Clinical and economic benefits of irinotecan in combination with 5-fluorouracil and folinic acid as first line treatment of metastatic colorectal cancer

The combination of irinotecan plus 5-fluorouracil and folinic acid has clinical and survival benefits over 5-fluorouracil and folinic acid alone in the setting of first line treatment of metastatic colorectal cancer. The aim of this cost-effectiveness analysis was to compare the economic implications, from a UK health commissioner perspective, of the two treatment arms (de Gramont regimen) in this setting. Resource utilisation data collected prospectively during the study were used as a basis for estimating cumulative drug dosage, chemotherapy admistration, and treatment of complications during first line therapy. Resource utilisation associated with further chemotherapy in patients who had progressed during the study was derived from a retrospective case note review. Drug acquisition costs were derived from the British National Formulary (September, 2001) and unit costs for clinical consultation and services were taken from the latest relevant cost database. Cumulative costs per patient associated with further chemotherapy were lower in the irinotecan plus 5-fluorouracil and folinic acid treatment arm. Based on incremental costs per life-year gained of £14 794, the combination of irinotecan plus 5-fluorouracil and folinic acid can be considered cost-effective by commonly accepted criteria compared with 5-fluorouracil and folinic acid alone. Thus, clinical and economic data demonstrate that irinotecan, either in combination with irinotecan plus 5-fluorouracil and folinic acid in the first line setting or as monotherapy in the second line setting, has a major role in the management of metastatic colorectal cancer

Chromosome mapping: radiation hybrid data and stochastic spin models

This work approaches human chromosome mapping by developing algorithms for ordering markers associated with radiation hybrid data. Motivated by recent work of Boehnke et al. [1], we formulate the ordering problem by developing stochastic spin models to search for minimum-break marker configurations. As a particular application, the methods developed are applied to 14 human chromosome-21 markers tested by Cox et al. [2]. The methods generate configurations consistent with the best found by others. Additionally, we find that the set of low-lying configurations is described by a Markov-like ordering probability distribution. The distribution displays cluster correlations reflecting closely linked loci.Comment: 26 Pages, uuencoded LaTex, Submitted to Phys. Rev. E, [email protected], [email protected]

Strain localization in a shear transformation zone model for amorphous solids

We model a sheared disordered solid using the theory of Shear Transformation Zones (STZs). In this mean-field continuum model the density of zones is governed by an effective temperature that approaches a steady state value as energy is dissipated. We compare the STZ model to simulations by Shi, et al.(Phys. Rev. Lett. 98 185505 2007), finding that the model generates solutions that fit the data,exhibit strain localization, and capture important features of the localization process. We show that perturbations to the effective temperature grow due to an instability in the transient dynamics, but unstable systems do not always develop shear bands. Nonlinear energy dissipation processes interact with perturbation growth to determine whether a material exhibits strain localization. By estimating the effects of these interactions, we derive a criterion that determines which materials exhibit shear bands based on the initial conditions alone. We also show that the shear band width is not set by an inherent diffusion length scale but instead by a dynamical scale that depends on the imposed strain rate.Comment: 8 figures, references added, typos correcte

A relativistic chiral quark model for pseudoscalar emission from heavy mesons

The amplitudes for one-pion mediated transitions between heavy meson excited states are obtained in the framework of the relativistic chiral quark model. The effective coupling constants to pions and the decay widths of excited heavy mesons with l<=2 for non-radially excited, and the l=0 radially excited mesons are presented for both charmed and beauty mesons. We also discuss the allowed decays of strange excited heavy mesons by emission of a K-meson.Comment: 20 pages, revte

Omega_{ccc} production via fragmentation at LHC

In the framework of the leading order of perturbative QCD and the nonrelativistic quark-diquark model of baryons we have obtained fragmentation function for c-quark to split into Omega_{ccc} baryon. It is shown that at LHC one can expect 3.5 10^3 events with Omega_{ccc} at p_t>5 GeV/c and -1<y<1 per year.Comment: LaTex, 5 pages and 2 figures. Talk presented at XIV Workshop on High Energy Physics and Quantum Field Theory, Moscow, May 27 - June 4, 199

Capacity of different cell types to stimulate cytotoxic T lymphocyte precursor cells in the presence of interleukin 2

