Tumor size and prognosis in aggressively treated osteosarcoma

PURPOSE: The aim of this retrospective analysis was to investigate the prognostic significance and optimal measures of tumor size in osteosarcoma treated with intensive neoadjuvant chemotherapy. PATIENTS AND METHODS: Initial anterior-posterior (AP) and lateral x-ray films of 128 patients treated within the trials Cooperative Osteosarcoma Study (COSS)-80, -82, and -86, were evaluated for the following three tumor diameters: length, width, and depth. Metastasis-free survival (MFS) analyses were performed in univariate and multivariate models with one, two, and three dimensions of the tumor as absolute or relative measures (tumor length, referred to bone length, plane and volume to body-surface area). RESULTS: Univariate analyses of MFS showed a high prognostic significance of all absolute measures. Relative measures, at best, showed a comparable predictive value. Cox regression analysis indicated the high prognostic significance of absolute tumor volume (ATV; P < .0001) and histologic response (P < .0001). None of 19 patients with an ATV < or = 70 cm3 and only four of 53 with an ATV < or = 150 cm3 relapsed, while in patients with an ATV more than 150 cm3, the relapse rate remained 40% to 60%, irrespective of further increase in volume. CONCLUSION: Initial tumor size is an important and easily obtainable prognostic factor in osteosarcoma and may serve as a basis for risk-adapted therapy. It is best represented by the absolute three-dimensional measure ATV. There is a cut-off point regarding the incidence of metastases at a tumor volume of approximately 150 cm3 as calculated from two-plane x-ray films.     

The small-cell variant of mycosis fungoides. A clinicopathological and quantitative electron microscopic study on 14 patients

Small-cell variants of Sézary syndrome and mycosis fungoides (MF) have been described. However, in these studies the nuclear area of the small-cell variant of MF (SC-MF) as compared to histological classical MF (CL-MF) was not characterized objectively by quantitative electron microscopy. In a 14-year follow-up period, of a total of 76 patch/plaque stage MF patients seen in the Department of Dermatology of the University Hospital Utrecht, 14 (18%) had an infiltrate composed of atypical lymphocytes characterized by a distinctly smaller cell diameter and smaller, hyperchromatic, deeply indented nuclei as compared to the usual cell type of MF. The aim of the investigation was to confirm this observation objectively using quantitative electron microscopy (morphometry) and to define SC-MF as compared to CL-MF. The study was performed on the 14 patients with SC-MF, and 10 patients with clinical and histological CL-MF and 4 patients with chronic eczema. Electron micrographs of sections obtained from each biopsy were analysed by computer to produce the following data: a nuclear contour index (NCI), the mean nuclear area (MNA), the mean nuclear area of the cells above the 75th percentile (P75NA) and the percentage of cells larger than 30 microm2. The values of MNA differed significantly between patients with SC-MF and those with CL-MF (17.6 vs 23.2 microm2; P = 0.02), as did the values of P75NA (20.7 vs 27.9 microm2; P = 0.01). The NCI of the SC-MF and CL-MF patients were similar. These results are consistent with our observations that SC-MF does indeed exist.     

DNA-Directed alkylating agents. 7. Synthesis, DNA interaction, and antitumor activity of bis(hydroxymethyl)- and bis(carbamate)-substituted pyrrolizines and imidazoles

