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Sökning: WFRF:(Johnston David)

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1.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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2.
  • Fresard, Laure, et al. (författare)
  • Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
  • 2019
  • Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
  • 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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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.
  • Nene, Vishvanath, et al. (författare)
  • Genome sequence of Aedes aegypti, a major arbovirus vector.
  • 2007
  • Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5832, s. 1718-23
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae. Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of approximately 4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster. Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of approximately 2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species.
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5.
  • Thompson, Paul M., et al. (författare)
  • The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
  • 2014
  • Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
  • Tidskriftsartikel (refereegranskat)abstract
    • The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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6.
  • Escott-Price, Valentina, et al. (författare)
  • Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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7.
  • Jones, Lesley, et al. (författare)
  • Convergent genetic and expression data implicate immunity in Alzheimer's disease
  • 2015
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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8.
  • Butler, Peter, et al. (författare)
  • Coulomb excitation of pear-shaped nuclei
  • 2019
  • Ingår i: - : EDP Sciences. ; , s. 01007-01007
  • Konferensbidrag (refereegranskat)abstract
    • There is a large body of evidence that atomic nuclei can undergo octupole distortion and assume the shape of a pear. This phenomenon is important for measurements of electric-dipole moments of atoms, which would indicate CP violation and hence probe physics beyond the Standard Model of particle physics. Isotopes of both radon and radium have been identified as candidates for such measurements. Here, we have observed the low-lying quantum states in 224Rn and 226Rn by accelerating beams of these radioactive nuclei. We show that radon isotopes undergo octupole vibrations but do not possess static pear-shapes in their ground states. We conclude that radon atoms provide less favourable conditions for the enhancement of a measurable atomic electric-dipole moment.
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9.
  • Foley, Jonathan A., et al. (författare)
  • Solutions for a cultivated planet
  • 2011
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 478:7369, s. 337-342
  • Tidskriftsartikel (refereegranskat)abstract
    • Increasing population and consumption are placing unprecedented demands on agriculture and natural resources. Today, approximately a billion people are chronically malnourished while our agricultural systems are concurrently degrading land, water, biodiversity and climate on a global scale. To meet the world's future food security and sustainability needs, food production must grow substantially while, at the same time, agriculture's environmental footprint must shrink dramatically. Here we analyse solutions to this dilemma, showing that tremendous progress could be made by halting agricultural expansion, closing 'yield gaps' on underperforming lands, increasing cropping efficiency, shifting diets and reducing waste. Together, these strategies could double food production while greatly reducing the environmental impacts of agriculture.
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10.
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11.
  • Johnston, Jennifer J., et al. (författare)
  • Molecular Analysis Expands the Spectrum of Phenotypes Associated with GLI3 Mutations
  • 2010
  • Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794. ; 31:10, s. 1142-1154
  • Tidskriftsartikel (refereegranskat)abstract
    • A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining 93 probands here. This includes 19 probands (12 mutations) who fulfilled clinical criteria for GCPS or PHS, 48 probands (16 mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), 21 probands (6 mutations) with features of PHS or GCPS and oral-facial- digital syndrome, and 5 probands (1 mutation) with nonsyndromic polydactyly. These data support previously identified genotype-phenotype correlations and demonstrate a more variable degree of severity than previously recognized. The finding of GLI3 mutations in patients with features of oral-facial-digital syndrome supports the observation that GLI3 interacts with cilia. We conclude that the phenotypic spectrum of GLI3 mutations is broader than that encompassed by the clinical diagnostic criteria, but the genotype-phenotype correlation persists. Individuals with features of either GCPS or PHS should be screened for mutations in GLI3 even if they do not fulfill clinical criteria. Hum Mutat 31:1142-1154, 2010. (C) 2010 Wiley-Liss, Inc.
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12.
  • Langrish, Jeremy, et al. (författare)
  • Contribution of endothelin-1 to the vascular effects of diesel exhaust inhalation in humans
  • 2009
  • Ingår i: Hypertension. - Dallas, Tex. : The Association. - 0194-911X .- 1524-4563. ; 54:4, s. 910-915
  • Tidskriftsartikel (refereegranskat)abstract
    • Diesel exhaust inhalation impairs vascular function, and, althoughthe underlying mechanism remains unclear, endothelin (ET) 1and NO are potential mediators. The aim of this study was toidentify whether diesel exhaust inhalation affects the vascularactions of ET-1 in humans. In a randomized, double-blind crossoverstudy, 13 healthy male volunteers were exposed to either filteredair or dilute diesel exhaust (331±13 µg/m3). Plasmaconcentrations of ET-1 and big-ET-1 were determined at baselineand throughout the 24-hour study period. Bilateral forearm bloodflow was measured 2 hours after the exposure during infusionof either ET-1 (5 pmol/min) or the ETA receptor antagonist,BQ-123 (10 nmol/min) alone and in combination with the ETB receptorantagonist, BQ-788 (1 nmol/min). Diesel exhaust exposure hadno effect on plasma ET-1 and big-ET-1 concentrations (P>0.05for both) or 24-hour mean blood pressure or heart rate (P>0.05for all). ET-1 infusion increased plasma ET-1 concentrationsby 58% (P<0.01) but caused vasoconstriction only after dieselexhaust exposure (–17% versus 2% after air; P<0.001).In contrast, diesel exhaust exposure reduced vasodilatationto isolated BQ-123 infusion (20% versus 59% after air; P<0.001)but had no effect on vasodilatation to combined BQ-123 and BQ-788administration (P>0.05). Diesel exhaust inhalation increasesvascular sensitivity to ET-1 and reduces vasodilatation to ETAreceptor antagonism despite unchanged plasma ET-1 concentrations.Given the tonic interaction between the ET and NO systems, weconclude that diesel exhaust inhalation alters vascular reactivityto ET-1 probably through its effects on NO bioavailability.
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13.
  • Maron, David J., et al. (författare)
  • Initial Invasive or Conservative Strategy for Stable Coronary Disease
  • 2020
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:15, s. 1395-1407
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain.Methods: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction.Results: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32).Conclusions: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, .) Patients with stable coronary disease were randomly assigned to an initial invasive strategy with angiography and revascularization if appropriate or to medical therapy alone. At 3.2 years, there was no significant difference between the groups with respect to the estimated rate of ischemic events. The findings were sensitive to the definition of myocardial infarction.
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14.
  • Spertus, John A, et al. (författare)
  • Health-Status Outcomes with Invasive or Conservative Care in Coronary Disease.
  • 2020
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:15, s. 1408-1419
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients.METHODS: We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency.RESULTS: At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina).CONCLUSIONS: In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
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15.
