Frequency division multiplexing readout of a transition edge sensor bolometer array with microstrip-type electrical bias lines.

We demonstrate multiplexed readout of 43 transition edge sensor (TES) bolometers operating at 90 mK using a frequency division multiplexing (FDM) readout chain with bias frequencies ranging from 1 to 3.5 MHz and a typical frequency spacing of 32 kHz. We improve the previously reported performance of our FDM system by two important steps. First, we replace the coplanar wires with microstrip wires, which minimize the cross talk from mutual inductance. From the measured electrical cross talk (ECT) map, the ECT of all pixels is carrier leakage dominated. Only five pixels show an ECT level higher than 1%. Second, we reduce the thermal response speed of the TES detectors by a factor of 20 by increasing the heat capacity of the TES, which allows us to bias all TES detectors below 50% in transition without oscillations. We compare the current-voltage curves and noise spectra of the TESs measured in single-pixel mode and multiplexing mode. We also compare the noise equivalent power (NEP) and the saturation power of the bolometers in both modes, where 38 pixels show less than 10% difference in NEP and 5% difference in saturation power when measured in the two different modes. The measured noise spectrum is in good agreement with the simulated noise based on measured parameters from an impedance measurement, confirming that our TES is dominated by phonon noise.

Frequency shift algorithm: Application to a frequency-domain multiplexing readout of x-ray transition-edge sensor microcalorimeters.

In the frequency-domain multiplexing (FDM) scheme, transition-edge sensors (TESs) are individually coupled to superconducting LC filters and AC biased at MHz frequencies through a common readout line. To make efficient use of the available readout bandwidth and to minimize the effect of non-linearities, the LC resonators are usually designed to be on a regular grid. The lithographic processes, however, pose a limit on the accuracy of the effective filter resonance frequencies. Off-resonance bias carriers could be used to suppress the impact of intermodulation distortions, which, nonetheless, would significantly affect the effective bias circuit and the detector spectral performance. In this paper, we present a frequency shift algorithm (FSA) to allow off-resonance readout of TESs, while preserving the on-resonance bias circuit and spectral performance, demonstrating its application to the FDM readout of an x-ray TES microcalorimeter array. We discuss the benefits in terms of mitigation of the impact of intermodulation distortions at the cost of increased bias voltage and the scalability of the algorithm to multi-pixel FDM readout. We show that with FSA, in the multi-pixel and frequencies shifted on-grid, the line noises due to intermodulation distortion are placed away from the sensitive region in the TES response and the x-ray performance is consistent with the single-pixel, on-resonance level.

Electrical cross talk of a frequency division multiplexing readout for a transition edge sensor bolometer array.

We have characterized and mapped the electrical cross talk (ECT) of a frequency division multiplexing (FDM) system with a transition edge sensor (TES) bolometer array, which is intended for space applications. By adding a small modulation at 120 Hz to the AC bias voltage of one bolometer and measuring the cross talk response in the current noise spectra of the others simultaneously, we have for the first time mapped the ECT level of 61 pixels with a nominal frequency spacing of 32 kHz in a 61 × 61 matrix and a carrier frequency ranging from 1 MHz to 4 MHz. We find that about 94% of the pixels show an ECT level of less than 0.4%. Only the adjacent pixels reach this level, and the ECT for the rest of the pixels is less than 0.1%. We also observe higher ECT levels, up to 10%, between some of the pixels, which have bundled long, parallel coplanar wires connecting TES bolometers to inductor-capacitor filters. In this case, the high mutual inductances dominate. To mitigate this source of ECT, the coplanar wires should be replaced by microstrip wires in the array. Our study suggests that an FDM system can have a relatively low ECT level, e.g., around 0.4% if the frequency spacing is 30 kHz. Our results successfully demonstrate a low electrical cross talk for a space FDM technology.

Movies of dopamine transporter occupancy with ultra-high resolution focusing pinhole SPECT.

A pivotal question in neuropharmacology is how the function of neurotransmitter systems relates to psychiatric diseases. In experimental neuropharmacology, we have dreamt about a looking glass that would allow us to see neurotransmitter systems in action, and about animals that would faithfully serve us as models for human psychiatric disease. Analysis of animal models has been limited by the availability of methods to study in vivo neurotransmitter dynamics. Now, a single photon emission computed tomography system called U-SPECT can localize dopamine transporters in sub-compartments of the mouse brain during a range of points in time. Applied to the midbrain dopamine system of different models of disease, this will aid the understanding of dynamic processes of this neurotransmitter that underlie brain functions and human brain pathology.

