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Sökning: WFRF:(Schouten Stefan)

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1.
  • Bejanyan, Nelli, et al. (författare)
  • Myeloablative Conditioning for Allogeneic Transplantation Results in Superior Disease-Free Survival for Acute Myelogenous Leukemia and Myelodysplastic Syndromes with Low/Intermediate but not High Disease Risk Index : A Center for International Blood and Marrow Transplant Research Study
  • 2021
  • Ingår i: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 27:1, s. 68.e1-68.e9
  • Tidskriftsartikel (refereegranskat)abstract
    • Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/ intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR],.74; 95% confidence interval [CI],.62 to.88; P <.001) but significantly greater relapse risk (HR, 1.54; 95% CI, 1.35 to 1.76; P <.001) and thus inferior disease-free survival (DFS) (HR, 1.19; 95% CI, 1.07 to 1.33; P =.001). In the high/ very high-risk DRI cohort, RIC was associated with marginally lower NRM (HR,.83; 95% CI,.68 to 1.00; P =.051) and significantly higher relapse risk (HR, 1.23; 95% CI, 1.08 to 1.41; P =.002), leading to similar DFS using either RIC or MAC. These data support MAC over RIC as the preferred conditioning intensity for patients with AML/MDS with low/intermediate-risk DRI, but with a similar benefit as RIC in high/very high-risk DRI. Novel MAC regimens with less toxicity could benefit all patients, but more potent antineoplastic approaches are needed for the high/ very-high risk DRI group.
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2.
  • Brandsma, J, et al. (författare)
  • A multi-proxy study of anaerobic ammonium oxidation in marine sediments of the Gullmar Fjord, Sweden
  • 2011
  • Ingår i: ENVIRONMENTAL MICROBIOLOGY REPORTS. - : Wiley. - 1758-2229. ; 3:3, s. 360-366
  • Tidskriftsartikel (refereegranskat)abstract
    • Anaerobic ammonium oxidation (anammox) is an important process for nitrogen removal in marine pelagic and benthic environments and represents a major sink in the global nitrogen cycle. We applied a suite of complementary methods for the detection and enumeration of anammox activity and anammox bacteria in marine sediments of the Gullmar Fjord, and compared the results obtained with each technique. 15N labelling experiments showed that nitrogen removal through N2 production was essentially limited to the upper 2 cm of the sediment, where anammox contributed 23–47% of the total production. The presence of marine anammox bacteria belonging to the genus ‘Candidatus Scalindua’ was shown by 16S rRNA gene sequence comparison. FISH counts of anammox bacteria correlated well with anammox activity, while quantitative PCR may have underestimated the number of anammox bacterial 16S rRNA gene copies at this site. Potential nitrogen conversion by anammox ranged from 0.6 to 4.8 fmol N cell−1 day−1, in agreement with previous measurements in the marine environment and in bioreactors. Finally, intact ladderane glycerophospholipid concentrations better reflected anammox activity and abundance than ladderane core lipid concentrations, most likely because the core lipid fraction contained a substantial fossil component, especially deeper in the sediment.
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4.
  • Brunstein, Claudio G, et al. (författare)
  • Effect of Conditioning Regimen Dose Reduction in Obese Patients Undergoing Autologous Hematopoietic Cell Transplantation
  • 2019
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 25:3, s. 480-487
  • Tidskriftsartikel (refereegranskat)abstract
    • Data are limited on whether to adjust high-dose chemotherapy before autologous hematopoietic cell transplant (autoHCT) in obese patients. This study explores the effects of dose adjustment on the outcomes of obese patients, defined as body mass index (BMI) ≥ 30 kg/m2. Dose adjustment was defined as a reduction in standard dosing ≥ 20%, based on ideal, reported dosing and actual weights. We included 2 groups of US patients who had received autoHCT between 2008 and 2014. Specifically, we included patients with multiple myeloma (MM, n = 1696) treated with high-dose melphalan and patients with Hodgkin or non-Hodgkin lymphomas (n = 781) who received carmustine, etoposide, cytarabine, and melphalan conditioning. Chemotherapy dose was adjusted in 1324 patients (78%) with MM and 608 patients (78%) with lymphoma. Age, sex, BMI, race, performance score, comorbidity index, and disease features (stage at diagnosis, disease status, and time to transplant) were similar between dose groups. In multivariate analyses for MM, adjusting for melphalan dose and for center effect had no impact on overall survival (P = .894) and treatment-related mortality (TRM) (P = .62), progression (P = .12), and progression-free survival (PFS; P = .178). In multivariate analyses for lymphoma, adjusting chemotherapy doses did not affect survival (P = .176), TRM (P = .802), relapse (P = .633), or PFS (P = .812). No center effect was observed in lymphoma. This study demonstrates that adjusting chemotherapy dose before autoHCT in obese patients with MM and lymphoma does not influence mortality. These results do not support adjusting chemotherapy dose in this population.
