CHARACTERISATION OF RADIOPHOTOLUMINESCENCE DOSIMETRY SYSTEM FOR INDIVIDUAL MONITORING.

Performance evaluation is typically assessed as part of the approval procedure to verify that a dosimetry system fulfils specified national or international type-test requirements under representative exposure conditions that are expected to mimic workplace fields from the radiological activities being monitored. The International Atomic Energy Agency Radiation Safety Technical Services Laboratory has recently implemented an integrated radiophotoluminescence (RPL) personal dosimetry system developed by Chiyoda Technol Corporation. This paper reports on the successful verification of dosimetric performance properties of the RPL dosimetry system to IEC 62387:2020, in which the badges were exposed to a range of radiation energies and angles of incidence as well as other influence parameters. Characteristics under test included the coefficient of variation, non-linearity of response due to dose dependence as well as the energy and angular response to photon and beta radiation.

Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel.

The field of transcranial electrical stimulation (tES) has experienced significant growth in the past 15 years. One of the tES techniques leading this increased interest is transcranial direct current stimulation (tDCS). Significant research efforts have been devoted to determining the clinical potential of tDCS in humans. Despite the promising results obtained with tDCS in basic and clinical neuroscience, further progress has been impeded by a lack of clarity on international regulatory pathways. We therefore convened a group of research and clinician experts on tDCS to review the research and clinical use of tDCS. In this report, we review the regulatory status of tDCS, and we summarize the results according to research, off-label and compassionate use of tDCS in the following countries: Australia, Brazil, France, Germany, India, Iran, Italy, Portugal, South Korea, Taiwan and United States. Research use, off label treatment and compassionate use of tDCS are employed in most of the countries reviewed in this study. It is critical that a global or local effort is organized to pursue definite evidence to either approve and regulate or restrict the use of tDCS in clinical practice on the basis of adequate randomized controlled treatment trials.

Cost and clinical implications of diabetes prevention in an Australian setting: a long-term modeling analysis.

AIMS/HYPOTHESIS: Metformin and intensive lifestyle changes (ILC) reduced the incidence of type 2 diabetes (T2D) versus standard care (control) in overweight or obese subjects with impaired glucose tolerance (IGT) in the Diabetes Prevention Program (DPP) trial and Diabetes Prevention Program Outcomes Study (DPPOS). We projected lifetime clinical and economic outcomes based on the results from the DPP+DPPOS, from a 3rd-party payer perspective in Australia. METHODS: A semi-Markov, 2nd-order Monte Carlo model was developed with four health states: "normal glucose regulation" (NGR); IGT; T2D and 'dead'. Outcomes were discounted at 5% annually. Univariate and probabilistic sensitivity analyses were performed. Incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS: Cumulative incidence (standard deviation) of T2D was 89.7% (0.2), 83.8% (0.2) and 73.4% (0.3%) for control, metformin and ILC respectively. Lifetime incremental direct costs were $1217 (4411) per subject for metformin versus control, with cost savings of $289 (4296) for ILC versus control. ILC therefore dominated control, with improvements in clinical outcomes and overall cost savings. Incremental costs per QALY-gained for metformin versus control were $10,142. Probability of cost-effectiveness at willingness-to-pay threshold of $50,000 was 78% and 100% for metformin or ILC respectively. Results were most sensitive to probabilities of developing T2D and costs of implementing the interventions. CONCLUSIONS/INTERPRETATION: Substantial improvements in lifetime clinical outcomes could be expected in high risk subjects treated with metformin or ILC. Prevention of T2D in this group of subjects is good value for money, and may even lead to long term cost savings.

Towards normalization of soybean somatic embryo maturation.

Soybean (Glycine max L. Merrill) somatic embryos have been useful for assaying seed-specific traits prior to plant recovery. Such traits could be assessed more accurately if somatic embryos more closely mimicked seed development. Amino acid supplements, carbon source, and abscisic acid and basal salt formulations were tested in an effort to modify existing soybean embryogenesis histodifferentiation/maturation media to further normalize the development of soybean somatic embryos. The resultant liquid medium, referred to as soybean histodifferentiation and maturation medium (SHaM), consists of FNL basal salts, 3% sucrose, 3% sorbitol, filter-sterilized 30 mM glutamine and 1 mM methionine. SHaM-derived somatic embryos are more similar to seed in terms of protein and fatty acid/lipid composition, and conversion ability, than somatic embryos obtained from traditional soybean histodifferentiation and maturation media.

