Granular aluminium nanojunction fluxonium qubit.

Mesoscopic Josephson junctions, consisting of overlapping superconducting electrodes separated by a nanometre-thin oxide layer, provide a precious source of nonlinearity for superconducting quantum circuits. Here we show that in a fluxonium qubit, the role of the Josephson junction can also be played by a lithographically defined, self-structured granular aluminium nanojunction: a superconductor-insulator-superconductor Josephson junction obtained in a single-layer, zero-angle evaporation. The measured spectrum of the resulting qubit, which we nickname gralmonium, is indistinguishable from that of a standard fluxonium. Remarkably, the lack of a mesoscopic parallel plate capacitor gives rise to an intrinsically large granular aluminium nanojunction charging energy in the range of tens of gigahertz, comparable to its Josephson energy. We measure coherence times in the microsecond range and we observe spontaneous jumps of the value of the Josephson energy on timescales from milliseconds to days, which offers a powerful diagnostics tool for microscopic defects in superconducting materials.

Circuit quantum electrodynamics of granular aluminum resonators.

Granular aluminum (grAl) is a promising high kinetic inductance material for detectors, amplifiers, and qubits. Here we model the grAl structure, consisting of pure aluminum grains separated by thin aluminum oxide barriers, as a network of Josephson junctions, and we calculate the dispersion relation and nonlinearity (self-Kerr and cross-Kerr coefficients). To experimentally study the electrodynamics of grAl thin films, we measure microwave resonators with open-boundary conditions and test the theoretical predictions in two limits. For low frequencies, we use standard microwave reflection measurements in a low-loss environment. The measured low-frequency modes are in agreement with our dispersion relation model, and we observe self-Kerr coefficients within an order of magnitude from our calculation starting from the grAl microstructure. Using a high-frequency setup, we measure the plasma frequency of the film around 70 GHz, in agreement with the analytical prediction.

Mindfulness-based cognitive therapy to treat multiple chemical sensitivities: a randomized pilot trial.

Multiple chemical sensitivities (MCS) is a medically unexplained and socially disabling disorder characterized by negative health effects attributed to exposure to common airborne chemicals. Currently, there is no evidence-based treatment. The objectives of the study were to assess the feasibility of an 8-week mindfulness-based cognitive therapy program (MBCT) for adults with MCS and to evaluate possible effects on psychological distress and illness perception. The study design was a randomized clinical trial. The MBCT programme comprised 8 weekly sessions of 2½ hours. Forty-two adults were screened for eligibility and 37 were included. Mean age of the participants was 51.6 years, 35 (94.6%) were female and 21 (56.8%) were unemployed. Measures of psychological distress and illness perceptions were assessed at baseline, 4 weeks, 8 weeks and at 3 months follow-up. No significant differences in effect measures were found between the groups. However, those who completed the MBCT program generally reported benefiting in terms of improved coping strategies and sleep quality. The positive verbal feedback from the participants in the MBCT group suggests that a larger randomized clinical trial on the effect of MBCT for MCS could be considered.

Production of the therapeutic radioisotope (114m)In through the (116)Cd(p,3n)(114m)In reaction.

Excitation curves for reactions induced by proton beams up to 36MeV on highly enriched (116)Cd targets were assessed. The standard stacked foil method, with monitoring of beam parameters over the whole energy region, and high resolution gamma spectrometry were used. We report cross sections for reactions leading to (113m)(,114m,115m,116m1)In and (115)Cd. A comparison with some earlier experimental data and with results of theoretical model codes ALICE-IPPE and EMPIRE are presented. Our previous estimation of use of the (116)Cd(p,3n) reaction for production of (114m)In is confirmed.

Cross section measurements of the (131)Xe(p,n) reaction for production of the therapeutic radionuclide (131)Cs.

(131)Cs is an X-ray emitter radioisotope gaining interest in prostate brachytherapy. It is generally produced via the (130)Ba(n,gamma)(131)Ba-->(131)Cs process in thermal-flux reactors. Here we investigate its cyclotron production possibilities. Excitation function of the (131)Xe(p,n)(131)Cs reaction was measured up to 35MeV using the stacked gascell technique and high-resolution X-ray spectrometry. The experimental data were compared with results of the ALICE-IPPE and EMPIRE-II codes and curves taken from the PADF and TENDL database. The calculated integral yield was 17MBq/microAh in the energy range E(p)=20-->7MeV. Comparison of cyclotron and reactor production routes was given.

