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- Fontani, F., et al.
(författare)
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Magnetically regulated fragmentation of a massive, dense, and turbulent clump
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 593
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Tidskriftsartikel (refereegranskat)abstract
- © ESO, 2016. Massive stars, multiple stellar systems, and clusters are born of the gravitational collapse of massive, dense, gaseous clumps, and the way these systems form strongly depends on how the parent clump fragments into cores during collapse. Numerical simulations show that magnetic fields may be the key ingredient in regulating fragmentation. Here we present ALMA observations at ∼ 0.25′′ resolution of the thermal dust continuum emission at ∼ 278 GHz towards a turbulent, dense, and massive clump, IRAS 16061-5048c1, in a very early evolutionary stage. The ALMA image shows that the clump has fragmented into many cores along a filamentary structure. We find that the number, the total mass, and the spatial distribution of the fragments are consistent with fragmentation dominated by a strong magnetic field. Our observations support the theoretical prediction that the magnetic field plays a dominant role in the fragmentation process of massive turbulent clumps.
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- Leung, Samuel CY, et al.
(författare)
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Analytical validation of a standardized scoring protocol for Ki67 immunohistochemistry on breast cancer excision whole sections: an international multicenter collaboration
- 2019
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 75:2, s. 225-235
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The nuclear proliferation marker Ki67 assayed by immunohistochemistry has multiple potential uses in breast cancer, but an unacceptable level of interlaboratory variability has hampered its clinical utility. The International Ki67 in Breast Cancer Working Group has undertaken a systematic programme to determine whether Ki67 measurement can be analytically validated and standardised among laboratories. This study addresses whether acceptable scoring reproducibility can be achieved on excision whole sections.Methods and results: Adjacent sections from 30 primary ER+ breast cancers were centrally stained for Ki67 and sections were circulated among 23 pathologists in 12 countries. All pathologists scored Ki67 by two methods: (i) global: four fields of 100 tumour cells each were selected to reflect observed heterogeneity in nuclear staining; (ii) hot‐spot: the field with highest apparent Ki67 index was selected and up to 500 cells scored. The intraclass correlation coefficient (ICC) for the global method [confidence interval (CI) = 0.87; 95% CI = 0.799–0.93] marginally met the prespecified success criterion (lower 95% CI ≥ 0.8), while the ICC for the hot‐spot method (0.83; 95% CI = 0.74–0.90) did not. Visually, interobserver concordance in location of selected hot‐spots varies between cases. The median times for scoring were 9 and 6 min for global and hot‐spot methods, respectively.Conclusions: The global scoring method demonstrates adequate reproducibility to warrant next steps towards evaluation for technical and clinical validity in appropriate cohorts of cases. The time taken for scoring by either method is practical using counting software we are making publicly available. Establishment of external quality assessment schemes is likely to improve the reproducibility between laboratories further.
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- Alexander, Peter, et al.
(författare)
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Drivers for global agricultural land use change: The nexus of diet, population, yield and bioenergy
- 2015
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Ingår i: Global Environmental Change. - : Elsevier BV. - 0959-3780. ; 35, s. 138-147
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Tidskriftsartikel (refereegranskat)abstract
- The nexus of population growth and changing diets has increased the demands placed on agriculture to supply food for human consumption, animal feed and fuel. Rising incomes lead to dietary changes, from staple crops, towards commodities with greater land requirements, e.g. meat and dairy products. Despite yield improvements partially offsetting increases in demand, agricultural land has still been expanding, causing potential harm to ecosystems, e.g. through deforestation. We use country-level panel data (1961-2011) to allocate the land areas used to produce food for human consumption, waste and biofuels, and to attribute the food production area changes to diet, population and yields drivers. The results show that the production of animal products dominates agricultural land use and land use change over the 50-year period, accounting for 65% of land use change. The rate of extensification of animal production was found to have reduced more recently, principally due to the smaller effect of population growth. The area used for bioenergy was shown to be relatively small, but formed a substantial contribution (36%) to net agricultural expansion in the most recent period. Nevertheless, in comparison to dietary shifts in animal products, bioenergy accounted for less than a tenth of the increase in demand for agricultural land. Population expansion has been the largest driver for agricultural land use change, but dietary changes are a significant and growing driver. China was a notable exception, where dietary transitions dominate food consumption changes, due to rapidly rising incomes. This suggests that future dietary changes will become the principal driver for land use change, pointing to the potential need for demand-side measures to regulate agricultural expansion. (C) 2015 Elsevier Ltd. All rights reserved.
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- Dodson, Lois M., et al.
(författare)
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From incomplete penetrance with normal telomere length to severe disease and telomere shortening in a family with monoallelic and biallelic PARN pathogenic variants
- 2019
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 40:12, s. 2414-2429
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Tidskriftsartikel (refereegranskat)abstract
- PARN encodes poly(A)‐specific ribonuclease. Biallelic and monoallelic PARN variants are associated with Hoyeraal‐Hreidarsson syndrome/dyskeratosis congenita and idiopathic pulmonary fibrosis (IPF), respectively. The molecular features associated with incomplete penetrance of PARN‐associated IPF have not been described. We report a family with a rare missense, p.Y91C, and a novel insertion, p.(I274*), PARN variant. We found PARN p.Y91C had reduced deadenylase activity and the p.(I274*) transcript was depleted. Detailed analysis of the consequences of these variants revealed that, while PARN protein was lowest in the severely affected biallelic child who had the shortest telomeres, it was also reduced in his mother with the p.(I274*) variant but telomeres at the 50th percentile. Increased adenylation of telomerase RNA, human telomerase RNA, and certain small nucleolar RNAs, and impaired ribosomal RNA maturation were observed in cells derived from the severely affected biallelic carrier, but not in the other, less affected biallelic carrier, who had less severely shortened telomeres, nor in the monoallelic carriers who were unaffected and had telomeres ranging from the 1st to the 50th percentiles. We identified hsa‐miR‐202‐5p as a potential negative regulator of PARN. We propose one or more genetic modifiers influence the impact of PARN variants on its targets and this underlies incomplete penetrance of PARN‐associated disease.
