| 1. |
- Falster, Daniel, et al.
(författare)
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AusTraits, a curated plant trait database for the Australian flora
- 2021
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Ingår i: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
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| 2. |
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| 3. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 4. |
- Chirinos, Julio A., et al.
(författare)
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Reduced Apolipoprotein M and Adverse Outcomes across the Spectrum of Human Heart Failure
- 2020
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Ingår i: Circulation. - 0009-7322. ; , s. 1463-1476
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Tidskriftsartikel (refereegranskat)abstract
- Background: Apo (apolipoprotein) M mediates the physical interaction between high-density lipoprotein (HDL) particles and sphingosine-1-phosphate (S1P). Apo M exerts anti-inflammatory and cardioprotective effects in animal models. Methods: In a subset of PHFS (Penn Heart Failure Study) participants (n=297), we measured apo M by Enzyme-Linked ImmunoSorbent Assay (ELISA). We also measured total S1P by liquid chromatography-mass spectrometry and isolated HDL particles to test the association between apo M and HDL-associated S1P. We confirmed the relationship between apo M and outcomes using modified aptamer-based apo M measurements among 2170 adults in the PHFS and 2 independent cohorts: the Washington University Heart Failure Registry (n=173) and a subset of TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial; n=218). Last, we examined the relationship between apo M and ≈5000 other proteins (SomaScan assay) to identify biological pathways associated with apo M in heart failure. Results: In the PHFS, apo M was inversely associated with the risk of death (standardized hazard ratio, 0.56 [95% CI, 0.51-0.61]; P<0.0001) and the composite of death/ventricular assist device implantation/heart transplantation (standardized hazard ratio, 0.62 [95% CI, 0.58-0.67]; P<0.0001). This relationship was independent of HDL cholesterol or apo AI levels. Apo M remained associated with death (hazard ratio, 0.78 [95% CI, 0.69-0.88]; P<0.0001) and the composite of death/ventricular assist device/heart transplantation (hazard ratio, 0.85 [95% CI, 0.76-0.94]; P=0.001) in models that adjusted for multiple confounders. This association was present in both heart failure with reduced and preserved ejection fraction and was replicated in the Washington University cohort and a cohort with heart failure with preserved ejection fraction only (TOPCAT). The S1P and apo M content of isolated HDL particles strongly correlated (R=0.81, P<0.0001). The top canonical pathways associated with apo M were inflammation (negative association), the coagulation system (negative association), and liver X receptor/retinoid X receptor activation (positive association). The relationship with inflammation was validated with multiple inflammatory markers measured with independent assays. Conclusions: Reduced circulating apo M is independently associated with adverse outcomes across the spectrum of human heart failure. Further research is needed to assess whether the apo M/S1P axis is a suitable therapeutic target in heart failure.
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| 5. |
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| 6. |
- Zaidi, Syed H., et al.
(författare)
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Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival
- 2020
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.
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| 7. |
- Abdesselam, A., et al.
(författare)
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Engineering for the ATLAS SemiConductor Tracker (SCT) end-cap
- 2008
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The ATLAS SemiConductor Tracker (SCT) is a silicon-strip tracking detector which forms part of the ATLAS inner detector. The SCT is designed to track charged particles produced in proton-proton collisions at the Large Hadron Collider (LHC) at CERN at an energy of 14 TeV. The tracker is made up of a central barrel and two identical end-caps. The barrel contains 2112 silicon modules, while each end-cap contains 988 modules. The overall tracking performance depends not only on the intrinsic measurement precision of the modules but also on the characteristics of the whole assembly, in particular, the stability and the total material budget. This paper describes the engineering design and construction of the SCT end-caps, which are required to support mechanically the silicon modules, supply services to them and provide a suitable environment within the inner detector. Critical engineering choices are highlighted and innovative solutions are presented - these will be of interest to other builders of large-scale tracking detectors. The SCT end-caps will be fully connected at the start of 2008. Further commissioning will continue, to be ready for proton-proton collision data in 2008.
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| 8. |
- Becker, Richard C, et al.
