Add-on Device Research Articles

Plume temperature emitted from metered dose inhalers

The temperature of the drug cloud emitted from a pressurised metered dose inhaler (pMDI) may result in patient discomfort and inconsistent or non-existent dose delivery to the lungs. The effects of variations in formulation (drug, propellant, co-solvent content) and device hardware (metering volume, actuator orifice diameter, add-on devices) upon the temperature of pMDI plumes, expressed as replicate mean minimum values (MMPT), collected into a pharmacopoeial dose unit sampling apparatus (DUSA), have been investigated. Ten commercially available and two development products, including chlorofluorocarbon (CFC) suspensions and hydrofluoroalkane (HFA) solutions or suspensions, were examined together with a number of drug products in late stage development and a variety of HFA 134a placebo pMDIs. Plume temperatures were observed to be lowest in the proximity of the product's actuator mouthpiece where rapid flashing and evaporation of the formulation's propellant and volatile excipients cause cooling. The ability to control plume temperature by judicious choice of formulation co-solvent content, metering volume and the actuator orifice diameter is identified. An ethanol based HFA 134a formulation delivered through a fine orifice is inherently warmer than one with 100% HFA 134a vehicle delivered through a coarse actuator orifice. Of the 10 commercial products evaluated, MMPTs ranged from −54 to +4 °C and followed the formulation class rank order, HFA suspensions < CFC suspensions < HFA solutions. For all systems examined it was possible to raise pMDI plume temperature to that of the ambient surroundings by use of an add-on or integrated spacer device.

MRI-guided breast biopsy at 3T using a dedicated large core biopsy set: Feasibility and initial results

Objective The increasing importance of breast MRI in the diagnostic processes concerning breast cancer yield often lesions that are visible on MRI only. To assess the nature of these lesions, pathologic analysis is necessary. Therefore, MR-guided biopsy should be available. Breast MRI at 3T has shown advantage over 1.5T. Unfortunately, current equipment for MR-guided biopsy is better suited for intervention at 1.5T due to the danger of heating titanium co-axial sleeves and large susceptibility artifacts. We evaluated a dedicated 3T breast biopsy set that uses plastic coaxial needles to overcome these problems. Materials and methods We performed MRI-guided breast biopsy in 23 women with 24 MRI-only visible breast lesions at 3T. Biopsy procedures were performed with plastic coaxial needles in a closed bore 3T clinical MR system on a dedicated phased array breast coil with a commercially available add-on stereotactic biopsy device. Results Width of the needle artifact was 2 mm in all 24 cases. Biopsy procedure was completed between 35 and 67 min. The procedure was judged moderately easy in 12 and normal in 10 cases. One procedure was judged difficult and there was one technical failure. Conclusion MRI-guided breast biopsy at 3T is a fast and accurate procedure. The plastic coaxial needles reduce the susceptibility artifact largely and do not increase the difficulty of the procedure. The diagnostic yield is at least equal to the diagnostic yield of the same procedure at 1.5T. Therefore, this technique can be safely used for lesions only visible at 3T MRI.

Relative Precision of Inhaler Aerodynamic Particle Size Distribution (APSD) Metrics by Full Resolution and Abbreviated Andersen Cascade Impactors (ACIs): Part 1

The purpose of this study was to compare relative precision of two different abbreviated impactor measurement (AIM) systems and a traditional multi-stage cascade impactor (CI). The experimental design was chosen to provide separate estimates of variability for each impactor type. Full-resolution CIs are useful for characterizing the aerosol aerodynamic particle size distribution of orally inhaled products during development but are too cumbersome, time-consuming, and resource-intensive for other applications, such as routine quality control (QC). This article presents a proof-of-concept experiment, where two AIM systems configured to provide metrics pertinent to QC (QC-system) and human respiratory tract (HRT-system) were evaluated using a hydrofluoroalkane-albuterol pressurized metered dose inhaler. The Andersen eight-stage CI (ACI) served as the benchmark apparatus. The statistical design allowed estimation of precision with each CI configuration. Apart from one source of systematic error affecting extra-fine particle fraction from the HRT-system, no other bias was detected with either abbreviated system. The observed bias was shown to be caused by particle bounce following the displacement of surfactant by the shear force of the airflow diverging above the collection plate of the second impaction stage. A procedure was subsequently developed that eliminated this source of error, as described in the second article of this series (submitted to AAPS PharmSciTech). Measurements obtained with both abbreviated impactors were very similar in precision to the ACI for all measures of in vitro performance evaluated. Such abbreviated impactors can therefore be substituted for the ACI in certain situations, such as inhaler QC or add-on device testing.

