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Previous studies have demonstrated the high reproducibility of heart rate variability (HRV) measures in adults while little information exists concerning HRV reproducibility in children. Subsequently, the aim of the current study was to examine the moderate-term reproducibility of heart rate and frequency domain measures of HRV during rest and light to moderate exercise in children. Ten healthy children (6 males, 4 females) aged between 7 and 12 years of age volunteered for this study with HRV recordings obtained during supine rest and three treadmill walking exercise work rates (< or =60% maximum heart rate), initially and then 8 weeks later. Differences (P < 0.05) between variables were examined using paired t-tests or Wilcoxon signed rank tests while reliability and reproducibility were examined by intraclass correlation coefficients (ICC), coefficients of variation (CV), and mean bias ratio and ratio limits of agreement (LOA). Heart rate and all measures of HRV at rest and exercise were unchanged after 8 weeks. Significant ICC were documented primarily during rest (0.72-0.85) while weaker relationships (-0.02-0.87) were evident during exercise. A large range of CV was identified during rest (6-33%) and exercise (3-128%) while the ratio LOA were variable and substantial (1.04-2.73). Despite similar HRV over an 8-week period, variable ICC and sizable CV and ratio LOA indicate moderate to poor reproducibility of HRV in children, particularly during light to moderate exercise. Studies examining HRV in children should include age- or maturation stage-matched control participants to address the age-related change in HRV and inadequate HRV reliability.

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Previous studies have demonstrated the high reproducibility of heart rate variability (HRV) measures in adults while little information exists concerning HRV reproducibility in children. Subsequently, the aim of the current study was to examine the moderate-term reproducibility of heart rate and frequency domain measures of HRV during rest and light to moderate exercise in children. Ten healthy children (6 males, 4 females) aged between 7 and 12 years of age volunteered for this study with HRV recordings obtained during supine rest and three treadmill walking exercise work rates (¡Ü60 percent maximum heart rate), initially and then 8 weeks later. Differences (P < 0.05) between variables were examined using paired t-tests or Wilcoxon signed rank tests while reliability and reproducibility were examined by intraclass correlation coefficients (ICC), coefficients of variation (CV), and mean bias ratio and ratio limits of agreement (LOA). Heart rate and all measures of HRV at rest and exercise were unchanged after 8 weeks. Significant ICC were documented primarily during rest (0.72-0.85) while weaker relationships (-0.02-0.87) were evident during exercise. A large range of CV was identified during rest (6-33 percent) and exercise (3-128 percent) while the ratio LOA were variable and substantial (1.04-2.73). Despite similar HRV over an 8-week period, variable ICC and sizable CV and ratio LOA indicate moderate to poor reproducibility of HRV in children, particularly during light to moderate exercise. Studies examining HRV in children should include age- or maturation stage-matched control participants to address the age-related change in HRV and inadequate HRV reliability.

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Incidence and mortality rates of cervical cancer among Native American women is two to five times that of comparable Whites. Social and cultural differences contribute to this problem. We studied thirty age 40 and older American Indian women, half of whom had obtained at least one Pap in the past three years, the other half of whom had not. We asked: Do the two groups differ in their attitudes concerning Pap tests and those with whom they interact concerning Pap tests? and: Do they interact differently with different social groups concerning Pap tests? Data were obtained from chart audits and Given's Health Belief Questionnaire. The groups did not differ as to who they discussed Pap tests with or whose opinions they respected. They respected healthcare professionals most, family/friends less, and co-workers/others least. These findings suggest that the advanced practice nurse has an opportunity to improve Pap screening rates in this population.