  • Torchia, Jonathon, et al. (författare)
  • Molecular subgroups of atypical teratoid rhabdoid tumours in children : an integrated genomic and clinicopathological analysis
  • 2015
  • Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 16:5, s. 569-582
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort of patients with atypical teratoid rhabdoid tumours to find out the molecular basis for clinical heterogeneity in these tumours. Methods We obtained 259 rhabdoid tumours from 37 international institutions and assessed transcriptional profiles in 43 primary tumours and copy number profiles in 38 primary tumours to discover molecular subgroups of atypical teratoid rhabdoid tumours. We used gene and pathway enrichment analyses to discover group-specific molecular markers and did immunohistochemical analyses on 125 primary tumours to evaluate clinicopathological significance of molecular subgroup and ASCL1-NOTCH signalling. Findings Transcriptional analyses identified two atypical teratoid rhabdoid tumour subgroups with differential enrichment of genetic pathways, and distinct clinicopathological and survival features. Expression of ASCL1, a regulator of NOTCH signalling, correlated with supratentorial location (p=0.004) and superior 5-year overall survival (35%, 95% CI 13-57, and 20%, 6-34, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.033) in 70 patients who received multimodal treatment. ASCL1 expression also correlated with superior 5-year overall survival (34%, 7-61, and 9%, 0-21, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.001) in 39 patients who received only chemotherapy without radiation. Cox hazard ratios for overall survival in patients with differential ASCL1 enrichment treated with chemotherapy with or without radiation were 2.02 (95% CI 1.04-3.85; p=0.038) and 3.98 (1.71-9.26; p=0.001). Integrated analyses of molecular subgroupings with clinical prognostic factors showed three distinct clinical risk groups of tumours with different therapeutic outcomes. Interpretation An integration of clinical risk factors and tumour molecular groups can be used to identify patients who are likely to have improved long-term radiation-free survival and might help therapeutic stratification of patients with atypical teratoid rhabdoid tumours.
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16.
  • 2017
  • swepub:Mat__t
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17.
  • Niemi, MEK, et al. (författare)
  • 2021
  • swepub:Mat__t
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18.
  • Bafadhel, Mona, et al. (författare)
  • Acute Exacerbations of Chronic Obstructive Pulmonary Disease : Identification of Biologic Clusters and Their Biomarkers
  • 2011
  • Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 184:6, s. 662-671
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to inflammation and etiology. Objectives: Investigate biomarker expression in COPD exacerbations to identify biologic clusters and determine biomarkers that recognize clinical COPD exacerbation phenotypes, namely those associated with bacteria, viruses, or eosinophilic airway inflammation. Methods: Patients with COPD were observed for 1 year at stable and exacerbation visits. Biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biologic phenotypes were explored using unbiased cluster analysis and biomarkers that differentiated clinical exacerbation phenotypes were investigated. Measurements and Main Results: A total of 145 patients (101 men and 44 women) entered the study. A total of 182 exacerbations were captured from 86 patients. Four distinct biologic exacerbation clusters were identified. These were bacterial-, viral-, or eosinophilic-predominant, and a fourth associated with limited changes in the inflammatory profile termed "pauciinflammatory." Of all exacerbations, 55%, 29%, and 28% were associated with bacteria, virus, or a sputum eosinophilia. The biomarkers that best identified these clinical phenotypes were sputum IL-1 beta, 0.89 (area under receiver operating characteristic curve) (95% confidence interval [CI], 0.83-0.95); serum CXCL10, 0.83 (95% CI, 0.70-0.96); and percentage peripheral eosinophils, 0.85 (95% CI, 0.78-0.93), respectively. Conclusions: The heterogeneity of the biologic response of COPD exacerbations can be defined. Sputum IL-1 beta, serum CXCL10, and peripheral eosinophils are biomarkers of bacteria-, virus-, or eosinophil-associated exacerbations of COPD. Whether phenotype-specific biomarkers can be applied to direct therapy warrants further investigation.
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19.
  • Bafadhel, Mona, et al. (författare)
  • Blood Eosinophils to Direct Corticosteroid Treatment of Exacerbations of Chronic Obstructive Pulmonary Disease A Randomized Placebo-Controlled Trial
  • 2012
  • Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 186:1, s. 48-55
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) and responses to treatment are heterogeneous. Objectives: Investigate the usefulness of blood eosinophils to direct corticosteroid therapy during exacerbations. Methods: Subjects with COPD exacerbations were entered into a randomized biomarker-directed double-blind corticosteroid versus standard therapy study. Subjects in the standard arm received prednisolone for 2 weeks, whereas in the biomarker-directed arm, prednisolone or matching placebo was given according to the blood eosinophil count biomarker. Both study groups received antibiotics. Blood eosinophils were measured in the biomarker-directed and standard therapy arms to define biomarker-positive and -negative exacerbations (blood eosinophil count > and <= 2%, respectively). The primary outcome was to determine noninferiority in health status using the chronic respiratory questionnaire (CRQ) and in the proportion of exacerbations associated with a treatment failure between subjects allocated to the biomarker-directed and standard therapy arms. Measurements and Main Results: There were 86 and 80 exacerbations in the biomarker-directed and standard treatment groups, respectively. In the biomarker-directed group, 49% of the exacerbations were not treated with prednisolone. CRQ improvement after treatment in the standard and biomarker-directed therapy groups was similar (0.8 vs. 1.1; mean difference, 0.3; 95% confidence interval, 0.0-0.6; P = 0.05). There was a greater improvement in CRQ in biomarker-negative exacerbations given placebo compared with those given prednisolone (mean difference, 0.45; 95% confidence interval, 0.01-0.90; P = 0.04). In biomarker-negative exacerbations, treatment failures occurred in 15% given prednisolone and 2% of those given placebo (P = 0.04). Conclusions: The peripheral blood eosinophil count is a promising biomarker to direct corticosteroid therapy during COPD exacerbations, but larger studies are required.
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20.
  • Bhattacharya, Prosun, 1962-, et al. (författare)
  • Prevalence of SARS-CoV-2 in Communities Through Wastewater Surveillance—a Potential Approach for Estimation of Disease Burden
  • 2021
  • Ingår i: Current Pollution Reports. - : Springer Nature. - 2198-6592. ; 7:2, s. 160-166
  • Tidskriftsartikel (refereegranskat)abstract
    • The episodic outbreak of COVID-19 due to SARS-CoV-2 is severely affecting the economy, and the global count of infected patients is increasing. The actual number of patients had been underestimated due to limited facilities for testing as well as asymptomatic nature of the expression of COVID-19 on individual basis. Tragically, for emerging economies with high population density, the situation has been more complex due to insufficient testing facilities for diagnosis of the disease. However, the recent reports about persistent shedding of viral RNA of SARS-CoV-2 in the human feces have created a possibility to track the prevalence and trends of the disease in communities, known as wastewater-based epidemiology (WBE). In this article, we highlight the current limitations and future prospects for WBE to manage pandemics.
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21.
  • Comas-Bru, Laia, et al. (författare)
  • Evaluating model outputs using integrated global speleothem records of climate change since the last glacial
  • 2019
  • Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 15:4, s. 1557-1579
  • Tidskriftsartikel (refereegranskat)abstract
    • Although quantitative isotope data from speleothems has been used to evaluate isotope-enabled model simulations, currently no consensus exists regarding the most appropriate methodology through which to achieve this. A number of modelling groups will be running isotope-enabled palaeoclimate simulations in the framework of the Coupled Model Intercomparison Project Phase 6, so it is timely to evaluate different approaches to using the speleothem data for data-model comparisons. Here, we illustrate this using 456 globally distributed speleothem delta O-18 records from an updated version of the Speleothem Isotopes Synthesis and Analysis (SISAL) database and palaeoclimate simulations generated using the ECHAM5-wiso isotope-enabled atmospheric circulation model. We show that the SISAL records reproduce the first-order spatial patterns of isotopic variability in the modern day, strongly supporting the application of this dataset for evaluating model-derived isotope variability into the past. However, the discontinuous nature of many speleothem records complicates the process of procuring large numbers of records if data-model comparisons are made using the traditional approach of comparing anomalies between a control period and a given palaeoclimate experiment. To circumvent this issue, we illustrate techniques through which the absolute isotope values during any time period could be used for model evaluation. Specifically, we show that speleothem isotope records allow an assessment of a model's ability to simulate spatial isotopic trends. Our analyses provide a protocol for using speleothem isotope data for model evaluation, including screening the observations to take into account the impact of speleothem mineralogy on delta O-18 values, the optimum period for the modern observational baseline and the selection of an appropriate time window for creating means of the isotope data for palaeo-time-slices.
