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2. |
- Bruijn, Laura E., et al.
(author)
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A histopathological classification scheme for abdominal aortic aneurysm disease
- 2021
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In: JVS-Vascular Science. - : Elsevier. - 2666-3503. ; 2, s. 260-273
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Journal article (peer-reviewed)abstract
- Objective: Two consensus histopathological classifications for thoracic aortic aneurysms (TAAs) and inflammatory aortic diseases have been issued to facilitate clinical decision-making and inter-study comparison. However, these consensus classifications do not specifically encompass abdominal aortic aneurysms (AAAs). Given its high prevalence and the existing profound pathophysiologic knowledge gaps, extension of the consensus classification scheme to AAAs would be highly instrumental. The aim of this study was to test the applicability of, and if necessary to adapt, the issued consensus classification schemes for AAAs.Methods: Seventy-two AAA anterolateral wall samples were collected during elective and emergency open aneurysm repair performed between 2002 and 2013. Histologic analysis (hematoxylin and eosin and Movat Pentachrome) and (semi-quantitative and qualitative) grading were performed in order to map the histological aspects of AAA. Immunohistochemistry was performed for visualization of aspects of the adaptive and innate immune system, and for a more detailed analysis of atherosclerotic lesions in AAA.Results: Because the existing consensus classification schemes do not adequately capture the aspects of AAA disease, an AAA-specific 11-point histopathological consensus classification was devised. Systematic application of this classification indicated several universal features for AAA (eg, [almost] complete elastolysis), but considerable variation for other aspects (eg, inflammation and atherosclerotic lesions).Conclusions: This first multiparameter histopathological AAA consensus classification illustrates the sharp histological contrasts between thoracic and abdominal aneurysms. The value of the proposed scoring system for AAA disease is illustrated by its discriminatory capacity to identify samples from patients with a nonclassical (genetic) variant of AAA disease.
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3. |
- Gabel, Gabor, et al.
(author)
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Parallel Murine and Human Aortic Wall Genomics Reveals Metabolic Reprogramming as Key Driver of Abdominal Aortic Aneurysm Progression
- 2021
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In: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 10:17
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Journal article (peer-reviewed)abstract
- Background: While numerous interventions effectively interfered with abdominal aortic aneurysm (AAA) formation/progression in preclinical models, none of the successes translated into clinical success. Hence, a systematic exploration of parallel and divergent processes in clinical AAA disease and its 2 primary models (the porcine pancreatic elastase and angiotensin-II infusion [AngII] murine model) was performed to identify mechanisms relevant for aneurysm disease.Methods and Results: This study combines Movat staining and pathway analysis for histological and genomic comparisons between clinical disease and its models. The impact of a notable genomic signal for metabolic reprogramming was tested in a rescue trial (AngII model) evaluating the impact of 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one (PFK15)-mediated interference with main glycolytic switch PFKFB3. Histological evaluation characterized the AngII model as a dissection model that is accompanied by adventitial fibrosis. The porcine pancreatic elastase model showed a transient inflammatory response and aortic dilatation, followed by stabilization and fibrosis. Normalization of the genomic responses at day 14 confirmed the self-limiting nature of the porcine pancreatic elastase model. Clear parallel genomic responses with activated adaptive immune responses, and particularly strong signals for metabolic switching were observed in human AAA and the AngII model. Rescue intervention with the glycolysis inhibitor PFK15 in the AngII model showed that interference with the glycolytic switching quenches aneurysm formation.Conclusions: Despite clear morphological contrasts, remarkable genomic parallels exist for clinical AAA disease and the AngII model. The metabolic response appears causatively involved in AAA progression and provides a novel therapeutic target. The clear transient genomic response classifies the porcine pancreatic elastase model as a disease initiation model.
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4. |
- Jones, Gregory T., et al.
(author)
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Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
- 2017
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In: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
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Journal article (peer-reviewed)abstract
- Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
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5. |
- Khosla, S., et al.