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5.
  • Buchbinder, David, et al. (författare)
  • Predictors of Loss to Follow-Up Among Pediatric and Adult Hematopoietic Cell Transplantation Survivors : A Report from the Center for International Blood and Marrow Transplant Research
  • 2020
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier. - 1083-8791 .- 1523-6536. ; 26:3, s. 553-561
  • Tidskriftsartikel (refereegranskat)abstract
    • Follow-up is integral for hematopoietic cell transplantation (HCT) care to ensure surveillance and intervention for complications. We characterized the incidence of and predictors for being lost to follow-up. Two-year survivors of first allogeneic HCT (10,367 adults and 3865 children) or autologous HCT (7291 adults and 467 children) for malignant/nonmalignant disorders between 2002 and 2013 reported to the Center for International Blood and Marrow Transplant Research were selected. The cumulative incidence of being lost to follow-up (defined as having missed 2 consecutive follow-up reporting periods) was calculated. Marginal Cox models (adjusted for center effect) were fit to evaluate predictors. The 10-year cumulative incidence of being lost to follow-up was 13% (95% confidence interval [CI], 12% to 14%) in adult allogeneic HCT survivors, 15% (95% CI, 14% to 16%) in adult autologous HCT survivors, 25% (95% CI, 24% to 27%) in pediatric allogeneic HCT survivors, and 24% (95% CI, 20% to 29%) in pediatric autologous HCT survivors. Factors associated with being lost to follow-up include younger age, nonmalignant disease, public/no insurance (reference: private), residence farther from the tranplantation center, and being unmarried in adult allogeneic HCT survivors; older age and testicular/germ cell tumor (reference: non-Hodgkin lymphoma) in adult autologous HCT survivors; older age, public/no insurance (reference: private), and nonmalignant disease in pediatric allogeneic HCT survivors; and older age in pediatric autologous HCT survivors. Follow-up focusing on minimizing attrition in high-risk groups is needed to ensure surveillance for late effects.
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7.
  • Casalbuoni, Sara, et al. (författare)
  • COLDDIAG: A Cold Vacuum Chamber for Diagnostics
  • 2011
  • Ingår i: IEEE Transactions on Applied Superconductivity. - 1051-8223. ; 21:3, s. 2300-2303
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the still open issues for the development of superconducting insertion devices is the understanding of the heat load induced by the beam passage. With the aim of measuring the beam heat load to a cold bore and in order to gain a deeper understanding in the beam heat load mechanisms, a cold vacuum chamber for diagnostics is under construction. We plan to have access with the same set-up to a number of different diagnostics, so we are implementing: i) retarding field analysers to measure the electron flux, ii) temperature sensors to measure the total heat load, iii) pressure gauges, iv) and mass spectrometers to measure the gas content. The inner vacuum chamber will be removable in order to test different geometries and materials. COLDDIAG is built to fit in a short straight section at ANKA, but we are proposing its installation in different synchrotron light sources with different energies and beam characteristics. A first installation in DIAMOND is planned in June 2011. Here we describe the technical design report of this device and the planned measurements with beam.
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8.
  • Cramwinckel, Margot J., et al. (författare)
  • A Warm, Stratified, and Restricted Labrador Sea Across the Middle Eocene and Its Climatic Optimum
  • 2020
  • Ingår i: Paleoceanography and Paleoclimatology. - 2572-4517 .- 2572-4525. ; 35:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies indicate that North Atlantic Deep Water (NADW) formation might have initiated during the globally warm Eocene (56–34 Ma). However, constraints on Eocene surface ocean conditions in source regions presently conducive to deep water formation are sparse. Here we test whether ocean conditions of the middle Eocene Labrador Sea might have allowed for deep water formation by applying (organic) geochemical and palynological techniques, on sediments from Ocean Drilling Program (ODP) Site 647. We reconstruct a long‐term sea surface temperature (SST) drop from ~30°C to ~27°C between 41.5 to 38.5 Ma, based on TEX86. Superimposed on this trend, we record ~2°C warming in SST associated with the Middle Eocene Climatic Optimum (MECO; ~40 Ma), which is the northernmost MECO record as yet, and another, likely regional, warming phase at ~41.1 Ma, associated with low‐latitude planktic foraminifera and dinoflagellate cyst incursions. Dinoflagellate cyst assemblages together with planktonic foraminiferal stable oxygen isotope ratios overall indicate low surface water salinities and strong stratification. Benthic foraminifer stable carbon and oxygen isotope ratios differ from global deep ocean values by 1–2‰ and 2–4‰, respectively, indicating geographic basin isolation. Our multiproxy reconstructions depict a consistent picture of relatively warm and fresh but also highly variable surface ocean conditions in the middle Eocene Labrador Sea. These conditions were unlikely conducive to deep water formation. This implies either NADW did not yet form during the middle Eocene or it formed in a different source region and subsequently bypassed the southern Labrador Sea.