(författare)
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Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial
- 2011
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 32:23, s. 2933-2944
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Tidskriftsartikel (refereegranskat)abstract
- AimsMore intense platelet-directed therapy for acute coronary syndrome (ACS) may increase bleeding risk. The aim of the current analysis was to determine the rate, clinical impact, and predictors of major and fatal bleeding complications in the PLATO study.Methods and resultsPLATO was a randomized, double-blind, active control international, phase 3 clinical trial in patients with acute ST elevation and non-ST-segment elevation ACS. A total of 18 624 patients were randomized to either ticagrelor, a non-thienopyridine, reversibly binding platelet P2Y(12) receptor antagonist, or clopidogrel in addition to aspirin. Patients randomized to ticagrelor and clopidogrel had similar rates of PLATO major bleeding (11.6 vs. 11.2%; P = 0.43), TIMI major bleeding (7.9 vs. 7.7%, P = 0.56) and GUSTO severe bleeding (2.9 vs. 3.1%, P = 0.22). Procedure-related bleeding rates were also similar. Non-CABG major bleeding (4.5 vs. 3.8%, P = 0.02) and non-procedure-related major bleeding (3.1 vs. 2.3%, P = 0.05) were more common in ticagrelor-treated patients, primarily after 30 days on treatment. Fatal bleeding and transfusion rates did not differ between groups. There were no significant interactions for major bleeding or combined minor plus major bleeding between treatment groups and age ≥75 years, weight <60 kg, region, chronic kidney disease, creatinine clearance <60 mL/min, aspirin dose >325 mg on the day of randomization, pre-randomization clopidogrel administration, or clopidogrel loading dose.Conclusion Ticagrelor compared with clopidogrel was associated with similar total major bleeding but increased non-CABG and non-procedure-related major bleeding, primarily after 30 days on study drug treatment. Fatal bleeding was low and did not differ between groups.
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| 9. |
- Body, Richard, et al.
(författare)
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The Use of Very Low Concentrations of High-sensitivity Troponin T to Rule Out Acute Myocardial Infarction Using a Single Blood Test
- 2016
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Ingår i: Academic Emergency Medicine. - : Wiley. - 1069-6563 .- 1553-2712. ; 23:9, s. 1005-1013
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent single-center and retrospective studies suggest that acute myocardial infarction (AMI) could be immediately excluded without serial sampling in patients with initial high-sensitivity cardiac troponin T (hs-cTnT) levels below the limit of detection (LoD) of the assay and no electrocardiogram (ECG) ischemia. Objective: We aimed to determine the external validity of those findings in a multicenter study at 12 sites in nine countries. Methods: TRAPID-AMI was a prospective diagnostic cohort study including patients with suspected cardiac chest pain within 6 hours of peak symptoms. Blood drawn on arrival was centrally tested for hs-cTnT (Roche; 99th percentile = 14 ng/L, LoD = 5 ng/L). All patients underwent serial troponin sampling over 4-14 hours. The primary outcome, prevalent AMI, was adjudicated based on sensitive troponin I (Siemens Ultra) levels. Major adverse cardiac events (MACE) including AMI, death, or rehospitalization for acute coronary syndrome with coronary revascularization were determined after 30 days. Results: We included 1,282 patients, of whom 213 (16.6%) had AMI and 231 (18.0%) developed MACE. Of 560 (43.7%) patients with initial hs-cTnT levels below the LoD, four (0.7%) had AMI. In total, 471 (36.7%) patients had both initial hs-cTnT levels below the LoD and no ECG ischemia. These patients had a 0.4% (n = 2) probability of AMI, giving 99.1% (95% confidence interval [CI] = 96.7% to 99.9%) sensitivity and 99.6% (95% CI = 98.5% to 100.0%) negative predictive value. The incidence of MACE in this group was 1.3% (95% CI = 0.5% to 2.8%). Conclusions: In the absence of ECG ischemia, the detection of very low concentrations of hs-cTnT at admission seems to allow rapid, safe exclusion of AMI in one-third of patients without serial sampling. This could be used alongside careful clinical assessment to help reduce unnecessary hospital admissions.
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| 10. |
- de Fréin, Ruairí, et al.
(författare)
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Integration of QoS Metrics, Rules and Semantic Uplift for Advanced IPTV Monitoring
- 2014
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Ingår i: Journal of Network and Systems Management. - : Springer. - 1573-7705 .- 1064-7570. ; 23:3, s. 1-36
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Tidskriftsartikel (refereegranskat)abstract
- Increasing and variable traffic demands due to triple play services pose significant Internet Protocol Television (IPTV) resource management challenges for service providers. Managing subscriber expectations via consolidated IPTV quality reporting will play a crucial role in guaranteeing return-on-investment for players in the increasingly competitive IPTV delivery ecosystem. We propose a fault diagnosis and problem isolation solution that addresses the IPTV monitoring challenge and recommends problem-specific remedial action. IPTV delivery-specific metrics are collected at various points in the delivery topology, the residential gateway and the Digital Subscriber Line Access Multiplexer through to the video Head-End. They are then pre-processed using new metric rules. A semantic uplift engine takes these raw metric logs; it then transforms them into World Wide Web Consortium’s standard Resource Description Framework for knowledge representation and annotates them with expert knowledge from the IPTV domain. This system is then integrated with a monitoring visualization framework that displays monitoring events, alarms, and recommends solutions. A suite of IPTV fault scenarios is presented and used to evaluate the feasibility of the solution. We demonstrate that professional service providers can provide timely reports on the quality of IPTV service delivery using this system.
