In 2008, a European registry of relapsed acute promyelocytic leukemia was established by the European LeukemiaNet. Outcome data were available for 155 patients treated with arsenic trioxide in first ...relapse. In hematological relapse (n=104), 91% of the patients entered complete hematological remission (CR), 7% had induction death and 2% resistance, 27% developed differentiation syndrome and 39% leukocytosis, whereas no death or side effects occurred in patients treated in molecular relapse (n=40). The rate of molecular (m)CR was 74% in hematological and 62% in molecular relapse (P=0.3). All patients with extramedullary relapse (n=11) entered clinical and mCR. After 3.2 years median follow-up, the 3-year overall survival (OS) and cumulative incidence of second relapse were 68% and 41% in hematological relapse, 66% and 48% in molecular relapse and 90 and 11% in extramedullary relapse, respectively. After allogeneic or autologous transplantation in second CR (n=93), the 3-year OS was 80% compared with 59% without transplantation (n=55) (P=0.03). Multivariable analysis demonstrated the favorable prognostic impact of first remission duration ⩾1.5 years, achievement of mCR and allogeneic or autologous transplantation on OS of patients alive after induction (P=0.03, P=0.01, P=0.01) and on leukemia-free survival (P=0.006, P<0.0001, P=0.003), respectively.
In the face of competing first-line treatment options for CML, early prediction of prognosis on imatinib is desirable to assure favorable survival or otherwise consider the use of a second-generation ...tyrosine kinase inhibitor (TKI). A total of 1303 newly diagnosed imatinib-treated patients (pts) were investigated to correlate molecular and cytogenetic response at 3 and 6 months with progression-free and overall survival (PFS, OS). The persistence of BCR-ABL transcript levels >10% according to the international scale (BCR-ABL(IS)) at 3 months separated a high-risk group (28% of pts; 5-year OS: 87%) from a group with >1-10% BCR-ABL(IS) (41% of pts; 5-year OS: 94%; P=0.012) and from a group with ≤1% BCR-ABL(IS) (31% of pts; 5-year OS: 97%; P=0.004). Cytogenetics identified high-risk pts by >35% Philadelphia chromosome-positive metaphases (Ph+, 27% of pts; 5-year OS: 87%) compared with ≤35% Ph+ (73% of pts; 5-year OS: 95%; P=0.036). At 6 months, >1% BCR-ABL(IS) (37% of pts; 5-year OS: 89%) was associated with inferior survival compared with ≤1% (63% of pts; 5-year OS: 97%; P<0.001) and correspondingly >0% Ph+ (34% of pts; 5-year OS: 91%) compared with 0% Ph+ (66% of pts; 5-year OS: 97%; P=0.015). Treatment optimization is recommended for pts missing these landmarks.
Aims.
We studied the accretion disk of the archetypal eruptive young star FU Orionis with the use of mid-infrared interferometry, which enabled us to resolve the innermost regions of the disk down to ...a spatial resolution of 3 milliarcseconds (mas) in the
L
band, that is, within 1 au of the protostar.
Methods.
We used the interferometric instrument MATISSE/VLTI to obtain observations of FU Ori’s disk in the
L
,
M
, and
N
bands with multiple baseline configurations. We also obtained contemporaneous photometry in the optical
(UBVRIr
′
i
′
;
SAAO and Konkoly Observatory) and near-infrared
(JHK
s
;
NOT). Our results were compared with radiative transfer simulations modeled by
RADMC
-3
D
.
Results.
