| 1. |
- Marconi, A., et al.
(författare)
-
ANDES, the high resolution spectrograph for the ELT : science case, baseline design and path to construction
- 2022
-
Ingår i: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY IX. - : SPIE - International Society for Optical Engineering. - 9781510653504 - 9781510653498
-
Konferensbidrag (refereegranskat)abstract
- The first generation of ELT instruments includes an optical-infrared high resolution spectrograph, indicated as ELT-HIRES and recently christened ANDES (ArmazoNes high Dispersion Echelle Spectrograph). ANDES consists of three fibre-fed spectrographs (UBV, RIZ, YJH) providing a spectral resolution of similar to 100,000 with a minimum simultaneous wavelength coverage of 0.4-1.8 mu m with the goal of extending it to 0.35-2.4 mu m with the addition of a K band spectrograph. It operates both in seeing- and diffraction-limited conditions and the fibre-feeding allows several, interchangeable observing modes including a single conjugated adaptive optics module and a small diffraction-limited integral field unit in the NIR. Its modularity will ensure that ANDES can be placed entirely on the ELT Nasmyth platform, if enough mass and volume is available, or partly in the Coude room. ANDES has a wide range of groundbreaking science cases spanning nearly all areas of research in astrophysics and even fundamental physics. Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars, tests on the stability of Nature's fundamental couplings, and the direct detection of the cosmic acceleration. The ANDES project is carried forward by a large international consortium, composed of 35 Institutes from 13 countries, forming a team of more than 200 scientists and engineers which represent the majority of the scientific and technical expertise in the field among ESO member states.
|
|
| 2. |
- Hakkaart, C, et al.
(författare)
-
Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers
- 2022
-
Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1061-
-
Tidskriftsartikel (refereegranskat)abstract
- The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09–1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.
|
|
| 3. |
- Marconi, Alessandro, et al.
(författare)
-
ELT-HIRES, the high resolution spectrograph for the ELT : Phase A study and path to construction
- 2020
-
Ingår i: Ground-based and Airborne Instrumentation for Astronomy VIII. - : SPIE - International Society for Optical Engineering. - 9781510636828 - 9781510636811
-
Konferensbidrag (refereegranskat)abstract
- HIRES is the high-resolution spectrograph of the European Extremely Large Telescope at optical and near-infrared wavelengths. It consists of three fibre-fed spectrographs providing a wavelength coverage of 0.4-1.8 µm (goal 0.35-2.4 µm) at a spectral resolution of 100,000. The fibre-feeding allows HIRES to have several, interchangeable observing modes including a SCAO module and a small diffraction-limited IFU in the NIR. Therefore, it will be able to operate both in seeing- and diffraction-limited modes. Its modularity will ensure that HIRES can be placed entirely on the Nasmyth platform, if enough mass and volume is available, or part on the Nasmyth and part in the Coud`e room. ELT-HIRES has a wide range of science cases spanning nearly all areas of research in astrophysics and even fundamental physics. Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars (PopIII), tests on the stability of Nature’s fundamental couplings, and the direct detection of the cosmic acceleration. The HIRES consortium is composed of more than 30 institutes from 14 countries, forming a team of more than 200 scientists and engineers.
|
|
| 4. |
- Dorn, R. J., et al.
(författare)
-
CRIRES+ on sky at the ESO Very Large Telescope : Observing the Universe at infrared wavelengths and high spectral resolution
- 2023
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 671
-
Tidskriftsartikel (refereegranskat)abstract
- The CRyogenic InfraRed Echelle Spectrograph (CRIRES) Upgrade project CRIRES+ extended the capabilities of CRIRES. It transformed this VLT instrument into a cross-dispersed spectrograph to increase the wavelength range that is covered simultaneously by up to a factor of ten. In addition, a new detector focal plane array of three Hawaii 2RG detectors with a 5.3 mu m cutoff wavelength replaced the existing detectors. Amongst many other improvements, a new spectropolarimetric unit was added and the calibration system has been enhanced. The instrument was installed at the VLT on Unit Telescope 3 at the beginning of 2020 and successfully commissioned and verified for science operations during 2021, partly remotely from Europe due to the COVID-19 pandemic. The instrument was subsequently offered to the community from October 2021 onwards. This article describes the performance and capabilities of the upgraded instrument and presents on sky results.
|
|
| 5. |
- Dubernet, M. L., et al.
