| 1. |
- Pihl, E., et al.
(författare)
-
Ten new insights in climate science 2020- A horizon scan
- 2020
-
Ingår i: Global Sustainability. - : Cambridge University Press. - 2059-4798.
-
Tidskriftsartikel (refereegranskat)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 of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in tropical ecosystems is weakening. Adverse impacts on human society include increasing water shortages and impacts on mental health. Options for solutions emerge from rethinking economic models, rights-based litigation, strengthened governance systems and a new social contract. The disruption caused by COVID-19 could be seized as an opportunity for positive change, directing economic stimulus towards sustainable investments. Technical summary A synthesis is made of ten fields within climate science where there have been significant advances since mid-2019, through an expert elicitation process with broad disciplinary scope. Findings include: (1) a better understanding of equilibrium climate sensitivity; (2) abrupt thaw as an accelerator of carbon release from permafrost; (3) changes to global and regional land carbon sinks; (4) impacts of climate change on water crises, including equity perspectives; (5) adverse effects on mental health from climate change; (6) immediate effects on climate of the COVID-19 pandemic and requirements for recovery packages to deliver on the Paris Agreement; (7) suggested long-term changes to governance and a social contract to address climate change, learning from the current pandemic, (8) updated positive cost-benefit ratio and new perspectives on the potential for green growth in the short- A nd long-term perspective; (9) urban electrification as a strategy to move towards low-carbon energy systems and (10) rights-based litigation as an increasingly important method to address climate change, with recent clarifications on the legal standing and representation of future generations. Social media summary Stronger permafrost thaw, COVID-19 effects and growing mental health impacts among highlights of latest climate science.
|
|
| 2. |
- Casar Borota, Olivera, et al.
(författare)
-
Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations
- 2021
-
Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:4, s. 1183-1194
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors. Objective: To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs. Design: We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored. Results: Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; 28%) than in those with APTs (4/30;13%). Lack of ATRX was most common in the corticotroph tumors, 7/22 (32%), versus tumors of the Pit-1 lineage, 2/24 (8%). Loss-of-function ATRX mutations were found in all 9 ATRX immunonegative cases: nonsense mutations (n = 4), frameshift deletions (n = 4), and large deletions affecting 22-28 of the 36 exons (n = 3). More than 1 ATRX gene defect was identified in 2 PCs. Conclusion: ATRX mutations occur in a subset of APTs and are more common in corticotroph tumors. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumors.
|
|
| 3. |
- Maroju, P. K., et al.
(författare)
-
Analysis of two-color photoelectron spectroscopy for attosecond metrology at seeded free-electron lasers
- 2021
-
Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 23:4
-
Tidskriftsartikel (refereegranskat)abstract
- The generation of attosecond pulse trains at free-electron lasers opens new opportunities in ultrafast science, as it gives access, for the first time, to reproducible, programmable, extreme ultraviolet (XUV) waveforms with high intensity. In this work, we present a detailed analysis of the theoretical model underlying the temporal characterization of the attosecond pulse trains recently generated at the free-electron laser FERMI. In particular, the validity of the approximations used for the correlated analysis of the photoelectron spectra generated in the two-color photoionization experiments are thoroughly discussed. The ranges of validity of the assumptions, in connection with the main experimental parameters, are derived.
|
|
| 4. |
- Blasiak, Robert, et al.
(författare)
-
Evolving Perspectives of Stewardship in the Seafood Industry
- 2021
-
Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Humanity has never benefited more from the ocean as a source of food, livelihoods, and well-being, yet on a global scale this has been accompanied by trajectories of degradation and persistent inequity. Awareness of this has spurred policymakers to develop an expanding network of ocean governance instruments, catalyzed civil society pressure on the public and private sector, and motivated engagement by the general public as consumers and constituents. Among local communities, diverse examples of stewardship have rested on the foundation of care, knowledge and agency. But does an analog for stewardship exist in the context of globally active multinational corporations? Here, we consider the seafood industry and its efforts to navigate this new reality through private governance. We examine paradigmatic events in the history of the sustainable seafood movement, from seafood boycotts in the 1970s through to the emergence of certification measures, benchmarks, and diverse voluntary environmental programs. We note four dimensions of stewardship in which efforts by actors within the seafood industry have aligned with theoretical concepts of stewardship, which we describe as (1) moving beyond compliance, (2) taking a systems perspective, (3) living with uncertainty, and (4) understanding humans as embedded elements of the biosphere. In conclusion, we identify emerging stewardship challenges for the seafood industry and suggest the urgent need to embrace a broader notion of ocean stewardship that extends beyond seafood.
|
|
| 5. |
- Fuchtbauer, Laila, et al.
(författare)
-
Increased Number of Retinal Vessels in Acromegaly.
