Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial

Carboplatin/taxane combination is first-line therapy for ovarian cancer. However, patients can encounter treatment delays, impaired quality of life, even death because of chemotherapy-induced gastrointestinal (GI) toxicity. A candidate gene study was conducted to assess potential association of genetic variants with GI toxicity in 808 patients who received carboplatin/taxane in the Scottish Randomized Trial in Ovarian Cancer 1 (SCOTROC1). Patients were randomized into discovery and validation cohorts consisting of 404 patients each. Clinical covariates and genetic variants associated with grade III/IV GI toxicity in discovery cohort were evaluated in replication cohort. Chemotherapy-induced GI toxicity was significantly associated with seven single-nucleotide polymorphisms in the ATP7B, GSR, VEGFA and SCN10A genes. Patients with risk genotypes were at 1.53 to 18.01 higher odds to develop carboplatin/taxane-induced GI toxicity (P<0.01). Variants in the VEGF gene were marginally associated with survival time. Our data provide potential targets for modulation/inhibition of GI toxicity in ovarian cancer patients

Probing Sub-Micron Forces by Interferometry of Bose-Einstein Condensed Atoms

We propose a technique, using interferometry of Bose-Einstein condensed alkali atoms, for the detection of sub-micron-range forces. It may extend present searches at 1 micron by 6 to 9 orders of magnitude, deep into the theoretically interesting regime of 1000 times gravity. We give several examples of both four-dimensional particles (moduli), as well as higher-dimensional particles -- vectors and scalars in a large bulk-- that could mediate forces accessible by this technique.Comment: 32 pages, 5 figures, RevTeX4, expanded discussion of interactions, references added, to appear in PR

An Earth-system prediction initiative for the twenty-first century

International audienceSome scientists have proposed the Earth-System Prediction Initiative (EPI) at the 2007 GEO Summit in Cape Town, South Africa. EPI will draw upon coordination between international programs for Earth system observations, prediction, and warning, such as the WCRP, WWRP, GCOS, and hence contribute to GEO and the GEOSS. It will link with international organizations, such as the International Council for Science (ICSU), Intergovernmental Oceanographic Commission (IOC), UNEP, WMO, and World Health Organization (WHO). The proposed initiative will provide high-resolution climate models that capture the properties of regional high-impact weather events, such as tropical cyclones, heat wave, and sand and dust storms associated within multi-decadal climate projections of climate variability and change. Unprecedented international collaboration and goodwill are necessary for the success of EPI

Countering Extremists on Social Media:Challenges for Strategic Communication and Content Moderation

Extremist exploitation of social media platforms is an important regulatory question for civil society, government, and the private sector. Extremists exploit social media for a range of reasons-from spreading hateful narratives and propaganda to financing, recruitment, and sharing operational information. Policy responses to this question fit under two headings, strategic communication and content moderation. At the center of both of these policy responses is a calculation about how best to limit audience exposure to extremist narratives and maintain the marginality of extremist views, while being conscious of rights to free expression and the appropriateness of restrictions on speech. This special issue on "Countering Extremists on Social Media: Challenges for Strategic Communication and Content Moderation" focuses on one form of strategic communication, countering violent extremism. In this editorial we discuss the background and effectiveness of this approach, and introduce five articles which develop multiple strands of research into responses and solutions to extremist exploitation of social media. We conclude by suggesting an agenda for future research on how multistakeholder initiatives to challenge extremist exploitation of social media are conceived, designed, and implemented, and the challenges these initiatives need to surmount

Q

The Qweak experiment, which took data at Jefferson Lab in the period 2010 - 2012, will precisely determine the weak charge of the proton by measuring the parity-violating asymmetry in elastic e-p scattering at 1.1 GeV using a longitudinally polarized electron beam and a liquid hydrogen target at a low momentum transfer of Q2 = 0.025 (GeV/c)2. The weak charge of the proton is predicted by the Standard Model and any significant deviation would indicate physics beyond the Standard Model. The technical challenges and experimental apparatus for measuring the weak charge of the proton will be discussed, as well as the method of extracting the weak charge of the proton. The results from a small subset of the data, that has been published, will also be presented. Furthermore an update will be given of the current status of the data analysis

On the sensitivity of the HAWC observatory to gamma-ray bursts

We present the sensitivity of HAWC to Gamma Ray Bursts (GRBs). HAWC is a very high-energy gamma-ray observatory currently under construction in Mexico at an altitude of 4100 m. It will observe atmospheric air showers via the water Cherenkov method. HAWC will consist of 300 large water tanks instrumented with 4 photomultipliers each. HAWC has two data acquisition (DAQ) systems. The main DAQ system reads out coincident signals in the tanks and reconstructs the direction and energy of individual atmospheric showers. The scaler DAQ counts the hits in each photomultiplier tube (PMT) in the detector and searches for a statistical excess over the noise of all PMTs. We show that HAWC has a realistic opportunity to observe the high-energy power law components of GRBs that extend at least up to 30 GeV, as it has been observed by Fermi LAT. The two DAQ systems have an energy threshold that is low enough to observe events similar to GRB 090510 and GRB 090902b with the characteristics observed by Fermi LAT. HAWC will provide information about the high-energy spectra of GRBs which in turn could help to understanding about e-pair attenuation in GRB jets, extragalactic background light absorption, as well as establishing the highest energy to which GRBs accelerate particles

The Great Markarian 421 Flare of 2010 February: Multiwavelength Variability and Correlation Studies

We report on variability and correlation studies using multiwavelength observations of the blazar Mrk 421 during the month of 2010 February, when an extraordinary flare reaching a level of ∼27 Crab Units above 1 TeV was measured in very high energy (VHE) γ-rays with the Very Energetic Radiation Imaging Telescope Array System (VERITAS) observatory. This is the highest flux state for Mrk 421 ever observed in VHE γ-rays. Data are analyzed from a coordinated campaign across multiple instruments, including VHE γ-ray (VERITAS, Major Atmospheric Gamma-ray Imaging Cherenkov), high-energy γ-ray (Fermi-LAT), X-ray (Swift, Rossi X-ray Timing Experiment, MAXI), optical (including the GASP-WEBT collaboration and polarization data), and radio (Metsahovi, Owens Valley Radio Observatory, University of Michigan Radio Astronomy Observatory). Light curves are produced spanning multiple days before and after the peak of the VHE flare, including over several flare "decline" epochs. The main flare statistics allow 2 minute time bins to be constructed in both the VHE and optical bands enabling a cross-correlation analysis that shows evidence for an optical lag of ∼25-55 minutes, the first time-lagged correlation between these bands reported on such short timescales. Limits on the Doppler factor (δ ⪆ 33) and the size of the emission region (δ-1RB≲ 3.8 × 1013cm) are obtained from the fast variability observed by VERITAS during the main flare. Analysis of 10 minute binned VHE and X-ray data over the decline epochs shows an extraordinary range of behavior in the flux-flux relationship, from linear to quadratic to lack of correlation to anticorrelation. Taken together, these detailed observations of an unprecedented flare seen in Mrk 421 are difficult to explain with the classic single-zone synchrotron self-Compton model.</p