(författare)
-
The virtual atomic and molecular data centre (VAMDC) consortium
- 2016
-
Ingår i: Journal of Physics B. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 49:7
-
Tidskriftsartikel (refereegranskat)abstract
- The Virtual Atomic and Molecular Data Centre (VAMDC) Consortium is a worldwide consortium which federates atomic and molecular databases through an e-science infrastructure and an organisation to support this activity. About 90% of the inter-connected databases handle data that are used for the interpretation of astronomical spectra and for modelling in many fields of astrophysics. Recently the VAMDC Consortium has connected databases from the radiation damage and the plasma communities, as well as promoting the publication of data from Indian institutes. This paper describes how the VAMDC Consortium is organised for the optimal distribution of atomic and molecular data for scientific research. It is noted that the VAMDC Consortium strongly advocates that authors of research papers using data cite the original experimental and theoretical papers as well as the relevant databases.
|
|
| 6. |
- Marconi, A., et al.
(författare)
-
ELT-HIRES, the high resolution spectrograph for the ELT : results from the Phase A study
- 2018
-
Ingår i: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY VII. - : SPIE-INT SOC OPTICAL ENGINEERING. - 9781510619586
-
Konferensbidrag (refereegranskat)abstract
- We present the results from the phase A study of ELT-HIRES, an optical-infrared High Resolution Spectrograph for ELT, which has just been completed by a consortium of 30 institutes from 12 countries forming a team of about 200 scientists and engineers. The top science cases of ELT-HIRES will be the detection of life signatures from exoplanet atmospheres, tests on the stability of Nature's fundamental couplings, the direct detection of the cosmic acceleration. However, the science requirements of these science cases enable many other groundbreaking science cases. The baseline design, which allows to fulfil the top science cases, consists in a modular fiber fed cross-dispersed echelle spectrograph with two ultra-stable spectral arms providing a simultaneous spectral range of 0.4-1.8 pm at a spectral resolution of 100, 000. The fiber-feeding allows ELT-HIRES to have several, interchangeable observing modes including a SCAO module and a small diffraction-limited IFU.
|
|
| 7. |
|
|
| 8. |
- Oliva, E., et al.
(författare)
-
Concept and optical design of the cross-disperser module for CRIRES
- 2014
-
Ingår i: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY V. - : SPIE. - 9780819496157
-
Konferensbidrag (refereegranskat)abstract
- CRIRES, the ESO high resolution infrared spectrometer, is a unique instrument which allows astronomers to access a parameter space which up to now was largely uncharted. In its current setup, it consists of a single-order spectrograph providing long-slit, single-order spectroscopy with resolving power up to R=100,000 over a quite narrow spectral range. This has resulted in sub-optimal efficiency and use of telescope time for all the scientific programs requiring broad spectral coverage of compact objects (e.g. chemical abundances of stars and intergalactic medium, search and characterization of extra-solar planets). To overcome these limitations, a consortium was set-up for upgrading CRIRES to a cross-dispersed spectrometer, called CRIRES+. This paper presents the updated optical design of the cross-dispersion module for CRIRES+. This new module can be mounted in place of the current pre-disperser unit. The new system yields a factor of >10 increase in simultaneous spectral coverage and maintains a quite long slit (10"), ideal for observations of extended sources and for precise sky-background subtraction.
|
|
| 9. |
- Follert, R., et al.
(författare)
-
CRIRES plus : a cross-dispersed high-resolution infrared spectrograph for the ESO VLT
- 2014
-
Ingår i: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY V. - : SPIE. - 9780819496157
-
Konferensbidrag (refereegranskat)abstract
- High-resolution infrared spectroscopy plays an important role in astrophysics from the search for exoplanets to cosmology. Yet, many existing infrared spectrographs are limited by a rather small simultaneous wavelength coverage. The AO assisted CRIRES instrument, installed at the ESO VLT on Paranal, is one of the few IR (0.92-5.2 mu m) high-resolution spectrographs in operation since 2006. However it has a limitation that hampers its efficient use: the wavelength range covered in a single exposure is limited to similar to 15 nanometers. The CRIRES Upgrade project (CRIRES+) will transform CRIRES into a cross-dispersed spectrograph and will also add new capabilities. By introducing cross-dispersion elements the simultaneously covered wavelength range will be increased by at least a factor of 10 with respect to the present configuration, while the operational wavelength range will be preserved. For advanced wavelength calibration, new custom made absorption gas cells and etalons will be added. A spectro-polarimetric unit will allow one for the first time to record circularly polarized spectra at the highest spectral resolution. This will be all supported by a new data reduction software which will allow the community to take full advantage of the new capabilities of CRIRES+.
|
|
| 10. |
- Seemann, U., et al.