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22.
  • Damineli, Augusto, et al. (författare)
  • The Long-term Spectral Changes of Eta Carinae : Are they Caused by a Dissipating Occulter as Indicated by CMFGEN Models?
  • 2023
  • Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 954
  • Tidskriftsartikel (refereegranskat)abstract
    • Eta Carinae (η Car) exhibits a unique set of P Cygni profiles with both broad and narrow components. Over many decades, the spectrum has changed-there has been an increase in observed continuum fluxes and a decrease in Fe II and H I emission-line equivalent widths. The spectrum is evolving toward that of a P Cygni star such as P Cygni itself and HDE 316285. The spectral evolution has been attributed to intrinsic variations such as a decrease in the mass-loss rate of the primary star or differential evolution in a latitudinal-dependent stellar wind. However, intrinsic wind changes conflict with three observational results: the steady long-term bolometric luminosity; the repeating X-ray light curve over the binary period; and the constancy of the dust-scattered spectrum from the Homunculus. We extend previous work that showed a secular strengthening of P Cygni absorptions by adding more orbital cycles to overcome temporary instabilities and by examining more atomic transitions. CMFGEN modeling of the primary wind shows that a time-decreasing mass-loss rate is not the best explanation for the observations. However, models with a small dissipating absorber in our line of sight can explain both the increase in brightness and changes in the emission and P Cygni absorption profiles. If the spectral evolution is caused by the dissipating circumstellar medium, and not by intrinsic changes in the binary, the dynamical timescale to recover from the Great Eruption is much less than a century, different from previous suggestions.
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24.
  • Dutia, Iain, et al. (författare)
  • Fatigue experienced by people with cerebral palsy : a systematic review of assessment tools and decision tree
  • 2024
  • Ingår i: Disability and Rehabilitation. - : Taylor & Francis. - 0963-8288 .- 1464-5165. ; 46:9, s. 1751-1759
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To conduct a systematic review of self- and proxy-report fatigue assessment tools used in studies of people with cerebral palsy (CP) of all ages, and to develop a fatigue assessment tool decision tree for clinicians and researchers.Materials and methods: Five electronic databases (MEDLINE, PsycInfo, CINAHL, Web of Science and Cochrane) were searched to September 2021 to identify studies assessing self-reported fatigue in people with CP of any age. The assessment tools utilised were extracted and two reviewers appraised the tool characteristics, clinical utility and psychometric properties. A decision tree for selecting fatigue assessment tools was constructed.Results: Ten assessment tools were identified across thirty-nine studies, three of which are valid and reliable for assessing fatigue severity and impact in people with CP. A four-level fatigue assessment tool decision tree was constructed. No valid and reliable tool for assessing cognitive fatigue was identified; responsiveness has not been evaluated in any tool for people with CP.Conclusions: Physical fatigue screening and assessment tools for people with CP are available and are presented in our decision tree, however their utility as outcome measures remains unclear. Cognitive fatigue is understudied and poorly understood, further work is required in this area.IMPLICATIONS FOR REHABILITATION Current measurement tools to screen and assess physical fatigue in people with cerebral palsy (CP) are valid and reliable and are presented in our 4-level decision tree to guide assessment tool selection.The responsiveness of these measurement tools to screen and assess physical fatigue has not been evaluated, therefore their utility as outcome measures in people with CP is unclear.Cognitive fatigue is understudied and poorly understood in people with CP.Valid and reliable tools to assess cognitive fatigue in people with CP are not available.
  •  
25.
  • Eckert, Christopher G., et al. (författare)
  • Plant mating systems in a changing world
  • 2010
  • Ingår i: Trends in Ecology & Evolution. - : Elsevier BV. - 0169-5347. ; In Press, Corrected Proof
  • Tidskriftsartikel (refereegranskat)abstract
    • There is increasing evidence that human disturbance can negatively impact plant-pollinator interactions such as outcross pollination. We present a meta-analysis of 22 studies involving 27 plant species showing a significant reduction in the proportion of seeds outcrossed in response to anthropogenic habitat modifications. We discuss the evolutionary consequences of disturbance on plant mating systems, and in particular whether reproductive assurance through selfing effectively compensates for reduced outcrossing. The extent to which disturbance reduces pollinator versus mate availability could generate diverse selective forces on reproductive traits. Investigating how anthropogenic change influences plant mating will lead to new opportunities for better understanding of how mating systems evolve, as well as of the ecological and evolutionary consequences of human activities and how to mitigate them.
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26.
  • Eggers, Kai M., 1962-, et al. (författare)
  • Sex-differences in circulating biomarkers during acute myocardial infarction : An analysis from the SWEDEHEART registry
  • 2021
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:4 April
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Sex-differences in the pathobiology of myocardial infarction are well established but incompletely understood. Improved knowledge on this topic may help clinicians to improve management of men and women with myocardial infarction. Methods In this registry-based cohort study (SWEDEHEART), we analyzed 175 circulating biomarkers reflecting various pathobiological axes in 856 men and 243 women admitted to Swedish coronary care units because of myocardial infarction. Two multimarker panels were applied (Proximity Extension Assay [Olink Bioscience], Multiple Reaction Monitoring mass spectrometry). Lasso analysis (penalized logistic regression), multiple testing-corrected Mann- Whitney tests and Cox regressions were used to assess sex-differences in the concentrations of these biomarkers and their implications on all-cause mortality and major adverse events (median follow-up up to 6.6 years). Results Biomarkers provided a very high discrimination between both sexes, when considered simultaneously (c-statistics 0.972). Compared to women, men had higher concentrations of six biomarkers with the most pronounced differences seen for those reflecting atherogenesis, myocardial necrosis and metabolism. Women had higher concentrations of 14 biomarkers with the most pronounced differences seen for those reflecting activation of the reninangiotensin- aldosterone axis, inflammation and for adipokines. There were no major variations between sexes in the associations of these biomarkers with outcome. Conclusions Severable sex-differences exist in the expression of biomarkers in patients with myocardial infarction. While these differences had no impact on outcome, our data suggest the presence of various sex-related pathways involved in the development of coronary atherosclerosis, the progression to plaque rupture and acute myocardial damage, with a greater heterogeneity in women.
  •  
27.
  • Emmert, Kirsten, et al. (författare)
  • Meta-analysis of real-time fMRI neurofeedback studies using individual participant data : How is brain regulation mediated?
