| 1. |
- Schiller, D, et al.
(författare)
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The Human Affectome
- 2024
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Ingår i: Neuroscience and biobehavioral reviews. - 1873-7528. ; 158, s. 105450-
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Smid, Marcel, et al.
(författare)
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Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP53, PIK3CA, PTEN, CCND1 and CDH1. We find that CCND3 expression levels do not correlate with amplification, while increased GATA3 expression in mutant GATA3 cancers suggests GATA3 is an oncogene. In luminal cases the total number of substitutions, irrespective of type, associates with cell cycle gene expression and adverse outcome, whereas the number of mutations of signatures 3 and 13 associates with immune-response specific gene expression, increased numbers of tumour-infiltrating lymphocytes and better outcome. Thus, while earlier reports imply that the sheer number of somatic aberrations could trigger an immune-response, our data suggests that substitutions of a particular type are more effective in doing so than others.
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| 3. |
- Donaldson, M., et al.
(författare)
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Optimal Pubertal Induction in Girls with Turner Syndrome Using Either Oral or Transdermal Estradiol: A Proposed Modern Strategy
- 2019
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 91:3, s. 153-163
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most girls with Turner syndrome (TS) require pubertal induction with estrogen, followed by long term replacement. However, no adequately powered prospective studies comparing transdermal with oral 17 beta-estradiol administration exist. This reflects the difficulty of securing funding to study a rare condition with relatively low morbidity/mortality when competing against conditions such as cancer and vascular disease. Protocol Consensus: The TS Working Group of the European Society for Paediatric Endocrinology (ESPE) has agreed to both a 3-year oral and a 3-year transdermal regimen for pubertal induction. Prerequisites include suitable 17 beta-estradiol tablets and matrix patches to allow the delivery of incremental doses based on body weight. Study Proposal: An international prospective cohort study with single centre analysis is proposed in which clinicians and families are invited to choose either of the agreed regimens, usually starting at 11 years. We hypothesise that pubertal induction with transdermal estradiol will result in better outcomes for some key parameters. The primary outcome measure chosen is height gain during the induction period. Analysis: Assessment of the demographics and drop-out rates of patients choosing either oral or transdermal preparations; and appropriate analysis of outcomes including pubertal height gain, final height, liver enzyme and lipid profile, adherence/acceptability, cardiovascular health, including systolic and diastolic blood pressure and aortic root diameter and bone health. Conclusion: The proposed model of prospective data collection according to internationally agreed protocols aims to break the current impasse in obtaining evidence-based management for TS and could be applied to other rare paediatric endocrine conditions. (C) 2019 S. Karger AG, Basel
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| 4. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 5. |
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Chatzikonstantinou, T, et al.
(författare)
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COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study
- 2021
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35:12, s. 3444-3454
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.
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| 11. |
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| 12. |
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| 13. |
- Rocha, W. R.M., et al.
(författare)
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JWST Observations of Young protoStars (JOYS+): Detecting icy complex organic molecules and ions: I. CH4, SO2, HCOO, OCN, H2CO, HCOOH, CH3CH2OH, CH3CHO, CH3OCHO, and CH3COOH
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 683
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Tidskriftsartikel (refereegranskat)abstract
