Development of improved higher-order correction for the NIF opacity spectrometer.

X-ray opacity measurements on the National Ignition Facility (NIF) are in the process of reproducing earlier measurements from the Sandia Z Facility, in particular for oxygen and iron plasmas. These measurements have the potential to revise our understanding of the "solar problem" and of the hot degenerate Q class white dwarf structure by probing plasma conditions near the base of their convection zones. Accurate opacity measurements using soft x-ray Bragg crystal spectrometers require correction for higher-order diffraction effects. Extending prior work in this area [Dutra et al., Review of Scientific Instruments 93, 113527 (2022)], we have developed a new method to remove higher-order spectral components from NIF opacity spectrometer data. By modeling absorption and backlighting continuum spectra and subtracting the second- and third-order components from the measured data, we are able to perform this correction while avoiding imprinting first-order model line features onto the data.

Design and characterization of the time-resolved opacity spectrometer (OpSpecTR) for the NIF iron opacity campaign.

A new time-resolved opacity spectrometer (OpSpecTR) is currently under development for the National Ignition Facility (NIF) opacity campaign. The spectrometer utilizes Icarus version 2 (IV2) hybridized complementary metal-oxide-semiconductor sensors to collect gated data at the time of the opacity transmission signal, unlocking the ability to collect higher-temperature measurements on NIF. Experimental conditions to achieve higher temperatures are feasible; however, backgrounds will dominate the data collected by the current time-integrating opacity spectrometer. The shortest available OpSpecTR integration time of ∼2 ns is predicted to reduce self-emission and other late-time backgrounds by up to 80%. Initially, three Icarus sensors will be used to collect data in the self-emission, backlighter, and absorption regions of the transmission spectrum, with plans to upgrade to five Daedalus sensors in future implementations with integration times of ∼1.3 ns. We present the details of the diagnostic design along with recent characterization results of the IV2 sensors.

2nd and 3rd order spectral energy corrections with penumbral de-blurring methodology for opacity platform used on the National Ignition Facility.

The Opacity Spectrometer (OpSpec) used in the National Ignition Facility's opacity experiments measures x-ray spectra from 0.9 to 2.1 keV from the different experimental regions: the backlight source, emission source, and the absorption region with the transmission calculated from these regions. The OpSpec designs have gone through several iterations to help improve the signal-to-noise ratio, remove alternate crystal plane reflections, and improve spectral resolution, which helps to increase the validity of the opacity measurements. However, the source spans well outside the current working spectral range, and higher-order reflections are intrinsic to the crystal, which increases the overall signal seen in the data regions. The recorded data are the convolution of 1st order transmission, higher-order reflections, and the penumbra blurring. This work represents the details for deconvolving the 2nd and 3rd order spectral energy corrections with a penumbral de-blurring to correct the relative measurement of x-ray intensity of different spectral energies and further analysis of datasets relevant to the opacity experiments.

Sub-keV design for the National Ignition Facility's soft x-ray Opacity Spectrometer (OpSpec) and expansion plans for time-resolved measurements.

When compared with the National Ignition Facility's (NIF) original soft x-ray opacity spectrometer, which used a convex cylindrical design, an elliptically shaped design has helped to increase the signal-to-noise ratio and eliminated nearly all reflections from alternate crystal planes. The success of the elliptical geometry in the opacity experiments has driven a new elliptical geometry crystal with a spectral range covering 520-1100 eV. When coupled with the primary elliptical geometry, which spans 1000-2100 eV, the new sub-keV elliptical geometry helps to cover the full iron L-shell and major oxygen transitions important to solar opacity experimentation. The new design has been built and tested by using a Henke x-ray source and shows the desired spectral coverage. Additional plans are underway to expand these opacity measurements into a mode of time-resolved detection, ∼1 ns gated, but considerations for the detector size and photometrics mean a crystal geometry redesign. The new low-energy geometry, including preliminary results from the NIF opacity experiments, is presented along with the expansion plans into a time-resolved platform.

Ground-state proton decay of 69Br and implications for the 68Se astrophysical rapid proton-capture process waiting point.

We report on the first direct measurement of the proton separation energy for the proton-unbound nucleus (69)Br. Bypassing the (68)Se waiting point in the rp process is directly related to the 2p-capture rate through (69)Br, which depends exponentially on the proton separation energy. We find a proton separation energy for (69)Br of Sp((69)Br )= -785(-40)(+34) keV; this is less bound compared to previous predictions which have relied on uncertain theoretical calculations. The influence of the extracted proton separation energy on the rp process occurring in type I x-ray bursts is examined within the context of a one-zone burst model.

