Detecting genetic structure in migrating bowhead whales off the coast of Barrow, Alaska.

We develop a general framework for analysing and testing genetic structure within a migratory assemblage that is based on measures of genetic differences between individuals. We demonstrate this method using microsatellite DNA data from the Bering-Chukchi-Beaufort stock of bowhead whales (Balaena mysticetus), sampled via Inuit hunting during the spring and autumn migration off Barrow, Alaska. This study includes a number of covariates such as whale ages and the time separation between captures. Applying the method to a sample of 117 bowhead whales, we use permutation methods to test for temporal trends in genetic differences that can be ascribed to age-related effects or to timing of catches during the seasons. The results reveal a pattern with elevated genetic differences among whales caught about a week apart, and are statistically significant for the autumn migration. In contrast, we find no effects of time of birth or age-difference on genetic differences. We discuss possible explanations for the results, including population substructuring, demographic consequences of historical overexploitation, and social structuring during migration.

Auditory processing skills and hearing aid satisfaction in a sample of older adults.

The present study investigated the relationship between central auditory processing skills and satisfaction with hearing aids in a hearing-impaired geriatric sample of 58 adult wearers of hearing aids who were between the ages of 65 and 91 years. Analysis suggests the importance of adding central auditory tasks such as compressed speech or dichotic listening tasks to the evaluation of candidacy for hearing aids. This could lead to the better understanding of satisfaction with amplification by the geriatric population.

Bootstrapping for pharmacokinetic models: visualization of predictive and parameter uncertainty.

PURPOSE: We explore use of "bootstrapping" methods to obtain a measure of reliability of predictions made in part from fits of individual drug level data with a pharmacokinetic (PK) model, and to help clarify parameter identifiability for such models. METHODS: Simulation studies use four sets (A-D) of drug concentration data obtained following a single oral dose. Each set is fit with a two compartment PK model, and the "bootstrap" is employed to examine the potential predictive variation in estimates of parameter sets. This yields an empirical distribution of plausible steady state (SS) drug concentration predictions that can be used to form a confidence interval for a prediction. RESULTS: A distinct, narrow confidence region in parameter space is identified for subjects A and B. The bootstrapped sets have a relatively large coefficient of variation (CV) (35-90% for A), yet the corresponding SS drug levels are tightly clustered (CVs only 2-9%). The results for C and D are dramatically different. The CVs for both the parameters and predicted drug levels are larger by a factor of 5 and more. The results reveal that the original data for C and D, but not A and B, can be represented by at least two different PK model manifestations, yet only one provides reliable predictions. CONCLUSIONS: The insights gained can facilitate making decisions about parameter identifiability. In particular, the results for C and D have important implications for the degree of implicit overparameterization that may exist in the PK model. In cases where the data support only a single model manifestation, the "bootstrap" method provides information needed to form a confidence interval for a prediction.

Perception of time-altered monosyllables in a specific group of phonologically disordered children.

Temporal auditory processing of open (e.g. pie) versus closed (e.g. pipe) syllables in a specific group of phonologically impaired children who deleted word-final consonants and normal phonologically developing children between the ages of 4 and 7 yr was investigated. The disordered group demonstrated significantly poorer discrimination at the faster but not slower rates of speech. Imitation of word-final consonants did not significantly increase in the disordered subjects when presented with time-expanded speech although certain individuals made noticeable improvements. Discussion of temporal auditory processing deficits from a neuropsychological perspective which suggests different etiologies is offered.

Renal ammoniagenic response to chronic acid loading: role of glucocorticoids.

Adrenalectomized (ADX) animals exhibit a blunted renal response to chronic acid loading. To determine whether this response truly reflects impaired renal ammoniagenesis from glutamine, urinary ammonium excretion was compared with acid intake in ADX, intact, and ADX rats supplemented with either a low dose (4 micrograms.100 g-1.day-1) or a high dose (40 micrograms.100 g-1.day-1) of triamcinolone. ADX rats consumed similar amounts of acid as did intact controls yet excreted only 37% of the load as ammonium; in contrast intact controls returned 86% and triamcinolone-supplemented animals returned 98 and 88% for low and high doses, respectively. Nor could the reduced ammonium excretion be attributed to increased renal venous release, since total ammonia production, the sum of renal venous and urine ammonium, was reduced to 49% of the intact controls; low- and high-dose triamcinolone restored and markedly increased the production rate. Underlying the impaired ammonia production rate in ADX rats was a reduced rate of glutamine extraction, 350 +/- 49 vs. 896 +/- 102 and 1,260 +/- 247 and 1,448 +/- 112 nmol.min-1.100 g-1 for intact and low and high doses, respectively. Unlike intact acidotic and glucocorticoid-supplemented ADX acidotic rats, glutamine extraction was disassociated from the delivered glutamine load consonant with the role of glucocorticoid in coupling cellular glutamine transport to its metabolic utilization.

