| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Ederle, Joerg, et al.
(författare)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 5. |
- Valdes-Marquez, E., et al.
(författare)
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Relative effects of LDL-C on ischemic stroke and coronary disease A Mendelian randomization study
- 2019
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:11
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Tidskriftsartikel (refereegranskat)abstract
- Objective To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach. We undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity. A 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32-1.68, p = 1.1 x 10(-8)). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96-1.30, p = 0.14; p for heterogeneity = 2.6 x 10(-3)) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 x 10(-3)) when compared with that for CHD. In contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.
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| 6. |
- Pulit, SL, et al.
(författare)
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Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study.
- 2016
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Ingår i: The Lancet. Neurology. - 1474-4465. ; 15:2, s. 174-84
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additional susceptibility genes for stroke and its subtypes.To identify genetic loci associated with ischaemic stroke, we did a two-stage GWAS. In the first stage, we included 16851 cases with state-of-the-art phenotyping data and 32473 stroke-free controls. Cases were aged 16 to 104 years, recruited between 1989 and 2012, and subtypes of ischaemic stroke were recorded by centrally trained and certified investigators who used the web-based protocol, Causative Classification of Stroke (CCS). We constructed case-control strata by identifying samples that were genotyped on nearly identical arrays and were of similar genetic ancestral background. We cleaned and imputed data by use of dense imputation reference panels generated from whole-genome sequence data. We did genome-wide testing to identify stroke-associated loci within each stratum for each available phenotype, and we combined summary-level results using inverse variance-weighted fixed-effects meta-analysis. In the second stage, we did in-silico lookups of 1372 single nucleotide polymorphisms identified from the first stage GWAS in 20941 cases and 364736 unique stroke-free controls. The ischaemic stroke subtypes of these cases had previously been established with the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification system, in accordance with local standards. Results from the two stages were then jointly analysed in a final meta-analysis.We identified a novel locus (G allele at rs12122341) at 1p13.2 near TSPAN2 that was associated with large artery atherosclerosis-related stroke (first stage odds ratio [OR] 1·21, 95% CI 1·13-1·30, p=4·50×10(-8); joint OR 1·19, 1·12-1·26, p=1·30×10(-9)). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29-1·49, p=3·26×10(-19); joint OR 1·37, 1·30-1·45, p=2·79×10(-32)) and ZFHX3 (first stage OR 1·19, 1·11-1·27, p=2·93×10(-7); joint OR 1·17, 1·11-1·23, p=2·29×10(-10)) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18-1·42, p=3·50×10(-8); joint OR 1·24, 1·15-1·33, p=4·52×10(-9)) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2, which has previously been associated with all ischaemic stroke but not with any specific subtype, exceeded genome-wide significance in the meta-analysis of small artery stroke (first stage OR 1·20, 1·12-1·28, p=6·82×10(-8); joint OR 1·17, 1·11-1·23, p=2·92×10(-9)). Other loci associated with stroke in previous studies, including NINJ2, were not confirmed.Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specific. We identified a novel gene associated with large artery atherosclerosis stroke susceptibility. Follow-up studies will be necessary to establish whether the locus near TSPAN2 can be a target for a novel therapeutic approach to stroke prevention. In view of the subtype-specificity of the associations detected, the rich phenotyping data available in the Stroke Genetics Network (SiGN) are likely to be crucial for further genetic discoveries related to ischaemic stroke.US National Institute of Neurological Disorders and Stroke, National Institutes of Health.
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| 11. |
- Padwal, R., et al.
(författare)
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The obesity paradox in heart failure patients with preserved versus reduced ejection fraction: a meta-analysis of individual patient data
- 2014
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 38:8, s. 1110-1114
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Tidskriftsartikel (refereegranskat)abstract
- Background:In heart failure (HF), obesity, defined as body mass index (BMI) >/=30 kg m-2, is paradoxically associated with higher survival rates compared with normal-weight patients (the 'obesity paradox'). We sought to determine if the obesity paradox differed by HF subtype (reduced ejection fraction (HF-REF) versus preserved ejection fraction (HF-PEF)).Patients and Methods:A sub-analysis of the MAGGIC meta-analysis of patient-level data from 14 HF studies was performed. Subjects were divided into five BMI groups: <22.5, 22.5-24.9 (referent), 25-29.9, 30-34.9 and >/=35 kg m-2. Cox proportional hazards models adjusted for age, sex, aetiology (ischaemic or non-ischaemic), hypertension, diabetes and baseline blood pressure, stratified by study, were used to examine the independent association between BMI and 3-year total mortality. Analyses were conducted for the overall group and within HF-REF and HF-PEF groups.Results:BMI data were available for 23 967 subjects (mean age, 66.8 years; 32% women; 46% NYHA Class II; 50% Class III) and 5609 (23%) died by 3 years. Obese patients were younger, more likely to receive cardiovascular (CV) drug treatment, and had higher comorbidity burdens. Compared with BMI levels between 22.5 and 24.9 kg m-2, the adjusted relative hazards for 3-year mortality in subjects with HF-REF were: hazard ratios (HR)=1.31 (95% confidence interval=1.15-1.50) for BMI <22.5, 0.85 (0.76-0.96) for BMI 25.0-29.9, 0.64 (0.55-0.74) for BMI 30.0-34.9 and 0.95 (0.78-1.15) for BMI >/=35. Corresponding adjusted HRs for those with HF-PEF were: 1.12 (95% confidence interval=0.80-1.57) for BMI <22.5, 0.74 (0.56-0.97) for BMI 25.0-29.9, 0.64 (0.46-0.88) for BMI 30.0-34.9 and 0.71 (0.49-1.05) for BMI >/=35.Conclusions:In patients with chronic HF, the obesity paradox was present in both those with reduced and preserved ventricular systolic function. Mortality in both HF subtypes was U-shaped, with a nadir at 30.0-34.9 kg m-2.International Journal of Obesity advance online publication, 26 November 2013; doi:10.1038/ijo.2013.203.
