622 research outputs found

    Therapy reduction in patients with Down syndrome and myeloid leukemia: the international ML-DS 2006 trial

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    Children with myeloid leukemia associated with Down syndrome (ML-DS) have superior outcome compared with non-DS patients, but suffer from higher constitutional cytotoxic drug susceptibility. We analyzed the outcome of 170 pediatric patients with ML-DS enrolled in the prospective, multicenter, open-label, nonrandomized ML-DS 2006 trial by Nordic Society for Pediatric Hematology and Oncology (NOPHO), Dutch Childhood Oncology Group (DCOG), and Acute Myeloid Leukemia–Berlin-Frankfurt-Münster (AML-BFM) study group. Compared with the historical control arm (reduced-intensity protocol for ML-DS patients from the AML-BFM 98 trial), treatment intensity was reduced by lowering the cumulative dose of etoposide (950 to 450 mg/m2) and intrathecal central nervous system prophylaxis while omitting maintenance therapy. Still, 5-year overall survival (89% 6 3% vs 90% 6 4%; Plog-rank 5 .64), event-free survival (EFS; 87% 6 3% vs 89% 6 4%; Plog-rank 5 .71), and cumulative incidence of relapse/ nonresponse (CIR/NR; 6% 6 3% vs 6% 6 2%; PGray 5 .03) did not significantly differ between the ML-DS 2006 trial and the historical control arm. Poor early treatment response (5-year EFS, 58% 6 16% vs 88% 6 3%; Plog rank 5 .0008) and gain of chromosome 8 (CIR/NR, 16% 6 7% vs 3% 6 2%, PGray 5 .02; 5-year EFS, 73% 6 8% vs 91% 6 4%, Plog rank 5 .018) were identified as independent prognostic factors predicting a worse EFS. Five of 7 relapsed patients (71%) with cytogenetic data had trisomy 8. Our study reveals prognostic markers for children with ML-DS and illustrates that reducing therapy did not impair excellent outcome. The trial was registered at EudraCT as #2007-006219-2. (Blood. 2017;129(25): 3314-3321

    Collectivity Embedded in Complex Spectra of Finite Interacting Fermi Systems: Nuclear Example

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    The mechanism of collectivity coexisting with chaos in a finite system of strongly interacting fermions is investigated. The complex spectra are represented in the basis of two-particle two-hole states describing the nuclear double-charge exchange modes in 48^{48}Ca. An example of Jπ=0J^{\pi}=0^- excitations shows that the residual interaction, which generically implies chaotic behavior, under certain specific and well identified conditions may create strong transitions, even much stronger than those corresponding to a pure mean-field picture. Such an effect results from correlations among the off-diagonal matrix elements, is connected with locally reduced density of states and a local minimum in the information entropy.Comment: 16 pages, LaTeX2e, REVTeX, 8 PostScript figures, to appear in Physical Review

    The KASCADE-Grande Experiment and the LOPES Project

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    KASCADE-Grande is the extension of the multi-detector setup KASCADE to cover a primary cosmic ray energy range from 100 TeV to 1 EeV. The enlarged EAS experiment provides comprehensive observations of cosmic rays in the energy region around the knee. Grande is an array of 700 x 700 sqm equipped with 37 plastic scintillator stations sensitive to measure energy deposits and arrival times of air shower particles. LOPES is a small radio antenna array to operate in conjunction with KASCADE-Grande in order to calibrate the radio emission from cosmic ray air showers. Status and capabilities of the KASCADE-Grande experiment and the LOPES project are presented.Comment: To appear in Nuclear Physics B, Proceedings Supplements, as part of the volume for the CRIS 2004, Cosmic Ray International Seminar: GZK and Surrounding

    Software engineering techniques for the development of systems of systems

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    This paper investigates how existing software engineering techniques can be employed, adapted and integrated for the development of systems of systems. Starting from existing system-of-systems (SoS) studies, we identify computing paradigms and techniques that have the potential to help address the challenges associated with SoS development, and propose an SoS development framework that combines these techniques in a novel way. This framework addresses the development of a class of IT systems of systems characterised by high variability in the types of interactions between their component systems, and by relatively small numbers of such interactions. We describe how the framework supports the dynamic, automated generation of the system interfaces required to achieve these interactions, and present a case study illustrating the development of a data-centre SoS using the new framework

    Potential of fecal microbiota for early-stage detection of colorectal cancer

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    Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC-associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor-free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early- and late-stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC-associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor-related host-microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism
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