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PubMed1995

[Evaluation of chemosensitivities of human breast cancers by primary culture assay in vitro].

Chemosensitivities of 32 human breast cancer to 6 antitumor drugs were assayed in vitro using MTT colorimetric method. The results showed that the chemosensitivity of primary breast cancer cultures varied remarkably from one patient, and from one drug, to another with hundred-to thousand-fold differences. The distribution of 50% inhibition concentration (IC50) was significantly deviated from normal distribution (P < 0.0001), and the drug sensitivity could be divided into four different catagories by means of percentile method. Preliminary results showed that the in vitro chemosensitivities of different antitumor drugs were consistent with the clinical therapeutic responses It seems that the herein reported assay might be useful on an individual basis to optimize chemotherapy of human breast cancer.

Antineoplastic Agents↗
PubMed1995

Frequent loss of heterozygosity in human primary squamous cell and colon carcinomas at 7q31.1: evidence for a broad range tumor suppressor gene.

Consistent deletions and loss of heterozygosity (LOH) in polymorphic markers in a determinate chromosomal fragment are known to be indicative of a closely mapping tumor suppressor gene. Deletion of the long arm of chromosome 7 is a frequent trait in many kinds of human primary tumors. We studied LOH of 14 markers on chromosome 7q in order to determine the location of a putative tumor suppressor gene in human primary squamous cell carcinoma of the head and neck and in human primary colon carcinomas. Samples were obtained from 18 primary squamous cell carcinomas of the head and neck and 18 primary colon carcinomas surgically removed from patients at the Fox Chase Cancer Center. Loss of heterozygosity was studied performing PCR amplifications of a set of 14 CA microsatellite repeats encompassing 7q21-qter. Of 18 squamous cell carcinomas of the head and neck cases studied, 12 had LOH at one or more loci on 7q. Fifty-three percent of 15 informative cases had LOH of the CA microsatellite dinucleotide repeat marker D7S522 at 7q31.1-7q31.2. Eleven of 18 colon carcinoma cases had LOH of one or more markers assayed, and the maximum LOH (80% of 10 informative cases) was at D7S522. Distributions of percentage of LOH in both tumor types were normally distributed around microsatellite D7S522. The high incidence of LOH in both tumor types studied suggests that a tumor suppressor gene relevant to the development of epithelial cancers is present on the 7q31.1-31.2, confirming our previous functional evidence for a tumor suppressor gene on chromosome 7.

Carcinoma, Squamous Cell↗
PubMed1993

Normal and abnormal proximal esophageal acid exposure: results of ambulatory dual-probe pH monitoring.

Ambulatory esophageal pH monitoring was performed in 26 normal volunteers, 20 patients with normal distal acid exposure, and 23 patients with abnormal distal acid exposure in an attempt to define normal values for proximal esophageal acid exposure using a standardized technique. We used a dual pH sensor with antimony electrodes spaced at 15 cm. The distal electrode was placed manometrically at 5 cm above the lower esophageal sphincter. Proximal electrode thus was located below the upper esophageal sphincter in the esophageal inlet. The patients underwent 24-h ambulatory pH monitoring and were told to pursue normal daily activities. The percentage of acid exposure time and number of episodes per 24 h at both pH < 4.0 and 5.0 were measured for the total, upright, and supine periods. Since the pH values were not normally distributed, the medians and 95th percentiles were used to define normal values. Minimal acid exposure occurred in the proximal esophagus (< 1% total; 0% supine) in volunteers and patients with normal distal reflux. Patients with abnormal distal acid exposure had significantly greater proximal reflux.

Adult↗
PubMedDate not supplied

[Noise exposure in a dry dock].

