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PubMed2006

Clinical correlates and familial aggregation of age at onset in bipolar disorder.

OBJECTIVE: To assess whether age at onset variation reflects underlying genetic heterogeneity in bipolar disorder, the authors examined the clinical and familial characteristics of age at onset in bipolar disorder subjects from families with multiple affected members. METHOD: A total of 211 families with 1,856 subjects were ascertained through bipolar I disorder probands. All the subjects were assessed with the Diagnostic Interview for Genetic Studies and assigned diagnoses by trained clinicians using best estimate procedures. Admixture analysis with the 211 bipolar disorder probands was used to decompose the age-at-onset distribution into a mixture of theoretical normal distributions. Logistic regression with general estimating equations was then used to examine clinical correlates and familial aggregation of age at onset in all 717 bipolar disorder subjects. RESULTS: The age-at-onset distribution consisted of a mixture of three normal distributions with means of 16.6 (SD=5.1), 26.0 (SD=1.4), and 34.7 (SD=6.6) years that comprised 79.7%, 7.2%, and 13.1% of the group, respectively. Cutoff points at ages 21 and 28 were derived from this analysis and used to define age-at-onset subgroups. Early-onset (age at onset </=21) subjects had higher risks of drug abuse, alcohol abuse, rapid cycling, and suicide attempts. Affected subjects from a family with an early-onset proband were more likely than others to have an early onset (odds ratio=4.53, 95% CI=3.09-6.64). Subjects from a family with a proband whose age at onset was <28 were also more likely to have higher risks of drug abuse (odds ratio=11.62, 95% CI=2.16-62.66). CONCLUSIONS: Age at onset is associated with clinical heterogeneity in bipolar disorder and aggregates, possibly along with drug abuse, within families. These findings are consistent with the conclusion that age at onset reflects underlying genetic heterogeneity in bipolar disorder. Thus, age at onset may conceivably be used to identify more homogeneous groups of bipolar disorder families and thereby facilitate the mapping of bipolar disorder susceptibility genes.

Adult↗
PubMed2004

The varying distribution of intra- and inter-vertebral height ratios determines the prevalence of vertebral fractures.

Credible inferences regarding the burden of vertebral fractures (VFs) cannot be made without a globally accepted quantitative definition of 'fracture'. Currently, differences in anterior, middle, or posterior vertebral heights (VHs) within a vertebra, or between adjacent vertebrae, are used to define 'fracture'. However, VH differences are essential for the construction of thoracolumbar curves, evolutionary adaptations that provide stability in bipedal stance and gait. As there is no reference standard to distinguish anatomical variation from fracture, approaches to defining a VF use a reference range of VH ratios derived in premenopausal women or derived by trimming, a method that iteratively removes the tails of a distribution of VH ratios to produce a normal distribution. From this, reference ranges of VH ratio means and standard deviations (SDs) are obtained and a nominal deviation of 15% or more, or 3 SD or more is regarded as a 'fracture'. We measured VHs by quantitative vertebral morphometry (QVM) and bone mineral density (BMD) by dual energy X-ray absorptiometry in 697 Lebanese women (age 20-89 years) to compare the prevalence of VF ascertained by published methods and a new method that uses the premenopausal range (without trimming) and requires two VH abnormalities. VF prevalence using published methods reached 60% to 70% in pre- and post-menopausal women, and in women with normal or high BMD because VH ratios were not normally distributed and cut-offs used to define VF fracture fell within the observed distribution of the data. The new method resulted in a VF prevalence of 3.3% in younger and 14% in older women, 7% (high), 10% (middle), and 20% (low) BMD tertiles consistent with the notion that the method detected VF due to bone fragility. We suggest that using a fixed trimming method to define reference range and cut-offs or applying fixed cut-offs to identify VFs in populations, where these ratios are not normally distributed, may result in the capture of anatomical variation, not structural failure. Thus, group differences in the VF prevalence may reflect differences in methodology, not bone fragility. Improved criteria to define VF are needed before credible inferences can be made regarding the burden of VFs in women and men, and between sexes, races, countries, decades, and placebo arms of clinical trials.

Absorptiometry, Photon↗
PubMed1990

Receiver operator characteristic (ROC) curves and non-normal data: an empirical study.

