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| 2. |
- Treat, C. C., et al.
(author)
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Effects of permafrost aggradation on peat properties as determined from a pan-Arctic synthesis of plant macrofossils
- 2016
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In: Journal of Geophysical Research - Biogeosciences. - 2169-8953 .- 2169-8961. ; 121:1, s. 78-94
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Journal article (peer-reviewed)abstract
- Permafrost dynamics play an important role in high-latitude peatland carbon balance and are key to understanding the future response of soil carbon stocks. Permafrost aggradation can control the magnitude of the carbon feedback in peatlands through effects on peat properties. We compiled peatland plant macrofossil records for the northern permafrost zone (515 cores from 280 sites) and classified samples by vegetation type and environmental class (fen, bog, tundra and boreal permafrost, and thawed permafrost). We examined differences in peat properties (bulk density, carbon (C), nitrogen (N) and organic matter content, and C/N ratio) and C accumulation rates among vegetation types and environmental classes. Consequences of permafrost aggradation differed between boreal and tundra biomes, including differences in vegetation composition, C/N ratios, and N content. The vegetation composition of tundra permafrost peatlands was similar to permafrost-free fens, while boreal permafrost peatlands more closely resembled permafrost-free bogs. Nitrogen content in boreal permafrost and thawed permafrost peatlands was significantly lower than in permafrost-free bogs despite similar vegetation types (0.9% versus 1.5% N). Median long-term C accumulation rates were higher in fens (23g C m(-2)yr(-1)) than in permafrost-free bogs (18g C m(-2)yr(-1)) and were lowest in boreal permafrost peatlands (14g C m(-2)yr(-1)). The plant macrofossil record demonstrated transitions from fens to bogs to permafrost peatlands, bogs to fens, permafrost aggradation within fens, and permafrost thaw and reaggradation. Using data synthesis, we have identified predominant peatland successional pathways, changes in vegetation type, peat properties, and C accumulation rates associated with permafrost aggradation.
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| 3. |
- Crombag, Marie-Rose B S, et al.
(author)
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Impact of Older Age on the Exposure of Paclitaxel : a Population Pharmacokinetic Study.
- 2019
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In: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 36:2, s. 33-
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Journal article (peer-reviewed)abstract
- PURPOSE: Limited available data suggest that older patients are more prone to develop paclitaxel-induced toxicity than their younger peers. It remains unclear whether this is related to age-dependent pharmacokinetics (PK) of paclitaxel. Primary objective of this study was to determine the influence of older age on the PK of paclitaxel.METHODS: PK data of patients aged ≥70 years who received paclitaxel intravenously at the Netherlands Cancer Institute (NKI) and the Radboud University Medical Center between September 2012 and May 2017 were collected. These prospectively collected data were pooled with previously published databases from multiple clinical trials conducted at the NKI and Erasmus MC Cancer Institute. A previously developed 3-compartment population PK model with saturable distribution and elimination was used to describe paclitaxel plasma concentration-time data. Hereafter, influence of age on paclitaxel PK was assessed in a previously established full covariate model.RESULTS: In total, paclitaxel PK data from 684 patients were available, consisting of 166 patients ≥70 years (24%). Median age of the cohort was 61 years (range 18 to 84 years). The impact of age, either treated as a continuous or dichotomous covariate (<70 versus ≥70 years), on the elimination of paclitaxel was only marginal but statistically significant (both p < 0.001 with no clinically relevant decrease in interindividual variability). For a typical patient, maximal elimination capacity decreased by only 5% for a 10-year increment of age.CONCLUSION: In this extensive multi-center dataset, which included a considerable number of older patients, older age had no clinically relevant impact on paclitaxel PK.
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| 5. |
- Sim, Thomas G., et al.