  • 2016
  • Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 124:Part A, s. 806-812
  • Tidskriftsartikel (refereegranskat)abstract
    • An increasing number of studies using real-time fMRI neurofeedback have demonstrated that successful regulation of neural activity is possible in various brain regions. Since these studies focused on the regulated region(s), little is known about the target-independent mechanisms associated with neurofeedback-guided control of brain activation, i.e. the regulating network. While the specificity of the activation during self-regulation is an important factor, no study has effectively determined the network involved in self-regulation in general. In an effort to detect regions that are responsible for the act of brain regulation, we performed a post-hoc analysis of data involving different target regions based on studies from different research groups. We included twelve suitable studies that examined nine different target regions amounting to a total of 175 subjects and 899 neurofeedback runs. Data analysis included a standard first-(single subject, extracting main paradigm) and second-level (single subject, all runs) general linear model (GLM) analysis of all participants taking into account the individual timing. Subsequently, at the third level, a random effects model GLM included all subjects of all studies, resulting in an overall mixed effects model. Since four of the twelve studies had a reduced field of view (FoV), we repeated the same analysis in a subsample of eight studies that had a well-overlapping FoV to obtain a more global picture of self-regulation. The GLM analysis revealed that the anterior insula as well as the basal ganglia, notably the striatum, were consistently active during the regulation of brain activation across the studies. The anterior insula has been implicated in interoceptive awareness of the body and cognitive control. Basal ganglia are involved in procedural learning, visuomotor integration and other higher cognitive processes including motivation. The larger FoV analysis yielded additional activations in the anterior cingulate cortex, the dorsolateral and ventrolateral prefrontal cortex, the temporo-parietal area and the visual association areas including the temporo-occipital junction. In conclusion, we demonstrate that several key regions, such as the anterior insula and the basal ganglia, are consistently activated during self-regulation in real-time fMRI neurofeedback independent of the targeted region-ofinterest. Our results imply that if the real-time fMRI neurofeedback studies target regions of this regulation network, such as the anterior insula, care should be given whether activation changes are related to successful regulation, or related to the regulation process per se. Furthermore, future research is needed to determine how activation within this regulation network is related to neurofeedback success.
  •  
28.
  • Engwall, Olov, et al. (författare)
  • Learner and teacher perspectives on robot-led L2 conversation practice
  • 2024
  • Tidskriftsartikel (refereegranskat)abstract
    • This article focuses on designing and evaluating conversation practice in a second language (L2) with a robot that employs human spoken and non-verbal interaction strategies. Based on an analysis of previous work and semi-structured interviews with L2 learners and teachers, recommendations for robot-led conversation practice for adult learners at intermediate level are first defined, focused on language learning, on the social context, on the conversational structure and on verbal and visual aspects of the robot moderation. Guided by these recommendations, an experiment is set up, in which 12 pairs of L2 learners of Swedish interact with a robot in short social conversations. These robot-learner interactions are evaluated through post-session interviews with the learners, teachers’ ratings of the robot’s behaviour and analyses of the video-recorded conversations, resulting in a set of guidelines for robot-led conversation practice, in particular: 1) Societal and personal topics increase the practice’s meaningfulness for learners. 2) Strategies and methods for providing corrective feedback during conversation practice need to be explored further. 3) Learners should be encouraged to support each other if the robot has difficulties adapting to their linguistic level. 4) The robot should establish a social relationship, by contributing with its own story, remembering the participants’ input, and making use of non-verbal communication signals. 5) Improvements are required regarding naturalness and intelligibility of text-to-speech synthesis, in particular its speed, if it is to be used for conversations with L2 learners. 
  •  
29.
  •  
30.
  • Goodwillie, Carol, et al. (författare)
  • Correlated evolution of mating system and floral display traits in flowering plants and its implications for the distribution of mating system variation
  • 2010
  • Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 185, s. 311-321
  • Tidskriftsartikel (refereegranskat)abstract
    • New Phytologist (2009)  Reduced allocation to structures for pollinator attraction is predicted in selfing species. We explored the association between outcrossing and floral display in a broad sample of angiosperms. We used the demonstrated relationship to test for bias against selfing species in the outcrossing rate distribution, the shape of which has relevance for the stability of mixed mating.  Relationships between outcrossing rate, flower size, flower number and floral display, measured as the product of flower size and number, were examined using phylogenetically independent contrasts. The distribution of floral displays among species in the outcrossing rate database was compared with that of a random sample of the same flora.  The outcrossing rate was positively associated with the product of flower size and number; individually, components of display were less strongly related to outcrossing. Compared with a random sample, species in the outcrossing rate database showed a deficit of small floral display sizes.  We found broad support for reduced allocation to attraction in selfing species. We suggest that covariation between mating systems and total allocation to attraction can explain the deviation from expected trade-offs between flower size and number. Our results suggest a bias against estimating outcrossing rates in the lower half of the distribution, but not specifically against highly selfing species.
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31.
  • Grohs, Melody N., et al. (författare)
  • Prenatal maternal and childhood bisphenol a exposure and brain structure and behavior of young children
  • 2019
  • Ingår i: Environmental Health. - : Springer Science and Business Media LLC. - 1476-069X. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Bisphenol A (BPA) is commonly used in the manufacture of plastics and epoxy resins. In North America, over 90% of the population has detectable levels of urinary BPA. Human epidemiological studies have reported adverse behavioral outcomes with BPA exposure in children, however, corresponding effects on children's brain structure have not yet been investigated. The current study examined the association between prenatal maternal and childhood BPA exposure and white matter microstructure in children aged 2 to 5 years, and investigated whether brain structure mediated the association between BPA exposure and child behavior.Methods: Participants were 98 mother-child pairs who were recruited between January 2009 and December 2012. Total BPA concentrations in spot urine samples obtained from mothers in the second trimester of pregnancy and from children at 3-4 years of age were analyzed. Children participated in a diffusion magnetic resonance imaging (MRI) scan at age 2-5 years (3.7 +/- 0.8 years). Associations between prenatal maternal and childhood BPA and children's fractional anisotropy and mean diffusivity of 10 isolated white matter tracts were investigated, controlling for urinary creatinine, child sex, and age at the time of MRI. Post-hoc analyses examined if alterations in white matter mediated the relationship of BPA and children's scores on the Child Behavior Checklist (CBCL).Results: Prenatal maternal urinary BPA was significantly associated with child mean diffusivity in the splenium and right inferior longitudinal fasciculus. Splenium diffusivity mediated the relationship between maternal prenatal BPA levels and children's internalizing behavior (indirect effect: beta = 0.213, CI [0.0167, 0.564]). No significant associations were found between childhood BPA and white matter microstructure.Conclusions: This study provides preliminary evidence for the neural correlates of BPA exposure in humans. Our findings suggest that prenatal maternal exposure to BPA may lead to alterations in white matter microstructure in preschool aged children, and that such alterations mediate the relationship between early life exposure to BPA and internalizing problems.
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32.
  • Jenniskens, Peter, et al. (författare)
  • Fall, recovery, and characterization of the Novato L6 chondrite breccia
  • 2014
  • Ingår i: Meteoritics and Planetary Science. - : Wiley. - 1086-9379. ; 49:8, s. 1388-1425
  • Tidskriftsartikel (refereegranskat)abstract
    • The Novato L6 chondrite fragmental breccia fell in California on 17 October 2012, and was recovered after the Cameras for Allsky Meteor Surveillance (CAMS) project determined the meteor's trajectory between 95 and 46 km altitude. The final fragmentation from 42 to 22 km altitude was exceptionally well documented by digital photographs. The first sample was recovered before rain hit the area. First results from a consortium study of the meteorite's characterization, cosmogenic and radiogenic nuclides, origin, and conditions of the fall are presented. Some meteorites did not retain fusion crust and show evidence of spallation. Before entry, the meteoroid was 35 +/- 5 cm in diameter (mass 80 +/- 35 kg) with a cosmic-ray exposure age of 9 +/- 1 Ma, if it had a one-stage exposure history. A two-stage exposure history is more likely, with lower shielding in the last few Ma. Thermoluminescence data suggest a collision event within the last similar to 0.1 Ma. Novato probably belonged to the class of shocked L chondrites that have a common shock age of 470 Ma, based on the U, Th-He age of 420 +/- 220 Ma. The measured orbits of Novato, Jesenice, and Innisfree are consistent with a proposed origin of these shocked L chondrites in the Gefion asteroid family, perhaps directly via the 5: 2 mean-motion resonance with Jupiter. Novato experienced a stronger compaction than did other L6 chondrites of shock-stage S4. Despite this, a freshly broken surface shows a wide range of organic compounds.