This paper evaluates the performance of several diagnostic kits for assessing levels of serum prostatic acid phosphatase on patients at different stages of cancer of the prostate. Each patient was studied with several kits. We compare results obtained for receiver operator characteristic (ROC) curve methodology with data assumed to follow a normal distribution, with log-transformed data assumed to follow a normal distribution, and when neither of these assumptions holds. There were important differences between the results of the different approaches. For these data, the normal distribution assumption should be used with extreme caution. The log-transformed based results compared favourably with the non-parametric, but unconsidered application of the method should be avoided.

Acid Phosphatase↗
PubMed1989

[Study on distribution form of mesiodistal crown diameter in large sample: Part II].

The purpose of this research was to examine the distribution of the tooth size in a large sample. The objective teeth were the left upper and lower fourteen teeth except the third molar. The tooth size of 1,000 dental casts from the Japanese female orthodontic patients was measured. On each of them, a histogram and a set of statistics (mean, standard deviation, coefficient of variation, skewness, kurtosis, Geary value) are given in order to examine the distribution. The findings are as follows: 1) Each tooth may be classified into the following four types of distribution except the congenitally missing data. TYPE I: A normal distribution was observed in the upper and lower central incisors, the lower lateral incisor, the lower canine, the upper and lower first premolars, the upper second premolar, the upper and lower first molars and the lower second molar. TYPE II: A positively skewed distribution was observed in the lower second premolar. TYPE III: A negatively skewed and leptokurtic distribution was observed in the upper canine and the upper second molar. TYPE IV: An extremely negatively skewed and leptokurtic distribution was observed in upper lateral incisor. 2) With the four teeth which were classified into TYPE II, TYPE III and TYPE IV, the distribution of the lower second premolar was concluded to be of normal distribution by logarithmic transformation. The distribution of the upper canine and the upper second molar was judged to be of lognormal distribution and the upper lateral incisor also was judged to be of three parameter lognormal distribution and four parameter lognormal distribution. 3) The distribution of thirteen teeth except the upper lateral incisor was judged to be of normal distribution, by considering the congenitally missing data and the outlier in statistical data of the tooth.

Asian People↗
PubMed1990

Analysis and presentation of intracellular measurements obtained with ion-selective microelectrodes.

We have considered the manner in which data obtained with ion-selective electrodes should be evaluated. The potential difference recorded by such electrodes, with respect to a stable reference, is converted to a concentration by a non-linear transformation--the Nernst or Nikolsky equation. The mean and standard deviation of such estimations of concentration are then usually presented, which assumes that the latter variable is normally distributed. If, however, the recorded potential difference (PD) is the normally distributed variable and the mean value calculated, then a different value of mean concentration will be obtained. We show here that the recorded PD is indeed the normally distributed variable using data from a variety of ion-selective electrode measurements and conclude that the mean values of quoted ion concentrations have been overestimated by 6-43%.

Animals↗
PubMed2006

WHO Child Growth Standards based on length/height, weight and age.

AIM: To describe the methods used to construct the WHO Child Growth Standards based on length/height, weight and age, and to present resulting growth charts. METHODS: The WHO Child Growth Standards were derived from an international sample of healthy breastfed infants and young children raised in environments that do not constrain growth. Rigorous methods of data collection and standardized procedures across study sites yielded very high-quality data. The generation of the standards followed methodical, state-of-the-art statistical methodologies. The Box-Cox power exponential (BCPE) method, with curve smoothing by cubic splines, was used to construct the curves. The BCPE accommodates various kinds of distributions, from normal to skewed or kurtotic, as necessary. A set of diagnostic tools was used to detect possible biases in estimated percentiles or z-score curves. RESULTS: There was wide variability in the degrees of freedom required for the cubic splines to achieve the best model. Except for length/height-for-age, which followed a normal distribution, all other standards needed to model skewness but not kurtosis. Length-for-age and height-for-age standards were constructed by fitting a unique model that reflected the 0.7-cm average difference between these two measurements. The concordance between smoothed percentile curves and empirical percentiles was excellent and free of bias. Percentiles and z-score curves for boys and girls aged 0-60 mo were generated for weight-for-age, length/height-for-age, weight-for-length/height (45 to 110 cm and 65 to 120 cm, respectively) and body mass index-for-age. CONCLUSION: The WHO Child Growth Standards depict normal growth under optimal environmental conditions and can be used to assess children everywhere, regardless of ethnicity, socio-economic status and type of feeding.

