ; 2114-2115, s. 2114-2115
  • Konferensbidrag (refereegranskat)abstract
    • We demonstrate a millimeter-wave sensing method based on a coplanar waveguide for biological membrane studies in an open-volume fluidic arrangement. On-wafer measurements of scattering parameters were performed up to 110 GHz. The sensor shows the ability to distinguish the addition of20% cholesterol in artificial biological membranes, which is an important component influencing the stability and fluidity of such systems. This is the first stage in the development of a millimeter-wave sensor for biological model membrane studies.
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32.
  • Kim, Anna, 1989, et al. (författare)
  • Open-volume microfluidic device for manipulation and monitoring of single-cells and tissues
  • 2014
  • Ingår i: Biosensors, 27-30 May 2014, Melbourne, Australia.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • We have previously reported a microfluidic pipette, which combines hydrodynamic flow confinement with solution switching for localized stimulation of single-cells and tissue slices. Some integration challenges still remain, pertaining to size and material properties. Here we present a novel pipette tip fabricated from the photo-polymer SU-8, for which a convenient process was developed, further expanding this technology for single-cell analysis.SU-8 micropipettes were patterned using standard photolithographic techniques and bonded using elevated temperature and high pressure. The fabrication procedure utilizes thermal release tape as a sacrificial layer facilitating release of the microstructures.The micropipettes were tested to withstand pressures between -0.6 and 0.95 bar, while featuring a tip width of only 200 μm. This new micropipette minimizes shadowing in experiments utilising tissue and offers different material composition for single-cell microscopy. The micropipettes have been designed for use in neuropharmacology, cardiac muscle research and for collection of biological substances from single-cells. The high chemical stability of the micropipettes will also allow application in surface chemistry research, for surface patterning with biomarkers and for guided cell growth. We aim to combine this device with THz impedance spectroscopy for monitoring physiological changes in single-cells. We present the first prototype of a millimetre wave coplanar waveguide (CPW), developed with ANSYS HFSS and to be used in combination with the device for single-cell impedance spectroscopy analysis. The CPW will be deposited on an independent glass substrate, separating the cell by a passivation layer. The cells will be exposed to various stimuli using the micropipette. The field of single-cell impedance spectroscopy analysis is at an early exploratory stage, and the combination of microfluidics with THz technology has the potential to bridge the gap between life science and engineering communities.
  •  
33.
  • Kim, Anna, 1989, et al. (författare)
  • SU-8 free-standing microfluidic probes
  • 2017
  • Ingår i: Biomicrofluidics. - : AIP Publishing. - 1932-1058. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a process for fabrication of free-standing SU-8 probes, with a dry, mechanical release of the final micro-devices. The process utilizes the thermal release tape, a commonly used cleanroom material, for facile heat-release from the sacrificial layer. For characterization of the SU-8 microfluidic probes, two liquid interfaces were designed: a disposable interface with integrated wells and an interface with external liquid reservoirs. The versatility of the fabrication and the release procedures was illustrated by further developing the process to functionalize the SU-8 probes for impedance sensing, by integrating metal thin-film electrodes. An additional interface scheme which contains electronic components for impedance measurements was developed. We investigated the possibilities of introducing perforations in the SU-8 device by photolithography, for solution sampling predominantly by diffusion. The SU-8 processes described here allow for a convenient batch production of versatile free-standing microfluidic devices with well-defined tip-geometry. (C) 2017 Author(s).
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34.
