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| 2. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 3. |
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| 4. |
- Roth, Gregory A, et al.
(författare)
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Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019 : Update From the GBD 2019 Study
- 2020
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 76:25, s. 2982-3021
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.
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| 5. |
- Clerbaux, C., et al.
(författare)
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CO measurements from the ACE-FTS satellite instrument: data analysis and validation using ground-based, airborne and spaceborne observations
- 2008
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 8, s. 2569-2594
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Tidskriftsartikel (refereegranskat)abstract
- The Atmospheric Chemistry Experiment (ACE) mission was launched in August 2003 to sound the atmosphere by solar occultation. Carbon monoxide (CO), a good tracer of pollution plumes and atmospheric dynamics, is one of the key species provided by the primary instrument, the ACE-Fourier Transform Spectrometer (ACE-FTS). This instrument performs measurements in both the CO 1-0 and 2-0 ro-vibrational bands, from which vertically resolved CO concentration profiles are retrieved, from the mid-troposphere to the thermosphere. This paper presents an updated description of the ACE-FTS version 2.2 CO data product, along with a comprehensive validation of these profiles using available observations (February 2004 to December 2006). We have compared the CO partial columns with ground-based measurements using Fourier transform infrared spectroscopy and millimeter wave radiometry, and the volume mixing ratio profiles with airborne (both high-altitude balloon flight and airplane) observations. CO satellite observations provided by nadir-looking instruments (MOPITT and TES) as well as limb-viewing remote sensors (MIPAS, SMR and MLS) were also compared with the ACE-FTS CO products. We show that the ACE-FTS measurements provide CO profiles with small retrieval errors (better than 5% from the upper troposphere to 40 km, and better than 10% above). These observations agree well with the correlative measurements, considering the rather loose coincidence criteria in some cases. Based on the validation exercise we assess the following uncertainties to the ACE-FTS measurement data: better than 15% in the upper troposphere (8–12 km), than 30% in the lower stratosphere (12–30 km), and than 25% from 30 to 100 km.
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| 6. |
- Guo, Hao, et al.
(författare)
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Heterogeneity and chemical reactivity of the remote troposphere defined by aircraft measurements
- 2021
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 21:18, s. 13729-13746
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Tidskriftsartikel (refereegranskat)abstract
- The NASA Atmospheric Tomography (ATom) mission built a photochemical climatology of air parcels based on in situ measurements with the NASA DC-8 aircraft along objectively planned profiling transects through the middle of the Pacific and Atlantic oceans. In this paper we present and analyze a data set of 10 s (21(m) merged and gap-filled observations of the key reactive species driving the chemical budgets of O-3 and CH4 (O-3, CH4, CO, H2O, HCHO, H2O2, CH3OOH, C2H6, higher alkanes, alkenes, aromatics, NOx, HNO3, HNO4, peroxyacetyl nitrate, other organic nitrates), consisting of 146 494 distinct air parcels from ATom deployments 1 through 4. Six models calculated the O-3 and CH4 photochemical tendencies from this modeling data stream for ATom 1. We find that 80 %-90 % of the total reactivity lies in the top 50 % of the parcels and 25 %-35 % in the top 10 %, supporting previous model-only studies that tropospheric chemistry is driven by a fraction of all the air. In other words, accurate simulation of the least reactive 50 % of the troposphere is unimportant for global budgets. Surprisingly, the probability densities of species and reactivities averaged on a model scale (100 km) differ only slightly from the 2 km ATom data, indicating that much of the heterogeneity in tropospheric chemistry can be captured with current global chemistry models. Comparing the ATom reactivities over the tropical oceans with climatological statistics from six global chemistry models, we find excellent agreement with the loss of O-3 and CH4 but sharp disagreement with production of O-3. The models sharply underestimate O-3 production below 4 km in both Pacific and Atlantic basins, and this can be traced to lower NOx levels than observed. Attaching photochemical reactivities to measurements of chemical species allows for a richer, yet more constrained-towhat-matters, set of metrics for model evaluation.
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| 7. |
- Guo, Hao, et al.
(författare)
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Heterogeneity and chemical reactivity of the remote troposphere defined by aircraft measurements – corrected
- 2023
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 23:1, s. 99-117
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Tidskriftsartikel (refereegranskat)abstract
- The NASA Atmospheric Tomography (ATom) mission built a photochemical climatology of air parcels based on in situ measurements with the NASA DC-8 aircraft along objectively planned profiling transects through the middle of the Pacific and Atlantic oceans. In this paper we present and analyze a data set of 10 s (2 km) merged and gap-filled observations of the key reactive species driving the chemical budgets of O3 and CH4 (O3, CH4, CO, H2O, HCHO, H2O2, CH3OOH, C2H6, higher alkanes, alkenes, aromatics, NOx, HNO3, HNO4, peroxyacetyl nitrate, and other organic nitrates), consisting of 146 494 distinct air parcels from ATom deployments 1 through 4. Six models calculated the O3 and CH4 photochemical tendencies from this modeling data stream for ATom 1. We find that 80 %–90 % of the total reactivity lies in the top 50 % of the parcels and 25 %–35 % in the top 10 %, supporting previous model-only studies that tropospheric chemistry is driven by a fraction of all the air. Surprisingly, the probability densities of species and reactivities averaged on a model scale (100 km) differ only slightly from the 2 km ATom 10 s data, indicating that much of the heterogeneity in tropospheric chemistry can be captured with current global chemistry models. Comparing the ATom reactivities over the tropical oceans with climatological statistics from six global chemistry models, we find generally good agreement with the reactivity rates for O3 and CH4. Models distinctly underestimate O3 production below 2 km relative to the mid-troposphere, and this can be traced to lower NOx levels than observed. Attaching photochemical reactivities to measurements of chemical species allows for a richer, yet more constrained-to-what-matters, set of metrics for model evaluation.
