Hendra in the Hunter Valley.

In June 2019 the first equine case of Hendra virus in the Hunter Valley, New South Wales, Australia was detected. An urgent human and animal health response took place, involving biosecurity measures, contact tracing, promotion of equine vaccinations and investigation of flying fox activity in the area. No human or additional animal cases occurred. Equine vaccination uptake increased by over 30-fold in the surrounding region in the three months following the case. Black flying fox and grey-headed flying fox species were detected in the Valley. The incident prompted review of Hendra virus resources at local and national levels. This event near the "horse capital of Australia", is the southernmost known equine Hendra case. Management of the event was facilitated by interagency collaboration involving human and animal health experts. Ongoing One Health partnerships are essential for successful responses to future zoonotic events.

Wire ablation dynamics model and its application to imploding wire arrays of different geometries.

The paper presents an extended description of the amplified wire ablation dynamics model (WADM), which accounts in a single simulation for the processes of wire ablation and implosion of a wire array load of arbitrary geometry and wire material composition. To investigate the role of wire ablation effects, the implosions of cylindrical and planar wire array loads at the university based generators Cobra (Cornell University) and Zebra (University of Nevada, Reno) have been analyzed. The analysis of the experimental data shows that the wire mass ablation rate can be described as a function of the current through the wire and some coefficient defined by the wire material properties. The aluminum wires were found to ablate with the highest rate, while the copper ablation is the slowest one. The lower wire ablation rate results in a higher inward velocity of the ablated plasma, a higher rate of the energy coupling with the ablated plasma, and a more significant delay of implosion for a heavy load due to the ablation effects, which manifest the most in a cylindrical array configuration and almost vanish in a single-planar array configuration. The WADM is an efficient tool suited for wire array load design and optimization in wide parameter ranges, including the loads with specific properties needed for the inertial confinement fusion research and laboratory astrophysics experiments. The data output from the WADM simulation can be used to simplify the radiation magnetohydrodynamics modeling of the wire array plasma.

Influence of induced axial magnetic field on plasma dynamics and radiative characteristics of Z pinches.

The influence of an induced axial magnetic field on plasma dynamics and radiative characteristics of Z pinches is investigated. An axial magnetic field was induced in a novel Z-pinch load: a double planar wire array with skewed wires (DPWAsk), which represents a planar wire array in an open magnetic configuration. The induced axial magnetic field suppressed magneto-Rayleigh-Taylor (MRT) instabilities (with m = 0 and m = 1 instability modes) in the Z-pinch plasma. The influence of the initial axial magnetic field on the structure of the plasma column at stagnation was manifested through the formation of a more uniform plasma column compared to a standard double planar wire array (DPWA) load [V. L. Kantsyrev et al., Phys. Plasmas 15, 030704 (2008)]. The DPWAsk load is characterized by suppression of MRT instabilities and by the formation of the sub-keV radiation pulse that occurs before the main x-ray peak. Gradients in plasma parameters along the cathode-anode gap were observed and analyzed for DPWAsk loads made from low atomic number Z (Al) and mid-Z (brass) wires.

Grazing incidence extreme ultraviolet spectrometer fielded with time resolution in a hostile z-pinch environment.

This recently developed diagnostic was designed to allow for time-gated spectroscopic study of the EUV radiation (4 nm < λ < 15 nm) present during harsh wire array z-pinch implosions. The spectrometer utilizes a 25 µm slit, an array of 3 spherical blazed gratings at grazing incidence, and a microchannel plate (MCP) detector placed in an off-Rowland position. Each grating is positioned such that its diffracted radiation is cast over two of the six total independently timed frames of the MCP. The off-Rowland configuration allows for a much greater spectral density on the imaging plate but only focuses at one wavelength per grating. The focal wavelengths are chosen for their diagnostic significance. Testing was conducted at the Zebra pulsed-power generator (1 MA, 100 ns risetime) at the University of Nevada, Reno on a series of wire array z-pinch loads. Within this harsh z-pinch environment, radiation yields routinely exceed 20 kJ in the EUV and soft x-ray. There are also strong mechanical shocks, high velocity debris, sudden vacuum changes during operation, energic ion beams, and hard x-ray radiation in excess of 50 keV. The spectra obtained from the precursor plasma of an Al double planar wire array contained lines of Al IX and AlX ions indicating a temperature near 60 eV during precursor formation. Detailed results will be presented showing the fielding specifications and the techniques used to extract important plasma parameters using this spectrometer.

