Hand posture affects brain-function measures associated with listening to speech.

A major difficulty in studies of the brain, from the molecular to large-scale network level, is ensuring the accuracy and reliability of results, since repeatability has been a problem in studies utilizing functional magnetic resonance imaging (f-MRI) near-infrared spectroscopy (NIRS), and positron-emission tomography (PET). More generally, an effort to replicate psychological studies has shown that the original results were unambiguously reobtained only 39% of the time. It has been suggested that researchers must undertake studies to identify factors that reduce reliability and conduct more carefully controlled studies to improve reliability. In our previous work, we examined whether changes in hand/arm posture can have a confounding effect on task-related brain activity. Here we show a solution to enhance reproducibility in a NIRS study in a hearing task. The results showed that crossed posture can lead to different results than parallel posture with respect to asymmetric functional connectivity, especially during non-resting state. Even when the only task is listening to speech stimuli, participants should be asked to place their hands on a surface and feet on the floor and keep the same stable posture to increase reproducibility of results. To achieve accurate reliability and reproductively of results, stable hand posture through the experiment is important.

Performance measures for a dialysis setting.

OBJECTIVES: This study from Japan extracted performance measures for dialysis unit management and investigated their characteristics from professional views. METHODS: Two surveys were conducted using self-administered questionnaires, in which dialysis managers/staff were asked to rate the usefulness of 44 performance indicators. A total of 255 managers and 2,097 staff responded. RESULTS: Eight performance measures were elicited from dialysis manager and staff responses: these were safety, operational efficiency, quality of working life, financial effectiveness, employee development, mortality, patient/employee satisfaction and patient-centred health care. These performance measures were almost compatible with those extracted in overall healthcare settings in a previous study. Internal reliability, content and construct validity of the performance measures for the dialysis setting were ensured to some extent. As a general trend, both dialysis managers and staff perceived performance measures as highly useful, especially for safety, mortality, operational efficiency and patient/employee satisfaction, but showed relatively low concerns for patient-centred health care and employee development. However, dialysis managers' usefulness perceptions were significantly higher than staff. CONCLUSIONS: Important guidelines for designing a holistic hospital/clinic management system were yielded. Performance measures must be balanced for outcomes and performance shaping factors (PSF); a common set of performance measures could be applied to all the healthcare settings, although performance indicators of each measure should be composed based on the application field and setting; in addition, sound causal relationships between PSF and outcome measures/indicators should be explored for further improvement.

Performance indicators: healthcare professionals' views.

Purpose - The purpose of this paper is to capture factors behind professional views of indicator usefulness as a common structure for assessing healthcare performance and their important characteristics to design limited key performance indicators (PIs) for holistic hospital management. Design/methodology/approach - Two surveys were conducted using self-administered questionnaires, in which hospital manager/staff respondents were asked to rate the 52 PIs' usefulness. In total, 228 manager and 894 staff responses were collected. Findings - Eight factors were elicited from manager and staff responses as performance measures with 72 percent cumulative variance accounted for. Hospital managers and staff showed similar performance measure perceptions: high-utility acknowledgment on safety, operational efficiency and patient/employee satisfaction but relatively low-employee development concerns. Manager indicator usefulness perceptions were rather homogeneous and significantly higher than staff for almost all performance measures. Practical implications - Homogeneous manager views mean that a single key PI set for hospital management may be established regardless of hospital attributes. The following aspects may be measures that should be managed in a healthcare organization based on their key PIs: patient/employee safety, operational efficiency, financial effectiveness and patient/employee satisfaction. Originality/value - This is a pilot study on hospital management PIs in Japan. The eight-dimensional factor structure and findings about healthcare provider perceptions may be useful for healthcare management.

Pharmacokinetics of S-Allyl-l-cysteine in Rats Is Characterized by High Oral Absorption and Extensive Renal Reabsorption.

