Pulse dilation gas Cherenkov detector for ultra-fast gamma reaction history at the NIF (invited).

The Cherenkov mechanism used in Gas Cherenkov Detectors (GCDs) is exceptionally fast. However, the temporal resolution of GCDs, such as the Gamma Reaction History diagnostic at the National Ignition Facility (NIF), has been limited by the current state-of-the-art photomultiplier tube technology to ∼100 ps. The soon-to-be deployed Pulse Dilation Photomultiplier Tube (PD-PMT) at NIF will allow for temporal resolution comparable to that of the gas cell or ∼10 ps. Enhanced resolution will contribute to the quest for ignition in a crucial way through precision measurements of reaction history and ablator areal density (ρR) history, leading to better constrained models. Features such as onset of alpha heating, shock reverberations, and burn truncation due to dynamically evolving failure modes may become visible for the first time. Test measurements of the PD-PMT at Atomic Weapons Establishment confirmed that design goals have been met. The PD-PMT provides dilation factors of 2 to 40× in 6 increments. The GCD-3 recently deployed at the NIF has been modified for coupling to a PD-PMT and will soon be making ultrafast measurements.

Characterisation of a sub-20 ps temporal resolution pulse dilation photomultiplier tube.

A pulse-dilation photomultiplier tube (PD-PMT) with sub-20 ps temporal resolution has been developed for use with γ-ray-sensitive gas Cherenkov detectors at the National Ignition Facility to improve the diagnosis of nuclear fusion burn history and the areal density of the remaining capsule ablator. The pulse-dilation mechanism entails the application of a time-dependent, ramp waveform to a photocathode-mesh structure, introducing a time-dependent photoelectron accelerating potential. The electric field imparts axial velocity dispersion to outgoing photoelectrons. The photoelectron pulse is dilated as it transits a drift region prior to amplification in a microchannel plate and read out with a digital oscilloscope. We report the first measurements with the prototype PD-PMT demonstrating nominal <20 ps FWHM across a 400 ps measurement window and <30 ps FWHM for an extracted charge up to 300 pC. The output peak areas are linear to within 20% over 3 orders of magnitude of input intensity. 3D particle in cell simulations, which included space charge effects, have been carried out to investigate the device temporal magnification, resolution, and linearity.

Calibration of X-ray spectrometers for opacity experiments at the Orion laser facility (invited).

Accurately calibrated and characterised x-ray diagnostics are a key requirement in the fielding of experiments on the Orion laser where absolute measurements of x-ray emission are used to underpin the validity of models of emissivity and opacity. Diffraction crystals are used in spectrometers on Orion to record the dispersed spectral features emitted by the laser produced plasma to obtain a measurement of the plasma conditions. The ability to undertake diffraction crystal calibrations supports the successful outcome of these Orion experiments. This paper details the design and commissioning of a system to undertake these calibrations in the energy range 2.0 keV to approximately 8.5 keV. Improvements to the design are detailed which will extend the commissioned range of energies to below 1 keV.

Improving the off-axis spatial resolution and dynamic range of the NIF X-ray streak cameras (invited).

We report simulations and experiments that demonstrate an increase in spatial resolution of the NIF core diagnostic x-ray streak cameras by at least a factor of two, especially off axis. A design was achieved by using a corrector electron optic to flatten the field curvature at the detector plane and corroborated by measurement. In addition, particle in cell simulations were performed to identify the regions in the streak camera that contribute the most to space charge blurring. These simulations provide a tool for convolving synthetic pre-shot spectra with the instrument function so signal levels can be set to maximize dynamic range for the relevant part of the streak record.

ORION laser target diagnostics.

The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics.

Evaluation of the sensitivity and fading characteristics of an image plate system for x-ray diagnostics.

Image plates (IPs) are a reusable recording media capable of detecting ionizing radiation, used to diagnose x-ray emission from laser-plasma experiments. Due to their superior performance characteristics in x-ray applications [C. C. Bradford, W. W. Peppler, and J. T. Dobbins III, Med. Phys. 26, 27 (1999) and J. Digit. Imaging. 12, 54 (1999)], the Fuji Biological Analysis System (BAS) IPs are fielded on x-ray diagnostics for the HELEN laser by the Plasma Physics Department at AWE. The sensitivities of the Fuji BAS IPs have been absolutely calibrated for absolute measurements of x-ray intensity in the energy range of 0-100 keV. In addition, the Fuji BAS IP fading as a function of time was investigated. We report on the characterization of three Fuji BAS IP responses to x-rays using a radioactive source, and discrete x-ray line energies generated by the Excalibur soft x-ray facility and the Defense Radiological Standards Centre filter-fluorescer hard x-ray system at AWE.

Lack of gender differences and large intrasubject variability in cytochrome P450 activity measured by phenotyping with dextromethorphan.