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Studies of intonation in the hearing impaired (HI) are often concerned with either objective measures or listener perceptions. Less often has the focus been on how these two aspects of communication interrelate. This study examined the relationship between certain acoustic parameters and listeners' perceptions of intonation contours produced by HI children. Six severe-to-profound HI children and 6 normal-hearing (NH) children, ages 7;9 to 14;7, were individually tape recorded while reading 10 declarative sentences and 10 phonemically matched interrogative sentences within the context of a script. Each sentence ended with a carefully chosen disyllabic (target) word. Twelve adult listeners, inexperienced with the speech of the HI, listened to a randomized audio tape presentation of all of these productions and categorized each one as a statement, question, or other. Fundamental frequency (F0) and duration measurements were obtained for the target (final) word of each sentence, and intensity measures were recorded for each entire sentence. Acoustic analysis showed that all 6 of the NH children and 4 of the 6 HI children produced acoustically different intonation contours for declarative versus interrogative sentences. The HI children's productions were, in general, similar to the NH children, in that they used F0, duration, and intensity cues to mark the distinction. Their contrastive use of these acoustic cues, however, was less pronounced than for the NH children. Analysis of listener responses indicated that, although listeners were able to differentiate between some of the declarative and interrogative sentences produced by these 4 HI children, judgments corresponded with their intended type less often for the HI than for the NH children. (Judgments of NH children's utterances were 100% correct.) Multiple logistic regression of listeners' responses to the HI children's utterances showed that 4 acoustic measures, all derived from the sentence-final word, were significantly predictive: (1) sentence-final F0, (2) slope between the target word's initial and final F0, (3) duration of the target word, and (4) dB difference between the target word's 1st and 2nd syllables. Results were similar for the NH children's data, except that the ratio of the 2 syllables' durations was significant, rather than total word duration. These findings differ in several important ways from previously published data for HI children's intonation contours and suggest that many HI children have the ability to benefit substantially from training in the production of intonation.

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An LC-MS-MS method for the analysis of the neuraminidase inhibitor, zanamivir, in human serum is described. Zanamivir was extracted from protein precipitated human serum samples using Isolute SCX solid-phase extraction cartridges and analysed using reversed-phase chromatography with TurboIonSpray atmospheric pressure ionisation followed by mass spectrometric detection. The method uses a stable isotope internal standard, is highly specific and sensitive for a compound of this type and has been used for the analysis of human serum and urine samples from clinical studies. The method was extended to the analysis of serum and plasma samples from pre-clinical studies involving the rat, ferret and cell culture media. The method has been shown to be robust and valid over a concentration range of 10-5000 ng/ml using a 0.2-ml sample volume. The main advantages of this method compared to earlier procedures are primarily specificity, sensitivity, ease of sample preparation, small sample volume and short analysis time (ca. 5 min).

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BACKGROUND: Several studies have highlighted the problem of back pain among helicopter pilots, but few have controlled for potential confounding factors in their analyses, or sought to examine the effects of back pain on operational readiness and flying performance. There have been no previous studies of the prevalence of back pain among Australian military pilots. METHODS: The prevalence, risk factors, and consequences of low back pain were assessed in a cross-sectional survey of 200 Australian military helicopter pilots by self-completion questionnaire. RESULTS: Responses were received from 131 (66%) of available pilots. The overall prevalence of reported back pain was 64% (95% CI 56%-72%), with a further 28% of pilots describing back discomfort while flying. More than half the pilots (55%) indicated that back pain had interfered with their concentration while flying, with 16% reporting that they had hurried flying missions because of pain. A minority of pilots (7%) had refused to fly because of back problems. After adjusting for age, education, BMI, posture and numbers of hours flown, multiple logistic regression modelling indicated that a prior history of back injury was the most significant predictor of back pain among rotary wing pilots (OR 2.63, 95% CI 1.11-6.23). CONCLUSIONS: We conclude that the prevalence of back pain in Australian military helicopter pilots is unacceptably high and may be limiting operational readiness, pilot performance, flying safety, and pilot health. Urgent attention needs to be given to improved ergonomic design in aircraft, and both back pain prevention and back injury rehabilitation programs.