X-ray spectroscopy of Cu impurities on NSTX and comparison with Z-pinch plasmas.

X-ray spectroscopy of mid-Z metal impurities is important in the study of tokamak plasmas and may reveal potential problems if their contribution to the radiated power becomes substantial. The analysis of the data from a high-resolution x-ray and extreme ultraviolet grating spectrometer, XEUS, installed on NSTX, was performed focused on a detailed study of x-ray spectra in the range 7-18 Å. These spectra include not only commonly seen iron spectra but also copper spectra not yet employed as an NSTX plasma impurity diagnostic. In particular, the L-shell Cu spectra were modeled and predictions were made for identifying contributions from various Cu ions in different spectral bands. Also, similar spectra, but from much denser Cu plasmas produced on the UNR Z-pinch facility and collected using the convex-crystal spectrometer, were analyzed and compared with NSTX results.

Planar wire-array Z-pinch implosion dynamics and X-ray scaling at multiple-MA drive currents for a compact multisource hohlraum configuration.

An indirect drive configuration is proposed wherein multiple compact Z-pinch x-ray sources surround a secondary hohlraum. Planar compact wire arrays allow reduced primary hohlraum surface area compared to cylindrical loads. Implosions of planar arrays are studied at up to 15 TW x-ray power on Saturn with radiated yields exceeding the calculated kinetic energy, suggesting other heating paths. X-ray power and yield scaling studied from 1-6 MA motivates viewfactor modeling of four 6-MA planar arrays producing 90 eV radiation temperature in a secondary hohlraum.

Mohs micrographic surgery for dermatofibrosarcoma protuberans of the vulva.

Introduction. Dermatofibrosarcoma Protuberans (DFSP) is a rare cutaneous tumour of low/intermediate malignant potential, which occasionally arises on the vulva. Historically, the treatment has been wide local excision (WLE). Mohs micrographic surgery (MMS) is now recommended to ensure precise margin control. MMS to treat DFSP of the trunk and extremities is well documented. However, no report to date has described its use in vulval DFSP. Case History. A 39 year old woman presented with a longstanding nodule in the left labium majus. Histology after surgical removal showed an incompletely excised DFSP. MMS was undertaken with primary closure of the defect. Three years following treatment there is no evidence of recurrence. Discussion. The local recurrence rate of DFSP after WLE ranges from 0-75%. Finger-like projections from DFSP into surrounding tissue often results in incomplete excision. Representative vertical sections used in WLE assess less than 1% of the total tumour margin. MMS uses systematic horizontal sectioning. 100% of the tumour margin is microscopically examined. MMS is now advocated to ensure precise margin control.

Observation of >400-eV precursor plasmas from low-wire-number copper arrays at the 1-MA zebra facility.

Experiments with cylindrical copper wire arrays at the 1-MA Zebra facility show that high temperatures exist in the precursor plasmas formed when ablated wire array material accretes on the axis prior to the stagnation of a z pinch. In these experiments, the precursor radiated approximately 20% of the >1000 eV x-ray output, and time-resolved spectra show substantial emission from Cu L-shell lines. Modeling of the spectra shows an increase in temperature as the precursor forms, up to approximately 450 eV, after which the temperature decreases to approximately 220-320 eV until the main implosion.

Diagnostic of charge balance in high-temperature tungsten plasmas using LLNL EBIT.

Diagnostic of high-temperature M-shell W plasmas is challenging because of contribution of numerous ionization stages in a relatively narrow x-ray spectral region. A method using LLNL EBIT data generated at different electron beam energies has been established for the identification of prominent spectral features and for the determination of charge balance in x-ray M-shell W spectra between 3.5 and 8.5 A. It extends previous work [A. S. Safronova et al., Can. J. Phys. 86, 267 (2008)] which used only Ni-like lines to include the neighboring ionization stages. This diagnostic procedure was tested with results from Z-pinch plasmas produced on the 1 MA pulse power generator Zebra at UNR. These results are of particular importance for fusion research.