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| 12. |
- Cooper, Michael W. D., et al.
(författare)
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Fission gas diffusion and release for Cr2O3-doped UO2 : From the atomic to the engineering scale
- 2021
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Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 545
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Tidskriftsartikel (refereegranskat)abstract
- The anticipated benefits of large grains in Cr2O3-doped UO2 pellets include improved mechanical and fission gas retention properties. To support the assessment of fission gas release (FGR) from doped pellets, the impact of doping on fission gas diffusivity for in-reactor conditions must be understood. In this work, we tackle this issue by informing the fission gas model within the BISON fuel performance code using material models developed at the atomic scale. The investigation of intra-granular fission gas diffusivity in Cr2O3-doped UO2 is carried out by adapting a cluster dynamics model that, accounting for UO2 thermochemistry, is capable of describing Xe diffusion under irradiation in undoped UO2 as the starting point. Using a thermodynamic analysis, it is shown that in stoichiometric UO2 with additions of Cr2O3, the oxygen potential is defined by the Cr-Cr2O3 two-phase equilibrium. Using the cluster dynamics model, the predicted Xe diffusivity in doped UO2 was significantly increased in both the intrinsic and irradiation-enhanced regimes compared to undoped UO2, as a result of higher concentrations of uranium and oxygen vacancies, respectively. This is a consequence of the more oxidizing conditions at high temperature, and more reducing conditions at low temperature, as a result of doping. Arrhenius functions have been fitted to the cluster dynamics results to enable implementation of the new diffusivities in the BISON fission gas behavior model. BISON simulations were carried out, showing the competing effects of the enlarged grains and the new fission gas diffusivity model, which act to suppress and enhance fission gas release, respectively. The new physics-informed model was validated against in-reactor experimental measurements under normal operation. Additionally, benchmarking was carried out for power ramp conditions. The predicted fission gas release agreed well with the experimental data, showing noticeable improvements over the standard UO2 model.
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| 15. |
- Gamble, LD, et al.
(författare)
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A G316A Polymorphism in the Ornithine Decarboxylase Gene Promoter Modulates MYCN-Driven Childhood Neuroblastoma
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- Ornithine decarboxylase (ODC1), a critical regulatory enzyme in polyamine biosynthesis, is a direct transcriptional target of MYCN, amplification of which is a powerful marker of aggressive neuroblastoma. A single nucleotide polymorphism (SNP), G316A, within the first intron of ODC1, results in genotypes wildtype GG, and variants AG/AA. CRISPR-cas9 technology was used to investigate the effects of AG clones from wildtype MYCN-amplified SK-N-BE(2)-C cells and the effect of the SNP on MYCN binding, and promoter activity was investigated using EMSA and luciferase assays. AG clones exhibited decreased ODC1 expression, growth rates, and histone acetylation and increased sensitivity to ODC1 inhibition. MYCN was a stronger transcriptional regulator of the ODC1 promoter containing the G allele, and preferentially bound the G allele over the A. Two neuroblastoma cohorts were used to investigate the clinical impact of the SNP. In the study cohort, the minor AA genotype was associated with improved survival, while poor prognosis was associated with the GG genotype and AG/GG genotypes in MYCN-amplified and non-amplified patients, respectively. These effects were lost in the GWAS cohort. We have demonstrated that the ODC1 G316A polymorphism has functional significance in neuroblastoma and is subject to allele-specific regulation by the MYCN oncoprotein.
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| 16. |
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| 17. |
- Lynch, S.A., et al.
(författare)
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Toward silicon-based lasers for terahertz sources
- 2006
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Ingår i: IEEE Journal of Selected Topics in Quantum Electronics. - 1077-260X .- 1558-4542. ; 12:6, s. 1570-1577
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Tidskriftsartikel (refereegranskat)abstract
- Producing an electrically pumped silicon-based laser at terahertz frequencies is gaining increased attention these days. This paper reviews the recent advances in the search for a silicon-based terahertz laser. Topics covered include resonant tunneling in p-type Si/SiGe, terahertz intersubband electroluminescence from quantum cascade structures, intersubband lifetime measurements in Si/SiGe quantum wells, enhanced optical guiding using buried suicide layers, and the potential for exploiting common impurity dopants in silicon such as boron and phosphorus to realize a terahertz laser. © 2006 IEEE.
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| 18. |
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| 19. |
- Nik-Zainal, Serena, et al.
(författare)
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Mutational Processes Molding the Genomes of 21 Breast Cancers
- 2012
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Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 149:5, s. 979-993
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Tidskriftsartikel (refereegranskat)abstract
- All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed "kataegis,'' was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed.
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| 20. |
- Nik-Zainal, Serena, et al.