Localizing acute stroke-related EEG changes: assessing the effects of spatial undersampling.

Because of its sensitivity to metabolic and ionic disturbances related to ischemia, the EEG can be a potentially useful tool for acute stroke detection and for monitoring affected tissue. However, the clinical use of the EEG in detecting stroke is determined in part by how accurately the spatial information is characterized. The purpose of the current study was to determine the effects of spatial undersampling on the distribution and interpretation of the stroke-related topographic EEG. Using a 128-channel sensor montage, EEG was recorded from six stroke patients acutely (between 8 and 36 hours) after symptom onset. The EEG was submitted to a spectral analysis and was compared with patient symptoms and MRI and computed tomographic findings. To determine loss of spatial and clinical information resulting from spatial undersampling, the average-referenced data from the original 128-channel recording montage were subsampled into 64-, 32-, and 19-channel arrays. Furthermore, the analytical findings were compared with a board-certified electroencephalographer's review of the raw EEG using a conventional clinical montage. As predicted, the results showed that accurate description of stroke-related topographic EEG changes is dependent on adequate spatial sampling density. Accurate description of the spatial distribution of the stroke-related EEG was achieved only with the 64- and 128-channel EEG. As the recording density decreases to 32 channels, the distribution of the scalp EEG spectra is distorted, potentially resulting in mislocalization of the affected region. Results of the clinical review by an expert electroencephalographer corroborated the quantitative analyses, and the results also demonstrated the shortcomings of the conventional 10-20 recording density for capturing focal EEG abnormalities in several cases. The EEG provides useful information about the localization of acute cerebral ischemia, but recording densities of 64 channels or higher are required for accurate spatial characterization of focal stroke-related EEG changes.

Regulating action: alternating activation of midline frontal and motor cortical networks.

OBJECTIVES: Focal electrical fields recorded over the midline prefrontal cortex have been found to index rapid evaluative decisions, including the recognition of having made an error in a speeded response task. The nature of these electrical fields and how they are related to cortical areas involved in response execution remains to be clarified. METHODS: As subjects performed a speeded response task the EEG was recorded with a 128-channel sensor array. By filtering out the large slow waves of the event-related potential, we found that the error-related negativity (Ne/ERN) arises from a midline frontal oscillation that alternates with oscillations over lateral sensorimotor cortex. Electrical source analyses were used to determine the brain sources involved in the generation of these oscillations. RESULTS: The results show that the midline and lateral oscillations have a period of about 200 ms (theta), and they are present for both correct and error responses. When an error is made, the midline error oscillation is recruited strongly, and it becomes correlated with the motor oscillation. Source analyses localized the midline error oscillation to centromedial frontal cortex and the lateral oscillation to sensorimotor cortices. CONCLUSIONS: Because of the similarity between the midline oscillation observed in the present study and frontal midline theta, the nature of the Ne/ERN may be clarified by the frontal midline theta literature. The correlation between the midline and sensorimotor oscillations suggests a possible mechanism for how midline frontal evaluative and monitoring networks contribute to action regulation.

Frontal evaluation and posterior representation in target detection.

This study examined the topography of the event-related potential in visual-spatial compared to visual-object target detection. The initial index of target detection in the ERP was an inferior anterior P2a accompanied by a posterior N2b. Single unit studies in the monkey indicate that the detection of task-relevant stimuli requires interaction between prefrontal cortex and perceptual representation areas in the posterior brain. The posterior brain processes the physical features of stimuli while frontal cortex performs higher-order operations, such as evaluating the task-relevance of a stimulus. Target detection requires an interaction between feature representations and relevance representations. We hypothesize that the P2a and N2b ERP indices of target detection reflect this frontal/posterior interaction. Visual-spatial feature information is processed in the dorsal posterior brain (posterior parietal cortex) and visual-object information is processed in the ventral posterior brain (inferior occipito-temporal cortex). We observed that at the peak of the P2a the N2b was located over posterior dorsal leads in visual-spatial target detection and over posterior ventral leads in visual-object target detection. The P2a was largest over inferior prefrontal leads in both tasks. We suggest that this distribution is consistent with interaction between orbitofrontal cortical areas of salience representation and posterior cortical areas of stimulus feature representation.