- Context. Complex organic molecules (COMs) are ubiquitously detected in the gas phase and thought to be mostly formed on icy grains. Nevertheless, there have not been any unambiguous detections of COMs larger than CH3OH in ices reported thus far. Exploring this matter in greater detail has now become possible with the unprecedented possibilities offered by the James Webb Space Telescope (JWST) within the infrared (IR) spectral range with its very high sensitivity and spectral resolution in the critical 5 10 μm range, the fingerprint region of oxygen-bearing COMs. Aims. In the JWST Observations of Young protoStars (JOYS+) program, more than 30 protostars are undergoing observation with the Medium Resolution Spectrograph (MRS) of the Mid-IR Instrument (MIRI). The goal of this study is to comprehensively explore the COMs ice signatures in one low- and one high-mass protostar: NGC 1333 IRAS 2A and IRAS 23385+6053, respectively. Methods. We performed global continuum and silicate subtractions of the MIRI-MRS spectra, followed by a local continuum subtraction in optical depth scale in the range around 6.8 and 8.6 μm, the ice COM fingerprint region. We explored different choices for the local continuum and silicate subtraction. Next, we fit the observational data with a large sample of available IR laboratory ice spectra. We used the ENIIGMA fitting tool, a genetic algorithm-based code that not only finds the best fit between the lab data and the observations, but also performs a statistical analysis of the solutions, such as deriving the confidence intervals and quantifying fit degeneracy. Results. We report the best fits for the spectral ranges between 6.8 and 8.6 μm in NGC 1333 IRAS 2A and IRAS 23385+6053, originating from simple molecules and COMs, as well as negative ions. Overall, we find that ten chemical species are needed to reproduce the astronomical data. The strongest feature in this range (7.7 μm) is dominated by CH4, with contributions from SO2 and OCN. Our results indicate that the 7.2 and 7.4 μm bands are mostly dominated by HCOO. We also find statistically robust detections of COMs based on multiple bands, most notably, CH3CHO, CH3CH2OH, and CH3OCHO. We also report a likely detection of CH3COOH. Based on the ice column density ratios between CH3CH2OH and CH3CHO of NGC 1333 IRAS 2A and IRAS 23385+6053, we find compelling evidence that these COMs are formed on icy grains. Finally, the derived ice abundances for NGC 1333 IRAS 2A correlate well with those in comet 67P/GC within a factor of 5. Conclusions. Based on the high-quality JWST (MIRI-MRS) spectra, we conclude that COMs are present in interstellar ices, thus providing additional proof for the solid-state origin of these species in star-forming regions. In addition, the good correlation between the ice abundances in comet 67P and NGC 1333 IRAS 2A is fully in line with the idea that cometary COMs may be inherited from the early protostellar phases to a significant extent.
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| 14. |
- Beuther, H., et al.
(författare)
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JWST Observations of Young protoStars (JOYS): Outflows and accretion in the high-mass star-forming region IRAS 23385+6053
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 673
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Tidskriftsartikel (refereegranskat)abstract
- Context. Understanding the earliest stages of star formation, and setting it in the context of the general cycle of matter in the interstellar medium, is a central aspect of research with the James Webb Space Telescope (JWST). Aims. The JWST program JOYS (JWST Observations of Young protoStars) aims to characterize the physical and chemical properties of young high- and low-mass star-forming regions, in particular the unique mid-infrared diagnostics of the warmer gas and solid-state components. We present early results from the high-mass star formation region IRAS 23385+6053. Methods. The JOYS program uses the Mid-Infrared Instrument (MIRI) Medium Resolution Spectrometer (MRS) with its integral field unit (IFU) to investigate a sample of high- and low-mass star-forming protostellar systems. Results. The full 5-? 28 μm MIRI MRS spectrum of IRAS 23385+6053 shows a plethora of interesting features. While the general spectrum is typical for an embedded protostar, we see many atomic and molecular gas lines boosted by the higher spectral resolution and sensitivity compared to previous space missions. Furthermore, ice and dust absorption features are also present. Here, we focus on the continuum emission, outflow tracers such as the H2(0-? 0)S(7), [FeII](4F9/2-6D9/2), and [NeII](2P1/2-2P3/2) lines, and the potential accretion tracer Humphreys α H I(7-6). The short-wavelength MIRI data resolve two continuum sources, A and B; mid-infrared source A is associated with the main millimeter continuum peak. The combination of mid-infrared and millimeter data reveals a young cluster in the making. Combining the mid-infrared outflow tracers H2, [FeII], and [NeII] with millimeter SiO data reveals a complex interplay of at least three molecular outflows driven by protostars in the forming cluster. Furthermore, the Humphreys α line is detected at a 3-?4σ? level toward the mid-infrared sources A and B. One can roughly estimate both accretion luminosities and corresponding accretion rates to be between ∼2.6 × 10-6 and ∼0.9 × 10-4 Mo yr-1. This is discussed in the context of the observed outflow rates. Conclusions. The analysis of the MIRI MRS observations for this young high-mass star-forming region reveals connected outflow and accretion signatures, as well as the enormous potential of JWST to boost our understanding of the physical and chemical processes at play during star formation.
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| 15. |
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| 16. |
- Gieser, C., et al.