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9.
  • Schouten, Stefan, et al. (författare)
  • An interlaboratory study of TEX86 and BIT analysis of sediments, extracts, and standard mixtures
  • 2013
  • Ingår i: Geochemistry Geophysics Geosystems. - 1525-2027. ; 14:12, s. 5263-5285
  • Tidskriftsartikel (refereegranskat)abstract
    • Two commonly used proxies based on the distribution of glycerol dialkyl glycerol tetraethers (GDGTs) are the TEX86 (TetraEther indeX of 86 carbon atoms) paleothermometer for sea surface temperature reconstructions and the BIT (Branched Isoprenoid Tetraether) index for reconstructing soil organic matter input to the ocean. An initial round-robin study of two sediment extracts, in which 15 laboratories participated, showed relatively consistent TEX86 values (reproducibility +/- 3-4 degrees C when translated to temperature) but a large spread in BIT measurements (reproducibility +/- 0.41 on a scale of 0-1). Here we report results of a second round-robin study with 35 laboratories in which three sediments, one sediment extract, and two mixtures of pure, isolated GDGTs were analyzed. The results for TEX86 and BIT index showed improvement compared to the previous round-robin study. The reproducibility, indicating interlaboratory variation, of TEX86 values ranged from 1.3 to 3.0 degrees C when translated to temperature. These results are similar to those of other temperature proxies used in paleoceanography. Comparison of the results obtained from one of the three sediments showed that TEX86 and BIT indices are not significantly affected by interlaboratory differences in sediment extraction techniques. BIT values of the sediments and extracts were at the extremes of the index with values close to 0 or 1, and showed good reproducibility (ranging from 0.013 to 0.042). However, the measured BIT values for the two GDGT mixtures, with known molar ratios of crenarchaeol and branched GDGTs, had intermediate BIT values and showed poor reproducibility and a large overestimation of the true (i.e., molar-based) BIT index. The latter is likely due to, among other factors, the higher mass spectrometric response of branched GDGTs compared to crenarchaeol, which also varies among mass spectrometers. Correction for this different mass spectrometric response showed a considerable improvement in the reproducibility of BIT index measurements among laboratories, as well as a substantially improved estimation of molar-based BIT values. This suggests that standard mixtures should be used in order to obtain consistent, and molar-based, BIT values.
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10.
  • Śliwińska, Kasia K., et al. (författare)
  • Sea surface temperature evolution of the North Atlantic Ocean across the Eocene-Oligocene transition
  • 2023
  • Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 19:1, s. 123-140
  • Tidskriftsartikel (refereegranskat)abstract
    • A major step in the long-term Cenozoic evolution toward a glacially driven climate occurred at the Eocene–Oligocene transition (EOT), ∼34.44 to 33.65 million years ago (Ma). Evidence for high-latitude cooling and increased latitudinal temperature gradients across the EOT has been found in a range of marine and terrestrial environments. However, the timing and magnitude of temperature change in the North Atlantic remains highly unconstrained. Here, we use two independent organic geochemical palaeothermometers to reconstruct sea surface temperatures (SSTs) from the southern Labrador Sea (Ocean Drilling Program – ODP Site 647) across the EOT. The new SST records, now the most detailed for the North Atlantic through the 1 Myr leading up to the EOT onset, reveal a distinctive cooling step of ∼3 ∘C (from 27 to 24 ∘C), between 34.9 and 34.3 Ma, which is ∼500 kyr prior to Antarctic glaciation. This cooling step, when compared visually to other SST records, is asynchronous across Atlantic sites, signifying considerable spatiotemporal variability in regional SST evolution. However, overall, it fits within a phase of general SST cooling recorded across sites in the North Atlantic in the 5 Myr bracketing the EOT.Such cooling might be unexpected in light of proxy and modelling studies suggesting the start-up of the Atlantic Meridional Overturning Circulation (AMOC) before the EOT, which should warm the North Atlantic. Results of an EOT modelling study (GFDL CM2.1) help reconcile this, finding that a reduction in atmospheric CO2 from 800 to 400 ppm may be enough to counter the warming from an AMOC start-up, here simulated through Arctic–Atlantic gateway closure. While the model simulations applied here are not yet in full equilibrium, and the experiments are idealised, the results, together with the proxy data, highlight the heterogeneity of basin-scale surface ocean responses to the EOT thermohaline changes, with sharp temperature contrasts expected across the northern North Atlantic as positions of the subtropical and subpolar gyre systems shift. Suggested future work includes increasing spatial coverage and resolution of regional SST proxy records across the North Atlantic to identify likely thermohaline fingerprints of the EOT AMOC start-up, as well as critical analysis of the causes of inter-model responses to help better understand the driving mechanisms.
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