Polarization splitting with cubic crystals evaluated with synchrotron radiation.

X-ray polarization-splitting crystals separate incident x rays into two components with perpendicular polarization by Bragg reflections at 45° from paired sets of internal planes. Here, the polarization-splitting properties of a germanium crystal are verified using incompletely polarized synchrotron radiation. Cleaner data would have come from a beam with a higher degree of polarization, which is achievable with small changes in the experimental geometry.

Extension of single-crystal x-ray spectropolarimetry with cubic crystals beyond perfect polarization-splitting geometries.

The single-crystal spectropolarimeter envisioned by Baronova and Stepanenko splits an incident x-ray beam into two beams with mutually orthogonal linear polarizations by using simultaneous reflections at the perfectly polarizing 45° Bragg angle on certain pairs of internal planes in hexagonal or cubic crystals. These planes intersect along a threefold symmetry axis, making a 120° angle with each other, and are typically symmetric with respect to the crystal surface. In practice, the wavelength of the diagnostic x-ray lines does not exactly satisfy Bragg's law for the crystal in the ideal polarizing orientation, so the extinction of reflections is incomplete. Accepting this limitation, this paper shows that for cubic crystals, other pairs of internal planes exist that satisfy the polarization requirements approximately. Typically, they are accessible from the perfect polarization-splitting geometry by small rotations of the crystal. This paper includes examples of such planes for cubic crystals with {110} and {211} surface cuts.

Characterization of Agfa Structurix series D4 and D3sc x-ray films in the 0.7-4.6 keV energy range.

X-ray films remain a key asset for high-resolution x-ray spectral imaging in high-energy-density experiments conducted at the National Ignition Facility (NIF). The soft x-ray Opacity Spectrometer (OpSpec) fielded at the NIF has an elliptically shaped crystal design that measures x rays in the 900-2100 eV range and currently uses an image plate as the detecting medium. However, Agfa D4 and D3sc x-ray films' higher spatial resolution provides increased spectral resolution to the data over the IP-TR image plates, driving the desire for regular use of x-ray film as a detecting medium. The calibration of Agfa D4 x-ray film for use in the OpSpec is communicated here. These calibration efforts are vital to the accuracy of the NIF opacity measurements and are conducted in a previously un-studied x-ray energy range under a new film development protocol required by NIF. The absolute response of Agfa D4 x-ray film from 705 to 4620 eV has been measured using the Nevada National Security Site Manson x-ray source. A broader range of energies was selected to compare results with previously published data. The measurements were taken using selected anodes, filters, and applied voltages to produce well-defined energy lines.

Upgrades and redesign of the National Ignition Facility's soft x-ray opacity spectrometer (OpSpec).

The soft x-ray Opacity Spectrometer (OpSpec) used on the National Ignition Facility (NIF) has recently incorporated an elliptically shaped crystal. The original OpSpec used two convex cylindrical crystals for time-integrated measurements of point-projection spectra from 540 to 2100 eV. However, with the convex geometry, the low-energy portion of the spectrum suffered from high backgrounds due to scattered x-rays as well as reflections from alternate crystal planes. An elliptically shaped crystal allows an acceptance aperture at the crossover focus between the crystal and the detector, which reduces background and eliminates nearly all reflections from alternate crystal planes. The current elliptical design is an improvement from the convex cylindrical design but has a usable energy range from 900 to 2100 eV. In addition, OpSpec is currently used on 18 NIF shots/year, in which both crystals are typically damaged beyond reuse, so efficient production of 36 crystals/year is required. Design efforts to improve the existing system focus on mounting reliability, reducing crystal strain to increase survivability between mounting and shot time, and extending the energy range of the instrument down to 520 eV. The elliptical design, results, and future options are presented.

Cubic crystals in an x-ray polarization-splitting geometry.

Hexagonal and cubic crystals contain paired sets of internal planes that reflect the linearly polarized components of certain x rays into two separate, perpendicular directions. For the cubic crystals, two distinct crystal orientations provide the same polarization-splitting geometry. One of the orientations may have advantages for plasma spectroscopy by suppressing unwanted reflections. This paper demonstrates the two orientations with a germanium crystal and K characteristic lines from copper and zirconium.

Spatially resolved single crystal x-ray spectropolarimetry of wire array z-pinch plasmas.