  • Litjens, Carlijn H. C., et al. (författare)
  • Protein binding of rifampicin is not saturated when using high-dose rifampicin
  • 2019
  • Ingår i: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091. ; 74:4, s. 986-990
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Higher doses of rifampicin are being investigated as a means to optimize response to this pivotal TB drug. It is unknown whether high-dose rifampicin results in saturation of plasma protein binding and a relative increase in protein-unbound (active) drug concentrations. Objectives To assess the free fraction of rifampicin based on an in vitro experiment and data from a clinical trial on high-dose rifampicin. Methods Protein-unbound rifampicin concentrations were measured in human serum spiked with increasing total concentrations (up to 64mg/L) of rifampicin and in samples obtained by intensive pharmacokinetic sampling of patients who used standard (10mg/kg daily) or high-dose (35mg/kg) rifampicin up to steady-state. The performance of total AUC(0-24) to predict unbound AUC(0-24) was evaluated. Results The in vitro free fraction of rifampicin remained unaltered (approximate to 9%) up to 21mg/L and increased up to 13% at 41mg/L and 17% at 64mg/L rifampicin. The highest (peak) concentration in vivo was 39.1mg/L (high-dose group). The arithmetic mean percentage unbound to total AUC(0-24)in vivo was 13.3% (range=8.1%-24.9%) and 11.1% (range=8.6%-13.6%) for the standard group and the high-dose group, respectively (P=0.214). Prediction of unbound AUC(0-24) based on total AUC(0-24) resulted in a bias of -0.05% and an imprecision of 13.2%. Conclusions Plasma protein binding of rifampicin can become saturated, but exposures after high-dose rifampicin are not high enough to increase the free fraction in TB patients with normal albumin values. Unbound rifampicin exposures can be predicted from total exposures, even in the higher dose range.
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35.
  • Lunt, Daniel J., et al. (författare)
  • The DeepMIP contribution to PMIP4 : experimental design for model simulations of the EECO, PETM, and pre-PETM (version 1.0)
  • 2017
  • Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 10:2, s. 889-901
  • Tidskriftsartikel (refereegranskat)abstract
    • Past warm periods provide an opportunity to evaluate climate models under extreme forcing scenarios, in particular high (>800 ppmv) atmospheric CO2 concentrations. Although a post hoc intercomparison of Eocene (similar to 50 Ma) climate model simulations and geological data has been carried out previously, models of past high-CO2 periods have never been evaluated in a consistent framework. Here, we present an experimental design for climate model simulations of three warm periods within the early Eocene and the latest Paleocene (the EECO, PETM, and pre-PETM). Together with the CMIP6 pre-industrial control and abrupt 4 x CO2 simulations, and additional sensitivity studies, these form the first phase of DeepMIP - the Deep-time Model Intercomparison Project, itself a group within the wider Paleo-climate Modelling Intercomparison Project (PMIP). The experimental design specifies and provides guidance on boundary conditions associated with palaeogeography, greenhouse gases, astronomical configuration, solar constant, land surface processes, and aerosols. Initial conditions, simulation length, and output variables are also specified. Finally, we explain how the geological data sets, which will be used to evaluate the simulations, will be developed.
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36.
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37.
  • Maringe, Camille, et al. (författare)
  • Stage at diagnosis and colorectal cancer survival in six high-income countries : A population-based study of patients diagnosed during 2000-2007
  • 2013
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 52:5, s. 919-932
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundLarge international differences in colorectal cancer survival exist, even between countries with similar healthcare. We investigate the extent to which stage at diagnosis explains these differences.MethodsData from population-based cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK were analysed for 313 852 patients diagnosed with colon or rectal cancer during 2000-2007. We compared the distributions of stage at diagnosis. We estimated both stage-specific net survival and the excess hazard of death up to three years after diagnosis, using flexible parametric models on the log-cumulative excess hazard scale.ResultsInternational differences in colon and rectal cancer stage distributions were wide: Denmark showed a distribution skewed towards later-stage disease, while Australia, Norway and the UK showed high proportions of 'regional' disease. One-year colon cancer survival was 67% in the UK and ranged between 71% (Denmark) and 80% (Australia and Sweden) elsewhere. For rectal cancer, one-year survival was also low in the UK (75%), compared to 79% in Denmark and 82-84% elsewhere. International survival differences were also evident for each stage of disease, with the UK showing consistently lowest survival at one and three years.ConclusionDifferences in stage at diagnosis partly explain international differences in colorectal cancer survival, with a more adverse stage distribution contributing to comparatively low survival in Denmark. Differences in stage distribution could arise because of differences in diagnostic delay and awareness of symptoms, or in the thoroughness of staging procedures. Nevertheless, survival differences also exist for each stage of disease, suggesting unequal access to optimal treatment, particularly in the UK.
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38.