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| 11. |
- Dennis, Martin, et al.
(författare)
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Effects of fluoxetine on functional outcomes after acute stroke (FOCUS) : a pragmatic, double-blind, randomised, controlled trial
- 2019
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 393:10168, s. 265-274
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Tidskriftsartikel (refereegranskat)abstract
- Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762.Findings Between Sept 10,2012, and March 31,2017,3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99.3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0.951 [95% CI 0.839-1.079]; p=0.439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13.43%] patients vs 269 [17.21%]; difference 3.78% [95% CI 1.26-6.30]; p=0.0033), but they had more bone fractures (45 [2.88%] vs 23 [1.47%]; difference 1.41% [95% CI 0.38-2.43]; p=0.0070). There were no significant differences in any other event at 6 or 12 months.Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.
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| 12. |
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| 13. |
- Figlioli, G, et al.
(författare)
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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| 14. |
- French, Roger H., et al.
(författare)
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Long range interactions in nanoscale science
- 2010
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Ingår i: Reviews of Modern Physics. - 0034-6861. ; 82:2, s. 1887-1944
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Forskningsöversikt (refereegranskat)abstract
- Our understanding of the “long range” electrodynamic, electrostatic, and polar interactions that dominate the organization of small objects at separations beyond an interatomic bond length is reviewed. From this basic-forces perspective, a large number of systems are described from which one can learn about these organizing forces and how to modulate them. The many practical systems that harness these nanoscale forces are then surveyed. The survey reveals not only the promise of new devices and materials, but also the possibility of designing them more effectively.
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| 15. |
- Garnett, Stephen T., et al.
(författare)
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A spatial overview of the global importance of Indigenous lands for conservation
- 2018
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Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 1:7, s. 369-374
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the scale, location and nature conservation values of the lands over which Indigenous Peoples exercise traditional rights is central to implementation of several global conservation and climate agreements. However, spatial information on Indigenous lands has never been aggregated globally. Here, using publicly available geospatial resources, we show that Indigenous Peoples manage or have tenure rights over at least similar to 38 million km(2) in 87 countries or politically distinct areas on all inhabited continents. This represents over a quarter of the world's land surface, and intersects about 40% of all terrestrial protected areas and ecologically intact landscapes (for example, boreal and tropical primary forests, savannas and marshes). Our results add to growing evidence that recognizing Indigenous Peoples' rights to land, benefit sharing and institutions is essential to meeting local and global conservation goals. The geospatial analysis presented here indicates that collaborative partnerships involving conservation practitioners, Indigenous Peoples and governments would yield significant benefits for conservation of ecologically valuable landscapes, ecosystems and genes for future generations.
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| 16. |
- Harlid, Sophia, 1978-, et al.
(författare)
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Diabetes mellitus in relation to colorectal tumor molecular subtypes : a pooled analysis of more than 9000 cases
- 2022
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 151:3, s. 348-360
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes is an established risk factor for colorectal cancer. However, colorectal cancer is a heterogeneous disease and it is not well understood whether diabetes is more strongly associated with some tumor molecular subtypes than others. A better understanding of the association between diabetes and colorectal cancer according to molecular subtypes could provide important insights into the biology of this association. We used data on lifestyle and clinical characteristics from the Colorectal Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), including 9756 colorectal cancer cases (with tumor marker data) and 9985 controls, to evaluate associations between reported diabetes and risk of colorectal cancer according to molecular subtypes. Tumor markers included BRAF and KRAS mutations, microsatellite instability and CpG island methylator phenotype. In the multinomial logistic regression model, comparing colorectal cancer cases to cancer-free controls, diabetes was positively associated with colorectal cancer regardless of subtype. The highest OR estimate was found for BRAF-mutated colorectal cancer, n = 1086 (ORfully adj: 1.67, 95% confidence intervals [CI]: 1.36-2.05), with an attenuated association observed between diabetes and colorectal cancer without BRAF-mutations, n = 7959 (ORfully adj: 1.33, 95% CI: 1.19-1.48). In the case only analysis, BRAF-mutation was differentially associated with diabetes (Pdifference = .03). For the other markers, associations with diabetes were similar across tumor subtypes. In conclusion, our study confirms the established association between diabetes and colorectal cancer risk, and suggests that it particularly increases the risk of BRAF-mutated tumors.
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| 17. |
- Kapur, Rick, et al.