A recently developed single-crystal x-ray spectropolarimeter has been used to record paired sets of polarization-dependent and axially resolved x-ray spectra emitted by wire array z-pinches. In this measurement, two internal planes inside a suitable crystal diffract the x-rays into two perpendicular directions that are normal to each other, thereby separating incident x-rays into their linearly polarized components. This paper gives considerations for fielding the instrument on extended sources. Results from extended sources are difficult to interpret because generally the incident x-rays are not separated properly by the crystal. This difficulty is mitigated by using a series of collimating slits to select incident x-rays that propagate in a plane of symmetry between the polarization-splitting planes. The resulting instrument and some of the spatially resolved polarized x-ray spectra recorded for a 1-MA aluminum wire array z-pinch at the Nevada Terawatt Facility at the University of Nevada, Reno will be presented.

Ambrosia beetle (Coleoptera: Scolytidae) species, flight, and attack on living eastern cottonwood trees.

In spring 2002, ambrosia beetles (Coleoptera: Scolytidae) infested an intensively managed 22-ha tree plantation on the upper coastal plain of South Carolina. Nearly 3,500 scolytids representing 28 species were captured in ethanol-baited traps from 18 June 2002 to 18 April 2004. More than 88% of total captures were exotic species. Five species [Dryoxylon onoharaensum (Murayama), Euwallacea validus (Eichhoff), Pseudopityophthorus minutissimus (Zimmermann), Xyleborus atratus Eichhoff, and Xyleborus impressus Eichhoff]) were collected in South Carolina for the first time. Of four tree species in the plantation, eastern cottonwood, Populus deltoides Bartram, was the only one attacked, with nearly 40% of the trees sustaining ambrosia beetle damage. Clone ST66 sustained more damage than clone S7C15. ST66 trees receiving fertilization were attacked more frequently than trees receiving irrigation, irrigation + fertilization, or controls, although the number of S7C15 trees attacked did not differ among treatments. The study location is near major shipping ports; our results demonstrate the necessity for intensive monitoring programs to determine the arrival, spread, ecology, and impact of exotic scolytids.

A randomized, double-blind, placebo-controlled trial of a glycine antagonist in neuropathic pain.

BACKGROUND: Nerve injury results in increases in spinal glutamate, which opens the NMDA ionophore channel, causing an influx of calcium. A glycine-binding site must be occupied for the channel to open. GV196771 is a selective antagonist of the glycine-binding site of the NMDA ionophore. OBJECTIVE: To determine the efficacy of GV196771 in subjects with chronic neuropathic pain in a proof-of-concept study. METHODS: With informed consent, 63 subjects (31 placebo, 32 GV196771) with neuropathic pain (diabetic neuropathy, postherpetic neuralgia, complex regional pain syndrome, or peripheral nerve injury), a visual analogue score averaging > or =30 mm during the screening period, and a well-defined primary area of mechanical allodynia were recruited for the study. A multicenter, randomized, double-blind, placebo-controlled, parallel-group study design was utilized. Subjects came to the research center for a total of five visits over a 21-day period, which consisted of a 14-day treatment period followed by a 7-day washout period. Spontaneous and evoked pain scores, mechanical sensory testing, quantitative sensory testing, Short Form McGill Pain Questionnaire, patient global satisfaction, and safety assessments were made during the study. RESULTS: There was no significant effect of GV196771 on spontaneous or evoked pain, quantitative sensory testing, or patient global satisfaction. There was a significant effect of GV196771 on the area of dynamic and static allodynia on days 7 and 14. The overall incidence of adverse events during treatment was similar for GV196771 (56%) and placebo (71%). The incidence of drug-related adverse events during treatment was higher for placebo (42%) than GV196771 (28%). CONCLUSIONS: Although the glycine antagonists show anti-hyperalgesic action in animal models of neuropathic pain, GV196771 does not appear to be an effective treatment in subjects with chronic neuropathic pain. This may be due to insufficient penetration of GV196771 to central sites of action, differences between the human and animal glycine receptors, or differences between neuropathic pain in animal models and humans.

Pain after breast surgery: a survey of 282 women.

