Effects of buprenorphine on model development in an adjuvant-induced monoarthritis rat model

Complete Freund’s adjuvant (CFA)-induced arthritis in rats is a common animal model for studying chronic inflammatory pain. However, modelling of the disease is associated with unnecessary pain and impaired animal wellbeing, particularly in the immediate post-induction phase. Few attempts have been made to counteract these adverse effects with analgesics. The present study investigated the effect of buprenorphine on animal welfare, pain-related behaviour and model-specific parameters during the disease progression in a rat model of CFA-induced monoarthritis. The aim was to reduce or eliminate unnecessary pain in this model, in order to improve animal welfare and to avoid suffering, without compromising the quality of the model. Twenty-four male Sprague Dawley rats were injected with 20 μl of CFA into the left tibio-tarsal joint to induce monoarthritis. Rats were treated with either buprenorphine or carprofen for 15 days during the disease development, and were compared to a saline-treated CFA-injected group or a negative control group. Measurements of welfare, pain-related behaviour and clinical model-specific parameters were collected. The study was terminated after 3 weeks, ending with a histopathologic analysis. Regardless of treatment, CFA-injected rats displayed mechanical hyperalgesia and developed severe histopathological changes associated with arthritis. However, no severe effects on general welfare were found at any time. Buprenorphine treatment reduced facial pain expression scores, improved mobility, stance and lameness scores and it did not supress the CFA-induced ankle swelling, contrary to carprofen. Although buprenorphine failed to demonstrate a robust analgesic effect on the mechanical hyperalgesia in this study, it did not interfere with the development of the intended pathology

Employing infrared microscopy (IRM) in combination with a pre-trained neural network to visualise and analyse the defect distribution in Cadmium Telluride crystals

While Cadmium Telluride (CdTe) excels in terms of photon radiation absorption properties and outperforms silicon (Si) in this respect, the crystal growth, characterization and processing into a radiation detector is much more complicated. Additionally, large concentrations of extended crystallographic defects, such as grain boundaries, twins, and tellurium (Te) inclusions, vary from crystal to crystal and can reduce the spectroscopic performance of the processed detector. A quality assessment of the material prior to the complex fabrication process is therefore crucial. To locate the Te-defects, we scan the crystals with infrared microscopy (IRM) in different layers, obtaining a 3D view of the defect distribution. This provides us with important information on the defect density and locations of Te inclusions, and thus a handle to assess the quality of the material. For the classification of defects in the large amount of IRM image data, a convolutional neural network is employed. From the post-processed and analysed IRM data, 3D defect maps of the CdTe crystals are created, which make different patterns of defect agglomerations inside the crystals visible. In total, more than 100 crystals were scanned with the current IRM setup. In this paper, we compare two crystal batches, each consisting of 12 samples. We find significant differences in the defect distributions of the crystals.Peer reviewe

Effects of buprenorphine on acute pain and inflammation in the adjuvant-induced monoarthritis rat model

Background and aim: Animal modelling of arthritis is often associated with pain and suffering. Severity may be reduced with the use of analgesia which is, however, often withheld due to concerns of introducing a confounding variable. It is therefore important to design and validate pain relief protocols that reduce pain without compromising the scientific objectives. The present study evaluated the effect of buprenorphine analgesia in the immediate post-induction period of an adjuvant-induced monoarthritic rat model. The aim of this study was to extend previous work on refinement of the model by alleviating unnecessary pain. Methods: Male and female Sprague Dawley rats were injected with 20 μl of complete Freund's adjuvant (CFA) into the left ankle. Rats were treated with buprenorphine, either injected subcutaneously or ingested voluntarily, and were compared to rats given subcutaneous injections with vehicle (saline or pure nut paste) or carprofen the first three days post CFA-injection. Measurements of welfare, clinical model-specific parameters and pain-related behaviour were assessed. Results: Buprenorphine, administered either subcutaneously (0.10 or 0.15 mg/kg, twice daily) or by voluntary ingestion in nut paste (1.0 or 3.0 mg/kg, twice daily), improved mobility, stance, rearing and lameness scores significantly 7 h post CFA-injection. Mechanical hyperalgesia peaked at 7 h and was significantly lower in buprenorphine-treated animals, compared to vehicle-treated animals. Joint circumference was highest 24–72 h after CFA injection. Animals treated with buprenorphine did not decrease in joint circumference, opposite carprofen treated animals. Conclusion: Buprenorphine, administered either subcutaneously or by voluntary ingestion, provides adequate analgesia for both sexes within the first 24 h post CFA-injection. Buprenorphine treatment improved clinical scores and appeared not to suppress the inflammatory response. The present study supports previous findings that voluntarily ingested buprenorphine is an effective alternative to repeated injections