  • Mc Goldrick, Niall, et al. (författare)
  • A multi-program analysis of cleft lip with cleft palate prevalence and mortality using data from 22 International Clearinghouse for Birth Defects Surveillance and Research programs, 1974–2014
  • 2023
  • Ingår i: Birth Defects Research. - 2472-1727. ; 115:10, s. 980-997
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cleft lip with cleft palate (CLP) is a congenital condition that affects both the oral cavity and the lips. This study estimated the prevalence and mortality of CLP using surveillance data collected from birth defect registries around the world. Methods: Data from 22 population- and hospital-based surveillance programs affiliated with the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) in 18 countries on live births (LB), stillbirths (SB), and elective terminations of pregnancy for fetal anomaly (ETOPFA) for CLP from 1974 to 2014 were analyzed. Prevalence and survival (survival for LB only) estimates were calculated for total and subclassifications of CLP and by pregnancy outcome. Results: The pooled prevalence of total CLP cases was 6.4 CLP per 10,000 births. The prevalence of CLP and all of the pregnancy outcomes varied across programs. Higher ETOPFA rates were recorded in most European programs compared to programs in other continents. In programs reporting low ETOPFA rates or where there was no ascertainment of ETOPFA, the rate of CLP among LB and SB was higher compared to those where ETOPFA rates were ascertained. Overall survival for total CLP was 91%. For isolated CLP, the survival was 97.7%. CLP associated with multiple congenital anomalies had an overall survival of 77.1%, and for CLP associated with genetic/chromosomal syndromes, overall survival was 40.9%. Conclusions: Total CLP prevalence reported in this study is lower than estimates from prior studies, with variation by pregnancy outcomes between programs. Survival was lower when CLP was associated with other congenital anomalies or syndromes compared to isolated CLP.
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39.
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40.
  • Moshontz, Hannah, et al. (författare)
  • The Psychological Science Accelerator: Advancing Psychology Through a Distributed Collaborative Network
  • 2018
  • Ingår i: Advances in Methods and Practices in Psychological Science. - : SAGE Publications. - 2515-2459 .- 2515-2467. ; 1:4, s. 501-515
  • Tidskriftsartikel (refereegranskat)abstract
    • Concerns about the veracity of psychological research have been growing. Many findings in psychological science are based on studies with insufficient statistical power and nonrepresentative samples, or may otherwise be limited to specific, ungeneralizable settings or populations. Crowdsourced research, a type of large-scale collaboration in which one or more research projects are conducted across multiple lab sites, offers a pragmatic solution to these and other current methodological challenges. The Psychological Science Accelerator (PSA) is a distributed network of laboratories designed to enable and support crowdsourced research projects. These projects can focus on novel research questions or replicate prior research in large, diverse samples. The PSA’s mission is to accelerate the accumulation of reliable and generalizable evidence in psychological science. Here, we describe the background, structure, principles, procedures, benefits, and challenges of the PSA. In contrast to other crowdsourced research networks, the PSA is ongoing (as opposed to time limited), efficient (in that structures and principles are reused for different projects), decentralized, diverse (in both subjects and researchers), and inclusive (of proposals, contributions, and other relevant input from anyone inside or outside the network). The PSA and other approaches to crowdsourced psychological science will advance understanding of mental processes and behaviors by enabling rigorous research and systematic examination of its generalizability.
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41.