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33.
  • Joffrin, E., et al. (författare)
  • Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
  • 2019
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
  • Forskningsöversikt (refereegranskat)abstract
    • For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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34.
  • Lawler, Mark, et al. (författare)
  • A Catalyst for Change: The European Cancer Patient's Bill of Rights.
  • 2014
  • Ingår i: The Oncologist. - : Oxford University Press (OUP). - 1549-490X .- 1083-7159.
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Cancer Concord is a unique patient-centered partnership that will act as a catalyst to achieve improved access to an optimal standard of cancer care and research for European citizens. In order to provide tangible benefits for European cancer patients, the partnership proposes the creation of a “European Cancer Patient's Bill of Rights,” a patient charter that will underpin equitable access to an optimal standard of care for Europe's citizens.
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35.
  • Leimbach, David, 1992, et al. (författare)
  • The electron affinity of astatine
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the most important properties influencing the chemical behavior of an element is the electron affinity (EA). Among the remaining elements with unknown EA is astatine, where one of its isotopes, 211At, is remarkably well suited for targeted radionuclide therapy of cancer. With the At− anion being involved in many aspects of current astatine labeling protocols, the knowledge of the electron affinity of this element is of prime importance. Here we report the measured value of the EA of astatine to be 2.41578(7) eV. This result is compared to state-of-the-art relativistic quantum mechanical calculations that incorporate both the Breit and the quantum electrodynamics (QED) corrections and the electron–electron correlation effects on the highest level that can be currently achieved for many-electron systems. The developed technique of laser-photodetachment spectroscopy of radioisotopes opens the path for future EA measurements of other radioelements such as polonium, and eventually super-heavy elements.
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36.
  • Lo, Hiu Kwan, et al. (författare)
  • Factors associated with work ability following exercise interventions for people with chronic whiplash-associated disorders : Secondary analysis of a randomized controlled trial
  • 2018
  • Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 50:9, s. 828-836
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the efficacy of exercise interventions and factors associated with changes in work ability for people with chronic whiplash-associated disorders. Design: Secondary analysis of a single-blind, randomized multi-centre controlled trial. Setting: Interventions were conducted in Swedish primary care settings. Patients: A total of 165 individuals with chronic whiplash-associated disorders grade II-III. Methods: Participants were randomly allocated to neck-specific exercise, neck-specific exercise with a behavioural approach, or prescribed physical activity interventions. Work ability was evaluated with the Work Ability Index at baseline, 3, 6 and 12 months. Results: The neck-specific exercise with a behavioural approach intervention significantly improved work ability compared with the prescribed physical activity intervention (3 months, p = 0.03; 6 months, p = 0.01; 12 months, p = 0.01), and neck-specific exercise at 12 months (p = 0.01). Neck-specific exercise was better than the prescribed physical activity intervention at 6 months (p = 0.05). An increase in work ability from baseline to one year for the neck-specific exercise with a behavioural approach group (p < 0.01) was the only significant within-group difference. Higher self-rated physical demands at work, greater disability, greater depression and poorer financial situation were associated with poorer work ability (p < 0.01). Conclusion: This study found that neck-specific exercise with a behavioural approach intervention was better at improving self-reported work ability than neck-specific exercise or prescribed physical activity. Improvement in work ability is associated with a variety of factors.
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37.
  • Mangerel, Joshua, et al. (författare)
  • Alternative lengthening of telomerases is enriched in, and impacts survival of TP53 mutant pediatric malignant brain tumors
  • 2014
  • Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 128:6, s. 853-862
  • Tidskriftsartikel (refereegranskat)abstract
    • Although telomeres are maintained in most cancers by telomerase activation, a subset of tumors utilize alternative lengthening of telomeres (ALT) to sustain self-renewal capacity. In order to study the prevalence and significance of ALT in childhood brain tumors we screened 517 pediatric brain tumors using the novel C-circle assay. We examined the association of ALT with alterations in genes found to segregate with specific histological phenotypes and with clinical outcome. ALT was detected almost exclusively in malignant tumors (p = 0.001). ALT was highly enriched in primitive neuroectodermal tumors (12 %), choroid plexus carcinomas (23 %) and high-grade gliomas (22 %). Furthermore, in contrast to adult gliomas, pediatric low grade gliomas which progressed to high-grade tumors did not exhibit the ALT phenotype. Somatic but not germline TP53 mutations were highly associated with ALT (p = 1.01 × 10(-8)). Of the other alterations examined, only ATRX point mutations and reduced expression were associated with the ALT phenotype (p = 0.0005). Interestingly, ALT attenuated the poor outcome conferred by TP53 mutations in specific pediatric brain tumors. Due to very poor prognosis, one year overall survival was quantified in malignant gliomas, while in children with choroid plexus carcinoma, five year overall survival was investigated. For children with TP53 mutant malignant gliomas, one year overall survival was 63 ± 12 and 23 ± 10 % for ALT positive and negative tumors, respectively (p = 0.03), while for children with TP53 mutant choroid plexus carcinomas, 5 years overall survival was 67 ± 19 and 27 ± 13 % for ALT positive and negative tumors, respectively (p = 0.07). These observations suggest that the presence of ALT is limited to a specific group of childhood brain cancers which harbor somatic TP53 mutations and may influence the outcome of these patients. Analysis of ALT may contribute to risk stratification and targeted therapies to improve outcome for these children.
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38.
  • Murari, A., et al. (författare)
  • A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
  • 2024
  • Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
  • 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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39.
  • Pakhira, Santanu, et al. (författare)
  • Suppression of antiferromagnetic order and strong ferromagnetic spin fluctuations in Ca(Co1−xNix)2−yAs2 single crystals
  • 2021
  • Ingår i: Physical Review B. - 2469-9950 .- 2469-9969. ; 104:9
  • Tidskriftsartikel (refereegranskat)abstract
    • CaCo2−yAs2 is a unique itinerant system having strong magnetic frustration. Here, we report the effect of electron doping on the physical properties resulting from Ni substitutions for Co. The single crystals of Ca(Co1−xNix)2−yAs2 were characterized by single-crystal x-ray diffraction, energy-dispersive x-ray spectroscopy, magnetization M versus temperature T, magnetic field H, time t, and heat capacity Cp(H,T) measurements. The A-type antiferromagnetic (AFM) transition temperature TN=52 K for x=0 decreases to 22 K with only 3% Ni substitution and is completely suppressed for x>0.16. For 0.11≤x≤0.52 strong ferromagnetic (FM) fluctuations develop as revealed by magnetic susceptibility χ(T)=M(T)/H measurements. For x=0.11 and 0.16 competing AFM and FM interactions result in a reentrant spin-glass behavior below TN, as evidenced by the observations of thermomagnetic hysteresis and magnetic relaxation. Enhanced FM fluctuations are also found for the x=0.21 and 0.31 crystals, where χc increases significantly at low T. A large χ anisotropy in these compositions where χc is up to a factor of two larger than χab suggests that the FM spin fluctuations are quasi-1D in nature. Weak ferromagnetic contributions to the magnetization are found at T=2 K for x=0.11–0.31. Heat-capacity Cp(T) measurements reveal the presence of FM quantum spin fluctuations for 0.11≤x≤0.52, where a logarithmic T dependence of Cp(T)/T is observed at low T. The suppression of AFM order by the development of strong FM fluctuations in Ca(Co1−xNix)2−yAs2 crystals suggests the presence of a FM quantum-critical point at x≈0.20. Our density-functional theory (DFT) calculations confirm that FM fluctuations are enhanced by Ni substitutions for Co in CaCo2−yAs2. The Sommerfeld electronic heat-capacity coefficient is enhanced for x=0, 0.21, and 0.42 by about a factor of two compared to DFT calculations of the density of states (DOS) at the Fermi energy, suggesting an enhancement of the DOS from electron-phonon and/or electron-electron interactions. The crystals with x>0.52 do not exhibit FM spin fluctuations or magnetic order at T≥1.8 K, which was found from the DFT calculations to arise from a Stoner transition. Superconductivity is not observed above 1.8 K for any of the compositions. Neutron-diffraction studies of crystals with x=0.11 and 0.16 in the crossover regime (0.1≲x≲0.2) show no evidence of A-type ordering as observed in the parent compound with x=0. Furthermore, no other common magnetic structures, such as ferromagnetic (FM), helical stacking of in-plane FM layers, or in-plane AFM structure, are found with an ordered moment greater than the uncertainty of 0.05μB per transition-metal atom.
