Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study.

RESONATE-2 is a phase 3 study of first-line ibrutinib versus chlorambucil in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Patients aged ≥65 years (n = 269) were randomized 1:1 to once-daily ibrutinib 420 mg continuously or chlorambucil 0.5-0.8 mg/kg for ≤12 cycles. With a median (range) follow-up of 60 months (0.1-66), progression-free survival (PFS) and overall survival (OS) benefits for ibrutinib versus chlorambucil were sustained (PFS estimates at 5 years: 70% vs 12%; HR [95% CI]: 0.146 [0.098-0.218]; OS estimates at 5 years: 83% vs 68%; HR [95% CI]: 0.450 [0.266-0.761]). Ibrutinib benefit was also consistent in patients with high prognostic risk (TP53 mutation, 11q deletion, and/or unmutated IGHV) (PFS: HR [95% CI]: 0.083 [0.047-0.145]; OS: HR [95% CI]: 0.366 [0.181-0.736]). Investigator-assessed overall response rate was 92% with ibrutinib (complete response, 30%; 11% at primary analysis). Common grade ≥3 adverse events (AEs) included neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), and hyponatremia (6%); occurrence of most events as well as discontinuations due to AEs decreased over time. Fifty-eight percent of patients continue to receive ibrutinib. Single-agent ibrutinib demonstrated sustained PFS and OS benefit versus chlorambucil and increased depth of response over time

Strong and auxiliary forms of the semi-Lagrangian method for incompressible flows

We present a review of the semi-Lagrangian method for advection-diusion and incompressible Navier-Stokes equations discretized with high-order methods. In particular, we compare the strong form where the departure points are computed directly via backwards integration with the auxiliary form where an auxiliary advection equation is solved instead; the latter is also referred to as Operator Integration Factor Splitting (OIFS) scheme. For intermediate size of time steps the auxiliary form is preferrable but for large time steps only the strong form is stable

Aperture calculation of the Pierre Auger Observatory surface detector

We determine the instantaneous aperture and integrated exposure of the surface detector of the Pierre Auger Observatory, taking into account the trigger efficiency as a function of the energy, arrival direction (with zenith angle lower than 60 degrees) and nature of the primary cosmic-ray. We make use of the so-called Lateral Trigger Probability function (or LTP) associated with an extensive air shower, which summarizes all the relevant information about the physics of the shower, the water tank Cherenkov detector, and the triggers.Comment: Proc. of the 29th ICRC (Pune, India), LaTeX, 4 pages, 5 figure

A new method to measure the attenuation of hadrons in extensive air showers

Extensive air showers are generated through interactions of high-energy cosmic rays impinging the Earth's atmosphere. A new method is described to infer the attenuation of hadrons in air showers. The numbers of electrons and muons, registered with the scintillator array of the KASCADE experiment are used to estimate the energy of the shower inducing primary particle. A large hadron calorimeter is used to measure the hadronic energy reaching observation level. The ratio of energy reaching ground level to the energy of the primary particle is used to derive an attenuation length of hadrons in air showers. In the energy range from $10^6$ GeV to $3\cdot10^7$ GeV the attenuation length obtained increases from 170 \gcm2 to 210 \gcm2. The experimental results are compared to predictions of simulations based on contemporary high energy interaction models.Comment: accepted for publication in Physical Review

Frequency spectra of cosmic ray air shower radio emission measured with LOPES

AIMS: We wish to study the spectral dependence of the radio emission from cosmic-ray air showers around 100 PeV (1017 eV). METHODS: We observe short radio pulses in a broad frequency band with the dipole-interferometer LOPES (LOFAR Prototype Station), which is triggered by a particle detector array named Karlsruhe Shower Core and Array Detector (KASCADE). LOFAR is the Low Frequency Array. For this analysis, 23 strong air shower events are selected using parameters from KASCADE. RESULTS: The resulting electric field spectra fall off to higher frequencies. An average electric field spectrum is fitted with an exponential, or alternatively, with a power law. The spectral slope obtained is not consistent within uncertainties and it is slightly steeper than the slope obtained from Monte Carlo simulations based on air showers simulated with CORSIKA (Cosmic Ray Simulations for KASCADE). One of the strongest events was measured during thunderstorm activity in the vicinity of LOPES and shows the longest pulse length measured of 110 ns and a spectral slope of -3.6. CONCLUSIONS: We show with two different methods that frequency spectra from air shower radio emission can be reconstructed on event-by-event basis, with only two dozen dipole antennae simultaneously over a broad range of frequencies. According to the obtained spectral slopes, the maximum power is emitted below 40 MHz. Furthermore, the decrease in power to higher frequencies indicates a loss in coherence determined by the shower disc thickness. We conclude that a broader bandwidth, larger collecting area, and longer baselines, as will be provided by LOFAR, are necessary to further investigate the relation of the coherence, pulse length, and spectral slope of cosmic ray air showers.Comment: 13 pages, 21 figures. Nigl, A. et al. (LOPES Collaboration), Frequency spectra of cosmic ray air shower radio emission measured with LOPES, accepted by A&A on 17/06/200

Advances in the Management of Spinal Metastases: What the Radiologist Needs to Know

Spine is the most frequently involved site of osseous metastases. With improved disease-specific survival in patients with Stage IV cancer, durability of local disease control has become an important goal for treatment of spinal metastases. Herein, we review the multidisciplinary management of spine metastases, including conventional external beam radiation therapy, spine stereotactic radiosurgery, and minimally invasive and open surgical treatment options. We also present a simplified framework for management of spinal metastases used at The University of Texas MD Anderson Cancer Center, focusing on the important decision points where the radiologist can contribute