(författare)
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JOYS: Disentangling the warm and cold material in the high-mass IRAS 23385+6053 cluster
- 2023
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 679
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Tidskriftsartikel (refereegranskat)abstract
- Context. High-mass star formation occurs in a clustered mode where fragmentation is observed from an early stage onward. Young protostars can now be studied in great detail with the recently launched James Webb Space Telescope (JWST). Aims. We study and compare the warm (>100 K) and cold (<100 K) material toward the high-mass star-forming region (HMSFR) IRAS 23385+6053 (IRAS 23385 hereafter) combining high-angular-resolution observations in the mid-infrared (MIR) with the JWST Observations of Young protoStars (JOYS) project and with the NOrthern Extended Millimeter Array (NOEMA) at millimeter (mm) wavelengths at angular resolutions of 0.a2 1.a0. Methods. We investigated the spatial morphology of atomic and molecular species using line-integrated intensity maps. We estimated the temperature and column density of different gas components using H2 transitions (warm and hot component) and a series of CH3CN transitions as well as 3 mm continuum emission (cold component). Results. Toward the central dense core of IRAS 23385, the material consists of relatively cold gas and dust ( 50 K), while multiple outflows create heated and/or shocked H2 and show enhanced temperatures ( 400 K) along the outflow structures. An energetic outflow with enhanced emission knots of [FeII] and [NiII] suggests J-type shocks, while two other outflows have enhanced emission of only H2 and [SI] caused by C-type shocks. The latter two outflows are also more prominent in molecular line emission at mm wavelengths (e.g., SiO, SO, H2CO, and CH3OH). Data of even higher angular resolution are needed to unambiguously identify the outflow-driving sources given the clustered nature of IRAS 23385. While most of the forbidden fine structure transitions are blueshifted, [NeII] and [NeIII] peak at the source velocity toward the MIR source A/mmA2 suggesting that the emission is originating from closer to the protostar. Conclusions. The warm and cold gas traced by MIR and mm observations, respectively, are strongly linked in IRAS 23385. The outflows traced by MIR H2 lines have molecular counterparts in the mm regime. Despite the presence of multiple powerful outflows that cause dense and hot shocks, a cold dense envelope still allows star formation to further proceed. To study and fully understand the spatially resolved MIR properties, a representative sample of low- and high-mass protostars has to be probed using JWST.
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| 17. |
- Linssen, Gerard C M, et al.
(författare)
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Clinical and prognostic effects of atrial fibrillation in heart failure patients with reduced and preserved left ventricular ejection fraction
- 2011
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 13:10, s. 1111-1120
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Atrial fibrillation (AF) is common in heart failure (HF), but few data regarding the prognostic relevance of AF are available in HF patients with preserved left ventricular ejection fraction (HF-PEF). We aimed to study the clinical impact of AF vs. sinus rhythm (SR) in stabilized HF patients with reduced left ventricular ejection fraction (HF-REF) and in those with preserved left ventricular ejection fraction (HF-PEF). METHODS AND RESULTS: We studied 927 patients with stable HF, of whom 336 (36%) had AF. N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations were measured at baseline and patients were followed for 18 months. We compared time to first HF (re-)hospitalization or death between patients with AF and SR. Atrial fibrillation was present at baseline in 215 (35%) patients with HF-REF (mean LVEF 0.25 + 0.08) and in 121 (40%) patients with HF-PEF (mean LVEF 0.50 + 0.09). Plasma NT-proBNP levels were similar in AF and SR patients (median 2398 vs. 2532 pg/mL, P = 0.74). Atrial fibrillation was independently associated with elevated NT-proBNP levels in HF-PEF, but not in HF-REF patients (multivariable B = 0.33, P= 0.047 and B = 0.03; P = 0.89, respectively). After 18 months of follow-up, the presence of AF was an independent predictor of death or HF hospitalization in HF-PEF (multivariable hazard ratio 1.49 (95% CI 1.04-2.14), P = 0.03), but not in HF-REF patients (1.05 (CI 95% 0.80-1.38), P = 0.72). CONCLUSION: Atrial fibrillation is equally common in patients with HF-PEF and HF-REF. In HF-PEF, but not in HF-REF patients, AF was associated with higher NT-proBNP levels and was independently related to death or HF hospitalization.
