Ultra-fast single-crystal CVD diamonds in the particle time-of-flight (PTOF) detector for low yield burn-history measurements on the NIF (invited).

The Particle Time of Flight (PTOF) diagnostic is a chemical vapor deposition diamond-based detector and is the only diagnostic for measuring nuclear bang times of low yield (<1013) shots on the National Ignition Facility. Recently, a comprehensive study of detector impulse responses revealed certain detectors with very fast and consistent impulse responses with a rise time of <50 ps, enabling low yield burn history measurements. At the current standoff of 50 cm, this measurement is possible with fast 14 MeV neutrons from deuterium-tritium (DT) fusion plasmas.

Neutron-induced backgrounds in coaxial cables on the South Pole neutron time-of-flight detector at the National Ignition Facility.

As neutron yields increase at fusion facilities, a universal symptom the community must deal with is MeV neutron-induced backgrounds in cables running to diagnostics. On the first Gain >1 plasmas in the world, the National Ignition Facility (NIF) neutron time-of-flight (nToF) diagnostic registered significant cable backgrounds that compromised key performance measurements. The South Pole nToF is uniquely located inside the NIF Target Bay shield walls, ∼18 m from the fusion source, and consequently has long coaxial cable runs (>20 m) that see significant neutron fluence.

Ibrutinib in Early-Stage Chronic Lymphocytic Leukemia: The Randomized, Placebo-Controlled, Double-Blind, Phase III CLL12 Trial.

Purpose: The CLL12 trial reassesses the watch-and-wait consensus for early-stage chronic lymphocytic leukemia (CLL) in the context of targeted therapies.

Methods: The German CLL Study Group conducted a randomized, double-blind, placebo-controlled phase III trial with 363 patients with asymptomatic, treatment-naïve Binet stage A CLL at increased risk of progression to receive ibrutinib (n = 182) at a daily dose of 420 mg or placebo (n = 181). Additionally, 152 low-risk patients were allocated to the watch-and-wait group.

Simultaneous analysis of collinear neutron time-of-flight (nToF) traces applied to pulsed fusion experiment.

On pulsed fusion experiments, the neutron time of flight (nToF) diagnostic provides critical information on the fusion neutron energy spectrum. This work presents an analysis technique that uses two collinear nToF detectors, potentially to measure nuclear bang time and directional flow velocities. Two collinear detectors may be sufficient to disambiguate the contributions of nuclear bang time and directional flow velocities to the first moment of the neutron energy spectrum, providing an independent measurement of nuclear bang time.

Neutron time of flight (nToF) detectors for inertial fusion experiments.

Neutrons generated in Inertial Confinement Fusion (ICF) experiments provide valuable information to interpret the conditions reached in the plasma. The neutron time-of-flight (nToF) technique is well suited for measuring the neutron energy spectrum due to the short time (100 ps) over which neutrons are typically emitted in ICF experiments. By locating detectors 10s of meters from the source, the neutron energy spectrum can be measured to high precision.

Constraining time-dependent ion temperature measurements in inertial confinement fusion (ICF) implosions with an intermediate distance neutron time-of-flight (nToF) detector.

A concept for using an intermediate distance (0.3-3.0 m) neutron time-of-flight (nToF) to provide a constraint on the measurement of the time-dependence of ion temperature in inertial confinement fusion implosions is presented.

Construction and study of instrument response functions for analysis of the National Ignition Facility (NIF) neutron time-of-flight detectors.

The analysis of the National Ignition Facility (NIF) neutron time-of-flight (nToF) detectors uses a forward-fit routine that depends critically on the instrument response functions (IRFs) of the diagnostics. The details of the IRFs used can have large impacts on measurements such as ion temperature and down-scattered ratio (DSR). Here, we report on the recent steps taken to construct and validate nToF IRFs at the NIF to an increased degree of accuracy, as well as remove the need for fixed DSR baseline offsets.

Design of a multi-detector, single line-of-sight, time-of-flight system to measure time-resolved neutron energy spectra.

