| 1. |
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| 2. |
- Jackson, N., et al.
(författare)
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LBCS: The LOFAR Long-Baseline Calibrator Survey
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595, s. Art no A86-
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Tidskriftsartikel (refereegranskat)abstract
- We outline the LOFAR Long-Baseline Calibrator Survey (LBCS), whose aim is to identify sources suitable for calibrating the highest-resolution observations made with the International LOFAR Telescope, which include baselines > 1000 km. Suitable sources must contain significant correlated flux density (greater than or similar to 50 - 100 mJy) at frequencies around 110-190 MHz on scales of a few hundred milliarcseconds. At least for the 200-300-km international baselines, we find around 1 suitable calibrator source per square degree over a large part of the northern sky, in agreement with previous work. This should allow a randomly selected target to be successfully phase calibrated on the international baselines in over 50% of cases. Products of the survey include calibrator source lists and fringe-rate and delay maps of wide areas-typically a few degrees-around each source. The density of sources with significant correlated flux declines noticeably with baseline length over the range 200-600 km, with good calibrators on the longest baselines appearing only at the rate of 0.5 per sq. deg. Coherence times decrease from 1-3 min on 200-km baselines to about 1 min on 600-km baselines, suggesting that ionospheric phase variations contain components with scales of a few hundred kilometres. The longest median coherence time, at just over 3 min, is seen on the DE609 baseline, which at 227 km is close to being the shortest. We see median coherence times of between 80 and 110 s on the four longest baselines (580-600 km), and about 2 min for the other baselines. The success of phase transfer from calibrator to target is shown to be influenced by distance, in a manner that suggests a coherence patch at 150-MHz of the order of 1 deg. Although source structures cannot be measured in these observations, we deduce that phase transfer is affected if the calibrator source structure is not known. We give suggestions for calibration strategies and choice of calibrator sources, and describe the access to the online catalogue and data products.
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| 3. |
- Andersen, M. R., et al.
(författare)
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Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88
- 2011
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 21:6, s. 885-897
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Tidskriftsartikel (refereegranskat)abstract
- The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces both organic acids and hydrolytic enzymes in high amounts, and some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. niger strain (CBS 513.88) has already been sequenced, the versatility and diversity of this species compel additional exploration. We therefore undertook wholegenome sequencing of the acidogenic A. niger wild-type strain (ATCC 1015) and produced a genome sequence of very high quality. Only 15 gaps are present in the sequence, and half the telomeric regions have been elucidated. Moreover, sequence information from ATCC 1015 was used to improve the genome sequence of CBS 513.88. Chromosome-level comparisons uncovered several genome rearrangements, deletions, a clear case of strain-specific horizontal gene transfer, and identification of 0.8 Mb of novel sequence. Single nucleotide polymorphisms per kilobase (SNPs/kb) between the two strains were found to be exceptionally high (average: 7.8, maximum: 160 SNPs/kb). High variation within the species was confirmed with exo-metabolite profiling and phylogenetics. Detailed lists of alleles were generated, and genotypic differences were observed to accumulate in metabolic pathways essential to acid production and protein synthesis. A transcriptome analysis supported up-regulation of genes associated with biosynthesis of amino acids that are abundant in glucoamylase A, tRNA-synthases, and protein transporters in the protein producing CBS 513.88 strain. Our results and data sets from this integrative systems biology analysis resulted in a snapshot of fungal evolution and will support further optimization of cell factories based on filamentous fungi
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| 4. |
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| 5. |
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| 6. |
- Vautard, R., et al.
(författare)
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Skill and uncertainty of a regional air quality model ensemble
- 2009
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310. ; 43:31, s. 4822-4832
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Tidskriftsartikel (refereegranskat)abstract
- Recently several regional air quality projects were carried out to support the negotiation under the Clean Air For Europe (CAFE) programme by predicting the impact of emission control policies with an ensemble of models. Within these projects, CITYDELTA and EURODELTA, the fate of air quality at the scale of European cities or that of the European continent was studied using several models. In this article we focus on the results of EURODELTA. The predictive skill of the ensemble of models is described for ozone, nitrogen dioxide and secondary inorganic compounds, and the uncertainty in air quality modelling is examined through the model ensemble spread of concentrations. For ozone daily maxima the ensemble spread origin differs from one region to another. In the neighbourhood of cities or in mountainous areas the spread of predicted values does not span the range of observed data, due to poorly resolved emissions or complex-terrain meteorology. By contrast in Atlantic and North Sea coastal areas the spread of predicted values is found to be larger than the observations. This is attributed to large differences in the boundary conditions used in the different models. For NO2 daily averages the ensemble spread is generally too small compared with observations. This is because models miss highest values occurring in stagnant meteorology in stable boundary layers near cities. For secondary particulate matter compounds the simulated concentration spread is more balanced, observations falling nearly equiprobably within the ensemble, and the spread originates both from meteorology and aerosol chemistry and thermodynamics. © 2008.