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- Nielsen, Torsten O, et al.
(författare)
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Abstract P2-03-01: Analytical validation of a standardized scoring protocol for Ki67 assessed on breast excision whole sections: An international multicenter collaboration
- 2018
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Ingår i: Cancer research. Supplement. - 1538-7445. ; 78:4
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Konferensbidrag (refereegranskat)abstract
- Aims: (i) Determine whether between-observer reproducibility for Ki67 when assessed on whole sections according to a standardized scoring protocol is adequate for clinical application. (ii) Compare between-observer reproducibility of Ki67 scores assessed on hot-spots to scores using a global method that averages across a tissue section.Background: The nuclear proliferation biomarker Ki67 has multiple potential roles in breast cancer, including aiding decisions based on prognosis, but unacceptable levels of between-laboratory variability have been observed. The International Ki67 in Breast Cancer Working Group has undertaken a systematic program to determine whether Ki67 measurement can be analytically validated and standardized across labs. In phase 1, variability in visual interpretation was identified as an important source of variability. Phases 2 and 3a showed that adherence to defined scoring methods substantially improved reproducibility in scoring tissue microarrays and core-cut biopsies. We now assess whether acceptable reproducibility can be achieved on whole sections.Methods: Adjacent sections from 30 primary ER+ breast cancers were centrally stained for Ki67 to assemble 4 sets of 30 stained tumor sections, circulated around 23 labs in 12 countries. Ki67 was scored by 2 methods by all labs: (a) global: 4 fields of 100 tumor cells each were selected to reflect observed heterogeneity in nuclear staining (b) hot-spot: the field with highest Ki67 percentage of tumor cells with nuclear staining was selected and up to 500 cells scored. Ki67 scores were log2-transformed for statistical analyses and back-transformed for presentation. The primary objective was to assess whether either method could achieve an intraclass correlation coefficient (ICC) significantly greater than 0.8, considered substantial to almost-perfect reproducibility. Secondary objectives were to assess which method had highest observed ICC and to assess whether observers identified the same “hot-spots”.Results: ICC for the global method was 0.87 (95%CI: 0.799-0.93), marginally meeting the prespecified success criterion. The ICC for the hot-spot method was 0.83 (95%CI: 0.74-0.90) and had a CI extending below the success criterion. Across the 23 labs, geometric mean value of the 30 scores ranged from 8.5 to 19.6 for the global method and from 12.8 to 30.3 for the hot-spot method. The overall mean (95% CI) of these values was 12.9 (11.9-14.0) and 20.9 (19.1-22.8), respectively. Visually, between-laboratory agreement in location of selected hot-spot varies between cases. The median times for scoring were 9 and 6 minutes for global and hot-spot methods respectively.Conclusions: The global method marginally met the prespecified criterion of success; it should now be evaluated for clinical validity in appropriate cohorts of cases. The hot-spot method was observed to have slightly less reproducibility between labs. The time taken for scoring by either method is practical using counting software we are making publicly available. Establishment of external quality assessment schemes is likely to improve the reproducibility between labs further
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- Trondman, Anna-Kari, et al.
(författare)
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Pollen-based quantitative reconstructions of Holocene regional vegetation cover (plant-functional types and land-cover types) in Europe suitable for climate modelling
- 2015
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 21:2, s. 676-697
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Tidskriftsartikel (refereegranskat)abstract
- We present quantitative reconstructions of regional vegetation cover in north-western Europe, western Europe north of the Alps, and eastern Europe for five time windows in the Holocene [around 6k, 3k, 0.5k, 0.2k, and 0.05k calendar years before present (bp)] at a 1 degrees x1 degrees spatial scale with the objective of producing vegetation descriptions suitable for climate modelling. The REVEALS model was applied on 636 pollen records from lakes and bogs to reconstruct the past cover of 25 plant taxa grouped into 10 plant-functional types and three land-cover types [evergreen trees, summer-green (deciduous) trees, and open land]. The model corrects for some of the biases in pollen percentages by using pollen productivity estimates and fall speeds of pollen, and by applying simple but robust models of pollen dispersal and deposition. The emerging patterns of tree migration and deforestation between 6k bp and modern time in the REVEALS estimates agree with our general understanding of the vegetation history of Europe based on pollen percentages. However, the degree of anthropogenic deforestation (i.e. cover of cultivated and grazing land) at 3k, 0.5k, and 0.2k bp is significantly higher than deduced from pollen percentages. This is also the case at 6k in some parts of Europe, in particular Britain and Ireland. Furthermore, the relationship between summer-green and evergreen trees, and between individual tree taxa, differs significantly when expressed as pollen percentages or as REVEALS estimates of tree cover. For instance, when Pinus is dominant over Picea as pollen percentages, Picea is dominant over Pinus as REVEALS estimates. These differences play a major role in the reconstruction of European landscapes and for the study of land cover-climate interactions, biodiversity and human resources.
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