| 1. |
- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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| 2. |
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| 4. |
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| 5. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 6. |
- Machiela, Mitchell J., et al.
(författare)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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| 7. |
- Dankiewicz, Josef, et al.
(författare)
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Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
- 2021
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
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Tidskriftsartikel (refereegranskat)abstract
- Hypothermia or Normothermia after Cardiac Arrest This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes. Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. Results A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. Conclusions In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)
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| 8. |
- Lewis, Cathryn M, et al.
(författare)
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Genome scan meta-analysis of schizophrenia and bipolar disorder, part II : Schizophrenia
- 2003
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Ingår i: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 73:1, s. 34-48
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.
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| 9. |
- Alexander, Peter, et al.
(författare)
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Assessing uncertainties in land cover projections
- 2017
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013. ; 23:2, s. 767-781
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Tidskriftsartikel (refereegranskat)abstract
- Understanding uncertainties in land cover projections is critical to investigating land-based climate mitigation policies, assessing the potential of climate adaptation strategies and quantifying the impacts of land cover change on the climate system. Here, we identify and quantify uncertainties in global and European land cover projections over a diverse range of model types and scenarios, extending the analysis beyond the agro-economic models included in previous comparisons. The results from 75 simulations over 18 models are analysed and show a large range in land cover area projections, with the highest variability occurring in future cropland areas. We demonstrate systematic differences in land cover areas associated with the characteristics of the modelling approach, which is at least as great as the differences attributed to the scenario variations. The results lead us to conclude that a higher degree of uncertainty exists in land use projections than currently included in climate or earth system projections. To account for land use uncertainty, it is recommended to use a diverse set of models and approaches when assessing the potential impacts of land cover change on future climate. Additionally, further work is needed to better understand the assumptions driving land use model results and reveal the causes of uncertainty in more depth, to help reduce model uncertainty and improve the projections of land cover.
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| 10. |
- Birkhofer, Klaus, et al.
(författare)
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Arthropod food webs in organic and conventional wheat farming systems: a stable isotope approach
- 2011
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Ingår i: Agricultural and Forest Entomology. - : Wiley. - 1461-9555. ; 13:2, s. 197-204
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Tidskriftsartikel (refereegranskat)abstract
- 1 Agricultural intensification not only alters the structure of arthropod communities, but also may affect biotic interactions by altering the availability of basal resources. We analyzed variations in stable isotope ratios (15N/14N and 13C/12C) of fertilizers, plants, prey and generalist predators in organic and conventional farming systems in a long-term agricultural experiment [DOK trial (bioDynamic, bioOrganic, Konventionell)]. Two basal resources with pronounced differences in carbon isotope signatures, wheat litter (C3 plant) and maize litter (C4 plant), were used to uncover differences in food web properties between the two farming systems (conventional versus organic). 2 Predators incorporated significantly higher proportions of carbon from wheat sources in organically managed fields, suggesting that they were more closely linked to wheat-consuming prey in this system. The δ15N values of three predaceous species were more than 2‰ greater in summer than in spring. 3 The results obtained suggest that generalist predators consumed higher proportions of herbivore prey in the organic system and that starvation and intraguild predation rates increased in some predator species with time. 4 Because the effects of farming system and sampling date on predators were species-specific, conserving a diverse natural enemy community including species with different phenologies and sensitivities to management practices may, in the long term, be a good strategy for maintaining high pest suppression throughout the growing season.
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| 11. |
- Birkhofer, Klaus, et al.
(författare)
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Cursorial spiders retard initial aphid population growth at low densities in winter wheat
- 2008
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Ingår i: Bulletin of Entomological Research. - 1475-2670. ; 98:3, s. 249-255
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Tidskriftsartikel (refereegranskat)abstract
- Generalist predators contribute to pest suppression in agroecosystems. Spider communities, which form a substantial fraction of the generalist predator fauna in arable land, are characterized by two functional groups: web-building and cursorial (non-web-building) species. We investigated the relative impact of these two functional groups on a common pest (Sitobion avenae, Aphididae) in wheat by combining a molecular technique that revealed species-specific aphid consumption rates with a factorial field experiment that analyzed the impact, separately and together, of equal densities of these two spider functional groups on aphid population growth. Only cursorial spiders retarded aphid population growth in our cage experiment, but this effect was limited to the initial aphid-population growth period and low-to-intermediate aphid densities. The molecular analysis, which used aphid-specific primers to detect aphid DNA in predator species, detected the highest proportion of aphid-consuming individuals in two cursorial spiders: the foliage-dwelling Xysticus cristatus (Thomisidae) and the ground-active Pardosa palustris (Lycosidae). The results suggest that manipulating the community composition in favour of pest-consuming functional groups may be more important for improving biological control than fostering predator biodiversity per se. Agricultural management practices that specifically foster effective species or functional groups (e.g. mulching for cursorial spiders) should receive more attention in low-pesticide farming systems.