Personal monitoring of noise exposure was conducted in a small dry dock, where mainly tug-boats and high sea fishing-boats are refitted. Manual tools were the prevalent noise sources. Noise exposure could be affected and amplified by factors extraneous to workers' tasks. The workers might be employed in different jobs simultaneously also in confined and small areas, and were mainly involved in non-routine tasks. Six different tasks were investigated: dry-dock supervisor, welder/ship-wrights, painters, electricians, woodworkers and unskilled workers. The number of workers employed in the tasks, with the exclusion of the supervisor, might change from day to day according to the particular work phase carried out on the boat. Daily personal exposure was measured using Larson Davis mod. 700 integrating sound level meters. The all shift time history of short equivalent continuous sound level with 10 s integrating time was collected for each selected worker. A 1/2 inch microphone was attached to the helmet at a distance of 11 +/- 1 cm from the right outer ear. Measurements were repeated over 13 days and randomly distributed over about four months. The number of data-points collected was nine for the supervisor, twenty-seven for the welders, eighteen for the painters, twelve for the electricians, six for the woodworkers and eleven for the unskilled workers. Ranges of the daily noise exposure level were from 15 to 30 dBA for all tasks, with the exclusion of the woodworkers. The time histories relative to workers grouped in the same task were matched to verify the correlation. The daily exposure levels derived from correlated samples were substituted by their arithmetic mean. The analysis of variance applied to experimental distributions of daily exposure for four of the welders indicates that the difference of means (p > 0.3) is not significant. A similar conclusion is reached for painters when only this task is considered. If we take into account the exposures of painters employed also in different tasks, the probability is included in a range of lower significance, between 0.1 and 0.05. The experimental distributions of daily noise exposure for all tasks fit the normal distribution. The Kolmogorov-Smirnov test was used at a p > 0.1 confidence level. These results may have an important role in defining sampling strategies for collecting noise exposure data both for compliance and epidemiological purposes.

Confidence Intervals↗
PubMed1999

[Normal values of vertebral heights in a representative population survey in Hungary].

The authors' aim was to derive Hungarian normal vertebral heights, height ratios and threshold values. The mean -3 SD of these ratios give them the threshold values for defining normal vertebraes. They examined the standardized vertebral morphometric measurements obtained in a cross-sectional population survey. Radiographs were taken according to standardized protocol and morphomeric measurements of anterior, central and posterior heights from thoracic 4 to lumbar 4 were made with a semiautomatic technique. The anterior, central, posterior I and posterior II height ratios were calculated for each vertebra. The mean and standard deviation of these ratios for each sex were derived using a statistical procedure to normalize the distribution. From the normally distributed vertebral height ratios the mean and standard deviation give us the threshold values for defining normal vertebraes. Anterior and central vertebral height ratios were smaller in males than females. The authors compared the ratios and threshold values in different European centers using the same method. The data confirm that vertebral height ratios vary between and within populations and the authors suggest that normal values for vertebral height ratios should be derived separately for males and females at each vertebral level. Having the normal values the knowledge of the Hungarian normal vertebral height ratios gives the possibility to carry on multicentre clinical, therapeutic and epidemiologic studies of vertebral deformity in Hungary. The authors suggest the widespread use of morphometry to evaluate vertebral osteoporosis because it can be done in every radiology unit, it is a cheap and easy method for measuring the bone mineral content.

Anthropometry↗
PubMed2006

On plotting species abundance distributions.

1. There has been a revival of interest in species abundance distribution (SAD) models, stimulated by the claim that the log-normal distribution gave an underestimate of the observed numbers of rare species in species-rich assemblages. This led to the development of the neutral Zero Sum Multinomial distribution (ZSM) to better fit the observed data. 2. Yet plots of SADs, purportedly of the same data, showed differences in frequencies of species and of statistical fits to the ZSM and log-normal models due to the use of different binning methods. 3. We plot six different binning methods for the Barro Colorado Island (BCI) tropical tree data. The appearances of the curves are very different for the different binning methods. Consequently, the fits to different models may vary depending on the binning system used. 4. There is no agreed binning method for SAD plots. Our analysis suggests that a simple doubling of the number of individuals per species in each bin is perhaps the most practical one for illustrative purposes. Alternatively rank-abundance plots should be used. 5. For fitting and testing models exact methods have been developed and application of these does not require binning of data. Errors are introduced unnecessarily if data are binned before testing goodness-of-fit to models.

Animals↗
PubMed1998

Muscle fiber type distribution in the normal human levator veli palatini muscle.