(författare)
-
Wavelength calibration from 1-5 mu m for the CRIRES plus high-resolution spectrograph at the VLT
- 2014
-
Ingår i: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY V. - : SPIE. - 9780819496157
-
Konferensbidrag (refereegranskat)abstract
- CRIRES at the VLT is one of the few adaptive optics enabled instruments that offer a resolving power of 10 5 from 1 - 5 mu m. An instrument upgrade (CRIRES+) is proposed to implement cross-dispersion capabilities, spectro-polarimetry modes, a new detector mosaic, and a new gas absorption cell. CRIRES+ will boost the simultaneous wavelength coverage of the current instrument (similar to lambda/70 in a single-order) by a factor of greater than or similar to 10 in the cross-dispersed configuration, while still retaining a 10 arcsec slit suitable for long-slit spectroscopy. CRIRES+ dramatically enhances the instrument's observing efficiency, and opens new scientific opportunities. These include high-precision radial-velocity studies on the 3m/s level to characterize extra-solar planets and their athmospheres, which demand for specialized, highly accurate wavelength calibration techniques. In this paper, we present a newly developed absorption gas-cell to enable high-precision wavelength calibration for CRIRES+. We also discuss the strategies and developments to cover the full operational spectral range (1-5 mu m), employing hollow-cathode emission lamps, Fabry-Perot etalons, and absorption gas-cells.
|
|
| 11. |
- Albert, Damien, et al.
(författare)
-
A Decade with VAMDC : Results and Ambitions
- 2020
-
Ingår i: Atoms. - : MDPI. - 2218-2004. ; 8:4
-
Tidskriftsartikel (refereegranskat)abstract
- This paper presents an overview of the current status of the Virtual Atomic and Molecular Data Centre (VAMDC) e-infrastructure, including the current status of the VAMDC-connected (or to be connected) databases, updates on the latest technological development within the infrastructure and a presentation of some application tools that make use of the VAMDC e-infrastructure. We analyse the past 10 years of VAMDC development and operation, and assess their impact both on the field of atomic and molecular (A&M) physics itself and on heterogeneous data management in international cooperation. The highly sophisticated VAMDC infrastructure and the related databases developed over this long term make them a perfect resource of sustainable data for future applications in many fields of research. However, we also discuss the current limitations that prevent VAMDC from becoming the main publishing platform and the main source of A&M data for user communities, and present possible solutions under investigation by the consortium. Several user application examples are presented, illustrating the benefits of VAMDC in current research applications, which often need the A&M data from more than one database. Finally, we present our vision for the future of VAMDC.
|
|
| 12. |
- Sollerman, J., et al.
(författare)
-
Supernova 2006aj and the associated X-Ray Flash 060218
- 2006
-
Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 454, s. 503-509
-
Tidskriftsartikel (refereegranskat)abstract
- We have studied the afterglow of the gamma-ray burst (GRB) of February 18, 2006. This is a nearby long GRB, with a very low peak energy, and is therefore classified as an X-ray Flash (XRF). XRF 060218 is clearly associated with a supernova - dubbed SN 2006aj. We present early spectra for SN 2006aj as well as optical lightcurves reaching out to 50 days past explosion. Our optical lightcurves define the rise times, the lightcurve shapes and the absolute magnitudes in the U, V and R bands, and we compare these data with data for other relevant supernovae. SN 2006aj evolved quite fast, somewhat similarly to SN 2002ap, but not as fast as SN 1994I. Our spectra show the evolution of the supernova over the peak, when the U-band portion of the spectrum rapidly fades due to extensive line blanketing. We compare to similar spectra of very energetic type Ic supernovae. Our first spectra are earlier than spectra for any other GRB-SN. The spectrum taken 12 days after burst in the rest frame is similar to somewhat later spectra of both SN 1998bw and SN 2003dh, implying a rapid early evolution. This is consistent with the fast lightcurve. From the narrow emission lines from the host galaxy we derive a redshift of z=0.0331±0.0007. This makes XRF 060218 the second closest gamma-ray burst detected. The flux of these emission lines indicate a high-excitation state, and a modest metallicity and star formation rate of the host galaxy.
|
|
| 13. |
- Pilheden, M., et al.
