Clinical and cost-effectiveness of capecitabine and tegafur with uracil for the treatment of metastatic colorectal cancer: systematic review and economic evaluation

Objectives: To evaluate the clinical and costeffectiveness of capecitabine and tegafur with uracil (UFT/LV) as first-line treatments for patients with metastatic colorectal cancer, as compared with 5- fluorouracil/folinic acid (5-FU/FA) regimens. Data sources: Electronic databases, reference lists of relevant articles and sponsor submissions were also consulted. Review methods: Systematic searches, selection against criteria and quality assessment were performed to obtain data from relevant studies. Costs were estimated through resource-use data taken from the published trials and the unpublished sponsor submissions. Unit costs were taken from published sources, where available. An economic evaluation was undertaken to compare the cost-effectiveness of capecitabine and UFT/LV with three intravenous 5- FU/LV regimens widely used in the UK: the Mayo, the modified de Gramont regimen and the inpatient de Gramont regimens. Results: The evidence suggests that treatment with capecitabine improves overall response rates and has an improved adverse effect profile in comparison with 5-FU/LV treatment with the Mayo regimen, with the exception of hand–foot syndrome. Time to disease progression or death after treatment with UFT/LV in one study appears to be shorter than after treatment with 5-FU/LV with the Mayo regimen, although it also had an improved adverse effect profile. Neither capecitabine nor UFT/LV appeared to improve healthrelated quality of life. Little information on patient preference was available for UFT/LV, but there was indicated a strong preference for this over 5-FU/LV. The total cost of capecitabine and UFT/LV treatments were estimated at £2111 and £3375, respectively, compared with the total treatment cost for the Mayo regimen of £3579. Cost estimates were also presented for the modified de Gramont and inpatient de Gramont regimens. These were £3684 and £6155, respectively. No survival advantage was shown in the RCTs of the oral drugs against the Mayo regimen. Cost savings of capecitabine and UFT/LV over the Mayo regimen were estimated to be £1461 and £209, respectively. Drug acquisition costs were higher for the oral therapies than for the Mayo regimen, but were offset by lower administration costs. Adverse event treatment costs were similar across the three regimens. It was inferred that there was no survival difference between the oral drugs and the de Gramont regimens. Cost savings of capecitabine and UFT/LV over the modified de Gramont regimen were estimated to be £1353 and £101, respectively, and over the inpatient de Gramont regimen were estimated to be £4123 and £2870, respectively. Conclusions: The results show that there are cost savings associated with the use of oral therapies. No survival difference has been proven between the oral drugs and the Mayo regimen. In addition, no evidence of a survival difference between the Mayo regimen and the de Gramont regimens has been identified. However, improved progression-free survival and an improved adverse event profile have been shown for the de Gramont regimen over the Mayo regimen. Further research is recommended into the following areas: quality of life data should be included in trials of colorectal cancer treatments; the place of effective oral treatments in the treatment of colorectal cancer, the safety mechanisms needed to ensure compliance and the monitoring of adverse effects; the optimum duration of treatment; the measurement of patient preference; and a phase III comparative trial of capecitabine and UFT/LV versus modified de Gramont treatment to determine whether there was any survival advantage and to collate the necessary economic data

Some properties of a 5-parameter bivariate probability distribution

A five-parameter bivariate gamma distribution having two shape parameters, two location parameters and a correlation parameter was developed. This more general bivariate gamma distribution reduces to the known four-parameter distribution. The five-parameter distribution gives a better fit to the gust data. The statistical properties of this general bivariate gamma distribution and a hypothesis test were investigated. Although these developments have come too late in the Shuttle program to be used directly as design criteria for ascent wind gust loads, the new wind gust model has helped to explain the wind profile conditions which cause large dynamic loads. Other potential applications of the newly developed five-parameter bivariate gamma distribution are in the areas of reliability theory, signal noise, and vibration mechanics

NASA participation in the 1980 PEPE/NEROS project: Data archive

Eight experimental air quality measurement systems were investigated during July and August 1980 as part of the EPA PEPE/NEROS fiel measurement program. Data from those efforts have been entered into an archive that may be accessed by other researchers. The data sets consists of airborne measurements of regional mixed layer heights and aerosol and ozone distributions as well as point measurements of meteorological parameters and ozone obtained during diurnal transitions in the planetary boundary layer. This report gives a discussion of each measurement system, a preliminary assessment of data quality, a description of the archive format for each data set, and a summary of several proposed scientific studies which will utilize these data

Do Gender Differences in Perceived Prototypical Computer Scientists and Engineers Contribute to Gender Gaps in Computer Science and Engineering?

