The physical mechanism driving mass ejection during a nova eruption is still poorly understood. Possibilities include ejection in a single ballistic event, a common-envelope interaction, a continuous ...wind, or some combination of these processes. Here, we present a study of 12 Galactic novae, for which we have premaximum high-resolution spectroscopy. All 12 novae show the same spectral evolution. Before optical peak, they show a slow P Cygni component. After peak, a fast component quickly arises, while the slow absorption remains superimposed on top of it, implying the presence of at least two physically distinct flows. For novae with high-cadence monitoring, a third, intermediate-velocity component is also observed. These observations are consistent with a scenario where the slow component is associated with the initial ejection of the accreted material and the fast component with a radiation-driven wind from the white dwarf. When these flows interact, the slow flow is swept up by the fast flow, producing the intermediate component. These colliding flows may produce theγ-ray emission observed in some novae. Our spectra also show that the transient heavy-element absorption lines seen in some novae have the same velocity structure and evolution as the other lines in the spectrum, implying an association with the nova ejecta rather than a preexisting circumbinary reservoir of gas or material ablated from the secondary. While this basic scenario appears to qualitatively reproduce multiwavelength observations of classical novae, substantial theoretical and observational work is still needed to untangle the rich diversity of nova properties.
We analyzed the long-term outcome of 1011 patients treated in five successive clinical trials (Total Therapy Studies 11, 12, 13A, 13B, and 14) between 1984 and 1999. The event-free survival improved ...significantly (P=0.003) from the first two trials conducted in the 1980s to the three more recent trials conducted in the 1990s. Approximately 75% of patients treated in the 1980s and 80% in the 1990s were cured. Early intensive triple intrathecal therapy, together with more effective systemic therapy, including consolidation and reinduction treatment (Studies 13A and 13B) as well as dexamethasone (Study 13B), resulted in a very low rate of isolated central nervous system (CNS) relapse rate (<2%), despite the reduced use of cranial irradiation. Factors consistently associated with treatment outcome were age, leukocyte count, immunophenotype, DNA index, and minimal residual disease level after remission induction treatment. Owing to concerns about therapy-related secondary myeloid leukemia and brain tumors, in our current trials we reserve the use of etoposide for patients with refractory or relapsed leukemia undergoing hematopoietic stem cell transplantation, and cranial irradiation for those with CNS relapse. The next main challenge is to further increase cure rates while improving quality of life for all patients.
Comprehensive studies on neutropenia and infection-related complications in patients with acute lymphoblastic leukemia (ALL) are lacking.
We evaluated infection-related complications that were grade ...≥3 on National Cancer Institute's Common Terminology Criteria for Adverse Events (version 3.0) and their risk factors in 409 children with newly diagnosed ALL throughout the treatment period.
Of the 2420 infection episodes, febrile neutropenia and clinically or microbiologically documented infection were seen in 1107 and 1313 episodes, respectively. Among documented infection episodes, upper respiratory tract was the most common site (n= 389), followed by ear (n= 151), bloodstream (n= 147), and gastrointestinal tract (n= 145) infections. These episodes were more common during intensified therapy phases such as remission induction and reinduction, but respiratory and ear infections, presumably viral in origin, also occurred during continuation phases. The 3-year cumulative incidence of infection-related death was low (1.0±0.9%, n= 4), including 2 from Bacillus cereus bacteremia. There was no fungal infection-related mortality. Age 1–9.9 years at diagnosis was associated with febrile neutropenia (P= 0.002) during induction and febrile neutropenia and documented infection (both P< 0.001) during later continuation. White race was associated with documented infection (P= 0.034) during induction. Compared with low-risk patients, standard- and high-risk patients received more intensive therapy during early continuation and had higher incidences of febrile neutropenia (P< 0.001) and documented infections (P= 0.043). Furthermore, poor neutrophil surge after dexamethasone pulses during continuation, which can reflect the poor bone marrow reserve, was associated with infections (P< 0.001).
