Surrogate endpoints for overall survival in advanced colorectal cancer: a clinician's perspective

Surrogate endpoints in oncology research and practice have garnered increasing attention over the past two decades. This activity has largely been driven by the promise surrogate endpoints appear to hold: the potential to get new therapies to seriously ill patients more rapidly. However, uncertainties abound. Even agreeing upon a definition of a "valid" surrogate endpoint has not been a straightforward exercise; this article begins by highlighting differences in how this term has been previously captured and applied, as well as laying out the basic criteria essential for its application in advanced colorectal cancer. Ideally, these elements include (but are not limited to) ease of measurement, rapid indication of treatment effect, and, most importantly, reliable and consistent prediction of the true impact of a treatment on the ultimate outcome of interest: overall survival. The strengths and weaknesses of current potential surrogate endpoints in advanced colorectal cancer, including performance status, carcinoembryonic antigen plasma level, overall response rate, time to progression, and disease-free survival, are each considered in turn. Finally, limitations of surrogate endpoints in the clinical setting, including challenges in extrapolation to new therapies, and the incomplete provision of information about potential adverse effects, are discussed. Work remains to be done between physicians and statisticians to bridge the gap between that which is statistically demonstrable and that which will be clinically useful.The term ;surrogate endpoint' was virtually unknown by most oncologists 15 years ago. A search in PubMed [http://www.ncbi.nlm.nih.gov] based on the words ;surrogate and cancer' shows that more than 2000 papers were published in medical journals in the last 20 years, with a dramatic increase of interest in the last five years. Interestingly, the same trend is observed when the words ;surrogate and heart' are entered into PubMed, suggesting that the issue of surrogate endpoints goes beyond the field of oncology, although the frequency of discussion varies (Figure 1; note different y-axis scales for oncology and cardiology).The goal of the present paper is to discuss the main issues surrounding surrogate endpoints from a clinician's point of view, using as an example surrogate endpoints of overall survival (OS) in advanced colorectal cancer (ACC).     

An omnidirectional microwave antenna for use on spacecraft

The qualitative theory, design, and development of a parallel-plate waveguide-fed antenna, suitable for flush-mounted broad-band spacecraft applications, are presented. The antenna makes use of wedge-like metal posts placed uniformly about the periphery of the feed plates to provide both structural strength and practical interconnection routes for cables without disrupting the antenna impedance and patterns. Measurements taken on the antenna, which is mounted on spheroids up to 50 wavelengths in circumference, are presented; equatorial patterns are omnidirectional withinpm 0.25dB, and polar patterns have beam widths similar to a half-wave dipole.     

Ocean Experiments And Remotely Sensed Images of Chemically Dispersed Oil Spills

A series of experiments was performed at sea where the effectiveness of dispersants applied from a helicopter was tested on fresh and weathered crude oils released from a surface research vessel. In conjunction with these experiments, remote sensing measurements using an array of airborne optical and microwave sensors were performed in order to aid in the interpretation of the dispersant effectiveness and to obtain quantitative images of oil on the sea under controlled conditions. Surface oil thickness and volume are inferred from airborne measurements using a dual-channel microwave imaging radiometer, aerial color photography, and an airborne oceanographic lidar. The remotely sensed measurements are compared with point sampled data obtained using a research vessel. The mass balance computations of surface versus subsurface oil volume using remotely sensed and point sampled data are consistent with each other and with the volumes of oil released. Data collected by the several techniques concur in indicating that, for the oils used and under the sea conditions encountered, the dispersant and application method are primarily useful when applied to fresh oil.     

