A molecular biology and phase II trial of lapatinib in children with refractory CNS malignancies: a pediatric brain tumor consortium study.

High expression of ERBB2 has been reported in medulloblastoma and ependymoma; EGFR is amplified and over-expressed in brainstem glioma suggesting these proteins as potential therapeutic targets. We conducted a molecular biology (MB) and phase II study to estimate inhibition of tumor ERBB signaling and sustained responses by lapatinib in children with recurrent CNS malignancies. In the MB study, patients with recurrent medulloblastoma, ependymoma, and high-grade glioma (HGG) undergoing resection were stratified and randomized to pre-resection treatment with lapatinib 900 mg/m(2) dose bid for 7-14 days or no treatment. Western blot analysis of ERBB expression and pathway activity in fresh tumor obtained at surgery estimated ERBB receptor signaling inhibition in vivo. Drug concentration was simultaneously assessed in tumor and plasma. In the phase II study, patients, stratified by histology, received lapatinib continuously, to assess sustained response. Eight patients, on the MB trial (four medulloblastomas, four ependymomas), received a median of two courses (range 1-6+). No intratumoral target inhibition by lapatinib was noted in any patient. Tumor-to-plasma ratios of lapatinib were 10-20 %. In the 34 patients (14 MB, 10 HGG, 10 ependymoma) in the phase II study, lapatinib was well-tolerated at 900 mg/m(2) dose bid. The median number of courses in the phase II trial was two (range 1-12). Seven patients (three medulloblastoma, four ependymoma) remained on therapy for at least four courses range (4-26). Lapatinib was well-tolerated in children with recurrent or CNS malignancies, but did not inhibit target in tumor and had little single agent activity.Fil: Fouladi, Maryam. St. Jude Children’s Research Hospital; Estados UnidosFil: Stewart, Clinton F.. St. Jude Children’s Research Hospital; Estados UnidosFil: Blaney, Susan M.. Baylor College of Medicine. Texas Children’s Cancer Center; Estados UnidosFil: Onar Thomas, Arzu. St. Jude Children’s Research Hospital; Estados UnidosFil: Schaiquevich, Paula Susana. St. Jude Children’s Research Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Packer, Roger J.. Children’s National Medical Center; Estados UnidosFil: Goldman, Stewart. Anne and Robert H. Lurie Children’s Hospital of Chicago; Estados UnidosFil: Geyer, J. Rusell. Children’s Hospital and Regional Medical Center; Estados UnidosFil: Gajjar, Amar. St. Jude Children’s Research Hospital; Estados UnidosFil: Kun, Larry E.. St. Jude Children’s Research Hospital; Estados UnidosFil: Boyett, James M.. St. Jude Children’s Research Hospital; Estados UnidosFil: Gilbertson, Richard J.. St. Jude Children’s Research Hospital; Estados Unido

Jet-induced ground effects on a parametric flat-plate model in hover

The jet-induced forces generated on short takeoff and vertical landing (STOVL) aircraft when in close proximity to the ground can have a significant effect on aircraft performance. Therefore, accurate predictions of these aerodynamic characteristics are highly desirable. Empirical procedures for estimating jet-induced forces during the vertical/short takeoff and landing (V/STOL) portions of the flight envelope are currently limited in accuracy. The jet-induced force data presented significantly add to the current STOVL configurations data base. Further development of empirical prediction methods for jet-induced forces, to provide more configuration diversity and improved overall accuracy, depends on the viability of this STOVL data base. The data base may also be used to validate computational fluid dynamics (CFD) analysis codes. The hover data obtained at the NASA Ames Jet Calibration and Hover Test (JCAHT) facility for a parametric flat-plate model is presented. The model tested was designed to allow variations in the planform aspect ratio, number of jets, nozzle shape, and jet location. There were 31 different planform/nozzle configurations tested. Each configuration had numerous pressure taps installed to measure the pressures on the undersurface of the model. All pressure data along with the balance jet-induced lift and pitching-moment increments are tabulated. For selected runs, pressure data are presented in the form of contour plots that show lines of constant pressure coefficient on the model undersurface. Nozzle-thrust calibrations and jet flow-pressure survey information are also provided

Providing Economic Incentives in Environmental Regulation

CHAIRMAN BREGER: Let me welcome you to this AdministrativeConference colloquy on providing economic incentives in environmentallitigation

Real-time simulation and control systems design by the Response Surface Methodology and designed experiments

This paper examines two cases where the fitting of a model to experimental data makes possible the solution of extremely difficult design and simulation problems. In the first (aerospace) case, designed experiments were conducted on a permanent magnet AC motor which provided the motive power for a flight surface actuator in a more electric aircraft application. The Response Surface Methodology is applied to the measured data to achieve inclusion of the component in a real-time distributed aircraft simulation. In the second (automotive) case, oscillatory acceleration responses are controlled via an electronically actuated (drive by wire) throttle. Designed experiments were conducted on the test vehicle to achieve a systematic excitation of the vehicle driveline. An approximation to the measured data is achieved by the Response Surface Methodology allowing a controller to be designed extremely rapidly

Spectral characteristics for a spherically confined -1/r + br^2 potential

We consider the analytical properties of the eigenspectrum generated by a class of central potentials given by V(r) = -a/r + br^2, b>0. In particular, scaling, monotonicity, and energy bounds are discussed. The potential $V(r)$ is considered both in all space, and under the condition of spherical confinement inside an impenetrable spherical boundary of radius R. With the aid of the asymptotic iteration method, several exact analytic results are obtained which exhibit the parametric dependence of energy on a, b, and R, under certain constraints. More general spectral characteristics are identified by use of a combination of analytical properties and accurate numerical calculations of the energies, obtained by both the generalized pseudo-spectral method, and the asymptotic iteration method. The experimental significance of the results for both the free and confined potential V(r) cases are discussed.Comment: 16 pages, 4 figure

Review of the prevalence of diabetic retinopathy in Indigenous Australians

Author version made available in accordance with Publisher copyright policy.The purpose of this review is to compare the prevalence of diabetic retinopathy (DR) between Indigenous and non-Indigenous Australians with Diabetes Mellitus (DM). Australian DR prevalence data from 6 Indigenous studies (n = 2865) and 5 non-Indigenous studies (n = 9801) conducted between 1985 and 2013 were included for analysis. Estimated prevalence of any DR among Indigenous Australians with DM was 23.4% compared with 28.9% for non-Indigenous Australians (χ2 = 26.9, P < 0.001). In studies performed after 1990, a significantly higher rate of diabetic macular edema was found in Indigenous compared with non-Indigenous Australians with DM (7.6% versus 4.9%, χ2 = 6.67, P = 0.01). Although there are limitations in comparing these studies, one explanation for the observed data could be a model in which Indigenous Australians are relatively resistant to early stage DR, but with a subset progressing to sight threatening DR due to individual genetic and environmental susceptibility factors coupled with poor glycemic control