Phase II Study of Cediranib in Patients with Malignant Pleural Mesothelioma: SWOG S0509

IntroductionMalignant pleural mesothelioma (MPM) tumors express vascular epithelial growth factor (VEGF) and VEGF receptors. We conducted a phase II study of the oral pan-VEGF receptor tyrosine kinase inhibitor, cediranib, in patients with MPM after platinum-based systemic chemotherapy.MethodsPatients with MPM previously treated with a platinum-containing chemotherapy regimen and a performance status 0 to 2 were eligible for enrollment. Cediranib 45 mg/d was administered until progression or unacceptable toxicity. The primary end point was response rate. Tumor measurements were made by RECIST criteria, with a subset analysis conducted using modified RECIST. A two-stage design with an early stopping rule based on response rate was used.ResultsFifty-four patients were enrolled. Of 47 evaluable patients, 4 patients (9%) had objective responses, 16 patients (34%) had stable disease, 20 patients (43%) had disease progression, 2 patients (4%) had symptomatic deterioration, and 1 patient (2%) had early death. The most common toxicities were fatigue (64%), diarrhea (64%), and hypertension (70%); 91% of patients required a dose reduction. Median overall survival was 9.5 months, 1-year survival was 36%, and median progression-free survival was 2.6 months.ConclusionCediranib monotherapy has modest single-agent activity in MPM after platinum-based therapy. However, some patient tumors were highly sensitive to cediranib. This study provides a rationale for further testing of cediranib plus chemotherapy in MPM and highlights the need to identify a predictive biomarker for cediranib

Locomotive Horn Detectability at Closely-Spaced Highway-Rail Grade Crossings

DTFR5317X00026Researchers assessed the feasibility of altering the locomotive horn sounding pattern of repetition at each crossing in a series of closely-spaced grade crossings by exploring the specific geometries and warning requirements for motorists in advance of such crossings. Acoustic modeling on five example scenarios showed that the locomotive horn would meet the auditory detection criteria out to a minimum of 1200 ft downstream of the primary crossing in those scenarios. The results from this analysis confirm that further exploration is needed on this topic, including assessing the feasibility and effectiveness for both detectability and driver response, to only sounding the locomotive horn prior to arriving at the first in a series of closely-spaced grade crossings

From plastic to elastic stress relaxation in highly mismatched SiGe/Si heterostructures

We present a detailed experimental and theoretical analysis of the epitaxial stress relaxation process in micro-structured compositionally graded alloys. We focus on the pivotal SiGe/Si(001) system employing patterned Si substrates at the micrometre-size scale to address the distribution of threading and misfit dislocations within the heterostructures. SiGe alloys with linearly increasing Ge content were deposited by low energy plasma enhanced chemical vapour deposition resulting in isolated, tens of micrometre tall 3D crystals. We demonstrate that complete elastic relaxation is achieved by appropriate choice of the Ge compositional grading rate and Si pillar width. We investigate the nature and distribution of dislocations along the [001] growth direction in SiGe crystals by transmission electron microscopy, chemical defect etching and etch pit counting. We show that for 3 μm wide Si pillars and a Ge grading rate of 1.5% μm−1, only misfit dislocations are present while their fraction is reduced for higher Ge grading rates and larger structures due to dislocation interactions. The experimental results are interpreted with the help of theoretical calculations based on linear elasticity theory describing the competition between purely elastic and plastic stress relaxation with increasing crystal width and Ge compositional grading rate

Transmittance and optical constants of Tm films in the 2.75–1600 eV spectral range

The optical constants of thulium (Tm) films were obtained in the 2.75-1600 eV range from transmittance measurements performed at room temperature. Thin films of Tm were deposited by evaporation in ultrahigh vacuum conditions and their transmittance was measured in situ. Tm films were deposited onto grids coated with a thin, C support film. Transmittance measurements were used to obtain the optical extinction coefficient k of Tm films. The refractive index n of Tm was calculated using the Kramers-Krönig analysis. k data were extrapolated both on the high and the low energy sides by using experimental and calculated extinction coefficient values available in the literature. Tm, similar to other lanthanides, has a low-absorption band below the O 2,3 edge onset; the lowest absorption was measured at ∼23 eV. Therefore, Tm is a promising material for filters and multilayer coatings in the energy range below the O2,3 edge in which materials typically have an absorption stronger than away. Good consistency of the data was obtained through f and inertial sum rules