The polymer Polyactive as a bone-filling substance: an experimental study in rabbits.

The biocompatible, osteoconductive and resorbable polymer Polyactive (PA) was investigated for its performance as a bone-graft substitute. The model consisted of a 4 mm borehole, 1.5 cm distal of the major trochanter in both femurs of a rabbit, of which one was filled with a cylinder of porous PA. The other was left untreated. PA70/30 and PA60/40 were investigated, both before and after being incubated with allogenic bone marrow. Analyses were performed after 4, 8, 26 and 52 weeks and comprised dual energy X-ray absorptiometry (DXA) and image analysis of histological sections. DXA revealed an increased bone mineral density in the filled defects compared to the controls, both at the defect and immediately proximal and distal of the defect. Histology showed that gap-bridging had occurred within 8 weeks, with 80%-90% of the pores of PA70/30 and PA60/40 occupied by new bone, and an intimate bone-PA contact. PA70/30 seemed to be more suitable compared to PA60/40, in that the highest amount of bone was formed within the shortest period of time. Incubation of PA with allogenic bone marrow resulted in inflammatory reactions at the sites of implantation, which delayed bone growth, but did not prevent it. It was concluded that PA70/30 and PA60/40 are suitable bone-graft substitutes.

Quantitative histological analysis of bony ingrowth within the biomaterial Polyactive implanted in different bone locations: an experimental study in rabbits.

The quantity of bone formed in cylinders of a newly developed erodible copolymer, Polyactive (PA60/40) was examined. PA60/40 was implanted in three different bone locations in the rabbit: in the cortex, in bone marrow and in trabecular subchondral bone. Bony ingrowth was assessed after 4, 8, 26 and 52 w after the operation and investigated by histology and image analysis. The ingrowth of bone was observed in PA60/40 placed in the cortex from 4 w onwards. After 8 w, more than 90% of the pores of the biomaterial were filled with dense bone. In bone marrow, initially some bone formation was seen. After 26 w, all newly formed bone was resorbed. Subchondral bone formation was less than in the cortex of the femur, but somewhat comparable to the amount of bone found in healthy trabecular bone. Bone formation appeared not to be affected by the degradation of the biomaterial. It was concluded that Polyactive is a suitable bone graft substitute. Bone formation within PA60/40 is site-dependent and this follows Wolff 's law.

A novel method to examine the phenotype of chondrocytes.

Tissue engineering of articular cartilage in order to restore the function of degenerated, diarthrodial joints is currently widely under investigation. The results obtained thus far indicate that proper control of the differentiation of the cells used for this purpose is essential to produce and maintain a hyaline-like matrix. In this study, a procedure is described by which differentiation of chondrocytes in vitro and ex vivo can be studied. The method involves quantitative assessment of mRNA for different collagens, which are markers for differentiation of chondrocytes, by competitive PCR. In a culture system employing human osteoarthritic chondrocytes, mRNAs for the alpha1-chains of collagen types I, II and X are quantified. The procedure is fast, specific and sensitive. However, several controls should be included to ascertain the reliability of the assessment.

Dystrophic kyphoscoliosis in neurofibromatosis type I: a report of two cases and review of the literature.

We report two cases of dystrophic scoliosis in neurofibromatosis, each of particular interest. In the first, kyphosis was present with vertebral rotatory subluxation but no neurologic impairment, while the second patient showed manifest paraplegia due to rapidly progressive kyphoscoliosis. The importance of early surgical stabilisation, both front and back if possible, is stressed. Very sharp curves with progressive myelopathy should not be treated with halo-femoral traction because of the potential danger of evoking permanent paraplegia.

Long-term results of rib perichondrial grafts for repair of cartilage defects in the human knee.

Eighty-eight patients with articular cartilage defects in the knee were treated by perichondrial arthroplasty between 1986 and 1992. An autogenous strip of costal perichondrium was fixed in place with fibrin glue, followed by immobilisation, continuous passive motion, and partial weightbearing. The results were evaluated using the Hospital for Special Surgery Score for knee function, radiographs, arthroscopy and the patient's subjective opinion. The results after a mean follow-up of 52 months were good in 38%, fair in 8% and poor in 55%. Previous drilling or shaving of a defect, concomitant osteoarthritis, older age and a long history of complaints proved to be contraindications. Good results were seen in 91% of isolated defects. Perichondrial arthroplasty can be beneficial in the repair of cartilage defects. It will reduce symptoms in carefully selected cases, and avoid more extensive operations for osteoarthritis.