(författare)
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The Life History of 21 Breast Cancers
- 2012
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Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 149:5
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Tidskriftsartikel (refereegranskat)abstract
- Cancer evolves dynamically as clonal expansions supersede one another driven by shifting selective pressures, mutational processes, and disrupted cancer genes. These processes mark the genome, such that a cancer's life history is encrypted in the somatic mutations present. We developed algorithms to decipher this narrative and applied them to 21 breast cancers. Mutational processes evolve across a cancer's lifespan, with many emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, and most mutations are found in just a fraction of tumor cells. Every tumor has a dominant subclonal lineage, representing more than 50% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent cell lineages capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis.
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| 21. |
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| 22. |
- Vergaro, Giuseppe, et al.
(författare)
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Cardiac biomarkers retain prognostic significance in patients with heart failure and chronic obstructive pulmonary disease
- 2021
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Ingår i: Journal of Cardiovascular Medicine. - : Wolters Kluwer. - 1558-2027 .- 1558-2035. ; 23:1, s. 28-36
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Chronic obstructive pulmonary disease (COPD) is a frequent comorbidity in patients with heart failure (HF). We assessed the influence of COPD on circulating levels and prognostic value of three HF biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), and soluble suppression of tumorigenesis-2 (sST2).Methods: Individual data from patients with chronic HF, known COPD status, NT-proBNP and hs-TnT values (n = 8088) were analysed. A subgroup (n = 3414) had also sST2 values.Results: Patients had a median age of 66 years (interquartile interval 57–74), 77% were men and 82% had HF with reduced ejection fraction. NT-proBNP, hs-TnT and sST2 were 1207 ng/l (487–2725), 17 ng/l (9–31) and 30 ng/ml (22–44), respectively. Patients with COPD (n = 1249, 15%) had higher NT-proBNP (P = 0.042) and hs-TnT (P < 0.001), but not sST2 (P = 0.165). Over a median 2.0-year follow-up (1.5–2.5), 1717 patients (21%) died, and 1298 (16%) died from cardiovascular causes; 2255 patients (28%) were hospitalized for HF over 1.8 years (0.9–2.1). NT-proBNP, hs-TnT and sST2 predicted the three end points regardless of COPD status. The best cut-offs from receiver-operating characteristics analysis were higher in patients with COPD than in those without. Patients with all three biomarkers higher than or equal to end-point- and COPD-status-specific cut-offs were also those with the worst prognosis.Conclusions: Among patients with HF, those with COPD have higher NT-proBNP and hs-TnT, but not sST2. All these biomarkers yield prognostic significance regardless of the COPD status.
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| 23. |
- Vergaro, Giuseppe, et al.
(författare)
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Circulating levels and prognostic cut-offs of sST2, hs-cTnT, and NT-proBNP in women vs. men with chronic heart failure
- 2022
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Ingår i: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 9:4, s. 2084-2095
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Tidskriftsartikel (refereegranskat)abstract
- Aims To define plasma concentrations, determinants, and optimal prognostic cut-offs of soluble suppression of tumorigenesis-2 (sST2), high-sensitivity cardiac troponin T (hs-cTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in women and men with chronic heart failure (HF). Methods and results Individual data of patients from the Biomarkers In Heart Failure Outpatient Study (BIOS) Consortium with sST2, hs-cTnT, and NT-proBNP measured were analysed. The primary endpoint was a composite of 1 year cardiovascular death and HF hospitalization. The secondary endpoints were 5 year cardiovascular and all-cause death. The cohort included 4540 patients (age 67 +/- 12 years, left ventricular ejection fraction 33 +/- 13%, 1111 women, 25%). Women showed lower sST2 (24 vs. 27 ng/mL, P < 0.001) and hs-cTnT level (15 vs. 20 ng/L, P < 0.001), and similar concentrations of NT-proBNP (1540 vs. 1505 ng/L, P = 0.408). Although the three biomarkers were confirmed as independent predictors of outcome in both sexes, the optimal prognostic cut-off was lower in women for sST2 (28 vs. 31 ng/mL) and hs-cTnT (22 vs. 25 ng/L), while NT-proBNP cut-off was higher in women (2339 ng/L vs. 2145 ng/L). The use of sex-specific cut-offs improved risk prediction compared with the use of previously standardized prognostic cut-offs and allowed to reclassify the risk of many patients, to a greater extent in women than men, and for hs-cTnT than sST2 or NT-proBNP. Specifically, up to 18% men and up to 57% women were reclassified, by using the sex-specific cut-off of hs-cTnT for the endpoint of 5 year cardiovascular death. Conclusions In patients with chronic HF, concentrations of sST2 and hs-cTnT, but not of NT-proBNP, are lower in women. Lower sST2 and hs-cTnT and higher NT-proBNP cut-offs for risk stratification could be used in women.
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| 24. |
- Vergaro, Giuseppe, et al.