(författare)
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Gastrointestinal microbiota contributes to the development of murine transfusion-related acute lung injury
- 2018
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 2:13, s. 1651-1663
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Tidskriftsartikel (refereegranskat)abstract
- Transfusion-related acute lung injury (TRALI) is a syndrome of respiratory distress upon blood transfusion and is the leading cause of transfusion-related fatalities. Whether the gut microbiota plays any role in the development of TRALI is currently unknown. We observed that untreated barrier-free (BF) mice suffered from severe antibody-mediated acute lung injury, whereas the more sterile housed specific pathogen-free (SPF) mice and gut flora-depleted BF mice were both protected from lung injury. The prevention of TRALI in the SPF mice and gut flora-depleted BF mice was associated with decreased plasma macrophage inflammatory protein-2 levels as well as decreased pulmonary neutrophil accumulation. DNA sequencing of amplicons of the 16S ribosomal RNA gene revealed a varying gastrointestinal bacterial composition between BF and SPF mice. BF fecal matter transferred into SPF mice significantly restored TRALI susceptibility in SPF mice. These data reveal a link between the gut flora composition and the development of antibody-mediated TRALI in mice. Assessment of gut microbial composition may help in TRALI risk assessment before transfusion.
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| 18. |
- Karlsson, Anneli, et al.
(författare)
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Notch1 is a frequent mutational target in chemically induced lymphoma in mouse
- 2008
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 123:11, s. 2720-2724
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Tidskriftsartikel (refereegranskat)abstract
- Activating Notch1 mutations have been reported in human T-lineage acute lymphoblastic leukemia (T-ALL) and lymphomas from genetically modified mice. We report that Notch1 is a prevalent and major mutational target in chemically induced mouse lymphoma. The regions of the gene that are frequently mutated are the hterodimerization domain and the N-terminal ligand-binding region, important for protein stability, and (he polypeptide rich in proline, glutamate, serine and threonine WEST) domains, which is critical for protein degradation. Another gene, CDC4, is also involved in Notch1 degradation and shows frequent mutations. Mutations in the heterodimerization and the ligand-binding regions may cause ligand-independent signaling. whereas mutations preventing protein degradation result in accumulation of intracellular Notch1. We analyzed 103 chemical-induced mouse lymphomas for mutations in the Notch1 gene using single strand conformation analysis (SSCA) and DNA sequencing. Genetic alterations resulting in premature truncation of Notch I were identified in 28 tumors, whereas 8 revealed alterations in the heterodimerization and 16 harbored deletions in the ligand-binding region. Dideoxycytidine-induced lymphomas displayed the highest frequency of Notch1 mutations (49%). whereas in butadiene- and phenolphthalein-indced tumors showed lower frequencies (26 10%, respectively). In total, 26 novel and 3 previously reported mutations were detected. This report shows that Notch1 is a prevalent and major mtational target for 2,3-dideoxycytidine and butadiene-induced lymphoma..
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| 19. |
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| 20. |
- McCord, James, et al.
(författare)
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Prognostic Utility of a Modified HEART Score in Chest Pain Patients in the Emergency Department
- 2017
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Ingår i: Circulation. Cardiovascular Quality and Outcomes. - : LIPPINCOTT WILLIAMS & WILKINS. - 1941-7713 .- 1941-7705. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Background-The TRAPID-AMI trial study ( High-Sensitivity Troponin-T Assay for Rapid Rule-Out of Acute Myocardial Infarction) evaluated high-sensitivity cardiac troponin-T ( hs-cTnT) in a 1-hour acute myocardial infarction ( AMI) exclusion algorithm. Our study objective was to evaluate the prognostic utility of a modified HEART score ( m-HS) within this trial. Methods and Results-Twelve centers evaluated 1282 patients in the emergency department for possible AMI from 2011 to 2013. Measurements of hs-cTnT ( 99th percentile, 14 ng/L) were performed at 0, 1, 2, and 4 to 14 hours. Evaluation for major adverse cardiac events ( MACEs) occurred at 30 days ( death or AMI). Low-risk patients had an m-HS <= 3 and had either hs-cTnT<14 ng/L over serial testing or had AMI excluded by the 1-hour protocol. By the 1-hour protocol, 777 ( 60%) patients had an AMI excluded. Of those 777 patients, 515 ( 66.3%) patients had an m-HS <= 3, with 1 ( 0.2%) patient having a MACE, and 262 ( 33.7%) patients had an m-HS <= 4, with 6 ( 2.3%) patients having MACEs ( P=0.007). Over 4 to 14 hours, 661 patients had a hs-cTnT<14 ng/L. Of those 661 patients, 413 ( 62.5%) patients had an m-HS <= 3, with 1 ( 0.2%) patient having a MACE, and 248 ( 37.5%) patients had an m-HS >= 4, with 5 ( 2.0%) patients having MACEs ( P=0.03). Conclusions-Serial testing of hs-cTnT over 1 hour along with application of an m-HS identified a low-risk population that might be able to be directly discharged from the emergency department.