Gender-based differences in cytochrome P450 (CYP) activity may occur due to endogenous hormonal fluctuations with the menstrual cycle, which are altered by oral contraceptives. This study assessed the average activity and within-subject variability in CYP3A4 and CYP2D6 in men, women taking Triphasil, and regularly menstruating women not receiving oral contraceptives. Thirty-three healthy volunteers participated in this 28-day pilot study (12 women receiving Triphasil) (OCs), 11 regularly menstruating women not on exogenous progesterone or estrogen (no OCs), and 10 men. CYP3A4 and CYP2D6 activities were phenotyped with dextromethorphan (DM) on study days 7, 14, 21, and 28 using urinary ratios of DM:3-methoxymorphinan (3MM) and DM:dextrorphan (DX), respectively. Serial blood concentrations of estrogen and progesterone and menstrual diaries were used to determine menstrual phase in both groups of women. Average urinary DM:3MM and DM:DX in the 28 extensive metabolizers of CYP2D6 did not differ between the three study populations (p = 0.86 and 0.93, respectively). Post hoc power analysis indicated that more than 1000 subjects would be needed for 80% power (alpha = 0.05) to detect a +/- 15% difference from the population mean in the urinary ratios of dextromethorphan and its metabolites 3MM and DX. Variability in CYP3A4 and CYP2D6 activity, characterized by intrasubject standard deviation, also did not differ. The varying doses of levonorgesterol and ethinyl estradiol in Triphasil, fluctuations in estrogen and progesterone, and menstrual phase did not influence CYP3A4 or CYP2D6 activity. It was concluded that CYP3A4 and CYP2D6 activity and intrasubject variability were not different in the three study populations, and thus a clinically important difference between men, women on Triphasil, and women not receiving oral contraceptives is unlikely. High inter- and intrasubject variability in DM:3MM and DM:DX were clearly demonstrated and limit the use of dextromethorphan to phenotype endogenous CYP3A4 and CYP2D6 activity.

Treating mammalian bite wounds.

The incidence of dog, cat and human bites has been increasing steadily and represents an important cause of morbidity and mortality in the United States. Approximately half of all Americans will suffer a bite wound during their lifetime, and the annual medical costs of managing these injuries has been estimated to be over $100 million. Possible complications may include disfigurement, dismemberment and infection. Effective management requires rapid medical evaluation and may necessitate surgical intervention and prophylactic antibiotic therapy. As bite wounds are microbiologically diverse and most often polymicrobial in nature, selection of an appropriate antibiotic regimen requires knowledge of common pathogens. Close clinical follow-up is recommended to minimize the risk of late complications.

The effects of fluvastatin, a CYP2C9 inhibitor, on losartan pharmacokinetics in healthy volunteers.

Losartan is an angiotensin II receptor antagonist that is metabolized by CYP2C9 and CYP3A4 to a more potent antihypertensive metabolite, E3174. Interaction studies with inhibitors of CYP3A4 have not demonstrated significant changes in the pharmacokinetics of losartan or E3174. The authors assessed the steady-state pharmacokinetics of losartan and E3174 when administered alone and concomitantly with fluvastatin, a specific CYP2C9 inhibitor. A prospective, open-label, crossover study was conducted in 12 healthy volunteers with losartan alone and in combination with fluvastatin. The baseline phase was 7 days of losartan (50 mg QAM), and the inhibition phase was 14 total days of fluvastatin (40 mg QHS), with the final 7 days including losartan. The authors found that fluvastatin did not significantly change the steady-state AUC0-24 or half-life of losartan or E3174. Losartan apparent oral clearance was not affected by fluvastatin. Inhibition of losartan metabolism appears to require both CYP2C9 and CYP3A4 inhibition.

Cost of managing anemia with and without prophylactic epoetin alfa therapy in breast cancer patients receiving combination chemotherapy.

The cost of managing anemia with prophylactic epoetin alfa therapy versus blood transfusions in breast cancer patients receiving combination chemotherapy was studied. A retrospective study of anemia in breast cancer patients treated with four cycles of cyclophosphamide and doxorubicin with fluorouracil (CAF) or without fluorouracil (CA) was conducted. For each cycle of chemotherapy, patients were assessed for fatigue, subsequent blood transfusions administered, and potential response to and adverse effects of blood transfusions. Transfusions were given at the prescriber's discretion rather than in accordance with standard guidelines. The lowest hemoglobin concentration and hematocrit of each patient per cycle were reported. Data on these patients, along with data from published studies of prophylactic use of epoetin alfa, were used in a decision analysis of the costs associated with using epoetin alfa versus red blood cell transfusions to manage anemia. The charts of 50 patients were reviewed. In the study group, the percentage of patients with anemia and the frequency of fatigue rose with each chemotherapy cycle. In general, blood transfusions were not used. The cost of using epoetin alfa prophylactically for all four cycles was estimated at $6483 per patient for the literature-based group versus $169 for the study group. The cost of managing anemia in breast cancer patients was substantially lower when blood transfusions were used than when epoetin alfa was given prophylactically throughout four cycles of therapy with CAF or CA; the absence of standard guidelines for transfusion might have exaggerated the difference in costs.

Clostridium difficile toxin-induced colitis after use of clindamycin phosphate vaginal cream.

OBJECTIVE: To report a case of toxin-positive Clostridium difficile-induced colitis (CDIC) after use of clindamycin phosphate vaginal cream. CASE SUMMARY: A 25-year-old postpartum white woman developed multiple watery stools and abdominal cramping on day 6 of therapy with clindamycin vaginal cream for bacterial vaginosis. She received no other concomitant medications. The patient's stool sample was found to be positive for the C. difficile toxin. Due to the costs and risks of standard therapy, we decided to manage the patient supportively. Complete resolution of the diarrhea occurred shortly thereafter. DISCUSSION: No published clinical studies in patients receiving clindamycin vaginal cream for bacterial vaginosis have documented C. difficile toxin in stool samples of patients with diarrhea. Approximately 5-6% of intravaginal clindamycin is absorbed in the bloodstream, making systemic effects possible. CONCLUSIONS: This report indicates clindamycin phosphate vaginal cream as the most probable cause of CDIC due to the temporal relationship between the occurrence of diarrhea and clindamycin administration, lack of concomitant medications, and documentation of C. difficile toxin.