Body Height↗
PubMed2007

Human growth hormone (GH1) gene polymorphism map in a normal-statured adult population.

OBJECTIVE: GH1 gene presents a complex map of single nucleotide polymorphisms (SNPs) in the entire promoter, coding and noncoding regions. The aim of the study was to establish the complete map of GH1 gene SNPs in our control normal population and to analyse its association with adult height. DESIGN, SUBJECTS AND MEASUREMENTS: A systematic GH1 gene analysis was designed in a control population of 307 adults of both sexes with height normally distributed within normal range for the same population: -2 standard deviation scores (SDS) to +2 SDS. An analysis was performed on individual and combined genotype associations with adult height. RESULTS: Twenty-five SNPs presented a frequency over 1%: 11 in the promoter (P1 to P11), three in the 5'UTR region (P12 to P14), one in exon 1 (P15), three in intron 1 (P16 to P18), two in intron 2 (P19 and P20), two in exon 4 (P21 and P22) and three in intron 4 (P23 to P25). Twenty-nine additional changes with frequencies under 1% were found in 29 subjects. P8, P19, P20 and P25 had not been previously described. P6, P12, P17 and P25 accounted for 6.2% of the variation in adult height (P = 0.0007) in this population with genotypes A/G at P6, G/G at P6 and A/G at P12 decreasing height SDS (-0.063 +/- 0.031, -0.693 +/- 0.350 and -0.489 +/- 0.265, Mean +/- SE) and genotypes A/T at P17 and T/G at P25 increasing height SDS (+1.094 +/- 0.456 and +1.184 +/- 0.432). CONCLUSIONS: This study established the GH1 gene sequence variation map in a normal adult height control population confirming the high density of SNPs in a relatively small gene. Our study shows that the more frequent SNPs did not significantly contribute to height determination, while only one promoter and two intronic SNPs contributed significantly to it. Studies in larger populations will have to confirm the associations and in vitro functional studies will elucidate the mechanisms involved. Systematic GH1 gene analysis in patients with growth delay and suspected GH deficiency/insufficiency will clarify whether different SNP frequencies and/or the presence of different sequence changes may be associated with phenotypes in them.

Adult↗
PubMed1992

Calcitonin gene-related peptide, substance P and GAP-43/B-50 immunoreactivity in the normal and arthrotic knee joint of the mouse.

The aim of this study was to describe the normal distribution of calcitonin gene-related peptide (CGRP) and substance P (SP) containing fibres in the knee joint of the mouse and to obtain insight into the changes in innervation associated with degenerative processes in the joint. Arthrosis was induced by a single subpatellar intra-articular injection of bacterial collagenase. After decalcification in EDTA solutions, the CGRP and SP fibres were visualized by peroxidase-antiperoxidase pre-embedding immunocytochemistry for light microscopy. Control experiments on the mouse brain as a reference for the effect of EDTA on the immunostaining showed that the decalcification procedure with EDTA had not impaired the immunostaining. A rich innervation of thin varicose CGRP and SP immunoreactive fibres was found in most peri- and intra-articular tissue components. The periosteum, synovial tissues, the joint capsule and the intra-articular fat tissues were richly innervated. Less intense innervations were also found in the subchondral bone plates of the tibio-femoral joint and of the patella. Fibres were also found in the soft tissues between the patellar tendon and the femoral groove. No differences could be found between the location of CGRP and SP fibres with respect to the localization in the joint, but generally more CGRP fibres were found. The collagenase-induced osteoarthrosis was characterized by sclerosis of the subchondral bone, patellar dislocation, osteophyte formation, synovial proliferation and by severe cartilage abrasion, particularly on the medial side of the femoro-tibial joint. The overall distribution of CGRP and SP fibres was the same as in the control joints. However, major differences were found in all studied joints at specific locations around the cruciate ligaments, in the synovium around the patella, in the soft tissues lateral of the patella and in plica tissue between the patella and femoral groove. The CGRP and SP innervation was no longer detectable by immunolabelling with the antibodies. With a polyclonal antibody to the growth associated protein GAP-43/B-50, signs of degenerated axonal profiles were observed in these locations. At other peripheral locations, such as the muscles, the GAP-43/B-50 distribution was normal. In conclusion, the present study provides detailed information on the localization of CGRP and SP fibres, which may be involved in pain perception. Knowledge of the changes that occur during arthrosis may give more insight into the clinical symptoms.