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| 21. |
- McCord, James, et al.
(författare)
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Symptoms Predictive of Acute Myocardial Infarction in the Troponin Era : Analysis From the TRAPID-AMI Study.
- 2019
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Ingår i: Critical Pathways in Cardiology. - 1535-282X .- 1535-2811. ; 18:1, s. 10-15
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Tidskriftsartikel (refereegranskat)abstract
- The TRAPID-AMI (High Sensitivity Cardiac Troponin T assay for rapid Rule-out of Acute Myocardial Infarction) study evaluated a rapid "rule-out" acute myocardial infarction (AMI). We evaluated what symptoms were associated with AMI as part of a substudy of TRAPID-AMI. There were 1282 patients evaluated from 12 centers in Europe, the United States of America, and Australia from 2011 to 2013. Multiple symptom variables were prospectively obtained and evaluated for association with the final diagnosis of AMI. Multivariate logistic regression analysis was done, and odds ratios (OR) were calculated. There were 213/1282 (17%) AMIs. Four independent predictors for the diagnosis of AMI were identified: radiation to right arm or shoulder [OR = 3.0; confidence interval (CI): 1.8-5.0], chest pressure (OR = 2.5; CI: 1.3-4.6), worsened by physical activity (OR = 1.7; CI: 1.2-2.5), and radiation to left arm or shoulder (OR = 1.7; CI: 1.1-2.4). In the entire group, 131 (10%) had radiation to right arm or shoulder, 897 (70%) had chest pressure, 385 (30%) worsened with physical activity, and 448 (35%) had radiation to left arm or shoulder. Duration of symptoms was not predictive of AMI. There were no symptoms predictive of non-AMI. Relationship between AMI size and symptoms was also studied. For 213 AMI patients, cardiac troponins I values were divided into 4 quartiles. Symptoms including pulling chest pain, supramammillary right location, and right arm/shoulder radiation were significantly more likely to occur in patients with larger AMIs. In a large multicenter trial, only 4 symptoms were associated with the diagnosis of AMI, and no symptoms that were associated with a non-AMI diagnosis.
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| 22. |
- McVey, Mark J., et al.
(författare)
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Platelet extracellular vesicles mediate transfusion-related acute lung injury by imbalancing the sphingolipid rheostat
- 2021
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 137:5, s. 690-701
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Tidskriftsartikel (refereegranskat)abstract
- Transfusion-related acute lung injury (TRALI) is a hazardous transfusion complication with an associated mortality of 5% to 15%. We previously showed that stored (5 days) but not fresh platelets (1 day) cause TRALI via ceramide-mediated endothelial barrier dysfunction. As biological ceramides are hydrophobic, extracellular vesicles (EVs) may be required to shuttle these sphingolipids from platelets to endothelial cells. Adding to complexity, EV formation in turn requires ceramide. We hypothesized that ceramide-dependent EV formation from stored platelets and EV-dependent sphingolipid shuttling induces TRALI. EVs formed during storage of murine platelets were enumerated, characterized for sphingolipids, and applied in a murine TRALI model in vivo and for endothelial barrier assessment in vitro. Five-day EVs were more abundant, had higher long-chain ceramide (C16:0, C18:0, C20:0), and lower sphingosine-1-phosphate (S1P) content than 1-day EVs. Transfusion of 5-day, but not 1-day, EVs induced characteristic signs of lung injury in vivo and endothelial barrier disruption in vitro. Inhibition or supplementation of ceramide-forming sphingomyelinase reduced or enhanced the formation of EVs, respectively, but did not alter the injuriousness per individual EV. Barrier failure was attenuated when EVs were abundant in or supplemented with S1P. Stored human platelet 4-day EVs were more numerous compared with 2-day EVs, contained more long-chain ceramide and less S1P, and caused more endothelial cell barrier leak. Hence, platelet-derived EVs become more numerous and more injurious (more long-chain ceramide, less S1P) during storage. Blockade of sphingomyelinase, EV elimination, or supplementation of S1P during platelet storage may present promising strategies for TRALI prevention. Key Points: • EVs derived from stored platelets cause TRALI as a function of their elevated ceramide and decreased S1P content. • Inhibiting ceramide formation, supplementing S1P, or washing stored platelets could potentially reduce TRALI incidence and severity.
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| 23. |
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| 24. |
- Mohammadi, Amir, et al.