(författare)
-
Duplex Sequencing Uncovers Recurrent Low-frequency Cancer-associated Mutations in Infant and Childhood KMT2A-rearranged Acute Leukemia
- 2022
-
Ingår i: Hemasphere. - : Ovid Technologies (Wolters Kluwer Health). - 2572-9241. ; 6:10
-
Tidskriftsartikel (refereegranskat)abstract
- Infant acute lymphoblastic leukemia (ALL) with KMT2A-gene rearrangements (KMT2A-r) have few mutations and a poor prognosis. To uncover mutations that are below the detection of standard next-generation sequencing (NGS), a combination of targeted duplex sequencing and NGS was applied on 20 infants and 7 children with KMT2A-r ALL, 5 longitudinal and 6 paired relapse samples. Of identified nonsynonymous mutations, 87 had been previously implicated in cancer and targeted genes recurrently altered in KMT2A-r leukemia and included mutations in KRAS, NRAS, FLT3, TP53, PIK3CA, PAX5, PIK3R1, and PTPN11, with infants having fewer such mutations. Of identified cancer-associated mutations, 62% were below the resolution of standard NGS. Only 33 of 87 mutations exceeded 2% of cellular prevalence and most-targeted PI3K/RAS genes (31/33) and typically KRAS/NRAS. Five patients only had low-frequency PI3K/RAS mutations without a higher-frequency signaling mutation. Further, drug-resistant clones with FLT3(D835H) or NRAS(G13D/G12S) mutations that comprised only 0.06% to 0.34% of diagnostic cells, expanded at relapse. Finally, in longitudinal samples, the relapse clone persisted as a minor subclone from diagnosis and through treatment before expanding during the last month of disease. Together, we demonstrate that infant and childhood KMT2A-r ALL harbor low-frequency cancer-associated mutations, implying a vast subclonal genetic landscape.
|
|
| 14. |
- Spurdle, Amanda B., et al.
(författare)
-
Common Genetic Variation at BARD1 Is Not Associated with Breast Cancer Risk in BRCA1 or BRCA2 Mutation Carriers
- 2011
-
Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 20:5, s. 1032-1038
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies. Methods: A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated. Results: The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71-1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59-1.29) in BRCA2 carriers. Further analysis of haplotypes at BARD1 also revealed no evidence that additional common genetic variation not captured by Cys557Ser was associated with breast cancer risk. Conclusion: Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers. Impact: Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. Our finding that BARD1 does not contribute to this risk modification may focus research on other genes that do modify BRCA1/2-associated cancer risk. Cancer Epidemiol Biomarkers Prev; 20(5); 1032-38. (C) 2011 AACR.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Hahlin, Axel, et al.
(författare)
-
Determination of small-scale magnetic fields on Sun-like stars in the near-infrared using CRIRES
- 2023
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 675
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: We aim to characterise the small-scale magnetic fields of a sample of 16 Sun-like stars and investigate the capabilities of the newly upgraded near-infrared (NIR) instrument CRIRES+ at the Very Large Telescope in the context of small-scale magnetic field studies. Our targets also had their magnetic fields studied with optical spectra, which allowed us to compare magnetic field properties at different spatial scales on the stellar surface and to contrast small-scale magnetic field measurements at different wavelengths.Methods: We analysed the Zeeman broadening signature for six magnetically sensitive and insensitive Fe I lines in the H-band to measure small-scale magnetic fields on the stellar surfaces of our sample. We used polarised radiative transfer modelling and non-local thermodynamic equilibrium departure coefficients in combination with Markov chain Monte Carlo sampling to determine magnetic field characteristics and non-magnetic stellar parameters. We used two different approaches to describe the small-scale magnetic fields. The first is a two-component model with a single magnetic region and a free magnetic field strength. The second model contains multiple magnetic components with fixed magnetic field strengths.Results: We found average magnetic field strengths ranging from & SIM;0.4 kG down to < 0.1 kG. The results align closely with other results from high-resolution NIR spectrographs, such as SPIRou. It appears that the typical magnetic field strength in the magnetic region is slightly stronger than 1.3 kG, and for most stars in our sample, this strength is between 1 and 2 kG. We also found that the small-scale fields correlate with the large-scale fields and that the small-scale fields are at least ten times stronger than the large-scale fields inferred with Zeeman Doppler imaging. The two- and multi-component models produce systematically different results, as the strong fields from the multi-component model increase the obtained mean magnetic field strength. When comparing our results with the optical measurements of small-scale fields, we found a systematic offset two to three times stronger than fields in the optical results. This discrepancy cannot be explained by uncertainties in stellar parameters. Care should therefore be taken when comparing results obtained at different wavelengths until a clear cause can be established.
|
|
| 18. |
|
|
| 19. |
- van Os, G M A, et al.