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| 7. |
- Dorfmeister, B, et al.
(författare)
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Effects of six APOA5 variants, identified in patients with severe hypertriglyceridemia, on in vitro lipoprotein lipase activity and receptor binding
- 2008
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 28:10, s. 1866-1871
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The purpose of this study was to identify rare APOA5 variants in 130 severe hypertriglyceridemic patients by sequencing, and to test their functionality, since no patient recall was possible. METHODS AND RESULTS: We studied the impact in vitro on LPL activity and receptor binding of 3 novel heterozygous variants, apoAV-E255G, -G271C, and -H321L, together with the previously reported -G185C, -Q139X, -Q148X, and a novel construct -Delta139 to 147. Using VLDL as a TG-source, compared to wild type, apoAV-G255, -L321 and -C185 showed reduced LPL activation (-25% [P=0.005], -36% [P<0.0001], and -23% [P=0.02]), respectively). ApoAV-C271, -X139, -X148, and Delta139 to 147 had little affect on LPL activity, but apoAV-X139, -X148, and -C271 showed no binding to LDL-family receptors, LR8 or LRP1. Although the G271C proband carried no LPL and APOC2 mutations, the H321L carrier was heterozygous for LPL P207L. The E255G carrier was homozygous for LPL W86G, yet only experienced severe hypertriglyceridemia when pregnant. CONCLUSIONS: The in vitro determined function of these apoAV variants only partly explains the high TG levels seen in carriers. Their occurrence in the homozygous state, coinheritance of LPL variants or common APOA5 TG-raising variant in trans, appears to be essential for their phenotypic expression.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- van Cappellen, W., et al.
(författare)
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Apertif: Phased array feeds for the Westerbork Synthesis Radio Telescope: System overview and performance characteristics
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
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Tidskriftsartikel (refereegranskat)abstract
- We describe the APERture Tile In Focus (Apertif) system, a phased array feed (PAF) upgrade of the Westerbork Synthesis Radio Telescope that transforms this telescope into a high-sensitivity, wide-field-of-view L-band imaging and transient survey instrument. Using novel PAF technology, up to 40 partially overlapping beams are formed on the sky simultaneously, significantly increasing the survey speed of the telescope. With this upgraded instrument, an imaging survey covering an area of 2300 deg2 is being performed that will deliver both continuum and spectral line datasets, of which the first data have been publicly released. In addition, a time domain transient and pulsar survey covering 15 000 deg2 is in progress. An overview of the Apertif science drivers, hardware, and software of the upgraded telescope is presented, along with its key performance characteristics.
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| 13. |
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| 14. |
- Van der Meer, J. M. R., et al.
(författare)
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IL-15 superagonist N-803 improves IFNγ production and killing of leukemia and ovarian cancer cells by CD34+ progenitor-derived NK cells
- 2020
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Ingår i: Cancer Immunology and Immunotherapy. - : Springer Science and Business Media Deutschland GmbH. - 0340-7004 .- 1432-0851.