BACKGROUND: S-Allylcysteine (SAC) is a key component of aged garlic extract, one of many garlic products. However, information on its pharmacokinetics has been scant except for data from a few animal studies. OBJECTIVE: We designed this study to determine the overall pharmacokinetics of SAC in rats. METHODS: After oral or intravenous administration of SAC to rats at a dose of 5 mg/kg, the plasma concentration-time profile of SAC and its metabolites, as well as the amounts excreted in bile and urine, were analyzed by using liquid chromatography tandem mass spectrometry. RESULTS: After oral administration, SAC was well absorbed with a bioavailability of 98%. Two major metabolites of SAC, N-acetyl-S-allylcysteine (NAc-SAC) and N-acetyl-S-allylcysteine sulfoxide (NAc-SACS), were detected in plasma, but their concentrations were markedly lower than those of SAC. SAC was metabolized to a limited extent, but most of the orally absorbed SAC was excreted into urine in the form of its N-acetylated metabolites. The amounts of SAC, NAc-SAC, and NAc-SACS excreted in urine over 24 h were 2.9%, 80%, and 11% of the orally administered SAC, respectively. The very low renal clearance (0.016 L ⋅ h(-1) ⋅ kg(-1)) of SAC indicated that it undergoes extensive renal reabsorption. These results collectively suggested that SAC was ultimately metabolized to NAc-SAC and NAc-SACS through the cycles of urinary excretion, renal reabsorption, and systemic recirculation. CONCLUSION: The pharmacokinetics of SAC in rats were characterized by high oral absorption, limited metabolism, and extensive renal reabsorption, all of which potentially contribute to its high and relatively long-lasting plasma concentrations.

Metabolism, excretion, and pharmacokinetics of S-allyl-L-cysteine in rats and dogs.

The metabolism, excretion, and pharmacokinetics of S-allyl-l-cysteine (SAC), an active key component of garlic supplements, were examined in rats and dogs. A single dose of SAC was administered orally or i.v. to rats (5 mg/kg) and dogs (2 mg/kg). SAC was well absorbed (bioavailability >90%) and its four metabolites-N-acetyl-S-allyl-l-cysteine (NAc-SAC), N-acetyl-S-allyl-l-cysteine sulfoxide (NAc-SACS), S-allyl-l-cysteine sulfoxide (SACS), and l-γ-glutamyl-S-allyl-l-cysteine-were identified in the plasma and/or urine. Renal clearance values (<0.01 l/h/kg) of SAC indicated its extensive renal reabsorption, which contributed to the long elimination half-life of SAC, especially in dogs (12 hours). The metabolism of SAC to NAc-SAC, principal metabolite of SAC, was studied in vitro and in vivo. Liver and kidney S9 fractions of rats and dogs catalyzed both N-acetylation of SAC and deacetylation of NAc-SAC. After i.v. administration of NAc-SAC, SAC appeared in the plasma and its concentration declined in parallel with that of NAc-SAC. These results suggest that the rate and extent of the formation of NAc-SAC are determined by the N-acetylation and deacetylation activities of liver and kidney. Also, NAc-SACS was detected in the plasma after i.v. administration of either NAc-SAC or SACS, suggesting that NAc-SACS could be formed via both N-acetylation of SACS and S-oxidation of NAc-SAC. In conclusion, this study demonstrated that the pharmacokinetics of SAC in rats and dogs is characterized by its high oral bioavailability, N-acetylation and S-oxidation metabolism, and extensive renal reabsorption, indicating the critical roles of liver and kidney in the elimination of SAC.

Brain activation associated with motor imagery of coordination exercises and social abilities.

The purposes of the present study were: (1) to investigate the brain activation associated with coordination exercises done by one person and those by two persons and (2) to examine the interrelationships between the brain activation and social abilities. We were interested in testing the hypothesis that viewing two-person coordination exercises evokes more sophisticated brain activation than viewing one-person coordination exercises. Thirty Japanese college students served as subjects. There were two sessions in this study: the functional magnetic resonance imaging (fMRI) session and the social ability session. In the fMRI session, the subjects were instructed to imagine they were performing coordination exercises. Also, we examined the social abilities from the viewpoint of empathising. Empathising was measured by self-reports on the Systemising, Empathy and Autism Spectrum Quotients (SQ, EQ and AQ). Regarding brain activation, blood oxygenation level dependent (BOLD) activation was significant in specific areas such as the left cuneus (Brodmann area: BA 17) when the subjects imagined they were performing exercises involving two persons, as compared with the cases when they imagined they were performing exercises involving only one person. The fMRI results showed that exercises done by two persons require more sophisticated communication than those done by one person. Furthermore, the results of this study suggested that those with more autistic traits may undergo difficulties in the exercises done by two persons, especially in the case of playing a role as a follower.