Corrosion failure due to flux residues in an electronic add-on device

Corrosion of components and sub-assemblies on an electronic Printed Circuit Board Assembly (PCBA) is a major reliability concern. Both process and user related contamination will influence the corrosion reliability of a PCBA and the electronic device as a whole. An important process related contamination is solder flux residues which can act as a corrosion promoter in humid atmosphere due to the presence of ionic substances and a resin component. The presence of ionic substances will increase the conductivity of a condensed water layer and influence corrosion processes, depending on the species present. The resin component can easily attract dust during operation, which will eventually make surfaces hydrophilic and are thus become a potential source for ions. This paper describes the failure analysis of tactile switches, used in PCBAs mounted in wind turbines. More detailed investigation of the electrochemical behavior metallic materials (alloys) used in the switch and risk of electrochemical migration (ECM) between the switch components in presence of flux residues was also carried out. Investigations included potentiodynamic polarization measurements on the switch electrodes using a micro-electrochemical technique, in situ ECM studies, and scanning electron microscopy (SEM). Failure of the switches was found to be either due to the flux residue acting as an insulating layer or as a corrosion accelerator causing ECM.

New drag reduction design for tractor-trailers using CFD

Tractor-trailers have a higher drag coefficient than other vehicles due to their bluff-body shape. Over the years, numerous add-on devices have been invented to help reduce the drag. The current research investigates new add-on devices in the form of humps to reduce the base-drag of tractor-trailers. In the current investigation, computational fluid dynamics (CFD) in the form of unsteady Reynolds-averaged Navier-Stokes simulations is used to determine viable design strategies and optimise the new add-on device designs. A baseline model was built using an Ahmed body in both 2D and 3D. The predicted drag coefficient of the 3D Ahmed baseline model showed good agreement with experimental data. The 2D and 3D simulations with hump(s) showed some difference in drag reduction that was dependent on the hump geometry. A significant 3D effect existed. Results from the baseline validations as well as from simulations of tractor-trailer-like configurations with hump add-on devices are shown to demonstrate the drag reduction possible. While the hump is a conceptual design and may not be applied to full-size semi-truck trailers due to the height limit, it still offers a significant result which makes the applications on other smaller vehicles possible.

INNOVATIVE TECHNOLOGIES: Microscopy Not to Dye For

Users of confocal microscopes now have access to a relatively inexpensive module that can be readily installed to dramatically increase the capabilities of these instruments. Members of Canada’s National Research Council (NRC) initiated the commercial development of this technology, hoping to provide researchers with cost-effective access to imaging strategies with distinct advantages for some applications. The price tag for the new system will be about US$57,000, a fraction of what it takes to acquire such a microscope. This new investment makes it possible to create detailed images of fatty structures that are typically nonfluorescent, such as the fibrous caps responsible for atherosclerosis and the myelin sheath surrounding nerve structures. Importantly, the method is label-free, meaning it does not rely on any dyes or stains. Moreover, images can be created in seconds rather than hours, offering real-time in-vivo representation of such complex processes as a virus infecting cells. The technology is called coherent anti-Stokes Raman scattering, or CARS. Developed in the mid-1960s as a spectroscopic tool by materials engineers at the Ford Motor Company, in the late 1990s the concept was extended to include microscopy. The technique builds on the same hardware used in confocal imaging, consisting of two lasers plus an elaborate array of lenses and mirrors. When this bright light reaches a specimen, it fluoresces to a significant depth, and with the proper resolution, yields a detailed three-dimensional image. Taking advantage of these same two lasers, CARS adds another light field based on a difference in frequency between these light sources, a difference that precisely matches a target molecule’s vibrational resonance. The resulting image can be obtained even as the rest of the microscope generates a standard confocal image. In 2007 NRC researcher Albert Stolow and his colleagues demonstrated that CARS images could be obtained using the same laser technology already found in confocal microscopes. The work taking place at the NRC also caught the attention of optics giant Olympus, which saw the prospect of a new product that would build on an established market of microscope users without asking them to convert exclusively to unfamiliar methodology or acquire another expensive, specialized piece of equipment. The company subsequently partnered with Stolow’s team to come up with the design for an add-on device that would mate seamlessly with the company’s existing confocal systems. The enhanced 300-nm spatial resolution of CARS is achieved without dyes or stains to provide the necessary contrast. This feature makes it easier to work with living tissue that might diffuse or react with these agents and compromise the outcome. That is a big selling point for Michael Sowa, an NRC researcher specializing in biodiagnostic spectroscopy and heart disease. CARS allows him to visualize fibrous patches of plaque building up inside veins and arteries; specifically, he can look for lesions that could burst and release material that could cause a stroke. “It’s a really powerful tool for investigating vascular walls, and atherosclerosis in particular,” he says. NRC investigator John Pezacki was one of the first to adopt CARS almost a decade ago. Before then, he would have relied primarily on fixed cell staining, which amounted to taking a handful of snapshots portraying a complex chemical interaction while whatever might be happening in between each picture remained unknown. “It’s the equivalent of doing very good quality photography versus cinematography,” he explains. “It allows us to do kinetic measurements, answering the question of when [events] happen during the viral life cycle.” And while the CARS system currently performs optimally with the molecules making up lipids, Pezacki envisions potential for this technology in environmental analysis. “The holy grail of this area going forward is to be able to do lower-abundance materials, such as peptides, proteins, and nucleic acids,” he says. “If you can . . . look at the unique CARS signals from [natural products or drugs] and get a label-free contrast image of where those things are in the cell or in a tissue, then you have the opportunity to do that with environmental toxicants as well.”