Renal regulation of interorgan glutamine flow in metabolic acidosis.

The regulation of interorgan glutamine flow was studied in control and chronically metabolically acidotic rats. Net glutamine extraction or production across the kidneys, gut, liver, and hindquarters was determined in fasted anesthetized animals from organ blood flows and the arteriovenous glutamine concentration difference. In control animals glutamine flows from the hindquarters to the splanchnic bed. In chronic acidosis glutamine production by the hindquarters rose threefold and was redirected to the kidneys; splanchnic bed glutamine uptake was eliminated. Associated with this was a 39% fall and a 62% rise in arterial glutamine and ammonia concentrations, respectively. Removing the kidneys from the circulation returned arterial glutamine and ammonia concentrations to control nonacidotic levels within 30 min. Net glutamine production by the hindquarters decreased, whereas splanchnic bed glutamine extraction increased. Hindquarter glutamine production appears to be modulated by renal venous ammonia; splanchnic bed glutamine extraction is load dependent, reflecting the influence of renal glutamine consumption on the steady-state arterial levels. Thus the removal of the kidneys returns interorgan glutamine flow to that observed in nonacidotic animals consistent with a major role of the kidneys in regulating glutamine flow and nitrogen metabolism in chronic metabolic acidosis.

Regulation of interorganal glutamine flow in metabolic acidosis.

Metabolic acidosis redirects interorgan glutamine flow from hepatic utilization to renal ammoniagenesis at the expense of ureagenesis. The roles of arterial glutamine load and organ glutaminase capacity in the regulation of glutamine balance across the gut, liver, and kidneys were studied in control and chronically acidotic rats. In control rats these organs combined to remove 733 nmol glutamine X min-1 X 100 g-1 in agreement with their respective glutaminase content, gut greater than liver greater than kidneys. In chronic metabolic acidosis renal glutamine extraction alone increased to 1,158 nmol X min-1 X 100 g-1 associated with an increased glutaminase capacity. However, the total glutamine deficit across these organs rose to only 1,043 nmol glutamine consumed X min-1 X 100 g-1 as a consequence of hepatic glutamine uptake reversing to net release. This reversal was not dependent on increased hepatic glutamine synthetase capacity, but rather appears to be dependent on the combined effect of reduced portal venous glutamine load and increased ammonia load. The reduction in portal glutamine load is, in turn, a consequence of renal glutamine extraction and reduced arterial glutamine concentration in metabolic acidosis as well as maintained gut glutamine extraction. Elevating arterial glutamine concentration in metabolic acidosis has no effect on renal uptake, but enhances splanchnic bed extraction with the restoration of ureagenesis. Thus the interorgan flow of glutamine and deposition of N into either urea or ammonia appears to be dependent on arterial glutamine concentration and hence glutamine availability in chronic metabolic acidosis in the rat.

Body position and acoustic admittance.

The purpose of this study was to determine the effects of body position on the acoustic admittance of the normal middle ear mechanism. Susceptance tympanograms were obtained and their values recorded to determine the significance of any differences among five different body positions. A positive pressure shift was found to occur at the point of maximum compliance between the upright body position and the remaining four recumbent body positions. Attention should be given to the effects that differing body positions have on acoustic admittance whenever assessment of this nature is anticipated.

Acoustic immittance testing of the Eustachian tube.

The pathophysiological relationship of Eustachian tube dysfunction to middle ear effusion is widely accepted. Several techniques have been developed for utilizing the clinical measurements of acoustic immittance to assess the ventilatory status of the Eustachian tube. This article describes the array of procedures currently in use as well as a selection of procedures being developed for clinical assessment of the Eustachian tube. Most studies in this area have concentrated on measurements of normal function. Clinicians and researchers are encouraged to increase the application of these techniques in order to broaden the data base that is currently available concerning normal and pathological function.

A brief review of the use of both tympanometric pressure equalization and middle-ear function in assessing eustachian tube patency.

This paper reviews recent studies on the tympanometric assessment of Eustachian tube patency involving the traditional technique of assessing pressure equilibration plus the analysis of changes in middle-ear ability to transmit energy through its system (middle-ear function). Normative data in the literature on 89 pediatric ears and 48 adult ears are discussed. The data illustrated a significant loss of information if pressure change is measured without consideration of middle-ear function change. Recommendations for the clinic are given and the need stated for extending such work to the pathological ear.

Estimation of auditory sensitivity from the acoustic reflex with mentally deficient children.