Use of statistical process control in the production of blood components.

Introduction of statistical process control in the setting of a small blood centre was tested, both on the regular red blood cell production and specifically to test if a difference was seen in the quality of the platelets produced, when a change was made from a relatively large inexperienced occasional component manufacturing staff to an experienced regular manufacturing staff. Production of blood products is a semi-automated process in which the manual steps may be difficult to control. This study was performed in an ongoing effort to improve the control and optimize the quality of the blood components produced and gives an example of how to meet EU legislative requirements in a small-scale production centre. Data included quality control measurements in 363 units of red blood cells, 79 units of platelets produced by an occasional staff with 11 technologists and 79 units of platelets produced by an experienced staff with four technologists. We applied statistical process control to examine if time series of quality control values were in statistical control. Leucocyte count in red blood cells was out of statistical control. Platelet concentration and volume of the platelets produced by the occasional staff were out of control, which was not the case with the experienced staff. Introduction of control charts to a small blood centre has elucidated the difficulties in controlling the blood production and shown the advantage of using experienced regular component manufacturing staff.

Intra-articular sodium hyaluronate 2 mL versus physiological saline 20 mL versus physiological saline 2 mL for painful knee osteoarthritis: a randomized clinical trial.

OBJECTIVE: Methodological constraints weaken previous evidence on intra-articular viscosupplementation and physiological saline distention for osteoarthritis. We conducted a randomized, patient- and observer-blind trial to evaluate these interventions in patients with painful knee osteoarthritis. METHODS: We centrally randomized 251 patients with knee osteoarthritis to four weekly intra-articular injections of sodium hyaluronate 2 mL (Hyalgan 10.3 mg/mL) versus physiological saline 20 mL (distention) versus physiological saline 2 mL (placebo) and followed patients for 26 weeks. Inclusion criteria were age over 59 years and daily knee pain more than 20 mm on a 100-mm visual analogue scale (VAS) without satisfactory response to analgesics. During the trial, rescue analgesic were allowed. The primary outcome was pain on movement. The secondary outcomes were pain at rest, pain during the night, Knee Injury and Osteoarthritis Outcome Score (KOOS), Osteoarthritis Research Society International (OARSI) criteria, and global assessment of the patient's condition. RESULTS: The mean age of the patients was 69.4 years; 55% were women. The effects of hyaluronate 2 mL, physiological saline 20 mL, and physiological saline 2 mL did not differ significantly in reducing knee pain, knee function, or consumption of analgesics. Using OARSI criteria, no significant differences were found. The VAS and KOOS outcomes all improved significantly over time (p<0.0005), regardless of intervention group. No adverse events were reported. CONCLUSIONS: Intra-articular hyaluronate or distention with physiological saline did not significantly reduce pain compared with physiological saline placebo in patients with osteoarthritis of the knee.

Optimization of production yields, radionuclidic purity and hotcell shielding of SPECT and PET radionuclides produced by proton irradiation in variable energy 30 MeV cyclotrons--Part 67Ga.

Optimization of the production parameters (incident and exit proton energy, thickness of the (68)Zn target layer, decay time to start chemical processing of an irradiated target after the end of bombardment) and of the thickness of the lead shield of the processing hotcell for the cyclotron production of (67)Ga by the (68)Zn(p,2n) threshold reaction are accomplished by powerful divide et impera and binary search algorithms with the Pharmacopoeia radionuclidic purity of the (67)Ga-citrate radiopharmaceutical at a reference time and the locally accepted dose rate level for the controlled area as boundary conditions. Two sets of equations are presented (one associated with the maximum production rate, the other with the use of a minimum target layer thickness) that allow the expression of the optimized production parameters, the radionuclide yields satisfying the Pharmacopoeia requirements at the start of distribution and the necessary shielding as a function of the required activity at the start of distribution and of the maximum allowable beam current on target.

Effect of uncertainty components such as recalibration on the performance of quality control charts.