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| 12. |
- Birkhofer, Klaus, et al.
(författare)
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Generalist predators in organically and conventionally managed grass-clover fields: implications for conservation biological control
- 2008
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Ingår i: Annals of Applied Biology. - : Wiley. - 0003-4746 .- 1744-7348. ; 153:2, s. 271-280
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Tidskriftsartikel (refereegranskat)abstract
- Organically managed agroecosystems rely in part on biological control to prevent pest outbreaks. Generalist predators (Araneae, Carabidae and Staphylinidae) are a major component of the natural enemy community in agroecosystems. We assessed the seasonal dynamics of major generalist predator groups in conventionally and organically managed grass–clover fields that primarily differed by fertilisation strategy. We further established an experiment, manipulating the abundant wolf spider genus Pardosa, to identify the importance of these predators for herbivore suppression in the same system and growth period. Organic management significantly enhanced ground-active spider numbers early and late in the growing season, with potentially positive effects of plant cover and non-pest decomposer prey. However, enhancing spider numbers in the field experiment did not improve biological control in organically managed grass–clover fields. Similar to the survey results, reduced densities of Pardosa had no short-term effect on any prey taxa; however, spider guild structure changed in response to Pardosa manipulation. In the presence of fewer Pardosa, other ground-running spiders were more abundant; therefore, their impact on herbivore numbers may have been elevated, possibly cancelling increases in herbivore numbers because of reduced predation by Pardosa. Our results indicate positive effects of organic farming on spider activity density; however, our survey data and the predator manipulation experiment failed to find evidence that ground-running spiders reduced herbivore numbers. We therefore suggest that a positive impact of organic fertilisers on wolf spiders in grass–clover agroecosystems may not necessarily improve biological control when compared with conventional farming.
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| 13. |
- Birkhofer, Klaus, et al.
(författare)
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Small-scale spatial pattern of web-building spiders (Araneae) in alfalfa: Relationship to disturbance from cutting, prey availability, and intraguild interactions
- 2007
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Ingår i: Environmental Entomology. - 1938-2936. ; 36:4, s. 801-810
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the development of spatial patterns in generalist predators will improve our ability to incorporate them into biological control programs. We studied the small-scale spatial patterns of spider webs in alfalfa by analyzing the relationship between web locations over distances ranging from 4 to 66 cm. Using a coordinate-based spatial statistic (O-ring) and assuming a heterogeneous distribution of suitable web sites, we analyzed the impact of cutting and changes in spider abundance on web distribution. We analyzed the influence of small-scale variation in prey availability by comparing web distributions to the pattern of sticky-trap captures of Aphididae and Diptera described by a count-based spatial statistic (SADIE). Cutting of alfalfa reduced the overall density of web-building spiders but had no immediate impact on the spatial distribution of their webs. Availability of aphids was highest before the alfalfa was cut and was clumped at a scale of 66 cm. Spider webs, however, were not clumped at any scale or date. In contrast, webs were regularly distributed at smaller distances (<20 cm) immediately before and after cutting. Because cursorial and web-building spiders were most active during this period, we hypothesize that the development of small-scale regularity in web locations was driven by intraguild interactions. Our results suggest that intraguild interactions contribute to the development of small-scale spatial patterns of spider webs in alfalfa. Variation in prey availability may have more of an influence on web distribution in crops with a different vegetation structure or if patterns are studied at larger spatial scales.
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| 14. |
- Birkhofer, Klaus, et al.
(författare)
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Subsidy from the Detrital Food Web, but Not Microhabitat Complexity, Affects the Role of Generalist Predators in an Aboveground Herbivore Food Web
- 2008
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Ingår i: Oikos. - : Wiley. - 1600-0706 .- 0030-1299. ; 117:4, s. 494-500
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Tidskriftsartikel (refereegranskat)abstract
- The activity and density of generalist predators, such as carabid beedes, rove beedes and spiders, may increase in response to: (1) increased availability of prey from the belowground subsystem and/ or (2) enhanced complexity of aboveground vegetation. Organic farming practices support decomposer populations and enhance habitat complexity due to an increased weed density. A response by generalist predators to such below-or aboveground changes could affect predation rates on herbivores in the aboveground food web. We tested this hypothesis in a replicated field experiment conducted in a winter wheat field, where increased predator activity could lead to improved control of herbivorous pests. In a crossed design, we increased and lowered densities of decomposer prey, and manipulated vegetation complexity using artificial plants in order to examine the effect of structural complexity in isolation from effects of plant-attracted additional prey. Isotomid Collembola exhibited lowest activity-densities (AD) in plots treated with soil insecticide and had gradually increasing AD in untreated plots and plots receiving detrital subsidies. Carabid beedes and cursorial spiders did not respond to increased availability of isotomid prey, and they unexpectedly displayed higher AD in the structurally less-complex plots. Aphid density mirrored the positive response of isotomids to detrital subsidies, suggesting that aphids benefited from reduced predation due to predators switching to abundant prey in the decomposer subsystem. The absence of a numerical response by surface-active predators apparendy strengthened this indirect effect of isotomids on aphids. Our results suggest that indirect predator-mediated prey-prey interactions can reduce beneficial effects of detrital subsidies on pest suppression. We further demonstrated that generalist predators may not per se benefit from structural complexity. Both results document the challenges associated with management practices that support generalist predators, as these measures may not necessarily improve herbivore suppression.