(författare)
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NT-proBNP for Risk Prediction in Heart Failure : Identification of Optimal Cutoffs Across Body Mass Index Categories
- 2021
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Ingår i: JACC. Heart failure. - : American College of Cardiology. - 2213-1779 .- 2213-1787. ; 9:9, s. 653-663
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThe goal of this study was to assess the predictive power of N-terminal pro–B-type natriuretic peptide (NT-proBNP) and the decision cutoffs in heart failure (HF) across body mass index (BMI) categories.BackgroundConcentrations of NT-proBNP predict outcome in HF. Although the influence of BMI to reduce levels of NT-proBNP is known, the impact of obesity on prognostic value remains uncertain.MethodsIndividual data from the BIOS (Biomarkers In Heart Failure Outpatient Study) consortium were analyzed. Patients with stable HF were classified as underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), and mildly (BMI 30-34.9 kg/m2), moderately (BMI 35-39.9 kg/m2), or severely (BMI ≥40 kg/m2) obese. The prognostic role of NT-proBNP was tested for the endpoints of all-cause and cardiac death.ResultsThe study population included 12,763 patients (mean age 66 ± 12 years; 25% women; mean left ventricular ejection fraction 33% ± 13%). Most patients were overweight (n = 5,176), followed by normal weight (n = 4,299), mildly obese (n = 2,157), moderately obese (n = 612), severely obese (n = 314), and underweight (n = 205). NT-proBNP inversely correlated with BMI (β = –0.174 for 1 kg/m2; P < 0.001). Adding NT-proBNP to clinical models improved risk prediction across BMI categories, with the exception of severely obese patients. The best cutoffs of NT-proBNP for 5-year all-cause death prediction were lower as BMI increased (3,785 ng/L, 2,193 ng/L, 1,554 ng/L, 1,045 ng/L, 755 ng/L, and 879 ng/L, for underweight, normal weight, overweight, and mildly, moderately, and severely obese patients, respectively) and were higher in women than in men.ConclusionsNT-proBNP maintains its independent prognostic value up to 40 kg/m2 BMI, and lower optimal risk-prediction cutoffs are observed in overweight and obese patients.
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| 25. |
- Willadsen, E., et al.
(författare)
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Inter-rater reliability in classification of canonical babbling status based on canonical babbling ratio in infants with isolated cleft palate randomised to Timing of Primary Surgery for Cleft Palate (TOPS)
- 2023
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Ingår i: Clinical Linguistics & Phonetics. - : Informa UK Limited. - 0269-9206 .- 1464-5076. ; 37:1, s. 77-98
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Tidskriftsartikel (refereegranskat)abstract
- Canonical babbling (CB) is commonly defined as present when at least 15% of all syllables produced are canonical, in other words a canonical babbling ratio (CBR) >= 0.15. However, there is limited knowledge about inter-rater reliability in classification of CB status based on CBR and inter-rater differences in assessment of CBR. We investigated inter-rater reliability of experienced Speech Language Therapists (SLTs) on: classification of CB status based on CBR >= 0.15, CBRs and the total number of syllables per infant used to calculate CBR. Each infant (n = 484) was video-recorded at a clinical site in play interaction with their parent as part of the randomised controlled trial Timing of Primary Surgery for Cleft Palate. Each recording was subsequently assessed by three independent SLTs, from a pool of 29 SLTs. They assessed the recordings in real time. The three assessing SLTs agreed in classification of CB status in 423 (87.4%) infants, with higher complete agreement for canonical (91%; 326/358) than non-canonical (77%; 97/126). The average difference in CBR and total number of syllables identified between the SLT assessments of each infant was 0.12 and 95, respectively. This study provided new evidence that one trained SLT can reliably classify CB status (CBR >= 0.15) in real time when there is clear distinction between the observed CBR and the boundary (0.15); however, when the observed CBR approaches the boundary multiple SLT assessments are beneficial. Thus, we recommend to include assessment of inter-rater reliability, if the purpose is to compare CBR and total syllable count across infants or studies.
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| 26. |
- Bauducco, Serena, 1988-, et al.
(författare)
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Adolescents’ Mental Health Hrajectories throughout the COVID-19 Pandemic and the Protective role of Healthy Sleep Patterns
- 2023
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Ingår i: SLEEP Advances. - : Oxford University Press. - 2632-5012. ; 4:Suppl. 1, s. A24-A24
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The COVID-19 pandemic has seen a rise in emotional problems among adolescents. Improving young people's mental health is a public health priority, and examining protective factors throughout the pandemic can offer insights on targets for prevention. This study aimed to investigate longitudinal trajectories of depressive and anxiety symptoms among a large sample of Australian adolescents and to examine sleep patterns in high- and low-risk trajectories.Methods: This study utilises data from the control group of the “Health4Life” cluster RCT. We used three waves of questionnaire data collected annually (from 2019) from Year 7 students at 71 secondary schools across New South Wales, Queensland and Western Australia (N = 2,781, Mage = 12.6, SD = .51; 47% boys and 1.4% ‘prefer not to say’). Adolescents reported on their mental health (i.e., depressive and anxiety symptoms) and sleep (i.e., sleepiness, weekday sleep duration, SOL, WASO, and chronotype).Results: We found four trajectories of depressive symptoms: low-stable (64.3%), average-increasing (19.2%), high-decreasing (7.1%), moderate-increasing (9.4%), and three anxiety symptom trajectories: low-stable (74.8%), average-increasing (11.6%), high-decreasing (13.6%). Adolescents in low-risk trajectories were more likely to be boys and to report shorter SOL and WASO, longer sleep duration, less sleepiness, and earlier chronotype. Where mental health waxed and waned, sleep patterns changed in the same direction.Discussion: This is the first study to thoroughly examine adolescents’ sleep patterns as a protective factor for the development of emotional problems during the pandemic. Healthy sleep was clearly linked to low-risk trajectories, although this association is likely bi-directional.
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| 27. |
- Bauducco, Serena, 1988-, et al.