Breast surgery is a common procedure performed in women. Many women who undergo breast surgery suffer from ill-defined pain syndromes. Although there exists a few reports on the incidence of post mastectomy pain, there are no published reports on chronic pain after breast reconstruction. This investigation attempts to characterize the pain after four types of breast surgery: (1) mastectomy, (2) mastectomy with reconstruction, (3) cosmetic augmentation, and (4) breast reduction. A questionnaire was mailed to 479 women who underwent breast surgery at the University of California, San Diego Medical Center between January 1988 and December 1992. A second mailing was sent to women who did not respond to the first mailing. Women were divided into four groups; mastectomy, mastectomy with reconstruction, cosmetic augmentation, and breast reduction. In the mastectomy and mastectomy with reconstruction groups, only women who had a lumpectomy with axillary dissection, a modified radical mastectomy, or a radical mastectomy were used in the study. 59% of the women responded. The incidence of pain occurring at least one year after surgery in the mastectomy + reconstruction group (49%) was significantly higher than the mastectomy (31%) and breast reduction (22%) groups. Thirty-eight percent of the women with breast augmentation complained of pain. Women who had reconstruction using breast implants had a higher incidence of pain (53%) than those without (30%). The pain incidence in women who had reconstruction without implants was identical to women who had a mastectomy without reconstruction. There was no relationship between the use of silicone or saline implants and pain (22% and 33% respectively). However, the submuscular placement of the implants resulted in a significantly higher incidence of pain (50%) than the subglandular placement (21%). Of the women that reported pain, arm pain was significantly higher in the mastectomy and mastectomy + reconstruction group (56% and 42%, respectively) as compared to the breast reduction group (0%). Most patients reported intermittent pain in all groups. Of the women that reported pain, the mastectomy and mastectomy + reconstruction group had higher pain related to movement (41% and 42%, respectively) than the augmentation and breast reduction groups (15% and 9%, respectively). The peak pain intensity was significantly higher in the augmentation group as compared to the mastectomy group. Our incidence of post mastectomy pain is higher than most reports. The incidence of breast pain is highest in the mastectomy + reconstruction and augmentation groups which is assumed to be secondary to breast implants. Every effort should be made to achieve the best cosmetic result in breast reconstruction which in many cases justifies the use of breast implants. However, these women should be counseled on the possibility of developing chronic pain.

Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain.

Both mu opioid agonists and N-methyl-D-aspartate (NMDA) receptor antagonists are implicated in the regulation of neuropathic pain in post-nerve injury preclinical pain models. This study characterizes the effects of intravenously infused alfentanil (a mu-receptor agonist) and ketamine (an NMDA-receptor antagonist) on human neuropathic pain states, characterized by allodynia and hyperalgesia. Using diphenhydramine as the placebo, alfentanil and ketamine infusions were given in a randomized double-blind fashion 1 week apart via a computer-controlled infusion (CCI) pump that was programmed to target plasma levels of alfentanil at 25, 50 and 75 ng/ml and ketamine at 50, 100 and 150 ng/ml. At the beginning of each infusion and each targeted plasma level, baseline vital signs, neurosensory testing that included thermal thresholds, thermal pain and von Frey filament thresholds, and spontaneous and evoked pain scores were obtained. Moreover, the areas of allodynia or hyperalgesia to stroking and a 5.18 von Frey filament were mapped at the beginning and the end of each infusion. A total of seven males and five females with post-nerve injury allodynia and hyperalgesia were enrolled in the study. Elevations of cold, warm, hot pain and von Frey tactile thresholds were noted. Dose-dependent increases in cold and cold pain thresholds, and reductions in stroking pain scores were noted in both the alfentanil and the ketamine infusions. In addition, alfentanil showed a statistically significant dose-dependent reduction in both spontaneous and von Frey pain scores. Both the alfentanil and ketamine infusions showed a reduction in the stroking hyperalgesic area and ketamine showed a significant reduction in the von Frey hyperalgesia area. No significant CNS side effects and changes in vital signs were noted. A partial deafferentation state was found in the post-nerve injury patients who presented with allodynia and hyperalgesia. The effects of alfentanil on cold and cold pain thresholds and spontaneous pain scores correlates with previous studies suggesting an opiate central analgesic effect. In addition, the reduction of the hyperalgesic area and evoked pain scores with the alfentanil infusion suggests that opioids may have some peripheral effects in the post-nerve injury patients. Therefore, clinical utilization of opioids with careful titration may be beneficial in post-nerve injury patients with partial deafferentation. With the absence of significant CNS side effects, the ketamine infusion not only demonstrated the well-documented spinal cord mechanism of the NMDA receptor, but the result of the current study also suggests that a peripheral mechanism of NMDA receptor may exist. The relationship between central sensitization and regulation of peripheral NMDA-receptor expression requires further investigation.

Emerging drugs for neuropathic pain.

Although there are many analgesics on the market for the treatment of nociceptive pain, there are none with FDA approval for the treatment of neuropathic pain. With a better understanding of the anatomy and physiology of pain, there is a significant effort in developing new drugs that interact specifically with pain pathways. This higher drug specificity is likely to result in drugs that are more efficacious with fewer side effects. This has led to the development of many drugs for the treatment of neuropathic pain. These drugs are divided into the following therapeutic classes: 1) N-methyl-D-aspartate (NMDA) receptor antagonists, 2) ion channel antagonists, 3) alpha2-agonists, 4) nicotinic receptor agonists, 5) prostaglandin receptor antagonists, 6) adenosine agonists and adenosine kinase inhibitors, 7) neuropeptide antagonists, and 8) prosaposins. The results of preclinical and clinical trials are promising for these new agents. Whether these agents will be efficacious as single agents is yet to be determined; however, preliminary results show that combination therapy may be more beneficial with fewer side effects.