OBJECTIVE: This study examined the muscle fiber type distribution within the normal adult levator veli palatini muscle. METHODS: Levator veli palatini muscle tissue was harvested from the palates of 12 (seven female, five male) adult noncleft cadavers. Adjacent sections were stained for adenosine triphosphatase at pH 10.4 or 4.2. After mounting, magnifying, and photographing, Type I versus Type II fiber types were differentiated by the intensity of, or by the inhibition of, staining of matched fibers at each pH level. Type I fibers stained light at pH 10.4 and dark at pH 4.2, while Type II fibers stained light at pH 4.2 and dark at pH 10.4. MAIN OUTCOME MEASURES: The number of fibers counted for each specimen ranged from 60 to 616. The numbers of Type I and Type II stained fibers appearing in each muscle tissue sample were determined and expressed as a percentage of the total number of fibers identified. A few identified fibers could not be labelled as either Type I or Type II. RESULTS: The overall proportion of Type I fibers, averaged across all specimens, was 59.8%. Male specimens had 67.4% Type I fibers and 31.8% Type II fibers, while female specimens had 54.4% Type I fibers and 44.4% Type II fibers. CONCLUSIONS: Observed fiber type distributions were similar to those reported for other articulatory muscles, but differed slightly from previously reported distributions for normal levator veli palatini. The distributions observed in this study provide a baseline against which to relate fiber type data from the levator veli palatini of cleft palates to the functional status of the velopharyngeal mechanism.

Adenosine Triphosphatases↗
PubMed1994

Quantal nature of synaptic transmission at the cytoneural junction in the frog labyrinth.

1. The mechanism of transmitter release at the cytoneural junction of the frog posterior canal was investigated by recording intracellularly subthreshold postsynaptic potentials (EPSPs), and performing a statistical analysis of time intervals and peak amplitudes. In single units EPSPs display highly variable size, so it is not clear whether they are generated by the release of single quanta of transmitter and whether large ones represent giant events, multiquantal events, or the random summation of independent unitary events. 2. In units with low resting EPSP rates, peak amplitudes and time intervals between EPSPs were measured directly. Peak amplitude histograms were continuous, unimodal and well fitted by log normal distributions. Time-interval histograms were well described by single exponentials. 3. At high EPSP rates (either at rest or during experimental treatments), where single events overlapped extensively, peak amplitude histograms were skewed markedly towards high values. Under these conditions, the EPSP waveform was estimated by autoregressive fit to the autocorrelation of the recorded signal. The fit was used to build a Wiener filter, for sharpening the original signal, before computing time-interval and peak amplitude histograms. This yielded consistent log normal peak amplitude distributions with no 'excess' skewness, similar to those obtained with low resting rates. 4. After sharpening by the Wiener filter, shoulders or small second peaks in amplitude distributions were observed only at the highest EPSP rates (> 300 s-1). The number of 'multiquantal' events was reduced by Wiener filtering, and was in general consistent with the expectation that more than one independent event occurred within the duration of the single event. This suggests that the events are uniquantal, random and independent, i.e. miniature EPSPs (mEPSPs). 5. In general, peak amplitude distributions obtained with modified external Ca2+ concentration ([Ca2+]o) and/or during mechanical stimulation or under efferent activation were not significantly altered with respect to those obtained in the same units at rest. Time-interval histograms were generally mono-exponential at rest as well as during mechanical or efferent stimulation, and irrespective of [Ca2+]o. Resting mEPSP rate was slightly increased by elevated [Ca2+]o and reduced by low [Ca2+]o. The increase in mEPSP rate produced by mechanical excitation was depressed by both high and low [Ca2+]o, whereas both conditions enhanced mechanical inhibition. Efferent inhibition was little affected. High [Ca2+]o hastened adaptation during efferent facilitation. Low [Ca2+]o reduced peak response during facilitation, but suppressed its warning. 6. In the presence of ATP a consistent though transient increase in resting mEPSP rate was observed in about 50% of units.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1995

Monte Carlo generation of SB and SU distributions.

Generating random variables from specific bounded or unbounded distributions is a problem frequently encountered in Monte Carlo studies. Of particular interest is that of transforming variables from a standard normal distribution to a given Johnson's SB or SU distribution with specified (gamma, delta) parameters. We use a composite standard normal generator N (0.1) to generate Johnson's SB or SU distributions with (gamma, delta) parameters. Goodness-of-fit tests and graphical illustrations demonstrate the adequacy of the empirical distributions.