(author)
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Regional variability in peatland burning at mid-to high-latitudes during the Holocene
- 2023
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In: Quaternary Science Reviews. - : Elsevier. - 0277-3791 .- 1873-457X. ; 305
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Journal article (peer-reviewed)abstract
- Northern peatlands store globally-important amounts of carbon in the form of partly decomposed plant detritus. Drying associated with climate and land-use change may lead to increased fire frequency and severity in peatlands and the rapid loss of carbon to the atmosphere. However, our understanding of the patterns and drivers of peatland burning on an appropriate decadal to millennial timescale relies heavily on individual site-based reconstructions. For the first time, we synthesise peatland macrocharcoal re-cords from across North America, Europe, and Patagonia to reveal regional variation in peatland burning during the Holocene. We used an existing database of proximal sedimentary charcoal to represent regional burning trends in the wider landscape for each region. Long-term trends in peatland burning appear to be largely climate driven, with human activities likely having an increasing influence in the late Holocene. Warmer conditions during the Holocene Thermal Maximum (similar to 9e6 cal. ka BP) were associated with greater peatland burning in North America's Atlantic coast, southern Scandinavia and the Baltics, and Patagonia. Since the Little Ice Age, peatland burning has declined across North America and in some areas of Europe. This decline is mirrored by a decrease in wider landscape burning in some, but not all sub-regions, linked to fire-suppression policies, and landscape fragmentation caused by agricultural expansion. Peatlands demonstrate lower susceptibility to burning than the wider landscape in several instances, probably because of autogenic processes that maintain high levels of near-surface wetness even during drought. Nonetheless, widespread drying and degradation of peatlands, particularly in Europe, has likely increased their vulnerability to burning in recent centuries. Consequently, peatland restoration efforts are important to mitigate the risk of peatland fire under a changing climate. Finally, we make recommendations for future research to improve our understanding of the controls on peatland fires.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 6. |
- Boosman, René J, et al.
(author)
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Toxicity of pemetrexed during renal impairment explained-Implications for safe treatment
- 2021
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In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 149:8, s. 1576-1584
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Journal article (peer-reviewed)abstract
- Pemetrexed is an important component of first line treatment in patients with non-squamous non-small cell lung cancer. However, a limitation is the contraindication in patients with renal impairment due to hematological toxicity. Currently, it is unknown how to safely dose pemetrexed in these patients. The aim of our study was to elucidate the relationship between pemetrexed exposure and toxicity to support the development of a safe dosing regimen in patients with renal impairment. A population pharmacokinetic/pharmacodynamic analysis was performed based on phase II study results in three patients with renal dysfunction, supplemented with data from 106 patients in early clinical studies. Findings were externally validated with data of different pemetrexed dosing regimens. Alternative dosing regimens were evaluated using the developed model. We found that pemetrexed toxicity was driven by the time above a toxicity threshold concentration. The threshold for vitamin-supplemented patients was 0.110 mg/mL (95% CI: 0.092-0.146 mg/mL). It was observed that in patients with renal impairment (estimated glomerular filtration rate [eGFR]: <45 mL/min) the approved dose of 500 mg/m2 would yield a high probability of severe neutropenia in the range of 51.0% to 92.6%. A pemetrexed dose of 20 mg for patients (eGFR: 20 mL/min) is shown to be neutropenic-equivalent to the approved dose in patients with adequate renal function (eGFR: 90 mL/min), but would result in an approximately 13-fold lower area under the concentration-time curve. The pemetrexed exposure-toxicity relationship is explained by a toxicity threshold and substantially different from previously thought. Without prophylaxis for toxicity, it is unlikely that a therapeutic dose can be safely administered to patients with renal impairment.
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| 7. |
- Charrier, D. S. H., et al.
(author)
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Bimolecular recombination in ambipolar organic field effect transistors
- 2009
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In: Organic electronics. - : Elsevier. - 1566-1199 .- 1878-5530. ; 10:5, s. 994-997
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Journal article (peer-reviewed)abstract
- In ambipolar organic field effect transistors (OFET) the shape of the channel potential is intimately related to the recombination zone width W, and hence to the electron-hole recombination strength. Experimentally, the recombination profile can be assessed by scanning Kelvin probe microscopy (SKPM). However, surface potentials as measured by SKPM are distorted due to spurious capacitive couplings. Here, we present a (de)convolution method with an experimentally calibrated transfer function to reconstruct the actual surface potential from a measured SKPM response and vice versa. Using this scheme, we find W = 0.5 mu m for a nickel dithiolene OFET, which translates into a recombination rate that is two orders of magnitude below the value expected for Langevin recombination. (C) 2009 Elsevier B.V. All rights reserved.