(author)
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Meta-analysis of peak wall stress in ruptured, symptomatic and intact abdominal aortic aneurysms
- 2014
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In: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 101:11, s. 1350-1357
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Research review (peer-reviewed)abstract
- Background: Abdominal aortic aneurysm (AAA) is an important cause of sudden death; however, there are currently incomplete means to predict the risk of AAA rupture. AAA peak wall stress (PWS) can be estimated using finite element analysis (FEA) methods from computed tomography (CT) scans. The question is whether AAA PWS can predict AAA rupture. The aim of this systematic review was to compare PWS in patients with ruptured and intact AAA. Methods: The MEDLINE database was searched on 25 May 2013. Case-control studies assessing PWS in asymptomatic intact, and acutely symptomatic or ruptured AAA from CT scans using FEA were included. Data were extracted independently. A random-effects model was used to calculate standard mean differences (SMDs) for PWS measurements. Results: Nine studies assessing 348 individuals were identified and used in the meta-analysis. Results from 204 asymptomatic intact and 144 symptomatic or ruptured AAAs showed that PWS was significantly greater in the symptomatic/ruptured AAAs compared with the asymptomatic intact AAAs (SMD 0.95, 95 per cent confidence interval 0. 71 to 1.18; P < 0. 001). The findings remained significant after adjustment for mean systolic blood pressure, standardized at 120 mmHg(SMD 0.68, 0.39 to 0.96; P < 0. 001). Minimal heterogeneity between studies was noted (I-2 = 0 per cent). Conclusion: This study suggests that PWS is greater in symptomatic or ruptured AAA than in asymptomatic intact AAA.
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6. |
- Martin, Maria A., et al.
(author)
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Ten new insights in climate science 2021 : a horizon scan
- 2021
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In: Global Sustainability. - : Cambridge University Press (CUP). - 2059-4798. ; 4, s. 1-20
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Research review (peer-reviewed)abstract
- Non-technical summary: We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding about the remaining options to achieve the Paris Agreement goals, through overcoming political barriers to carbon pricing, taking into account non-CO2 factors, a well-designed implementation of demand-side and nature-based solutions, resilience building of ecosystems and the recognition that climate change mitigation costs can be justified by benefits to the health of humans and nature alone. We consider new insights about what to expect if we fail to include a new dimension of fire extremes and the prospect of cascading climate tipping elements.Technical summary: A synthesis is made of 10 topics within climate research, where there have been significant advances since January 2020. The insights are based on input from an international open call with broad disciplinary scope. Findings include: (1) the options to still keep global warming below 1.5 °C; (2) the impact of non-CO2 factors in global warming; (3) a new dimension of fire extremes forced by climate change; (4) the increasing pressure on interconnected climate tipping elements; (5) the dimensions of climate justice; (6) political challenges impeding the effectiveness of carbon pricing; (7) demand-side solutions as vehicles of climate mitigation; (8) the potentials and caveats of nature-based solutions; (9) how building resilience of marine ecosystems is possible; and (10) that the costs of climate change mitigation policies can be more than justified by the benefits to the health of humans and nature.Social media summary: How do we limit global warming to 1.5 °C and why is it crucial? See highlights of latest climate science.
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7. |
- Matthews, Evan O., et al.