BACKGROUND: Uncertainty components (recalibration, new reagent lots, etc.) may be the source of random changes in the level of quality control (QC) values, thus causing false alarms. We propose a method for reducing false alarms. MATERIAL AND METHODS: Daily QC measurements of 22 biochemical quantities were recorded over 5 months, while methods and analyser showed no signs of malfunctioning. Each time series of QC values was subdivided according to reagent lot, electrolyte diluent or disposable electrode used. Analysis of variance (ANOVA) was used to examine whether mean levels changed significantly between subseries. For each quantity, the entire time series and each subseries were examined for autocorrelation. An X chart and an exponentially weighted moving average (EWMA) chart (or EWMAST [EWMA for stationary processes] in autocorrelated series) were calculated from the first 50 values of each series or subseries and applied to the whole series. Values falling outside the three standard deviation control limits were noted. RESULTS: In 22 out of 24 time series, the mean level differed significantly between subseries. These changes caused spurious autocorrelation. However, in 51.3 % of all subseries a significant autocorrelation could also be demonstrated. In total, 5.6 % and 29.1 % of all time series values fell outside the control limits of the X charts and the EWMA or EWMAST charts, respectively. These percentages were significantly reduced to 0.44 and 0.70 when the subseries-specific control charts were used. CONCLUSIONS: The mean level may change because of recalibrations or change of electrolyte diluent lot with subsequent false alarms. False alarms may be significantly reduced by revising QC charts when significant changes occur.

Serial correlation of quality control data--on the use of proper control charts.

BACKGROUND: Biochemical quality control (QC) data have been reported to be autocorrelated. Serial correlation may increase the rate of false alarms if the traditional exponentially weighted moving average (EWMA) control chart to monitoring the process mean is used. False alarms are the focus of this paper, where an alarm is defined as the occurrence of a QC value outside the three standard deviation control limits. METHODS: Daily QC measurements of common biochemical (Vitros 500) and hematological (SF-3000 and Behring Coagulation Timer (BCT)) quantities were recorded during several months while methods and analyzers showed no signs of malfunctioning. The time series were examined for autocorrelation and the performance of the EWMAST chart was compared with that of the EWMA chart when autocorrelation was present. RESULTS: Many of the time series showed significant signs of autocorrelation. Using the EWMA chart to monitor the process mean, false alarms were noted for positively autocorrelated time series, while this was seldom the case when the EWMAST chart was used. For some quantities, the EWMAST chart gave alarms. However, when the process autocorrelation and therefore the limits of the control chart were updated, the alarms given by the EWMAST chart were reduced or disappeared. In some cases the mean level changed over time, which is expected due to calibrations. This problem will be the topic of a subsequent paper. CONCLUSIONS: Positive autocorrelation may be present in QC data. In this case the EWMAST chart should be used in place of the EWMA chart.

Magnesium bioavailability from mineral water. A study in adult men.

OBJECTIVE: To assess magnesium enteral absorption from a magnesium-rich mineral water. DESIGN: Experimental study. SETTING: Department of Nuclear Medicine, Brugmann Hospital, Brussels, Belgium. SUBJECTS: Ten healthy male volunteers in the age range 25-42 y. INTERVENTION: Each subject completed two sessions in a random order. At one session, they received an oral load of 300 ml of water (containing 1.2 mmol Mg), traced with (28)Mg, and at the other session they received an intravenous injection of (28)Mg, in order to take into account the metabolism of endogenous magnesium. The dietary consumption was further noted on a weekly diary. RESULTS: The mean bioavailability was 59.1% (s.d.+/-13.6). Magnesium absorption and age were significantly inversely correlated (r=-0.68, P=0.035). CONCLUSION: Magnesium-rich mineral water is a reliable source of magnesium. Our observation of decreased magnesium absorption with age deserves further investigations. SPONSORSHIP: The study was sponsored by SEV, Bourg la Reine, France.

Parameters ruling optimization of radiolabelling of polyamino polycarboxylated functionalized peptide derivatives: a case study report.