Conceptual framework for holistic dialysis management based on key performance indicators.

This paper develops a theoretical framework of holistic hospital management based on performance indicators that can be applied to dialysis hospitals, clinics or departments in Japan. Selection of a key indicator set and its validity tests were performed primarily by a questionnaire survey to dialysis experts as well as their statements obtained through interviews. The expert questionnaire asked respondents to rate the degree of "usefulness" for each of 66 indicators on a three-point scale (19 responses collected). Applying the theoretical framework, we selected a minimum set of key performance indicators for dialysis management that can be used in the Japanese context. The indicator set comprised 27 indicators and items that will be collected through three surveys: patient satisfaction, employee satisfaction, and safety culture. The indicators were confirmed by expert judgment from viewpoints of face, content and construct validity as well as their usefulness. This paper established a theoretical framework of performance measurement for holistic dialysis management from primary healthcare stakeholders' perspectives. In this framework, performance indicators were largely divided into healthcare outcomes and performance shaping factors. Indicators of the former type may be applied for the detection of operational problems or weaknesses in a dialysis hospital, clinic or department, while latent causes of each problem can be more effectively addressed by the latter type of indicators in terms of process, structure and culture/climate within the organization.

Synthesis and SAR of novel parenteral anti-pseudomonal cephalosporins: discovery of FR264205.

We describe herein the synthesis and biological evaluation of a series of novel cephalosporins with potent activity against Pseudomonas aeruginosa. Introduction of various amino groups to the 4-position of a 3-amino-2-methylpyrazole cephalosporin 3-side chain resulted in enhanced MIC values against multiple Pseudomonas aeruginosa strains and ultimately led to the discovery of FR264205 (15) with excellent anti-bacterial activity and weak convulsion effect by direct intracerebroventricular injection assay.

The influence of gender and personality traits on individual difference in auditory mismatch: a magnetoencephalographic (MMNm) study.

The mismatch negativity (MMN; and its magnetic counterpart, MMNm) is widely used to assess early-stage auditory cortical function in humans and its impairment in various neuropsychiatric disorders. To establish MMN as a useful clinical tool for objective monitoring of auditory cortical function in an individual, we investigated the effect of gender and personality traits on individual difference in MMNm in healthy subjects. Participants were 88 healthy adults (31 women and 57 men). The MMNm in response to the duration or frequency change of tones and those in response to across-phoneme change between vowels /a/ and /o/ were recorded using 204-channel whole-head magnetoencephalography. The temperament and character inventory (TCI) was used to assess individual personality traits. Women were associated with significantly delayed peak latency of phonetic MMNm for the right hemisphere compared with men. Men had greater strength of tonal duration MMNm for the left hemisphere than women. Additionally, the persistence score predicted the strength of phonetic MMNm for the left hemisphere in the combined sample and the tonal duration MMNm for the left hemisphere in men; reward dependence predicted the latency of the tonal duration MMNm for the left hemisphere in men; and cooperativeness predicted the strength of the tonal frequency MMNm for the right hemisphere in women. These results suggest that gender and personality traits have an effect on individual variability of the MMNm. Our observation may provide useful information to establish MMN/MMNm as a clinical tool for monitoring auditory cortical function on an individual basis.

Latency variation of auditory N1m responses to vocal and nonvocal sounds.

To investigate the temporal aspect of timbre processing, we recorded auditory-evoked neuromagnetic responses to periodic complex sounds, which were matched in all acoustic parameters except for two fundamental frequencies (F0s) and 12 spectral envelopes of vocal and nonvocal categories. Only for nonvocal sounds, a significant difference in N1m latency for F0 was detected in both hemispheres. A significant difference among stimuli was detected in both hemispheres for vocal and linear sounds, whereas only in the right hemisphere for instrumental sounds. Moreover, the results of paired comparison among F0s revealed that not only the vocal sounds but also some of the nonvocal sounds were F0-independent. This latency independence may be attributed to the relatively high power in the higher frequency spectrum.

A magnetoencephalographic study of Japanese vowel processing.