In the dynamic environment of burning, thermonuclear deuterium-tritium plasmas, diagnosing the time-resolved neutron energy spectrum is of critical importance. Strategies exist for this diagnosis in magnetic confinement fusion plasmas, which presently have a lifetime of ∼10 longer than inertial confinement fusion (ICF) plasmas. Here, we present a novel concept for a simple, precise, and scale-able diagnostic to measure time-resolved neutron spectra in ICF plasmas.

The CLL12 trial: ibrutinib vs placebo in treatment-naïve, early-stage chronic lymphocytic leukemia.

Observation is the current standard of care for patients with early-stage asymptomatic chronic lymphocytic leukemia (CLL), as chemotherapy-based interventions have failed to prolong survival. We hypothesized that early intervention with ibrutinib would be well tolerated and lead to superior disease control in a subgroup of early-stage patients with CLL. The phase 3, double-blind, placebo-controlled CLL12 trial randomly assigned asymptomatic, treatment-naïve Binet stage A CLL patients at increased risk of progression in a 1:1 ratio to receive ibrutinib (n = 182) or placebo (n = 181) at a dose of 420 mg daily.

Observation of Hydrodynamic Flows in Imploding Fusion Plasmas on the National Ignition Facility.

Inertial confinement fusion implosions designed to have minimal fluid motion at peak compression often show significant linear flows in the laboratory, attributable per simulations to percent-level imbalances in the laser drive illumination symmetry. We present experimental results which intentionally varied the mode 1 drive imbalance by up to 4% to test hydrodynamic predictions of flows and the resultant imploded core asymmetries and performance, as measured by a combination of DT neutron spectroscopy and high-resolution x-ray core imaging. Neutron yields decrease by up to 50%, and anisotropic neutron Doppler broadening increases by 20%, in agreement with simulations.

Interpolating individual line-of-sight neutron spectrometer measurements onto the "sky" at the National Ignition Facility (NIF).

Nuclear diagnostics provide measurements of inertial confinement fusion implosions used as metrics of performance for the shot. The interpretation of these measurements for shots with low mode asymmetries requires a way of combining the data to produce a "sky map" where the individual line-of-sight values are used to interpolate to other positions in the sky. These interpolations can provide information regarding the orientation of the low mode asymmetries.

Three-dimensional diagnostics and measurements of inertial confinement fusion plasmas.

Recent inertial confinement fusion measurements have highlighted the importance of 3D asymmetry effects on implosion performance. One prominent example is the bulk drift velocity of the deuterium-tritium plasma undergoing fusion ("hotspot"), v. Upgrades to the National Ignition Facility neutron time-of-flight diagnostics now provide v to better than 1 part in 10 and enable cross correlations with other measurements.

The Randomized AMBORA Trial: Impact of Pharmacological/Pharmaceutical Care on Medication Safety and Patient-Reported Outcomes During Treatment With New Oral Anticancer Agents.

Purpose: Oral anticancer drugs (eg, kinase inhibitors) play an important role in cancer therapy. However, considerable challenges regarding medication safety of oral anticancer drugs have been reported. Randomized, controlled, multicenter studies on the impact of intensified clinical pharmacological/pharmaceutical care on patient safety and patient treatment perception are lacking.

Optimal choice of multiple line-of-sight measurements determining plasma hotspot velocity at the National Ignition Facility.

The measurement of plasma hotspot velocity provides an important diagnostic of implosion performance for inertial confinement fusion experiments at the National Ignition Facility. The shift of the fusion product neutron mean kinetic energy as measured along multiple line-of-sight time-of-flight spectrometers provides velocity vector components from which the hotspot velocity is inferred. Multiple measurements improve the hotspot velocity inference; however, practical considerations of available space, operational overhead, and instrumentation costs limit the number of possible line-of-sight measurements.

Prognostic model for newly diagnosed CLL patients in Binet stage A: results of the multicenter, prospective CLL1 trial of the German CLL study group.

The heterogeneity of early stage CLL challenges prognostication, and refinement of prognostic indices for risk-adapted management in this population is essential. The aim of the multicenter, prospective CLL1 trial was to explore a novel prognostic model (CLL1-PM) developed to identify risk groups, separating patients with favorable from others with dismal prognosis. A cohort of 539 clinically, biochemically, and genetically characterized Binet stage A patients were observed until progression, first-line treatment, or death.