(författare)
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Application of Diffusive Gradients in Thin Films for Monitoring Groundwater Quality br
- 2022
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Ingår i: ACS - ES & T Water. - : American Chemical Society (ACS). - 2690-0637. ; 2:4, s. 518-526
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Tidskriftsartikel (refereegranskat)abstract
- Diffusive gradients in thin films (DGTs) provide time-weighted solute concentrations in well-mixed fluvial environments. However, the DGT method has rarely been applied to relatively slowly moving groundwater systems, where the increased length of the diffusive boundary layer (DBL) must be accounted for, to give accurate concentration measurements. Because the DGT method pre-concentrates trace-level solutes (e.g., Cd2+) and averages out fluctuations in more dynamic contaminants (e.g., NO3-), it has potential advantages over conventional methods. This study evaluated the application of DGT methods for monitoring trace contaminants in groundwater, which are often present at levels below standard instrumental detection limits. We tested three different DGT deployment approaches using NO3- to estimate the DBL thickness: a static DGT suspension, a DGT shaker, and a pumped flow-cell unit coined the "universal DGT monitoring system" (UDMS). Unlike static and DGT shaker approaches, the UDMS reduced the DBL thickness (similar to 0.02 cm) to values within the range of well-mixed waters (DBL <= 0.03 cm). Comparable DBL thicknesses for NO3- and Cd2+ and correlations with grab sample measurements (R-2 = 0.99 and 0.98, respectively) demonstrate the suitability of DGTs combined with the UDMS for groundwater monitoring. This approach is particularly suitable for analysis of trace-level solutes including organic contaminants.
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| 25. |
- Mueller, Christian, et al.
(författare)
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Multicenter Evaluation of a 0-Hour/1-Hour Algorithm in the Diagnosis of Myocardial Infarction With High-Sensitivity Cardiac Troponin T
- 2016
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Ingår i: Annals of Emergency Medicine. - : Elsevier BV. - 0196-0644 .- 1097-6760. ; 68:1, s. 76-87
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Tidskriftsartikel (refereegranskat)abstract
- Study objective: We aim to prospectively validate the diagnostic accuracy of the recently developed 0-h/1-h algorithm, using high-sensitivity cardiac troponin T (hs-cTnT) for the early rule-out and rule-in of acute myocardial infarction. Methods: We enrolled patients presenting with suspected acute myocardial infarction and recent (<6 hours) onset of symptoms to the emergency department in a global multicenter diagnostic study. Hs-cTnT (Roche Diagnostics) and sensitive cardiac troponin I (Siemens Healthcare) were measured at presentation and after 1 hour, 2 hours, and 4 to 14 hours in a central laboratory. Patient triage according to the predefined hs-cTnT 0-hour/1-hour algorithm (hs-cTnT beloow 12 ng/L and Delta 1 hour below 3 ng/L to rule out; hs-cTnT at least 52 ng/L r Delta 1 hour at least 5 ng/L to rule in; remaining patients to the "observational zone") was compared against a centrally adjudicated final diagnosis by 2 independent cardiologists (reference standard). The final diagnosis was based on all available information, including coronary angiography and echocardiography results, follow-up data, and serial measurements of sensitive cardiac troponin I, whereas adjudicators remained blinded to hs-cTnT. Results: Among 1,282 patients enrolled, acute myocardial infarction was the final diagnosis for 213 (16.6%) patients. Applying the hs-cTnT 0-hour/1-hour algorithm, 813 (63.4%) patients were classified as rule out, 184 (14.4%) were classified as rule in, and 285 (22.2%) were triaged to the observational zone. This resulted in a negative predictive value and sensitivity for acute myocardial infarction of 99.1% (95% confidence interval [CI] 98.2% to 99.7%) and 96.7% (95% CI 93.4% to 98.7%) in the rule-out zone (7 patients with false-negative results), a positive predictive value and specificity for acute myocardial infarction of 77.2% (95% CI 70.4% to 83.0%) and 96.1% (95% CI 94.7% to 97.2%) in the rule-in zone, and a prevalence of acute myocardial infarction of 22.5% in the observational zone. Conclusion: The hs-cTnT 0-hour/1-hour algorithm performs well for early rule-out and rule-in of acute myocardial infarction.
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| 26. |
- Mueller-Hennessen, Matthias, et al.