Magnetic brain responses were recorded to clarify the cortical representation of vowel processing in Japanese. We investigated the peak latencies and equivalent current dipoles of the auditory N1m responses to the Japanese vowels [a], [i], [o], and [u]. In intraindividual analyses for a single participant, well-replicated results for the dipole parameters supported the existence of phoneme-specific cortical maps for vowels. In the interindividual analyses for the eight participants, [a] and [i] elicited significantly earlier N1m responses than [u], and the dipole for [i] was more posteriorly oriented than [a] in the left hemisphere. The results of the current study suggest left hemispheric predominance in vowel processing and that factors associated with a different language system may modify the cortical map.

Neuromagnetic responses to binaural beat in human cerebral cortex.

The dichotic presentation of two sinusoids with a slight difference in frequency elicits subjective fluctuations called binaural beat (BB). BBs provide a classic example of binaural interaction considered to result from neural interaction in the central auditory pathway that receives input from both ears. To explore the cortical representation of the fluctuation of BB, we recorded magnetic fields evoked by slow BB of 4.00 or 6.66 Hz in nine normal subjects. The fields showed small amplitudes; however, they were strong enough to be distinguished from the noise accompanying the recordings. Spectral analyses of the magnetic fields recorded on single channels revealed that the responses evoked by BBs contained a specific spectral component of BB frequency, and the magnetic fields were confirmed to represent an auditory steady-state response (ASSR) to BB. The analyses of spatial distribution of BB-synchronized responses and minimum-norm current estimates revealed multiple BB ASSR sources in the parietal and frontal cortices in addition to the temporal areas, including auditory cortices. The phase of synchronized waveforms showed great variability, suggesting that BB ASSR does not represent changing interaural phase differences (IPD) per se, but instead it reflects a higher-order cognitive process corresponding to subjective fluctuations of BB. Our findings confirm that the activity of the human cerebral cortex can be synchronized with slow BB by using information on the IPD.

Auditory imagery mismatch negativity elicited in musicians.

A mismatch between auditory sensation and expectant imagery of syllables elicited a possible equivalent of mismatch negativity in a previous study. The purpose of this study was to verify whether auditory imagery from musical notation could also mediate such imagery-based mismatch negativity. Neuromagnetic recording was obtained from eight musicians, who were instructed to identify unpredictably occurring pitch mismatches between a random tone sequence and a visually presented musical score. The difference between incongruent and congruent responses showed a magnetic distribution consistent with two frontal-negative current dipoles bilaterally located in the vicinity of Heschl's gyrus, peaking at approximately 150 ms in latency. This imagery-based mismatch negativity may represent an early neural process of deviance detection between the sensory input and expectant imagery.

Delayed automatic detection of change in speech sounds in adults with autism: a magnetoencephalographic study.

OBJECTIVE: Autism is a form of pervasive developmental disorder in which dysfunction in interpersonal relationships and communication is fundamental. This study evaluated neurophysiological abnormalities at the basic level of language processing, i.e. automatic change detection of speech and non-speech sounds, using magnetoencephalographic recording of mismatch response elicited by change in vowels and tones. METHODS: The auditory magnetic mismatch field (MMF) was evaluated in 9 adults with autism and 19 control subjects using whole-head magnetoencephalography. The MMF in response to the duration change of a pure tone or vowel /a/ and that in response to across-phoneme change between vowels /a/ and /o/, were recorded. RESULTS: The groups were not significantly different in MMF power under any conditions. However, the autism group showed a left-biased latency prolongation of the MMF particularly under the across-phoneme change condition, and this latency delay was significantly associated with greater symptom severity. CONCLUSIONS: These results suggest that adults with autism are associated with delayed processing for automatic change detection of speech sounds. These electrophysiological abnormalities at the earliest level of information processing may contribute to the basis for language deficits observed in autism. SIGNIFICANCE: These results provide the first evidence for delayed latency of phonetic MMF in adults with autism.

Audiovisual phonological mismatch produces early negativity in auditory cortex.

During silent reading, visual information provided by letters is converted to auditory information in the mind. The purpose of this study was to identify the primary locus for auditory verbal imagery in the brain. Neuromagnetic recording was obtained from 10 right-handed study participants, who were instructed to identify infrequently occurring phonological mismatches between a random-ordered sequence of syllable sounds and a visually presented syllabogram sequence. The activity difference in early latency, calculated by subtracting the averaged responses to matched syllables from the averaged responses to mismatched syllables, showed a spatiotemporal profile strikingly similar to that of mismatch negativity. Auditory imagery of forthcoming verbal sounds may establish a memory trace as a template for imagery-based mismatch negativity generation in the auditory cortex.

