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Background: To identify variables predicting outcome in neuroblastoma patients assigned to the high-risk group solely by the presence of MYCN oncogene amplification (MNA). Methods: Clinical characteristics, genomic information, and outcome of 190 patients solely assigned to high-risk neuroblastoma by MNA were analyzed and compared to 205 patients with stage 4 neuroblastoma aged ≥18 months with MNA (control group). Results: Event-free survival (EFS) and overall survival (OS) at 10 years were 47% (95%-CI 39–54%) and 56% (95%-CI 49–63%), respectively, which was significantly better than EFS and OS of the control group (EFS 25%, 95%-CI 18–31%, p < 0.001; OS 32% 95%-CI 25–39%, p < 0.001). The presence of RAS-/p53-pathway gene alterations was associated with impaired 10-year EFS and OS (19% vs. 55%, and 19% vs. 67%, respectively; both p < 0.001). In time-dependent multivariable analyses, alterations of RAS-/p53-pathway genes and the extent of the best primary tumor resection were the only independent prognostic variables for OS (p < 0.001 and p = 0.011, respectively). Conclusions: Neuroblastoma patients attributed to high risk solely by MYCN amplification have generally a more favorable outcome. Mutations of genes of the RAS and/or p53 pathways and incomplete resection are the main risk factors predicting poor outcome.
Two-particle correlation functions of negative hadrons over wide phase space, and transverse mass spectra of negative hadrons and deuterons near mid-rapidity have been measured in central Pb+Pb collisions at 158 GeV per nucleon by the NA49 experiment at the CERN SPS. A novel Coulomb correction procedure for the negative two-particle correlations is employed making use of the measured oppositely charged particle correlation. Within an expanding source scenario these results are used to extract the dynamic characteristics of the hadronic source, resolving the ambiguities between the temperature and transverse expansion velocity of the source, that are unavoidable when single and two particle spectra are analysed separately. The source shape, the total duration of the source expansion, the duration of particle emission, the freeze-out temperature and the longitudinal and transverse expansion velocities are deduced.
The large acceptance TPCs of the NA49 spectrometer allow for a systematic multidimensional study of two-particle correlations in different part of phase space. Results from Bertsch-Pratt and Yano-Koonin-Podgoretskii parametrizations are presented differentially in transverse pair momentum and pair rapidity. These studies give an insight into the dynamical space-time evolution of relativistic Pb+Pb collisions, which is dominated by longitudinal expansion.
Lambda and Antilambda reconstruction in central Pb+Pb collisions using a time projection chamber
(1997)
The large acceptance time projection chambers of the NA49 experiment are used to record the trajectory of charged particles from Pb + Pb collisions at 158 GeV per nucleon. Neutral strange hadrons have been reconstructed from their charged decay products. To obtain distributions of Λ, and Ks0 in discrete bins of rapidity, y, and transverse momentum, pT, calculations have been performed to determine the acceptance of the detector and the efficiency of the reconstruction software as a function of both variables. The lifetime distributions obtained give values of cτ = 7.8 ± 0.6 cm for Λ and cτ = 2.5 ± 0.3 cm for Ks0, consistent with data book values.
Three-dimensional multicellular aggregates such as spheroids provide reliable in vitro substitutes for tissues. Quantitative characterization of spheroids at the cellular level is fundamental. We present the first pipeline that provides three-dimensional, high-quality images of intact spheroids at cellular resolution and a comprehensive image analysis that completes traditional image segmentation by algorithms from other fields. The pipeline combines light sheet-based fluorescence microscopy of optically cleared spheroids with automated nuclei segmentation (F score: 0.88) and concepts from graph analysis and computational topology. Incorporating cell graphs and alpha shapes provided more than 30 features of individual nuclei, the cellular neighborhood and the spheroid morphology. The application of our pipeline to a set of breast carcinoma spheroids revealed two concentric layers of different cell density for more than 30,000 cells. The thickness of the outer cell layer depends on a spheroid’s size and varies between 50% and 75% of its radius. In differently-sized spheroids, we detected patches of different cell densities ranging from 5 × 105 to 1 × 106 cells/mm3. Since cell density affects cell behavior in tissues, structural heterogeneities need to be incorporated into existing models. Our image analysis pipeline provides a multiscale approach to obtain the relevant data for a system-level understanding of tissue architecture.
A non-monotonic energy dependence of the K + / pi + ratio with a sharp maximum close to 30 A GeV is observed in central Pb+Pb collisions. Within a statistical model of the early stage, this is interpreted as a sign of the phase transition to a QGP, which causes a sharp change in the energy dependence of the strangeness to entropy ratio. This observation naturally motivates us to study the production of multistrange hyperons (Xi, Omega) as a function of the beam energy. Furthermore it was suggested that the kinematic freeze-out of Omega takes place directly at QGP hadronization. If this is indeed the case, the transverse momentum spectra of the Omega directly reflect the transverse expansion velocity of a hadronizing QGP. In this report we show preliminary NA49 results on Omega - and Omega + production in central Pb+Pb collisions at 40 and 158 A GeV and compare them to measurements of Xi - and Xi + production in central Pb+Pb collisions at 30, 40, 80 and 158 A GeV.