Evaluation of add-on devices for the prevention of phlebitis and other complications associated with the use of peripheral catheters in hospitalised adults: a randomised controlled study

The aim of this study was to assess the role of add-on devices for the prevention of phlebitis and other complications associated with the use of peripheral catheters. Patients admitted to an infectious diseases ward and requiring the insertion of a peripheral catheter for at least 24h were randomly allocated to be managed with or without add-on devices. Incidence of phlebitis and all complications were the primary outcomes. Extravasation, inadvertent withdrawal, obstruction and rupture were considered to be mechanical complications, and analysis was performed using survival methods. Of 683 evaluated catheters, 351 were allocated to the add-on device arm and 332 to the control arm. Despite randomisation, patients in the add-on device group were older (P=0.048), less likely to have human immunodeficiency virus (P=0.02) and more likely to have received antibiotics (P=0.05). After adjustment for these variables, the hazard ratio for phlebitis remained non-significant (hazard ratio: 0.95; 95% confidence interval: 0.7-1.3), but the risk of mechanical complications became lower in the add-on device arm (0.68; 0.5-0.94). This translated into a trend towards a lower risk of any complication (0.83; 0.67-1.01). The beneficial effect on mechanical or all complications was noticeable after six days of catheterisation. Add-on devices do not reduce the incidence of phlebitis but may prevent mechanical complications. However, the impact of add-on devices on the incidence of all complications is at most small and only apparent after the sixth day of catheter use.

Feasibility of MRI-guided large-core-needle biopsy of suspiscious breast lesions at 3 T

The feasibility of large-core-needle magnetic resonance imaging (MRI)-guided breast biopsy at 3 T was assessed. Thirty-one suspicious breast lesions shown only by MRI were detected in 30 patients. Biopsy procedures were performed in a closed-bore 3-T clinical MR system on a dedicated phased-array breast coil with a commercially available add-on stereotactic biopsy device. Tissue sampling was technically successful in 29/31 (94%) lesions. Median lesion size (n = 29) was 9 mm. Histopathological analysis showed 19 benign lesions (66%) and one inconclusive biopsy result (3%). At follow-up of these lesions, 15 lesions showed no malignancy, no information was available in three patients and two lesions turned out to be malignant (one lesion at surgical excision 1 month after biopsy and one lesion at a second biopsy because of a more malignant enhancement curve at 12-months follow-up MRI). Nine biopsy results showed a malignant lesion (31%) which were all surgically removed. No complications occurred. MRI-guided biopsy at 3 T is a safe and effective method for breast biopsy in lesions that are occult on mammography and ultrasound. Follow-up MRI at 6 months after the biopsy should be performed in case of a benign biopsy result.