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic natural killer (NK) cell transfer is a potential immunotherapy to eliminate and control cancer. A promising source are CD34 + hematopoietic progenitor cells (HPCs), since large numbers of cytotoxic NK cells can be generated. Effective boosting of NK cell function can be achieved by interleukin (IL)-15. However, its in vivo half-life is short and potent trans-presentation by IL-15 receptor α (IL-15Rα) is absent. Therefore, ImmunityBio developed IL-15 superagonist N-803, which combines IL-15 with an activating mutation, an IL-15Rα sushi domain for trans-presentation, and IgG1-Fc for increased half-life. Here, we investigated whether and how N-803 improves HPC-NK cell functionality in leukemia and ovarian cancer (OC) models in vitro and in vivo in OC-bearing immunodeficient mice. We used flow cytometry-based assays, enzyme-linked immunosorbent assay, microscopy-based serial killing assays, and bioluminescence imaging, for in vitro and in vivo experiments. N-803 increased HPC-NK cell proliferation and interferon (IFN)γ production. On leukemia cells, co-culture with HPC-NK cells and N-803 increased ICAM-1 expression. Furthermore, N-803 improved HPC-NK cell-mediated (serial) leukemia killing. Treating OC spheroids with HPC-NK cells and N-803 increased IFNγ-induced CXCL10 secretion, and target killing after prolonged exposure. In immunodeficient mice bearing human OC, N-803 supported HPC-NK cell persistence in combination with total human immunoglobulins to prevent Fc-mediated HPC-NK cell depletion. Moreover, this combination treatment decreased tumor growth. In conclusion, N-803 is a promising IL-15-based compound that boosts HPC-NK cell expansion and functionality in vitro and in vivo. Adding N-803 to HPC-NK cell therapy could improve cancer immunotherapy.
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| 15. |
- Waszczuk-Gajda, A, et al.
(författare)
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Complications of Autologous Stem Cell Transplantation in Multiple Myeloma: Results from the CALM Study
- 2022
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: The main goal of this post hoc analysis of the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study was to evaluate the rate of short- and long-term infectious and non-infectious complications occurring after ASCT in patients with multiple myeloma (MM). Methods: The analysis included all patients with MM from the CALM study who underwent ≥1 ASCT. The primary endpoint of the analysis was to determine the rate of infectious and non-infectious complications after ASCT and to compare them in three time periods: 0–100 days, 101 days–1 year, and >1 year after the first transplant. Results: The analysis included a total of 3552 patients followed up for a median of 56.7 months (range 0.4–108.1). Complication rates decreased with the time from ASCT with 24.85 cases per 100 patient-years from day 0 to 100 days after the transplant, and <2.31 cases per 100 patient-years from the 101st day. At 100 days after ASC T, 45.7% of patients had complications, with infectious events being twice as frequent as non-infectious complications. Bacterial infections (6.5 cases per 100 patient-years, 95% CI: 6.1–7.0) and gastrointestinal complications (4.7 cases per 100 patient-years, 95% CI: 4.3–5.1) were the most common early events. The pattern of complications changed with time from ASCT. The presence of complications after ASCT was not associated with overall survival. Conclusions: Our data provide a solid basis for comparing ASCT-related complications to those caused by emerging treatments in multiple myeloma, such as CAR T-cell therapy and other immunotherapies.
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| 16. |
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| 17. |
- de Groot, P. F., et al.
(författare)
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Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study
- 2017
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Objective Environmental factors driving the development of type 1 diabetes (T1D) are still largely unknown. Both animal and human studies have shown an association between altered fecal microbiota composition, impaired production of short-chain fatty acids (SCFA) and T1D onset. However, observational evidence on SCFA and fecal and oral microbiota in adults with longstanding T1D vs healthy controls (HC) is lacking. We included 53 T1D patients without complications or medication and 50 HC matched for age, sex and BMI. Oral and fecal microbiota, fecal and plasma SCFA levels, markers of intestinal inflammation (fecal IgA and calprotectin) and markers of low-grade systemic inflammation were measured. Oral microbiota were markedly different in T1D (eg abundance of Streptococci) compared to HC. Fecal analysis showed decreased butyrate producing species in T1D and less butyryl-CoA transferase genes. Also, plasma levels of acetate and propionate were lower in T1D, with similar fecal SCFA. Finally, fecal strains Christensenella and Subdoligranulum correlated with glycemic control, inflammatory parameters and SCFA. We conclude that T1D patients harbor a different amount of intestinal SCFA (butyrate) producers and different plasma acetate and propionate levels. Future research should disentangle cause and effect and whether supplementation of SCFA-producing bacteria or SCFA alone can have disease-modifying effects in T1D.
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| 18. |
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| 19. |
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| 20. |
- Kirişli, Hortense, et al.