Plastic-adherent cells enriched for dendritic cells (AC) were found to be among the most potent stimulator cells for the activation of cytotoxic T lymphocytes (CTL) in vitro in the presence of interleukin 2 (IL 2) and a constant second set of allogeneic stimulator cells. Concanavalin A-activated nylon wool-nonadherent spleen cells ( CNWT ), concanavalin A-activated unfractionated spleen cells ( Cspl ), and some variants of the ESb T lymphoma line were equally effective as stimulator cells, however, and provoked a substantial cytotoxic response at concentrations of 10(4) cells per culture or less. In contrast, nonactivated nylon wool-nonadherent spleen cells ( NWT ) or unfractionated spleen cells (Spl) and cells of the P815 mastocytoma, the Meth A fibrosarcoma, and the T cell lymphomas Ly 5178 Eb and ESb did not stimulate cytotoxic responses at these cell concentrations. The strong stimulatory potential of the Cspl preparation was reduced by treatment with anti-Thy-1 antibody plus complement, whereas the stimulatory activity of the AC preparation was resistant to this treatment. All cell types tested expressed class I major histocompatibility antigens. Nonactivated NWT cells, in contrast to the CNWT preparation, showed no detectable staining with anti-I-E or anti-I-A antibodies and also a slightly weaker staining with class I antisera. Experiments with the tumor cell lines revealed, however, that there was no strict correlation between stimulatory potential and density of class I alloantigens or the expression of I-E determinants. Experiments on primary cytotoxic responses in vivo gave similar results. Experiments in cultures with a single set of stimulator cells and I region-compatible responder cells indicated that AC and Cspl or CNWT also have a markedly stronger capacity than NWT to induce IL 2-dependent DNA synthesis

Rate dependent shear bands in a shear transformation zone model of amorphous solids

We use Shear Transformation Zone (STZ) theory to develop a deformation map for amorphous solids as a function of the imposed shear rate and initial material preparation. The STZ formulation incorporates recent simulation results [Haxton and Liu, PRL 99 195701 (2007)] showing that the steady state effective temperature is rate dependent. The resulting model predicts a wide range of deformation behavior as a function of the initial conditions, including homogeneous deformation, broad shear bands, extremely thin shear bands, and the onset of material failure. In particular, the STZ model predicts homogeneous deformation for shorter quench times and lower strain rates, and inhomogeneous deformation for longer quench times and higher strain rates. The location of the transition between homogeneous and inhomogeneous flow on the deformation map is determined in part by the steady state effective temperature, which is likely material dependent. This model also suggests that material failure occurs due to a runaway feedback between shear heating and the local disorder, and provides an explanation for the thickness of shear bands near the onset of material failure. We find that this model, which resolves dynamics within a sheared material interface, predicts that the stress weakens with strain much more rapidly than a similar model which uses a single state variable to specify internal dynamics on the interface.Comment: 10 pages, 13 figures, corrected typos, added section on rate strengthening vs. rate weakening material

Australopithecus afarensis endocasts suggest ape-like brain organization and prolonged brain growth

Human brains are three times larger, are organized differently, and mature for a longer period of time than those of our closest living relatives, the chimpanzees. Together, these characteristics are important for human cognition and social behavior, but their evolutionary origins remain unclear. To study brain growth and organization in the hominin species Australopithecus afarensis more than 3 million years ago, we scanned eight fossil crania using conventional and synchrotron computed tomography. We inferred key features of brain organization from endocranial imprints and explored the pattern of brain growth by combining new endocranial volume estimates with narrow age at death estimates for two infants. Contrary to previous claims, sulcal imprints reveal an ape-like brain organization and no features derived toward humans. A comparison of infant to adult endocranial volumes indicates protracted brain growth in A. afarensis, likely critical for the evolution of a long period of childhood learning in hominins

Phenomenological Study of Strong Decays of Heavy Hadrons in Heavy Quark Effective Theory

The application of the tensor formalism of the heavy quark effective theory (HQET) at leading order to strong decays of heavy hadrons is presented. Comparisons between experimental and theoretical predictions of ratios of decay rates for B mesons, D mesons and kaons are given. The application of HQET to strange mesons presents some encouraging results. The spin-flavor symmetry is used to predict some decay rates that have not yet been measured.Comment: 10 page