Neutron Time-of-Flight Measurements of Charged-Particle Energy Loss in Inertial Confinement Fusion Plasmas.

Neutron spectra from secondary ^{3}H(d,n)α reactions produced by an implosion of a deuterium-gas capsule at the National Ignition Facility have been measured with order-of-magnitude improvements in statistics and resolution over past experiments. These new data and their sensitivity to the energy loss of fast tritons emitted from thermal ^{2}H(d,p)^{3}H reactions enable the first statistically significant investigation of charged-particle stopping via the emitted neutron spectrum. Radiation-hydrodynamic simulations, constrained to match a number of observables from the implosion, were used to predict the neutron spectra while employing two different energy loss models.

Imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the German Chronic Myeloid Leukemia-Study IV.

Standard first-line therapy of chronic myeloid leukemia is treatment with imatinib. In the randomized German Chronic Myeloid Leukemia-Study IV, more potent BCR-ABL inhibition with 800 mg ('high-dose') imatinib accelerated achievement of a deep molecular remission. However, whether and when a de-escalation of the dose intensity under high-dose imatinib can be safely performed without increasing the risk of losing deep molecular response is unknown.

Uncertainty analysis of response functions and -backgrounds on T and t measurements from Cherenkov neutron detectors at the National Ignition Facility (NIF).

Cherenkov radiators deployed to measure the neutron time-of-flight spectrum have response times associated with the neutron transit across the detector and are free from long time response tails characteristic of scintillation detectors. The Cherenkov radiation results from simple physical processes which makes them amenable to high fidelity Monte Carlo simulation. The instrument response function of neutron time-of-flight systems is a major contributor to both the systematic and statistical uncertainties of the parameters used to describe these spectra; in particular, the first and second moments of these distributions are associated with arrival time, t, and ion temperature, T.

Characterization of photodetector temporal response for neutron time-of-flight (nToF) diagnostics at the National Ignition Facility.

The temporal response of a microchannel plate photomultiplier tube used in the suite of neutron time of flight (nToF) diagnostics at the National Ignition Facility has been characterized to reduce uncertainty in, and understanding of, shot parameters obtained from nTOF data. A short pulse laser, neutral density glass filters, and electrical attenuators were used to gather statistically significant samples of photodetector impulse response functions (IRF) in rapid succession. Individual components have been absolutely calibrated to minimize systematic uncertainties.

Testing a Cherenkov neutron time-of-flight detector on OMEGA.

A Cherenkov neutron time-of-flight (nTOF) detector developed and constructed at Lawrence Livermore National Laboratory was tested at 13 m from the target in a collimated line of sight (LOS) and at 5.3 m from the target in the open space inside the OMEGA Target Bay. Neutrons interacting with the quartz rod generate gammas, which through Compton scattering produce relativistic electrons that give rise to Cherenkov light.

A fused silica Cherenkov radiator for high precision time-of-flight measurement of DT and neutron spectra (invited).

A fused silica Cherenkov radiator has been implemented at the National Ignition Facility to provide a new high precision measurement of the time-of-flight spectrum of 14.1 MeV DT fusion neutrons. This detector enables a high precision (<30 ps) co-registered measurement of both a thresholded -ray and a neutron spectrum on a single record.

response functions for Cherenkov-based neutron detectors.

Neutron time-of-flight diagnostics at the NIF were recently outfitted with Cherenkov detectors. A fused silica radiator delivers sub-nanosecond response time and is optically coupled to a microchannel plate photomultiplier tube with gain from ∼1 to 10. Capitalizing on fast time response and gamma-ray sensitivity, these systems can provide better than 30 ps precision for measuring first moments of neutron distributions.

Using multiple neutron time of flight detectors to determine the hot spot velocity.

An important diagnostic value of a shot at the National Ignition Facility is the resultant center-of-mass motion of the imploding capsule. This residual velocity reduces the efficiency of converting laser energy into plasma temperature. A new analysis method extracts the effective hot spot motion by using information from multiple neutron time-of-flight (nToF) lines-of-sight (LoSs).

Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants.

Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years.