(författare)
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Standardized evaluation framework for evaluating coronary artery stenosis detection, stenosis quantification and lumen segmentation algorithms in computed tomography angiography
- 2013
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Ingår i: Medical Image Analysis. - : Elsevier. - 1361-8415 .- 1361-8423. ; 17:8, s. 859-876
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Tidskriftsartikel (refereegranskat)abstract
- Though conventional coronary angiography (CCA) has been the standard of reference for diagnosing coronary artery disease in the past decades, computed tomography angiography (CIA) has rapidly emerged, and is nowadays widely used in clinical practice. Here, we introduce a standardized evaluation framework to reliably evaluate and compare the performance of the algorithms devised to detect and quantify the coronary artery stenoses, and to segment the coronary artery lumen in CIA data. The objective of this evaluation framework is to demonstrate the feasibility of dedicated algorithms to: (I) (semi-)automatically detect and quantify stenosis on CIA, in comparison with quantitative coronary angiography (QCA) and CIA consensus reading, and (2) (semi-)automatically segment the coronary lumen on CIA, in comparison with expert's manual annotation. A database consisting of 48 multicenter multivendor cardiac CIA datasets with corresponding reference standards are described and made available. The algorithms from 11 research groups were quantitatively evaluated and compared. The results show that (1) some of the current stenosis detection/quantification algorithms may be used for triage or as a second-reader in clinical practice, and that (2) automatic lumen segmentation is possible with a precision similar to that obtained by experts. The framework is open for new submissions through the website, at http://coronary.bigr.nl/stenoses/.
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Schaap, M. M., et al.
(författare)
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Effect of nationwide tobacco control policies on smoking cessation in high and low educated groups in 18 European countries
- 2008
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Ingår i: Tobacco Control. - : BMJ. - 0964-4563 .- 1468-3318. ; 17:4, s. 248-255
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recently a scale was introduced to quantify the implementation of tobacco control policies at country level. Our study used this scale to examine the potential impact of these policies on quit ratios in European countries. Special attention was given to smoking cessation among lower educational groups. Methods: Cross-sectional data were derived from national health surveys from 18 European countries. In the analyses we distinguished between country, sex, two age groups (25-39 and 40-59 years) and educational level. Age-standardised quit ratios were calculated as total former-smokers divided by total ever-smokers. In regression analyses we explored the correlation between national quit ratios and the national score on the Tobacco Control Scale (TCS). Results: Quit ratios were especially high (> 45%) in Sweden, England, The Netherlands, Belgium and France and relatively low (< 30%) in Lithuania and Latvia. Higher educated smokers were more likely to have quit smoking than lower educated smokers in all age-sex groups in all countries. National score on the tobacco control scale was positively associated with quit ratios in all age-sex groups. The association of quit ratios with score on TCS did not show consistent differences between high and low education. Of all tobacco control policies of which the TCS is constructed, price policies showed the strongest association with quit ratios, followed by an advertising ban. Conclusion: Countries with more developed tobacco control policies have higher quit ratios than countries with less developed tobacco control policies. High and low educated smokers benefit about equally from the nationwide tobacco control policies.
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| 25. |
- Schaap, M., et al.
(författare)
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Performance of European chemistry transport models as function of horizontal resolution
- 2015
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1873-2844 .- 1352-2310. ; 112, s. 90-105
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Tidskriftsartikel (refereegranskat)abstract
- Air pollution causes adverse effects on human health as well as ecosystems and crop yield and also has an impact on climate change trough short-lived climate forcers. To design mitigation strategies for air pollution, 3D Chemistry Transport Models (CTMs) have been developed to support the decision process. Increases in model resolution may provide more accurate and detailed information, but will cubically increase computational costs and pose additional challenges concerning high resolution input data. The motivation for the present study was therefore to explore the impact of using finer horizontal grid resolution for policy support applications of the European Monitoring and Evaluation Programme (EMEP) model within the Long Range Transboundary Air Pollution (LRTAP) convention. The goal was to determine the "optimum resolution" at which additional computational efforts do not provide increased model performance using presently available input data. Five regional CTMs performed four runs for 2009 over Europe at different horizontal resolutions. The models' responses to an increase in resolution are broadly consistent for all models. The largest response was found for NO2 followed by PM10 and O-3. Model resolution does not impact model performance for rural background conditions. However, increasing model resolution improves the model performance at stations in and near large conglomerations. The statistical evaluation showed that the increased resolution better reproduces the spatial gradients in pollution regimes, but does not help to improve significantly the model performance for reproducing observed temporal variability. This study clearly shows that increasing model resolution is advantageous, and that leaving a resolution of 50 km in favour of a resolution between 10 and 20 km is practical and worthwhile. As about 70% of the model response to grid resolution is determined by the difference in the spatial emission distribution, improved emission allocation procedures at high spatial and temporal resolution are a crucial factor for further model resolution improvements. (C) 2015 Elsevier Ltd. All rights reserved.