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| 8. |
- Crombag, Marie-Rose B S, et al.
(author)
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Does Older Age Lead to Higher Risk for Neutropenia in Patients Treated with Paclitaxel?
- 2019
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In: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 36:12, s. 163-
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Journal article (peer-reviewed)abstract
- PURPOSE: There is ongoing concern regarding increased toxicity from paclitaxel in elderly patients, particularly of severe neutropenia. Yet, data so far is controversial and this concern is not supported by a clinically relevant age-dependent difference in pharmacokinetics (PK) of paclitaxel. This study assessed whether age is associated with increased risk for paclitaxel-induced neutropenia.METHODS: Paclitaxel plasma concentration-time data, pooled from multiple different studies, was combined with available respective neutrophil count data during the first treatment cycle. Paclitaxel pharmacokinetic-pharmacodynamic (PK-PD) data was modeled using a non-linear mixed effects approach and a semiphysiological neutropenia model, where systemic paclitaxel exposure was linked to reduced proliferation of neutrophils. The impact of age was evaluated on relevant variables in the model, using a significance threshold of p < 0.005.RESULTS: Paclitaxel PK-PD data was evaluated from 300 patients, with a median age of 65 years (range 23-84 years), containing 116 patients ≥70 years (39%). First cycle neutrophil counts were adequately described by a threshold effect model of paclitaxel on the proliferation rate of neutrophils. Age as a continuous or dichotomous variable (≥70 versus <70 years) did not significantly impact sensitivity of the bone marrow to paclitaxel nor the average maturation time of neutrophils (both p > 0.005), causing a decline in the respective interindividual variability of <1%.CONCLUSION: Results from this large retrospective patient cohort do not suggest elderly patients to be at an increased risk of developing paclitaxel-associated neutropenia during the first treatment cycle. Reflexive dose reductions of paclitaxel in elderly patients are unlikely to improve the risk of severe neutropenia and may be deleterious.
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| 9. |
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| 10. |
- Toxopeus, Eelke L. A., et al.
(author)
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Association between Paclitaxel Clearance and Tumor Response in Patients with Esophageal Cancer
- 2019
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In: Cancers. - : MDPI. - 2072-6694. ; 11:2
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Journal article (peer-reviewed)abstract
- Inter-individual variability in paclitaxel pharmacokinetics may play a role in the response to chemotherapy. Therefore, we studied the association between paclitaxel clearance and treatment response in patients with esophageal cancer. All patients who received paclitaxel (plus carboplatin) treatment for esophageal cancer between 2007 and 2013 were included. The treatment was given as neoadjuvant chemoradiotherapy (nCRT), induction chemotherapy (iCT), or palliative chemotherapy (pCT). The treatment response was assessed by the tumor regression grade (TRG) or by the RECIST1.1 criteria, respectively. The unbound paclitaxel clearance (CL) was estimated with NONMEM. The log-transformed clearance was related to response with ANOVA and independent sample t-tests. A total of 166 patients were included, of whom 113 received nCRT, 23 iCT and 30 pCT. In patients receiving nCRT, paclitaxel clearance was not associated with tumor regression grade (p-value = 0.25), nor with pathologically complete response (geometric mean 561.6 L/h) and residual disease (geometric mean 566.1 L/h, p-value = 0.90). In patients who underwent iCT or pCT, also no association between paclitaxel clearance and RECIST outcome was identified (iCT: p-value = 0.08 and pCT: p-value = 0.81, respectively). In conclusion, systemic paclitaxel exposure was not associated with response to common paclitaxel-based treatment regimens for esophageal cancer. Future studies should focus on tumor exposure in relation to systemic exposure and treatment outcome.
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