A series of bis(hydroxymethyl)-substituted imidazoles, thioimidazoles, and pyrrolizines and related bis(carbamates), linked to either 9-anilinoacridine (intercalating) or 4-(4-quinolinylamino)benzamide (minor groove binding) carriers, were synthesized and evaluated for sequence-specific DNA alkylation and cytotoxicity. The imidazole and thioimidazole analogues were prepared by initial synthesis of [(4-aminophenyl)alkyl]imidazole-, thioimidazole-, or pyrrolizine dicarboxylates, coupling of these with the desired carrier, and reduction to give the required bis(hydroxymethyl) alkylating moiety. The pyrrolizines were the most reactive alkylators, followed by the thioimidazoles, while the imidazoles were unreactive. The pyrrolizines and some of the thioimidazoles cross-linked DNA, as measured by agarose gel electrophoresis. Strand cleavage assays showed that none of the compounds reacted at purine N7 or N3 sites in the gpt region of the plasmid gpt2Eco, but the polymerase stop assay showed patterns of G-alkylation in C-rich regions. The corresponding thioimidazole bis(carbamates) were more selective than the bis(hydroxymethyl) pyrrolizines, with high-intensity bands at 5'-NCCN, 5'-NGCN and 5'-NCGN sequences in the PCR stopping assay ( indicates block sites). The data suggest that these targeted compounds, like the known thioimidazole bis(carbamate) carmethizole, alkylate exclusively at guanine residues via the 2-amino group, with little or no alkylation at N3 and N7 guanine or adenine sites. The cytotoxicities of the compounds correlated broadly with their reactivities, with the bis(hydroxymethyl)imidazoles being the least cytotoxic (IC50s >1 microM; P388 leukemia) and with the intercalator-linked analogues being more cytotoxic than the corresponding minor-groove-targeted ones. This was true also for the more reactive thioimidazole bis(carbamates) (IC50s 0.8 and 11 microM, respectively), but both were more active than the analogous "untargeted" carmethizole (IC50 20 microM). The bis(hydroxymethyl)pyrrolizine analogues were the most cytotoxic, with IC50s as low as 0.03 microM.     

Signal transduction in vertebrate growth cones navigating in vivo

Navigating growth cones need signal transduction machinery to amplify and transmit the effects of extracellular signals throughout the growth cone. In culture, many drugs that affect second messengers are known to modulate neurite extension (with different effects on different neurons), and gradients of calcium influx and cyclic nucleotide analogs can cause growth cones to turn. However, it is not clear which of these responses are physiologically relevant, as axons grow through much more complex environments in vivo. The "exposed brain" preparation in Xenopus embryos provides an experimentally tractable system in which it is possible to study growth, pathfinding, and target recognition of retinal growth cones in vivo, while pharmacologically manipulating their signal transduction systems. These growth cones can also be easily studied in explant culture. We describe preliminary results of parallel in vivo and in vitro experiments using an array of drugs that perturb transduction molecules. Surprisingly, calcium ionophores and cyclic nucleotide analogs have no significant effect on retinal axon growth or pathfinding. Several agents including herbimycin A, ML-7, mastoparan, and RHC80267 inhibit retinal axon growth, both in vivo and in vitro, suggesting that tyrosine kinases, myosin, heterotrimeric G-proteins, and diacylglycerol lipase are important for retinal growth cones navigating in the optic pathway.     

Online segmentation of time series based on polynomial least-squares approximations

The paper presents SwiftSeg, a novel technique for online time series segmentation and piecewise polynomial representation. The segmentation approach is based on a least-squares approximation of time series in sliding and/or growing time windows utilizing a basis of orthogonal polynomials. This allows the definition of fast update steps for the approximating polynomial, where the computational effort depends only on the degree of the approximating polynomial and not on the length of the time window. The coefficients of the orthogonal expansion of the approximating polynomial-obtained by means of the update steps-can be interpreted as optimal (in the least-squares sense) estimators for average, slope, curvature, change of curvature, etc., of the signal in the time window considered. These coefficients, as well as the approximation error, may be used in a very intuitive way to define segmentation criteria. The properties of SwiftSeg are evaluated by means of some artificial and real benchmark time series. It is compared to three different offline and online techniques to assess its accuracy and runtime. It is shown that SwiftSeg-which is suitable for many data streaming applications-offers high accuracy at very low computational costs.     

World lines

In this paper we present World Lines as a novel interactive visualization that provides complete control over multiple heterogeneous simulation runs. In many application areas, decisions can only be made by exploring alternative scenarios. The goal of the suggested approach is to support users in this decision making process. In this setting, the data domain is extended to a set of alternative worlds where only one outcome will actually happen. World Lines integrate simulation, visualization and computational steering into a single unified system that is capable of dealing with the extended solution space. World Lines represent simulation runs as causally connected tracks that share a common time axis. This setup enables users to interfere and add new information quickly. A World Line is introduced as a visual combination of user events and their effects in order to present a possible future. To quickly find the most attractive outcome, we suggest World Lines as the governing component in a system of multiple linked views and a simulation component. World Lines employ linking and brushing to enable comparative visual analysis of multiple simulations in linked views. Analysis results can be mapped to various visual variables that World Lines provide in order to highlight the most compelling solutions. To demonstrate this technique we present a flooding scenario and show the usefulness of the integrated approach to support informed decision making.     