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| 18. |
- Look, M, et al.
(författare)
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Pooled analysis of prognostic impact of uPA and PAI-I in breast cancer patients
- 2003
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 90:3, s. 538-548
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Tidskriftsartikel (refereegranskat)abstract
- In this report we present an extension of the pooled analysis of the prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-I in breast cancer patients. We analyzed a different endpoint, metastasis-free survival (MFS). We checked the consistency of the estimates for uPA and PAI-I for relapse-free survival (RFS) and MFS exploring possible sources of heterogeneity. Nodal status, the most important prognostic factor for breast cancer, introduced heterogeneity in the uPA/PAI-I survival analyses, reflecting the interaction between nodal status and uPA/PAI-I. The estimates for uPA and PAI-I were found to be consistent, even when a different transformation of their values was used. The heterogeneity of the separate data sets decreased if the levels of uPA and PAI-I were ranked, data sets were pooled, and the analyses corrected for the base model that included all traditional prognostic factors, and stratified by data set. We conclude that uPA and PAI-I are ready to be used in the clinic to help classify breast cancer patients into high and low risk groups.
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| 19. |
- Look, MP, et al.
(författare)
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Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 8377 breast cancer patients
- 2002
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 94:2, s. 116-128
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Tidskriftsartikel (refereegranskat)abstract
- Background: Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play essential roles in tumor invasion and metastasis. High levels of both uPA and PAT-1 are associated with poor prognosis in breast cancer patients. To confirm the prognostic value of uPA and PAI-1 in primary breast cancer, we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG). Methods: The study included 18 datasets involving 8377 breast cancer patients. During follow-up (median 79 months), 35% of the patients relapsed and 27% died. Levels of uPA and PAI-1 in tumor tissue extracts were determined by different immunoassays; values were ranked within each dataset and divided by the number of patients in that dataset to produce fractional ranks that could be compared directly across datasets. Associations of ranks of uPA and PAI-1 levels with relapse-free survival (RFS) and overall survival (OS) were analyzed by Cox multivariable regression analysis stratified by dataset, including the following traditional prognostic variables: age, menopausal status, lymph node status, tumor size, histologic grade, and steroid hormone-receptor status. All P values were two-sided. Results: Apart from lymph node status, high levels of uPA and PAI-1 were the strongest predictors of both poor RFS and poor OS in the analyses of all patients. Moreover, in both lymph node-positive and lymph nodenegative patients, higher uPA and PAI-1 values were independently associated with poor RFS and poor OS. For (untreated) lymph node-negative patients in particular, uPA and PAI-1 included together showed strong prognostic ability (all P<.001). Conclusions: This pooled analysis of the EORTC-RBG datasets confirmed the strong and independent prognostic value of uPA and PAI-1 in primary breast cancer. For patients with lymph node-negative breast cancer, uPA and PAI-1 measurements in primary tumors may be especially useful for designing individualized treatment strategies.
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| 20. |
- Ray, T. P., et al.
(författare)
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Outflows from the youngest stars are mostly molecular
- 2023
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 622, s. 48-52
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Tidskriftsartikel (refereegranskat)abstract
- The formation of stars and planets is accompanied not only by the build-up of matter, namely accretion, but also by its expulsion in the form of highly supersonic jets that can stretch for several parsecs1,2. As accretion and jet activity are correlated and because young stars acquire most of their mass rapidly early on, the most powerful jets are associated with the youngest protostars3. This period, however, coincides with the time when the protostar and its surroundings are hidden behind many magnitudes of visual extinction. Millimetre interferometers can probe this stage but only for the coolest components3. No information is provided on the hottest (greater than 1,000 K) constituents of the jet, that is, the atomic, ionized and high-temperature molecular gases that are thought to make up the jet's backbone. Detecting such a spine relies on observing in the infrared that can penetrate through the shroud of dust. Here we report near-infrared observations of Herbig-Haro 211 from the James Webb Space Telescope, an outflow from an analogue of our Sun when it was, at most, a few times 104 years old. These observations reveal copious emission from hot molecules, explaining the origin of the 'green fuzzies'4-7 discovered nearly two decades ago by the Spitzer Space Telescope8. This outflow is found to be propagating slowly in comparison to its more evolved counterparts and, surprisingly, almost no trace of atomic or ionized emission is seen, suggesting its spine is almost purely molecular. Near-infrared imagery and spectroscopy from JWST of the Herbig-Haro 211 system, an analogue of the young Sun, reveals supersonic jets of hot molecules that can explain the origin of the 'green fuzzies' phenomenon.
