Final results of the phase III, randomized, double-blind AVOREN trial of first-line bevacizumab (BEV) + interferon-α2a (IFN) in metastatic renal cell carcinoma (mRCC)

5020 Background: In the AVOREN trial, BEV (Avastin) + IFN significantly improved PFS and ORR compared with placebo + IFN in pts with mRCC [Escudier, Lancet. 2007]. The study was unblinded after interim analysis due to significant superiority of BEV + IFN and the DSMB recommended crossover of pts from placebo to BEV (n = 13). We report here the results of the final analysis. Methods: Eligible pts had predominantly clear-cell mRCC, prior nephrectomy, no prior systemic therapy for metastatic disease, KPS ≥70%, no CNS metastases and adequate organ function. Pts were randomised to IFN (9MIU tiw) + BEV (10 mg/kg q2w) or placebo until disease progression. Primary endpoint was OS, with pre-planned stratified and unstratified analyses according to regional regulatory requirements. Results: 649 pts were randomised to BEV + IFN (n = 327) or placebo + IFN (n = 322). An independent radiological review confirmed previous investigator assessments, showing PFS of 10.4 vs 5.5 months (HR 0.57) and a response rate of 31% vs 12% in the two arms, verifying the robustness of the investigator analysis. At the time of final OS analysis (444 events), median follow-up was 22.9 months in the BEV arm and 20.6 months in the placebo arm. Final median OS stratified for region and Motzer score was 23.3 months in the BEV + IFN arm and 21.3 months in the IFN + placebo arm (HR 0.86 [95% CI: 0.72–1.04], p = 0.1291). No new or unexpected AEs were observed. More pts in the IFN + placebo arm than the BEV + IFN arm received post-protocol therapy, including TKIs, mTOR inhibitors, cytokines and chemotherapy: 180 (55%) in the BEV + IFN arm and 202 (63%) in the IFN + placebo arm. Exploratory analysis showed that median OS in pts receiving second-line TKI therapy (BEV + IFN, n = 96; IFN + placebo, n = 81) was 38.6 months vs 33.2 months (HR = 0.77 [95% CI: 0.51–1.15], p = 0.1948). Further subgroup analyses will be presented. Conclusions: BEV + IFN is a first-line standard of care for pts with mRCC, improving PFS and ORR, with a trend toward improved OS, compared with IFN. The observed OS results may have been influenced by subsequent anti-neoplastic therapy, which was not prespecified in the protocol and represents an uncontrolled element of the OS analysis. [Table: see text]

Experimental Evaluation of a Metal Mesh Bearing Damper

Metal mesh is a commercially available material used in many applications including seals, heat shields, filters, gaskets, aircraft engine mounts, and vibration absorbers. This material has been tested by the authors as a bearing damper in a rotordynamic test rig. The test facility was originally used to support the design of a turboprop engine, developing squirrel cages and squeeze film dampers for both the gas generator and power turbine rotors. To design the metal mesh damper, static stiffness and dynamic rap test measurements were first made on metal mesh samples in a specially designed nonrotating test fixture. These property tests were performed on samples of various densities and press fits. One sample was also tested in an Instron machine as an ancillary and redundant way to determine the stiffness. Using the stiffness test results and equations derived by a previous investigator, a spreadsheet program was written and used to size metal mesh donuts that have the radial stiffness value required to replace the squirrel cage in the power turbine. The squirrel cage and squeeze film bearing damper developed for the power turbine rotor was then replaced by a metal mesh donut sized by the computer code. Coast down tests were conducted through the first critical speed of the power turbine. The results of the metal mesh tests are compared with those obtained from previous testing with the squeeze film damper and show that the metal mesh damper has the same damping as the squeeze film at room temperature but does not lose its damping at elevated temperatures up to 103°C. Experiments were run under several different conditions, including balanced rotor, unbalanced rotor, heated metal mesh, and wet (with oil) metal mesh. The creep, or sag, of the metal mesh supporting the rotor weight was also measured over a period of several weeks and found to be very small. Based on these tests, metal mesh dampers appear to be a viable and attractive substitute for squeeze film dampers in gas turbine engines. The advantages shown by these tests include less variation of damping with temperature, ability to handle large rotor unbalance, and the ability (if required) to operate effectively in an oil free environment. Additional testing is required to determine the endurance properties, the effect of high impact or maneuver loads, and the ability to sustain blade loss loads (which squeeze films cannot handle). [S0742-4795(00)01002-4]

