New method for time alignment and time calibration of the TOFOR time-of-flight neutron spectrometer at JET.

The TOFOR time-of-flight (TOF) neutron spectrometer at the Joint European Torus (JET) is composed of 5 start (S1) and 32 stop (S2) scintillation detectors. Recently, the data acquisition system (DAQ) of TOFOR was upgraded to equip each of the 37 detectors with its own waveform digitizer to allow for correlated time and pulse height analysis of the acquired data. Due to varying cable lengths and different pulse processing pathways in the new DAQ system, the 160 (5 · 32) different TOF pairs of start-stop detectors must be time-aligned to enable the proper construction of a summed TOF spectrum. Given the time (energy) resolution required by the entire spectrometer system to measure different plasma neutron emission components, it is of importance to align the detector pairs to each other with sub-nanosecond precision. Previously, the alignment partially depended on using fusion neutron data from Ohmic heating phases of JET experimental pulses. The dependence on fusion neutron data in the time alignment process is, however, unsatisfactory as it involves data one would wish to include in an independent analysis for physics results. In this work, we describe a method of time-aligning the detector pairs by using gamma rays. Given the known geometry and response of TOFOR to gamma rays, the time alignment of the detector pairs is found by examining gamma events interacting in coincidence in both S1-S1 and S1-S2 detector combinations. Furthermore, a technique for separating neutron and gamma events in the different detector sets is presented. Finally, the time-aligned system is used to analyze neutron data from Ohmic phases for different plasma conditions and to estimate the Ohmic fuel ion temperature.

Thin foil proton recoil spectrometer performance study for application in DT plasma measurements.

The Thin foil Proton Recoil (TPR) technique has previously been used for deuterium-tritium fusion neutron diagnostics [N. P. Hawkes et al., Rev. Sci. Instrum. 70, 1134 (1999)] and is one of the candidates put forward for use in ITER as part of the high resolution neutron spectrometer (HRNS) system [E. A. Sundén et al., Nucl. Instrum. Methods Phys. Res., Sect. A 701, 62 (2013)]. For ITER, the neutron spectrometer's main purposes are to determine the fuel ion density ratio as well as the ion temperature in DT plasma. This work focuses on testing the capability of a proton telescope detector intended for use as part of the TPR spectrometer. The proton telescope has been tested using proton energies in the range of 3-8 MeV. The experimental results cover energy calibration, resolution estimation, and testing the spectrometer's capability to perform background separation using ΔE - E energy cuts. In addition, spectrometer performance in terms of signal to background ratios for ITER-like DT plasma conditions is estimated using Monte-Carlo simulations. Results show that the TPR spectrometer geometry dominates in determining the energy resolution and the ΔE - E energy cuts will significantly reduce the background. In addition, the estimated spectrometer count rates in ITER-like conditions fall below 20 kHz per detector segment.

Velocity-space sensitivities of neutron emission spectrometers at the tokamaks JET and ASDEX Upgrade in deuterium plasmas.

Future fusion reactors are foreseen to be heated by the energetic alpha particles produced in fusion reactions. For this to happen, it is important that the energetic ions are sufficiently confined. In present day fusion experiments, energetic ions are primarily produced using external heating systems such as neutral beam injection and ion cyclotron resonance heating. In order to diagnose these fast ions, several different fast-ion diagnostics have been developed and implemented in the various experiments around the world. The velocity-space sensitivities of fast-ion diagnostics are given by so-called weight functions. Here instrument-specific weight functions are derived for neutron emission spectrometry detectors at the tokamaks JET and ASDEX Upgrade for the 2.45 MeV neutrons produced in deuterium-deuterium reactions in deuterium plasmas. Using these, it is possible to directly determine which part of velocity space each detector observes.

Neutron emission spectroscopy of DT plasmas at enhanced energy resolution with diamond detectors.

This work presents measurements done at the Peking University Van de Graaff neutron source of the response of single crystal synthetic diamond (SD) detectors to quasi-monoenergetic neutrons of 14-20 MeV. The results show an energy resolution of 1% for incoming 20 MeV neutrons, which, together with 1% detection efficiency, opens up to new prospects for fast ion physics studies in high performance nuclear fusion devices such as SD neutron spectrometry of deuterium-tritium plasmas heated by neutral beam injection.