Upright stereotactic vacuum‐assisted needle biopsy of suspicious breast microcalcifications

Stereotactic core needle biopsy is a useful technique for evaluation of suspicious breast microcalcifications. The development of the 11-G vacuum-assisted biopsy system offers another method of minimally invasive biopsy carried out on a conventional mammography unit. We evaluate its usefulness, efficacy and safety in Asian women. Vacuum-assisted biopsy was carried out through the lateral approach using an add-on stereotactic device attached to a mammography unit. One hundred and five lesions were sampled in 97 patients. Excisional biopsy was subsequently Carried out for diagnosis of atypical ductal hyperplasia or carcinoma in high-risk patients. Patients with benign diagnosis underwent mammographic follow up. The technical success rate was 97%. An average of 13.5 tissue cores were retrieved for each lesion. The histopathological result obtained from mammotome was benign in 84.8% and malignant in 15.2%. The benign microcalcifications were predominantly fibrocystic change (n = 42) whereas the malignant microcalcifications included ductal carcinoma in situ (n = 15) and invasive carcinoma (n = 1). Twenty-two patients underwent subsequent open surgical biopsy but no underestimation of disease was seen. Only two patients had vasovagal syncope and three others felt unwell during the biopsy. Nine patients had small haematomas, which resolved spontaneously. Vacuum-assisted biopsy carried out on an upright stereotactic mammography unit is a safe and effective method for evaluation of suspicious microcalcifications.

Design of a Device for Simultaneous Particle Size and Electrostatic Charge Measurement of Inhalation Drugs

To develop a device for simultaneous measurement of particle aerodynamic diameter and electrostatic charge of inhalation aerosols. An integrated system consisting of an add-on charge measurement device and a liquid impinger was developed to simultaneously determine particle aerodynamic diameter and electrostatic charge. The accuracy in charge measurement and fine particle fraction characterization of the new system was evaluated. The integrated system was then applied to analyze the electrostatic charges of a DPI formulation composed of salbutamol sulphate-Inhalac 230 dispersed using a Rotahaler. The charge measurement accuracy was comparable with the Faraday cage method, and incorporation of the charge measurement module had no effect on the performance of the liquid impinger. Salbutamol sulphate carried negative charges while the net charge of Inhalac 230 and un-dispersed salbutamol sulphate was found to be positive after being aerosolized from the inhaler. The instantaneous current signal was strong with small noise to signal ratio, and good reproducibility of charge to mass ratio was obtained for the DPI system investigated. A system for simultaneously measuring particle aerodynamic diameter and aerosol electrostatic charges has been developed, and the system provides a non-intrusive and reliable electrostatic charge characterization method for inhalation dosage forms.

Passive Control of Vortex-Induced Vibrations: An Overview

Vortex-Induced Vibration (VIV) is a possible phenomenon in situations where a bluff body interacts with a fluid flow. There are many potential areas where this phenomenon could be observed such as in heat exchanger tube bundles, marine structures, bridges, power transmission lines etc. Due to VIV, the structures could be subjected to very large transverse vibrations which may lead to their fatigue failure. Hence, controlling vortex-induced vibrations or if possible, suppressing them is of paramount importance in practical situations, particularly in a situation like marine deep water environment where the fault diagnosis and repair would be extremely difficult. This could be achieved by passive and active control means. In this paper, a review of the passive control of VIV through various means is presented particularly emphasizing some recent inventions patented in this area. The review indicates that, in practical applications especially in marine engineering situations, passive control measures such as employing a streamline fairing or a helical strake, prolong the life of offshore structures by protecting them from vortex-induced vibrations. The paper includes recent patents on this topic and concludes with a note on the current and future developments expected in the passive control of VIV. Keywords: Vortex-induced vibrations, passive control, damping, streamlining, add-on device, surface modification, boundary layer control, control cylinder

Stereotactic Vacuum-Assisted Biopsy of Microcalcifications Using an Upright Add-On Type Stereotactic Mammography Unit