Experimental Evaluation of a Metal Mesh Bearing Damper

Metal mesh is a commercially available material used in many applications including seals, heat shields, filters, gaskets, aircraft engine mounts, and vibration absorbers. This material has been tested by the authors as a bearing damper in a rotordynamic test rig. The test facility was originally used to support the design of a turboprop engine, developing squirrel cages and squeeze film dampers for both the gas generator and power turbine rotors. To design the metal mesh damper, static stiffness and dynamic rap test measurements were first made on metal mesh samples in a specially designed nonrotating test fixture. These property tests were performed on samples of various densities and press fits. One sample was also tested in an Instron machine as an ancillary and redundant way to determine the stiffness. Using the stiffness test results and equations derived by a previous investigator, a spreadsheet program was written and used to size metal mesh donuts that have the radial stiffness value required to replace the squirrel cage in the power turbine. The squirrel cage and squeeze film bearing damper developed for the power turbine rotor was then replaced by a metal mesh donut sized by the computer code. Coast down tests were conducted through the first critical speed of the power turbine. The results of the metal mesh tests are compared with those obtained from previous testing with the squeeze film damper and Show that the metal mesh damper has the same damping as the squeeze film at room temperature but does not lose its damping at elevated temperatures up to 103 °C. Experiments were run under several different conditions, including balanced rotor, unbalanced rotor, heated metal mesh, and wet (with oil) metal mesh. The creep, or sag, of the metal mesh supporting the rotor weight was also measured over a period of several weeks and found to be very small. Based on these tests, metal mesh dampers appear to be a viable and attractive substitute for squeeze film dampers in gas turbine engines. The advantages shown by these tests include less variation of damping with temperature, ability to handle large rotor unbalance, and the ability (if required) to operate effectively in an oil free environment. Additional testing is required to determine the endurance properties, the effect of high impact or maneuver loads, and the ability to sustain blade loss loads (which squeeze films cannot handle).

Certain Heat Conduction Problems In a Perforated Circular Cyliner

Employing a new class of basis functions, certain steady-state two-dimensional heat conduction problems for a multihole circular cylinder are solved. It is assumed that the outer boundary of the cylinder is subject to convection, while the cases of the following inner boundary conditions are investigated. (1) The inner boundaries are subject to a constant temperature. (2) The inner boundaries are subject to convection. (3) The inner circular cylinders consist of a different material containing uniform heat sources. It is also assumed that the properties of the materials involved, and the factors such as the convection heat transfer coefficients are temperature independent. Numerical results for all of the three aforementioned cases are presented, and for a particular case, the result is compared with that of a previous investigator.

Evaluation of 1,10-Phenanthroline as a Reagent for Sialic Acid Determinations

Use of o-phenanthroline as a reagent for determination of sialic acids was proposed by a previous investigator. This method was based on an increase in absorbance at 307 nm that occurred when solutions of o-phenanthroline and various sialic acids were mixed. It was postulated that the increased absorbance was a result of formation of specific complexes. Using N-acetylneuraminic acid, we found no evidence for complex formation. Our results indicate that the observations of the previous investigator resulted from shifts in the pH of the medium rather than from formation of specific complexes. Therefore o-phenanthroline is not a specific reagent for sialic acids and its use is not recommended.

Microstructure of a CoCrNiTa Alloy System

The effect of tantalum additions to a 40-30-30 CoCrNi alloy has been studied by electron diffraction, transmission and scanning electron microscopy, and energy dispersive x-ray analysis in an attempt to identify the microstructure associated wit£ mechanical properties determined by a previous investigator.Samples were prepared by conventional investment casting techniques and thinned electrolytically in perchloric acid-ethanol solution at 20-35 volts for transmission electron microscopy. This solution also etched the surfaces of the specimens sufficiently to yield good sca ning electron micrographs.Energy dispersive k=ray analysis showed that the castings contain an average of 19% more Ta, 8% more Cr, 9% less Co and 6% less Ni than the weighed amounts.

The rate of decay in relation to soil types and vegetative covering in Glamorgan

Summary1. The object of this investigation was to determine the extent to which the decomposing power of soils within a climatic region is influenced by:(a) the geological character of the rocks from which the soils are derived,(b) the nature of the vegetative covering.2. A short account is given of the geography, climatology, geology and pedology of Glamorgan. The soils of South Glamorgan appear in general to be Brown Earth types.3. In studying the rate of decay it is necessary to obtain an index of the intensity of the total biochemical processes taking place. One of the best and most suitable of indices for this purpose is CO2 evolution.4. A type of apparatus used by a previous investigator (Neller) to measure the CO2 evolved from soil was tested and found to be unsatisfactory. Thus a suitable apparatus had to be evolved. This apparatus is described in detail.

XIV. Researches illustrative of the physico-chemical theory of fermentation, and of the conditions favouring archebiosis in previously boiled fluids.—No. I

The author first calls attention to the fact that no previous investigator has professed to have seen well-marked fermentation set up in urine that had been boiled for a few minutes, if it has thereafter been guarded from contamination. The previous invariable barrenness of this fluid after boiling has been ascribed by germ-theorists to the fact that any organisms or germs of organisms which it may have contained were killed by raising it to the temperature of 212° F. (100° C.). In executing some of the experiments with urine described in this communication, two chemical agents have been brought into operation under novel conditions, and an ordinary physical influence has been employed to an entirely new extent. In several respects, therefore, these new experiments differ much, as regards the conditions made use of, from those hitherto devised for throwing light upon the much-vexed questions as to the possible origin of fermentations independently of living organisms or germs, and as to the present occurrence or non-occurrence of Archebiosis.