Continuous-time quantum Monte Carlo impurity solvers

Continuous-time quantum Monte Carlo impurity solvers are algorithms that sample the partition function of an impurity model using diagrammatic Monte Carlo techniques. The present paper describes codes that implement the interaction expansion algorithm originally developed by Rubtsov, Savkin, and Lichtenstein, as well as the hybridization expansion method developed by Werner, Millis, Troyer, et al. These impurity solvers are part of the ALPS-DMFT application package and are accompanied by an implementation of dynamical mean-field self-consistency equations for (single orbital single site) dynamical mean-field problems with arbitrary densities of states.

Program summary

Program title: dmftCatalogue identifier: AEIL_v1_0Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEIL_v1_0.htmlProgram obtainable from: CPC Program Library, Queen's University, Belfast, N. IrelandLicensing provisions: ALPS LIBRARY LICENSE version 1.1No. of lines in distributed program, including test data, etc.: 899 806No. of bytes in distributed program, including test data, etc.: 32 153 916Distribution format: tar.gzProgramming language: C++Operating system: The ALPS libraries have been tested on the following platforms and compilers:

• • 

  Linux with GNU Compiler Collection (g++ version 3.1 and higher), and Intel C++ Compiler (icc version 7.0 and higher)

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  MacOS X with GNU Compiler (g++ Apple-version 3.1, 3.3 and 4.0)

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  IBM AIX with Visual Age C++ (xlC version 6.0) and GNU (g++ version 3.1 and higher) compilers

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  Compaq Tru64 UNIX with Compq C++ Compiler (cxx)

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  SGI IRIX with MIPSpro C++ Compiler (CC)

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  HP-UX with HP C++ Compiler (aCC)

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  Windows with Cygwin or coLinux platforms and GNU Compiler Collection (g++ version 3.1 and higher)

RAM: 10 MB–1 GBClassification: 7.3External routines: ALPS [1], BLAS/LAPACK, HDF5Nature of problem: (See [2].) Quantum impurity models describe an atom or molecule embedded in a host material with which it can exchange electrons. They are basic to nanoscience as representations of quantum dots and molecular conductors and play an increasingly important role in the theory of “correlated electron” materials as auxiliary problems whose solution gives the “dynamical mean field” approximation to the self-energy and local correlation functions.Solution method: Quantum impurity models require a method of solution which provides access to both high and low energy scales and is effective for wide classes of physically realistic models. The continuous-time quantum Monte Carlo algorithms for which we present implementations here meet this challenge. Continuous-time quantum impurity methods are based on partition function expansions of quantum impurity models that are stochastically sampled to all orders using diagrammatic quantum Monte Carlo techniques. For a review of quantum impurity models and their applications and of continuous-time quantum Monte Carlo methods for impurity models we refer the reader to [2].Additional comments: Use of dmft requires citation of this paper. Use of any ALPS program requires citation of the ALPS [1] paper.Running time: 60 s–8 h per iteration.References:

• [1] 

  A. Albuquerque, F. Alet, P. Corboz, et al., J. Magn. Magn. Mater. 310 (2007) 1187.

• [2] 

  http://arxiv.org/abs/1012.4474, Rev. Mod. Phys., in press.

     

The State of the Art in Topology‐Based Visualization of Unsteady Flow

Vector fields are a common concept for the representation of many different kinds of flow phenomena in science and engineering. Methods based on vector field topology are known for their convenience for visualizing and analysing steady flows, but a counterpart for unsteady flows is still missing. However, a lot of good and relevant work aiming at such a solution is available. We give an overview of previous research leading towards topology‐based and topology‐inspired visualization of unsteady flow, pointing out the different approaches and methodologies involved as well as their relation to each other, taking classical (i.e. steady) vector field topology as our starting point. Particularly, we focus on Lagrangian methods, space–time domain approaches, local methods and stochastic and multifield approaches. Furthermore, we illustrate our review with practical examples for the different approaches.     

Dynamic Programming for Minimum Steiner Trees

We present a new dynamic programming algorithm that solves the minimum Steiner tree problem on graphs with k terminals in time O^*(c^k) for any c > 2. This improves the running time of the previously fastest parameterized algorithm by Dreyfus-Wagner of order O^*(3^k) and the so-called "full set dynamic programming" algorithm solving rectilinear instances in time O^*(2.38^k).