(författare)
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Adolescents’ trajectories of depression and anxiety symptoms prior to and during the COVID-19 pandemic and their association with healthy sleep patterns
- 2024
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic has seen a rise in anxiety and depression among adolescents. This study aimed to investigate the longitudinal associations between sleep and mental health among a large sample of Australian adolescents and examine whether healthy sleep patterns were protective of mental health in the context of the COVID-19 pandemic. We used three waves of longitudinal control group data from the Health4Life cluster-randomized trial (N= 2781, baseline Mage= 12.6, SD= 0.51; 47% boys and 1.4% ‘prefer not to say’). Latent class growth analyses across the 2 years period identifed four trajectories of depressive symptoms: low-stable (64.3%), average-increasing (19.2%), high-decreasing (7.1%), moderate-increasing (9.4%), and three anxiety symptom trajectories: lowstable (74.8%), average-increasing (11.6%), high-decreasing (13.6%). We compared the trajectories on sociodemographic and sleep characteristics. Adolescents in low-risk trajectories were more likely to be boys and to report shorter sleep latency and wake after sleep onset, longer sleep duration, less sleepiness, and earlier chronotype. Where mental health improved or worsened, sleep patterns changed in the same direction. The subgroups analyses uncovered two important fndings: (1) the majority of adolescents in the sample maintained good mental health and sleep habits (low-stabletrajectories), (2) adolescents with worsening mental health also reported worsening sleep patterns and vice versa in the improving mental health trajectories. These distinct patterns of sleep and mental health would not be seen using mean-centred statistical approaches.
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| 28. |
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| 29. |
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| 31. |
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| 32. |
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| 33. |
- Gamble, Beau, et al.
(författare)
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Digitalizing a Brief Intervention to Reduce Intrusive Memories of Psychological Trauma : Qualitative Interview Study
- 2021
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Ingår i: JMIR Mental Health. - : JMIR Publications. - 2368-7959. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: The COVID-19 pandemic has escalated the global need for remotely delivered and scalable interventions after psychological trauma. A brief intervention involving a computer game as an imagery-competing task has shown promising results for reducing the number of intrusive memories of trauma—one of the core clinical symptoms of posttraumatic stress disorder. To date, the intervention has only been delivered face-to-face. To be tested and implemented on a wider scale, digital adaptation for remote delivery is crucial. An important first step is to develop digitalized intervention materials in a systematic way based on feedback from clinicians, researchers, and students in preparation for pilot testing with target users.Objective: The first aim of this study is to obtain and analyze qualitative feedback on digital intervention materials, namely two animated videos and two quizzes that explain the target clinical symptoms and provide intervention instructions. The second aim is to refine the digitalized materials based on this feedback.Methods: We conducted semistructured interviews with 12 participants who had delivered or had knowledge of the intervention when delivered face-to-face. We obtained in-depth feedback on the perceived feasibility of using the digitalized materials and suggestions for improvements. Interviews were assessed using qualitative content analysis, and suggested improvements were evaluated for implementation using a systematic method of prioritization.Results: A total of three overarching themes were identified from the data. First, participants were highly positive about the potential benefits of using these digital materials for remote delivery, reporting that the videos effectively conveyed key concepts of the symptom and its treatment. Second, some modifications to the materials were suggested for improving clarity. On the basis of this feedback, we made nine specific changes. Finally, participants raised some key challenges for remote delivery, mainly in overcoming the lack of real-time communication during the intervention.Conclusions: Clinicians, researchers, and clinical psychology students were overall confident in the use of digitalized materials to remotely deliver a brief intervention to reduce intrusive memories of trauma. Guided by participant feedback, we identified and implemented changes to refine the intervention materials. This study lays the groundwork for the next step: pilot testing remote delivery of the full intervention to trauma survivors.
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| 34. |
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| 35. |
- Gumz, Michelle L, et al.
(författare)
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Toward Precision Medicine : Circadian Rhythm of Blood Pressure and Chronotherapy for Hypertension - 2021 NHLBI Workshop Report
- 2023
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Ingår i: Hypertension. - : Wolters Kluwer. - 0194-911X .- 1524-4563. ; 80:3, s. 503-522
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Tidskriftsartikel (refereegranskat)abstract
- Healthy individuals exhibit blood pressure variation over a 24-hour period with higher blood pressure during wakefulness and lower blood pressure during sleep. Loss or disruption of the blood pressure circadian rhythm has been linked to adverse health outcomes, for example, cardiovascular disease, dementia, and chronic kidney disease. However, the current diagnostic and therapeutic approaches lack sufficient attention to the circadian rhythmicity of blood pressure. Sleep patterns, hormone release, eating habits, digestion, body temperature, renal and cardiovascular function, and other important host functions as well as gut microbiota exhibit circadian rhythms, and influence circadian rhythms of blood pressure. Potential benefits of nonpharmacologic interventions such as meal timing, and pharmacologic chronotherapeutic interventions, such as the bedtime administration of antihypertensive medications, have recently been suggested in some studies. However, the mechanisms underlying circadian rhythm-mediated blood pressure regulation and the efficacy of chronotherapy in hypertension remain unclear. This review summarizes the results of the National Heart, Lung, and Blood Institute workshop convened on October 27 to 29, 2021 to assess knowledge gaps and research opportunities in the study of circadian rhythm of blood pressure and chronotherapy for hypertension.
