| 1. |
- Baldermann, Andre, et al.
(författare)
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Palaeo-environmental evolution of Central Asia during the Cenozoic : New insights from the continental sedimentary archive of the Valley of Lakes (Mongolia)
- 2021
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 17:5, s. 1955-1972
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Tidskriftsartikel (refereegranskat)abstract
- The Valley of Lakes basin (Mongolia) contains a unique continental sedimentary archive, suitable for constraining the influence of tectonics and climate change on the aridification of Central Asia in the Cenozoic. We identify the sedimentary provenance, the (post)depositional environment and the palaeo-climate based on sedimentological, petrographical, mineralogical, and (isotope) geochemical signatures recorded in authigenic and detrital silicates as well as soil carbonates in a sedimentary succession spanning from ~ 34 to 21 Ma. The depositional setting was characterized by an ephemeral braided river system draining prograding alluvial fans, with episodes of lake, playa or opensteppe sedimentation. Metamorphics from the northern adjacent Neoarchean to late Proterozoic hinterlands provided a continuous influx of silicate detritus to the basin, as indicated by K-Ar ages of detrital muscovite (~ 798-728 Ma) and discrimination function analysis. The authigenic clay fraction is dominated by illite-smectite and "hairy"illite (K-Ar ages of ~ 34-25 Ma), which formed during coupled petrogenesis and precipitation from hydrothermal fluids originating from major basalt flow events (~32-29 and ~ 29-25 Ma). Changes in hydroclimate are recorded in δ18 O and δ13 C profiles of soil carbonates and in silicate mineral weathering patterns, indicating that comparatively humid to semi-arid conditions prevailed in the late(st) Eocene, changing into arid conditions in the Oligocene and back to humid to semi-arid conditions in the early Miocene. Aridification steps are indicated at ~ 34-33, ~ 31, ~ 28 and ~ 23 Ma and coincide with some episodes of high-latitude ice-sheet expansion inferred from marine deep-sea sedimentary records. This suggests that long-term variations in the ocean-atmosphere circulation patterns due to pCO2 fall, reconfiguration of ocean gateways and ice-sheet expansion in Antarctica could have impacted the hydroclimate and weathering regime in the basin. We conclude that the aridification in Central Asia was triggered by reduced moisture influx by westerly winds driven by Cenozoic climate forcing and the exhumation of the Tian Shan and Altai Mountains and modulated by global climate events.
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| 2. |
- El Jellas, Khadija, et al.
(författare)
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Two New Mutations in the CEL Gene Causing Diabetes and Hereditary Pancreatitis : How to Correctly Identify MODY8 Cases
- 2022
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:4, s. 1455-1466
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Tidskriftsartikel (refereegranskat)abstract
- Context: Maturity onset diabetes of the young, type 8 (MODY8) is associated with mutations in the CEL gene, which encodes the digestive enzyme carboxyl ester lipase. Several diabetes cases and families have in recent years been attributed to mutations in CEL without any functional or clinical evidence provided. Objective: To facilitate correct MODY8 diagnostics, we screened 2 cohorts of diabetes patients and delineated the phenotype. Methods: Young, lean Swedish and Finnish patients with a diagnosis of type 2 diabetes (352 cases, 406 controls) were screened for mutations in the CEL gene. We also screened 58 Czech MODY cases who had tested negative for common MODY genes. For CEL mutation-positive subjects, family history was recorded, and clinical investigations and pancreatic imaging performed. Results: Two cases (1 Swedish and 1 Czech) with germline mutation in CEL were identified. Clinical and radiological investigations of these 2 probands and their families revealed dominantly inherited insulin-dependent diabetes, pancreatic exocrine dysfunction, and atrophic pancreas with lipomatosis and cysts. Notably, hereditary pancreatitis was the predominant phenotype in 1 pedigree. Both families carried single-base pair deletions in the proximal part of the CEL variable number of tandem repeat (VNTR) region in exon 11. The mutations are predicted to lead to aberrant protein tails that make the CEL protein susceptible to aggregation. Conclusion: The diagnosis of MODY8 requires a pancreatic exocrine phenotype and a deletion in the CEL VNTR in addition to dominantly inherited diabetes. CEL screening may be warranted also in families with hereditary pancreatitis of unknown genetic etiology.
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| 3. |
- Holmberg, Marcus, et al.
(författare)
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Outcome after resection for invasive intraductal papillary mucinous neoplasia is similar to conventional pancreatic ductal adenocarcinoma
- 2021
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Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 21:7, s. 1371-1377
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Tidskriftsartikel (refereegranskat)abstract
- Background/objectives: Resections for intraductal papillary mucinous neoplasm (IPMN) have increased last decades. Overall survival (OS) for conventional pancreatic ductal adenocarcinoma (PDAC) is well known but OS for invasive IPMN (inv-IPMN) is not as conclusive. This study aims to elucidate potential differences in clinicopathology and OS between these tumor types and to investigate if the raised number of resections have affected outcome.Methods: Consecutive patients ≥18 years of age resected for inv-IPMN and PDAC at Karolinska University Hospital between 2009 and 2018 were included. Clinicopathological variables were analyzed in multivariable regression models. Outcome was assessed calculating two-year OS, estimating OS using the Kaplan-Meier model and comparing survival functions with log-rank test.Results: 513 patients were included, 122 with inv-IPMN and 391 with PDAC. During the study period both the proportion resected inv-IPMN and two-year OS, irrespective of tumor type, increased (2.5%–45%; p < 0.001 and 44%–57%; p = 0.005 respectively). In Kaplan-Meier survival analysis inv-IPMN had more favorable median OS (mOS) compared to PDAC (33.6 months vs 19.3 months, p = 0.001). However, in multivariable Cox Regression analysis, tumor type was not a predictor for death, but so were resection period, tumor subtype and N-stage (all p < 0.001).Conclusion: In this large single center observational cohort study, inv-IPMN seemed to have favorable survival outcome compared to PDAC, but after adjusting for predictors for death this benefit vanished. The combination of a pronounced increase in resected inv-IPMN and a concurrent hazard abatement for death within 2 years during the study period proved to be a principal factor.
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