Phase II study of CC-486 (oral azacitidine) in previously treated patients with locally advanced or metastatic nasopharyngeal carcinoma

BACKGROUND: Treatment options are limited for recurrent nasopharyngeal carcinoma (NPC). We report results from a phase II study of CC-486 (oral azacitidine) in advanced NPC. PATIENTS AND METHODS: Patients with locally advanced or metastatic NPC and 1-2 prior treatment regimens received CC-486 300 mg daily on days 1-14 of 21-day cycles until disease progression or unacceptable toxicity. The first 6 patients of Asian-Pacific Islander (API) ethnicity received a reduced dose of 200 mg to preserve safety and tolerability; if well tolerated, subsequent API patients received CC-486 300 mg. The study could advance to stage 2 if > 4 patients achieved a response. Co-primary end-points were overall response rate (ORR) and progression-free survival (independent review). Key secondary end-points were overall survival and safety. RESULTS: Owing to faster-than-anticipated enrolment, 36 patients, including 13 of API ethnicity, were enrolled; the median age was 54.0 years. Most patients were male (81%) and had an Eastern Cooperative Oncology Group performance status 64 1 (97%). Among 25 efficacy-evaluable patients, the ORR was 12%; the median progression-free and overall survival were 4.7 and 18.0 months, respectively. The most common grade III/IV treatment-emergent adverse events were neutropenia (33%) and febrile neutropenia (11%). Twenty-one posttreatment deaths, primarily due to progressive disease or disease complications, and 1 on-treatment death (epistaxis, unrelated to study drug) occurred. The study did not advance to stage 2. CONCLUSION: CC-486 did not show sufficient clinical activity to support further development as monotherapy in this patient population. The safety profile of CC-486 in NPC was consistent with that in other solid tumours

New evidence for strong nonthermal effects in Tycho's supernova remnant

For the case of Tycho's supernova remnant (SNR) we present the relation between the blast wave and contact discontinuity radii calculated within the nonlinear kinetic theory of cosmic ray (CR) acceleration in SNRs. It is demonstrated that these radii are confirmed by recently published Chandra measurements which show that the observed contact discontinuity radius is so close to the shock radius that it can only be explained by efficient CR acceleration which in turn makes the medium more compressible. Together with the recently determined new value $E_{sn}=1.2\times 10^{51}$ erg of the SN explosion energy this also confirms our previous conclusion that a TeV gamma-ray flux of $(2-5)\times 10^{-13}$ erg/(cm$^2$s) is to be expected from Tycho's SNR. Chandra measurements and the HEGRA upper limit of the TeV gamma-ray flux together limit the source distance $d$ to $3.3\leq d\leq 4$ kpc.Comment: 5 pages, 4 figures. Accepted for publication in Astrophysics and Space Science, Proc. of "The Multi-Messenger Approach to High-Energy Gamma-ray Sources (Third Workshop on the Nature of Unidentified High-Energy Sources)", Barcelona, July 4-7, 200

Pilot study evaluating catheter-directed contrast-enhanced ultrasound compared to catheter-directed computed tomography arteriography as adjuncts to digital subtraction angiography to guide transarterial chemoembolization

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Serological response in RT-PCR confirmed h1n1-2009 influenza a by hemagglutination inhibition and virus neutralization assays: An observational study

10.1371/journal.pone.0012474PLoS ONE58

Measuring Black Hole Spin using X-ray Reflection Spectroscopy

I review the current status of X-ray reflection (a.k.a. broad iron line) based black hole spin measurements. This is a powerful technique that allows us to measure robust black hole spins across the mass range, from the stellar-mass black holes in X-ray binaries to the supermassive black holes in active galactic nuclei. After describing the basic assumptions of this approach, I lay out the detailed methodology focusing on "best practices" that have been found necessary to obtain robust results. Reflecting my own biases, this review is slanted towards a discussion of supermassive black hole (SMBH) spin in active galactic nuclei (AGN). Pulling together all of the available XMM-Newton and Suzaku results from the literature that satisfy objective quality control criteria, it is clear that a large fraction of SMBHs are rapidly-spinning, although there are tentative hints of a more slowly spinning population at high (M>5*10^7Msun) and low (M<2*10^6Msun) mass. I also engage in a brief review of the spins of stellar-mass black holes in X-ray binaries. In general, reflection-based and continuum-fitting based spin measures are in agreement, although there remain two objects (GROJ1655-40 and 4U1543-475) for which that is not true. I end this review by discussing the exciting frontier of relativistic reverberation, particularly the discovery of broad iron line reverberation in XMM-Newton data for the Seyfert galaxies NGC4151, NGC7314 and MCG-5-23-16. As well as confirming the basic paradigm of relativistic disk reflection, this detection of reverberation demonstrates that future large-area X-ray observatories such as LOFT will make tremendous progress in studies of strong gravity using relativistic reverberation in AGN.Comment: 19 pages. To appear in proceedings of the ISSI-Bern workshop on "The Physics of Accretion onto Black Holes" (8-12 Oct 2012). Revised version adds a missing source to Table 1 and Fig.6 (IRAS13224-3809) and corrects the referencing of the discovery of soft lags in 1H0707-495 (which were in fact first reported in Fabian et al. 2009

Thermal Resonance in Signal Transmission

We use temperature tuning to control signal propagation in simple one-dimensional arrays of masses connected by hard anharmonic springs and with no local potentials. In our numerical model a sustained signal is applied at one site of a chain immersed in a thermal environment and the signal-to-noise ratio is measured at each oscillator. We show that raising the temperature can lead to enhanced signal propagation along the chain, resulting in thermal resonance effects akin to the resonance observed in arrays of bistable systems.Comment: To appear in Phys. Rev.

Generation of Kelly and dip type sidebands soliton employing Topological insulator (Bi2Te3) as saturable absorber

Conventional Kelly sidebands soliton and dip-type sidebands soliton were observed with the employment of Bi2Te3 as saturable absorber (SA) in Erbium-Doped Fiber Laser (EDFL). The fabricated Bi2Te3 possessed the following characteristics: Isat 102 MW/cm2, modulation depth 41.4%, and non-saturable absorption at 10%. The Bi2Te3 solution was transferred to the end of the fiber ferrule by the optical deposition method. Conventional Kelly sidebands soliton was obtained with a fundamental repetition rate and pulse width of 24 MHz and 0.78 ps, respectively. The existing cavity length was extended and with the appropriate tuning of light polarization, dip-peak intensity soliton sidebands with bunched pulses were observed. The oscillation trace revealed the repetition rate of dip-peak intensity sidebands soliton was ascertained at 13.5 MHz, which was in accordance with the cavity length. There was a total of 144 pulses in a single bunch envelope under the maximum available pump power. With the appropriate tuning of light polarization, constructive and destructive interference between soliton and dispersive waves took place in EDFL resulting in the formation of peak intensity (Kelly sidebands) and dip-peak intensity on the soliton spectrum. To the best of the author’s knowledge, this is the first demonstration of dip-peak intensity sidebands soliton using Bi2Te3