Scalp electrode impedance, infection risk, and EEG data quality.

OBJECTIVES: Breaking the skin when applying scalp electroencephalographic (EEG) electrodes creates the risk of infection from blood-born pathogens such as HIV, Hepatitis-C, and Creutzfeldt-Jacob Disease. Modern engineering principles suggest that excellent EEG signals can be collected with high scalp impedance ( approximately 40 kOmega) without scalp abrasion. The present study was designed to evaluate the effect of electrode-scalp impedance on EEG data quality. METHODS: The first section of the paper reviews electrophysiological recording with modern high input-impedance differential amplifiers and subject isolation, and explains how scalp-electrode impedance influences EEG signal amplitude and power line noise. The second section of the paper presents an experimental study of EEG data quality as a function of scalp-electrode impedance for the standard frequency bands in EEG and event-related potential (ERP) recordings and for 60 Hz noise. RESULTS: There was no significant amplitude change in any EEG frequency bands as scalp-electrode impedance increased from less than 10 kOmega (abraded skin) to 40 kOmega (intact skin). 60 Hz was nearly independent of impedance mismatch, suggesting that capacitively coupled noise appearing differentially across mismatched electrode impedances did not contribute substantially to the observed 60 Hz noise levels. CONCLUSIONS: With modern high input-impedance amplifiers and accurate digital filters for power line noise, high-quality EEG can be recorded without skin abrasion.

Regional head tissue conductivity estimation for improved EEG analysis.

We develop a method for estimating regional head tissue conductivities in vivo, by injecting small (1-10 microA) electric currents into the scalp, and measuring the potentials at the remaining electrodes of a dense-array electroencephalography net. We first derive analytic expressions for the potentials generated by scalp current injection in a four-sphere model of the human head. We then use a multistart downhill simplex algorithm to find regional tissue conductivities which minimize the error between measured and computed scalp potentials. Two error functions are studied, with similar results. The results show that, despite the low skull conductivity and expected shunting by the scalp, all four regional conductivities can be determined to within a few percent error. The method is robust to the noise levels expected in practice. To obtain accurate results the cerebrospinal fluid must be included in the forward solution, but may be treated as a known parameter in the inverse solution.

Measurement and validation of benchmark-quality thick-target tungsten X-ray spectra below 150 kVp.

Pulse-height distributions of two constant potential X-ray tubes with fixed anode tungsten targets were measured and unfolded. The measurements employed quantitative alignment of the beam, the use of two different semiconductor detectors (high-purity germanium and cadmium-zinc-telluride), two different ion chamber systems with beam-specific calibration factors, and various filter and tube potential combinations. Monte Carlo response matrices were generated for each detector for unfolding the pulse-height distributions into spectra incident on the detectors. These response matrices were validated for the low error bars assigned to the data. A significant aspect of the validation of spectra, and a detailed characterization of the X-ray tubes, involved measuring filtered and unfiltered beams at multiple tube potentials (30-150 kVp). Full corrections to ion chamber readings were employed to convert normalized fluence spectra into absolute fluence spectra. The characterization of fixed anode pitting and its dominance over exit window plating and/or detector dead layer was determined. An Appendix of tabulated benchmark spectra with assigned error ranges was developed for future reference.

Using measured 30-150 kVp polychromatic tungsten x-ray spectra to determine ion chamber calibration factors, Nx (Gy C(-1)).

Two methods for determining ion chamber calibration factors (Nx) are presented for polychromatic tungsten x-ray beams whose spectra differ from beams with known Nx. Both methods take advantage of known x-ray fluence and kerma spectral distributions. In the first method, the x-ray tube potential is unchanged and spectra of differing filtration are measured. A primary standard ion chamber with known Nx for one beam is used to calculate the x-ray fluence spectrum of a second beam. Accurate air energy absorption coefficients are applied to the x-ray fluence spectra of the second beam to calculate actual air kerma and Nx. In the second method, two beams of differing tube potential and filtration with known Nx are used to bracket a beam of unknown Nx. A heuristically derived Nx interpolation scheme based on spectral characteristics of all three beams is described. Both methods are validated. Both methods improve accuracy over the current half value layer Nx estimating technique.