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1. Drug-related material was well absorbed following oral administration of 14C-famciclovir to the male rat at doses up to 4000 mg/kg and to the male dog at doses up to 250 mg/kg, as judged by the early onset of the peak blood or plasma concentrations of radioactivity (usually < or = 1.5h) and the rapid extensive excretion of radioactivity in the urine (57-76 and 86-89% of dose in rat and dog respectively). 2. Famciclovir underwent extensive first-pass metabolism in both species. In rat, following dosing at 40 mg/kg, famciclovir was rapidly and extensively metabolized to the active antiviral compound penciclovir, which reached peak concentrations in the plasma (mean 3.5 micrograms/ml) at 0.5 h. The 6-deoxy precursor of penciclovir, BRL 42359, was the only other major metabolite detected in rat plasma. Cmax values for BRL 42359 (mean 2.2 micrograms/ml) were also achieved at 0.5 h. In dog, extensive conversion of famciclovir to penciclovir, via BRL 42359, also occurred, but its rate of formation from BRL 42359 was somewhat slower than in rat. In dog, following dosing at 25 mg/kg, Cmax values for penciclovir (mean 4.4 micrograms/ml) occurred at 3 h and were lower than the Cmax values for BRL 42359 (mean 10.0 micrograms/ml) which were achieved at 1h. 3. A dose-dependent decrease in the conversion of BRL 42359 to penciclovir occurred in both species, resulting a changes in the ratios of the plasma concentrations of the two metabolites with increasing dose. In rat, the urinary excretion of penciclovir decreased from 36% of dose at 40 mg/kg to 21% at 4000 mg/kg, and was accompanied by a corresponding increase in the urinary excretion of BRL 42359. In dog, a similar decrease in the urinary excretion of penciclovir occurred on increasing the dose of famciclovir from 25 to 250 mg/kg. 4. Penciclovir and BRL 42359 were the major metabolites detected in urine and faeces. In rat, following dosing at 40 mg/kg, 54 and 22% of dose were recovered in the excreta as penciclovir and BRL 42359 respectively. Corresponding recoveries of the two metabolites in the dog were 34 and 50% of dose. The metabolic fate of famciclovir in these animal species is, therefore, similar to that reported previously in man.

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A very sensitive and specific quantitative assay for BRL 46470, a selective 5-HT3 receptor antagonist, in human plasma was developed. The method uses HPLC with serial UV absorbance detection followed by post-column photochemical reaction and fluorescence detection to provide an ultra-sensitive and specific method with a wide quantitative range. The post-column photochemical reaction enhances the very weak native fluorescence of BRL 46470 by a factor of approximately 150. The quantification ranges were determined to be 0.1-1.5 ng ml-1 (fluorescence detection) and 1.5-200 ng ml-1 (UV absorbance detection) for BRL 46470. Results from a 3 d validation at nominal BRL 46470 concentrations of 0.1, 0.4, 1.0 and 1.5 ng ml-1, using post-column photochemical reaction and fluorescence detection, demonstrated precision ranges of 3.4-5.8% (average within-day) and 1.6-5.6% (between-day). The average accuracy ranged from 93.4 to 114.5%. Results from a 3 d validation at nominal BRL 46470 concentrations of 1.5, 4.0, 25 and 200 ng ml-1, using UV absorbance detection, demonstrated precision ranges of 2.0-8.2% (average within-day) and 1.0-3.4% (between-day). The average accuracy ranged from 86.3 to 103.7%. The recovery of BRL 46470 from human plasma was approximately 64%. Assay specificity was confirmed by HPLC-MS.

