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- Van Bockstal, MR, et al.
(författare)
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Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:19
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Tidskriftsartikel (refereegranskat)abstract
- Patients with advanced triple-negative breast cancer (TNBC) benefit from treatment with atezolizumab, provided that the tumor contains ≥1% of PD-L1/SP142-positive immune cells. Numbers of tumor-infiltrating lymphocytes (TILs) vary strongly according to the anatomic localization of TNBC metastases. We investigated inter-pathologist agreement in the assessment of PD-L1/SP142 immunohistochemistry and TILs. Ten pathologists evaluated PD-L1/SP142 expression in a proficiency test comprising 28 primary TNBCs, as well as PD-L1/SP142 expression and levels of TILs in 49 distant TNBC metastases with various localizations. Interobserver agreement for PD-L1 status (positive vs. negative) was high in the proficiency test: the corresponding scores as percentages showed good agreement with the consensus diagnosis. In TNBC metastases, there was substantial variability in PD-L1 status at the individual patient level. For one in five patients, the chance of treatment was essentially random, with half of the pathologists designating them as positive and half negative. Assessment of PD-L1/SP142 and TILs as percentages in TNBC metastases showed poor and moderate agreement, respectively. Additional training for metastatic TNBC is required to enhance interobserver agreement. Such training, focusing on metastatic specimens, seems worthwhile, since the same pathologists obtained high percentages of concordance (ranging from 93% to 100%) on the PD-L1 status of primary TNBCs.
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- Morris, A. M., et al.
(författare)
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Evidence for low‐pressure crustal anatexis during the northeast atlantic break‐up
- 2024
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Ingår i: Geochemistry Geophysics Geosystems. - : American Geophysical Union (AGU). - 1525-2027. ; 25:7
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Tidskriftsartikel (refereegranskat)abstract
- While basaltic volcanism is dominant during rifting and continental breakup, felsic magmatism may be a significant component of some rift margins. During International Ocean Discovery Program (IODP) Expedition 396 on the continental margin of Norway, a graphite-garnet-cordierite bearing dacitic unit (the Mimir dacite) was recovered in two holes within early Eocene sediments on Mimir High (Site U1570), a marginal high on the Vøring Transform Margin. Here, we present a comprehensive textural, petrological, and geochemical study of the Mimir dacite in order to assess its origin and discuss the geodynamic implications. The major mineral phases (garnet, cordierite, quartz, plagioclase, alkali feldspar) are hosted in a fresh rhyolitic, vesicular, glassy matrix that is locally mingled with sediments. The major element chemistry of garnet and cordierite, the presence of zircon inclusions with inherited cores, and thermobarometric calculations all support an upper crustal metapelitic origin. While most magma-rich margin models favor crustal anatexis in the lower crust, thermobarometric calculations performed here show that the Mimir dacite was produced at upper-crustal depths (<5 kbar, 18 km depth) and high temperature (750–800°C) with up to 3 wt% water content. In situ U-Pb analyses on zircon inclusions give a magmatic crystallization age of 54.6 ± 1.1 Ma, consistent with emplacement that post-dates the Paleocene-Eocene Thermal Maximum. Our results suggest that the opening of the Northeast Atlantic was associated with a phase of low-pressure, high-temperature crustal anatexis preceding the main phase of magmatism.
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- Reinardy, Benedict T. I., et al.
(författare)
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Repeated advance and retreat of the East Antarctic Ice Sheet on the continental shelf during the early Pliocene warm period
- 2015
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Ingår i: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier BV. - 0031-0182 .- 1872-616X. ; 422, s. 65-84
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Tidskriftsartikel (refereegranskat)abstract
- Diatom analysis of a sediment core recovered at IODP Site U1358 on the continental shelf off the Adélie Coast indicated that the lower section of the core contained an assemblage dating back to the Thalassiosira innura Zone of the lower Pliocene that ranges from 4.2 to 5.12. Ma. Based on lithological descriptions at both a macro- and micro-scale of this early Pliocene part of the core, four facies were interpreted from the diamictons representing the progressive advance and retreat of the grounding line over the site. Facies 1a and 1b contain a distinct directional signal from the orientation of the a-axis of clasts with several phases of fabric development along with both brittle and ductile deformation features that are common in sediments that have been subglacially deformed. Facies 1c and 1d are finely laminated and were deposited in open marine conditions. The four facies within the depositional model provide for the first time direct evidence for ice advancing across the shelf adjacent to the Wilkes Subglacial Basin on at least four occasions separated by three periods of open marine conditions indicating retreat of grounded ice inland of the site during a warmer than present early Pliocene. The times of open marine conditions are correlated with previous findings from the neighbouring rise sites that also indicated an oscillating ice margin. This has significant implications because firstly it suggests a dynamic East Antarctic Ice Sheet (EAIS) that is probably far more sensitive to climatic and oceanic forcing even during relatively short time periods than had previously been thought. Secondly it suggests that proxies used to interpret the advance and retreat of the grounding line from the rise can be linked with direct evidence of grounding line migration from the shelf. It also has important implications for the future behaviour and sensitivity of the EAIS under present continuing warming conditions. Together with results from the rise, this paper provides a crucial ice extent target for a new ice sheet model of this region during the Pliocene.
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