Purpose: This study examined the yield of mammographically detected calcifications following a stereotactic vacuum-assisted biopsy (SVAB) using an upright add-on type stereotactic device. Materials and Methods: Ninety-two women underwent a SVAB between April 2002 and December 2005, and 90 calcifications obtained by the SVAB were evaluated retrospectively. The calcification retrieval rate was examined. The false negative and underestimation rates were determined by comparing the biopsy results with the results from surgery and follow-up mammography. Results: The calcification retrieval rate was 97.8% (90/92). The histopathology of the 90 lesions was benign for 66 (73.3%), borderline for 3 (3.3%) and malignant for 21 (23.3%). A total of 22 malignancies were confirmed surgically. SVAB had a false negative rate of 4.5 % (1/22). The underestimation rate of a surgically excised atypical ductal hyperplasia (ADH) and of ductal carcinoma in situ (DCIS) was 50% (1/2) and 10% (2/20), respectively. Conclusion: The use of SVAB with an upright add-on type stereotactic device is an efficient biopsy method for mammographically detected microcalcifications, with low false negative and high calcification retrieval rates.

Hybrid Nutation Damper for Controlling Galloping Power Lines

A novel add-on device, called a hybrid nutation damper (HND), is proposed to control galloping on both single and bundled conductors of overhead power lines. An HND employs a nutation damper (also called a tuned liquid damper) as an energy dissipator, and a tuned mass damper as the mechanism to transfer a conductor's plunge motion into a nutation damper's rotational motion. An HND is in principle effective for any type of galloping. It is particularly effective for a plunge galloping-the one most often observed in the field and existing control devices have difficulty handling. An HND is simplified as an equivalent two degrees-of-freedom model and is then incorporated into existing three degrees-of-freedom based, galloping software. A two-tiered procedure is established to optimize an HND's performance. Numerical examples show that an HND is invariably very promising in controlling galloping

Bioluminescence Detection Using a Novel MEMS Modulation Technique

A novel modulation microelectromechanical systems (MEMS) technique is introduced to overcome the low-frequency (flicker) noise of photodiodes. The transmissive shutter is placed as an add-on device between an optical source and a photodiode, and is implemented as a method to enhance the signal-to-noise ratio, adapted for the detection of low-intensity bioluminescence. The detection of the signal below the noise level of photodetector is demonstrated by implementing a lock-in amplifier that registers the modulated signal at four times the frequency of the electrical excitation signal of the modulator. This work represents the first reported attempt to use a MEMS modulation technique for the detection of low-intensity signals

Force Free Add-on Position Measurement Device for the TCP of Parallel Kinematic Manipulators

The position of the tool center point (TCP) of a parallel kinematic manipulator (PKM) is traditionally being measured indirectly by means of the position measurement of the drives. Cutting forces and acceleration forces cause displacements of the TCP, which cannot be detected from the position measurement of the drives. To improve the position accuracy of the TCP a force free add-on position measurement device is suggested. The kinematic design of such a measurement device, the calibration and its application for feedback control and improved TCP positioning in the presence of external forces is described. Experimental results are presented to illustrate the expected improvements in TCP positioning.

Innovating lifetime microscopy: a compact and simple tool for life sciences, screening, and diagnostics

Fluorescence lifetime imaging microscopy (FLIM) allows the investigation of the physicochemical environment of fluorochromes and protein-protein interaction mapping by Forster resonance energy transfer (FRET) in living cells. However, simpler and cheaper solutions are required before this powerful analytical technique finds a broader application in the life sciences. Wide-field frequency-domain FLIM represents a solution whose application is currently limited by the need for multichannel-plate image intensifiers. We recently showed the feasibility of using a charge-coupled device/complementory metal-oxide semiconductor (CCD/CMOS) hybrid lock-in imager, originally developed for 3-D vision, as an add-on device for lifetime measurements on existing wide-field microscopes. In the present work, the performance of the setup is validated by comparison with well-established wide-field frequency-domain FLIM measurements. Furthermore, we combine the lock-in imager with solid-state light sources. This results in a simple, inexpensive, and compact FLIM system, operating at a video rate and capable of single-shot acquisition by virtue of the unique parallel retrieval of two phase-dependent images. This novel FLIM setup is used for cellular and FRET imaging, and for high-throughput and fast imaging applications. The all-solid-state design bridges the technological gap that limits the use of FLIM in areas such as drug discovery and medical diagnostics.