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| 36. |
- Ju, Young Seok, et al.
(författare)
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Somatic mutations reveal asymmetric cellular dynamics in the early human embryo
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 543:7647, s. 714-718
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Tidskriftsartikel (refereegranskat)abstract
- Somatic cells acquire mutations throughout the course of an individual's life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and their contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. This study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.
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| 37. |
- Kanstrup, Marie, et al.
(författare)
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A simple cognitive task intervention to prevent intrusive memories after trauma in patients in the Emergency Department : A randomized controlled trial terminated due to COVID-19
- 2021
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Ingår i: BMC Research Notes. - : BioMed Central (BMC). - 1756-0500. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThis randomised controlled trial (RCT) aimed to investigate the effects of a simple cognitive task intervention on intrusive memories ("flashbacks") and associated symptoms following a traumatic event. Patients presenting to a Swedish emergency department (ED) soon after a traumatic event were randomly allocated (1:1) to the simple cognitive task intervention (memory cue + mental rotation instructions + computer game "Tetris" for at least 20 min) or control (podcast, similar time). We planned follow-ups at one-week, 1-month, and where possible, 3- and 6-months post-trauma. Anticipated enrolment was N = 148.ResultsThe RCT was terminated prematurely after recruiting N = 16 participants. The COVID-19 pandemic prevented recruitment/testing in the ED because: (i) the study required face-to-face contact between participants, psychology researchers, ED staff, and patients, incurring risk of virus transmission; (ii) the host ED site received COVID-19 patients; and (iii) reduced flow of patients otherwise presenting to the ED in non-pandemic conditions (e.g. after trauma). We report on delivery of study procedures, recruitment, treatment adherence, outcome completion (primary outcome: number of intrusive memories during week 5), attrition, and limitations. The information presented and limitations may enable our group and others to learn from this terminated study.
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| 38. |
- Kanstrup, Marie, et al.
(författare)
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Reducing intrusive memories after trauma via a brief cognitive task intervention in the hospital emergency department : an exploratory pilot randomised controlled trial
- 2021
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Intrusive memories are common after trauma, and can cause significant distress. Interventions to prevent/reduce the occurrence of this core clinical feature of posttraumatic stress disorder are needed; they should be easy to deliver, readily disseminated and scalable. A novel one-session intervention by Iyadurai et al. 2018, Molecular Psychiatry, resulted in intrusion reduction over the subsequent week. Its feasibility in a different setting and longer-term effects (>1 month) need investigation. We conducted an exploratory open-label pilot randomised controlled trial (RCT) to investigate the feasibility and effects of a brief behavioural intervention to reduce intrusive memories in trauma-exposed patients in a Swedish hospital emergency department (ED). Participants (final N = 41) were randomly allocated to either intervention (including memory reminder cue then visuospatial cognitive task “Tetris” with mental rotation instructions) or active control (podcast) condition within 72 h of presenting to the ED (both conditions using their smartphone). Findings were examined descriptively. We estimated between-group effect sizes for the number of intrusive memories post-intervention at week 1 (primary outcome) and week 5 (secondary outcome). Compared to the control condition, participants in the intervention condition reported fewer intrusive memories of trauma, both at week 1 and week 5. Findings extend the previous evaluation in the UK. The intervention was readily implemented in a different international context, with a mixed trauma sample, with treatment gains maintained at 1 month and associated with some functional improvements. Findings inform future trials to evaluate the capacity of the cognitive task intervention to reduce the occurrence of intrusive memories after traumatic events.
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| 39. |
- Malik, Rainer, et al.
(författare)
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Low-frequency and common genetic variation in ischemic stroke : The METASTROKE collaboration
- 2016
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Ingår i: Neurology. - 1526-632X. ; 86:13, s. 26-1217
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the influence of common and low-frequency genetic variants on the risk of ischemic stroke (all IS) and etiologic stroke subtypes.METHODS: We meta-analyzed 12 individual genome-wide association studies comprising 10,307 cases and 19,326 controls imputed to the 1000 Genomes (1 KG) phase I reference panel. We selected variants showing the highest degree of association (p < 1E-5) in the discovery phase for replication in Caucasian (13,435 cases and 29,269 controls) and South Asian (2,385 cases and 5,193 controls) samples followed by a transethnic meta-analysis. We further investigated the p value distribution for different bins of allele frequencies for all IS and stroke subtypes.RESULTS: We showed genome-wide significance for 4 loci: ABO for all IS, HDAC9 for large vessel disease (LVD), and both PITX2 and ZFHX3 for cardioembolic stroke (CE). We further refined the association peaks for ABO and PITX2. Analyzing different allele frequency bins, we showed significant enrichment in low-frequency variants (allele frequency <5%) for both LVD and small vessel disease, and an enrichment of higher frequency variants (allele frequency 10% and 30%) for CE (all p < 1E-5).CONCLUSIONS: Our findings suggest that the missing heritability in IS subtypes can in part be attributed to low-frequency and rare variants. Larger sample sizes are needed to identify the variants associated with all IS and stroke subtypes.
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| 40. |
- Patterson, Nick, et al.
(författare)
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Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
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Tidskriftsartikel (refereegranskat)abstract
- Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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| 41. |
- Persson, Christina, 1959, et al.