X-ray diagnostics of imploding plasmas from planar wire arrays composed of Cu and few tracer Al wires on the 1MA pulsed power generator at UNR.

Tracer aluminum alloyed wires (Al5056) are used to provide additional information for x-ray diagnostics of implosions of Cu planar wire arrays (PWAs). Specifically, the analysis of combined PWA experiments using the extensive set of x-ray diagnostics is presented. In these experiments, which were conducted at the 1MA pulsed power generator at University of Nevada, Reno, the Z-pinch load consisted of several (eight) Cu alloyed (main material) and one to two Al alloyed (tracer) wires mounted in a single plane row or double parallel plane rows, single planar wire array (SPWA) or double planar wire array (DPWA), respectively. The analysis of x-ray spatially resolved spectra from the main material indicates the increase in the electron temperature T(e) near the cathode. In general, the axial gradients in T(e) are more pronounced for SPWA than for DPWA due to the more "columnlike" plasma formation for SPWA compared to "hot-spot-like" plasma formation for DPWA. In addition, x-ray spectra from tracer wires are studied, and estimated plasma parameters are compared with those from the main material. It is observed that the x-ray K-shell Al spectra manifest more opacity features for the case of SPWA with about 18% of Al mass (to the total load mass) compared to the case of DPWA with about 11% of Al mass. The analysis of time-gated spectra shows that the relative intensity of the most intense K-shell Al line, small before the x-ray burst, increases with time and peaks close to the maximum of the sub-keV signal.

Extreme ultraviolet spectroscopy diagnostics of low-temperature plasmas based on a sliced multilayer grating and glass capillary optics.

New extreme ultraviolet (EUV) spectroscopic diagnostics of relatively low-temperature plasmas based on the application of an EUV spectrometer and fast EUV diodes combined with glass capillary optics is described. An advanced high resolution dispersive element sliced multilayer grating was used in the compact EUV spectrometer. For monitoring of the time history of radiation, filtered fast EUV diodes were used in the same spectral region (>13 nm) as the EUV spectrometer. The radiation from the plasma was captured by using a single inexpensive glass capillary that was transported onto the spectrometer entrance slit and EUV diode. The use of glass capillary optics allowed placement of the spectrometer and diodes behind the thick radiation shield outside the direction of a possible hard x-ray radiation beam and debris from the plasma source. The results of the testing and application of this diagnostic for a compact laser plasma source are presented. Examples of modeling with parameters of plasmas are discussed.

Extreme ultraviolet spectroscopy of low-Z ion plasmas for fusion applications.

The study of impurities is a key component of magnetic fusion research as it is directly related to plasma properties and steady-state operation. Two of the most important low-Z impurities are carbon and oxygen. The appropriate method of diagnosing these ions in plasmas is extreme ultraviolet (EUV) spectroscopy. In this work the results of two different sets of experiments are considered, and the spectra in a spectral region from 40 to 300 A are analyzed. The first set of experiments was carried out at the Sustained Spheromak Physics Experiment at LLNL, where EUV spectra of oxygen ions were recorded. The second set of experiments was performed at the compact laser-plasma x-ray/EUV facility "Sparky" at UNR. In particular, Mylar and Teflon slabs were used as targets to produce carbon, oxygen, and fluorine ions of different ionization stages. Nonlocal thermodynamic equilibrium kinetic models of O, F, and C were applied to identify the most diagnostically important spectral features of low-Z ions between 40 to 300 A and to provide plasma parameters for both sets of experiments.

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.

Effect of fluoxetine on carvedilol pharmacokinetics, CYP2D6 activity, and autonomic balance in heart failure patients.

