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Reduced disorderliness of growth hormone release in biochemically inactive acromegaly after pituitary surgery.

The episodicity of 24 h GH release was studied in 18 patients with active acromegaly, 12 patients 7-10 days after pituitary surgery, 14 patients long after operation (3-17 years), and 21 healthy gender- and age-matched control subjects, using a recently introduced scale- and model-independent regularity statistic, approximate entropy (ApEn). Blood samples were taken at 10-min intervals for 24 h, and plasma GH concentrations were measured by immunofluorometric assay (detection limit 11.5 ng/l). For this study we selected operated patients who were biochemically in remission, defined by normal circulating IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3) concentrations, normal glucose-suppressed plasma GH concentration (<0.38 microg/l), and the normalization of the paradoxical rise of GH to TRH or GnRH. In patients with active acromegaly ApEn was 1.23+/-0.04, with no overlap with the control subjects (P = 1.2 x 10[-16]), who had an ApEn of 0.40+/-0.04. ApEn in patients shortly after surgery was 0.71+/-0.09 (P < 0.001 vs controls), and long after surgery 0.56+/-0.05 (P < 0.011 vs controls). ApEn values in treated and untreated patients correlated significantly with the plasma concentration of IGF-I (r=0.531) and IGFBP-3 (r=0.598), and the log-transformed 24h GH secretion rate (r=0.749). Shortly after surgery only one-third of the patients had a normal ApEn value, whereas long after surgery about 70% of the patients had a normal ApEn value. Although ApEn eventually normalized in about 70% of the operated patients, the cause of the persistence of abnormal GH release in the remainder of the subjects is not known, and might reflect permanent hypothalamic-pituitary dysfunction or a very early recurrence of the somatotroph adenoma.

Acromegaly↗

Multiple-quantum magic-angle spinning spectroscopy using nonlinear sampling.

NMR spectroscopy is a relatively insensitive technique and many biomolecular applications operate near the limits of sensitivity and resolution. A particularly challenging example is detection of the quadrupolar nucleus 17O, due to its low natural abundance, large quadrupole couplings, and low gyromagnetic ratio. Yet the chemical shift of 17O spans almost 1000 ppm in organic molecules and it serves as a potentially unique reporter of hydrogen bonding in peptides, nucleic acids, and water, and as a valuable complement to 13C and 15N NMR. Recent developments including the multiple-quantum magic-angle spinning (MQMAS) experiment have enabled the detection of 17O in biological solids, but very long data acquisitions are required to achieve sufficient sensitivity and resolution. Here, we perform nonlinear sampling in the indirect dimension of MQMAS experiments to substantially reduce the total acquisition time and improve sensitivity and resolution. Nonlinear sampling prevents the use of the discrete Fourier transform; instead, we employ maximum entropy (MaxEnt) reconstruction. Nonlinearly sampled MQMAS spectra are shown to provide high resolution and sensitivity in several systems, including lithium sulfate monohydrate (LiSO(4)-H(2)17O) and L-asparagine monohydrate (H(2)17O). The combination of nonlinear sampling and MaxEnt reconstruction promises to make the application of 17O MQMAS practical in a wider range of biological systems.

Anisotropy↗

Discriminating the relation between relations: the role of entropy in abstract conceptualization by baboons (Papio papio) and humans (Homo sapiens).

Two baboons (Papio papio) successfully learned relational matching-to-sample: They picked the choice display that involved the same relation among 16 pictures (same or different) as the sample display, although the sample display shared no pictures with the choice displays. The baboons generalized relational matching behavior to sample displays created from novel pictures. Further experiments varying the number of sample pictures and the mixture of same and different sample pictures suggested that entropy plays a key role in the baboons' conceptual behavior. Two humans (Homo sapiens) were similarly trained and tested; their behavior was both similar to and different from the baboons' behavior. The results suggest that animals other than humans and chimpanzees can discriminate the relation between relations. They further suggest that entropy detection may underlie same-different conceptualization, but that additional processes may participate in human conceptualization.

Animals↗

Sample sizes for identifying the key types of container occupied by dengue-vector pupae: the use of entropy in analyses of compositional data.

A method has been developed for estimating the sample sizes needed to identify categories that comprise a large proportion of a compositional data-set. The method is to be used in the design of surveys of mosquito pupae, for identifying the key container types from which the majority of adult dengue vectors emerge. Although a finite-population correction was devised for estimating the mean of a negative binomial distribution, other complications of parametric approaches make them unlikely to yield methods simple enough to be practically applicable. The Shannon-Wiener index was therefore investigated as a more useful alternative, at the cost of theoretical generalizability, in an approach based on re-sampling methods in conjunction with the use of entropy. This index can be used to summarize the degree to which pupae are either concentrated in a few container types, or dispersed among many. An empirical relationship between the index and the repeatability of surveys of differing sample sizes was observed. A step-wise rule, based on the entropy of the cumulative data, was devised for determining the sample size, in terms of the number of houses positive for pupae, at which a pupal survey might reasonably be stopped.

