Concurrent irinotecan, oxaliplatin and UFT in first-line treatment of metastatic colorectal cancer: a Phase I study

The feasibility of combining UFT plus leucovorin (LV) with alternating irinotecan and oxaliplatin was investigated in the first-line treatment of patients with advanced colorectal cancer. Twenty-five patients, median age 63 (range 24–79) years, World Health Organisation performance status 0–2 and median four marker lesions, received irinotecan 180 mg m−2 on day 1, oxaliplatin 85–100 mg m−2 on day 15 and UFT 200–300 mg m−2 day−1 with LV 90 mg day−1, days 1–21 of a 28-day cycle. Patients were treated in cohorts of three. At the highest dose (irinotecan 180 mg m−2, oxaliplatin 100 mg m−2 and UFT 300 mg m−2 day−1), three of four patients experienced grade 3 toxicity. Diarrhoea, lethargy and vomiting were dose-limiting. Three of nine patients had grade 2 toxicities at the maximum tolerated dose (irinotecan 180 mg m−2, oxaliplatin 100 mg m−2 and UFT 250 mg m−2 day−1). There were no grade 3 toxicities in the first month of therapy. The overall response rate was 71% in 21 evaluable patients; progression-free survival was 8.8 months. Alternating irinotecan and oxaliplatin plus UFT is an effective and well-tolerated first-line treatment for patients with advanced colorectal cancer. We recommend a dose of irinotecan 180 mg m−2 on day 1, oxaliplatin 100 mg m−2 on day 15 and UFT 250 mg m−2 day−1 with LV 90 mg day−1 on days 1–21 of a 28-day cycle for future studies

The Prelude to and Aftermath of the Giant Flare of 2004 December 27: Persistent and Pulsed X-ray Properties of SGR 1806-20 from 1993 to 2005

On 2004 December 27, a highly-energetic giant flare was recorded from the magnetar candidate SGR 1806-20. In the months preceding this flare, the persistent X-ray emission from this object began to undergo significant changes. Here, we report on the evolution of key spectral and temporal parameters prior to and following this giant flare. Using the Rossi X-ray Timing Explorer, we track the pulse frequency of SGR 1806-20 and find that the spin-down rate of this SGR varied erratically in the months before and after the flare. Contrary to the giant flare in SGR 1900+14, we find no evidence for a discrete jump in spin frequency at the time of the December 27th flare (|dnu/nu| < 5 X 10^-6). In the months surrounding the flare, we find a strong correlation between pulsed flux and torque consistent with the model for magnetar magnetosphere electrodynamics proposed by Thompson, Lyutikov & Kulkarni (2002). As with the flare in SGR 1900+14, the pulse morphology of SGR 1806-20 changes drastically following the flare. Using the Chandra X-ray Observatory and other publicly available imaging X-ray detector observations, we construct a spectral history of SGR 1806-20 from 1993 to 2005. The usual magnetar persistent emission spectral model of a power-law plus a blackbody provides an excellent fit to the data. We confirm the earlier finding by Mereghetti et al. (2005) of increasing spectral hardness of SGR 1806-20 between 1993 and 2004. Contrary to the direct correlation between torque and spectral hardness proposed by Mereghetti et al., we find evidence for a sudden torque change that triggered a gradual hardening of the energy spectrum on a timescale of years. Interestingly, the spectral hardness, spin-down rate, pulsed, and phase-averaged of SGR 1806-20 all peak months before the flare epoch.Comment: 37 pages, 8 figures, 8 tables. Accepted for publication in ApJ. To appear in the Oct 20 2006 editio

The Formaldehyde Masers in NGC 7538 and G29.96-0.02: VLBA, MERLIN, and VLA Observations

