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BACKGROUND Variable chemotherapy exposure may cause toxicity or lack of efficacy. This study was initiated to validate pharmacokinetically (PK)-guided paclitaxel dosing in patients with advanced non-small-cell lung cancer (NSCLC) to avoid supra- or subtherapeutic exposure. PATIENTS AND METHODS Patients with newly diagnosed, advanced NSCLC were randomly assigned to receive up to 6 cycles of 3-weekly carboplatin AUC 6 or cisplatin 80 mg/m(2) either with standard paclitaxel at 200 mg/m(2) (arm A) or PK-guided dosing of paclitaxel (arm B). In arm B, initial paclitaxel dose was adjusted to body surface area, age, sex, and subsequent doses were guided by neutropenia and previous-cycle paclitaxel exposure [time above a plasma concentration of 0.05 µM (Tc>0.05)] determined from a single blood sample on day 2. The primary end point was grade 4 neutropenia; secondary end points included neuropathy, radiological response, progression-free survival (PFS) and overall survival (OS). RESULTS Among 365 patients randomly assigned, grade 4 neutropenia was similar in both arms (19% versus 16%; P = 0.10). Neuropathy grade ≥2 (38% versus 23%, P < 0.001) and grade ≥3 (9% versus 2%, P < 0.001) was significantly lower in arm B, independent of the platinum drug used. The median final paclitaxel dose was significantly lower in arm B (199 versus 150 mg/m(2), P < 0.001). Response rate was similar in arms A and B (31% versus 27%, P = 0.405), as was adjusted median PFS [5.5 versus 4.9 months, hazard ratio (HR) 1.16, 95% confidence interval (CI) 0.91-1.49, P = 0.228] and OS (10.1 versus 9.5 months, HR 1.05, 95% CI 0.81-1.37, P = 0.682). CONCLUSION PK-guided dosing of paclitaxel does not improve severe neutropenia, but reduces paclitaxel-associated neuropathy and thereby improves the benefit-risk profile in patients with advanced NSCLC. CLINICAL TRIAL INFORMATION NCT01326767 (https://clinicaltrials.gov/ct2/show/NCT01326767).

A fast neutron coincidence counter using BC454/BGO phoswich detectors has been evaluated for the purpose of rapid verification measurements of uranium items. This counter uses custom electronics to identify and count coincidence neutrons in the presence of background radiation. Measurements of uranium standards were performed to evaluate the counter. This counter is successful in measuring uranium items but has a low efficiency that results in minimal improvement over current technology. An optimized counter can be built with better performance capabilities, but it is recommended that newer technologies be used instead.

There has been a recent rapid increase in interest in the measurement of soft X-ray magnetic scattering (SoXMaS) to characterize the distribution of magnetic moments in thin films and multilayers. The Daresbury Laboratory team has adapted a high-vacuum two-circle diffractometer for pioneering measurements in this field. The principal features of the diffractometer and the alignment procedure for SoXMaS measurements are presented. A flexible data acquisition system is used, which allows a wide variety of scan modes and control of the various beamlines on which the experiments have been performed.

In order to determine if differences in human muscle EMG response to steady-state (STD) dynamic load and transient (TRN) load could be detected, two distinct sinusoidal loads having identical amplitude and frequency were applied to the forearm, which was held in a fixed posture. The first condition used application of a constant amplitude, constant frequency, STD sinusoid, and the second condition used application of a single sinusoid of identical amplitude and frequency as the STD load. Time-domain parameters of Half-Mass, Dispersion Moments, Asymmetry Moments, Peak Ratio (ratio of cycle peak RMS EMG to cycle mean RMS EMG) and Time-to-Peak Ratio (ratio of cycle time to reach peak RMS EMG to cycle time duration) were used to quantify responses in the time domain. A single frequency-domain parameter, Dispersion Moments, was used to quantify responses in the frequency domain. Individual ANOVA's of the time domain parameter results revealed that p =0.689 for Dispersion Moments, p =0.111 for Half-Mass, p =0.007 for Asymmetry Moments, p =0.001 for Peak Ratio, and p =0.001 for Time-to-Peak Ratio. The time-domain MANOVA and frequency-domain ANOVA revealed that EMG responses resulting from STD and TRN applied loads were statistically different in the time domain ( p =0.001), but not in the frequency domain ( p =0.810). Thus, use of Asymmetry Moments, Peak Ratio, and Time-to-Peak Ratio parameters can distinguish EMG responses to STD and TRN loads.

Neutron detection and multiplicity counting has been investigated using a boron-loaded plastic scintillator (BC454)/bismuth germanate (BGO) phoswich detector array. Boron-loaded plastic combines neutron moderation (H) and detection ({sup 10}B) at the molecular level, thereby physically coupling increasing detection efficiency and decreasing die-away time with detector volume. Separation of the phoswich response into its plastic scintillator and bismuth germanate components was accomplished on an event-by-event basis using custom integrator and timing circuits, enabling a prompt coincidence requirement between the BC454 and BGO to be used to identify neutron captures. In addition, a custom time-tag module was used to provide a time for each detector event. Time-correlation analysis was subsequently performed on the filtered event stream to obtain shift-register-type singles and doubles count rates.