(författare)
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Combined testing of copeptin and high-sensitivity cardiac troponin T at presentation in comparison to other algorithms for rapid rule-out of acute myocardial infarction
- 2019
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 276, s. 261-267
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We aimed to directly compare the diagnostic and prognostic performance of a dual maker strategy (DMS) with combined testing of copeptin and high-sensitivity (hs) cardiac troponin T (cTnT) at time of presentation with other algorithms for rapid rule-out of acute myocardial infarction (AMI).METHODS: 922 patients presenting to the emergency department with suspected AMI and available baseline copeptin measurements qualified for the present TRAPID-AMI substudy. Diagnostic measures using the DMS (copeptin <10, <14 or < 20 pmol/L and hs-cTnT≤14 ng/L), the 1 h-algorithm (hs-cTnT<12 ng/L and change <3 ng/L at 1 h), as well as the hs-cTnT limit-of-blank (LoB, <3 ng/L) and -detection (LoD, <5 ng/L) were compared. Outcomes were assessed as combined end-points of death and myocardial re-infarction.RESULTS: True-negative rule-out using the DMS could be achieved in 50.9%-62.3% of all patients compared to 35.0%, 45.3% and 64.5% using LoB, LoD or the 1 h-algorithm, respectively. The DMS showed NPVs of 98.1%-98.3% compared to 99.2% for the 1 h-algorithm, 99.4% for the LoB and 99.3% for the LoD. Sensitivities were 93.5%-94.8%, as well as 96.8%, 98.7% and 98.1%, respectively. Addition of clinical low-risk criteria such as a HEART-score ≤ 3 to the DMS resulted in NPVs and sensitivities of 100% with a true-negative rule-out to 33.8%-41.6%. Rates of the combined end-point of death/MI within 30 days ranged between 0.2% and 0.3% for all fast-rule-out protocols.CONCLUSION: Depending on the applied copeptin cut-off and addition of clinical low-risk criteria, the DMS might be an alternative to the hs-cTn-only-based algorithms for rapid AMI rule-out with comparable diagnostic measures and outcomes.
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| 27. |
- Mueller-Hennessen, Matthias, et al.
(författare)
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Diagnostic and prognostic implications using age- and gender-specific cut-offs for high-sensitivity cardiac troponin T - Sub-analysis from the TRAPID-AMI study
- 2016
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 209, s. 26-33
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate the impact of age-and gender-specific cut-offs for high-sensitivity cardiac troponin T (hs-cTnT) compared to the general 99th percentile hs-cTnT cut-off on diagnosis and prognosis of acute myocardial infarction (AMI).Methods: 1282 unselected patients presenting to the emergency department with suspected AMI were enrolled as part of the TRAPID-AMI study. In the present sub-analysis, reclassification of AMI diagnosis was performed by comparing the general hs-cTnT cut-off of 14 ng/L to previously proposed age-and gender-dependent hs-cTnT 99th percentile cut-offs (28 ng/L for >= 65 years, 9 ng/L for female and 15.5 ng/L for male patients). Patients were further clinically adjudicated into acute coronary syndrome (ACS) and non-ACS.Results: For patients >= 65 years, application of age-specified cut-offs resulted in a decrease of AMI from 29.8% to 18.3% in the entire cohort (n = 557) and 54.7% to 40.9% in the ACS subcohort (n = 225). Using gender-specific cut-offs, AMI-rate increased from 16.6% to 22.6% (entire cohort, n = 477) and 62.6% to 71.7% (ACS subcohort, n = 99) in women, whereas in men, rates decreased from 23.1% to 21.1% (entire cohort, n = 805) and 48.8% to 45.9% (ACS, n = 281), respectively. Age-specified cut-offs significantly reclassified patients for outcomes of 1-month and 3-month mortality in the entire and ACS cohort (14.2% net reclassification improvement, p < 0.001, respectively). Contrary, no significant differences in outcomes could be found using gender-specific cut-offs.Conclusions: While influence of gender-specific hs-cTnT cut-offs on diagnostic and prognostic reclassification was only modest in patients with suspected AMI, age-specific cut-offs showed a significant impact and may be considered for further validation.
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| 28. |
- Nowak, Richard, et al.