(författare)
-
Induction of Auto-Antibodies Against β(2) -Glycoprotein I in Mice by Protein H of Streptococcus Pyogenes.
- 2011
-
Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 9:12, s. 2447-2456
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The antiphospholipid syndrome (APS) is characterized by the persistent presence of auto-antibodies against β(2) -Glycoprotein I (β(2) -GPI). β(2) -GPI can exist in two conformations. In plasma it is a circular protein, whereas it adopts a fish-hook shape after binding to phospholipids. Only the latter conformation is recognized by patient antibodies. β(2) -GPI has been shown to interact with Streptococcus pyogenes. Objective: Here we evaluated the potential of S. pyogenes derived proteins to induce auto-antibodies against β(2) -GPI. Methods and results: Four S. pyogenes surface proteins (M1 protein, protein H, SclA and SclB) were found to interact with β(2) -GPI. Only binding to protein H induces a conformational change in β(2) -GPI, thereby exposing a cryptic epitope for APS-related auto-antibodies. Mice were injected with the four proteins. Only mice injected with protein H developed antibodies against the patient antibody related epitope in domain I of β(2) -GPI. Patients with pharyngotonsillitis caused by S. pyogenes who developed antibodies towards protein H also generated anti-β(2) -GPI antibodies. Conclusion: Our study demonstrated that a bacterial protein can induce a conformational change in β(2) -GPI resulting in the formation of auto-antibodies against β(2) -GPI. This constitutes a novel mechanism for the formation of auto-antibodies against β(2) -GPI.
|
|
| 20. |
- Yan, F., et al.
(författare)
-
CRIRES+ detection of CO emissions lines and temperature inversions on the dayside of WASP-18b and WASP-76b
- 2023
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 672
-
Tidskriftsartikel (refereegranskat)abstract
- The dayside atmospheres of ultra-hot Jupiters (UHJs) are predicted to possess temperature inversion layers with extremely high temperatures at high altitudes. We observed the dayside thermal emission spectra of WASP-18b and WASP-76b with the new CRIRES+ high-resolution spectrograph at near-infrared wavelengths. Using the cross-correlation technique, we detected strong CO emission lines in both planets, which confirms the existence of temperature inversions on their dayside hemispheres. The two planets are the first UHJs orbiting F-type stars with CO emission lines detected; previous detections were mostly for UHJs orbiting A-type stars. Evidence of weak H2O emission signals is also found for both planets. We further applied forward-model retrievals on the detected CO lines and retrieved the temperature-pressure profiles along with the CO volume mixing ratios. The retrieved logarithmic CO mixing ratio of WASP-18b (-2.2(-1.5)(+1.4)) is slightly higher than the value predicted by the self-consistent model assuming solar abundance. For WASP-76b, the retrieved CO mixing ratio (-3.6(-1.6)(+1.8)) is broadly consistent with the value of solar abundance. In addition, we included the equatorial rotation velocity (upsilon(eq)) in the retrieval when analyzing the line profile broadening. The obtained upsilon(eq) is 7.0 +/- 2.9 km s(-1) for WASP-18b and 5.2(-3.0)(+2.5) km s(-1) for WASP-76b, which are consistent with the tidally locked rotational velocities.
|
|
| 21. |
- Enshaei, Amir, et al.