The disk of FU Orionis is marginally resolved with MATISSE, suggesting that the region emitting in the thermal infrared is rather compact. An upper limit of ~1.3 ± 0.1 mas (in
L
) can be given for the diameter of the disk region probed in the
L
band, corresponding to 0.5 au at the adopted
Gaia
EDR3 distance. This represents the hot, gaseous region of the accretion disk. The
N
-band data indicate that the dusty passive disk is silicate-rich. Only the innermost region of said dusty disk is found to emit strongly in the
N
band, and it is resolved at an angular size of ~5 mas, which translates to a diameter of about 2 au. The observations therefore place stringent constraints for the outer radius of the inner accretion disk. Dust radiative transfer simulations with
RADMC
-3
D
provide adequate fits to the spectral energy distribution from the optical to the submillimeter and to the interferometric observables when opting for an accretion rate
M ~
2 × 10
−5
M
⊙
yr
−1
and assuming
M
*
= 0.6
M
⊙
, Most importantly, the hot inner accretion disk’s outer radius can be fixed at 0.3 au. The outer radius of the dusty disk is placed at 100 au, based on constraints from scattered-light images in the literature. The dust mass contained in the disk is 2.4 × 10
−4
M
⊙
, and for a typical gas-to-dust ratio of 100, the total mass in the disk is approximately 0.02
M
⊙
. We did not find any evidence for a nearby companion in the current interferometric data, and we tentatively explored the case of disk misalignment. For the latter, our modeling results suggest that the disk orientation is similar to that found in previous imaging studies by ALMA. Should there be an asymmetry in the very compact, inner accretion disk, this might be resolved at even smaller spatial scales (≤1 mas).
High mortality rates of invasive fungal disease (IFD), especially invasive aspergillosis (IA), in immunocompromised haematological patients and current diagnostic limitations require improvement of ...detection of fungal pathogens by defining the optimal use of biomarkers and clinical samples. Concurrent bronchoalveolar lavage (BAL) and peripheral blood samples of 99 haematological patients with suspected IFD were investigated within a multicentre prospective study. Diagnostic performance of a galactomannan (GM) enzyme immune assay (EIA), a 1,3-β-D-glucan assay (BDG), an Aspergillus PCR, and a multifungal DNA-microarray (Chip) alone or in combination were calculated. IFD were classified as proven (n=3), probable (n=34), possible (n=33), and no IFD (n=29) according to EORTC/MSG criteria. GM, PCR, and Chip showed superior diagnostic performance in BAL than in blood, whereas specificity of BDG in BAL was poor (48% (14/29)). The combination of GM (BAL) with BDG (blood) showed sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and DOR (diagnostic odds ratio) of 92% (34/37), 93% (27/29), 94%, 90%, and 153.0, respectively. Combining GM (BAL) with PCR (BAL) showed convincing diagnostic potential for diagnosing IA with sensitivity, specificity, PPV, NPV, and DOR of 85% (17/20), 97% (28/29), 94%, 90%, and 158.7. Addition of the DNA-microarray resulted in further detection of two mucormycetes infections. In 1 out of 15 Aspergillus DNA-positive samples a triazole resistance-mediating Cyp51A mutation was found. Combination of biomarkers is superior to their sole use in diagnosing IFD, particularly IA. Integrating blood and BAL samples into a diagnostic algorithm is an advantageous approach.
Context. Studying the physical conditions in circumstellar disks is a crucial step toward understanding planet formation and disk evolution. Of particular interest is the case of HD 100546, a Herbig ...Be star that presents a gap within the first 13 AU of its protoplanetary disk, a gap that may originate in the dynamical interactions of a forming planet with its hosting disk. Aims. We seek a more detailed understanding of the structure of the circumstellar environment of HD 100546 and refine our previous disk model that is composed of a tenuous inner disk, a gap and a massive outer disk (see Benisty et al. 2010, A&A, 511, A75). We also investigate whether planetary formation processes can explain the complex density structure observed in the disk. Methods. We gathered a large amount of new interferometric data using the AMBER/VLTI instrument in the H- and K-bands to spatially resolve the warm inner disk and constrain its structure. Then, combining these measurements with photometric observations, we analyze the circumstellar environment of HD 100546 in the light of a passive disk model based on 3D Monte-Carlo radiative transfer. Finally, we use hydrodynamical simulations of gap formation by planets to predict the radial surface density profile of the disk and test the hypothesis of ongoing planet formation. Results. The SED (spectral energy distribution) from the UV to the millimeter range, and the NIR (near-infrared) interferometric data are adequately reproduced by our model. We show that the H- and K-band emissions are coming mostly from the inner edge of the internal dust disk, located near 0.24 AU from the star, i.e., at the dust sublimation radius in our model. At such a short distance, the survival of hot (silicate) dust requires the presence of micron-sized grains, heated at ~1750 K. We directly measure an inclination of 33° ± 11° and a position angle of 140° ± 16° for the inner disk. This is similar to the values found for the outer disk (i ≃ 42°, PA ≃ 145°), suggesting that both disks may be coplanar. We finally show that 1 to 8 Jupiter mass planets located at ~8 AU from the star would have enough time to create the gap and the required surface density jump of three orders of magnitude between the inner and outer disk. However, no information on the amount of matter left in the gap is available, which precludes us from setting precise limits on the planet mass, for now.