Animals↗
PubMed1984

Heavy metals at trace level in edible mussels (Mytilus galloprovincialis Lamarck) from the gulf of Trieste.

The concentration of heavy metals (cobalt, nickel, copper, cadmium, mercury and lead), which are present at trace levels in the edible part of mussels (Mytilus galloprovincialis Lamarck) from hatcheries in the gulf of Trieste, is normally or log-normally distributed, according to a statistical test sensitive to asymmetry of the distribution. A log-normal distribution appears valid for describing nearly all trace metals, in particular toxic heavy metals like cadmium, mercury and lead. The frequency distribution of these metals has nearly the same asymmetry, although the one-way analysis of the variance shows that sample means come from different population means characterising the particular hatchery.

Animals↗
PubMed1998

Illness duration and neuropsychological impairments in schizophrenia.

This study aims to verify whether cognitive disturbances in schizophrenic patients are associated with illness duration, and to examine the influence of other covariates on neuropsychological disturbances. Sixty-nine consecutive admissions of schizophrenic patients (DSM-III-R, APA, 1987) were included to an acute psychiatric unit. Patients were evaluated by a semistructured interview and assessed with the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS). A wide neuropsychological battery, adapted to Spanish, was used. Variables were transformed to z-scores when their distribution was normal, or to log-values in the case of non-normal distributions. Pearson's correlation coefficients with a Bonferroni correction showed strong relationships between illness duration and cognitive performance in neuropsychological tests on visuomotor processes and delayed visual memory. In order to examine the influence of potential covariates on neuropsychological disturbances, stepwise multiple regression procedures were performed with each neuropsychological measure as a dependent variable, and years of education, age, gender, neuroleptic does in chlorpromazine equivalents, biperidene doses and illness duration as independent variables. The longer the illness duration, the poorer the performance on visuomotor process and delayed visual memory tasks. Moreover, the neuropsychological disturbances associated with illness duration were different from those related to aging, educational background, gender and treatment status. These findings suggest the existence of a relationship between cognitive decline in visuomotor and delayed visual memory functions and the length of schizophrenic illness.

Adolescent↗
PubMed2000

Intestinal trehalase activity in a UK population: establishing a normal range and the effect of disease.

Trehalose is a disaccharide, the main dietary source being mushrooms. It has been approved as an additive in the preparation of dried food. Isolated intestinal trehalase deficiency is found in 8% of Greenlanders, but is rare elsewhere. The normal range of trehalase activity and the incidence of isolated trehalase deficiency in the UK have not been reported. Patients (n 400) were investigated for suspected malabsorption. Endoscopic distal duodenal biopsies were taken for histological assessment and maltase, sucrase, lactase and trehalase estimation. Disaccharidase activities were determined by Dahlqvist's technique (Dahlqvist, 1968). Most patients (n 369) had normal duodenal histology. In these, square root transformation of trehalase activity produced a normal distribution. The normal range (mean +/- 2 SD) was 4.79-37.12 U/g protein. One patient had an isolated borderline trehalase deficiency. The thirty-one patients with villous atrophy had significantly reduced disaccharidase activities. With ingestion of a gluten-free diet, maltase, sucrase and trehalase activities recovered to normal in most patients, whereas lactase activity did not. The normal range and very low incidence of isolated enzyme deficiency is comparable with that described in populations from the USA and mainland Europe. Activity is significantly reduced in untreated coeliac disease and recovers with treatment with a gluten-free diet. There is no place for routine determination of trehalase activity in the UK population and there should be no concern over the introduction of trehalose-containing dried foods.

Adolescent↗
PubMedDate not supplied

Langerhans cell histiocytosis of the female genital tract: a literature review.

Langerhans cell histiocytosis (LCH) is a rare malignant disease involving the accumulation of a monoclonal proliferation of cells in various organs, that phenotypically resemble Langerhans cells (LC). LCH is not merely a hyperplasia of LC, as it typically affects organs that are outside of their normal physiologic distribution. Normal Langerhans cells are bone marrow-derived dendritic cells that populate the epidermis and are distinguished by the presence of Birbeck granules and cell surface protein CD1a. LC act as sentinels; they recognize, internalize, and process antigens encountered in the skin. Upon encountering an antigen, LC become activated with subsequent maturation and induction of their migratory capacity. Langerhans cells in patients with LCH are aberrant and profoundly differ from normal LC. The clinical spectrum of LCH is quite diverse; multiple organs can be affected. "Pure" genital Langerhans cell histiocytosis is a rare presentation, with only 12 previously reported cases. Due to the rarity of this disease, treatment of genital LCH is still very diverse. No modality is proven to be superior in improving patient outcome, and relapses frequently occur after surgery. Dramatic responses of cutaneous and ano-genital lesions to thalidomide and interferons have been reported. We advocate the use of immuno-modulating agents in LCH of the female genital tract first, rather than surgery.