Prospects for measuring the fuel ion ratio in burning ITER plasmas using a DT neutron emission spectrometer.

The fuel ion ratio nt/nd is an essential parameter for plasma control in fusion reactor relevant applications, since maximum fusion power is attained when equal amounts of tritium (T) and deuterium (D) are present in the plasma, i.e., nt/nd = 1.0. For neutral beam heated plasmas, this parameter can be measured using a single neutron spectrometer, as has been shown for tritium concentrations up to 90%, using data obtained with the MPR (Magnetic Proton Recoil) spectrometer during a DT experimental campaign at the Joint European Torus in 1997. In this paper, we evaluate the demands that a DT spectrometer has to fulfill to be able to determine nt/nd with a relative error below 20%, as is required for such measurements at ITER. The assessment shows that a back-scattering time-of-flight design is a promising concept for spectroscopy of 14 MeV DT emission neutrons.

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET.

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR.

Fully digital data acquisition system for the neutron time-of-flight spectrometer TOFOR at JET.

A prototype of a fully digital data acquisition system based on 1 Gsps 12 bit digitizers for the TOFOR fusion neutron spectrometer at JET is assessed. The prototype system enables the use of geometry-based background discrimination techniques, which are modeled, evaluated, and compared to experimental data. The experimental results are in line with the models and show a significant improvement in signal-to-background ratio in measured time-of-flight spectrum compared to the existing data acquisition system.

Gain stabilization control system of the upgraded magnetic proton recoil neutron spectrometer at JET.

Burning plasma experiments such as ITER and DEMO require diagnostics capable of withstanding the harsh environment generated by the intense neutron flux and to maintain stable operating conditions for times longer than present day systems. For these reasons, advanced control and monitoring (CM) systems will be necessary for the reliable operation of diagnostics. This paper describes the CM system of the upgraded magnetic proton recoil neutron spectrometer installed at the Joint European Torus focusing in particular on a technique for the stabilization of the gain of the photomultipliers coupled to the neutron detectors. The results presented here show that this technique provides good results over long time scales. The technique is of general interest for all diagnostics that employ scintillators coupled to photomultiplier tubes.

Validating TRANSP simulations using neutron emission spectroscopy with dual sight lines.

A method to generate modeled neutron spectra from bulk and fast ion distributions simulated by TRANSP has been developed. In this paper, modeled data generated from fuel ion distributions modeled with TRANSP is compared to measured data from two neutron spectrometers with different lines of sight; TOFOR with a radial one and the MPRu with a tangential one. The information obtained from the analysis of the measured neutron spectra such as the relative intensity of the emission from different ion populations places additional constraints on the simulation and can be used to adjust the parameters of the simulation.

Neutron emission spectroscopy results for internal transport barrier and mode conversion ion cyclotron resonance heating experiments at JET.

The effect of ion cyclotron resonance heating (ICRH) on (3He)D plasmas at JET was studied with the time of flight optimized rate (TOFOR) spectrometer dedicated to 2.5 MeV dd neutron measurements. In internal transport barrier (ITB) plasma experiments with large 3He concentrations (X(3He)>15%) an increase in neutron yield was observed after the ITB disappeared but with the auxiliary neutral beam injection and ICRH power still applied. The analysis of the TOFOR data revealed the formation of a high energy (fast) D population in this regime. The results were compared to other mode conversion experiments with similar X(3He) but slightly different heating conditions. In this study we report on the high energy neutron tails originating from the fast D ions and their correlation with X(3He) and discuss the light it can shed on ICRH-plasma power coupling mechanisms.

A neural networks framework for real-time unfolding of neutron spectroscopic data at JET.

A determination of fast ion population parameters such as intensity and kinetic temperature is important for fusion reactors. This becomes more challenging with finer time resolution of the measurements, since the limited data in each time slice cause increasing statistical variations in the data. This paper describes a framework using Bayesian-regularized neural networks (NNs) designed for such a task. The method is applied to the TOFOR 2.5 MeV fusion neutron spectrometer at JET. NN training data are generated by random sampling of variables in neutron spectroscopy models. Ranges and probability distributions of the parameters are chosen to match the experimental data. Results have shown good performance both on synthetic and experimental data. The latter was assessed by statistical considerations and by examining the robustness and time consistency of the results. The regularization of the training algorithm allowed for higher time resolutions than simple forward methods. The fast execution time makes this approach suitable for real-time analysis with a time resolution limit in the microsecond time scale.

Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults.

OBJECTIVES: To study the occurrence of relapse of herpes simplex encephalitis (HSE) and to find out whether soluble activity markers in cerebrospinal fluid (CSF) indicate direct viral or immune- mediated events. METHODS: A consecutive series of 32 adult survivors of HSE were followed to determine the incidence of clinical relapse of HSE. Four patients had neurological deterioration interpreted as relapsing HSE. Four non-relapsing HSE cases were selected as matched controls. Fifty nine batched, paired CSF and serum samples from the eight HSE patients were analysed for soluble activity markers, predominantly cytokines and mediators (interferon-gamma, soluble CD8, tumour necrosis factor-alpha, and interleukin-10), amount of HSV-DNA and markers of glial and neuronal destruction (neurofilament protein, glial fibrillary acidic protein, S-100-beta, and neuron specific enolase). RESULTS: Relapse of HSE was diagnosed in 3 of 26 (12 %) acyclovir-treated patients (5 episodes during 6.1 years of followup) and in 1 of 6 vidarabine-recipients. All relapses occurred from 1 to 4 months after acute HSE, except for a second relapse after 3.3 years in one patient. Computer tomography at relapses revealed few abnormalities apart from those found during the primary disease. Intravenous acyclovir and corticosteroids were given for 7-21 days in all the relapse patients. All relapse patients seemed to recover to the pre-relapse condition. HSV-DNA was demonstrated in CSF in all patients during the acute stage but not in any of 13 CSF samples taken during relapse phases. The HSV viral load during the acute stage of HSE was not higher or of longer duration in the relapsing patients than in the non-relapsing HSE controls. The levels of sCD8 were increased in nearly all CSF samples tested with peaks of sCD8 at one month of acute HSE. In all episodes of relapse, sCD8 peaks were detected during the first week at high levels. CSF levels of neuron-specific enolase, S-100 and glial fibrillary acidic protein were markedly lower at relapse than at the acute stage of HSV-1 encephalitis. CONCLUSION: The lack of demonstrable HSV DNA in CSF, the lack of acute CSF signs and the lack of signs of neural and glia cells destruction indicate that a direct viral cytotoxicity is not the major pathogenic mechanism in relapse. Instead, the pronounced CSF proinflammatory immunological response and the relative lack of CSF anti-inflammatory cytokine IL-10 response suggest immunologically-mediated pathogenicity.

The mammary gland-infant intestine immunologic dyad.

The human infant has a very small immune system and needs the support of the mother with the transplacentally arrived IgG antibodies to protect tissues with inflammatogenic and energy-consuming defense. The mucous membranes, where most infections occur, need support via the specialized secretory IgA antibodies and the many other mucosal defense mechanisms provided via the mother's milk. This defense is not inflammatogenic and energy-consuming. We learn about additional defense factors in the milk, like the anti-secretory factor, which seems to protect against diarrhoea. The milk contains numerous growth factors and cytokines, like leptin, which may promote the development of the intestine as well as the immune system. Results are appearing giving interesting evidence for enhanced protection against infection also after the termination of breastfeeding. This may occur via the priming of the infant's immune system after uptake of anti-idiotypic antibodies and lymphocytes from the milk. A breastfeeding motivation study in a large Pakistani village resulted in a 50% decrease of diarrhoea and infant mortality. Deep interviews with the mothers and the traditional birth attendants suggested that even better results may be obtained.

Temporal and subcellular localization of infectious pancreatic necrosis virus structural proteins.

The temporal subcellular localization of the structural proteins VP2 and VP3 of infectious pancreatic necrosis virus was analyzed with monoclonal antibodies conjugated with fluorochromes. Early in the infection both proteins were colocalized in the cytosol, at later times, VP2 was visualized as inclusion bodies around the nuclei of the cells and, sometimes, it was found in elongated tubular structures that might correspond to the type I tubules seen in cells infected with another Birnavirus. As VP2 is a glycosylated protein we determined its subcellular localization compared with that of ER and Golgi probes. These results suggest that VP2 is glycosylated freely in the cytoplasm.