Context. Astrometric monitoring of directly imaged exoplanets allows the study of their orbital parameters and system architectures. Because most directly imaged planets have long orbital periods ...(>20 AU), accurate astrometry is challenging when based on data acquired on timescales of a few years and usually with different instruments. The LMIRCam camera on the Large Binocular Telescope is being used for the LBT Exozodi Exoplanet Common Hunt (LEECH) survey to search for and characterize young and adolescent exoplanets in L′ band (3.8 μm), including their system architectures. Aims. We first aim to provide a good astrometric calibration of LMIRCam. Then, we derive new astrometry, test the predictions of the orbital model of 8:4:2:1 mean motion resonance proposed for the system, and perform new orbital fitting of the HR 8799 bcde planets. We also present deep limits on a putative fifth planet inside the known planets. Methods. We use observations of HR 8799 and the Θ1 Ori C field obtained during the same run in October 2013. Results. We first characterize the distortion of LMIRCam. We determine a platescale and a true north orientation for the images of 10.707 ± 0.012 mas/pix and −0.430 ± 0.076°, respectively. The errors on the platescale and true north orientation translate into astrometric accuracies at a separation of 1′′ of 1.1 mas and 1.3 mas, respectively. The measurements for all planets agree within 3σ with a predicted ephemeris. The orbital fitting based on the new astrometric measurements favors an architecture for the planetary system based on 8:4:2:1 mean motion resonance. The detection limits allow us to exclude a fifth planet slightly brighter or more massive than HR 8799 b at the location of the 2:1 resonance with HR 8799 e (~9.5 AU) and about twice as bright as HR 8799 cde at the location of the 3:1 resonance with HR 8799 e (~7.5 AU).
A novel design strategy for adaptive impedance matching network which consists of two tunable components is presented. The input resistance is controlled by the first tunable component and ...independent of the second tunable component. Additionally, the proposed strategies ensure that the input resistance is proportional to the first tunable component and input reactance is proportional to the second tunable component. Therefore, the binary search algorithm is employed to calibrate the tunable matching network. In contrast to the single-step method, the convergence speed is improved from O(N) to O(log N).
The T-box transcription factor eomesodermin (Eomes) has been implicated as an important component in germ layer induction and patterning in vertebrate embryos. In the mouse, Eomes is essential for ...development of the trophectoderm lineage and Eomes loss-of-function mutants arrest at implantation. Here, we have used a novel Eomes conditional allele to test Eomes functions in the embryo proper. Eomes-deficient embryos express both Fgf8 and its downstream target Snail at normal levels but surprisingly fail to downregulate E-cadherin. Eomes functional loss thus efficiently and profoundly blocks EMT and concomitant mesoderm delamination. Marker analysis as well as fate-mapping and chimera studies demonstrate for the first time that Eomes is required for specification of the definitive endoderm lineage. We also describe developmental abnormalities in Eomes/Nodal double heterozygotes, and demonstrate that these phenotypes reflect Eomes and Nodal interactions in different tissue sites. Collectively, our experiments establish that Eomes is a key regulator of anteroposterior axis formation, EMT and definitive endoderm specification in the mouse.
In this work, the quasi-analog to discrete transition occurring in the current-voltage characteristic of oxygen engineered yttrium oxide-based resistive random-access memory (RRAM) devices is ...investigated in detail. In particular, the focus of our research is not on the absolute conductance values of this characteristic but on the magnitude of its conductance changes occurring during the reset process of the device. It is found that the detected changes correspond to conductance values predominantly of the order of the quantum unit of conductance G
= 2e
/h, where e is the electron charge and h the Planck constant. This feature is observed even at conductance levels far above G
, i.e. where electron transport is seemingly diffusive. It is also observed that such behavior is reproducible across devices comprising yttrium oxide layers with different oxygen concentrations and measured under different voltage sweep rates. While the oxygen deficiency affects the total number of quantized conductance states, the magnitude of the changes in conductance, close to 1 G
, is invariant to the oxygen content of the functional layer.
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