Adjuvants, Immunologic↗
PubMed2002

Reduction of variability of exhaled nitric oxide in healthy volunteers.

Exhaled nitric oxide (eNO) is elevated in patients with asthma in contrast to healthy subjects, although the variability is high. In this study, we tried to reduce the variability of eNO in healthy subjects. We measured eNO using ERS guidelines with a fixed exhalation flow of 250 ml/s in 117 (72 women, 45 men) non-smoking healthy subjects and correlated this to antropometric data and standard lung function measurements. Using a model previously defined by Hyde et al., we selected parameters that were likely to have a high correlation with eNO. ENO was log-normally distributed. The normal values for eNO are significantly (P < 0.001) different for men and women: in women mean ln eNO levels (SD) were 1.49 (0.34), in men 1.74 (0.41) (back-transformed value 4.43 resp. 5.73 ppb). Using multiple regression analysis, only In D(m,CO), InTLC and In sG(aw) showed a significant positive correlation with In eNO in men, although only 20% of the variability of eNO could be explained. In women no correlation was observed and only 5% ofthe variability was explained. The high variability of eNO could only partly be explained in men, which makes the use of reference equations not very helpful.

Adult↗
PubMed2002

Statistical methods for analysing discrete and categorical data recorded in performance analysis.

In this paper, we identify appropriate statistical methods for analysing categorical differences in discrete variables or 'performance indicators' resulting from performance analysis. The random mechanisms associated with discrete events do not follow a normal distribution; that is, the normal distribution is a continuous not a discrete probability distribution. We propose appropriate statistical methods based on two key discrete probability distributions, the Poisson and binomial distributions. Two approaches are proposed and compared using examples from notational analysis. The first approach is based on the classic chi-square test of significance (both the goodness-of-fit test and the test of independence). The second approach adopts a more contemporary method based on log-linear and logit models fitted using the statistical software GLIM. Provided relatively simple one-way and two-way comparisons in categorical data are required, both of these approaches result in very similar conclusions. However, as soon as more complex models or higher-order comparisons are required, the approach based on log-linear and logit models is shown to be more effective. Indeed, when investigating those factors and categorical differences associated with binomial or binary response variables, such as the proportion of winners when attempting decisive shots in squash or the proportion of goals scored from all shots in association football, logit models become the only realistic method available. By applying log-linear and logit models to discrete events resulting from notational analysis, greater insight into the underlying mechanisms associated with sport performance can be achieved.

Humans↗
PubMedDate not supplied

Multiple peak alignment in sequential data analysis: a scale-space-based approach.

In this paper, we address the multiple peak alignment problem in sequential data analysis with an approach based on the Gaussian scale-space theory. We assume that multiple sets of detected peaks are the observed samples of a set of common peaks. We also assume that the locations of the observed peaks follow unimodal distributions (e.g., normal distribution) with their means equal to the corresponding locations of the common peaks and variances reflecting the extension of their variations. Under these assumptions, we convert the problem of estimating locations of the unknown number of common peaks from multiple sets of detected peaks into a much simpler problem of searching for local maxima in the scale-space representation. The optimization of the scale parameter is achieved using an energy minimization approach. We compare our approach with a hierarchical clustering method using both simulated data and real mass spectrometry data. We also demonstrate the merit of extending the binary peak detection method (i.e., a candidate is considered either as a peak or as a nonpeak) with a quantitative scoring measure-based approach (i.e., we assign to each candidate a possibility of being a peak).

Algorithms↗
PubMedDate not supplied

Sensitive thyroid-stimulating antibody assay with high concentrations of polyethylene glycol for the diagnosis of Graves' disease.

