| 1. |
- Levis, Mark, et al.
(author)
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Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse
- 2011
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 117:12, s. 3294-3301
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Journal article (peer-reviewed)abstract
- In a randomized trial of therapy for FMS-like tyrosine kinase-3 (FLT3) mutant acute myeloid leukemia in first relapse, 224 patients received chemotherapy alone or followed by 80 mg of the FLT3 inhibitor lestaurtinib twice daily. Endpoints included complete remission or complete remission with incomplete platelet recovery (CR/CRp), overall survival, safety, and tolerability. Correlative studies included pharmacokinetics and analysis of in vivo FLT3 inhibition. There were 29 patients with CR/CRp in the lestaurtinib arm and 23 in the control arm (26% vs 21%; P = .35), and no difference in overall survival between the 2 arms. There was evidence of toxicity in the lestaurtinib-treated patients, particularly those with plasma levels in excess of 20 mu M. In the lestaurtinib arm, FLT3 inhibition was highly correlated with remission rate, but target inhibition on day 15 was achieved in only 58% of patients receiving lestaurtinib. Given that such a small proportion of patients on this trial achieved sustained FLT3 inhibition in vivo, any conclusions regarding the efficacy of combining FLT3 inhibition with chemotherapy are limited. Overall, lestaurtinib treatment after chemotherapy did not increase response rates or prolong survival of patients with FLT3 mutant acute myeloid leukemia in first relapse. This study is registered at www.clinicaltrials.gov as #NCT00079482. (Blood. 2011;117(12): 3294-3301)
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| 2. |
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| 3. |
- Piao, Shilong, et al.
(author)
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Evaluation of terrestrial carbon cycle models for their response to climate variability and to CO2 trends
- 2013
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In: Global Change Biology. - : Wiley. - 1354-1013. ; 19:7, s. 2117-2132
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Journal article (peer-reviewed)abstract
- The purpose of this study was to evaluate 10 process-based terrestrial biosphere models that were used for the IPCC fifth Assessment Report. The simulated gross primary productivity (GPP) is compared with flux-tower-based estimates by Jung etal. [Journal of Geophysical Research 116 (2011) G00J07] (JU11). The net primary productivity (NPP) apparent sensitivity to climate variability and atmospheric CO2 trends is diagnosed from each model output, using statistical functions. The temperature sensitivity is compared against ecosystem field warming experiments results. The CO2 sensitivity of NPP is compared to the results from four Free-Air CO2 Enrichment (FACE) experiments. The simulated global net biome productivity (NBP) is compared with the residual land sink (RLS) of the global carbon budget from Friedlingstein etal. [Nature Geoscience 3 (2010) 811] (FR10). We found that models produce a higher GPP (133 +/- 15Pg Cyr-1) than JU11 (118 +/- 6Pg Cyr-1). In response to rising atmospheric CO2 concentration, modeled NPP increases on average by 16% (5-20%) per 100ppm, a slightly larger apparent sensitivity of NPP to CO2 than that measured at the FACE experiment locations (13% per 100ppm). Global NBP differs markedly among individual models, although the mean value of 2.0 +/- 0.8Pg Cyr-1 is remarkably close to the mean value of RLS (2.1 +/- 1.2 Pg Cyr-1). The interannual variability in modeled NBP is significantly correlated with that of RLS for the period 1980-2009. Both model-to-model and interannual variation in model GPP is larger than that in model NBP due to the strong coupling causing a positive correlation between ecosystem respiration and GPP in the model. The average linear regression slope of global NBP vs. temperature across the 10 models is -3.0 +/- 1.5Pg Cyr-1 degrees C-1, within the uncertainty of what derived from RLS (-3.9 +/- 1.1Pg Cyr-1 degrees C-1). However, 9 of 10 models overestimate the regression slope of NBP vs. precipitation, compared with the slope of the observed RLS vs. precipitation. With most models lacking processes that control GPP and NBP in addition to CO2 and climate, the agreement between modeled and observation-based GPP and NBP can be fortuitous. Carbon-nitrogen interactions (only separable in one model) significantly influence the simulated response of carbon cycle to temperature and atmospheric CO2 concentration, suggesting that nutrients limitations should be included in the next generation of terrestrial biosphere models.
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| 4. |
- Piao, Shilong, et al.
(author)
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Evidence for a weakening relationship between interannual temperature variability and northern vegetation activity.
- 2014
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
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Journal article (peer-reviewed)abstract
- Satellite-derived Normalized Difference Vegetation Index (NDVI), a proxy of vegetation productivity, is known to be correlated with temperature in northern ecosystems. This relationship, however, may change over time following alternations in other environmental factors. Here we show that above 30°N, the strength of the relationship between the interannual variability of growing season NDVI and temperature (partial correlation coefficient RNDVI-GT) declined substantially between 1982 and 2011. This decrease in RNDVI-GT is mainly observed in temperate and arctic ecosystems, and is also partly reproduced by process-based ecosystem model results. In the temperate ecosystem, the decrease in RNDVI-GT coincides with an increase in drought. In the arctic ecosystem, it may be related to a nonlinear response of photosynthesis to temperature, increase of hot extreme days and shrub expansion over grass-dominated tundra. Our results caution the use of results from interannual time scales to constrain the decadal response of plants to ongoing warming.
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