The objective of this study was to examine the pharmacokinetic and pharmacodynamic consequences of concomitant administration of fluoxetine and carvedilol in heart failure patients. Fluoxetine (20 mg) or matching placebo was administered in a randomized, double-blind, two-period crossover study to 10 patients previously identified as extensive metabolizers of CYP2D6 substrates. Patients were maintained on a carvedilol dose of 25 or 50 mg bid and given fluoxetine/placebo for a minimum of 28 days. Plasma was collected over the 12-hour carvedilol dosing interval, and the concentrations of the R(+) and S(-) enantiomers of carvedilol were measured. CYP2D6 phenotype was assessed during each study period using dextromethorphan (30 mg). Changes in autonomic modulation between study periods were measured by heart rate variability in the time and frequency domains using ambulatory electrocardiographic monitoring. Compared to placebo, fluoxetine coadministration resulted in a 77% increase in mean (+/- SD) R(+) enantiomer AUC0-12 (522 +/- 413 vs. 927 +/- 506 ng.h/mL, p = 0.01) and a nonsignificant increase in S(-) enantiomer AUC (244 +/- 185 vs. 330 +/- 179 ng.h/mL, p = 0.17). Mean apparent oral clearance for both enantiomers decreased significantly with fluoxetine administration (R(+): 10.3 +/- 7.2 vs. 4.5 +/- 2.2 mL/min/kg; S(-): 22.5 +/- 12.3 vs. 12.6 +/- 7.4 mL/min/kg; p = 0.004 and 0.03, respectively). No differences in adverse effects, blood pressure, or heart rate were noted between treatment groups, and there were no consistent changes in heart rate variability parameters. In conclusion, fluoxetine administration resulted in a stereospecific inhibition of carvedilol metabolism, with the R(+) enantiomer increasing to a greater extent than the S(-) enantiomer. However, this interaction was of little clinical significance in our sample population.

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.

Digoxin toxicity: an evaluation in current clinical practice.

BACKGROUND: Serum digoxin concentrations (SDCs) are frequently sampled before completion of drug distribution. If elevated, these concentrations may be misinterpreted, potentially leading to a misdiagnosis of digoxin toxicity. OBJECTIVES: To determine the frequency of elevated SDCs (>2.6 nmol/L [>2.0 ng/mL]) obtained at appropriate postdosing intervals and to evaluate the frequency of clinically defined digoxin toxicity in patients with elevated SDCs. METHODS: The medical records of adult patients with SDCs assayed at 5 general hospitals in North Carolina during a 3-month period (May 1 through July 31, 1996) were prospectively evaluated. Data on SDC, inpatient or outpatient status, and medical or surgical service were collected for all patients. Data on patient demographics, serum chemistry values, indication for digoxin treatment, clinical evidence of digoxin toxicity, and timing of the blood sample relative to administration of the last dose of digoxin were collected for patients with SDCs higher than 2.6 nmol/L (>2.0 ng/mL). RESULTS: Of 3434 SDCs assayed in 2009 patients, 320 (9.3%) were higher than 2.6 nmol/L (>2.0 ng/mL). Fifty-one (15.9%) of the 320 SDCs were drawn at 6 hours or less following a digoxin dose. Sampling time relative to the digoxin dose could not be determined in 70 (21.9%) of the 320 elevated SDCs, leaving 199 (62.2%) of 320 SDCs in 138 patients evaluable for digoxin toxicity. Eighty-three of the 138 patients had clinical evidence of digoxin toxicity for an overall incidence of 4.1%. CONCLUSIONS: Digoxin toxicity occurs less frequently than historically reported. Continued emphasis needs to be placed on obtaining appropriately timed SDCs.

Intraperitoneal bupivacaine or lidocaine does not provide analgesia after total abdominal hysterectomy.