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| 26. |
- Schaap, M., et al.
(författare)
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Standardized evaluation methodology and reference database for evaluating coronary artery centerline extraction algorithms
- 2009
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Ingår i: Medical Image Analysis. - : Elsevier. - 1361-8415 .- 1361-8423. ; 13:5, s. 701-714
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Tidskriftsartikel (refereegranskat)abstract
- Efficiently obtaining a reliable coronary artery centerline from computed tomography angiography data is relevant in clinical practice. Whereas numerous methods have been presented for this purpose, up to now no standardized evaluation methodology has been published to reliably evaluate and compare the performance of the existing or newly developed coronary artery centerline extraction algorithms. This paper describes a standardized evaluation methodology and reference database for the quantitative evaluation of coronary artery centerline extraction algorithms. The contribution of this work is fourfold: (1) a method is described to create a consensus centerline with multiple observers, (2) well-defined measures are presented for the evaluation of coronary artery centerline extraction algorithms, (3) a database containing 32 cardiac CTA datasets with corresponding reference standard is described and made available, and (4) 13 coronary artery centerline extraction algorithms, implemented by different research groups, are quantitatively evaluated and compared. The presented evaluation framework is made available to the medical imaging community for benchmarking existing or newly developed coronary centerline extraction algorithms.
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| 27. |
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| 28. |
- Schetelig, J, et al.
(författare)
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Haplotype Motif-Based Models for KIR-Genotype Informed Selection of Hematopoietic Cell Donors Fail to Predict Outcome of Patients With Myelodysplastic Syndromes or Secondary Acute Myeloid Leukemia
- 2021
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 11, s. 584520-
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Tidskriftsartikel (refereegranskat)abstract
- Results from registry studies suggest that harnessing Natural Killer (NK) cell reactivity mediated through Killer cell Immunoglobulin-like Receptors (KIR) could reduce the risk of relapse after allogeneic Hematopoietic Cell Transplantation (HCT). Several competing models have been developed to classify donors as KIR-advantageous or disadvantageous. Basically, these models differ by grouping donors based on distinct KIR–KIR–ligand combinations or by haplotype motif assignment. This study aimed to validate different models for unrelated donor selection for patients with Myelodysplatic Syndromes (MDS) or secondary Acute Myeloid Leukemia (sAML). In a joint retrospective study of the European Society for Blood and Marrow Transplantation (EBMT) and the Center for International Blood and Marrow Transplant Research (CIBMTR) registry data from 1704 patients with secondary AML or MDS were analysed. The cohort consisted mainly of older patients (median age 61 years) with high risk disease who had received chemotherapy-based reduced intensity conditioning and anti-thymocyte globulin prior to allogeneic HCT from well-matched unrelated stem cell donors. The impact of the predictors on Overall Survival (OS) and relapse incidence was tested in Cox regression models adjusted for patient age, a modified disease risk index, performance status, donor age, HLA-match, sex-match, CMV-match, conditioning intensity, type of T-cell depletion and graft type. KIR genes were typed using high-resolution amplicon-based next generation sequencing. In univariable and multivariable analyses none of the models predicted OS and the risk of relapse consistently. Our results do not support the hypothesis that optimizing NK-mediated alloreactivity is possible by KIR-genotype informed selection of HLA-matched unrelated donors. However, in the context of allogeneic transplantation, NK-cell biology is complex and only partly understood. KIR-genes are highly diverse and current assignment of haplotype motifs based on the presence or absence of selected KIR genes is over-simplistic. As a consequence, further research is highly warranted and should integrate cutting edge knowledge on KIR genetics, and NK-cell biology into future studies focused on homogeneous groups of patients and treatment modalities.
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| 29. |
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| 31. |
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| 33. |
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| 34. |
- Ciarelli, Giancarlo, et al.