(author)
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Athero-occlusive Disease Appears to be Associated with Slower Abdominal Aortic Aneurysm Growth : An Exploratory Analysis of the TEDY Trial
- 2022
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In: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 63:4, s. 632-640
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Journal article (peer-reviewed)abstract
- Objective: The role of atherosclerosis in abdominal aortic aneurysm (AAA) pathogenesis is controversial. The aim of this study was to compare AAA growth in patients who did and did not have concurrent athero-occlusive disease (AOD). Methods: Patients with an AAA measuring 35 - 49 mm in maximum diameter were recruited as part of the TElmisartan in the management of abdominal aortic aneurysm (TEDY) trial. TEDY participants who had infrarenal aortic volume and orthogonal diameter assessed by computed tomography at entry and at least one other time point during the trial (12 and/or 24 months) were included. AOD was defined by prior diagnoses of coronary heart disease, stroke, or peripheral arterial disease or an ankle brachial pressure index < 0.90. The increase in AAA volume and diameter from entry for participants who did and did not have AOD was assessed using linear mixed effects models; 131 of the 210 participants recruited to TEDY were included. Results: In an unadjusted analysis, the mean (95% confidence interval) annual increases in AAA volume and diameter for participants with AOD were 3.26 (0.82 - 5.70) cm(3) and 0.70 (0.19 - 1.22) mm slower than those without AOD, p = .008 and.007 respectively. The association between AOD and significantly slower AAA growth was maintained after adjusting for risk factors and medications, significantly unequally distributed between participants with and without an AOD diagnosis. Conclusion: In an exploratory analysis of a selective cohort from the TEDY trial, AOD was associated with slower AAA growth. Validation of these findings in other cohorts is needed.
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8. |
- Rainsley, Eleanor, et al.
(author)
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Pleistocene glacial history of the New Zealand subantarctic islands
- 2019
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In: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 15:2, s. 423-448
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Journal article (peer-reviewed)abstract
- The New Zealand subantarctic islands of Auckland and Campbell, situated between the subtropical front and the Antarctic Convergence in the Pacific sector of the Southern Ocean, provide valuable terrestrial records from a globally important climatic region. Whilst the islands show clear evidence of past glaciation, the timing and mechanisms behind Pleistocene environmental and climate changes remain uncertain. Here we present a multidisciplinary study of the islands-including marine and terrestrial geomorphological surveys, extensive analyses of sedimentary sequences, a comprehensive dating programme, and glacier flow line modelling-to investigate multiple phases of glaciation across the islands. We find evidence that the Auckland Islands hosted a small ice cap 384 000 +/- 26 000 years ago (384 +/- 26 ka), most likely during Marine Isotope Stage 10, a period when the subtropical front was reportedly north of its present-day latitude by several degrees, and consistent with hemispheric-wide glacial expansion. Flow line modelling constrained by field evidence suggests a more restricted glacial period prior to the LGM that formed substantial valley glaciers on the Campbell and Auckland Islands around 72-62 ka. Despite previous interpretations that suggest the maximum glacial extent occurred in the form of valley glaciation at the Last Glacial Maximum (LGM; similar to 21 ka), our combined approach suggests minimal LGM glaciation across the New Zealand subantarctic islands and that no glaciers were present during the Antarctic Cold Reversal (ACR; similar to 15-13 ka). Instead, modelling implies that despite a regional mean annual air temperature depression of similar to 5 degrees C during the LGM, a combination of high seasonality and low precipitation left the islands incapable of sustaining significant glaciation. We suggest that northwards expansion of winter sea ice during the LGM and subsequent ACR led to precipitation starvation across the middle to high latitudes of the Southern Ocean, resulting in restricted glaciation of the subantarctic islands.
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9. |
- Singh, Tejas P., et al.