This study applied conventional pure-tone and/or speech audiometric screening, tympanometry, and acoustic reflex threshold (ART) testing to 33 mentally deficient children (I.Q. less than 25), who nevertheless exhibited ability to respond to conventional screening. The SPAR procedure (Jerger et al, J. Speech Hear. Dis., 1974, 39, 11-22) and bivariate plotting procedures (Margolis and Fox, J. Speech Hear. Res., 1977, 20, 241-253) were used to estimate hearing loss (normal, mild-moderate, severe) from ipsilateral and/or contralateral ART's to pure-tone and to broadband noise stimuli. Both techniques were found to be useful, the bivariate plotting procedure yielding somewhat more accurate estimates of hearing loss. However, caution was suggested when using these techniques with Ss who have passed traditional audiometric screening.

Revision behaviors of normal and hearing-impaired children.

Children's response to communicative failure was evaluated in terms of linguistic and nonlinguistic behaviors. Six hearing-impaired and six normal-hearing children served as subjects. Each group was comprised of three children at each of brown's language stages I and III. Each child was engaged in spontaneous play and received the communicative failure cure "What?" on 20 occasions. Videorecorded responses were scored as repetitions, revisions, or no responses. Revisions were analyzed and categorized into one of nine categories according to linguistic and nonlinguistic structures. Results revealed that both groups of subjects used linguistic and nonlinguistic information in this revision behavior. However, the two groups differed in their pattern of revision behaviors. The hearing-impaired subjects, unlike the normal-hearing subjects, used less linguistic revision behaviors regardless of language development. Findings showed that the nonlinguistic as well as linguistic information may be important considerations when evaluating language with the hearing impaired.

Consonant identification in quiet and in noise with the normal and the sensorineural hearing-impaired.

This study determined the effect on consonant identification of speech-to-noise ratio; the California Consonant Test (CCT) was given to 20 normal-hearing young adults and 14 patients (mm age: 56.1 yrs) with sloping sensorineural hearing losses, SRT greater than 20 db, and DS less than 90% at MCL. The CCT was given individually at MCL in quiet and at that level in broad-band noise adjusted to yield 20, 10, 0, and -10 db S/N, consecutively. Mean percent-correct scores for the patients were 50, 44, 40, 38, and 32 in order, and were 97, 90, 73, 47, and 37 for the controls. Differences were significant between groups except for the 2 most difficult ratios. For the patients, regression analysis revealed that the slope of the line of best fit was not significantly different from zero. Confusion matrices constructed for each of the 5 noise conditions for each group revealed that at S/N of 10 db, normal Ss began consistent and systematic substitutions in manner and in place of articulation, never in voicing or nasality. This pattern was in general followed by the patients, except that substantial confusions existed also at the 2 easiest ratios.

A systematic investigation of measurement parameters of acoustic-reflex adaptation.

Acoustic-reflex adaptation was assessed in 49 normal ears. Acoustic reflexes were elicited by the use of contralateral stimulation at four frequencies and five sensation levels. The results displayed the effects of stimulus frequency and sensation level on the amount of acoustic-reflex adaptation. Suggestions are presented for clinical procedures for obtaining contralateral acoustic reflex adaptation measures.

An examination of variables involved in tympanometric assessment of eustachian tube function in adults.

Eustachian tube function was assessed tympanometrically in a group of normal adults. A pressure-swallow technique of assessing Eustachian tube ventilatory function was administered with positive and negative induced pressures in the range of +/- 200 mm to +/- 400 mm H2O. This study indicated the relative efficiency of measurement of Eustachian tube function under each of the experimental conditions. Recommendations of procedures for further clinical data collection are presented.

Fluorescent staining of hair cells with ethidium bromide.

The present study evaluated ethidium bromide, a nucleic acid-specific fluorescing stain for cochlear applications. Tissue exposed to acoustic stimulation did not exhibit the loss of fluorescence in hair cells described in studies on other fluorescing stains. The ethidium bromide fluorescence technique was, however, found to be useful in detecting subtle damage in cell nuclei even before gross structural alterations in cochlear cytoarchitecture appeared. The implications of the use to ethidium bromide staining for histologists are discussed.

Discrimination of speech intensity differences via vibrotactile stimulation.

This study investigated vibrotactile difference limen judgments for intensity using certain speech signals as stimuli. The variables under investigation were those of stimulus presentation level, direction of intensity increment or decrement within each paired-comparison stimulus complex, and the spectral composition of the speech signals. The results indicate that the level of stimulus presentation did not affect difference limen decisions among any of the sensation levels utilized. The largest most consistent effect upon difference limen judgments was in the direction of intensity change. The difference limen judgments were smaller when the second stimulus of the pair was of less intensity than the first. There was no effect upon difference limen decision as the result of stimuli having different spectral compositions.

Tympanometric assessment of eustachian tube patency in children.

Eustachian tube patency was assessed tympanometrically in a group of otologically normal children at a pediatric outpatient clinic. A pressure-swallow technique of assessing eustachian tube patency was administered. The results indicated the importance of the examination of both middle ear pressure and function changes in the evaluation of eustachian tube test results.