  • Müller-Sienerth, Nicole, et al. (författare)
  • A panel of recombinant proteins from human-infective Plasmodium species for serological surveillance
  • 2020
  • Ingår i: Malaria Journal. - : BMC. - 1475-2875. ; 19
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Malaria remains a global health problem and accurate surveillance of Plasmodium parasites that are responsible for this disease is required to guide the most effective distribution of control measures. Serological surveillance will be particularly important in areas of low or periodic transmission because patient antibody responses can provide a measure of historical exposure. While methods for detecting host antibody responses to Plasmodium falciparum and Plasmodium vivax are well established, development of serological assays for Plasmodium knowlesi, Plasmodium ovale and Plasmodium malariae have been inhibited by a lack of immunodiagnostic candidates due to the limited availability of genomic information.Methods: Using the recently completed genome sequences from P. malariae, P. ovale and P. knowlesi, a set of 33 candidate cell surface and secreted blood-stage antigens was selected and expressed in a recombinant form using a mammalian expression system. These proteins were added to an existing panel of antigens from P. falciparum and P. vivax and the immunoreactivity of IgG, IgM and IgA immunoglobulins from individuals diagnosed with infections to each of the five different Plasmodium species was evaluated by ELISA. Logistic regression modelling was used to quantify the ability of the responses to determine prior exposure to the different Plasmodium species.Results: Using sera from European travellers with diagnosed Plasmodium infections, antigens showing species-specific immunoreactivity were identified to select a panel of 22 proteins from five Plasmodium species for serological profiling. The immunoreactivity to the antigens in the panel of sera taken from travellers and individuals living in malaria-endemic regions with diagnosed infections showed moderate power to predict infections by each species, including P. ovale, P. malariae and P. knowlesi. Using a larger set of patient samples and logistic regression modelling it was shown that exposure to P. knowlesi could be accurately detected (AUC=91%) using an antigen panel consisting of the P. knowlesi orthologues of MSP10, P12 and P38.Conclusions: Using the recent availability of genome sequences to all human-infective Plasmodium spp. parasites and a method of expressing Plasmodium proteins in a secreted functional form, an antigen panel has been compiled that will be useful to determine exposure to these parasites.
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42.
  • Rau, Anna-Lena, et al. (författare)
  • Linking concepts of change and ecosystem services research: A systematic review
  • 2018
  • Ingår i: Change and Adaptation in Socio-Ecological Systems. - : Portico. - 2300-3669. ; 4, s. 33-45
  • Tidskriftsartikel (refereegranskat)abstract
    • Transformation, transition and regime shift are increasingly applied concepts in the academic literature to describe changes in society and the environment. Ecosystem services represent one framework that includes the implicit aim of supporting transformation towards a more sustainable system. Nevertheless, knowledge and systematic reviews on the use of these concepts within ecosystem services research are so far lacking. Therefore, we present a systematic literature review to analyse the interlinkages between these concepts and ecosystem services. Using a search string we identified 258 papers that we analysed based on 40 review criteria. Our results show that transformation was mentioned most often (197 articles), followed by transition (183 articles) and regime shifts (43 articles). Moreover, there is no consolidation of these concepts. Only 13% of all articles gave definitions for the three concepts. These definitions strongly overlapped in their use. Moreover, most papers described changes that happened in the past (73%). We conclude that research would benefit from being directed towards the future rather than evaluating what has happened in the past. Based on our results, we present: i) clear definitions for the three concepts; and ii) a framework highlighting the interlinkages between the ecosystem services cascade and the concepts of change.
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43.
  • Rodilla, Helena, 1982, et al. (författare)
  • Applying THz Technology in Life Science
  • 2014
  • Ingår i: Swedish Microwave Days. Gigahertz Symposium, March 11-12, 2014. Gothenburg, Sweden.
  • Konferensbidrag (refereegranskat)abstract
    • Bio-molecules, due to their structure and size, have vibrational and rotational resonances at THz frequencies (0.1 to 10 THz) [1]. This unique interaction promises a multitude of applications in life sciences, wherein the latest development of THz sources and detectors has enabled this field of research to grow. Although being at an early and mostly exploratory stage of development, this field is riddled with many challenges that should be overcome; measurements of inhomogeneous media, short interaction lengths with few molecules, strong water absorption, and also the cultural gap between medical and engineering communities. In this work we present our preliminary results for three experiments within this field.
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44.
  • Rodilla, Helena, 1982, et al. (författare)
  • Millimeter-wave sensor based on a λ/2-line resonator for identification and dielectric characterization of non-ionic surfactants
  • 2016
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies of biological and artificial membrane systems, such as niosomes, currently rely on the use of fluorescent tags, which can influence the system under investigation. For this reason, the development of label-free, non-invasive detection techniques is of great interest. We demonstrate an open volume label-free millimeter-wave sensing platform based on a coplanar waveguide, developed for identification and characterization of niosome constituents. A design based on a λ/2-line resonator was used and on-wafer measurements of transmission and reflection parameters were performed up to 110 GHz. Our sensor was able to clearly distinguish between common niosome constituents, non-ionic surfactants Tween 20 and Span 80, measuring a resonance shift of 3 GHz between them. The complex permittivities of the molecular compounds have been extracted. Our results indicate insignificant frequency dependence in the investigated frequency range (3 GHz – 110 GHz). Values of permittivity around 3.0 + 0.7i and 2.2 + 0.4i were obtained for Tween 20 and Span 80, respectively.