Statistical control of artifacts in dense array EEG/MEG studies.

With the advent of dense sensor arrays (64-256 channels) in electroencephalography and magnetoencephalography studies, the probability increases that some recording channels are contaminated by artifact. If all channels are required to be artifact free, the number of acceptable trials may be unacceptably low. Precise artifact screening is necessary for accurate spatial mapping, for current density measures, for source analysis, and for accurate temporal analysis based on single-trial methods. Precise screening presents a number of problems given the large datasets. We propose a procedure for statistical correction of artifacts in dense array studies (SCADS), which (1) detects individual channel artifacts using the recording reference, (2) detects global artifacts using the average reference, (3) replaces artifact-contaminated sensors with spherical interpolation statistically weighted on the basis of all sensors, and (4) computes the variance of the signal across trials to document the stability of the averaged waveform. Examples from 128-channel recordings and from numerical simulations illustrate the importance of careful artifact review in the avoidance of analysis errors.

Differentiating the N3 and N4 electrophysiological semantic incongruity effects.

An event-related potential termed the N4 has been widely studied due to its sensitivity to semantic incongruity. A recent report (Nobre & McCarthy, 1994) indicates there is also an N3 component that is sensitive to semantic incongruity. To differentiate these two components, an existing data set with 65 electrode sites, 78 subjects, and 120 sentences was examined. Instead of the usual procedure of averaging over the stimuli within distinct categories for each subject, a new approach--averaging over subjects--was employed. In this item average approach, 120 averages (one per sentence) were produced. Correlational analyses indicate that the N3 is equally sensitive to cloze probability and sentential constraint. The N4, by contrast, is more sensitive to sentential constraint and less to cloze probability; it is also correlated with familiarity. We interpret these results as evidence that the N3 is more responsive to semantic fit whereas the N4 is more responsive to semantic expectancy.

Medial frontal cortex in action monitoring.

Effective behavior requires continuous action monitoring. Electrophysiological studies in both monkeys and humans have shown activity in the medial frontal cortex that reflects dynamic control and monitoring of behavioral acts. In humans, the centromedial frontal cortex shows an electrical response within 100 msec of an error, the error-related negativity (ERN). The ERN occurs only when subjects are aware of making an error, suggesting that a critical factor may be self-monitoring of the action process. In the present study, we examined late responses in a deadline reaction time task, in which the subject becomes increasingly aware of making an error as the response becomes increasingly late. We found evidence of response conflict before errors defined by late responses but not before errors defined by incorrect responses. The results also show a linear increase in the amplitude of the ERN with increasingly late responses. These data suggest that frontal networks provide dynamic representations that monitor and evaluate the unfolding action plan.

Modification and benchmarking of MCNP for low-energy tungsten spectra.

The MCNP Monte Carlo radiation transport code was modified for diagnostic medical physics applications. In particular, the modified code was thoroughly benchmarked for the production of polychromatic tungsten x-ray spectra in the 30-150 kV range. Validating the modified code for coupled electron-photon transport with benchmark spectra was supplemented with independent electron-only and photon-only transport benchmarks. Major revisions to the code included the proper treatment of characteristic K x-ray production and scoring, new impact ionization cross sections, and new bremsstrahlung cross sections. Minor revisions included updated photon cross sections, electron-electron bremsstrahlung production, and K x-ray yield. The modified MCNP code is benchmarked to electron backscatter factors, x-ray spectra production, and primary and scatter photon transport.

The polar average reference effect: a bias in estimating the head surface integral in EEG recording.