Long-term methadone treatment: effect on CD4+ lymphocyte counts and HIV-1 plasma RNA level in patients with HIV infection.

The objective was to examine the effect of methadone on CD4+ lymphocyte counts and viral load and to expect to document the safety of methadone maintenance in patients with human immune deficiency syndrome. This is a retrospective chart analysis comparing the trends in CD4+ count and viral load in two populations of 21 human immunodeficiency virus (HIV) infected patients, one on methadone maintenance and a methadone non-using group. Each methadone user was matched with a control methadone non-user that had a similar CD4+ at the beginning of the study. For the CD4+ count we compared the slope of regression for each couple of patients. In 15 patients we also collected the viral load, which was measured at 4-6 monthly intervals. The mean length of follow-up was 811 days for the methadone group and 797 days in the control group. There was no statistical difference in the treatment received by the two groups of patients during the study. The slope of regression of CD4+ count showed a significantly steeper decline in the methadone-using patients compared with the methadone non-users (r= 0.487; p< 0.05). The evolution of the HIV-1 RNA levels was the same during the follow-up of mean 186 months in a few of the patients in each of the two groups. Long-term methadone use was associated with a significantly faster decrease of CD4+ count in HIV-1 affected patients compared with methadone non-users. HIV-1 RNA data were found in too few patients to enable any conclusions about the development of viral load in the two groups.

The pharmacokinetics of lignocaine in humans during a computer-controlled infusion.

Several types of chronic pain syndromes are effectively treated with sodium channel blockers such as lignocaine. Further investigation of this therapeutic modality would be facilitated by refinement of the parameters describing lignocaine distribution and elimination. This would allow precise lignocaine infusion by a computer-controlled infusion to attain and maintain stable target lignocaine concentrations. Arterial blood samples were obtained at frequent intervals during a computer-controlled infusion of lignocaine in 12 adult human volunteers. Plasma lignocaine concentrations of 1, 2, 3, 4 and 5 microg/ml were targeted for 15 min at each concentration. A three-compartment mammillary pharmacokinetic model best described the resulting concentration vs time profile. A population pharmacokinetic analysis was performed using three different techniques; the two-stage, pooled and mixed effects modelling. There was marked overshoot of the plasma concentration above the target prior to refinement of the pharmacokinetic parameters. The best parameters of a three-compartment mammillary model fit to the measured concentration using the pooled data approach were: V(1) = 7.44, V(2) =11.5 and V(3) = 97.71; Cl(1) = 0.585, Cl(2) = 2.23 and Cl(3) =1.64 l/min. Similarly calculated parameters using NONMEM were V(1) = 6.99, V(2) =12.2 and V(3) =1341; Cl(1) = 0.703, Cl(2) =1.24 and Cl(3) =1.49 l/min. The addition of age as a covariate of the pharmacokinetic parameters improved the model in both cases. Height, lean body mass and body surface area as covariates of the pharmacokinetic parameters did not improve the predicted value of the model. Prospective testing of the pharmacokinetic parameters will be required to define whether they function well. The refinement of pharmacokinetic parameters for the computer-controlled intravenous infusion of lignocaine will facilitate further research in pain therapy. Published lignocaine pharmacokinetic values have a relatively large central volume of distribution, and hence, when implemented as a computer-controlled infusion, result in dramatic overshoot shortly after targeting a higher plasma concentration. In light of the long-lasting pain relief provided by sodium channel blockade in neuropathic pain states, overshoot of plasma concentrations must be avoided if the concentration vs effect relationship is to be defined.

Calcium and sodium channel antagonists for the treatment of pain.

Several lines of evidence developed in preclinical models suggest that both spontaneous and evoked pain are mediated in part by voltage-sensitive sodium and calcium channels, which are in abundance in both the peripheral and the central nervous system. There is an abundance of research, both preclinical and clinical, on the effects of the sodium and calcium channel antagonists on nociceptive processing. Clinical studies on the efficacy of the sodium channel antagonists in the treatment of acute and chronic pain have had mixed results. Preliminary studies of the N-type calcium channel antagonists for the treatment of acute and chronic pain are promising but too early to enable researchers to make firm conclusions. This review summarizes the current literature on the effects of the sodium and calcium channel antagonists on acute nociceptive processing, facilitated pain, and neuropathic pain.