(author)
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Association between aortic peak wall stress and rupture index with abdominal aortic aneurysm–related events
- 2023
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In: European Radiology. - : Springer Nature. - 0938-7994 .- 1432-1084. ; 33:8, s. 5698-5706
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Journal article (peer-reviewed)abstract
- Objective: The aim of this study was to assess whether aortic peak wall stress (PWS) and peak wall rupture index (PWRI) were associated with the risk of abdominal aortic aneurysm (AAA) rupture or repair (defined as AAA events) among participants with small AAAs. Methods: PWS and PWRI were estimated from computed tomography angiography (CTA) scans of 210 participants with small AAAs (≥ 30 and ≤ 50 mm) prospectively recruited between 2002 and 2016 from two existing databases. Participants were followed for a median of 2.0 (inter-quartile range 1.9, 2.8) years to record the incidence of AAA events. The associations between PWS and PWRI with AAA events were assessed using Cox proportional hazard analyses. The ability of PWS and PWRI to reclassify the risk of AAA events compared to the initial AAA diameter was examined using net reclassification index (NRI) and classification and regression tree (CART) analysis. Results: After adjusting for other risk factors, one standard deviation increase in PWS (hazard ratio, HR, 1.56, 95% confidence intervals, CI 1.19, 2.06; p = 0.001) and PWRI (HR 1.74, 95% CI 1.29, 2.34; p < 0.001) were associated with significantly higher risks of AAA events. In the CART analysis, PWRI was identified as the best single predictor of AAA events at a cut-off value of > 0.562. PWRI, but not PWS, significantly improved the classification of risk of AAA events compared to the initial AAA diameter alone. Conclusion: PWS and PWRI predicted the risk of AAA events but only PWRI significantly improved the risk stratification compared to aortic diameter alone. Key Points: • Aortic diameter is an imperfect measure of abdominal aortic aneurysm (AAA) rupture risk. • This observational study of 210 participants found that peak wall stress (PWS) and peak wall rupture index (PWRI) predicted the risk of aortic rupture or AAA repair. • PWRI, but not PWS, significantly improved the risk stratification for AAA events compared to aortic diameter alone.
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10. |
- Singh, Tejas P., et al.
(author)
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Effect of Telmisartan on the Peak Wall Stress and Peak Wall Rupture Index of Small Abdominal Aortic Aneurysms : An Exploratory Analysis of the TEDY Trial
- 2022
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In: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 64:4, s. 396-404
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Journal article (peer-reviewed)abstract
- Objective: This study was an unplanned exploratory analysis of a subset of participants from the Telmisartan in the Management of Abdominal Aortic Aneurysm (TEDY) trial. It aimed to assess the efficacy of the angiotensin 1 receptor blocker telmisartan in reducing abdominal aortic aneurysm (AAA) peak wall stress (PWS) and peak wall rupture index (PWRI) among individuals with small AAAs. Methods: Participants with AAAs measuring 35 - 49 mm in maximum diameter were randomised to receive telmisartan 40 mg or identical placebo in the TEDY trial. Participants who had computed tomography angiography performed at entry and at least one other time point during the trial (12 or 24 months) were included in the current study. Orthogonal AAA diameter, PWS, and PWRI were measured using previously validated methods. The annual change in PWS and PWRI from baseline was compared between participants allocated telmisartan or placebo using linear mixed effects models. These models were either unadjusted or adjusted for risk factors that were different in the groups at entry (p <.100) or systolic blood pressure (SBP) at one year. Results: Of the 207 participants recruited to TEDY, 124 were eligible for inclusion in this study. This study included 65 and 59 participants from the telmisartan and placebo groups, respectively. The PWS and PWRI were not significantly different in the two groups at baseline. Participants allocated telmisartan had a slower annual increase in PWS (-4.19; 95% CI -8.24, -0.14 kPa/year; p = .043) and PWRI (-0.014; 95% CI -0.026, -0.001; p = .032) compared with those allocated placebo after adjusting for risk factors. After adjustment for SBP at one year, telmisartan did not significantly reduce annual increases in PWS or PWRI. Conclusion: The findings of this study suggest that telmisartan limits the rate of increase in PWS and PWRI of small AAAs by reducing blood pressure.
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11. |
- Singh, Tejas P., et al.