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40.
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41.
  • Sangeetha, N. S., et al. (författare)
  • First-order antiferromagnetic transitions of SrMn2P2 and CaMn2P2 single crystals containing corrugated-honeycomb Mn sublattices
  • 2021
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:44
  • Tidskriftsartikel (refereegranskat)abstract
    • SrMn2P2 and CaMn2P2 are insulators that adopt the trigonal CaAl2Si2-type structure containing corrugated Mn honeycomb layers. Magnetic susceptibility χ and heat capacity versus temperature T data reveal a weak first-order antiferromagnetic (AFM) transition at the Néel temperature TN=53(1) K for SrMn2P2 and a strong first-order AFM transition at TN=69.8(3) K for CaMn2P2. Both compounds exhibit isotropic and nearly T-independent χ(T≤TN), suggesting magnetic structures in which nearest-neighbor moments are aligned at ≈120° to each other. The 31P NMR measurements confirm the strong first-order transition in CaMn2P2 but show critical slowing down above TN for SrMn2P2, thus also evidencing second-order character. The 31P NMR measurements indicate that the AFM structure of CaMn2P2 is commensurate with the lattice whereas that of SrMn2P2 is incommensurate. These first-order AFM transitions are unique among the class of (Ca, Sr, Ba)Mn2 (P, As, Sb, Bi)2 compounds that otherwise exhibit second-order AFM transitions. This result challenges our understanding of the circumstances under which first-order AFM transitions occur.
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42.
  • Shrestha, Shakti R., Dr, et al. (författare)
  • Understanding the wider social and economic context of post-earthquake cordons : A comparative case study between Christchurch, Aotearoa (New Zealand) and L'Aquila, Italy
  • 2022
  • Ingår i: Earthquake spectra. - : Sage Publications. - 8755-2930 .- 1944-8201. ; 38:4, s. 2731-2753
  • Tidskriftsartikel (refereegranskat)abstract
    • Post-earthquake cordons have been used after seismic events around the world. However, there is limited understanding of cordons and how contextual information such as geography, sociocultural characteristics, economy, and institutional and governance structures affects decisions and operational procedures, including aspects related to spatial and temporal attributes of cordon establishment. This research aims to fill the gap in cordon knowledge through a qualitative comparative case study of two cities: Christchurch, New Zealand (Mw 6.2 earthquake, February 2011) and L’Aquila, Italy (Mw 6.3 earthquake, 2009). Both cities suffered comprehensive damage to their city centers and had cordons established for extended periods of time. Data collection was done through purposive and snowball sampling whereby 23 key informants were interviewed in total. Research participants held expert knowledge in their roles and responsibilities, that is, council members, emergency managers, politicians, business/insurance representatives, academics, and police. Results illustrate that cordons were primarily established to ensure safety of people and to maintain security. The extent and duration of the cordons were affected by the recovery approaches taken in respective cities, that is, in Christchurch demolition was widely undertaken which supported recovery and allowed for faster removal of cordons. In contrast, authorities in L’Aquila placed high value on heritage buildings which led to recovery strategy based on preserving and restoring most of the buildings which extended the duration of cordon. Extended cordons have many similarities but evolve overtime. This evolution of cordons is affected by site-specific needs; thus, cordons should be understood and planned based on contextual realities.
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43.
  • Shrestha, Shakti, Dr, et al. (författare)
  • To cordon or not to cordon : The inherent complexities of post-earthquake cordoning learned from Christchurch and Wellington experiences
  • 2021
  • Ingår i: Bulletin of the New Zealand Society for Earthquake Engineering. - : New Zealand Society for Earthquake Engineering. - 1174-9857 .- 2324-1543. ; 54:1, s. 40-48
  • Tidskriftsartikel (refereegranskat)abstract
    • The use of post-earthquake cordons as a tool to support emergency managers after an event has been documented around the world. However, there is limited research that attempts to understand the inherent complexities of cordoning once applied, particularly the longer-term impacts and consequences. This research aims to fill the gap by providing a detailed understanding of cordons, their management, and the implications of cordoning in a post-earthquake environment. We use a qualitative method to understand cordons through case studies of two cities where cordons were used at different temporal and spatial scales: Christchurch (M6.3, February 2011) and Wellington (M7.8 in Kaikōura, November 2016), New Zealand. Data was collected through 21 key informant interviews obtained through purposive and snowball sampling of participants who were directly or indirectly involved in a decision-making role and/or had influence in relation to the cordoning process. The participants were from varying backgrounds and roles i.e. emergency managers, council members, business representatives, insurance representatives, police, and communication managers. We find that cordons are used primarily as a tool to control access for the purpose of life safety and security, but cordons can also be adapted to support recovery. Broadly, our analysis suggests two key aspects, ‘decision-making’ and ‘operations and management’, which overlap and interact as part of a complex system. The underlying complexity arises in large part due to the multitude of sectors affected by cordons: economics, law, politics, governance, evacuation, civil liberties, available resources etc. The complexity further increases as the duration of cordoning is extended.
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44.
  • Shultz, M. E., et al. (författare)
  • MOBSTER - III. HD62658 : a magnetic Bp star in an eclipsing binary with a non-magnetic 'identical twin'
  • 2019
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 490:3, s. 4154-4165
  • Tidskriftsartikel (refereegranskat)abstract
    • HD62658 (B9p V) is a little-studied chemically peculiar star. Light curves obtained by the Kilodegree Extremely Little Telescope (KELT) and Transiting Exoplanet Survey Satellite (TESS) show clear eclipses with a period of about 4.75 d, as well as out-of-eclipse brightness modulation with the same 4.75 d period, consistent with synchronized rotational modulation of surface chemical spots. High-resolution ESPaDOnS circular spectropolarimetry shows a clear Zeeman signature in the line profile of the primary; there is no indication of a magnetic field in the secondary. PHOEBE modelling of the light curve and radial velocities indicates that the two components have almost identical masses of about 3 M-circle dot. The primary's longitudinal magnetic field < B-z > varies between about +100 and -250 G, suggesting a surface magnetic dipole strength B-d = 850 G. Bayesian analysis of the Stokes V profiles indicates B-d = 650 G for the primary and B-d < 110 G for the secondary. The primary's line profiles are highly variable, consistent with the hypothesis that the out-of-eclipse brightness modulation is a consequence of rotational modulation of that star's chemical spots. We also detect a residual signal in the light curve after removal of the orbital and rotational modulations, which might be pulsational in origin; this could be consistent with the weak line profile variability of the secondary. This system represents an excellent opportunity to examine the consequences of magnetic fields for stellar structure via comparison of two stars that are essentially identical with the exception that one is magnetic. The existence of such a system furthermore suggests that purely environmental explanations for the origin of fossil magnetic fields are incomplete.