(författare)
-
A validated novel continuous prognostic index to deliver stratified medicine in pediatric acute lymphoblastic leukemia
- 2020
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 135:17, s. 1438-1446
-
Tidskriftsartikel (refereegranskat)abstract
- Risk stratification is essential for the delivery of optimal treatment in childhood acute lymphoblastic leukemia. However, current risk stratification algorithms dichotomize variables and apply risk factors independently, which may incorrectly assume identical associations across biologically heterogeneous subsets and reduce statistical power. Accordingly, we developed and validated a prognostic index (PIUKALL) that integrates multiple risk factors and uses continuous data. We created discovery (n = 2405) and validation (n = 2313) cohorts using data from 4 recent trials (UKALL2003, COALL-03, DCOG-ALL10, and NOPHO-ALL2008). Using the discovery cohort, multivariate Cox regression modeling defined a minimal model including white cell count at diagnosis, pretreatment cytogenetics, and end-of-induction minimal residual disease. Using this model, we defined PIUKALL as a continuous variable that assigns personalized risk scores. PIUKALL correlated with risk of relapse and was validated in an independent cohort. Using PIUKALL to risk stratify patients improved the concordance index for all end points compared with traditional algorithms. We used PIUKALL to define 4 clinically relevant risk groups that had differential relapse rates at 5 years and were similar between the 2 cohorts (discovery: low, 3% [95% confidence interval (CI), 2%-4%]; standard, 8% [95% CI, 6%-10%]; intermediate, 17% [95% CI, 14%-21%]; and high, 48% [95% CI, 36%-60%; validation: low, 4% [95% CI, 3%-6%]; standard, 9% [95% CI, 6%-12%]; intermediate, 17% [95% CI, 14%-21%]; and high, 35% [95% CI, 24%-48%]). Analysis of the area under the curve confirmed the PIUKALL groups were significantly better at predicting outcome than algorithms employed in each trial. PIUKALL provides an accurate method for predicting outcome and more flexible method for defining risk groups in future studies.
|
|
| 22. |
- Modvig, S, et al.
(författare)
-
Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia
- 2019
-
Ingår i: Leukemia. - : Nature Publishing Group. - 0887-6924 .- 1476-5551. ; 33:6, s. 1324-1336
-
Tidskriftsartikel (refereegranskat)abstract
- Minimal residual disease (MRD) measured by PCR of clonal IgH/TCR rearrangements predicts relapse in T-cell acute lymphoblastic leukemia (T-ALL) and serves as risk stratification tool. Since 10% of patients have no suitable PCR-marker, we evaluated flowcytometry (FCM)-based MRD for risk stratification. We included 274 T-ALL patients treated in the NOPHO-ALL2008 protocol. MRD was measured by six-color FCM and real-time quantitative PCR. Day 29 PCR-MRD (cut-off 10-3) was used for risk stratification. At diagnosis, 93% had an FCM-marker for MRD monitoring, 84% a PCR-marker, and 99.3% (272/274) had a marker when combining the two. Adjusted for age and WBC, the hazard ratio for relapse was 3.55 (95% CI 1.4-9.0, p = 0.008) for day 29 FCM-MRD ≥ 10-3 and 5.6 (95% CI 2.0-16, p = 0.001) for PCR-MRD ≥ 10-3 compared with MRD < 10-3. Patients stratified to intermediate-risk therapy on day 29 with MRD 10-4-<10-3 had a 5-year event-free survival similar to intermediate-risk patients with MRD < 10-4 or undetectable, regardless of method for monitoring. Patients with day 15 FCM-MRD < 10-4 had a cumulative incidence of relapse of 2.3% (95% CI 0-6.8, n = 59). Thus, FCM-MRD allows early identification of patients eligible for reduced intensity therapy, but this needs further studies. In conclusion, FCM-MRD provides reliable risk prediction for T-ALL and can be used for stratification when no PCR-marker is available.
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Agar, Cetin, et al.
(författare)
-
beta(2)-Glycoprotein I can exist in 2 conformations: implications for our understanding of the antiphospholipid syndrome
- 2010
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 116:8, s. 1336-1343
-
Tidskriftsartikel (refereegranskat)abstract
- The antiphospholipid syndrome is defined by the presence of antiphospholipid antibodies in blood of patients with thrombosis or fetal loss. There is ample evidence that beta(2)-glycoprotein I (beta(2)GPI) is the major antigen for antiphospholipid antibodies. The autoantibodies recognize beta(2)GPI when bound to anionic surfaces and not in solution. We showed that beta(2)GPI can exist in at least 2 different conformations: a circular plasma conformation and an "activated" open conformation. We also showed that the closed, circular conformation is maintained by interaction between the first and fifth domain of beta(2)GPI. By changing pH and salt concentration, we were able to convert the conformation of beta(2)GPI from the closed to the open conformation and back. In the activated open conformation, a cryptic epitope in the first domain becomes exposed that enables patient antibodies to bind and form an antibody-beta(2)GPI complex. We also demonstrate that the open conformation of beta(2)GPI prolonged the activated partial thromboplastin time when added to normal plasma, whereas the activated partial thromboplastin time is further prolonged by addition of anti-beta(2)GPI antibodies. The conformational change of beta(2)GPI, and the influence of the autoantibodies may have important consequences for our understanding of the antiphospholipid syndrome. (Blood. 2010; 116(8): 1336-1343)
|
|
| 26. |
- Doronin, M., et al.