(author)
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Systematic Review and Meta-Analysis of Peak Wall Stress and Peak Wall Rupture Index in Ruptured and Asymptomatic Intact Abdominal Aortic Aneurysms
- 2021
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In: Journal of the American Heart Association. - : WILEY. - 2047-9980. ; 10:8
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Research review (peer-reviewed)abstract
- Background Prior studies have suggested aortic peak wall stress (PWS) and peak wall rupture index (PWRI) can estimate the rupture risk of an abdominal aortic aneurysm (AAA), but whether these measurements have independent predictive ability over assessing AAA diameter alone is unclear. The aim of this systematic review was to compare PWS and PWRI in participants with ruptured and asymptomatic intact AAAs of similar diameter. Methods and Results Web of Science, Scopus, Medline, and The Cochrane Library were systematically searched to identify studies assessing PWS and PWRI in ruptured and asymptomatic intact AAAs of similar diameter. Random-effects meta-analyses were performed using inverse variance-weighted methods. Leave-one-out sensitivity analyses were conducted to assess the robustness of findings. Risk of bias was assessed using a modification of the Newcastle-Ottawa scale and standard quality assessment criteria for evaluating primary research papers. Seven case-control studies involving 309 participants were included. Meta-analyses suggested that PWRI (standardized mean difference, 0.42; 95% CI, 0.14-0.70; P=0.004) but not PWS (standardized mean difference, 0.13; 95% CI, -0.18 to 0.44; P=0.418) was greater in ruptured than intact AAAs. Sensitivity analyses suggested that the findings were not dependent on the inclusion of any single study. The included studies were assessed to have a medium to high risk of bias. Conclusions Based on limited evidence, this study suggested that PWRI, but not PWS, is greater in ruptured than asymptomatic intact AAAs of similar maximum aortic diameter.
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12. |
- Thanigaimani, Shivshankar, et al.
(author)
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Association Between Metformin Prescription and Abdominal Aortic Aneurysm Growth and Clinical Events : a Systematic Review and Meta-Analysis.
- 2021
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In: European Journal of Vascular and Endovascular Surgery. - : Elsevier. - 1078-5884 .- 1532-2165. ; 62:5, s. 747-756
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Research review (peer-reviewed)abstract
- OBJECTIVE: A meta-analysis of the association between metformin prescription and abdominal aortic aneurysm (AAA) growth and events (rupture or surgical repair) was performed.METHODS: Open source databases were searched for observational studies reporting the association between metformin prescription and AAA growth or events. Meta-analyses were performed using random effects models. The risk of bias of included studies was assessed using a quality assessment tool developed in a previous systematic review. Sensitivity analyses restricted to people with diabetes, leave one out analyses, and an individual patient risk factor adjusted sub-analysis were performed. Funnel plots assessed reporting bias.RESULTS: Eight studies comprising 153 553 patients were included, of whom 35 240 were and 118 313 were not prescribed metformin. Pooled weighted mean (± standard deviation) AAA growth was significantly reduced in patients prescribed metformin (0.9 ± 0.4 mm/year) compared with those not receiving the medication (1.8 ± 0.4 mm/year; weighted mean difference [WMD] 0.8 mm/year, 95% confidence interval [CI] 0.5 - 1.1; p < .001; I2 = 89%). Leave one out analysis suggested that the significance of findings did not change after removal of individual studies. A sub-analysis within people with diabetes suggested that metformin reduced AAA growth (WMD 0.7 mm/year, 95% CI 0.3 - 1.0). Metformin prescription was associated with a reduced risk of AAA events (risk ratio 0.6, 95% CI 0.4 - 0.9, p = .028). Three, four, and one studies had low, moderate, and high risk of bias, respectively. Individual patient data analysis suggested that metformin prescription slowed annual AAA growth by 0.5 mm/year (95% CI 0.2 - 0.7). The GRADE summary suggested that the certainty of evidence that metformin limited AAA growth and prevented AAA events was very low.CONCLUSION: Observational studies suggest that metformin prescription is associated with a clinically important significant reduction in both growth and clinically relevant events in people with AAA. These findings support the need for randomised trials to examine the benefit of metformin.
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13. |
- Thomas, Zoë A., et al.