(författare)
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Trends of inorganic and organic aerosols and precursor gases in Europe: Insights from the EURODELTA multi-model experiment over the 1990-2010 period
- 2019
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 12:12, s. 4923-4954
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Tidskriftsartikel (refereegranskat)abstract
- In the framework of the EURODELTA-Trends (EDT) modeling experiment, several chemical transport models (CTMs) were applied for the 1990-2010 period to investigate air quality changes in Europe as well as the capability of the models to reproduce observed long-term air quality trends. Five CTMs have provided modeled air quality data for 21 continuous years in Europe using emission scenarios prepared by the International Institute for Applied Systems Analysis/Greenhouse Gas - Air Pollution Interactions and Synergies (IIASA/GAINS) and corresponding year-by-year meteorology derived from ERA-Interim global reanalysis. For this study, long-term observations of particle sulfate (SO2 4-), total nitrate (TNO3), total ammonium (TNHx) as well as sulfur dioxide (SO2) and nitrogen dioxide (NO2) for multiple sites in Europe were used to evaluate the model results. The trend analysis was performed for the full 21 years (referred to as PT) but also for two 11-year subperiods: 1990-2000 (referred to as P1) and 2000-2010 (referred to as P2). The experiment revealed that the models were able to reproduce the faster decline in observed SO2 concentrations during the first decade, i.e., 1990-2000, with a 64%-76% mean relative reduction in SO2 concentrations indicated by the EDT experiment (range of all the models) versus an 82% mean relative reduction in observed concentrations. During the second decade (P2), the models estimated a mean relative reduction in SO2 concentrations of about 34%-54%, which was also in line with that observed (47%). Comparisons of observed and modeled NO2 trends revealed a mean relative decrease of 25% and between 19% and 23% (range of all the models) during the P1 period, and 12% and between 22% and 26% (range of all the models) during the P2 period, respectively. Comparisons of observed and modeled trends in SO4 2- concentrations during the P1 period indicated that the models were able to reproduce the observed trends at most of the sites, with a 42%-54% mean relative reduction indicated by the EDT experiment (range of all models) versus a 57% mean relative reduction in observed concentrations and with good performance also during the P2 and PT periods, even though all the models overpredicted the number of statistically significant decreasing trends during the P2 period. Moreover, especially during the P1 period, both modeled and observational data indicated smaller reductions in SO42- concentrations compared with their gas-phase precursor (i.e., SO2), which could be mainly attributed to increased oxidant levels and pH-dependent cloud chemistry. An analysis of the trends in TNO3 concentrations indicated a 28%-39% and 29% mean relative reduction in TNO3 concentrations for the full period for model data (range of all the models) and observations, respectively. Further analysis of the trends in modeled HNO3 and particle nitrate (NO-3 ) concentrations revealed that the relative reduction in HNO3 was larger than that for NO-3 during the P1 period, which was mainly attributed to an increased availability of "free ammonia". By contrast, trends in modeled HNO3 and NO-3 concentrations were more comparable during the P2 period. Also, trends of TNHx concentrations were, in general, underpredicted by all models, with worse performance for the P1 period than for P2. Trends in modeled anthropogenic and biogenic secondary organic aerosol (ASOA and BSOA) concentrations together with the trends in available emissions of biogenic volatile organic compounds (BVOCs) were also investigated. A strong decrease in ASOA was indicated by all the models, following the reduction in anthropogenic non-methane VOC (NMVOC) precursors. Biogenic emission data provided by the modeling teams indicated a few areas with statistically significant increase in isoprene emissions and monoterpene emissions during the 1990-2010 period over Fennoscandia and eastern European regions (i.e., around 14 %-27 %), which was mainly attributed to the increase of surface temperature. However, the modeled BSOA concentrations did not linearly follow the increase in biogenic emissions. Finally, a comprehensive evaluation against positive matrix factorization (PMF) data, available during the second period (P2) at various European sites, revealed a systematic underestimation of the modeled SOA fractions of a factor of 3 to 11, on average, most likely because of missing SOA precursors and formation pathways, with reduced biases for the models that accounted for chemical aging of semi-volatile SOA components in the atmosphere.
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| 35. |
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| 36. |
- Hayden, PJ, et al.