Parameters studies revealed that successful labeling of DTPA-Neurotensin(8-13) analogues depend on several physico-chemical parameters. The pH of the reaction mixture seemed to be the most critical parameter for obtaining high labeling yields; quantitative radiolabelling was only guaranteed at a pH between 4.2 and 5.5. At a pH of 4.5, metal ion contaminants originating from peptide synthesis and purification procedures were shown not to effect radiolabelling. Nevertheless, proper reducing agents were included in a proposed Kit labeling procedure in order to avoid potential competition from trivalent metal ion contamination, and thus guarantee successful 111In-complexation. The complexing capacity of DTPA for radioactive In(3+) strongly depends upon the pH. As a consequence, labeling yields must be expressed as [[K(ass) x alpha(4) x [DTPA-NT](0)/(1+ K(ass) x alpha(4) x [DTPA-NT](0))], to where K(ass) is the association constant and alpha(4) is a pH dependent correction factor of the association constant.

Cortical and total bone mineral content of the radius: accuracy of peripheral computed tomography.

The aim of the study was to evaluate the accuracy of an XCT 960 Stratec peripheral quantitative computed tomography (pQCT) device in assessing bone mineral content of the radius. We scanned 27 left forearm specimens excised from cadavers and focused on cortical bone mineral content (BMCc) at the junction of the middle and distal third and on total bone mineral content (BMCtot) at the distal end of the radius. Cylindrical specimens matched with those two sites were cut using a diamond circular saw, embedded in a polyester resin and subsequently submitted to two reference methods, nondestructive neutron activation analysis and flame atomic absorption spectrometry. Mineral contents measured by pQCT were closely correlated with those assessed by using the two reference methods, with correlation coefficients ranging from 0.862 to 0.960. The standard error of the estimate amounted 7-10% for the BMCc (junction of the middle and distal third), and 17-18% for the BMCtot (distal end). We conclude that pQCT is able to measure either cortical or total mineral content of the radius with a high degree of accuracy.

Plasma magnesium during human liver transplantation.

Patients with severe liver disease and accompanying malnutrition may exhibit electrolyte disturbances including the magnesium balance. In 18 patients plasma magnesium (p-Mg) was determined at the start of the liver transplantation and during the anhepatic and reperfusion phases of the operation. The blood loss was 6.9 (2.5-8.8) 1 (median and range) and the cumulative transfusion volume was 10.2 (5.0-17.2) 1 of which 5.9 (2.5-14.2) 1 was with fresh frozen plasma. p-Mg was 0.72 (0.58-0.88) mmol.l-1 and it did not change significantly during the operation. Thus, in 4 patients it was at or below the lower reference value of 0.67 mmol.l-1. In 11 patients it changed less than 0.05 mmol.l-1, while in 4 patients the concentration was rose, and in 3 patients we noted a fall in each of 0.08 mmol.l-1. There was no correlation between p-Mg and the blood loss or the administered volume of fresh frozen plasma. In 10 randomly chosen fresh frozen plasma units, the p-Mg was 0.64 (0.61-0.71) mmol.l-1. These observations do not support a need for close monitoring or substitution of magnesium during human liver transplantation. On the other hand, the finding of a low value in 4 of 18 patients suggests that plasma magnesium should be monitored and eventually corrected while the patient is on the waiting list.

Automated laboratory protocols.

A protocol is a program which controls, monitors and modifies the requests for laboratory services during the diagnostic work-up and/or monitoring of a patient. A protocol language and an OS/2 based system for the compilation, interpretation and execution of laboratory protocols written in this language is presented. The system is easily interfaced with any patient data base that supports the structured query language (SQL). A compiled protocol may be assigned to a patient and executed as specified in the protocol itself (regularly and/or when certain events such as test requests or arrival of results, occur). In the laboratory protocol language a patient's data are viewed as a set of test procedure groups each comprising data (request time, result, etc.) describing the status of one or more simultaneously made laboratory test requests. A pattern specification is a statement saying that a sequence of test procedure groups of specified types and ages is present in the data. Pattern specifications are linked to Boolean variables. If a pattern matching a pattern specification is found in the patient's database the corresponding Boolean variable is set equal to TRUE. The Boolean variables are utilized in the decision logic of the protocol.

Cortical mineral content of the radius assessed by peripheral QCT predicts compressive strength on biomechanical testing.