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| 21. |
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| 22. |
- Tychoniec, Łukasz, et al.
(författare)
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JWST Observations of Young protoStars (JOYS) Linked accretion and ejection in a Class I protobinary system
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 687
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Tidskriftsartikel (refereegranskat)abstract
- Context. Accretion and ejection dictate the outcomes of star and planet formation processes. The mid-infrared (MIR) wavelength range offers key tracers of processes that have been difficult to detect and spatially resolve in protostars until now. Aims. We aim to characterize the interplay between accretion and ejection in the low-mass Class I protobinary system TMC1, comprising two young stellar objects: TMC1-W and TMC1-E at a 85 au separation. Methods. Using the James Webb Space Telescope (JWST) Mid-Infrared Instrument (MIRI) observations in 5–28 µm range, we measured the intensities of emission lines of H2, atoms, and ions, for instance, the [Fe II] and [Ne II], and HI recombination lines. We analyzed the spatial distribution of the different species using the MIRI Medium Resolution Spectrometer (MRS) capabilities to spatially resolve emission at 0'.́2–0'.́7 scales. we compared these results with the corresponding Atacama Large Millimeter/submillimeter Array (ALMA) maps tracing cold gas and dust. Results. We detected H2 outflow coming from TMC1-E, with no significant H2 emission from TMC1-W. The H2 emission from TMC1-E outflow appears narrow and extends to wider opening angles with decreasing Eup from S(8) to S(1) rotational transitions, indicating the disk wind as its origin. The outflow from TMC1-E protostar shows spatially extended emission lines of [Ne II], [Ne III], [Ar II], and [Ar III], with their line ratios consistent with UV radiation as a source of ionization. With ALMA, we detected an accretion streamer infalling from >1000 au scales onto the TMC1-E component. The TMC1-W protostar powers a collimated jet, detected with [Fe II] and [Ni II], making it consistent with energetic flow. A much weaker ionized jet is observed from TMC1-E, and both jets appear strikingly parallel to each other, indicating that the disks are co-planar. TMC1-W is associated with strong emission from hydrogen recombination lines, tracing the accretion onto the young star. Conclusions. MIRI-MRS observations provide an unprecedented view of protostellar accretion and ejection processes on 20 au scales. Observations of a binary Class I protostellar system show that the two processes are clearly intertwined, with accretion from the envelope onto the disk influencing a wide-angle wind ejected on disk scales. Finally, the accretion from the protostellar disk onto the protostar is associated with the source launching a collimated high-velocity jet within the innermost regions of the disk.
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| 29. |
- Francis, L., et al.
(författare)
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JOYS: MIRI/MRS spectroscopy of gas-phase molecules from the high-mass star-forming region IRAS 23385+6053
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 683
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Tidskriftsartikel (refereegranskat)abstract
- Context. Space-based mid-infrared (IR) spectroscopy is a powerful tool for the characterization of important star formation tracers of warm gas which are unobservable from the ground. The previous mid-IR spectra of bright high-mass protostars with the Infrared Space Observatory (ISO) in the hot-core phase typically show strong absorption features from molecules such as CO2, C2H2, and HCN. However, little is known about their fainter counterparts at earlier stages. Aims. We aim to characterize the gas-phase molecular features in James Webb Space Telescope Mid-Infrared Instrument Medium Resolution Spectrometer (MIRI/MRS) spectra of the young and clustered high-mass star-forming region IRAS 23385+6053. Methods. Spectra were extracted from several locations in the MIRI/MRS field of view, targeting two mid-IR sources tracing embedded massive protostars as well as three H2 bright outflow knots at distances of >8000 au from the multiple. Molecular features in the spectra were fit with local thermodynamic equilibrium (LTE) slab models, with their caveats discussed in detail. Results. Rich molecular spectra with emission from CO, H2, HD, H2O, C2H2, HCN, CO2, and OH are detected towards the two mid-IR sources. However, only CO and OH are seen towards the brightest H2 knot positions, suggesting that the majority of the observed species are associated with disks or hot core regions rather than outflows or shocks. The LTE model fits to 12CO2, C2H2, HCN emission suggest warm 120a-200 K emission arising from a disk surface around one or both protostars. The abundances of CO2 and C2H2 of ~10âà  à  7 are consistent with previous observations of high-mass protostars. Weak ~500 K H2O emission at ~6a-7 μm is detected towards one mid-IR source, whereas 250a-1050 K H2O absorption is found in the other. The H2O absorption may occur in the disk atmosphere due to strong accretion-heating of the midplane, or in a disk wind viewed at an ideal angle for absorption. CO emission may originate in the hot inner disk or outflow shocks, but NIRSpec