Modeling the impact of defects on the charge collection efficiency of a Cadmium Telluride detector

Cadmium telluride is a favorable material for X-ray detection as it has an outstanding characteristic for room temperature operation. It is a high-Z material with excellent photon radiation absorption properties. However, CdTe single crystals may include a large number of extended crystallographic defects, such as grain boundaries, twins, and tellurium (Te) inclusions, which can have an impact on detector performance. A Technology Computer Aided Design (TCAD) local defect model has been developed to investigate the effects of local defects on charge collection efficiency (CCE). We studied a 1 mm thick Schottky-type CdTe radiation detector with transient current technique by using a red laser at room temperature. By raster scanning the detector surface we were able to study signal shaping within the bulk, and to locate surface defects by observing their impact on the CCE. In this paper we present our TCAD model with localized defect, and compare the simulation results to TCT measurements. In the model an inclusion with a diameter of 10 mu m was assumed. The center of the defect was positioned at 6 mu m distance from the surface. We show that the defect has a notable effect on current transients, which in turn affect the CCE of the CdTe detector. The simulated charge collection at the position of the defect decreases by 80 % in comparison to the defect-free case. The simulations show that the defects give a characteristic shape to TCT signal. This can further be used to detect defects in CdTe detectors and to estimate the overall defect density in the material.Peer reviewe

Contributions to Loss Across the Magnetopause During an Electron Dropout Event

Dropout events are dramatic decreases in radiation belt electron populations that can occur in as little as 30 minutes. Loss to magnetopause due to a combination of magnetopause shadowing and outward radial transport plays a significant role in these events. We examine the dropout of relativistic electron populations during the October 2012 geomagnetic storm using simulated electron phase space density, evaluating the contribution of different processes to losses across the magnetopause. We compare loss contribution from outward transport calculated using a standard empirical radial diffusion model that assumes a dipolar geomagnetic field to an event-specific radial diffusion model evaluated with a non-dipolar geomagnetic field. We additionally evaluate the contribution of Shabansky type 1 particles, which bounce along magnetic field lines with local equatorial maxima, to the loss calculated during this event. We find that the empirical radial diffusion model with a dipolar background field underestimates the contribution of radial diffusion to this dropout event by up to 10% when compared to the event-specific, non-dipolar radial diffusion model. We additionally find that including Shabansky type 1 particles in the initial electron phase space density, that is, allowing some magnetic field lines distorted from the typical single-minima configuration in drift shell construction, increases the calculated loss by an average of 0.75%. This shows that the treatment of the geomagnetic field significantly impacts the calculation of electron losses to the magnetopause during dropout events, with the non-dipolar treatment of radial diffusion being essential to accurately quantify the loss of outer radiation belt populations.Peer reviewe

Processing of AC-coupled n-in-p pixel detectors on MCz silicon using atomic layer deposited aluminium oxide

We report on the fabrication of capacitively (AC) coupled n(+)-in-p pixel detectors on magnetic Czochralski silicon substrates. In our devices, we employ a layer of aluminium oxide (Al2O3) grown by atomic layer deposition (ALD) as dielectric and field insulator, instead of the commonly used silicon dioxide (SiO2). As shown in earlier research, Al2O3 thin films exhibit high negative oxide charge, and can thus serve as a substitute for p-stop/p-spray insulation implants between pixels. In addition, they provide far higher capacitance densities than SiO2 due to their high dielectric constant, permitting more efficient capacitive coupling of pixels. Furthermore, metallic titanium nitride (TiN) bias resistors are presented as an alternative to punch-through or poly-Si resistors. Devices obtained by the above mentioned process are characterized by capacitance-voltage and current-voltage measurements, and by 2 MeV proton microprobe. Results show the expected high negative charge of the Al2O3 dielectric, uniform charge collection efficiency over large areas of pixels, and acceptable leakage current densities.Peer reviewe