Combined Affinity and Catalytic Biosensor: In Situ Enzymatic Activity Monitoring of Surface-Bound Enzymes

Surface Plasmon Resonance Spectroscopy (SPR) and miniature Fiber Optic Absorbance Spectroscopy (FOAS) were combined to monitor in situ and quantitatively an enzymatic model reaction catalyzed by beta-lactamase. The enzyme was covalently immobilized to the gold surface of a SPR chip, which was functionalized with NeutrAvidin through a biotinylated alkanethiol self-assembled monolayer, thus serving as a highly sensitive affinity biosensor. SPR was used to control the density of the surface-bound enzyme. Nitrocefin as the enzymatic substrate was allowed to react with the immobilized enzyme in the SPR flow cell, and its turnover was detected with the FOAS system acting as the catalytic biosensor. The coupling of the two techniques has a substantial potential for highly controlled on-line monitoring of surface-bound enzyme activity. The FOAS technique may also be easily employed as an add-on device to other types of affinity sensing instruments.

Add-on Device for Stereotactic Core-Needle Breast Biopsy: How Many Biopsy Specimens Are Needed for a Reliable Diagnosis?

To prospectively determine whether there is a minimum number of cores required for histopathologic diagnosis of mammographically detected nonpalpable breast lesions with an add-on 14-gauge stereotactic core-needle biopsy device. The study was approved by the ethics committee of the hospital; informed consent was obtained. Biopsy was performed in 197 patients with 205 lesions (97 masses, 108 microcalcifications). The first sample (from the center) was collected in container A; second and third samples (2 mm from center), in container B; and additional samples, in container C. Malignancies, atypical ductal hyperplasia (ADH), and radial scars were excised. Benign lesions were followed up mammographically (mean, 24 months). Strict sensitivity and working sensitivity were calculated separately. Stereotactic biopsy with diagnosis of a nonmalignant lesion that, after surgery, proved to be malignant was considered false-negative when strict sensitivity was calculated. Stereotactic biopsy with diagnosis of ADH or radial scar was considered true-positive if the findings at surgery corresponded to the results at biopsy or indicated malignancy and was considered false-positive if the findings at surgery were benign when working sensitivity was calculated. Sensitivity, specificity, and overall accuracy of stereotactic biopsy were determined for masses and microcalcifications in all three containers by using surgical samples and findings at mammographic follow-up as reference. At chi2 analysis, P < .05 was considered to indicate significant difference. Strict sensitivity of the first sample was 77% (66 of 86) (90% [35 of 39] for masses, 66% [31 of 47] for microcalcifications). Results of the first sample were false-negative significantly more often in microcalcifications (n = 16) than in masses (n = 4) (P = .010). Combined results of containers A and B (ie, three samples) yielded higher strict sensitivity than those with first sample alone (95% [37 of 39] for masses [P = .196], 91% [43 of 47] for microcalcifications [P < .001]). With multiple samples, strict and working sensitivity were both 100% (39 of 39) for masses and 91% (43 of 47) and 98% (46 of 47), respectively, for microcalcifications. Four false-negative diagnoses (ADH, three cases; lesion with discordant mammographic and stereotactic biopsy findings, one case) were microcalcifications. More than three samples are needed (a minimum number was not determined) for a histologic diagnosis of a mass lesion by using an add-on stereotactic biopsy device.

Laser assisted electron beam conditioning for free electron lasers

A new method for electron beam conditioning in free electron lasers is proposed. It uses the electron beam interaction with a laser light in two wiggler magnets separated by a strong-focusing channel. The effect of the conditioning is illustrated by the example of a hypothetical single-pass, high-gain free electron laser operating in the self-amplified spontaneous emission mode with the x-ray emission at ${\ensuremath{\lambda}}_{x}=1.5\text{ }\AA{}$. The proposed conditioner is relatively compact and can be used as a practical add-on device to short x-ray wavelength free electron lasers.

A low-noise preamplifier for [formula omitted]-ray sensors with add-on device for large-signal management

A new charge-sensitive preamplifier for High Purity Germanium γ -ray detectors has been built and tested. It comprises an over-load recovery device that reduces the dead time brought about by hits of energetic particles. The amplitude of the large signals is reconstructed from Time-Over-Threshold measurements performed along the reset transients. Using such a technology an extremely wide energy range of 10 keV to 30 MeV, or 70 dB, is obtained. With a count rate of 6 kHz a resolution of 1.1 keV fwhm is obtained on the 152Eu 122 keV line and of ∼5 perthousand on pulser lines in the energy range of 5–30 MeV.