data covering the 4.6 μm band head are required to determine the physical conditions of the CO gas, as the high temperatures seen in the MIRI data may be due to optical depth. OH emission is detected towards both mid-IR source positions and one of the shocks, and is likely excited by water photodissociation or chemical formation pumping in a highly non-LTE manner. Conclusions. The observed molecular spectra are consistent with disks having already formed around two protostars in the young IRAS 23385+6054 system. Molecular features mostly appear in emission from a variety of species, in contrast to the more evolved hot core phase protostars which typically show only absorption; however, further observations of young high-mass protostars are needed to disentangle geometry and viewing angle effects from evolution.
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| 30. |
- Gelder, Marion E Meijer-Van, et al.
(författare)
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Long-term survival of patients with CLL after allogeneic transplantation : A report from the European Society for Blood and Marrow Transplantation
- 2017
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 52:3, s. 372-380
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Tidskriftsartikel (refereegranskat)abstract
- Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients.
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| 32. |
- Kirchhof, Paulus, et al.
(författare)
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A roadmap to improve the quality of atrial fibrillation management : proceedings from the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference
- 2016
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 18:1, s. 37-50
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Tidskriftsartikel (refereegranskat)abstract
- At least 30 million people worldwide carry a diagnosis of atrial fibrillation (AF), and many more suffer from undiagnosed, subclinical, or 'silent' AF. Atrial fibrillation-related cardiovascular mortality and morbidity, including cardiovascular deaths, heart failure, stroke, and hospitalizations, remain unacceptably high, even when evidence-based therapies such as anticoagulation and rate control are used. Furthermore, it is still necessary to define how best to prevent AF, largely due to a lack of clinical measures that would allow identification of treatable causes of AF in any given patient. Hence, there are important unmet clinical and research needs in the evaluation and management of AF patients. The ensuing needs and opportunities for improving the quality of AF care were discussed during the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference in Nice, France, on 22 and 23 January 2015. Here, we report the outcome of this conference, with a focus on (i) learning from our 'neighbours' to improve AF care, (ii) patient-centred approaches to AF management, (iii) structured care of AF patients, (iv) improving the quality of AF treatment, and (v) personalization of AF management. This report ends with a list of priorities for research in AF patients.
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| 33. |
- Kotecha, Dipak, et al.
(författare)
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Integrating new approaches to atrial fibrillation management : the 6th AFNET/EHRA Consensus Conference.
- 2018
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 20:3, s. 395-407
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Tidskriftsartikel (refereegranskat)abstract
- There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse cardiovascular events. New approaches to AF management, including the use of novel technologies and structured, integrated care, have the potential to enhance clinical phenotyping or result in better treatment selection and stratified therapy. Here, we report the outcomes of the 6th Consensus Conference of the Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association (EHRA), held at the European Society of Cardiology Heart House in Sophia Antipolis, France, 17-19 January 2017. Sixty-two global specialists in AF and 13 industry partners met to develop innovative solutions based on new approaches to screening and diagnosis, enhancing integration of AF care, developing clinical pathways for treating complex patients, improving stroke prevention strategies, and better patient selection for heart rate and rhythm control. Ultimately, these approaches can lead to better outcomes for patients with AF.
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| 34. |
- Linz, Dominik, et al.
(författare)
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Longer and better lives for patients with atrial fibrillation : the 9th AFNET/EHRA consensus conference
- 2024
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 26:4
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA).Methods and results: Eighty-three international experts met in Munster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF.Conclusions: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF. Graphical Abstract
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| 37. |
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| 38. |
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| 39. |
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| 40. |
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| 41. |
- Schetelig, J, et al.