Effects of Transdermal Fentanyl Treatment on Acute Pain and Inflammation in Rats with Adjuvant-induced Monoarthritis

Eliminating unnecessary pain is an important requirement of performing animal experimentation, including reducing and controlling pain of animals used in pain research. The goal of this study was to refine an adjuvant-induced monoarthritis model in rats by providing analgesia with a transdermal fentanyl solution (TFS). Male and female Sprague-Dawley rats, single- or pair-housed, were injected with 20 μL of complete Freund adjuvant (CFA) into the left ankle joint. CFA-injected rats treated with a single dose of transdermal fentanyl solution (0.33 or 1 mg/kg) were compared with an untreated CFA-injected group and sham groups that received either no treatment or TFS treatment (1 mg/kg) during 72 h. At the tested doses, TFS reduced mechanical hyperalgesia and improved the mobility, stance, rearing, and lameness scores at 6 h after CFA injection. Joint circumferences were not reduced by TFS treatment, and no significant differences were detected between the 2 doses of TFS, or between single- and pair-housed rats. Treatment with TFS did not appear to interfere with model development and characteristics. However, overall, the analgesic effect was transient, and several opioid-related side effects were observed

Characterization of magnetic Czochralski silicon devices with aluminium oxide field insulator : effect of oxygen precursor on electrical properties and radiation hardness

Aluminium oxide (Al2O3) has been proposed as an alternative to thermal silicon dioxide (SiO2) as field insulator and surface passivation for silicon detectors, where it could substitute p-stop/p-spray insulation implants between pixels due to its negative oxide charge, and enable capacitive coupling of segments by means of its higher dielectric constant. Al2O3 is commonly grown by atomic layer deposition (ALD), which allows the deposition of thin layers with excellent precision. In this work, we report the electrical characterization of single pad detectors (diodes) and MOS capacitors fabricated on magnetic Czochralski silicon substrates and using Al2O3 as field insulator. Devices are studied by capacitance-voltage, current-voltage, and transient current technique measurements. We evaluate the influence of the oxygen precursors in the ALD process, as well as the effect of gamma irradiation, on the properties of these devices. We observe that leakage currents in diodes before the onset of breakdown are low for all studied ALD processes. Charge collection as measured by transient current technique (TCT) is also independent of the choice of oxygen precursor. The Al2O3 films deposited with O-3 possess a higher negative oxide charge than films deposited by H2O, However, in diodes a higher oxide charge is linked to earlier breakdown, as has been predicted by simulation studies. A combination of H2O and O-3 precursors results in a good compromise between the beneficial properties provided by the respective individual precursors.Peer reviewe

Quality assessment of cadmium telluride as a detector material for multispectral medical imaging

Cadmiumtelluride (CdTe) is a high-Z material with excellent photon radiation absorption properties, making it a promising material to include in radiation detection technologies. However, the brittleness of CdTe crystals as well as their varying concentration of defects necessitate a thorough quality assessment before the complex detector processing procedure. We present our quality assessment of CdTe as a detector material for multispectralmedical imaging, a research which is conducted as part of the Consortium Project Multispectral Photon-counting for Medical Imaging and Beam characterization (MPMIB). The aim of the project is to develop novel CdTe detectors and obtain spectrum-per-pixel information that make the distinction between different radiation types and tissues possible. To evaluate the defect density inside the crystals - which can deteriorate the detector performance - we employ infrared microscopy (IRM). Posterior data analysis allows us to visualise the defect distributions as 3D defect maps. Additionally, we investigate front and backside differences of the material with current-voltage (IV) measurements to determine the preferred surface for the pixelisation of the crystal, and perform test measurements with the prototypes to provide feedback for further processing. We present the different parts of our quality assessment chain and will close with first experimental results obtained with one of our prototype photon-counting detectors in a small tomographic setup.Peer reviewe