Evaluation of prognostic markers for canine mast cell tumors treated with vinblastine and prednisone

<p>Abstract</p> <p>Background</p> <p>Canine cutaneous mast cell tumor (MCT) is a common neoplastic disease associated with a variable biologic behavior. Surgery remains the primary treatment for canine MCT; however, radiation therapy (RT) and chemotherapy are commonly used to treat aggressive MCT. The goals of this study were to evaluate the prognostic utility of histologic grade, <it>c-KIT </it>mutations, KIT staining patterns, and the proliferation markers Ki67 and AgNORs in dogs postoperatively treated with vinblastine and prednisone +/- RT, and to compare the outcome of dogs treated with post-operative chemotherapy +/- RT to that of a prognostically matched group treated with surgery alone. Associations between prognostic markers and survival were evaluated. Disease-free intervals (DFI) and overall survival times (OS) of dogs with similar pretreatment prognostic indices postoperatively treated with chemotherapy were compared to dogs treated with surgery alone.</p> <p>Results</p> <p>Histologic grade 3 MCTs, MCTs with c-<it>KIT </it>mutations, MCTs with increased cytoplasmic KIT, and MCTs with increased Ki67 and AgNOR values were associated with decreased DFI and OS. Dogs with histologic grade 3 MCT had significantly increased DFI and OS when treated with chemotherapy vs. surgery alone. Although not statistically significant due to small sample sizes, MCTs with <it>c-KIT </it>mutations had increased DFI and OS when treated with chemotherapy vs. surgery alone.</p> <p>Conclusion and clinical importance</p> <p>This study confirms the prognostic value of histologic grade, c-<it>KIT </it>mutations, KIT staining patterns, and proliferation analyses for canine MCT. Additionally, the results of this study further define the benefit of postoperative vinblastine and prednisone for histologic grade 3 MCTs.</p

Toward a descriptive model of solar particles in the heliosphere

During a workshop on the interplanetary charged particle environment held in 1987, a descriptive model of solar particles in the heliosphere was assembled. This model includes the fluence, composition, energy spectra, and spatial and temporal variations of solar particles both within and beyong 1 AU. The ability to predict solar particle fluences was also discussed. Suggestions for specific studies designed to improve the basic model were also made

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias (Integrated Cardiovascular) will quantify the extent of long-duration space flightassociated cardiac atrophy (deterioration) on the International Space Station crewmembers

Four-Body Effects in Globular Cluster Black Hole Coalescence

In the high density cores of globular clusters, multibody interactions are expected to be common, with the result that black holes in binaries are hardened by interactions. It was shown by Sigurdsson & Hernquist (1993) and others that 10 solar mass black holes interacting exclusively by three-body encounters do not merge in the clusters themselves, because recoil kicks the binaries out of the clusters before the binaries are tight enough to merge. Here we consider a new mechanism, involving four-body encounters. Numerical simulations by a number of authors suggest that roughly 20-50% of binary-binary encounters will eject one star but leave behind a stable hierarchical triple. If the orbital plane of the inner binary is strongly tilted with respect to the orbital plane of the outer object, a secular Kozai resonance, first investigated in the context of asteroids in the Solar System, can increase the eccentricity of the inner body significantly. We show that in a substantial fraction of cases the eccentricity is driven to a high enough value that the inner binary will merge by gravitational radiation, without a strong accompanying kick. Thus the merged object remains in the cluster; depending on the binary fraction of black holes and the inclination distribution of newly-formed hierarchical triples, this mechanism may allow massive black holes to accumulate through successive mergers in the cores of globular clusters. It may also increase the likelihood that stellar-mass black holes in globular clusters will be detectable by their gravitational radiation.Comment: Submitted to ApJ Letters (includes emulateapj.sty

Implications of the PSR 1257+12 Planetary System for Isolated Millisecond Pulsars

The first extrasolar planets were discovered in 1992 around the millisecond pulsar PSR 1257+12. We show that recent developments in the study of accretion onto magnetized stars, plus the existence of the innermost, moon-sized planet in the PSR 1257+12 system, suggest that the pulsar was born with approximately its current rotation frequency and magnetic moment. If so, this has important implications for the formation and evolution of neutron star magnetic fields as well as for the formation of planets around pulsars. In particular, it suggests that some and perhaps all isolated millisecond pulsars may have been born with high spin rates and low magnetic fields instead of having been recycled by accretion.Comment: 17 pages including one figure, uses aaspp4, accepted by Ap

Gender Differences in Russian Colour Naming

In the present study we explored Russian colour naming in a web-based psycholinguistic experiment (http://www.colournaming.com). Colour singletons representing the Munsell Color Solid (N=600 in total) were presented on a computer monitor and named using an unconstrained colour-naming method. Respondents were Russian speakers (N=713). For gender-split equal-size samples (NF=333, NM=333) we estimated and compared (i) location of centroids of 12 Russian basic colour terms (BCTs); (ii) the number of words in colour descriptors; (iii) occurrences of BCTs most frequent non-BCTs. We found a close correspondence between females’ and males’ BCT centroids. Among individual BCTs, the highest inter-gender agreement was for seryj ‘grey’ and goluboj ‘light blue’, while the lowest was for sinij ‘dark blue’ and krasnyj ‘red’. Females revealed a significantly richer repertory of distinct colour descriptors, with great variety of monolexemic non-BCTs and “fancy” colour names; in comparison, males offered relatively more BCTs or their compounds. Along with these measures, we gauged denotata of most frequent CTs, reflected by linguistic segmentation of colour space, by employing a synthetic observer trained by gender-specific responses. This psycholinguistic representation revealed females’ more refined linguistic segmentation, compared to males, with higher linguistic density predominantly along the redgreen axis of colour space

Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas

Background: The prognosis for malignant gliomas remains dismal. We addressed the safety, feasibility and preliminary clinical activity of the vaccinations using autologous glioma cells and interleukin (IL)-4 gene transfected fibroblasts. Methods: In University of Pittsburgh Cancer Institute (UPCI) protocol 95-033, adult participants with recurrent glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) received gross total resection (GTR) of the recurrent tumors, followed by two vaccinations with autologous fibroblasts retrovirally transfected with TFG-IL4-Neo-TK vector admixed with irradiated autologous glioma cells. In UPCI 99-111, adult participants with newly diagnosed GBM or AA, following GTR and radiation therapy, received two intradermal vaccinations with the TFG-IL4-Neo-TK-transfected fibroblasts admixed with type-1 dendritic cells (DC) loaded with autologous tumor lysate. The participants were evaluated for occurrence of adverse events, immune response, and clinical response by radiological imaging. Results and Discussion: In UPCI 95-033, only 2 of 6 participants received the vaccinations. Four other participants were withdrawn from the trial because of tumor progression prior to production of the cellular vaccine. However, both participants who received two vaccinations demonstrated encouraging immunological and clinical responses. Biopsies from the local vaccine sites from one participant displayed IL-4 dose-dependent infiltration of CD4+ as well as CD8+ T cells. Interferon (IFN)-γ Enzyme-Linked Immuno-SPOT (ELISPOT) assay in another human leukocyte antigen (HLA)-A2+ participant demonstrated systemic T-cell responses against an HLA-A2-restricted glioma-associated antigen (GAA) epitope EphA2883-891. Moreover, both participants demonstrated clinical and radiological improvement with no evidence of allergic encephalitis, although both participants eventually succumbed with the tumor recurrence. In 99-111, 5 of 6 enrolled participants received scheduled vaccinations with no incidence of major adverse events. Monocyte-derived DCs produced high levels of IL-12 p70. Treatment was well tolerated; however, we were unable to observe detectable IFN-γ post-vaccine responses or prolonged progression-free survival in these participants. Conclusion: Feasibility challenges inherent in the generation of a patient-specific gene transfection-based vaccine strongly suggests the need for more practical formulations that would allow for the timely administration of vaccines. Nevertheless, successful generation of type-1 DCs and preliminary safety in the current study provide a strong rationale for further efforts to develop novel glioma vaccines. © 2007 Okada et al; licensee BioMed Central Ltd

A statistical review of light curves and the prevalence of contact binaries in the Kuiper Belt

We investigate what can be learned about a population of distant Kuiper Belt Objects (KBOs) by studying the statistical properties of their light curves. Whereas others have successfully inferred the properties of individual, highly variable KBOs, we show that the fraction of KBOs with low amplitudes also provides fundamental information about a population. Each light curve is primarily the result of two factors: shape and orientation. We consider contact binaries and ellipsoidal shapes, with and without flattening. After developing the mathematical framework, we apply it to the existing body of KBO light curve data. Principal conclusions are as follows. (1) When using absolute magnitude H as a proxy for the sizes of KBOs, it is more accurate to use the maximum of the light curve (minimum H) rather than the mean. (2) Previous investigators have noted that smaller KBOs tend to have higher-amplitude light curves, and have interpreted this as evidence that they are systematically more irregular in shape than larger KBOs; we show that a population of flattened bodies with uniform proportions, independent of size, could also explain this result. (3) Our method of analysis indicates that prior assessments of the fraction of contact binaries in the Kuiper Belt may be artificially low. (4) The pole orientations of some KBOs can be inferred from observed changes in their light curves over time scales of decades; however, we show that these KBOs constitute a biased sample, whose pole orientations are not representative of the population overall. (5) Although surface topography, albedo patterns, limb darkening, and other surface properties can affect individual light curves, they do not have a strong influence on the statistics overall. (6) Photometry from the Outer Solar System Origins Survey (OSSOS) survey is incompatible with previous results and its statistical properties defy easy interpretation. We also discuss the promise of this approach for the analysis of future, much larger data sets such as the one anticipated from the upcoming Vera C. Rubin Observatory

A statistical review of light curves and the prevalence of contact binaries in the Kuiper Belt

We investigate what can be learned about a population of distant Kuiper Belt Objects (KBOs) by studying the statistical properties of their light curves. Whereas others have successfully inferred the properties of individual, highly variable KBOs, we show that the fraction of KBOs with low amplitudes also provides fundamental information about a population. Each light curve is primarily the result of two factors: shape and orientation. We consider contact binaries and ellipsoidal shapes, with and without flattening. After developing the mathematical framework, we apply it to the existing body of KBO light curve data. Principal conclusions are as follows. (1) When using absolute magnitude H as a proxy for the sizes of KBOs, it is more accurate to use the maximum of the light curve (minimum H) rather than the mean. (2) Previous investigators have noted that smaller KBOs tend to have higher-amplitude light curves, and have interpreted this as evidence that they are systematically more irregular in shape than larger KBOs; we show that a population of flattened bodies with uniform proportions, independent of size, could also explain this result. (3) Our method of analysis indicates that prior assessments of the fraction of contact binaries in the Kuiper Belt may be artificially low. (4) The pole orientations of some KBOs can be inferred from observed changes in their light curves over time scales of decades; however, we show that these KBOs constitute a biased sample, whose pole orientations are not representative of the population overall. (5) Although surface topography, albedo patterns, limb darkening, and other surface properties can affect individual light curves, they do not have a strong influence on the statistics overall. (6) Photometry from the Outer Solar System Origins Survey (OSSOS) survey is incompatible with previous results and its statistical properties defy easy interpretation. We also discuss the promise of this approach for the analysis of future, much larger data sets such as the one anticipated from the upcoming Vera C. Rubin Observatory