Chi-Square Distribution↗
PubMed1992

Immunocytochemical analysis reveals differences between the subcellular localization of normal and delta Phe508 recombinant cystic fibrosis transmembrane conductance regulator.

Cystic fibrosis (CF) is caused by mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation responsible for CF is the deletion of amino acid residue Phe508, with an average allelic frequency of 70%. We have isolated an anti-CFTR monoclonal antibody which specifically recognizes recombinant normal and delta Phe508-CFTR produced by a vaccinia virus expression system. Immunocytochemical analysis of L cells expressing either normal or delta Phe508-CFTR showed a marked difference in subcellular distribution. Normal CFTR had a distinct localization in the perinuclear area and was also associated with the plasma membrane. delta Phe508-CFTR essentially lacked the membrane-associated distribution and was present throughout the cytoplasm. This heterologous expression system thus provides a model system for studying the subcellular localization of different mutant forms of CFTR.

Animals↗
PubMedDate not supplied

Clinical trials: Renewed attention to the interpretation of the P values--review.

The P values tell us the chance of making a type I error of finding a difference where there is none. In the 1970s, exact P values were laborious to calculate and were generally approximated from statistical tables, in the form of P < 0.01 or 0.05 < P < 0.10, etc. In the past decades with the advent of computers, it became easy to calculate exact P values such as 0.84 or 0.007. The cut-off P values have not been completely abandoned, but broader attention is given to the interpretation of the exact P values. This article reviews standard and renewed interpretations of P values. (1) Standard interpretation of cut-off P values such as P < 0.05: The null hypothesis of no difference can be rejected on the limitations/assumptions that we have up to a 5% chance of a type I error of finding a difference where there is none, we have 50% chance of a type II error of finding no difference where there is one, the data are normally distributed, they follow exactly the same distribution as that of the population from which the sample was taken. (2) A common misunderstanding of the P value: It is actually the chance that the null hypothesis is true and consequently that a P > 0.05 indicates a significant similarity in the data. P > 0.05 may indeed indicate similarity. However, a study sample too small or study design inadequate to detect the difference must be considered. (3) Renewed interpretations of the P values: Exact P values enable more refined conclusions from the research than cut-off levels. Instead of concluding significantly yes/no, we are able to consider levels of probabilities from very likely to be true to very likely to be untrue. Very large P values are not compatible with a normal gaussian frequency distribution; very small P values do not completely confirm prior expectations. They must be scrutinized and may have been inadequately improved.

Clinical Trials as Topic↗
PubMed1996

Estimation of the size of the media necessary to construct a medical image database.

To estimate the size of the media necessary to construct a medical image database, a statistical analysis was made of the radiological data in our hospital information system database. The distribution of the total radiological image data storage required during one working day can be regarded as a normal distribution, and the distribution per patient was different from a normal one. Therefore, the mean amount required for the data storage of radiological images during one working day is very useful in estimating the data storage required for radiological images during a given number of working days.

Computer Systems↗
PubMed1989

Age of onset, age at examination, and other covariates in the analysis of family data.

Information on age of onset can easily be incorporated into regressive logistic models by assuming that age of onset follows a logistic distribution. This is analogous to previously proposed models based on the normal distribution. The two distributions, and hence the two types of models, are very similar. In each case the generalized modules power transformation can be used as a basis for more flexibly modeling the age of onset distribution.

Affective Disorders, Psychotic↗
PubMed2006

A pattern-mixture model for the analysis of censored quality-of-life data.

We propose a pattern-mixture model for describing the joint distribution of incomplete repeated measurements of quality of life (QoL) and right-censored survival times. The model assumes that the survival times follow a multinomial distribution and that the quality of life outcome follows a multivariate normal distribution conditional on the survival time. We estimate the model using a Bayesian approach by importance sampling. We then use simulated parameters to create multiple imputations of the censored QoL outcomes, which can then be used to calculate individual values of quality-adjusted life-years (QALYs). We apply the method to data from the Randomized Evaluation of Mechanical Assistance in the Treatment of Congestive Heart Failure (REMATCH) clinical trial.

Bayes Theorem↗
PubMed1992

Oscillation of interspike interval length in substantia nigra dopamine neurons: effects of nicotine and the dopaminergic D2 agonist LY 163502 on electrophysiological activity.