We have compared pain scores at rest and on standardized movement, and morphine consumption using patient-controlled analgesia in 60 patients who had undergone total abdominal hysterectomy. Patients were allocated randomly to one of three groups: in the saline group, 0.9% sodium chloride 50 ml was administered into the pelvic cavity before closure of the peritoneum; in the second group, the solution administered was 20 ml of 0.5% bupivacaine solution with epinephrine 1:200,000 diluted with saline to a final volume of 50 ml; in the third group, the solution used was 20 ml [corrected] of 2% lidocaine with epinephrine 1:200,000 diluted with saline to a final volume of 50 ml. We found that there was no significant difference between the three groups in visual analogue pain scores at 8, 12, 36 or 48 h after operation at rest or on movement, and no significant difference in sedation or dose of antiemetic administered. Mean morphine consumption in the first 24 h was 54.6 (SEM 5.9) mg in the saline group, 55.5 (6.4) mg in the bupivacaine group and 52.5 (5.3) mg in the lidocaine group. In the second 24 h, morphine consumption was 34.9 (6.6) mg, 28.1 (3.5) mg and 28.0 (3.5) mg in the three groups, respectively. We conclude that i.p. administration of local anaesthetic solution into the pelvic cavity did not confer appreciable analgesia in patients undergoing abdominal hysterectomy.

Effects of erythromycin or rifampin on losartan pharmacokinetics in healthy volunteers.

BACKGROUND: Losartan is metabolized by CYP2C9 and CYP3A4 to an active metabolite, E3174, which has greater antihypertensive activity than the parent compound. Coadministered drugs that inhibit or induce metabolic processes may therefore alter the pharmacokinetics and pharmacologic response of losartan and E3174. OBJECTIVE AND METHODS: Ten healthy volunteers were studied to assess the effects of CYP3A4 inhibition and nonspecific P450 enzyme induction on the pharmacokinetics of losartan and E3174. Subjects completed three 1-week phases separated by 6 days: 50 mg losartan every morning, losartan plus 500 mg erythromycin four times a day, and losartan plus 300 mg rifampin (INN, rifampicin) twice a day. On the eighth day of each phase, serial plasma concentrations of losartan and E3174 were obtained over 32 hours and steady-state pharmacokinetics were determined. RESULTS: Rifampin decreased the area under the concentration-time curve from time zero to 24 hours after the dose (AUC[0-24]) of losartan by 35% (349 +/- 246 versus 225 +/- 130; p = 0.0001) and decreased the AUC(0-24) of E3174 by 40% (1336 +/- 445 versus 792 +/- 302; p < 0.005). Losartan oral clearance was increased by 44% (p = 0.0001). The half-life values of both compounds were decreased by 50% (p < 0.005). In contrast, erythromycin did not significantly affect the AUC(0-24) or half-life of either losartan or E3174. CONCLUSIONS: Rifampin is a potent inducer of losartan and E3174 elimination. Given the magnitude of the effect, this interaction is likely to be clinically significant. On the basis of the minimal inhibitory effects observed with erythromycin, CYP3A4 appears to play a minor role in the in vivo metabolism of losartan to E3174. Further studies are needed to define the contribution of other isozymes, particularly CYP2C9, to the pharmacokinetics of losartan and E3174.

The AHCPR clinical practice guideline for heart failure revisited.

OBJECTIVE: To review the Agency for Health Care Policy and Research (AHCPR) clinical practice guideline for heart failure and comment on the guideline regarding pharmacotherapy from the perspective of the latest clinical trial data and the authors' clinical experience. DATA SOURCES: A MEDLINE search (1966 to June 1997) of English-language literature pertaining to the pharmacotherapy of heart failure was performed. Special emphasis was placed on literature published in the last 5 years. Additional literature was obtained from reference lists of key articles identified through the search. DATA SYNTHESIS: Pertinent clinical trials were reviewed and considered along with information from the authors' database of over 800 patients with heart failure. Evidence concerning the use of angiotensin-converting enzyme inhibitors at appropriate dosages in all New York Heart Association classes of heart failure and the inclusion of digoxin as part of triple therapy in all symptomatic patients with left ventricular systolic dysfunction are reviewed. Strategies to circumvent clinical problems that may limit the proper application of standard therapeutic agents are considered, and the possible future role of beta-blockers as the therapeutic agents in patients with heart failure is discussed. CONCLUSIONS: The AHCPR guideline provides the clinician with an excellent framework for treating the patient with heart failure. Building on the fundamentals of the guideline, the clinician can carefully apply current therapy at appropriate dosages and in the best combinations to individualize and thereby optimize pharmacologic therapy for this patient population.