Perceptual categorization of sound spectral envelopes reflected in auditory-evoked N1m.

Magnetic responses to periodic complex sounds with equivalent acoustic parameters except for two different fundamental frequencies (F0) and 12 different spectral envelopes of vocal, instrumental, and linear shapes were recorded to determine the cortical representation of timbre categorization in humans. Responses at approximately 100 ms (N1m) to vocal and instrumental (nonlinear) sounds were localized significantly anterior to linear sound responses. N1m source strength for nonlinear sounds was significantly larger than that for linear sounds, and this difference was more marked in the left hemisphere than in the right. N1m peak latency only for vocal sounds was not affected by F0. Perceptual categorization was reflected in N1m source strength and location (linear or nonlinear), and in N1m latency (vocal or nonvocal).

A modified parallel paradigm for clinical evaluation of auditory echoic memory.

We established a new parallel paradigm for mismatch negativity by presenting repetitive trains of three consonant-vowel syllables and those of three sinusoidal tones alternately. Magnetoencephalography was performed to test the new method, and mismatch negativities in six study participants with normal hearing were compared with the results of the conventional oddball paradigm. Peak amplitude and latencies of mismatch negativity showed no significant difference between the methods. The maximum amplitude in short memory probe interval of 1.0 s was significantly larger than in long memory probe interval of 3.0 s, demonstrating decay in auditory echoic memory caused by a prolonged memory probe interval. The new method facilitated simultaneous evaluation of mismatch negativity with various stimuli in a shorter period.

No effect of gender on tonal and phonetic mismatch negativity in normal adults assessed by a high-resolution EEG recording.

The auditory mismatch negativity (MMN) of event-related potential components has been widely used to assess the ability of auditory automatic change discrimination of verbal and nonverbal stimuli in healthy individuals and patients with various illnesses. To clarify the role of gender differences in the MMN, we compared the amplitude, latency, and topography of tonal and phonetic MMN between healthy males and females, using a high-density (128 channel) electroencephalography montage. The MMN was evaluated in 18 right-handed male and ten age-matched female adults. The MMN in response to a duration change of pure tone and that in response to a phonetic change (Japanese vowel /a/ versus /o/ with 150-ms duration) were recorded. There were no significant differences in amplitude, latency, or laterality for either tonal or phonetic MMN between male and female subjects. This lack of evidence for effects of gender on MMN in response to duration change of tones or that in response to changes of phonemes with a short duration in normal adults may be of relevance to a growing number of researchers who are studying the MMN in healthy individuals and various clinical groups.

Do high or low doses of anxiolytics and hypnotics affect mismatch negativity in schizophrenic subjects? An EEG and MEG study.

OBJECTIVE: Many studies have demonstrated mismatch negativity (MMN) attenuation in schizophrenia. Recently, investigators have shown that GABAergic inhibitory neurons may regulate MMN generation. Considering that a substantial proportion of schizophrenic patients receive anxiolytics and hypnotics that have affinity to GABA(A) receptors to reduce their comorbid symptoms of anxiety and sleep disturbances, we need to assess whether anxiolytics/hypnotics might affect their MMN generation. The aim of this study is to assess the possibility that high or low doses of anxiolytics/hypnotics received by schizophrenic subjects affect their mismatch negativity (MMN), using event-related potentials (ERPs) and magnetoencephalography (MEG). METHODS: Twenty-three and 16 patients with schizophrenia participated in the ERP and MEG studies, respectively. Three types of MMN (MMN in response to a duration change of pure-tone stimuli, within-category vowel change (Japanese vowel /a/ with short versus long duration), and across-category vowel change (vowel /a/ versus /o/)) were recorded. RESULTS: High or low doses of benzodiazepine had no significant effects on MMN amplitude/magnetic MMN power, topography/laterality, or latency under any conditions of the ERP or MEG study. CONCLUSIONS: These results suggest that chronic administration of anxiolytics/hypnotics does not significantly affect MMN in schizophrenia.