Two first-in-human studies of xentuzumab, a humanised insulin-like growth factor (IGF)-neutralising antibody, in patients with advanced solid tumours

BACKGROUND: Xentuzumab, an insulin-like growth factor (IGF)-1/IGF-2-neutralising antibody, binds IGF-1 and IGF-2, inhibiting their growth-promoting signalling. Two first-in-human trials assessed the maximum-tolerated/relevant biological dose (MTD/RBD), safety, pharmacokinetics, pharmacodynamics, and activity of xentuzumab in advanced/metastatic solid cancers. METHODS: These phase 1, open-label trials comprised dose-finding (part I; 3 + 3 design) and expansion cohorts (part II; selected tumours; RBD [weekly dosing]). Primary endpoints were MTD/RBD. RESULTS: Study 1280.1 involved 61 patients (part I: xentuzumab 10–1800 mg weekly, n = 48; part II: 1000 mg weekly, n = 13); study 1280.2, 64 patients (part I: 10–3600 mg three-weekly, n = 33; part II: 1000 mg weekly, n = 31). One dose-limiting toxicity occurred; the MTD was not reached for either schedule. Adverse events were generally grade 1/2, mostly gastrointestinal. Xentuzumab showed dose-proportional pharmacokinetics. Total plasma IGF-1 increased dose dependently, plateauing at ~1000 mg/week; at ≥450 mg/week, IGF bioactivity was almost undetectable. Two partial responses occurred (poorly differentiated nasopharyngeal carcinoma and peripheral primitive neuroectodermal tumour). Integration of biomarker and response data by Bayesian Logistic Regression Modeling (BLRM) confirmed the RBD. CONCLUSIONS: Xentuzumab was well tolerated; MTD was not reached. RBD was 1000 mg weekly, confirmed by BLRM. Xentuzumab showed preliminary anti-tumour activity

Measurement of Pressure Dependent Fluorescence Yield of Air: Calibration Factor for UHECR Detectors

In a test experiment at the Final Focus Test Beam of the Stanford Linear Accelerator Center, the fluorescence yield of 28.5 GeV electrons in air and nitrogen was measured. The measured photon yields between 300 and 400 nm at 1 atm and 29 deg C are Y(760 Torr, air) = 4.42 +/- 0.73 and Y(760 Torr, nitrogen) = 29.2 +/- 4.8 photons per electron per meter. Assuming that the fluorescence yield is proportional to the energy deposition of a charged particle traveling through air, good agreement with measurements at lower particle energies is observed.Comment: 22 pages, 14 figures, 2 tables, submitted to Astroparticle Physic

Results from beam tests of MEGA's low-mass, high-rate cylindrical MWPCs

One of the leading experimental projects at LAMPF has been the MEGA experiment. This is an experiment to search for the rare decay {mu} {yields} e{gamma} with a sensitivity of 10{sup {minus}13}. A prime component of this project has been the design and construction of high-rate, low mass MWPCs for the tracking of positrons from muon decay. With rate capabilities of 2 {times} 10{sup 4} e{sup +}/mm{sup 2}/s and a thickness of 3 {times} 10{sup {minus}4} radiation lengths, these chambers are state-of-the-art cylindrical MWPCs. Cylindrical chambers of this size (0.9 m{sup 2}) and thinness have never been previously constructed. The MEGA project at LAMPF has recently succeeded in building chambers with these necessary performance characteristics as demonstrated by data taken from muon decays, cosmic rays, and sources

Two first-in-human studies of xentuzumab, a humanised insulin-like growth factor (IGF)-neutralising antibody, in patients with advanced solid tumours

BACKGROUND: Xentuzumab, an insulin-like growth factor (IGF)-1/IGF-2-neutralising antibody, binds IGF-1 and IGF-2, inhibiting their growth-promoting signalling. Two first-in-human trials assessed the maximum-tolerated/relevant biological dose (MTD/RBD), safety, pharmacokinetics, pharmacodynamics, and activity of xentuzumab in advanced/metastatic solid cancers. METHODS: These phase 1, open-label trials comprised dose-finding (part I; 3 + 3 design) and expansion cohorts (part II; selected tumours; RBD [weekly dosing]). Primary endpoints were MTD/RBD. RESULTS: Study 1280.1 involved 61 patients (part I: xentuzumab 10–1800 mg weekly, n = 48; part II: 1000 mg weekly, n = 13); study 1280.2, 64 patients (part I: 10–3600 mg three-weekly, n = 33; part II: 1000 mg weekly, n = 31). One dose-limiting toxicity occurred; the MTD was not reached for either schedule. Adverse events were generally grade 1/2, mostly gastrointestinal. Xentuzumab showed dose-proportional pharmacokinetics. Total plasma IGF-1 increased dose dependently, plateauing at ~1000 mg/week; at ≥450 mg/week, IGF bioactivity was almost undetectable. Two partial responses occurred (poorly differentiated nasopharyngeal carcinoma and peripheral primitive neuroectodermal tumour). Integration of biomarker and response data by Bayesian Logistic Regression Modeling (BLRM) confirmed the RBD. CONCLUSIONS: Xentuzumab was well tolerated; MTD was not reached. RBD was 1000 mg weekly, confirmed by BLRM. Xentuzumab showed preliminary anti-tumour activity

A measurement of the average longitudinal development profile of cosmic ray air showers between 10(17) and 10(18) eV

Copyright © 2001 Elsevier Science B.V. All rights reserved.The average extensive air shower longitudinal development profile is measured. Events between 1017 and 1018 eV recorded by the HiRes/MIA hybrid experiment are used for the average profile. Several functional forms are examined using this average profile. The best-fit parameters for the above functions are determined. © 2001 Elsevier Science B.V.http://www.elsevier.com/wps/find/journaldescription.cws_home/523319/description#descriptio

Present and future: a trend forecasting and ranking of university types for innovative development from an intellectual capital perspective

[[abstract]]In today’s knowledge-based economy, by well intellectual capital (IC) managing to enhance innovative ability and performance has become critical as many nations struggle to gain sustainable competitive advantage. Knowledge, innovation, and IC are at a university’s core. Given its function of cultivating innovative assets, R&D researchers, hi-tech professions and interdisciplinary talent, universities have become a critical factor in building sustainable competitive advantages worldwide. The important role universities play is particularly essential in Taiwan. The hi-tech industry, as the most profitable industry sector, directly impacts the growth of the Taiwanese economy. However, as global competition in higher education becomes fierce, higher education in Taiwan is losing its competitive standing and global market share for students and, additionally, Taiwan is losing its overall competitive advantage in the global economy. Universities today face significantly unbalanced student enrollment numbers and several universities have failed to keep operating from late 2008 to 2009. In order to understand both current and future development trends in higher education and to conquer above difficulties, it has become crucial to understand the manifestation of innovative development with respect to IC for different university types. In this regard, the aim of this study was to explore the rankings of five university types in terms of innovative development from an IC perspective and to provide recommendations for future improvements, taking basic development trends into account. Trend forecasting from Grey Model (GM) was initially used to investigate and forecast current and future Taiwanese birth rates and the basic development trends of five university types. After that, VIKOR was utilized to rank the five university types in accordance with opinions from twenty senior experts with regard to IC. In agreement with the research findings, universities in Taiwan are encouraged to improve their innovative ability from an IC perspective in order to regain a sustainable competitive advantage globally in the future.[[journaltype]]國外[[incitationindex]]SCI[[booktype]]紙本[[countrycodes]]NL