(författare)
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Second allogeneic transplants for multiple myeloma: a report from the EBMT Chronic Malignancies Working Party
- 2021
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Ingår i: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 56:10, s. 2367-2381
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Tidskriftsartikel (refereegranskat)abstract
- The EBMT Chronic Malignancies Working Party performed a retrospective analysis of 215 patients who underwent a second allo-HCT for myeloma between 1994 and 2017, 159 for relapse and 56 for graft failure. In the relapse group, overall survival (OS) was 38% (30–46%) at 2 years and 25% (17–32%) at 5 years. Patients who had a HLA-identical sibling (HLAid-Sib) donor for their first and second transplants had superior OS (5 year OS: HLAid-Sib/HLAid-Sib: 35% (24–46%); Others 9% (0–17%), p < 0.001). There was a significantly higher incidence of acute grade II-IV GvHD in those patients who had also developed GvHD following their initial HLA-identical sibling allo-HCT (HLAid-Sib/HLAid-Sib: 50% (33–67%); Other 22% (8–36%), p = 0.03). More as opposed to fewer than 2 years between transplants was associated with superior 5-yr OS (31% (21–40%) vs. 10% (1–20%), P = 0.005). On multivariate analysis, consecutive HLA-identical sibling donor transplants conferred a significant OS advantage (0.4 (0.24–0.67), p < 0.001). In the graft failure group, OS was 41% at 2 years. In summary, a second allo-HCT using a HLA-identical sibling donor, if available, provides the best transplant outcomes for relapsed myeloma in this setting.
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| 37. |
- Kootte, R. S., et al.
(författare)
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Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition
- 2017
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 26:4, s. 611-619
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Tidskriftsartikel (refereegranskat)abstract
- The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We therefore studied the effect of lean donor (allogenic) versus own (autologous) fecal microbiota transplantation (FMT) to male recipients with the metabolic syndrome. Whereas we did not observe metabolic changes at 18 weeks after FMT, insulin sensitivity at 6 weeks after allogenic FMT was significantly improved, accompanied by altered microbiota composition. We also observed changes in plasma metabolites such as gamma-aminobutyric acid and show that metabolic response upon allogenic FMT (defined as improved insulin sensitivity 6 weeks after FMT) is dependent on decreased fecal microbial diversity at baseline. In conclusion, the beneficial effects of lean donor FMT on glucose metabolism are associated with changes in intestinal microbiota and plasma metabolites and can be predicted based on baseline fecal microbiota composition.
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| 38. |
- Mackenbach, Johan P, et al.
(författare)
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Socioeconomic inequalities in health in 22 European countries
- 2008
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 358:23, s. 2468-2481
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Tidskriftsartikel (refereegranskat)abstract
- We observed variation across Europe in the magnitude of inequalities in health associated with socioeconomic status. These inequalities might be reduced by improving educational opportunities, income distribution, health-related behavior, or access to health care.
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- Raj, Kavita, et al.
(författare)
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Family Mismatched Allogeneic Stem Cell Transplantation for Myelofibrosis : Report from the Chronic Malignancies Working Party of European Society for Blood and Marrow Transplantation
- 2019
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 25:3, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- This analysis included 56 myelofibrosis (MF) patients transplanted from family mismatched donor between 2009 and 2015 enrolled in the European Society for Blood and Marrow Transplantation database. The median age was 57 years (range, 38 to 72); 75% had primary MF and 25% had secondary MF. JAK2 V617F was mutated in 61%. Donors were HLA mismatched at 2 or more loci. Stem cells were sourced from bone marrow in 66% and peripheral blood in 34%. The median CD34(+) cell dose was 4.8 x 10(6)/kg (range, 1.7 to 22.9; n = 43). Conditioning was predominantly myeloablative in 70% and reduced intensity in the remainder. Regimens were heterogeneous with thiotepa, busulfan, fludarabine, and post-transplant cyclophosphamide used in 59%. The incidence of neutrophil engraftment by 28 days was 82% (range, 70% to 93%), at a median of 21 days (range, 19 to 23). At 2 years the cumulative incidence of primary graft failure was 9% (95% CI 1% to 16%) and secondary graft failure was 13% (95% CI 4% to 22%). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and Ill to IV was 28% (95% CI 16% to 40%) and 9% (95% CI 2% to 17%) at 100 days. The cumulative incidence of chronic GVHD at 1 year was 45% (95% CI 32% to 58%), but the cumulative incidence of death without chronic GVHD by 1 year was 20% (95% CI 10% to 31%). With a median follow-up of 32 months, the 1- and 2-year overall survival was 61% (95% CI 48% to 74%) and 56% (95% CI 41% to 70%), respectively. The 1- and 2- year progression-free survival was 58% (95% CI 45% to 71%) and 43% (95% CI 28% to 58%), respectively, with a 2-year cumulative incidence of relapse of 19% 95% CI 7% to 31%). The 2-year nonrelapse mortality was 38% (95% CI 24% to 51%). This retrospective study of MF allo-SCT using family mismatched donors demonstrated feasibility of the approach, timely neutrophil engraftment in over 80% of cases, and acceptable overall and progression-free survival rates with relapse rates not dissimilar to the unrelated donor setting. However, strategies to minimize the risk of graft failure and the relatively high nonrelapse mortality need to be used, ideally in a multicenter prospective fashion.