A reference-independent measure of potential is helpful for studying the multichannel EEG. The potentials integrated over the surface of the body is a constant, i.e. inactive across time, regardless of the activity and distribution of brain electric sources. Therefore, the average reference, the mean of all recording channels at each time point, may be used to approximate an inactive reference. However, this approximation is valid only with accurate spatial sampling of the scalp fields. Accurate sampling requires a sufficient electrode density and full coverage of the head's surface. If electrodes are concentrated in one region of the surface, such as just on the scalp, then the average is biased toward that region. Differences from the average will then be smaller in the center of the region, e.g. the vertex, than at the periphery. In this paper, we illustrate how this polar average reference effect (PARE) may be created by both the inadequate density and the uneven distribution of EEG electrodes. The greater the coverage of the surface of the volume conductor, the more the average reference approaches the ideal inactive reference.

Mood and spatial memory: emotion and right hemisphere contribution to spatial cognition.

Depressed persons show an impairment of spatial cognition that may reflect the influence of affective arousal on right hemisphere cognition. We examined normal university students to determine whether individual differences in mood and arousal levels would be related to performance on a spatial memory task. Right-hemisphere specialization for this spatial memory task was confirmed by a left field advantage for the targets and this field asymmetry was enhanced as task difficulty was increased. Event-related brain potentials (ERPs), assessed with a 64-channel sensor array, showed a processing negativity contralateral to the target in the P300 interval (300-500 ms after the target appeared). This effect increased as task difficulty was increased. A stronger posterior negativity for good (rather than bad) targets may suggest that attention was allocated toward the good locations. A suggestion of right hemisphere sensitivity to mood in this normal sample was a tendency for the subjects high in Negative Arousal not to show the normal right hemisphere (left field) superiority for the spatial memory task. Interestingly, a medial frontal lobe negativity was elicited in the ERPs by the bad targets, perhaps paralleling the error-related negativity observed in other paradigms. This medial frontal negativity was also seen in response to the feedback stimulus for the bad targets. Motivation may be important to this frontal effect: It was enhanced for subjects describing themselves as high in either positive or negative affective arousal during the task.

EEG coherency II: experimental comparisons of multiple measures.

OBJECTIVE: A concentric spheres model was used in an earlier paper to estimate the effects of volume conduction, reference electrode and spatial filtering on different EEG coherence measures. EEG data are used here to verify theoretical predictions. METHODS: Three EEG data sets were: (1) 64 channel, recorded during 7 alternating periods of resting and mental calculation. (2) 128 channel, for comparison of eyes open versus eyes closed coherence. (3) 128 channel, recorded during deep sleep (stages 3 and 4) and REM. RESULTS: The directions of large scale (lobeal) coherency changes between brain states are relatively independent of coherence measure. However, coherence between specific electrode pairs is sensitive to method and frequency. Average reference and digitally linked mastoids provide reasonable semi-quantitative estimates of large-scale neocortical source coherence. Close bipolar, Laplacian, and dura image methods remove most reference electrode and volume conduction distortion, but may underestimate coherence by spatial filtering. CONCLUSION: Each EEG coherence method has its own potential sources of error and provides coherence estimates for different neural population sizes located in different locations. Thus, studies of coherence and brain state should include several different kinds of estimates to take full advantage of information in recorded signals.

Dense sensor array topography of the event-related potential to task-relevant auditory stimuli.

High spatial density recording and better topographic mapping algorithms have improved the spatial resolving power of the event-related potential (ERP), adding to its already excellent temporal resolution. This study used a 64 channel recording array and spherical spline interpolation to create topographic descriptions of the voltage and current density scalp distributions of the ERP in an auditory oddball paradigm. Frequent (standard) and infrequent (target) tones were presented at a rate of one every approximately 2500 ms to a group of 20 college undergraduates in passive listening and active (count the infrequent tones) task blocks. ANOVAs and topographic analyses were performed on the primary deflections in the 'late' portion of the ERP: the P1, N1, P2, N2 and P3. A target minus standard difference wave was also created for each task. The difference wave contained a mismatch negativity (MMN), an N2b and a P3d. The MMN did not differ between the passive and active tasks and had a topography similar to the N1; also the difference wave P3d was topographically similar to the target P3. The N2b, which occurred only to targets in the active condition, and was the first index of target detection, had a scalp distribution consistent with generation in frontal and superior temporal cortex, suggesting activity in cortical areas of selective attention and auditory stimulus representation.