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45.
  • Soultan, Alaaeldin, et al. (författare)
  • The future distribution of wetland birds breeding in Europe validated against observed changes in distribution
  • 2022
  • Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9318 .- 1748-9326. ; 17:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Wetland bird species have been declining in population size worldwide as climate warming and land-use change affect their suitable habitats. We used species distribution models (SDMs) to predict changes in range dynamics for 64 non-passerine wetland birds breeding in Europe, including range size, position of centroid, and margins. We fitted the SDMs with data collected for the first European Breeding Bird Atlas and climate and land-use data to predict distributional changes over a century (the 1970s-2070s). The predicted annual changes were then compared to observed annual changes in range size and range centroid over a time period of 30 years using data from the second European Breeding Bird Atlas. Our models successfully predicted ca. 75% of the 64 bird species to contract their breeding range in the future, while the remaining species (mostly southerly breeding species) were predicted to expand their breeding ranges northward. The northern margins of southerly species and southern margins of northerly species, both, predicted to shift northward. Predicted changes in range size and shifts in range centroids were broadly positively associated with the observed changes, although some species deviated markedly from the predictions. The predicted average shift in core distributions was ca. 5 km yr-1 towards the north (5% northeast, 45% north, and 40% northwest), compared to a slower observed average shift of ca. 3.9 km yr-1. Predicted changes in range centroids were generally larger than observed changes, which suggests that bird distribution changes may lag behind environmental changes leading to 'climate debt'. We suggest that predictions of SDMs should be viewed as qualitative rather than quantitative outcomes, indicating that care should be taken concerning single species. Still, our results highlight the urgent need for management actions such as wetland creation and restoration to improve wetland birds' resilience to the expected environmental changes in the future.
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46.
  • Tayleur, Catherine, et al. (författare)
  • Rise of the generalists: evidence for climate driven homogenization in avian communities
  • 2012
  • Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-8238 .- 1466-822X. ; 21:5, s. 568-578
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Biogeographical evidence suggests a strong link between climate and patterns of species diversity, and climate change is known to cause range shifts. However, there is little understanding of how shifts affect community composition and we lack empirical evidence of recent impacts of climate change on the diversity of vertebrates. Using a long-term comprehensive dataset on bird abundance, we explore recent patterns of change in different components of species diversity and avian communities, and postulate a process to explain the observed changes in diversity and specialization. Location Britain. Methods We used Breeding Bird Survey data for Britain from 1994 to 2006 to calculate site-specific diversity and community specialization indices. We modelled these indices using generalized additive models to examine the relationship between local climate and spatial and temporal trends in community metrics and the relationship between changes in diversity and specialization. Results Local temperature was positively associated with alpha diversity, which increased over the study period, supporting empirical and theoretical predictions of the effect of climate warming. Diversity increased in all habitats, but the rate of increase was greatest in upland areas. However, temperature was negatively associated with community specialization indices, which declined over the same period. Our modelling revealed a nonlinear relationship between community specialization and species diversity. Main conclusions Our models of diversity and specialization provide stark empirical evidence for a link between warming climate and community homogenization. Over a 13-year period of warming temperatures, diversity indices increased while average community specialization decreased. We suggest that the observed diversity increases were most likely driven by range expansion of generalist species and that future warming is likely to increase homogenization of community structure. When assessed in combination, diversity and specialization measures provide a powerful index for monitoring the impacts of climate change.
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47.
  • Thompson, Rachel, et al. (författare)
  • RD-Connect : An Integrated Platform Connecting Databases, Registries, Biobanks and Clinical Bioinformatics for Rare Disease Research
  • 2014
  • Ingår i: Journal of general internal medicine. - : Springer Science and Business Media LLC. - 0884-8734 .- 1525-1497. ; 29:S3, s. S780-S787
  • Forskningsöversikt (refereegranskat)abstract
    • Research into rare diseases is typically fragmented by data type and disease. Individual efforts often have poor interoperability and do not systematically connect data across clinical phenotype, genomic data, biomaterial availability, and research/trial data sets. Such data must be linked at both an individual-patient and whole-cohort level to enable researchers to gain a complete view of their disease and patient population of interest. Data access and authorization procedures are required to allow researchers in multiple institutions to securely compare results and gain new insights. Funded by the European Union's Seventh Framework Programme under the International Rare Diseases Research Consortium (IRDiRC), RD-Connect is a global infrastructure project initiated in November 2012 that links genomic data with registries, biobanks, and clinical bioinformatics tools to produce a central research resource for rare diseases.
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48.
  • Titov, Nickolai, et al. (författare)
  • MindSpot Clinic : An Accessible, Efficient, and Effective Online Treatment Service for Anxiety and Depression.
  • 2015
  • Ingår i: Psychiatric Services. - : American Psychiatric Association Publishing. - 1075-2730 .- 1557-9700. ; 66:10, s. 1043-1050
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The main objective of this study was to report the feasibility of delivering online cognitive-behavioral therapy (iCBT) treatments for anxiety and depression in a national public mental health service.METHODS: A prospective noncontrolled cohort study was conducted of all patients who began assessment or treatment at the MindSpot Clinic from January through December 2013. Clinic services were used by a representative cross-section of the Australian population. Mean age at assessment was 36.4±13.0 years, and age range was 18-86 years. Patients completed one of four online courses over eight weeks, during which they received weekly support from a therapist via telephone or secure e-mail. Primary outcome measures were the nine-item Patient Health Questionnaire (PHQ-9) and the seven-item Generalized Anxiety Disorder scale (GAD-7) administered at posttreatment and three months posttreatment.RESULTS: A total of 10,293 adults who self-identified as having problems with anxiety or depression commenced assessment, and 7,172 completed the assessment and were eligible for analysis. Of these, 2,049 enrolled in a course and 1,471 completed the course, for a course completion rate of 71.8%. Moderate to large noncontrolled effect sizes (Cohen's d=.67-1.66, 95% confidence interval=.08-2.07) were found from assessment to three-month follow-up. At posttreatment and follow-up, reliable recovery ranged from 46.7% to 51.1%, and deterioration ranged from 1.9% to 3.8%. Mean total therapist time per patient was 111.8±61.6 minutes.CONCLUSIONS: The MindSpot Clinic produced treatment outcomes that were comparable to results from published clinical trials of iCBT. This model of service delivery represents an innovative method of providing accessible, low-cost, effective, and acceptable mental health services to many people who currently are not receiving care.
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49.