(författare)
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Data quality initiative in CLL
- 2012
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Ingår i: BONE MARROW TRANSPLANTATION. - 0268-3369. ; 47, s. S35-S35
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 42. |
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| 43. |
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| 44. |
- Schnabel, Renate B, et al.
(författare)
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Early diagnosis and better rhythm management to improve outcomes in patients with atrial fibrillation : the 8th AFNET/EHRA consensus conference
- 2023
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 25:1, s. 6-27
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Tidskriftsartikel (refereegranskat)abstract
- Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current therapy. This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021. Results of the interdisciplinary, hybrid discussions in breakout groups and the plenary based on recently published and unpublished observations are summarized in this consensus paper to support improved care for patients with AF by guiding prevention, individualized management, and research strategies. The main outcomes are (i) new evidence supports a simple, scalable, and pragmatic population-based AF screening pathway; (ii) rhythm management is evolving from therapy aimed at improving symptoms to an integrated domain in the prevention of AF-related outcomes, especially in patients with recently diagnosed AF; (iii) improved characterization of atrial cardiomyopathy may help to identify patients in need for therapy; (iv) standardized assessment of cognitive function in patients with AF could lead to improvement in patient outcomes; and (v) artificial intelligence (AI) can support all of the above aims, but requires advanced interdisciplinary knowledge and collaboration as well as a better medico-legal framework. Implementation of new evidence-based approaches to AF screening and rhythm management can improve outcomes in patients with AF. Additional benefits are possible with further efforts to identify and target atrial cardiomyopathy and cognitive impairment, which can be facilitated by AI.
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| 45. |
- Van Gelder, M. L., et al.
(författare)
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JOYS+: Mid-infrared detection of gas-phase SO 2 emission in a low-mass protostar
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 682
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Tidskriftsartikel (refereegranskat)abstract
- Context. Thanks to the Mid-InfraRed Instrument (MIRI) on the James Webb Space Telescope (JWST), our ability to observe the star formation process in the infrared has greatly improved. Due to its unprecedented spatial and spectral resolution and sensitivity in the mid-infrared, JWST/MIRI can see through highly extincted protostellar envelopes and probe the warm inner regions. An abundant molecule in these warm inner regions is SO2, which is a common tracer of both outflow and accretion shocks as well as hot core chemistry. Aims. This paper presents the first mid-infrared detection of gaseous SO2 emission in an embedded low-mass protostellar system rich in complex molecules and aims to determine the physical origin of the SO2 emission. Methods. JWST/MIRI observations taken with the Medium Resolution Spectrometer (MRS) of the low-mass protostellar binary NGC 1333 IRAS 2A in the JWST Observations of Young protoStars (JOYS+) program are presented. The observations reveal emission from the SO2 ν3 asymmetric stretching mode at 7.35 µm. Using simple slab models and assuming local thermodynamic equilibrium (LTE), we derived the rotational temperature and total number of SO2 molecules. We then compared the results to those derived from high-angular-resolution SO2 data on the same scales (∼50−100 au) obtained with the Atacama Large Millimeter/submillimeter Array (ALMA). Results. The SO2 emission from the ν3 band is predominantly located on ∼50−100 au scales around the mid-infrared continuum peak of the main component of the binary, IRAS 2A1. A rotational temperature of 92 ± 8 K is derived from the ν3 lines. This is in good agreement with the rotational temperature derived from pure rotational lines in the vibrational ground state (i.e., ν = 0) with ALMA (104 ± 5 K), which are extended over similar scales. However, the emission of the ν3 lines in the MIRI-MRS spectrum is not in LTE given that the total number of molecules predicted by a LTE model is found to be a factor of 2 × 104 higher than what is derived for the ν = 0 state from the ALMA data. This difference can be explained by a vibrational temperature that is ∼100 K higher than the derived rotational temperature of the ν = 0 state: Tvib ∼ 200 K versus Trot = 104 ± 5 K. The brightness temperature derived from the continuum around the ν3 band (∼7.35 µm) of SO2 is ∼180 K, which confirms that the ν3 = 1 level is not collisionally populated but rather infrared-pumped by scattered radiation. This is also consistent with the non-detection of the ν2 bending mode at 18−20 µm. The similar rotational temperature derived from the MIRI-MRS and ALMA data implies that they are in fact tracing the same molecular gas. The inferred abundance of SO2 , determined using the LTE fit to the lines of the vibrational ground state in the ALMA data, is 1.0 ± 0.3 × 10−8 with respect to H2, which is on the lower side compared to interstellar and cometary ices (10−8−10−7). Conclusions. Given the rotational temperature, the extent of the emission (∼100 au in radius), and the narrow line widths in the ALMA data (∼3.5 km s−1), the SO2 in IRAS 2A likely originates from ice sublimation in the central hot core around the protostar rather than from an accretion shock at the disk–envelope boundary. Furthermore, this paper shows the importance of radiative pumping and of combining JWST observations with those from millimeter interferometers such as ALMA to probe the physics on disk scales and to infer molecular abundances.