(författare)
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Adding a fourth rater to three had little impact in pre-linguistic outcome classification
- 2021
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Ingår i: Clinical Linguistics & Phonetics. - : Informa UK Limited. - 0269-9206 .- 1464-5076. ; 35:2, s. 138-153
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Tidskriftsartikel (refereegranskat)abstract
- The consequence of differing levels of agreement across raters is rarely studied. Subsequently, knowledge is limited on how number of raters affects the outcome. The present study aimed to examine the impact on pre-linguistic outcome classifications of 12-month-old infants when using four raters compared to three. Thirty experienced Speech and Language Therapists (SLTs) from five countries assessed 20 minute video recordings of four 12-month-old infants during a play session with a parent. One recording was assessed twice. A naturalistic listening method in real time was used. This involved: (1) assessing, each syllable as canonical or non-canonical, and (2) following the recording, assessing if the infant was babbling canonically and listing the syllables the infant produced with command. The impact that four raters had on outcome, compared to three, was explored by classifying the outcome based on all possible combinations of three raters and determining the frequency that the outcome assessment changed when a fourth assessor was added. Results revealed that adding a fourth rater had a minimal impact on canonical babbling ratio assessment. Presence/absence of canonical babbling and size of consonant inventory showed a negligible impact on three out of four recordings, whereas the size of syllable inventory and presence/absence of canonical babbling was minimally affected in one recording by adding a fourth rater. In conclusion, adding a forth rater in assessment of pre-linguistic utterances in 12-month-old infants with naturalistic assessment in real time does not affect outcome classifications considerably. Thus, using three raters, as opposed to four, is recommended.
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| 42. |
- Shaw, W, et al.
(författare)
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Timing Of Primary Surgery for cleft palate (TOPS): protocol for a randomised trial of palate surgery at 6 months versus 12 months of age
- 2019
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Cleft palate is among the most common birth abnormalities. The success of primary surgery in the early months of life is crucial for successful feeding, speech, hearing, dental development and facial growth. Over recent decades, age at palatal surgery in infancy has reduced. This has led to palatal closure in one-stage procedures being carried out around the age of 12 months, but in some cases as early as 6 months. The primary objective of the Timing Of Primary Surgery for Cleft Palate (TOPS)trial is to determine whether surgery for cleft palate performed at 6 or 12 months of age is most beneficial for speech outcomes. Methods and analysis Infants with a diagnosis of non-syndromic isolated cleft palate will be randomised to receive standardised primary surgery (Sommerlad technique) for closure of the cleft at either 6 months or 12 months, corrected for gestational age. The primary outcome will be perceived insufficient velopharyngeal function at 5 years of age. Secondary outcomes measured across 12 months, 3 years and 5 years will include growth, safety of the procedure, dentofacial development, speech, hearing level and middle ear function. Video and audio recordings of speech will be collected in a standardised age-appropriate manner and analysed independently by multiple speech and language therapists. The trial aims to recruit and follow-up 300 participants per arm. Data will be analysed according to the intention-to-treat principle using a 5% significance level. All analyses will be prespecified within a full and detailed statistical analysis plan. Ethics and dissemination Ethical approval has been sought in each participating country according to country-specific procedures. Trial results will be presented at conferences, published in peer-reviewed journals and disseminated through relevant patient support groups.
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| 43. |
- Singh, Laura, et al.
(författare)
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A first remotely-delivered guided brief intervention to reduce intrusive memories of psychological trauma for healthcare staff working during the ongoing COVID-19 pandemic : Study protocol for a randomised controlled trial
- 2022
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Ingår i: Contemporary Clinical Trials Communications. - : Elsevier BV. - 2451-8654. ; 26
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Tidskriftsartikel (refereegranskat)abstract
- Addressing the mental health needs of healthcare staff exposed to psychologically traumatic events at work during the COVID-19 pandemic is a pressing global priority. We need to swiftly develop interventions to target the psychological consequences (e.g., persistent intrusive memories of trauma). Interventions for healthcare staff must be brief, flexible, fitted around the reality and demands of working life under the pandemic, and repeatable during ongoing/further trauma exposure. Intervention delivery during the pandemic should be remote to mitigate risk of infection; e.g., here using a blend of digitalized self-administered materials (e.g., video instructions) and guided (remote) support from a researcher. This parallel groups, two-arm, randomised controlled trial (RCT) with healthcare staff working during the COVID-19 pandemic is the first evaluation of whether a digitalized form of a brief cognitive task intervention, which is remotely-delivered (guided), reduces intrusive memories. Healthcare staff who experience intrusive memories of work-related traumatic event(s) during the COVID-19 pandemic (≥2 in the week before inclusion) will be randomly allocated (1:1) to receive either the cognitive task intervention or an active (attention placebo) control, and followed up at 1-week, 1-month, 3-months, and 6-months post-intervention. The primary outcome will be the number of intrusive memories reported during Week 5; secondary and other outcomes include the number of intrusive memories reported during Week 1, and other intrusive symptoms. Findings will inform further development and dissemination of a brief cognitive task intervention to target intrusive memories.
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| 44. |
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| 45. |
- Thorarinsdottir, Kristjana, et al.