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45.
  • Rodilla, Helena, 1982, et al. (författare)
  • Millimetre-wave dielectric spectroscopy for cell analysis
  • 2014
  • Ingår i: International Conference on Infrared, Millimeter, and Terahertz Waves, IRMMW-THz. - 2162-2027 .- 2162-2035. - 9781479938773 ; , s. Art. no. 6956057-
  • Konferensbidrag (refereegranskat)abstract
    • A millimeter-wave sensor based on a CPW line has been designed and fabricated as a first prototype for impedance spectroscopy to be combined with a multifunctional micropipette for cell and membrane analysis. The first mm-wave measurement results show the sensitivity of the layout by distinguishing the cells from the media and monitoring the attachment process of the cells to the sensor surface. Measurements were performed on umbilical cord stem cells and cartilage thumb cells.
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46.
  • Shelton, Jennifer M. G., et al. (författare)
  • Genetic determinants of anti-malarial acquired immunity in a large multi-centre study
  • 2015
  • Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels. Methods: Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP) 4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels. Results: Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)(4) epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2. Conclusion: Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of combining data from sites with heterogeneous malaria transmission levels across Africa and Asia with which to explore genetic effects on anti-malarial immunity.
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47.
  • Shijun, Xu, 1984, et al. (författare)
  • A rapid microfluidic technique for integrated viability determination of adherent single cells
  • 2015
  • Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 407:5, s. 1295-1301
  • Tidskriftsartikel (refereegranskat)abstract
    • Here, we report on a novel protocol for determining the viability of individual cells in an adherent cell culture, without adversely affecting the remaining cells in the sample. This is facilitated using a freestanding microfluidic perfusion device, the Multifunctional Pipette (MFP), which generates a virtual flow cell around selected single cells. We investigated the utility on four different cell lines, NG108-15, HEK 293, PC12, and CHO, and combined the assay with a cell poration experiment, in which we apply the pore-forming agent digitonin, followed by fluorescein diphosphate, a pre-fluorescent substrate for alkaline phosphatase, in order to monitor intracellular enzyme activity. The cell viability was instantly assessed through simultaneous perfusion with fluorescein diacetate (FDA) and propidium iodide (PI), both being dispensed through the same superfusion device used to porate and deliver the enzyme substrate. In this fluorescence assay, viable and non-viable cells were distinguished by their green and red emission, respectively, within 10 s. In addition, the enzyme activity was monitored over time as a secondary test for cellular activity. Our findings demonstrate that this microfluidic technology-assisted approach is a facile, rapid, and reliable means to determine the viability in single-cell experiments and that viability studies can be performed routinely alongside typical substrate delivery protocols. This approach would remove the need for global cell viability testing and would enable viability studies of only the cells under experimental analysis.
  •  
48.
  • Stanaway, Jeffrey D., et al. (författare)
  • Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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49.
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50.
  • Stöckl, Anna, et al. (författare)
  • Allometric scaling of a superposition eye optimizes sensitivity and acuity in large and small hawkmoths
  • 2022
  • Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 289:1979
  • Tidskriftsartikel (refereegranskat)abstract
    • Animals vary widely in body size within and across species. This has consequences for the function of organs and body parts in both large and small individuals. How these scale, in relation to body size, reveals evolutionary investment strategies, often resulting in trade-offs between functions. Eyes exemplify these trade-offs, as they are limited by their absolute size in two key performance features: sensitivity and spatial acuity. Due to their size polymorphism, insect compound eyes are ideal models for studying the allometric scaling of eye performance. Previous work on apposition compound eyes revealed that allometric scaling led to poorer spatial resolution and visual sensitivity in small individuals, across a range of insect species. Here, we used X-ray microtomography to investigate allometric scaling in superposition compound eyes-the second most common eye type in insects-for the first time. Our results reveal a novel strategy to cope with the trade-off between sensitivity and spatial acuity, as we show that the eyes of the hummingbird hawkmoth retain an optimal balance between these performance measures across all body sizes. 
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