Identification of IPNV-specified components released from productively infected RTG-2 cells following massive cytopathic effect.

Rainbow trout gonad cells (RTG-2) display a dramatic cytopathic effect and lysis following productive infection by infectious pancreatic necrosis virus (IPNV). In this study viruses were efficiently released into the growth medium together with low amounts of the monomeric free form of the structural protein VP3, heterodimers of VP2-VP3, aggregates of pVP2 and viral RNA associated with VP3. Ribonucleoprotein complexes of RNA-VP3 contained RNA equivalent to at the most 25% of full length viral genomes. Infectivity of material released into the growth medium late in infection was only associated with fully assembled viruses and isolated subviral RNA-VP3 complexes were not infectious. Upon purification of IPNV, viral hexa- and pentagonal particles of approx. 15 nm diameter were occasionally co-purified with the virus and then appeared in large quantities. Similar particle-like structures were seen as substructures of purified viruses that were treated with and partially disintegrated by CsCl of virus isodensity concentration.

TCID50 determination by an immuno dot blot assay as exemplified in a study of storage conditions of infectious pancreatic necrosis virus.

Some cell lines are difficult to grow in confluent monolayers and, therefore, the plaque assay cannot be applied since plaques may be hard to distinguish from other blank areas of the cell monolayers. To avoid this problem a rapid and sensitive immuno dot blot TCID50 method was developed using antibodies against virus antigens to detect infection and virus production. An alternative statistical method was developed to treat the scoring data and thereby obtained a coefficient of variation of 10%. To speed up the total procedure and to increase the proliferation rate of cells grown in 96-well cell culture plates, the plates were pretreated for 4 h at 4 degrees C with growth medium obtained from cell culturing flasks containing confluent cell monolayers. This immuno dot blot TCID50 method was applied for a study of the infectivity maintenance upon storage of infectious pancreatic necrosis virus (IPNV). Storage of IPNV at -70 degrees C with a cryoprotective agent (10% glycerol) preserved the TCID50 level even after as many as ten cycles of freezings and thawings, whereas the infectivity decreased by four orders of magnitude after storage at 4-8 degrees C for 2 months in the salt buffer used commonly.

Infectious pancreatic necrosis virus: identification of a VP3-containing ribonucleoprotein core structure and evidence for O-linked glycosylation of the capsid protein VP2.

Virions of infectious pancreatic necrosis virus (IPNV) were completely disintegrated upon dialysis against salt-free buffers. Direct visualization of such preparations by electron microscopy revealed 5.0- to 6.5-nm-thick entangled filaments. By using a specific colloidal gold immunolabeling technique, these structures were shown to contain the viral protein VP3. Isolation by sucrose gradient centrifugation of the filaments, followed by serological analysis, demonstrated that the entire VP3 content of the virion was recovered together with the radiolabeled genomic material forming the unique threadlike ribonucleoprotein complexes. In a sensitive blotting assay, the outer capsid component of IPNV, i.e., the major structural protein VP2, was shown to specifically bind lectins recognizing sugar moieties of N-acetylgalactosamine, mannose, and fucose. Three established metabolic inhibitors of N-linked glycosylation did not prevent addition of sugar residues to virions, and enzymatic deglycosylation of isolated virions using N-glycosidase failed to remove sugar residues of VP2 recognized by lectins. However, gentle alkaline beta elimination clearly reduced the ability of lectins to recognize VP2. These results suggest that the glycosylation of VP2 is of the O-linked type when IPNV is propagated in RTG-2 cells.

Electrical stimulation versus coronary artery bypass surgery in severe angina pectoris: the ESBY study.