(författare)
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High sensitivity cardiac troponin T in patients not having an acute coronary syndrome : results from the TRAPID-AMI study
- 2017
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Ingår i: Biomarkers. - 1354-750X .- 1366-5804. ; 22:8, s. 709-714
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe the baseline, 1hr and delta high sensitivity cardiac troponin (hs-cTnT) values in patients with suspected acute myocardial infarction (AMI) but without a final acute coronary syndrome (ACS) diagnosis.Materials and methods: hs-cTnT assay for RAPID rule out of acute myocardial infarction (TRAPID-AMI) was a prospective diagnostic trial that enrolled emergency department (ED) patients with suspected AMI. Final patient diagnoses were adjudicated by a clinical events committee and subjects placed in different clinical groups: AMI, unstable angina, non-ACS cardiac, non-cardiac and unknown origin. The baseline, 1hr and delta hs-cTnT values were analysed in the 902 non-ACS patients.Results: Amongst the 1282 studied the patient groups were 213 (17%) AMI, 167 (13%) unstable angina, 113 (9%) non-ACS cardiac, 288 (22%) non-cardiac and 501 (39%) unknown origin. The hs-cTnT values in the non-cardiac and unknown origin groups were combined. The median hs-cTnT values (ng/L) were higher (p<0.001) in the non-ACS cardiac compared to the non-cardiac/unknown origin group at baseline (11.8,<5) and 1hr (12.3,<5). Their negative predictive values were 0.955 (baseline) and 0.954 (1hr) for predicting non-ACS cardiac versus non-cardiac/unknown origin diagnoses.Conclusions: Hs-cTnT may help predict whether non-ACS ED patients have a final non-ACS cardiac or non-cardiac/unknown origin diagnoses.
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| 29. |
- Pei, Zhangcheng, et al.
(författare)
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Assessing the cloud radiative bias at Macquarie Island in the ACCESS-AM2 model
- 2023
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Ingår i: Atmospheric Chemistry And Physics. - 1680-7316 .- 1680-7324. ; 23:23, s. 14691-14714
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Tidskriftsartikel (refereegranskat)abstract
- As a long-standing problem in climate models, large positive shortwave radiation biases exist at the surface over the Southern Ocean, impacting the accurate simulation of sea surface temperature, atmospheric circulation, and precipitation. Underestimations of low-level cloud fraction and liquid water content are suggested to predominantly contribute to these radiation biases. Most model evaluations for radiation focus on summer and rely on satellite products, which have their own limitations. In this work, we use surface-based observations at Macquarie Island to provide the first long-term, seasonal evaluation of both downwelling surface shortwave and longwave radiation in the Australian Community Climate and Earth System Simulator Atmosphere-only Model version 2 (ACCESS-AM2) over the Southern Ocean. The capacity of the Clouds and the Earth’s Radiant Energy System (CERES) product to simulate radiation is also investigated. We utilize the novel lidar simulator, the Automatic Lidar and Ceilometer Framework (ALCF), and all-sky cloud camera observations of cloud fraction to investigate how radiation biases are influenced by cloud properties.Overall, we find an overestimation of + 9.5 ± 33.5 W m−2 for downwelling surface shortwave radiation fluxes and an underestimation of −2.3 ± 13.5 W m−2 for downwelling surface longwave radiation in ACCESS-AM2 in all-sky conditions, with more pronounced shortwave biases of +25.0 ± 48.0 W m−2 occurring in summer. CERES presents an overestimation of +8.0 ± 18.0 W m−2 for the shortwave and an underestimation of −12.1 ± 12.2 W m−2 for the longwave in all-sky conditions. For the cloud radiative effect (CRE) biases, there is an overestimation of +4.8 ± 28.0 W m−2 in ACCESS-AM2 and an underestimation of −7.9 ± 20.9 W m−2in CERES. An overestimation of downwelling surface shortwave radiation is associated with an underestimated cloud fraction and low-level cloud occurrence. We suggest that modeled cloud phase is also having an impact on the radiation biases. Our results show that the ACCESS-AM2 model and CERES product require further development to reduce these radiation biases not just in shortwave and in all-sky conditions, but also in longwave and in clear-sky conditions.
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| 30. |
- Peret, Benjamin, et al.
(författare)
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Sequential induction of auxin efflux and influx carriers regulates lateral root emergence
- 2013
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Ingår i: Molecular Systems Biology. - : Nature Publishing Group. - 1744-4292 .- 1744-4292. ; 9, s. Article number 699-
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Tidskriftsartikel (refereegranskat)abstract
- In Arabidopsis, lateral roots originate from pericycle cells deep within the primary root. New lateral root primordia ( LRP) have to emerge through several overlaying tissues. Here, we report that auxin produced in new LRP is transported towards the outer tissues where it triggers cell separation by inducing both the auxin influx carrier LAX3 and cell-wall enzymes. LAX3 is expressed in just two cell files overlaying new LRP. To understand how this striking pattern of LAX3 expression is regulated, we developed a mathematical model that captures the network regulating its expression and auxin transport within realistic three-dimensional cell and tissue geometries. Our model revealed that, for the LAX3 spatial expression to be robust to natural variations in root tissue geometry, an efflux carrier is required-later identified to be PIN3. To prevent LAX3 from being transiently expressed in multiple cell files, PIN3 and LAX3 must be induced consecutively, which we later demonstrated to be the case. Our study exemplifies how mathematical models can be used to direct experiments to elucidate complex developmental processes.
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