Preliminary data on phi production in central Pb + Pb collisions at 158 GeV per nucleon are presented, measured by the NA49 experiment in the hadronic decay channel phi - K+K-. At mid-rapidity, the kaons were separated from pions and protons by combining dE/dx and time-of-flight information; in the forward rapidity range only dE/dx identification was used to obtain the rapidity distribution and a rapidity-integrated mt-spectrum. The mid-rapidity yield obtained was dN/dy = 1.85 ± 0.3 per event; the total phi multiplicity was estimated to be 5.0 ± 0.7 per event. Comparison with published pp data shows a slight, but not very significant strangeness enhancement.
The energy dependence of hadron production in central Pb+Pb collisions is presented and discussed. In particular, midrapidity m_T-spectra for pi-, K-, K+, p, bar p, d, phi, Lambda and bar Lambda at 40, 80 and 158 AGeV are shown. In addition Xi and Omega spectra are available at 158 AGeV. The spectra allow to determine the thermal freeze-out temperature T and the transverse flow velocity beta_T at the three energies. We do not observe a significant energy dependence of these parameters; furthermore there is no indication of early thermal freeze-out of Xi and Omega at 158 AGeV. Rapidity spectra for pi-, K-, K+ and phi at 40, 80 and 158 AGeV are shown, as well as first results on Omega rapidity distributions at 158 AGeV. The chemical freeze-out parameters T and mu_B at the three energies are determined from the total yields. The parameters are close to the expected phase boundary in the SPS energy range and above. Using the total yields of kaons and lambdas, the energy dependence of the strangeness to pion ratio is discussed. A maximum in this ratio is found at 40 AGeV. This maximum could indicate the formation of deconfined matter at energies above 40 AGeV. A search for open charm in a large sample of 158 AGeV events is presented. No signal is observed. This result is compared to several model predictions.
The large acceptance and high momentum resolution as well as the significant particle identification capabilities of the NA49 experiment at the CERN SPS allow for a broad study of fluctuations and correlations in hadronic interactions. In the first part recent results on event-by-event charge and p_t fluctuations are presented. Charge fluctuations in central Pb+Pb reactions are investigated at three different beam energies (40, 80, and 158 AGeV), while for the p_t fluctuations the focus is put on the system size dependence at 158 AGeV. In the second part recent results on Bose Einstein correlations of h-h- pairs in minimum bias Pb+Pb reactions at 40 and 158 AGeV, as well as of K+K+ and K-K- pairs in central Pb+Pb collisions at 158 AGeV are shown. Additionally, other types of two particle correlations, namely pi p, Lambda p, and Lambda Lambda correlations, have been measured by the NA49 experiment. Finally, results on the energy and system size dependence of deuteron coalescence are discussed.
Background: Due to the large amount of data produced by advanced microscopy, automated image analysis is crucial in modern biology. Most applications require reliable cell nuclei segmentation. However, in many biological specimens cell nuclei are densely packed and appear to touch one another in the images. Therefore, a major difficulty of three-dimensional cell nuclei segmentation is the decomposition of cell nuclei that apparently touch each other. Current methods are highly adapted to a certain biological specimen or a specific microscope. They do not ensure similarly accurate segmentation performance, i.e. their robustness for different datasets is not guaranteed. Hence, these methods require elaborate adjustments to each dataset.
Results: We present an advanced three-dimensional cell nuclei segmentation algorithm that is accurate and robust. Our approach combines local adaptive pre-processing with decomposition based on Lines-of-Sight (LoS) to separate apparently touching cell nuclei into approximately convex parts. We demonstrate the superior performance of our algorithm using data from different specimens recorded with different microscopes. The three-dimensional images were recorded with confocal and light sheet-based fluorescence microscopes. The specimens are an early mouse embryo and two different cellular spheroids. We compared the segmentation accuracy of our algorithm with ground truth data for the test images and results from state-of-the-art methods. The analysis shows that our method is accurate throughout all test datasets (mean F-measure: 91%) whereas the other methods each failed for at least one dataset (F-measure≤69%). Furthermore, nuclei volume measurements are improved for LoS decomposition. The state-of-the-art methods required laborious adjustments of parameter values to achieve these results. Our LoS algorithm did not require parameter value adjustments. The accurate performance was achieved with one fixed set of parameter values.
Conclusion: We developed a novel and fully automated three-dimensional cell nuclei segmentation method incorporating LoS decomposition. LoS are easily accessible features that ensure correct splitting of apparently touching cell nuclei independent of their shape, size or intensity. Our method showed superior performance compared to state-of-the-art methods, performing accurately for a variety of test images. Hence, our LoS approach can be readily applied to quantitative evaluation in drug testing, developmental and cell biology.