BACKGROUND: Spinal cord stimulation (SCS) has been shown to have antianginal and anti-ischemic effects in severe angina pectoris. The present study was performed to investigate whether SCS can be used as an alternative to coronary artery bypass grafting (CABG) in selected patient groups, ie, patients with no proven prognostic benefit from CABG and with an increased surgical risk. METHODS AND RESULTS: One hundred four patients were randomized (SCS, 53; CABG, 51). The patients were assessed with respect to symptoms, exercise capacity, ischemic ECG changes during exercise, rate-pressure product, mortality, and cardiovascular morbidity before and 6 months after the operation. Both groups had adequate symptom relief (P<.0001), and there was no difference between SCS and CABG. The CABG group had an increase in exercise capacity (P=.02), less ST-segment depression on maximum (P=.005) and comparable (P=.0009) workloads, and an increase in the rate-pressure product both at maximum (P=.0003) and comparable (P=.03) workloads compared with the SCS group. Eight deaths occurred during the follow-up period, 7 in the CABG group and 1 in the SCS group. On an intention-to-treat basis, the mortality rate was lower in the SCS group (P=.02). Cerebrovascular morbidity was also lower in the SCS group (P=.03). CONCLUSIONS: CABG and SCS appear to be equivalent methods in terms of symptom relief in this group of patients. Effects on ischemia, morbidity, and mortality should be considered in the choice of treatment method. Taking all factors into account, it seems reasonable to conclude that SCS may be a therapeutic alternative for patients with an increased risk of surgical complications.

Effect of pimobendan on exercise capacity in patients with heart failure: main results from the Pimobendan in Congestive Heart Failure (PICO) trial.

PRIMARY OBJECTIVE: To determine the effects of pimobendan 2.5 and 5 mg daily on exercise capacity in patients with chronic heart failure. DESIGN: A randomised, double blind, placebo controlled trial of the addition of pimobendan to conventional treatment with a minimum follow up of 24 weeks. SETTING: Outpatient cardiology clinics in six European countries. PATIENTS: 317 patients with stable symptomatic heart failure, objectively impaired exercise capacity, and an ejection fraction of 45% or lower who were treated with at least an angiotensin converting enzyme inhibitor and a diuretic and who tolerated a test dose of pimobendan. RESULTS: Compared with placebo, both pimobendan 2.5 and 5 mg daily improved exercise duration (bicycle ergometry) by 6% (P = 0.03 and 0.05) after 24 weeks of treatment. At that time 63% of patients allocated to pimobendan and 59% of those allocated to placebo were alive and able to exercise to at least the same level as at entry (P = 0.5). No significant effects on oxygen consumption (assessed in a subgroup of patients) and on quality of life (assessed by questionnaire) were observed. Pimobendan was well tolerated. Proarrhythmic effects (24-hour electrocardiography) were not observed. In both pimobendan groups combined the hazard of death was 1.8 (95% confidence interval 0.9 to 3.5) times higher than in the placebo group. CONCLUSIONS: Pimobendan improves exercise capacity in patients with chronic heart failure who are also on conventional treatment. The balance between benefit and risk of treatment with this compound remains to be established however.

Quality of life on treatment with metoprolol in dilated cardiomyopathy: results from the MDC trial. Metoprolol in Dilated Cardiomyopathy trial.

Quality of life in heart failure patients is receiving increased attention as a reflection of a treatment's potential secondary benefit of general well-being and daily functioning. The Metoprolol in Dilated Cardiomyopathy (MDC) trial was conducted as a large, multicenter trial to establish the effects of metoprolol on mortality and need for heart transplantation in patients with symptomatic idiopathic cardiomyopathy. It was found that metoprolol was well tolerated, improved symptoms and cardiac function, and prevented clinical deterioration in patients with symptomatic idiopathic dilated cardiomyopathy. Quality of life was evaluated as a secondary endpoint in 345 out of 383 randomized patients using a disease-specific questionnaire, the Quality of Life in Heart Failure Questionnaire, depicting physical activity, somatic symptoms, emotions, and life satisfaction. In a comparison of patients treated with metoprolol or placebo, patients treated with metoprolol noted a significantly more favorable response than those treated with placebo in terms of the overall treatment evaluation (p < 0.05). Additionally, an analysis of the changes from baseline to 18 months, using 95% confidence intervals, revealed that patients treated with metoprolol showed a significant improvement from baseline to 18 months in life satisfaction, physical activity, and the total score, while patients treated with placebo did not change at all. The improvement in quality of life was supported by the correlations with improvement in traditional clinical parameters.