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| 8. |
- Singel, Kelly L., et al.
(författare)
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Mature neutrophils suppress T cell immunity in ovarian cancer microenvironment
- 2019
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Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 4:5
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial ovarian cancer (EOC) often presents with metastases and ascites. Granulocytic myeloid-derived suppressor cells are an immature population that impairs antitumor immunity. Since suppressive granulocytes in the ascites of patients with newly diagnosed EOC were morphologically mature, we hypothesized that PMN were rendered suppressive in the tumor microenvironment (TME). Circulating PMN from patients were not suppressive but acquired a suppressor phenotype (defined as ≥1 log10 reduction of anti-CD3/CD28-stimulated T cell proliferation) after ascites supernatant exposure. Ascites supernatants (20 of 31 supernatants) recapitulated the suppressor phenotype in PMN from healthy donors. T cell proliferation was restored with ascites removal and restimulation. PMN suppressors also inhibited T cell activation and cytokine production. PMN suppressors completely suppressed proliferation in naive, central memory, and effector memory T cells and in engineered tumor antigen-specific cytotoxic T lymphocytes, while antigen-specific cell lysis was unaffected. Inhibition of complement C3 activation and PMN effector functions, including CR3 signaling, protein synthesis, and vesicular trafficking, abrogated the PMN suppressor phenotype. Moreover, malignant effusions from patients with various metastatic cancers also induced the C3-dependent PMN suppressor phenotype. These results point to PMN impairing T cell expansion and activation in the TME and the potential for complement inhibition to abrogate this barrier to antitumor immunity.
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| 9. |
- Singel, Kelly L., et al.
(författare)
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Mitochondrial DNA in the tumor microenvironment activates neutrophils and is associated with worsened outcomes in patients with advanced epithelial ovarian cancer
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Advanced cancer causes necrosis and releases damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs activate neutrophils, including generation of neutrophil extracellular traps (NETs), which are injurious, thrombogenic, and implicated in metastasis. We hypothesized that extracellular mitochondrial DNA (mtDNA) in ascites from patients with epithelial ovarian cancer (EOC) would correlate with worsened outcomes.Banked ascites supernatants from patients with newly diagnosed advanced EOC were analyzed for mtDNA, neutrophil elastase, and activation of healthy donor neutrophils and platelets. TCGA was mined for expression of SELPand ELANE. The highest quartile of ascites mtDNA correlated with reduced progression-free survival (PFS) and a higher likelihood of disease progression within 12-months following primary surgery (n=68, log-rank, p=0.0178). NETs were detected in resected tumors. Ascites supernatants chemoattracted neutrophils, induced NETs, and activated platelets. Ascites exposure rendered neutrophils suppressive, based on abrogation of ex vivostimulated T cell proliferation. Increased SELPmRNA expression correlated with worsened overall survival (n=302, Cox model, p=0.02).In this single-center retrospective analysis, ascites mtDNA correlated with worsened PFS in advanced EOC. Our results support mitochondrial and other DAMPs activating neutrophil and platelet responses that facilitate metastasis and obstruct anti-tumor immunity. These pathways are potential prognostic markers and therapeutic targets.
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| 10. |
- Singel, Kelly L., et al.
(författare)
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Mitochondrial DNA in the tumour microenvironment activates neutrophils and is associated with worse outcomes in patients with advanced epithelial ovarian cancer
- 2019
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 120:2, s. 207-217
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Advanced cancer causes necrosis and releases damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs activate neutrophils, including generation of neutrophil extracellular traps (NETs), which are injurious, thrombogenic, and implicated in metastasis. We hypothesised that extracellular mitochondrial DNA (mtDNA) in ascites from patients with epithelial ovarian cancer (EOC) would correlate with worse outcomes.METHODS: Banked ascites supernatants from patients with newly diagnosed advanced EOC were analysed for mtDNA, neutrophil elastase, and activation of healthy donor neutrophils and platelets. TCGA was mined for expression of SELP and ELANE.RESULTS: The highest quartile of ascites mtDNA correlated with reduced progression-free survival (PFS) and a higher likelihood of disease progression within 12-months following primary surgery (n = 68, log-rank, p = 0.0178). NETs were detected in resected tumours. Ascites supernatants chemoattracted neutrophils, induced NETs, and activated platelets. Ascites exposure rendered neutrophils suppressive, based on abrogation of ex vivo stimulated T cell proliferation. Increased SELP mRNA expression correlated with worse overall survival (n = 302, Cox model, p = 0.02).CONCLUSION: In this single-centre retrospective analysis, ascites mtDNA correlated with worse PFS in advanced EOC. Mitochondrial and other DAMPs in ascites may activate neutrophil and platelet responses that facilitate metastasis and obstruct anti-tumour immunity. These pathways are potential prognostic markers and therapeutic targets.
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