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.

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.

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.

Ventricular adenine nucleotide translocator mRNA is upregulated in dilated cardiomyopathy.

OBJECTIVE: A disturbed energy transfer involving the adenine nucleotide translocator across the inner mitochondrial membrane has been suggested to be one specific pathogenetic mechanism in dilated cardiomyopathy. Pretranslational steady state expression of this protein in dilated cardiomyopathy was investigated. METHODS: Concentrations of adenine nucleotide translocator were quantified by solution hybridisation. The enzyme or protein expressions of citrate synthase, lactate dehydrogenase, and creatine kinase with isozymes were determined. Analysis was performed on specimens from the left and right ventricles from six organ donor hearts, six explanted hearts with dilated cardiomyopathy, two explanted hearts with ischaemic cardiomyopathy, and from papillary muscles from seven patients operated on for mitral regurgitation. RESULTS: The ejection fraction in patients with mitral regurgitation was 50(10)%, significantly higher (p < 0.001) than in patients with dilated cardiomyopathy (23(5))%. In mitral regurgitation and in ischaemic cardiomyopathy left ventricular adenine nucleotide translocator mRNA concentrations did not differ from those in donor hearts. In dilated cardiomyopathy, adenine nucleotide translocator mRNA concentrations were significantly increased (p < 0.001). Upregulation was more pronounced in right ventricular than in left ventricular myocardium (p < 0.01). The lactate dehydrogenase M subunit fraction was increased to a similar degree in dilated cardiomyopathy and in mitral regurgitation (p < 0.05). Citrate synthase activity was significantly decreased only in dilated cardiomyopathy (p < 0.005). On the other hand, the creatine kinase B subunit content was significantly higher in mitral regurgitation than in dilated cardiomyopathy (p < 0.001). CONCLUSIONS: Despite signs of increased anaerobic and depressed oxidative capacities, dilated cardiomyopathy was specifically characterised by pretranslational upregulation of adenine nucleotide translocator.

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.

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.

The time course in acute myocardial infarction evaluated with precordial mapping and standard ECG.

Fifty-six patients with acute transmural anterior wall myocardial infarction (MI) were investigated with a 24-electrode grid and 34 patients with an acute transmural inferior wall MI were investigated with standard ECG leads II, III, and aVF in order to study the length of time after the onset of pain during which the development of Q waves and reduction of R waves progress. These ECG changes continued for 18-26 h after onset of pain but the majority appeared during the first 12 h.

Delay time in suspected acute myocardial infarction and the importance of its modification.

This paper summarizes the present knowledge of delay time in suspected acute myocardial infarction. More than 50% of deaths in acute myocardial infarction occur outside of the hospital setting. Recent experiences indicate that early and even late mortality can be dramatically reduced by intervention in the early phase. This points up the importance of bringing patients with suspected acute myocardial infarction to the hospital as early in the course of MI as possible. The predominating cause of delay is the time it takes for the patient to decide to go to hospital regardless of a previous history of cardiovascular disease. Patients arriving in hospital in later stages of MI are at a very high risk of mortality. Therefore one of the most important problems to be resolved is how to reduce delay time in suspected acute myocardial infarction. Such efforts have been surprisingly few. Limited experiences indicate that public education can reduce delay time dramatically.

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.

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.

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.

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.

Health consequences of giving up smoking in a prospective population study of middle-aged Swedish men.

The effect when persons quit smoking was studied in a prospective study of 855 50-year old men randomly selected from the general population of Gothenburg, Sweden. These men have been followed since 1963. For this report, data from the first ten years of follow-up were used. The survivors from this period were divided into three groups: those who had never smoked, those who were smokers at the first examination but not since (ex-smokers), and those who were smokers at all three examinations. Compared to ex-smokers, the smokers had a steeper decrease of bronchial peak flow, more days of sick leave, more complaints and poorer self-assessed life situation score. After adjusting for possible confounding factors and differences in morbidity prevalence between the groups at the start of the study, the smokers still had a more unfavorable health course than the ex-smokers.