The 6 cm formaldehyde (H2CO) maser sources in the compact HII regions NGC 7538-IRS1 and G29.96-0.02 have been imaged at high resolution (beams < 50 mas). Using the VLBA and MERLIN, we find the angular sizes of the NGC 7538 masers to be ~10 mas (30 AU) corresponding to brightness temperatures ~10^8 K. The angular sizes of the G29.96-0.02 masers are ~20 mas (130 AU) corresponding to brightness temperatures ~10^7 K. Using the VLA, we detect 2 cm formaldehyde absorption from the maser regions. We detect no emission in the 2 cm line, indicating the lack of a 2 cm maser and placing limits on the 6 cm excitation process. We find that both NGC 7538 maser components show an increase in intensity on 5-10 year timescales while the G29.96-0.02 masers show no variability over 2 years. A search for polarization provides 3-sigma upper limits of 1% circularly polarized and 10% linearly polarized emission in NGC 7538 and of 15% circularly polarized emission in G29.96-0.02. A pronounced velocity gradient of 28 km/s/arcsecond (1900 km/s/pc) is detected in the NGC 7538 maser gas.Comment: accepted to ApJ, 15 figures, 11 table

Continuum theory of vacancy-mediated diffusion

We present and solve a continuum theory of vacancy-mediated diffusion (as evidenced, for example, in the vacancy driven motion of tracers in crystals). Results are obtained for all spatial dimensions, and reveal the strongly non-gaussian nature of the tracer fluctuations. In integer dimensions, our results are in complete agreement with those from previous exact lattice calculations. We also extend our model to describe the vacancy-driven fluctuations of a slaved flux line.Comment: 25 Latex pages, subm. to Physical Review

Anomalous relaxation and self-organization in non-equilibrium processes

We study thermal relaxation in ordered arrays of coupled nonlinear elements with external driving. We find, that our model exhibits dynamic self-organization manifested in a universal stretched-exponential form of relaxation. We identify two types of self-organization, cooperative and anti-cooperative, which lead to fast and slow relaxation, respectively. We give a qualitative explanation for the behavior of the stretched exponent in different parameter ranges. We emphasize that this is a system exhibiting stretched-exponential relaxation without explicit disorder or frustration.Comment: submitted to PR

Topological Orthoalgebras

We define topological orthoalgebras (TOAs) and study their properties. While every topological orthomodular lattice is a TOA, the lattice of projections of a Hilbert space is an example of a lattice-ordered TOA that is not a toplogical lattice. On the other hand, we show that every compact Boolean TOA is a topological Boolean algebra. We also show that a compact TOA in which 0 is an isolated point is atomic and of finite height. We identify and study a particularly tractable class of TOAs, which we call {\em stably ordered}: those in which the upper-set generated by an open set is open. This includes all topological OMLs, and also the projection lattices of Hilbert spaces. Finally, we obtain a topological version of the Foulis-Randall representation theory for stably ordered TOAsComment: 16 pp, LaTex. Minor changes and corrections in sections 1; more substantial corrections in section

On chirp stimuli and neural synchrony in the suprathreshold auditory brainstem response

The chirp-evoked ABR has been regarded as a more synchronous response than the click-evoked ABR, referring to the belief that the chirp stimulates lower-, mid-, and higher-frequency regions of the cochlea simultaneously. In this study a variety of tools were used to analyze the synchronicity of ABRs evoked by chirp- and click-stimuli at 40 dB HL in 32 normal hearing subjects aged 18 to 55 years (mean=24.8 years, SD=7.1 years). Compared to the click-evoked ABRs, the chirp-evoked ABRs showed larger wave V amplitudes, but an absence of earlier waves in the grand averages, larger wave V latency variance, smaller FFT magnitudes at the higher component frequencies, and larger phase variance at the higher component frequencies. These results strongly suggest that the chirp-evoked ABRs exhibited less synchrony than the click-evoked ABRs in this study. It is proposed that the temporal compensation offered by chirp stimuli is sufficient to increase neural recruitment (as measured by wave V amplitude), but that destructive phase interactions still exist along the cochlea partition, particularly in the low frequency portions of the cochlea where more latency jitter is expected. The clinical implications of these findings are discussed. (C) 2010 Acoustical Society of America. [DOI: 10.1121/1.3436527