The rates and patterns of discharge activity exhibited by 16 spontaneously active substantia nigra pars compacta dopamine neurons were studied in halothane-anesthetized rats using three types of quantitative measures: 1) mean discharge rates, 2) population characteristics of interspike interval samples, and 3) interspike interval time-series measures which were used to examine patterns in the ordering of interspike intervals. The mean discharge rate of these 16 cells was 2.9 +/- 0.3 spikes/sec, and each cell was classified as bursting (25% of the cells) or non-bursting (75%). The distribution of interspike intervals of non-bursting neurons were more normally distributed. Time-series analyses (raw time-series plots, return maps, and phase portraits) revealed a substantial oscillatory tendency in the magnitudes of consecutive interspike intervals in these neurons under baseline conditions: Successive interspike intervals tended to alternate between short and long durations, although short bursts often occurred. Under baseline conditions, these cells exhibited both multispike bursts and consecutive long intervals less frequently than would have been predicted by chance ordering of the interspike intervals. These results imply that there are mechanisms acting to reduce the probability of these types of events. Locally infused nicotine enhanced discharge rates in these neurons. Burst firing increased in four neurons, while five neurons did not show any change in burst firing. LY 163502 induced significant decreases in both discharge rate and bursting activity in all cells tested. The variation coefficient, skew, and kurtosis of the interspike interval distributions were not consistently altered by either drug. The local infusion of either nicotine or LY 163502 decreased the oscillatory phenomenon seen in the baseline condition. Neither the nicotine or LY 163502 time-series data exhibited a larger proportion of long-short and short-long pairs (relative to the median interval) than would be expected by chance. It is hypothesized that these neurons have intrinsic mechanisms, made manifest under anesthesia, which induce oscillations in interspike interval length. The oscillatory effect of these mechanisms can be overridden by tonic increases in either excitatory or inhibitory tone.

Anesthesia↗
PubMed2000

Effect of Polydispersity and Charge Heterogeneity on the Depletion Interaction in Colloidal Systems.

The effect of polydispersity in the macromolecule size and surface potential on the depletion attraction and structural repulsion between two charged spherical particles in a solution of nonadsorbing charged spherical macromolecules was investigated using a modified form of the force-balance model of J. Y. Walz and A. Sharma [J. Colloid Interface Sci. 168, 495 (1994)]. The distribution of sizes and potentials was described by a log-normal distribution with values of the coefficient of variation (CV) as large as 60%. Comparisons with the case of purely monodisperse macromolecules were made under the condition of either constant macromolecule number density, rho(infinity), or constant volume fraction, &phi;. For purely hard spheres, polydispersity increases the depletion attraction at constant rho(infinity) but decreases the interaction at constant &phi;. A simple scaling analysis is used to show that these trends are true for any arbitrary distribution of macromolecule size. Surface charge is found to amplify the effect of polydispersity at constant &phi; but actually negates the effect at constant rho(infinity). The repulsive structural contribution, arising from the interaction between the macromolecules themselves, is significantly decreased by polydispersity except for the case of charged macromolecules at constant rho(infinity), where the effect is relatively small. Finally, polydispersity in the macromolecule surface potential (no polydispersity in size) has only a minor effect on both the depletion attraction and structural repulsion, even for CV values as large as 60%. Copyright 2000 Academic Press.

Journal Article↗
PubMed1976

Electrophysiological studies of normal and degenerating mouse neuromuscular junctions.

A quantitative study of the functional changes occurring at end-plates of phrenicotomised mouse hemidiaphragms was made. Analysis of the frequency of spontaneous transmitter release revealed large scale deviations from a Poisson based process commencing 6-7 h post-phrenicotomy. Short term bursts of miniature end-plate potentials (minEPPs) lasting 0.5-1.0 sec frequently occurred and also long term bursts of minEPPs which lasted from several minutes to 0.5 h or more. Following the long term bursts there was regularly a lasting silence at the end-plates. MinEPP amplitudes were analysed. Probability analyses suggest that the minEPPs are often normally distributed amongst two or more populations. This relationship was maintained during degeneration of the end-plate. No significant differences between the distribution of mean minEPP amplitudes of degenerating end-plates and normal end-plates were found. This suggests that no change in the quantal unit of transmitter release occurs during degeneration of the end-plate.

Action Potentials↗