Femoral canal occlusion in total hip replacement using a resorbable and flexible cement restrictor.

We have investigated the use of a conically-shaped cement plug made of Polyactive (PA), a biodegradable copolymer. The flexibility and hydrogel properties were thought to facilitate occlusion of the femoral canal even when it was oval or irregular in shape. The function of the plug was first compared with that of the Thackray polyethylene model in 16 artificial plastic femora. The maximum intramedullary pressure achieved during cementing was ten times higher with the biodegradable model. Migration or leakage of cement did not occur when the diameter of the femoral canal was equal to or smaller than the diameter of the plug. We also showed that the biodegradable properties of this implant were such that it did not require removal during revision. The new plug was tested in a pilot clinical trial. At two years only two out of 21 patients had evidence of migration or leakage of cement, probably due to a mismatch in the size of plug and femoral canal. There were no local changes in the femur.

Local corticosteroid injection versus Cyriax-type physiotherapy for tennis elbow.

We performed a prospective, randomised trial on 106 patients to compare the effects of local corticosteroid injections with physiotherapy as advocated by Cyriax in the treatment of tennis elbow. The main outcome measures were the severity of pain, pain provoked by resisted dorsiflexion of the wrist, and patient satisfaction. At six weeks 22 of 53 patients in the injection group were free from pain compared with only three in the physiotherapy group. In the corticosteroid-treated group 26 patients had no pain on resisted dorsiflexion of the wrist compared with only three in the physiotherapy group. Thirty-five patients who had injections and 14 who had physiotherapy were satisfied with the outcome of treatment at six weeks. At the final assessment there were 18 excellent and 18 good results in the corticosteroid group and one excellent and 12 good results in the physiotherapy group. There was a significant increase in grip strength in both groups but those with injections had a significantly better result. After one year there were no significant differences between the two groups. Half of the patients, however, had received only the initial treatment, 20% had had combined therapy and 30% had had surgery. We conclude that at six weeks, treatment with corticosteroid injections was more effective than Cyriax physiotherapy and we recommend it because of its rapid action, reduction of pain and absence of side-effects.

The effect in vitro of irrigating solutions on intact rat articular cartilage.

Rat patellae were preincubated with culture medium M199 for one hour and then with either fresh culture medium or Ringer's solution, Ringer lactate, Ringer glucose, normal saline or Betadine for another hour. The rate of proteoglycan synthesis in the articular cartilage was then measured by uptake of 35SO4 for the next 16 hours. Cartilage metabolism was inhibited by all of the solutions even after a recovery time of 16 hours. The inhibition was by 5% for Ringer's solution, 10% for Ringer glucose (p < 0.01), 20% for saline and Ringer lactate (p < 0.001) and 55% for Betadine (p < 0.001). Ringer's solution is therefore the best choice for joint irrigation during arthroscopy or other procedures.

Prevalence of blindness and low vision of people over 30 years in the Wenchi district, Ghana, in relation to eye care programmes.

A population based survey on the prevalence of major blinding disorders was conducted in the Wenchi district in central Ghana between March and May 1991. In 10 villages, 1425 people of 30 years and older were screened, using the WHO eye examination record. The prevalence of bilateral blindness above 30 years proved to be 1.7% (best acuity < 3/60): the prevalence of low vision above 30 years was 2.0% (best visual acuity 6/18 to 3/60). The causes of blindness were determined as cataract (62.5%), onchocerciasis (12.5%), corneal opacity (non-trachomatous) (8.2%), refraction anomalies (4.2%), phthisis bulbi (4.2%), optic atrophy (4.2%), and vascular retinopathy (4.2%). In the Wenchi district, 1.0% of the population over the age of 30 years was found to need a cataract extraction because of blindness of both eyes. Another potential 1.0% needs a cataract extraction because of low vision. A minor second study (n = 149) was undertaken in the same district, but in a village in an area near the Black Volta river in which onchocerciasis is endemic. The prevalence of blindness (8.1%) and low vision (3.4%) caused by onchocerciasis and cataract both proved to be higher. The survey provided the basis for a preventive and curative eye care programme.

Thionin staining of paraffin and plastic embedded sections of cartilage.