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1. Following oral administration of 14C-famciclovir (500 mg) to three healthy male subjects, drug-related material was rapidly absorbed as judged by peak plasma concentrations of radioactive material being achieved by 0.75 h (6.7 +/- 0.9 microgram equiv./ml (mean +/- SD). 2. Famciclovir underwent extensive first-pass metabolism and was only detected in the plasma of one subject at low concentrations (0.5 microgram/ml). Famciclovir was rapidly and extensively metabolized to the active antiviral compound penciclovir, which reached peak concentrations in the plasma of 3.6 +/- 0.7 microgram/ml (0.75 h). The plasma elimination half-life value for penciclovir was 2.1 +/- 0.1 h. The 6-deoxy precursor of penciclovir, BRL 42359, was the only other relatively major metabolite detected in plasma. Peak plasma concentrations of BRL 42359 (1.0 +/- 0.1 microgram/ml) were achieved at 0.5 h. 3. After 3 days, 73.0 +/- 6.1% of the radioactive dose was excreted in urine, showing that good absorption of drug-related material occurred. Renal excretion was rapid since 60.2 +/- 4.2 and 72.3 +/- 5.7% of the dose was recovered in the urine samples collected up to 6 and 24 h, respectively. A good recovery of the administered radioactive dose was obtained since a further 26.6 +/- 5.1% of the dose was excreted in the faeces over a 72-h period. 4. Penciclovir and BRL 42359 were the major metabolites detected in urine and faeces. Penciclovir accounted for 59.2 +/- 4.9 and 4.2 +/- 1.4% of the dose in 0-24 h urine and 0-48 h faeces, respectively. Corresponding values for BRL 42359 were 5.0 +/- 0.5 and 17.0 +/- 6.2%, respectively. These metabolites were identified in the biological samples using hplc-ms and ms-ms with thermospray ionization.

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This paper describes a computerized system for the administration of the Wingate anaerobic test. The rate of pedal revolutions on a cycle ergometer is measured automatically to determine the maximal anaerobic capacity, total energy output and decline of power output over time. The system is cost effective, provides high accuracy and is incorporated into a fitness-analysis system that allows the user to recall and print present and past test results for the monitoring of anaerobic performance.

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Technological advancement in the area of synthetic speech has made it increasingly difficult to distinguish quality of speech based solely on intelligibility scores obtained in benign laboratory conditions. Intelligibility scores obtained for natural speech and a high-quality text-to-speech system (DECtalk) are not substantially different. This study examined the perceived intelligibility and speech interference thresholds of DECtalk male and female voices and compared them with data obtained for natural speech. Results revealed that decreasing signal-to-noise levels had more deleterious effects on the perception of DECtalk male and female voices than on the perception of natural speech. Analysis of pattern of phoneme errors revealed that similar general patterns of errors tended to occur in DECtalk and in natural speech. The speech interference test did not demonstrate any significant difference between the DECtalk male and female voices. These results were supported by the absence of a significant difference between DECtalk male and female voices during intelligibility testing at different signal-to-noise ratios.

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Previous work has demonstrated that muscular injury in rat soleus muscles resulting from eccentric contractions (downhill walking) is accompanied by elevations in mitochondrial [Ca2+] (MCC). Muscles are stretched during eccentric contractions, and there is evidence in the literature that stretch of the cell membrane induces Ca2+ influx in various tissues, including skeletal muscle. The purpose of this study was to determine if passive stretch of rat soleus muscles will induce increases in total muscle [Ca2+] (TCC) and MCC. Soleus muscles from female rats (51-122 g) were isolated and incubated in vitro for 2 h at resting length (Lo) or at the maximal in situ length (S). TCC (+62%) and MCC (+56%) were elevated in the S muscles. Also, there was a 63% reduction in maximal twitch tension in the S muscles. ATP concentration, phosphocreatine concentration, and lactate release between Lo and S muscles were the same, indicating that impaired metabolism was not responsible for the observed differences in [Ca2+] and force production between Lo and S muscles. Increases in TCC in the S condition indicate that stretch results in Ca2+ influx from the extracellular space, which is supported by the observation that when S muscles were incubated in Ca(2+)-free buffer, TCC and MCC did not increase. High concentrations of verapamil (0.25-0.75 mM) blocked the elevations in TCC and MCC in the S muscles, but the magnitude of the drug concentration required makes it questionable whether the effect resulted from specific blockade of slow voltage-sensitive Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)

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This study evaluated normally developing preschoolers' imitation of intonation contours modeled in a sentence elicitation task. Three intonation contours (declarative, interrogative, and monotone) were presented to 3- and 5-year-old children. Acoustic analyses using the Visi-Pitch and Apple IIe computer system, along with perceptual ratings, measured the extent to which preschoolers imitated a modeled intonation contour. The results indicated that, as a group, the children were perceived to imitate or partially imitate the preceding intonation contour modeled by the adult. The 5-year-old children imitated modeled contours more frequently than did the 3-year-old children. In contrast, the 3-year-old children primarily partially imitated the intonation contours. Further analysis revealed that between-group differences were due largely to accuracy in imitating the interrogative contour. These findings establish reference data on normal children and implicate the use of both acoustic and perceptual analyses in order to develop and interpret intervention strategies aimed at children with prosodic problems.