- 2020
-
Ingår i: European journal of endocrinology. - 1479-683X. ; 182:3
-
Tidskriftsartikel (refereegranskat)abstract
- Excess of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), as in acromegaly, is associated with an increased risk of diabetes, but whether retinal vessels are altered is unknown. The aim of this study was to evaluate retinal vessel morphology in patients with acromegaly at diagnosis and after treatment and to describe the prevalence of diabetic retinopathy in patients with long-standing acromegaly and diabetes.Two independent observational studies, one being prospective and the other retrospective and cross-sectional.Retinal vessel morphology of 26 patients with acromegaly was examined at diagnosis and 1 year after treatment and compared to 13 healthy controls. Cross-sectional evaluation of 39 patients with long-standing acromegaly and diabetes was performed. Fundus photographs were digitally analyzed for vessel morphology.Patients with acromegaly had a median (interquartile range) of 34.3 (30.0-39.0) vessel branching points compared to 27.0 (24.0-29.0) for healthy controls (P < 0.001). Tortuosity of arterioles and venules remained unchanged. Vessel morphology did not change significantly after treatment. Patients with acromegaly and diabetes for a median of 14 years also had a high number of branching points [34.2 (32.5-35.6)], but the prevalence of diabetic retinopathy was not higher than expected in diabetic patients without acromegaly.Patients with acromegaly have an increased number of vascular branching points in the retina without an alteration of macroscopic vessel morphology. This is consistent with an angiogenic effect of GH/IGF-1 in humans. The prevalence of diabetic retinopathy was not increased in patients with acromegaly and diabetes.
|
|
| 6. |
- Holm Nielsen, S., et al.
(författare)
-
The novel collagen matrikine, endotrophin, is associated with mortality and cardiovascular events in patients with atherosclerosis
- 2021
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 290:1, s. 179-189
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Rupture of atherosclerotic plaques is the major cause of acute cardiovascular events. The biomarker PRO-C6 measuring Endotrophin, a matrikine of collagen type VI, may provide valuable information detecting subjects in need of intensified strategies for secondary prevention. Objective: In this study, we evaluate endotrophin in human atherosclerotic plaques and circulating levels of PRO-C6 in patients with atherosclerosis, to determine the predictive potential of the biomarker. Methods: Sections from the stenotic human carotid plaques were stained with the PRO-C6 antibody. PRO-C6 was measured in serum of patients enrolled in the Carotid Plaque Imagining Project (CPIP) (discovery cohort, n = 577) and the innovative medicines initiative surrogate markers for micro- and macrovascular hard end-points for innovative diabetes tools (IMI-SUMMIT, validation cohort, n = 1,378). Median follow-up was 43 months. Kaplan–Meier curves and log-rank tests were performed in the discovery cohort. Cox proportional hazard regression analysis (HR with 95% CI) was used in the discovery cohort and binary logistic regression (OR with 95% CI) in the validation cohort. Results: PRO-C6 was localized in the core and shoulder of the atherosclerotic plaque. In the discovery cohort, PRO-C6 independently predicted future cardiovascular events (HR 1.089 [95% CI 1.019 −1.164], p = 0.01), cardiovascular death (HR 1.118 [95% CI 1.008 −1.241], p = 0.04) and all-cause death (HR 1.087 [95% CI 1.008 −1.172], p = 0.03). In the validation cohort, PRO-C6 predicted future cardiovascular events (OR 1.063 [95% CI 1.011 −1.117], p = 0.017). Conclusion: PRO-C6 is present in the atherosclerotic plaque and associated with future cardiovascular events, cardiovascular death and all-cause mortality in two large prospective cohorts.
|
|
| 7. |
- Petrie, Mark C, et al.
(författare)
-
Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes.