  • Weber, Roland, et al. (författare)
  • Dioxin- and POP-contaminated sites—contemporary and future relevance and challenges : Overview on background, aims and scope of the series
  • 2008
  • Ingår i: Environmental Science and Pollution Research. - : Springer Science and Business Media LLC. - 0944-1344 .- 1614-7499. ; 15:5, s. 363-393
  • Tidskriftsartikel (refereegranskat)abstract
    • Background, aim and scope: Once they have been generated, polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and other persistent organic pollutants (POPs) can persist in soils and sediments and in waste repositories for periods extending from decades to centuries. In 1994, the US EPA concluded that contaminated sites and other reservoirs are likely to become the major source of contemporary pollution problems with these substances. With this in mind, this article is the first in a new series in ESPR under the title ‘Case Studies on Dioxin and POP Contaminated Sites—Contemporary and Future Relevance and Challenges’, which will address this important issue. The series will document various experiences from sites contaminated with PCDD/F and other POPs. This article provides an overview of the content of the articles comprising the series. In addition, it provides a review of the subject in its own right and identifies the key issues arising from dioxin/POP-contaminated sites. Additionally, it highlights the important conclusions that can be drawn from these examples. The key aim of this article and of the series as a whole is to provide a comprehensive overview of the types of PCDD/F contaminated sites that exist as a result of historical activities. It details the various processes whereby these sites became contaminated and attempts to evaluate their contemporary relevance as sources of PCDD/Fs and other POPs. It also details the various strategies used to assess these historical legacies of contamination and the concepts developed, or which are under development, to effect their remediation.Main features: Special sessions on ‘Contaminated sites—Cases, remediation, risk and policy’ were held at the DIOXIN conferences in 2006 and 2007, and this theme will be continued at DIOXIN 2008 to be held in Birmingham. Selected cases from the approximately 70 contributions made to these sessions, together with some additional invited case studies are outlined together with the key issues they raise. By evaluating these cases and adding details of experiences published in the current literature, an overview will be given of the different features and challenges of dioxin and POP-contaminated sites.Results: This article provides a systematic categorisation of types of PCDD/F and POP-contaminated sites. These are categorised according to the chemical or manufacturing process, which generated the PCDD/Fs or POPs and also includes the use and disposal aspects of the product life cycle in question. The highest historical PCDD/F and dioxin-like polychlorinated biphenyl (PCB) contamination burdens have arisen as a result of the production of chlorine and of chlorinated organic chemicals. In particular, the production of chlorinated pesticides, PCBs and the related contaminated waste streams are identified being responsible for historical releases of toxic equivalents (TEQs) at a scale of many tonnes. Along with such releases, major PCDD/F contaminated sites have been created through the application or improper disposal of contaminated pesticides, PCBs and other organochlorine chemicals, as well through the recycling of wastes and their attempted destruction. In some extreme examples, PCDD/F contaminated sites have also resulted from thermal processes such as waste incinerators, secondary metal industries or from the recycling or deposition of specific waste (e.g. electronic waste or car shredder wastes), which often contain chlorinated or brominated organic chemicals. The examples of PCDD/F and dioxin-like PCB contamination of fish in European rivers or the impact of contaminated sites upon fishing grounds and upon other food resources demonstrate the relevance of these historical problems to current and future human generations. Many of the recent food contamination problems that have emerged in Europe and elsewhere demonstrate how PCDD/F and dioxin like PCBs from historical sources can directly contaminate human and animal feedstuffs and indeed highlight their considerable contemporary relevance in this respect. Accordingly, some key experiences and lessons learnt regarding the production, use, disposal and remediation of POPs from the contaminated sites are summarised.Discussion: An important criterion for evaluating the significance and risks of PCDD/Fs and other POPs at contaminated sites is their present or future potential for mobility. This, in turn, determines to a large degree their propensity for off-site transport and environmental accessibility. The detailed evaluation of contaminated site cases reveals different site-specific factors, which influence the varied pathways through which poor water-soluble POPs can be mobilised. Co-contaminants with greater water solubility are also typically present at such sites. Hence, pumping of groundwater (pump and treat) is often required in addition to attempting to physically secure a site. At an increasing number of contaminated sites, securing measures are failing after relatively short time spans compared to the time horizon, which applies to persistent organic pollutant contamination. Due to the immense costs and challenges associated with remediation of contaminated sites ‘monitored natural attenuation’ is increasingly gaining purchase as a conceptual remediation approach. However, these concepts may well prove limited in their practical application to contaminated sites containing persistent organic pollutants and other key pollutants like heavy metals.Conclusions: It is inevitable, therefore, that dioxin/POP-contaminated sites will remain of contemporary and future relevance. They will continue to represent an environmental issue for future generations to address. The securing and/or remediation of dioxin/POP-contaminated sites is very costly, generally in the order of tens or hundreds of millions of dollars. Secured landfills and secured production sites need to be considered as constructions not made for ‘eternity’ but built for a finite time scale. Accordingly, they will need to be controlled, supervised and potentially repaired/renewed. Furthermore, the leachates and groundwater impacted by these sites will require ongoing monitoring and potential further remediation. These activities result in high maintenance costs, which are accrued for decades or centuries and should, therefore, be compared to the fully sustainable option of complete remediation. The contaminated site case studies highlight that, while extensive policies and established funds for remediation exist in most of the industrialised western countries, even these relatively well-regulated and wealthy countries face significant challenges in the implementation of a remediation strategy. This highlights the fact that ultimately only the prevention of contaminated sites represents a sustainable solution for the future and that the Polluter Pays Principle needs to be applied in a comprehensive way to current problems and those which may emerge in the future.Recommendations and perspectives: With the continuing shift of industrial activities in developing and transition economies, which often have poor regulation (and weak self-regulation of industries), additional global challenges regarding POPs and other contaminated sites may be expected. In this respect, a comprehensive application of the “polluter pays principle” in these countries will also be a key to facilitate the clean-up of contaminated areas and the prevention of future contaminated sites. The threats and challenges of contaminated sites and the high costs of securing/remediating the problems highlight the need for a comprehensive approach based upon integrated pollution prevention and control. If applied to all polluting (and potentially polluting) industrial sectors around the globe, such an approach will prove to be both the cheapest and most sustainable way to underpin the development of industries in developing and transition economies.
  •  
50.
  • Winn, Alice A., et al. (författare)
  • Analysis of inbreeding depression in mixed-mating plants provides evidence for selective interference and stable mixed mating
  • 2011
  • Ingår i: Evolution. - : Wiley. - 0014-3820 .- 1558-5646. ; , s. 10.1111/j.1558-5646.2011.01462.x
  • Tidskriftsartikel (refereegranskat)abstract
    • Hermaphroditic individuals can produce both selfed and outcrossed progeny, termed mixed mating. General theory predicts that mixed-mating populations should evolve quickly toward high rates of selfing, driven by rapid purging of genetic load and loss of inbreeding depression (ID), but the substantial number of mixed-mating species observed in nature calls this prediction into question. Lower average ID reported for selfing than for outcrossing populations is consistent with purging and suggests that mixed-mating taxa in evolutionary transition will have intermediate ID. We compared the magnitude of ID from published estimates for highly selfing (r > 0.8), mixed-mating (0.2 ?r? 0.8), and highly outcrossing (r < 0.2) plant populations across 58 species. We found that mixed-mating and outcrossing taxa have equally high average lifetime ID (?= 0.58 and 0.54, respectively) and similar ID at each of four life-cycle stages. These results are not consistent with evolution toward selfing in most mixed-mating taxa. We suggest that prevention of purging by selective interference could explain stable mixed mating in many natural populations. We identify critical gaps in the empirical data on ID and outline key approaches to filling them.
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