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This paper describes the development of a system with an intelligent interface for analysis of physiological correlates of athletes' physical performance capacities. The system improves the interface between the physiologist and the coach and provides scientific information in a systematic and coherent fashion. The recommendations provided are based on the results of a series of physiological tests. The implementation of the system is described with emphasis placed on recognition of the internal structure of the knowledge, independence from a particular shell, design for future expansion and maintenance and the integration with existing information resources.

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Many English-speaking children with specific language impairment have been found to be especially weak in their use of grammatical morphology. In a separate literature, many children meeting the same subject description have shown significant limitations on tasks involving the perception of rapid acoustic changes. In this study, we attempted to determine whether there were parallels between the grammatical morphological limitations of children with specific language impairment and their performance profiles across several perceptual contrasts. Because most English grammatical morphemes have shorter durations relative to adjacent morphemes in the speech stream, we hypothesized that children with specific language impairment would be especially weak in discriminating speech stimuli whose contrastive portions had shorter durations than the noncontrastive portions. Results from a group of eight children with specific language impairment with documented morphological difficulties confirmed these predictions. Several possible accounts of the observed morphology-perception parallels are offered.

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Seven elite boardsailors reporting nonradiating low back pain without leg pain during sailing volunteered for detailed examination. In these subjects, the onset of pain was limited to those occasions when sailing positions were held for a significant period of time, e.g., close hauled sailing or in light winds. No pain was described at any other time. The determination of possible antecedent factors was based on the results of clinical assessment, radiological evaluation, and computer tomography (CT) scanning. Apart from limited flexibility in some subjects, the clinical examination of these athletes was normal; CT changes in this group were limited to disc protrusions and bulges, and pars interarticularis defects. Despite the small number of subjects in the present report, it appears that the frequency of these problems exceeds that in the normal population. It may be possible to suggest that risk factors such as body position during prolonged sailing, particularly under light wind conditions without a harness, and limited flexibility may be associated with the radiological findings and may be implicated in the presence of low back pain, although further investigations appears warranted.

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The relationship between the selective serotonin reuptake inhibitor paroxetine and the sparteine oxidation polymorphism was investigated in a combined single-dose (30 mg) and steady-state (30 mg/day for 2 weeks) study including a panel of nine extensive metabolizers and eight poor metabolizers of sparteine. The median area under the plasma concentration-time curve (AUC) after the first paroxetine dose was about seven times higher in poor metabolizers than in extensive metabolizers (3910 versus 550 nmol.hr/L), whereas at steady state the median AUCss tau interphenotype difference was only twofold (4410 versus 2550 nmol.hr/L). Plasma half-life and steady-state plasma concentration were significantly longer and higher, respectively, in poor metabolizers than in extensive metabolizers (41 versus 16 hours and 151 versus 81 nmol/L). Paroxetine pharmacokinetics were linear in poor metabolizers and nonlinear only in extensive metabolizers. Sparteine metabolic ratio (MR = 12 hour urinary ratio of sparteine/dehydrosparteine), increased during treatment with paroxetine in subjects who were extensive metabolizers, and after 14 days treatment two extensive metabolizers were phenotyped as poor metabolizers and the remaining extensive metabolizers were changed into extremely slow extensive metabolizers with sparteine MRs of 5.7 to 16.5. The inhibition of sparteine metabolism was rapidly reversed after cessation of paroxetine administration. In the poor metabolizers there were no significant changes in MRs during the study. It is concluded that paroxetine and sparteine metabolism cosegregates, but the interphenotype difference in metabolism was less prominent at steady state than after a single dose, presumably because of saturation of the sparteine oxygenase (CYP2D6) in subjects who were extensive metabolizers. Paroxetine is a potent inhibitor of sparteine oxidation by CYP2D6 in vivo.

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