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- Geyer, C. E., et al.
(författare)
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Overall survival in the OlympiA phase Ill trial of adjuvant olaparib in patients with germime pathogenic variants in BRCA1/2 and high-risk, early breast cancer
- 2022
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 33:12, s. 1250-1268
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Tidskriftsartikel (refereegranskat)abstract
- Background: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Delta 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Delta 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Delta 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion: With 35 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDES and DDFS with no new safety signals.
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| 5. |
- Jackson, R B, et al.
(författare)
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Belowground consequences of vegetation change and their treatment in models
- 2000
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Ingår i: Ecological Applications. - 1051-0761. ; 10:2, s. 470-483
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Tidskriftsartikel (refereegranskat)abstract
- The extent and consequences of global land-cover and land-use change are increasingly apparent. One consequence not so apparent is the altered structure of plants belowground. This paper examines such belowground changes, emphasizing the interaction of altered root distributions with other factors and their treatment in models. Shifts of woody and herbaceous vegetation with deforestation, afforestation, and woody plant encroachment typically alter the depth and distribution of plant rests, influencing soil nutrients, the water balance, and net primary productivity (NPP). For example, our analysis of global soil data sets shows that the major plant nutrients C, N, P, and K are more shallowly distributed than are Ca, Mg, and Na, but patterns for each element vary with the dominant vegetation type. After controlling for climate, soil C and N are distributed more deeply in arid shrublands than in arid grasslands, and subhumid forests have shallower nutrient distributions than do subhumid grasslands. Consequently, changes in vegetation may influence the distribution of soil carbon and nutrients over time (perhaps decades to centuries). Shifts in the water balance are typically much more rapid. Catchment studies indicate that the water yield decreases 25-40 mm for each 10% increase in tree cover, and increases in transpiration of water taken up by deep roots may account for as much as 50% of observed responses. Because models are increasingly important for predicting the consequences of vegetation change, we discuss the treatment of belowground processes and how different treatments affect model outputs. Whether models are parameterized by biome or plant life form (or neither), use single or multiple soil layers, or include N and water limitation will all affect predicted outcomes. Acknowledging and understanding such differences should help constrain predictions of vegetation change.
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| 8. |
- Georgiou, Katerina, et al.
(författare)
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Emergent temperature sensitivity of soil organic carbon driven by mineral associations
- 2024
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Ingår i: Nature Geoscience. - 1752-0894. ; 17:3, s. 205-212
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Tidskriftsartikel (refereegranskat)abstract
- Soil organic matter decomposition and its interactions with climate depend on whether the organic matter is associated with soil minerals. However, data limitations have hindered global-scale analyses of mineral-associated and particulate soil organic carbon pools and their benchmarking in Earth system models used to estimate carbon cycle–climate feedbacks. Here we analyse observationally derived global estimates of soil carbon pools to quantify their relative proportions and compute their climatological temperature sensitivities as the decline in carbon with increasing temperature. We find that the climatological temperature sensitivity of particulate carbon is on average 28% higher than that of mineral-associated carbon, and up to 53% higher in cool climates. Moreover, the distribution of carbon between these underlying soil carbon pools drives the emergent climatological temperature sensitivity of bulk soil carbon stocks. However, global models vary widely in their predictions of soil carbon pool distributions. We show that the global proportion of model pools that are conceptually similar to mineral-protected carbon ranges from 16 to 85% across Earth system models from the Coupled Model Intercomparison Project Phase 6 and offline land models, with implications for bulk soil carbon ages and ecosystem responsiveness. To improve projections of carbon cycle–climate feedbacks, it is imperative to assess underlying soil carbon pools to accurately predict the distribution and vulnerability of soil carbon.
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| 9. |
- Luo, Yiqi, et al.
(författare)
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Toward more realistic projections of soil carbon dynamics by Earth system models
- 2016
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Ingår i: Global Biogeochemical Cycles. - 0886-6236. ; 30:1, s. 40-56
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Tidskriftsartikel (refereegranskat)abstract
- Soil carbon (C) is a critical component of Earth system models (ESMs), and its diverse representations are a major source of the large spread across models in the terrestrial C sink from the third to fifth assessment reports of the Intergovernmental Panel on Climate Change (IPCC). Improving soil C projections is of a high priority for Earth system modeling in the future IPCC and other assessments. To achieve this goal, we suggest that (1) model structures should reflect real-world processes, (2) parameters should be calibrated to match model outputs with observations, and (3) external forcing variables should accurately prescribe the environmental conditions that soils experience. First, most soil C cycle models simulate C input from litter production and C release through decomposition. The latter process has traditionally been represented by first-order decay functions, regulated primarily by temperature, moisture, litter quality, and soil texture. While this formulation well captures macroscopic soil organic C (SOC) dynamics, better understanding is needed of their underlying mechanisms as related to microbial processes, depth-dependent environmental controls, and other processes that strongly affect soil C dynamics. Second, incomplete use of observations in model parameterization is a major cause of bias in soil C projections from ESMs. Optimal parameter calibration with both pool- and flux-based data sets through data assimilation is among the highest priorities for near-term research to reduce biases among ESMs. Third, external variables are represented inconsistently among ESMs, leading to differences in modeled soil C dynamics. We recommend the implementation of traceability analyses to identify how external variables and model parameterizations influence SOC dynamics in different ESMs. Overall, projections of the terrestrial C sink can be substantially improved when reliable data sets are available to select the most representative model structure, constrain parameters, and prescribe forcing fields.
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| 10. |
- Schimel, D, et al.
(författare)
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Contribution of increasing CO2 and climate to carbon storage by ecosystems in the United States
- 2000
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 287:5460, s. 2004-2006
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Tidskriftsartikel (refereegranskat)abstract
- The effects of increasing carbon dioxide (CO2) and climate on net carbon storage in terrestrial ecosystems of the conterminous United States for the period 1895-1993 were modeled with new, detailed historical climate information. For the period 1980-1993, results from an ensemble of three models agree within 25%, simulating a land carbon sink from CO2 and climate effects of 0.08 gigaton of carbon per year. The best estimates of the total sink from inventory data are about three times larger, suggesting that processes such as regrowth on abandoned agricultural land or in forests harvested before 1980 have effects as large as or larger than the direct effects of CO2 and climate. The modeled sink varies by about 100% from year to year as a result of climate variability.
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