(author)
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Tipping elements and amplified polar warming during the Last Interglacial
- 2020
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In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 233
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Research review (peer-reviewed)abstract
- Irreversible shifts of large-scale components of the Earth system (so-called ‘tipping elements’) on policy-relevant timescales are a major source of uncertainty for projecting the impacts of future climate change. The high latitudes are particularly vulnerable to positive feedbacks that amplify change through atmosphere-ocean-ice interactions. Unfortunately, the short instrumental record does not capture the full range of past or projected climate scenarios (a situation particularly acute in the high latitudes). Natural archives from past periods warmer than present day, however, can be used to explore drivers and responses to forcing, and provide data against which to test models, thereby offering insights into the future. The Last Interglacial (129–116,000 years before present) — the warmest interglacial of the last 800,000 years — was the most recent period during which global temperatures were comparable with low-end 21st Century projections (up to 2 °C warmer, with temperature increase amplified over polar latitudes), providing a potentially useful analogue for future change. Substantial environmental changes happened during this time. Here we synthesise the nature and timing of potential high-latitude tipping elements during the Last Interglacial, including sea ice, extent of the boreal forest, permafrost, ocean circulation, and ice sheets/sea level. We also review the thresholds and feedbacks that likely operated through this period. Notably, substantial ice mass loss from Greenland, the West Antarctic, and possibly sectors of the East Antarctic drove a 6–9 m rise in global sea level. This was accompanied by reduced summer sea-ice extent, poleward-extended boreal forest, and reduced areas of permafrost. Despite current chronological uncertainties, we find that tipping elements in the high latitudes all experienced rapid and abrupt change (within 1–2 millennia of each other) across both hemispheres, while recovery to prior conditions took place over multi-millennia. Our synthesis demonstrates important feedback loops between tipping elements, amplifying polar and global change during the Last Interglacial. The high sensitivity and tight interconnections between polar tipping elements suggests that they could exhibit similar thresholds of vulnerability in the future, particularly if the aspirations of the Paris Agreement are not met.
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14. |
- Turney, Chris S M, et al.
(author)
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Rapid global ocean-atmosphere response to Southern Ocean freshening during the last glacial
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Journal article (peer-reviewed)abstract
- Contrasting Greenland and Antarctic temperatures during the last glacial period (115,000 to 11,650 years ago) are thought to have been driven by imbalances in the rates of formation of North Atlantic and Antarctic Deep Water (the 'bipolar seesaw'). Here we exploit a bidecadally resolved 14C data set obtained from New Zealand kauri (Agathis australis) to undertake high-precision alignment of key climate data sets spanning iceberg-rafted debris event Heinrich 3 and Greenland Interstadial (GI) 5.1 in the North Atlantic (~30,400 to 28,400 years ago). We observe no divergence between the kauri and Atlantic marine sediment 14C data sets, implying limited changes in deep water formation. However, a Southern Ocean (Atlantic-sector) iceberg rafted debris event appears to have occurred synchronously with GI-5.1 warming and decreased precipitation over the western equatorial Pacific and Atlantic. An ensemble of transient meltwater simulations shows that Antarctic-sourced salinity anomalies can generate climate changes that are propagated globally via an atmospheric Rossby wave train.
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16. |
- Wanhainen, Anders, et al.
(author)
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Surrogate Markers of Abdominal Aortic Aneurysm Progression
- 2016
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In: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 36:2, s. 236-244
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Journal article (peer-reviewed)abstract
- The natural course of many abdominal aortic aneurysms (AAA) is to gradually expand and eventually rupture and monitoring the disease progression is essential to their management. In this publication, we review surrogate markers of AAA progression. AAA diameter remains the most widely used and important marker of AAA growth. Standardized reporting of reproducible methods of measuring AAA diameter is essential. Newer imaging assessments, such as volume measurements, biomechanical analyses, and functional and molecular imaging, as well as circulating biomarkers, have potential to add important information about AAA progression. Currently, however, there is insufficient evidence to recommend their routine use in clinical practice.
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