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- Schaap, Maartje M, et al.
(författare)
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Female ever-smoking, education, emancipation and economic development in 19 European countries
- 2009
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Ingår i: Social Science and Medicine. - : Elsevier BV. - 0277-9536 .- 1873-5347. ; 68:7, s. 1271-1278
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Tidskriftsartikel (refereegranskat)abstract
- Large differences in ever-smoking rates among women are found between countries and socio-economic groups. This study examined the socio-economic inequalities in female ever-smoking rates in 19 European countries, and explored the association between cross-national differences in these inequalities and economic development and women's emancipation. Data on smoking were derived from national health interview surveys from 19 European countries. For each country, age group (25-39, 40-59 and 60+ years), educational level (4 standard levels), and cumulative ever-smoking rates were calculated as the proportion of current and former smokers of the total survey population. A Relative Index of Inequality was estimated for women in the three age groups to measure the magnitude of educational differences. In regression analyses the association of ever-smoking rates of women age 25-39 years with the gross domestic product (GDP) and the Gender Empowerment Measure (GEM) was explored. Less educated women aged 25-39 years were more likely to have ever smoked than more educated women in all countries, except Portugal. In the age groups 40-59 years the educational pattern differed between countries. Women aged 60+ years who were less educated were less likely to have ever smoked in all countries, except Norway and England. The size of inequalities varied considerably between countries and reversed within three age groups. For women 25-39 years, the association of ever-smoking rates with GDP was positive, especially for more educated women. The association of ever-smoking rates with GEM was positive for less educated women, but negative for more educated women. The results are consistent with the idea that economic development and social-cultural processes related to gender empowerment have affected the diffusion of smoking in different ways for more and less educated women.
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- Schmid, C, et al.
(författare)
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Long-term results and GvHD after prophylactic and preemptive donor lymphocyte infusion after allogeneic stem cell transplantation for acute leukemia
- 2022
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Ingår i: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 57:2, s. 215-223
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Tidskriftsartikel (refereegranskat)abstract
- We report on 318 patients with acute leukemia, receiving donor lymphocyte infusion (DLI) in complete hematologic remission (CHR) after allogeneic stem cell transplantation (alloSCT). DLI were applied preemptively (preDLI) for minimal residual disease (MRD, n = 23) or mixed chimerism (MC, n = 169), or as prophylaxis in high-risk patients with complete chimerism and molecular remission (proDLI, n = 126). Median interval from alloSCT to DLI1 was 176 days, median follow-up was 7.0 years. Five-year cumulative relapse incidence (CRI), non-relapse mortality (NRM), leukemia-free and overall survival (LFS/OS) of the entire cohort were 29.1%, 12.7%, 58.2%, and 64.3%. Cumulative incidences of acute graft-versus-host disease (aGvHD) grade II–IV°/chronic GvHD were 11.9%/31%. Nineteen patients (6%) died from DLI-induced GvHD. Age ≥60 years (p = 0.046), advanced stage at transplantation (p = 0.003), shorter interval from transplantation (p = 0.018), and prior aGvHD ≥II° (p = 0.036) were risk factors for DLI-induced GvHD. GvHD did not influence CRI, but was associated with NRM and lower LFS/OS. Efficacy of preDLI was demonstrated by decreasing MRD/increasing blood counts in 71%, and increasing chimerism in 70%. Five-year OS after preDLI for MRD/MC was 51%/68% among responders, and 37% among non-responders. The study describes response and outcome of DLI in CHR and helps to identify candidates without increased risk of severe GvHD.
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