(författare)
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Reducing Intrusive Memories of Childhood Trauma Using a Visuospatial Intervention: Case Study in Iceland
- 2021
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Ingår i: JMIR Formative Research. - : JMIR Publications. - 2561-326X. ; 5:11, s. e29873-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Additional interventions are needed for survivors of psychological trauma because of several barriers to and limitations of existing treatment options (eg, need to talk about the trauma in detail). Case studies are an important step in exploring the development of novel interventions, allowing detailed examination of individual responses to treatment over time. Here, we present a case study that aims to test a novel intervention designed to disrupt memory reconsolidation, taking a single-symptom approach by focusing on intrusive memories of a traumatic event.Objective: This study aims to examine a novel brief cognitive intervention to reduce the number of intrusive memories of trauma in an Icelandic setting and to extend previous studies by examining long-term effects for up to 3 months. The intervention was guided by a clinical psychologist and comprised a brief memory reminder, followed by Tetris gameplay with mental rotation, targeting one memory at a time in each session.Methods: This was a single case study in Iceland with a woman in her 50s (drawn from an epidemiological study of trauma) with subthreshold posttraumatic stress disorder and a diagnosis of obsessive-compulsive disorder and social anxiety disorder. The participant had four different intrusive memories from a traumatic event that happened in her childhood. The primary outcome was the change in the number of intrusive memories from baseline to intervention phase and to follow-ups. The number of intrusions was monitored in a daily diary for 4 weeks preintervention, 8 weeks during the intervention, and 1 week at 1-month and 3-month follow-ups. Intrusions were targeted one by one over six intervention sessions, creating four repetitions of an AB design (ie, length of baseline A and intervention phase B varied for each memory). We examined changes in both the total number of intrusions (summed across all four memories) and individually for each memory. In addition, we explored whether having fewer intrusive memories would have an impact on functioning, posttraumatic stress, and depression or anxiety symptoms.Results: The total number of intrusions per week was 12.6 at baseline, 6.1 at the intervention phase (52% reduction from baseline), 3.0 at the 1-month follow-up (76% reduction), and 1.0 at the 3-month follow-up (92% reduction). Reductions in the symptoms of posttraumatic stress and depression were observed postintervention. Sleep, concentration, stress, and functioning improved. The participant considered the gameplay intervention acceptable and helpful in that she found that the memories disappeared while she was playing.Conclusions: This guided brief cognitive intervention reduced the number of intrusive memories over the intervention phase and follow-ups. The brief memory reminder was well tolerated, removing the need to discuss trauma in detail. The next steps require an extension to more cases and exploring remote delivery of the intervention.
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| 47. |
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| 48. |
- Vestweber, Dietmar, et al.
(författare)
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Report from the 2023 workshop on endothelial permeability, edema and inflammation
- 2023
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Ingår i: Nature Cardiovascular Research. - : Springer Nature. - 2731-0590. ; 2:12, s. 1120-1124
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- A key consequence of increased and sustained vascular permeability in several inflammatory and cardiovascular disorders is the development of interstitial protein-rich proinflammatory edema. This response remains poorly understood mechanistically and its potential adverse effect on local and systemic diseases is often underestimated. To discuss current findings and identify crucial unresolved questions, a workshop was held in Berlin from 12-15 April 2023. Key topics that were discussed included regulation of endothelial cell junctions, neutrophil-dependent vascular leakage, resolution of edema, exemplar diseases, and anti-edema therapies. This report is a summary of the meeting.
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| 49. |
- Waight, Tod E., et al.
(författare)
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Hf isotope evidence for variable slab input and crustal addition in basalts and andesites of the Taupo Volcanic Zone, New Zealand
- 2017
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Ingår i: Lithos. - : ELSEVIER SCIENCE BV. - 0024-4937 .- 1872-6143. ; 284-285, s. 222-236
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Tidskriftsartikel (refereegranskat)abstract
- Crustal contamination complicates the identification of primary mantle-derived magma compositions in continental arcs. However, when crustal processes and components are well characterised, it is possible to extrapolate through continental arc magma compositional arrays towards the Hf and Nd isotope compositions of uncontaminated primary magmas. This is because of the similar behaviour of Hf and Nd during fractional crystallisation and mantle melting, and the subsequent limited variation in Hf/Nd in mantle-derived magmas and in many crustal lithologies, resulting in linear contamination trends for Hf-Nd isotopes. Here we present new Hf isotope data for a selection of volcanic rocks and crustal lithologies from the Taupo Volcanic Zone (TVZ), New Zealand and propose that the scatter in Hf-Nd isotopes indicates heterogeneity in the parental magmas prior to interactions with crustal lithologies. The observed variations likely represent variability in primary magma compositions as a result of different degrees of sediment addition at the slab-wedge interface. Coupled variations in isotopic composition, LILE/HFSE ratios (e.g. Rb/Zr and Ba/La) and SiO2 also clearly indicate that shallower level crustal interactions have occurred. Andesites from Ruapehu Volcano have more consistent parental magma compositions, and require greater amounts of a source sediment contribution. Notably, the compositions of older Ruapehu lavas can be modelled by interactions between mantle-derived magmas and lower crustal granulites, whereas younger lavas have probably interacted more with mid- to shallow crustal meta-sedimentary greywacke-argillite lithologies of the Permian to Cretaceous composite Torlesse Terrane. Hf-Nd isotopic compositions of meta-igneous granulite xenoliths from Mt. Ruapehu are consistent with previous interpretations that they are derived from oceanic crust that underlies the Torlesse meta-sediments. The results indicate that interactions with sediments at both the slab-wedge interface and in the lithosphere must be considered when evaluating trace element and isotopic variations in continental arcs.
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