Women are vastly underrepresented in the fields of computer science and engineering (CS&E). We examined whether women might view the intellectual characteristics of prototypical individuals in CS&E in more stereotype-consistent ways than men might and, consequently, show less interest in CS&E. We asked 269 U.S. college students (187, 69.5% women) to describe the prototypical computer scientist (Study 1) or engineer (Study 2) through open-ended descriptions as well as through a set of trait ratings. Participants also rated themselves on the same set of traits and rated their similarity to the prototype. Finally, participants in both studies were asked to describe their likelihood of pursuing future college courses and careers in computer science (Study 1) or engineering (Study 2). Across both studies, we found that women offered more stereotype-consistent ratings than did men of the intellectual characteristics of prototypes in CS (Study 1) and engineering (Study 2). Women also perceived themselves as less similar to the prototype than men did. Further, the observed gender differences in prototype perceptions mediated the tendency for women to report lower interest in CS&E fields relative to men. Our work highlights the importance of prototype perceptions for understanding the gender gap in CS&E and suggests avenues for interventions that may increase women’s representation in these vital fields

Fe I Oscillator Strengths for the Gaia-ESO Survey

The Gaia-ESO Public Spectroscopic Survey (GES) is conducting a large-scale study of multi-element chemical abundances of some 100 000 stars in the Milky Way with the ultimate aim of quantifying the formation history and evolution of young, mature and ancient Galactic populations. However, in preparing for the analysis of GES spectra, it has been noted that atomic oscillator strengths of important Fe I lines required to correctly model stellar line intensities are missing from the atomic database. Here, we present new experimental oscillator strengths derived from branching fractions and level lifetimes, for 142 transitions of Fe I between 3526 {\AA} and 10864 {\AA}, of which at least 38 are urgently needed by GES. We also assess the impact of these new data on solar spectral synthesis and demonstrate that for 36 lines that appear unblended in the Sun, Fe abundance measurements yield a small line-by-line scatter (0.08 dex) with a mean abundance of 7.44 dex in good agreement with recent publications.Comment: Accepted for publication in Mon. Not. R. Astron. So

Study of the application of hydrogen fuel to long-range subsonic transport aircraft, volume 2

The feasibility, practicability, and potential advantages/disadvantages of using liquid hydrogen as fuel in long range, subsonic transport aircraft of advanced design were studied. Both passenger and cargo-type aircraft were investigated. To provide a valid basis for comparison, conventional hydrocarbon (Jet A) fueled aircraft were designed to perform identical missions using the same advanced technology and meeting the same operational constraints. The liquid hydrogen and Jet A fueled aircraft were compared on the basis of weight, size, energy utilization, cost, noise, emissions, safety, and operational characteristics. A program of technology development was formulated

Penning traps with unitary architecture for storage of highly charged ions

Penning traps are made extremely compact by embedding rare-earth permanent magnets in the electrode structure. Axially-oriented NdFeB magnets are used in unitary architectures that couple the electric and magnetic components into an integrated structure. We have constructed a two- magnet Penning trap with radial access to enable the use of laser or atomic beams, as well as the collection of light. An experimental apparatus equipped with ion optics is installed at the NIST electron beam ion trap (EBIT) facility, constrained to fit within 1 meter at the end of a horizontal beamline for transporting highly charged ions. Highly charged ions of neon and argon, extracted with initial energies up to 4000 eV per unit charge, are captured and stored to study the confinement properties of a one-magnet trap and a two-magnet trap. Design considerations and some test results are discussed

Cumulus cloud venting of mixed layer ozone

Observations are presented which substantiate the hypothesis that significant vertical exchange of ozone and aerosols occurs between the mixed layer and the free troposphere during cumulus cloud convective activity. The experiments utilized the airborne Ultra-Violet Differential Absorption Lidar (UV-DIAL) system. This system provides simultaneous range resolved ozone concentration and aerosol backscatter profiles with high spatial resolution. Evening transects were obtained in the downwind area where the air mass had been advected. Space-height analyses for the evening flight show the cloud debris as patterns of ozone typically in excess of the ambient free tropospheric background. This ozone excess was approximately the value of the concentration difference between the mixed layer and free troposphere determined from independent vertical soundings made by another aircraft in the afternoon

Monotonic Prefix Consistency in Distributed Systems

We study the issue of data consistency in distributed systems. Specifically, we consider a distributed system that replicates its data at multiple sites, which is prone to partitions, and which is assumed to be available (in the sense that queries are always eventually answered). In such a setting, strong consistency, where all replicas of the system apply synchronously every operation, is not possible to implement. However, many weaker consistency criteria that allow a greater number of behaviors than strong consistency, are implementable in available distributed systems. We focus on determining the strongest consistency criterion that can be implemented in a convergent and available distributed system that tolerates partitions. We focus on objects where the set of operations can be split into updates and queries. We show that no criterion stronger than Monotonic Prefix Consistency (MPC) can be implemented.Comment: Submitted pape