The incidence of infection-related death was low. However, young age, white race, intensive chemotherapy, and lack of neutrophil surge after dexamethasone treatment were associated with infection-related complications. Close monitoring for prompt administration of antibiotics and modification of chemotherapy should be considered in these patients.
With improved contemporary therapy, we reassess long-term outcome in patients completing treatment for childhood acute lymphoblastic leukemia (ALL) to determine when cure can be declared with a high ...degree of confidence. In six successive clinical trials between 1984 and 2007, 1291 (84.5%) patients completed all therapies in continuous complete remission. The post-therapy cumulative risk of relapse or development of a second neoplasm and the event-free survival rate and overall survival were analyzed according to the presenting features and the three treatment periods defined by relative outcome. Over the three treatment periods, there has been progressive increase in the rate of event-free survival (65.2% vs 74.8% vs 85.1% (P<0.001)) and overall survival (76.5% vs 81.1% vs 91.7% (P<0.001)) at 10 years. The most important predictor of outcome after completion of therapy was the type of treatment. In the most recent treatment period, which omitted the use of prophylactic cranial irradiation, the post-treatment cumulative risk of relapse was 6.4%, death in remission 1.5% and development of a second neoplasm 2.3% at 10 years, with all relapses except one occurring within 4 years of therapy. None of the 106 patients with the t(9;22)/BCR-ABL1, t(1;19)/TCF3-PBX1 or t(4;11)/MLL-AFF1 had relapsed after 2 years from completion of therapy. These findings demonstrate that with contemporary effective therapy that excludes cranial irradiation, approximately 6% of children with ALL may relapse after completion of treatment, and those who remain in remission at 4 years post treatment may be considered cured (that is, less than 1% chance of relapse).
Global comparisons of barotropic and internal tides generated in an eddy‐resolving ocean circulation model are made with tidal estimates obtained from altimetric sea surface heights and an ...altimetry‐constrained tide model. As far as we know, our Hybrid Coordinate Ocean Model (HYCOM) simulations shown here and in an earlier paper are the only published high‐resolution global simulations to contain barotropic tides, internal tides, the general circulation, and mesoscale eddies concurrently. Comparing the model barotropic tide with a global data‐assimilative shallow water tide model shows that the global tidal elevation differences are approximately evenly split between discrepancies in tidal amplitude and phase. Both the model and observations show strong generation of internal tides at a limited number of “hot spot” regions with propagation of beams of energy for thousands of kilometers away from the sources. The model internal tidal amplitudes compare well with observations near these energetic tidal regions. Averaged over these regions, the model and observation internal tide amplitude estimates agree to approximately 15% for the four largest semidiurnal constituents and 23% for the four largest diurnal constituents. Away from the hot spots, the comparison between the model and altimetric amplitude is not as good due, in part, to two problems, errors in the model barotropic tides and overestimation of the altimetric tides in regions of strong mesoscale eddy activity. Examining the general energy distribution of the simulated internal tide is an important first step in the evaluation of internal tides in HYCOM.
Key Points
Model and observations show generation of internal tides in limited regions
Our global model is able to generate internal waves consistent with observations
Barotropic phase errors are a major source of errors in the model internal tide
We performed a genomewide association study (GWAS) of primary erythrocyte thiopurine S‐methyltransferase (TPMT) activity in children with leukemia (n = 1,026). Adjusting for age and ancestry, TPMT ...was the only gene that reached genomewide significance (top hit rs1142345 or 719A>G; P = 8.6 × 10‐61). Additional genetic variants (in addition to the three single‐nucleotide polymorphisms SNPs, rs1800462, rs1800460, and rs1142345, defining TPMT clinical genotype) did not significantly improve classification accuracy for TPMT phenotype. Clinical mercaptopurine tolerability in 839 patients was related to TPMT clinical genotype (P = 2.4 × 10‐11). Using 177 lymphoblastoid cell lines (LCLs), there were 251 SNPs ranked higher than the top TPMT SNP (rs1142345; P = 6.8 × 10‐5), revealing a limitation of LCLs for pharmacogenomic discovery. In a GWAS, TPMT activity in patients behaves as a monogenic trait, further bolstering the utility of TPMT genetic testing in the clinic.