(författare)
-
“Virtual Atomic and Molecular Data Centre” and Astrophysics : Level 2 Release
- 2012
-
Ingår i: Astronomical Data Analysis Software and Systems XXI.
-
Konferensbidrag (refereegranskat)abstract
- The Virtual Atomic and Molecular Data Centre (VAMDC, \lta href=’http://www.vamdc.eu/’\gthttp://www.vamdc.eu/\lt/a\gt) is a consortium between groups involved in the generation, evaluation, and use of atomic and molecular data, funded by the European Union. VAMDC aims to build a reliable, open, flexible and interoperable e-science interface to existing atomic and molecular data. The project will cover establishing the core consortium, the development and deployment of the infrastructure and the development of interfaces to the existing atomic and molecular databases. This paper describes the organisation of the project and the achievements at the end of its second year.
|
|
| 27. |
|
|
| 28. |
- Östlin, Göran, et al.
(författare)
-
THE Ly alpha REFERENCE SAMPLE. I. SURVEY OUTLINE AND FIRST RESULTS FOR MARKARIAN 259
- 2014
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 797:1
-
Tidskriftsartikel (refereegranskat)abstract
- The Ly alpha Reference Sample (LARS) is a substantial program with the Hubble Space Telescope (HST) that provides a sample of local universe laboratory galaxies in which to study the detailed astrophysics of the visibility and strength of the Ly alpha line of neutral hydrogen. Ly alpha is the dominant spectral line in use for characterizing high-redshift (z) galaxies. This paper presents an overview of the survey, its selection function, and HST imaging observations. The sample was selected from the combined GALEX+Sloan Digital Sky Survey catalog at z = 0.028-0.19, in order to allow Ly alpha to be captured with combinations of long-pass filters in the Solar Blind Channel (SBC) of the Advanced Camera for Surveys (ACS) onboard HST. In addition, LARS utilizes H alpha and H beta narrowband and u, b, i broadband imaging with ACS and the Wide Field Camera 3 (WFC3). In order to study galaxies in which large numbers of Ly alpha photons are produced (whether or not they escape), we demanded an H alpha equivalent width W(H alpha) >= 100 angstrom. The final sample of 14 galaxies covers far-UV (FUV, lambda similar to 1500 angstrom) luminosities that overlap with those of high-z Ly alpha emitters (LAEs) and Lyman break galaxies (LBGs), making LARS a valid comparison sample. We present the reduction steps used to obtain the Ly alpha images, including our LARS eXtraction software (LaXs), which utilizes pixel-by-pixel spectral synthesis fitting of the energy distribution to determine and subtract the continuum at Ly alpha. We demonstrate that the use of SBC long-pass-filter combinations increase the signal-to-noise ratio by an order of magnitude compared to the nominal Ly alpha filter available in SBC. To exemplify the science potential of LARS, we also present some first results for a single galaxy, Mrk 259 (LARS #1). This irregular galaxy shows bright and extended (indicative of resonance scattering) but strongly asymmetric Ly alpha emission. Spectroscopy from the Cosmic Origins Spectrograph on board HST centered on the brightest UV knot shows a moderate outflow in the neutral interstellar medium (probed by low ionization stage absorption features) and Ly alpha emission with an asymmetric profile. Radiative transfer modeling is able to reproduce the essential features of the Ly alpha line profile and confirms the presence of an outflow. From the integrated photometry we measure an Ly alpha luminosity of L-Ly alpha= 1.3x10(42) erg s(-1) an equivalent width W(Ly alpha) = 45 angstrom and an FUV absolute magnitude M-FUV = -19.2 (AB). Mrk 259 would hence be detectable in high-z Ly alpha and LBG surveys. The total Ly alpha escape fraction is 12%. This number is higher than the low-z average, but similar to that at z > 4, demonstrating that LARS provides a valid comparison sample for high-z galaxy studies.
|
|