Lead zirconate titanate thin film capacitors on electroless nickel coated copper foils for embedded passive applications

Lead zirconate titanate (PZT, 52/48) thin film capacitors were prepared on electroless Ni coated Cu foil by chemical solution deposition for printed wiring board embedded capacitor applications. Phase development, dielectric properties, and leakage characteristics of capacitors were investigated, in particular as a function of the process temperature. Dielectric properties of the capacitors were dependent on the crystallization temperature, and capacitance densities of more than 350 nF/cm² and loss tangent of less than 0.03 were measured for capacitors crystallized below 600 °C. Lowest leakage current densities (around 2 × 10^− 7 A/cm² at 10 V direct current (DC)) and highest breakdown fields could be obtained for capacitors crystallized at 650 °C.Capacitors with different thickness and a two-layer capacitor model were used in analyzing the interface layer between PZT and the underlying electroless Ni. From the capacitance and leakage measurements, it is suggested that the interface reaction layer has low permittivity (K around 30) and high defect concentration, which has an important effect on the electrical properties of capacitors. This interface is from the reaction of the electroless nickel layer with the adjacent PZT, and may specifically be moderated by the nickel phosphide (Ni-P) phase, transformed from amorphous Ni during the annealing step.The results have significant implications for embedded capacitors in printed wiring boards. They demonstrate that the process can be tuned to produce either voltage independent capacitors with low leakage and high breakdown fields (above 30 V DC), or the more usual hysteretic, switching, ferroelectric capacitors with higher capacitance densities.     

Computations of the aperture admittance of an axial slot on a dielectric coated cylinder

An extensive set of curves for the aperture admittance of a waveguide-fed axial slot on a coated metal cylinder is presented for both an underdense plasma and a Teflon coating. Examination of these curves shows that a slot on a cylinder with aKaof 2 to 3 has about the same aperture admittance as the identical slot opening onto a flat ground plane.     

The Input Admittance of a Rectangular Waveguide-Fed Aperture Under an Inhomogeneous Plasma: Theory and Experiment

The admittance of a waveguide-fed rectangular aperture under an inhomogeneous plasma is derived and experimentally verified. For both flowing and stationary inhomogeneoas plasmas, the agreement is at least as accurate as presently available plasma diagnostic techniques will allow. It is shown that there is a clear separation of the dependence of aperture-admittance properties upon plasma properties, such as electron density, profile shape and collision frequency, over two to three decades of peak electron density, change. The collision frequency primarily affects the aperture conductance, particularly for critical and overdense plasmas. The profile shape, i.e., a boundary layer, primarily affects the aperture susceptance.     

A dielectric-coated circumferential slot array for omnidirectional coverage at microwave frequencies

The design and development of a resonant array of circumferential shunt slots cut into the broad wall of a ring waveguide are presented. This antenna, which is recessed into a metal cylinder and dielectric coated, provides nearly omnidirectional coverage. Calculations using an idealized model consisting of a dielectric-coated flush-mounted array on a metal cylinder were performed and used as the primary basis for design. The array recess design was experimentally determined and shown to control the elevation pattern when the recessed array is mounted on a variety of spacecraft shapes. The tolerance problems and the related trapped wave effects encountered in the development of the array are discussed.     

Effect of polysilicon gate type on the flatband voltage shift forultrathin oxide-nitride gate stacks

In this work, we demonstrate that the magnitude of flatband voltage (V_FB) shift for ultrathin (<2 nm) silicon dioxide-silicon nitride (ON) gate stacks in MOSFET's depends on the Fermi level position in the gate material. In addition, a fixed positive charge at the oxide-nitride interface was observed     

Analysis of the radiation patterns of reflector antennas

The development and application of a numerical technique for the rapid calculation of the far-field radiation patterns of a reflector antenna from either a measured or computed feed pattern are reported. The reflector is defined by the intersection of a cone with any surface of revolution or an offset sector of any surface of revolution. The feed is assumed to be linearly polarized and can have an arbitrary location. Both the copolarized and the cross polarized reflector radiation patterns are computed. Calculations using the technique compare closely with measured radiation patterns of a waveguide-fed offset parabolic reflector. The unique features of this technique are the freedom from restrictive feed assumptions and the numerical methods used in preparing the aperture plane electric field data for integration.     

Calculated scan characteristics of a large spherical reflector antenna

A previously published numerical method to calculate the radiation properties of parabolic reflectors has been modified to also include very large spherical reflectors. The method has been verified by comparing the calculated and the measured results for a 120-wavelength spherical reflector.