ETV6-RUNX1 fusion is the most common genetic aberration in childhood acute lymphoblastic leukemia (ALL). To evaluate whether outcomes for this drug-sensitive leukemia are improved by contemporary ...risk-directed therapy, we studied clinical features, response and adverse events of 168 children with newly diagnosed ETV6-RUNX1-positive ALL on St Jude Total Therapy studies XIIIA (N=36), XIIIB (N=38) and XV (N=94). Results were compared with 494 ETV6-RUNX1-negative B-precursor ALL patients. ETV6-RUNX1 was associated with age 1-9 years, pre-treatment classification as low risk and lower levels of minimal residual disease (MRD) on day 19 of therapy (P<0.001). Event-free survival (EFS) or overall survival (OS) did not differ between patients with or without ETV6-RUNX1 in Total XIIIA or XIIIB. By contrast, in Total XV, patients with ETV6-RUNX1 had significantly better EFS (P=0.04; 5-year estimate, 96.8±2.4% versus 88.3±2.5%) and OS (P=0.04; 98.9±1.4% versus 93.7±1.8%) than those without ETV6-RUNX1. Within the ETV6-RUNX1 group, the only significant prognostic factor associated with higher OS was the treatment protocol Total XV (versus XIIIA or XIIIB) (P=0.01). Thus, the MRD-guided treatment schema including intensive asparaginase and high-dose methotrexate in the Total XV study produced significantly better outcomes than previous regimens and demonstrated that nearly all children with ETV6-RUNX1 ALL can be cured.
When massive stars exhaust their fuel, they collapse and often produce the extraordinarily bright explosions known as core-collapse supernovae. On occasion, this stellar collapse also powers an even ...more brilliant relativistic explosion known as a long-duration gamma-ray burst. One would then expect that these long gamma-ray bursts and core-collapse supernovae should be found in similar galactic environments. Here we show that this expectation is wrong. We find that the gamma-ray bursts are far more concentrated in the very brightest regions of their host galaxies than are the core-collapse supernovae. Furthermore, the host galaxies of the long gamma-ray bursts are significantly fainter and more irregular than the hosts of the core-collapse supernovae. Together these results suggest that long-duration gamma-ray bursts are associated with the most extremely massive stars and may be restricted to galaxies of limited chemical evolution. Our results directly imply that long gamma-ray bursts are relatively rare in galaxies such as our own Milky Way.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ABSTRACT
Classical novae are shock-powered multiwavelength transients triggered by a thermonuclear runaway on an accreting white dwarf. V1674 Her is the fastest nova ever recorded (time to declined ...by two magnitudes is t2 = 1.1 d) that challenges our understanding of shock formation in novae. We investigate the physical mechanisms behind nova emission from GeV γ-rays to cm-band radio using coordinated Fermi-LAT, NuSTAR, Swift, and VLA observations supported by optical photometry. Fermi-LAT detected short-lived (18 h) 0.1–100 GeV emission from V1674 Her that appeared 6 h after the eruption began; this was at a level of (1.6 ± 0.4) × 10−6 photons cm−2 s−1. Eleven days later, simultaneous NuSTAR and Swift X-ray observations revealed optically thin thermal plasma shock-heated to kTshock = 4 keV. The lack of a detectable 6.7 keV Fe Kα emission suggests super-solar CNO abundances. The radio emission from V1674 Her was consistent with thermal emission at early times and synchrotron at late times. The radio spectrum steeply rising with frequency may be a result of either free-free absorption of synchrotron and thermal emission by unshocked outer regions of the nova shell or the Razin–Tsytovich effect attenuating synchrotron emission in dense plasma. The development of the shock inside the ejecta is unaffected by the extraordinarily rapid evolution and the intermediate polar host of this nova.
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