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| 15. |
- Dankiewicz, Josef, et al.
(författare)
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Targeted hypothermia versus targeted Normothermia after out-of-hospital cardiac arrest (TTM2): A randomized clinical trial - Rationale and design
- 2019
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 217, s. 23-31
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Tidskriftsartikel (refereegranskat)abstract
- Background: Less than 500 participants have been included in randomized trials comparing hypothermia with regular care for out-of-hospital cardiac arrest patients, and many of these trials were small and at a high risk of bias. Consequently, the accrued data on this potentially beneficial intervention resembles that of a drug following small phase II trials. A large confirmatory trial is therefore warranted. Methods: The TTM2-trial is an international, multicenter, parallel group, investigator-initiated, randomized, superiority trial in which a target temperature of 33°C after cardiac arrest will be compared with a strategy to maintain normothermia and early treatment of fever (≥37.8°C). Participants will be randomized within 3 hours of return of spontaneous circulation with the intervention period lasting 40 hours in both groups. Sedation will be mandatory for all patients throughout the intervention period. The clinical team involved with direct patient care will not be blinded to allocation group due to the inherent difficulty in blinding the intervention. Prognosticators, outcome-assessors, the steering group, the trial coordinating team, and trial statistician will be blinded. The primary outcome will be all-cause mortality at 180 days after randomization. We estimate a 55% mortality in the control group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The main secondary neurological outcome will be poor functional outcome (modified Rankin Scale 4–6) at 180 days after arrest. Discussion: The TTM2-trial will compare hypothermia to 33°C with normothermia and early treatment of fever (≥37.8°C) after out-of-hospital cardiac arrest. © 2019
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| 16. |
- Frydland, Martin, et al.
(författare)
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Usefulness of Serum B-Type Natriuretic Peptide Levels in Comatose Patients Resuscitated from Out-of-Hospital Cardiac Arrest to Predict Outcome
- 2016
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 118:7, s. 998-1005
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Tidskriftsartikel (refereegranskat)abstract
- N-terminal pro-B-type natriuretic (NT-proBNP) is expressed in the heart and brain, and serum levels are elevated in acute heart and brain diseases. We aimed to assess the possible association between serum levels and neurological outcome and death in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). Of the 939 comatose OHCA patients enrolled and randomized in the Targeted Temperature Management (TTM) trial to TTM at 33°C or 36°C for 24 hours, 700 were included in the biomarker substudy. Of these, 647 (92%) had serum levels of NT-proBNP measured 24, 48, and 72 hours after return of spontaneous circulation (ROSC). Neurological outcome was evaluated by the Cerebral Performance Category (CPC) score and modified Rankin Scale (mRS) at 6 months. Six hundred thirty-eight patients (99%) had serum NT-proBNP levels ≥125 pg/ml. Patients with TTM at 33°C had significantly lower NT-proBNP serum levels (median 1,472 pg/ml) than those in the 36°C group (1,914 pg/ml) at 24 hours after ROSC, p <0.01 but not at 48 and 72 hours. At 24 hours, an increase in NT-proBNP quartile was associated with death (Plogrank <0.0001). In addition, NT-proBNP serum levels > median were independently associated with poor neurological outcome (odds ratio, ORCPC 2.02, CI 1.34 to 3.05, p <0.001; ORmRS 2.28, CI 1.50 to 3.46, p <0.001) adjusted for potential confounders. The association was diminished at 48 and 72 hours after ROSC. In conclusion, NT-proBNP serum levels are increased in comatose OHCA patients. Furthermore, serum NT-proBNP levels are affected by level of TTM and are associated with death and poor neurological outcome.
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| 17. |
- Wasserman, D, et al.
(författare)
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Compulsory admissions of patients with mental disorders: State of the art on ethical and legislative aspects in 40 European countries
- 2020
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Ingår i: European psychiatry : the journal of the Association of European Psychiatrists. - : Royal College of Psychiatrists. - 1778-3585. ; 63:1, s. e82-
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Tidskriftsartikel (refereegranskat)abstract
- Background.Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care.Methods.The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions.Results.We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures.Conclusions.We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.
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