Gamma-ray and neutron spectrometers (GRS and NS, respectively) are included in the payload complement of Lunar Prospector (LP) that is currently orbiting the Moon. Specific objectives of the GRS are to map abundances of O, Si, Fe, Ti, U, Th, K, and perhaps, Mg, Al, and Ca, to depths of about 20 cm. Those of the NS are to search for water ice to depths of about 50 cm near the lunar poles and to map regolith maturity. The designs of both spectrometers are described and their performance in both the laboratory and in lunar orbit are presented.

The results from simulations and laboratory experiments with boron-loaded plastic scintillating fibers as a nondestructive assay (NDA) tool are presented. Single and multi-clad fibers in three diameters of 0.25, 0.5, and 1 mm were examined for their application in neutron coincidence counting. For this application, the simulation results show that various configurations of boron-loaded plastic scintillating fibers have a die-away time (τ) of 12 μs with an efficiency (e) of 50%. For a comparable efficiency, 3He proportional tubes have a typical die-away time of 50 μs. The shortened die-away time can reduce the relative error for measurement of similar samples by up to 50%. Plastic scintillating fibers (PSF) also offer flexible configurations with the potential to discriminate between signals from gamma-ray and neutron events. Quantitative calculations and experiments have been conducted to determine the light output, evaluate the noise, quantify light attenuation, and determine neutron detection efficiency. Current experimental data support the analytical results that boron-loaded plastic fibers can detect thermal neutrons.

Monte Carlo simulations were carried out to simulate the response of a boron-loaded plastic scintillator array. These detectors offer potential advantages compared to moderated 3He systems because of their fast response and high efficiency. Tallies were made of neutron capture probability as a function of time and the results were coupled to assay variance estimates to evaluate detector performance. Orders-of-magnitude reductions in count time relative to a 50% efficient thermal counter are possible, in principle, for high (α,n) samples.

We have designed several neutron detectors for use in measuring neutrons from cold-fusion experiments. The high-efficiency detectors are based on 3He gas tubes in a CH2 moderator. The total efficiency of our most advanced detector for 2.3 MeV (252Cf) neutrons is 44%. The detector consists of two independent segments making up inner and outer rings of 3He tubes. The inner detector has nine 3He tubes and the outer detector has 42 3He tubes. The low-background inner detector has a singles count background of 97 counts/h and a coincidence count background of only 0.7 counts/h. The corresponding singles efficiency is 19%. The inside ring of tubes is undermoderated and it is more sensitive to lower-energy source neutrons. The outside ring of tubes is overmoderated and thus more sensitive to high-energy neutrons. The ratio of the outside tubes to the inside tubes gives the approximate average neutron energy based on differential transmission as a function of energy. Monte Carlo transport calculations have been performed to establish the energy calibration of the outside/inside tube-ring ratio. The time-correlation (coincidence) information is required to investigate neutron pulsing, bursts and other nonrandom emissions caused by nonequilibrium conditions and instabilities in the samples. The time correlations in our detector are obtained by using the shift register-type electronic circuitry. Our detector system has been applied successfully to the measurement of neutron yield and multiplicity distribution from cold-fusion electrolysis samples and D2-gas-type samples.

The crystal structure of cobalt orthophosphate has been refined by full-matrix least-squares procedures using automatic diffractometer data to a residual R = 0.039 (Rw = 0.058). The space group is P2 l c , with a = 5.063(1), b = 8.361(2), c = 8.788(2) A, and β = 121.00(2)°. Co3(PO4)2 is isotypic with the previously reported γ-Zn3(PO4)2 and Mg3(PO4)2. Cobalt ions occupy two distinct coordination polyhedra, one five and one six-coordinated, in a ratio of two to one. The structure is described in detail.

One hundred seventy-eight patients who had radical hysterectomy performed for management of invasive carcinoma of the cervix over 22 year period at the Medical University of South Carolina were critically analyzed. The degree of differentiation of the malignancy appeared to be of more significance than tumor size in Stage 1 lesions. With proper patient selection and excellent operative technique, survival rates well over 90% with minimal complications can be obtained. The radical hysterectomy should never be used in association with irradiation.

The trend in the use of structural analysis programs is towards larger, more integrated user-orientated systems. The main aim of organizing structural analysis systems of programs appears to be to provide users with more versatile tools to reduce the required man-days and computing costs and to increase the scope and potential of the programs. A large modular system is described constituting the most widely used structural analysis packages developed by the CEGB. The principal motivation in developing the system is to rationalize and simplify the considerable diversification of applications and techniques currently available. The applications encompass elastic, thermal, dynamic, creep and plastic analyses of arbitrary two-dimensional and three-dimensional structures. The system uses a standardized form of input for all applications and provides user-aids such as mesh generation, error facilities, output facilities (online and graphical) as integrated system modules. Calculational packages at present integrated into the system comprise FLHE-BERSAFE (thermal and elastic, two and three dimensions), TESS (creep and plasticity, two dimensions), STAG21 (visco-elastic, two dimensions). Various element types and a comprehensive selection of different solution techniques based mainly on finite element displacement model can be used in the analyses. All data presented to the system are in the form of files (datalists) stored on 3330 magnetic disks. A comprehensive permanent disk library containing thermal and mechanical properties of the most commonly used materials is available to all users. The system is designed to be ‘open-ended’ in the sense that new subsystems can be augmented easily. It is envisaged that these additions will include structural analysis applications which are strictly outside the area of finite element analysis, e.g. frameworks. The internal structure and mode of operation of the system are described in detail. Several diverse examples of nuclear design problems which have been studied are given. An examination and comparison with other large structural analysis systems currently available are given, together with a discussion of possible future developments in this field.