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Sökning: WFRF:(Siegenthaler A.)

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  • Mitchell, E. A. D, et al. (författare)
  • Contrasted effects of increased N and CO2 supply on two keystone species in peatland restoration and implications for global change
  • 2002
  • Ingår i: Journal of Ecology. - : Wiley. - 0022-0477 .- 1365-2745. ; 90:3, s. 529-533
  • Tidskriftsartikel (refereegranskat)abstract
    • 1  Significant areas of temperate bogs have been damaged by peat harvesting but may regenerate. These secondary mires, if well managed, may act as strong C sinks, regulate hydrology and buffer regional climate.2 The potential effects of bog regeneration will, however, depend on the successful establishment of the principal peat formers –Sphagnum mosses. The influence of hydrology and microclimate on Sphagnum re-growth is well studied but effects of elevated CO2 and N deposition are not known.3 We carried out two in-situ experiments in a cutover bog during three growing seasons in which we raised either CO2 (to 560 p.p.m.) or N (by adding NH4NO3, 3 g m−2 year−1). The two treatments had contrasting effects on competition between the initial coloniser Polytrichum strictum (favoured by high N) and the later coloniser Sphagnum fallax (favoured by high CO2).4  Such changes may have important consequences for bog regeneration and hence for carbon sequestration in cutover bogs, with potential feedback on regional hydrological and climatic processes.
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  • Jungen, SH, et al. (författare)
  • Spatial distribution of CD3- and CD8-positive lymphocytes as pretest for POLE wild-type in molecular subgroups of endometrial carcinoma
  • 2023
  • Ingår i: Frontiers in medicine. - : Frontiers Media SA. - 2296-858X. ; 10, s. 1110529-
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the years, the molecular classification of endometrial carcinoma has evolved significantly. Both POLEmut and MMRdef cases share tumor biological similarities like high tumor mutational burden and induce strong lymphatic reactions. While therefore use case scenarios for pretesting with tumor-infiltrating lymphocytes to replace molecular analysis did not show promising results, such testing may be warranted in cases where an inverse prediction, such as that of POLEwt, is being considered. For that reason we used a spatial digital pathology method to quantitatively examine CD3+ and CD8+ immune infiltrates in comparison to conventional histopathological parameters, prognostics and as potential pretest before molecular analysis.MethodsWe applied a four-color multiplex immunofluorescence assay for pan-cytokeratin, CD3, CD8, and DAPI on 252 endometrial carcinomas as testing and compared it to further 213 cases as validation cohort from a similar multiplexing assay. We quantitatively assessed immune infiltrates in microscopic distances within the carcinoma, in a close distance of 50 microns, and in more distant areas.ResultsRegarding prognostics, high CD3+ and CD8+ densities in intra-tumoral and close subregions pointed toward a favorable outcome. However, TCGA subtyping outperforms prognostication of CD3 and CD8 based parameters. Different CD3+ and CD8+ densities were significantly associated with the TCGA subgroups, but not consistently for histopathological parameter. In the testing cohort, intra-tumoral densities of less than 50 intra-tumoral CD8+ cells/mm2 were the most suitable parameter to assume a POLEwt, irrespective of an MMRdef, NSMP or p53abn background. An application to the validation cohort corroborates these findings with an overall sensitivity of 95.5%.DiscussionMolecular confirmation of POLEmut cases remains the gold standard. Even if CD3+ and CD8+ cell densities appeared less prognostic than TCGA, low intra-tumoral CD8+ values predict a POLE wild-type at substantial percentage rates, but not vice versa. This inverse correlation might be useful to increase pretest probabilities in consecutive POLE testing. Molecular subtyping is currently not conducted in one-third of cases deemed low-risk based on conventional clinical and histopathological parameters. However, this percentage could potentially be increased to two-thirds by excluding sequencing of predicted POLE wild-type cases, which could be determined through precise quantification of intra-tumoral CD8+ cells.
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  • Siegenthaler, MP, et al. (författare)
  • Mechanical reliability of the Jarvik 2000 Heart - Discussion
  • 2006
  • Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 81:5, s. 1752-1759
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Device failure is a limitation of permanent mechanical circulatory support. We studied the mechanical reliability of the Jarvik 2000 Heart, an axial flow pump with ceramic bearings designed to provide more than 10 years' durability. Methods. The Jarvik 2000 Heart was implanted in 102 patients between April 2000 and December 2004. Eighty-three pumps with an abdominal driveline were implanted as a bridge-to-transplantation, and 19 with post-auricular power supply as lifetime therapy. Eighteen pumps were recovered intact after clinical use and run continuously on the bench to further assess durability. Results. No implantable component failure occurred either in patients or during bench testing. The cumulative pump run-time was 110 years: 59 years overall in vivo and 51 years in vitro. The mean support time for bridge-to-transplant recipients was 159 days, and for discharged lifetime-therapy recipients 551 days. Six recipients were supported moer than 2 years, with the longest ongoing approaching 5 years. External cables caused three system failures, with a 95% freedom from system failure at 4 years. Device malfunctions, related to external cables ( 9) and lack of a backup battery ( 1), caused no adverse consequences. Before introduction of noncorrosive, gold-plated stainless steel connectors, corrosion was observed on three connectors to the retroauricular power supply. Conclusions. The Jarvik 2000 Heart has had no implantable component failure. Meaningful durability data and failure mode can only be established by real-time testing in patients. The reliability and dependability of this device, in addition to the exchangeability of external components, give promise for long-term circulatory support in critically ill heart failure patients.
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