Our aim was to evaluate the role of cortical bone in resistance to compression in the human radius. Thirty-three left cadaver forearms were scanned on an XCT 960 Stratec CT scanner. Cortical density and cortical thickness were measured at the junction of the middle and distal third of the radius. Subsequently, 2-cm-high cylindrical specimens, centrated on the level of the CT slice, were cut. After removal of the endosteal trabecular bone, the specimens were submitted to compressive testing, using an Instron machine, and load deformation curves were obtained. Maximal stress (load corrected for cross-sectional area) showed a significant relationship with the density (r = 0.78) as well as with the thickness (r = 0.74) of the cortex. The closest correlation involved the maximal load and the mineral content of the cortex specimens (r = 0.87). We conclude that the mineral content of these radius cortex specimens, measured using peripheral QCT, predicts their compressive strength on biomechanical testing.

Cortical thickness assessed by peripheral quantitative computed tomography: accuracy evaluated on radius specimens.

The purpose of the present study was to evaluate the accuracy of peripheral quantitative computed tomography (pQCT) in measuring the thickness of the radial cortex. Thirty left forearm specimens were scanned on an XCT 960 Stratec pQCT device using a 2.5 mm thick slice at the junction of the middle and the distal third of the radius. Cortical and trabecular areas were assessed using a threshold procedure; cortical thickness was subsequently calculated assuming a circular ring model for the radius. Cortical thickness was also measured on the true shape of bone using an iterative contour detection procedure. Subsequently 2.5 mm thick resin-embedded cylindrical radial specimens, matched with the site of pQCT examination, were obtained and contact radiographs were performed. After tenfold magnification, the cortical and trabecular areas of the specimens were measured using computerized planimetry and cortical thickness was calculated assuming a circular ring model. The cortical thickness could be assessed by pQCT in all cases using the threshold algorithm (mean (SD) 2.51 (0.58) mm) and in 21 cases could be directly measured on the true shape of bone (2.62 (0.32) mm). The cortical thickness of the specimens showed good correlation and high proportionality with that measured using pQCT with either the threshold algorithm (r = 0.941, slope = 0.976) or the iterative contour detection procedure (r = 0.883, slope = 0.987). In conclusion, pQCT is able to assess the thickness of the radial cortex, at the junction of the middle and the distal third, with high accuracy.

Application of time series analysis in the clinical setting.

A growth curve time series model is characterized by a biological growth pattern with random deviations added to this basic pattern. Various types are reviewed including the homeostatic model which is a special and simple type characterized by zero growth. The limitations to the use of time series analysis in the clinical setting include lack of initial baseline values and difficulties in specifying in quantitative terms a relevant hypothesis alternative to the one postulated by the time series model. Some ongoing research addressing these problems is discussed.

Mineral content of vertebral trabecular bone: accuracy of dual energy quantitative computed tomography evaluated against neutron activation analysis and flame atomic absorption spectrometry.

The goal of this study was to evaluate the accuracy of preprocessing dual energy quantitative computed tomography (QCT) for assessment of trabecular bone mineral content (BMC) in lumbar vertebrae. The BMC of 49 lumbar vertebrae taken from 16 cadavers was measured using dual energy QCT with advanced software and hardware capabilities, including an automated definition of the trabecular region of interest (ROI). The midvertebral part of each vertebral body was embedded in a polyester resin and, subsequently, an experimental ROI was cut out using a scanjet image transmission procedure and a computer-assisted milling machine in order to mimic the ROI defined on QCT. After low temperature ashing, the experimental ROIs reduced to a bone powder were submitted to either nondestructive neutron activation analysis (n = 49) or to flame atomic absorption spectrometry (n = 45). BMC obtained with neutron activation analysis was closely related (r = 0.896) to that derived from atomic absorption spectrometry, taken as the gold standard, with, however, a slight overestimation. BMC values measured by QCT were highly correlated with those assessed using the two reference methods, all correlation coefficients being > 0.841. The standard errors of the estimate ranged 47.4-58.9 mg calcium hydroxyapatite in the regressions of BMC obtained with reference methods against BMC assessed by single energy QCT, 47.1-51.9 in the regressions involving dual energy QCT. We conclude that the trabecular BMC of lumbar vertebrae can be accurately measured by QCT and that the superiority in accuracy of dual energy is moderate, which is possible a characteristic of the preprocessing method.