The usefulness of thionin for staining cartilage sections embedded in glycol methacrylate (GMA) and the effect of decalcification on cartilage sections embedded in paraffin and GMA were assessed. Short decalcification periods using 5% formic acid or 10% EDTA did not influence the staining properties or the morphology of cartilage matrix and chondrocytes. The standard stain safranin O-fast green for differential staining of cartilage was used as control in these experiments. Prolonged exposure of safranin O stained sections to fast green resulted in disappearance of the safranin O stained matrix, thereby hampering the quantitative measurement of negatively charged glycosaminoglycans (GAG). Thionin stained evenly throughout all cartilage layers, independent of the staining times. In contrast to safranin O, thionin did not show metachromasia in nondehydrated cartilage sections, which made it more suitable for assessing cartilage quality in GMA embedded cartilage. To evaluate the selectivity of thionin staining in cartilage, chondroitinase ABC and trypsin digestions were carried out. Thionin staining was prevented by these enzymes in the territorial matrix, representing the interlacunar network and the chondrocyte capsule. Staining with thionin of the interterritorial matrix was only slightly reduced, possibly representing keratan sulfate and hyaluronic acid in cartilage of elderly patients. Comparison of thionin stained GMA embedded cartilage with safranin O stained paraffin embedded sections showed significant similarity in optical densitometry, indicative of the specificity of thionin bound to negatively charged GAG in cartilage. In GMA embedded cartilage morphology was relatively intact compared to paraffin embedded sections due to less shrinkage of chondrocytes and the interlacunar network.

The effect of piroxicam on the metabolism of isolated human chondrocytes.

The effect of piroxicam on the metabolism of healthy and osteoarthrotic (OA) chondrocytes was studied in vitro. The chondrocytes were obtained from five healthy, five moderately OA, and four severely OA hips or knees. The chondrocytes were cultured in a high-density, short-term in vitro model. In this culture, the healthy chondrocytes as well as the OA chondrocytes retain their metabolic properties. Piroxicam was used in concentrations ranging from 0 to 10 micrograms/ml, which is comparable to the concentrations reached in vivo after oral administration. In cultures of healthy chondrocytes, piroxicam inhibited proliferation and synthesis of proteoglycans. The metabolism of moderately damaged chondrocytes was not influenced by piroxicam. In severely damaged chondrocytes, the proliferation was significantly inhibited by piroxicam. In order to avoid the possible negative side effects of piroxicam on the metabolism of healthy and severely OA chondrocytes, piroxicam treatment of an OA joint with synovitis should be restricted to the period of the effusion.

The reliability of the Mankin score for osteoarthritis.

For the histopathological classification of the severity of osteoarthritic lesions of cartilage, the Mankin score is frequently used. A necessary constraint on the validity of this scoring system is the consistency with which cartilage lesions are classified. The intra- and interobserver agreement of the Mankin score was determined. The intra- and interobserver agreement of the 14-point Mankin score was adequate. Between observers 95% of differences were less than approximately 7 points. By a more strict definition of the elements of the Mankin score, the intraobserver differences were reduced only for some observers. The interobserver differences were only slightly reduced: between observers 95% of differences were less than approximately 6 points. We found the Mankin score to be an adequate histopathological tool.

Repair of sheep articular cartilage defects with a rabbit costal perichondrial graft.

A xenograft of costal rabbit perichondrium was transplanted to an articular cartilage defect in a sheep knee. After 12 weeks, cartilage was formed with increased calcification of the basal layer and a mean of 74 percent collagen type II. The synovium did not show any infiltration, indicating the absence of any immunologic reaction.

[Alleviation of pain through posterolateral spondylodesis in patients with prolonged severe backache]. / Pijnvermindering door posterolaterale spondylodese bij patiënten met langdurige ernstige rugklachten.

In order to study the effect of posterolateral spinal fusion on pain and returning to work of patients with chronic lower back pain, a retrospective study was carried out at the University Hospital, Maastricht. Fifty-nine patients with spondylolisthesis I or II, spondylolysis, hemisacralisation, disc degeneration and pseudoarthrosis after spinal fusion were treated by posterolateral spinal fusion. A questionnaire and visual analogue scale were used to assess the pain. The mean preoperative pain level was 8.6; the postoperative pain level was 4.5; 13 patients were without pain. Before operation 41 patients had a job; after operation 34 returned to work. Sex, age, period of complaints, indication or level of operation did not significantly affect the pain score. In particular cases, posterolateral spinal fusion diminishes pain in patients with spondylolisthesis I or II, spondylolysis or hemisacralisation in whom pain does not improve after non-operative therapy. After the operation most patients return to their work.