- 2020
-
Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 323:14, s. 1353-1368
-
Tidskriftsartikel (refereegranskat)abstract
- Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients with HFrEF, even those without diabetes.To evaluate the effects of dapagliflozin in patients with HFrEF with and without diabetes.Exploratory analysis of a phase 3 randomized trial conducted at 410 sites in 20 countries. Patients with New York Heart Association classification II to IV with an ejection fraction less than or equal to 40% and elevated plasma N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019.Addition of once-daily 10 mg of dapagliflozin or placebo to recommended therapy.The primary outcome was the composite of an episode of worsening heart failure or cardiovascular death. This outcome was analyzed by baseline diabetes status and, in patients without diabetes, by glycated hemoglobin level less than 5.7% vs greater than or equal to 5.7%.Among 4744 patients randomized (mean age, 66 years; 1109 [23%] women; 2605 [55%] without diabetes), 4742 completed the trial. Among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73 [95% CI, 0.60-0.88]). In patients with diabetes, the primary outcome occurred in 215 of 1075 (20.0%) in the dapagliflozin group and 271 of 1064 (25.5%) in the placebo group (hazard ratio, 0.75 [95% CI, 0.63-0.90]) (P value for interaction = .80). Among patients without diabetes and a glycated hemoglobin level less than 5.7%, the primary outcome occurred in 53 of 438 patients (12.1%) in the dapagliflozin group and 71 of 419 (16.9%) in the placebo group (hazard ratio, 0.67 [95% CI, 0.47-0.96]). In patients with a glycated hemoglobin of at least 5.7%, the primary outcome occurred in 118 of 860 patients (13.7%) in the dapagliflozin group and 160 of 888 (18.0%) in the placebo group (hazard ratio, 0.74 [95% CI, 0.59-0.94]) (P value for interaction = .72). Volume depletion was reported as an adverse event in 7.3% of patients in the dapagliflozin group and 6.1% in the placebo group among patients without diabetes and in 7.8% of patients in the dapagliflozin group and 7.8% in the placebo group among patients with diabetes. A kidney adverse event was reported in 4.8% of patients in the dapagliflozin group and 6.0% in the placebo group among patients without diabetes and in 8.5% of patients in the dapagliflozin group and 8.7% in the placebo group among patients with diabetes.In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status.ClinicalTrials.gov Identifier: NCT03036124.
|
|
| 8. |
- Shrestha, Sarita, 1991-, et al.
(författare)
-
The use of ICD codes to identify IBD subtypes and phenotypes of the Montreal classification in the Swedish National Patient Register
- 2020
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 55:4, s. 430-435
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Whether data on International Classification of Diseases (ICD)-codes from the Swedish National Patient Register (NPR) correctly correspond to subtypes of inflammatory bowel disease (IBD) and phenotypes of the Montreal classification scheme among patients with prevalent disease is unknown. Materials and methods: We obtained information on IBD subtypes and phenotypes from the medical records of 1403 patients with known IBD who underwent biological treatment at ten Swedish hospitals and retrieved information on their IBD-associated diagnostic codes from the NPR. We used previously described algorithms to define IBD subtypes and phenotypes. Finally, we compared these register-generated subtypes and phenotypes with the corresponding information from the medical records and calculated positive predictive values (PPV) with 95% confidence intervals. Results: Among patients with clinically confirmed disease and diagnostic listings of IBD in the NPR (N = 1401), the PPV was 97 (96-99)% for Crohn's disease, 98 (97-100)% for ulcerative colitis, and 8 (4-11)% for IBD-unclassified. The overall accuracy for age at diagnosis was 95% (when defined as A1, A2, or A3). Examining the validity of codes representing disease phenotype, the PPV was 36 (32-40)% for colonic Crohn's disease (L2), 61 (56-65)% for non-stricturing/non-penetrating Crohn's disease behaviour (B1) and 83 (78-87)% for perianal disease. Correspondingly, the PPV was 80 (71-89)% for proctitis (E1)/left-sided colitis (E2) in ulcerative colitis. Conclusions: Among people with known IBD, the NPR is a reliable source of data to classify most subtypes of prevalent IBD, even though misclassification commonly occurred in Crohn's disease location and behaviour and also among IBD-unclassified patients.
|
|
| 9. |
- Tjondro, Harry C., et al.
(författare)
-
Hyper-truncated Asn355- And Asn391-glycans modulate the activity of neutrophil granule myeloperoxidase
- 2021
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 296
-
Tidskriftsartikel (refereegranskat)abstract
- Myeloperoxidase (MPO) plays essential roles in neutrophil-mediated immunity via the generation of reactive oxidation products. Complex carbohydrates decorate MPO at discrete sites, but their functional relevance remains elusive. To this end, we have characterised the structure–biosynthesis–activity relationship of neutrophil MPO (nMPO). Mass spectrometry demonstrated that nMPO carries both characteristic under-processed and hyper-truncated glycans. Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation. Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer. Longitudinal profiling of maturing, mature, granule-separated and pathogen-stimulated neutrophils demonstrated that nMPO is dynamically expressed during granulopoiesis, unevenly distributed across granules and degranulated upon activation. We also show that proMPO-to-MPO maturation occurs during early/mid-stage granulopoiesis. While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations. Enzymatic trimming of the Asn355-/Asn391-glycans recapitulated the activity gain and showed that nMPO carrying hyper-truncated glycans at these positions exhibits increased thermal stability, polypeptide accessibility and ceruloplasmin-mediated inhibition potential relative to native nMPO. Finally, molecular modelling revealed that hyper-truncated Asn355-glycans positioned in the MPO-ceruloplasmin interface are critical for uninterrupted inhibition. Here, through an innovative and comprehensive approach, we report novel functional roles of MPO glycans, providing new insight into neutrophil-mediated immunity.
|
|
| 10. |
|
|