The aim of the present study was to determine the usefulness of a newly developed thyroid-stimulating antibody (TSAb) assay. We developed a highly sensitive TSAb (sTSAb) assay with 22.5% polyethylene glycol-precipitated crude IgG. The thyroid-stimulating hormone (TSH) receptor antibody (TRAb) causes Graves' disease and TRAb has been measured as TSH-binding inhibitor immunoglobulin (TBII) and thyroid-stimulating antibody (TSAb). The TSAb stimulates the thyroid glands and causes hyperthyroidism. In addition to investigating the usefulness of the newly developed sTSAb assay, we also investigated the frequencies of positive TRAb in thyrotoxic patients with subacute thyroiditis, painless thyroiditis or a solitary toxic nodule. We studied 700 untreated Graves' patients with hyperthyroidism and 923 normal controls. We also studied thyrotoxic patients with subacute thyroiditis, painless thyroiditis or a solitary toxic nodule. Conventional TSAb (cTSAb) and sTSAb were measured as TSAb, whereas porcine TBII (pTBII) and human recombinant TBII (hTBII) were measured as TBII. Levels of cTSAb and sTSAb were determined in 923 normal controls and 629 untreated Graves' patients and cTSAb and sTSAb were found to be normally distributed in normal controls, but not in untreated Graves' patients. Receiver operating characteristic (ROC) curve analysis demonstrated that cTSAb and sTSAb had high sensitivity and specificity for Graves' disease. Of the patients investigated, 96.5% of untreated Graves' patients were positive for sTSAb and/or pTBII. Some untreated Graves' patients who were negative for cTSAb were positive for sTSAb. Paired determinations of cTSAb and sTSAb were performed in 146 untreated Graves' patients. A positive correlation was found between cTSAb and sTSAb. Titres of sTSAb were higher than those of cTSAb and sTSAb had high sensitivity. Of the 35 untreated Graves' hyperthyroid patients who were negative for cTSAb, 18 (51%) were positive for sTSAb. Of the 36 untreated Graves' patients who were negative for hTBII, nine (25%) were positive for sTSAb. Some untreated Graves' patients who were negative for cTSAb were positive for sTSAb and some who were negative for hTBII and pTBII were positive for sTSAb. 5. Some thyrotoxic patients with subacute thyroiditis or painless thyroiditis were positive for TRAb. However, the frequency of TRAb-positive patients was low in this group. None of the patients with a solitary toxic nodule was positive for TRAb. In conclusion, sTSAb had higher sensitivity than cTSAb. Graves' patients who were cTSAb negative and hTBII negative could be sTSAb positive. The sTSAb indicates TSAb activity, but pTBII and hTBII do not necessarily do so. We recommended that the sTSAb is used in Graves' patients.

Adult↗
PubMed1979

Control chart for urinary oestriol excretion during pregnancy.

Calculations to define the distribution of normal urinary oestriol excretion values during pregnancy are presented. The values had a normal distribution, uniform variance and increased linearly with time after logarithmic conversion. The variance could, therefore, be partitioned and a control chart constructed.

Analysis of Variance↗
PubMed1993

Lung volume changes during relatively fluent speech in stutterers.

We investigated breathing patterns in stutterers during relatively fluent speech and compared these with normal subjects for similar speech tasks. Rib cage and abdominal displacements and esophageal, gastric, and transdiaphragmatic pressures provided indexes of diaphragmatic, rib cage, and abdominal muscle contraction. We found that stutterers spoke either at substantially higher or lower lung volumes than normal subjects, confining their speech to the inspiratory capacity or expiratory reserve volume. During spontaneous speech, stutterers did not cross functional residual capacity (FRC) for most breaths. In addition, stutterers used several different motion pathways from breath to breath. At high lung volumes stutterers used the diaphragm to provide inspiratory braking. At lung volumes below FRC stutterers recruited their abdominals. This contrasted with normal subjects who spoke in the middle part of the vital capacity and who recruited inspiratory and expiratory rib cage muscles above and below FRC, respectively. Breath sizes were log-normally distributed in stutterers compared with a gaussian distribution in normal subjects (P < 0.001). During reading, stutterers tended to cross FRC (P < 0.01), used very similar initiation lung volumes from breath to breath (P < 0.001), and used similar motion pathways to achieve deflation. We conclude that stutterers sustain fluency by speaking at abnormally high or low lung volumes and that this may account for the different muscle patterns observed in stutterers compared with normal subjects.

Diaphragm↗