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| 46. |
- van Veldhuisen, D. J., et al.
(författare)
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Implementation of device therapy (cardiac resynchronization therapy and implantable cardioverter defibrillator) for patients with heart failure in Europe: changes from 2004 to 2008
- 2009
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Ingår i: European Journal of Heart Failure. - 1879-0844. ; 11:12, s. 1143-51
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Heart failure (HF) patients increasingly receive device therapy, either an implantable cardioverter defibrillator (ICD) or a biventricular pacemaker, also called cardiac resynchronization therapy (CRT), or a CRT device with an ICD (CRT-D). However, epidemiological data on the use of device therapy in Europe are limited. METHODS AND RESULTS: Data on implantation rates for conventional pacemakers, ICD, CRT, and CRT-D in 15 Western European countries were obtained from the Eucomed Registry for the 5-year period 2004-2008. Implantation of conventional pacemakers increased by 9% in Europe over the 5 years (reaching 907/million in 2008) and there were significant differences between countries. Implantable cardioverter defibrillator implantations increased by 75% from 80/million in 2004 to 140/million in 2008, and differences between countries were larger than those for conventional pacemakers. Implantation rates for CRT-P alone increased slightly from 2004 to 2006, but remained at 25/million thereafter in Europe overall. The total number of CRT implants (CRT-P and -D) markedly increased from 46/million in 2004 to 99/million in 2008 (115%), but this was mainly due to more CRT-D implants, i.e. an increase in the proportion of CRT-D (from 55% in 2004 to 75% in 2008). Implantation rates for ICD, CRT, and CRT-D remained markedly different throughout the study period between countries. CONCLUSION: Implantation rates of devices for HF, in particular ICD and CRT-D, have increased significantly between 2004 and 2008 in Europe, but there remain major differences between countries.
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| 47. |
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| 48. |
- Bouamar, R., et al.
(författare)
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Tacrolimus Predose Concentrations Do Not Predict the Risk of Acute Rejection After Renal Transplantation: A Pooled Analysis From Three Randomized-Controlled Clinical Trials
- 2013
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 13:5, s. 1253-1261
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic drug monitoring (TDM) for tacrolimus (Tac) is universally applied. However, the concentrationeffect relationship for Tac is poorly defined. This study investigated whether Tac concentrations are associated with acute rejection in kidney transplant recipients. Data from three large trials were pooled. We used univariate and multivariate analysis to investigate the relationship between biopsy-proven acute rejection (BPAR) and Tac predose concentration at five time points (day 3, 10 and 14, and month 1 and 6 after transplantation). A total of 136/1304 patients experienced BPAR, giving an overall incidence of 10.4%. We did not find any significant correlations between Tac predose concentrations and the incidence of BPAR at the different time points. In the multivariate analysis, only delayed graft function (DGF) and the use of induction therapy were independently correlated with BPAR, with an odds ratio of 2.7 [95% CI: 1.84.0; p < 0.001] for DGF and 0.66 [95% CI: 0.440.99; p = 0.049] for induction therapy. The other variables, including the Tac predose concentrations, were not statistically significantly associated with BPAR. We did not find an association between the Tac predose concentrations measured at five time points after kidney transplantation and the incidence of acute rejection occurring thereafter. Based on this study it is not possible to define the optimal target concentrations for Tac.
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