Aedes↗

Improved resolution in triple-resonance spectra by nonlinear sampling in the constant-time domain.

Nonlinear sampling along the constant-time dimension is applied to the constant-time HNCO spectrum of the dimerization domain of Gal4. Nonlinear sampling was used for the nitrogen dimension, while the carbon and proton dimensions were sampled linearly. A conventional ct-HNCO spectrum is compared with a nonlinearly sampled spectrum, where the gain in experiment time obtained from nonlinear sampling is used to increase the resolution in the carbonyl dimension. Nonlinearly sampled data are processed by maximum entropy reconstruction. It is shown that the nonlinearly sampled spectrum has a higher resolution, although it was recorded in less time. The constant intensity of the signal in the constant-time dimension allows for a variety of sampling schedules. A schedule of randomly distributed sampling points yields the best results. This general method can be used to significantly increase the quality of heteronuclear constant-time spectra.

Algorithms↗

A comparison of adaptive and nonadaptive filters for reduction of power line interference in the ECG.

We have investigated the relative performance of an adaptive and nonadaptive 60-Hz notch filter applied to an ECG signal. We evaluated the performance of the two implementations with respect to adaptation rate (or transient response time), signal distortion, and implementation complexity. We also investigated the relative effect of adaptive and nonadaptive 60-Hz filtering on ECG data compression. With a 360 Hz sample rate and an adaptation time of approximately 0.3 s for a 1 mV 60-Hz signal, the adaptive implementation is less complex and introduces less noise, particularly in the ST-segment, into a typical ECG signal. When applied to ECG signals, prior to data compression by average beat subtraction and residual differencing, the residual signal resulting from the adaptively filtered signal had an average entropy 0.37 bits per sample (bps) lower than the unfiltered signal. The nonadaptive 60-Hz filter produced an average entropy decrease of 0.08 bps relative to the unfiltered ECG.

Algorithms↗

Substrate hydroxylation in methane monooxygenase: quantitative modeling via mixed quantum mechanics/molecular mechanics techniques.

Using broken-symmetry unrestricted density functional theory quantum mechanical (QM) methods in concert with mixed quantum mechanics/molecular mechanics (QM/MM) methods, the hydroxylation of methane and substituted methanes by intermediate Q in methane monooxygenase hydroxylase (MMOH) has been quantitatively modeled. This protocol allows the protein environment to be included throughout the calculations and its effects (electrostatic, van der Waals, strain) upon the reaction to be accurately evaluated. With the current results, recent kinetic data for CH3X (X = H, CH3, OH, CN, NO2) substrate hydroxylation in MMOH (Ambundo, E. A.; Friesner, R. A.; Lippard, S. J. J. Am. Chem. Soc. 2002, 124, 8770-8771) can be rationalized. Results for methane, which provide a quantitative test of the protocol, including a substantial kinetic isotope effect (KIE), are in reasonable agreement with experiment. Specific features of the interaction of each of the substrates with MMO are illuminated by the QM/MM modeling, and the resulting effects upon substrate binding are quantitatively incorporated into the calculations. The results as a whole point to the success of the QM/MM methodology and enhance our understanding of MMOH catalytic chemistry. We also identify systematic errors in the evaluation of the free energy of binding of the Michaelis complexes of the substrates, which most likely arise from inadequate sampling and/or the use of harmonic approximations to evaluate the entropy of the complex. More sophisticated sampling methods will be required to achieve greater accuracy in this aspect of the calculation.

Acetonitriles↗

Protein side-chain conformational entropy derived from fusion data--comparison with other empirical scales.

The loss of conformational entropy of protein side-chains is a major effect in the energetics of folding. The simplest approach is to enumerate the number of freely rotatable bonds. Recently, two scales of side-chain conformational entropy have been proposed based on the definition of entropy as the Boltzmann sampling over all accessible states (S = -R sigma p(i)lnp(i), where p(i) is the probability of being in a rotameric state). In one scale, derived only for aliphatic and aromatic side-chains, the values of p(i) were obtained from Monte Carlo simulations. In the other scale, the observed frequencies of different rotameric states in a database of protein crystal structures yielded an estimate for p(i). Here an empirical estimation of the fusion entropy of the side-chains is used to derive a third scale. The fusion entropy is obtained as a sum of empirically derived contributions from component hydrocarbon and functional groups. There is a good agreement between the fusion scale and the other two scales. This suggests that the magnitude of conformational entropy is being correctly established.

Computer Simulation↗

Empirical scale of side-chain conformational entropy in protein folding.

A major effect in the energetics of protein folding is the loss of conformational entropy of the side-chains. The definition of entropy as the Boltzmann sampling over all states (S = -R sigma p(i) ln p(i)) requires evaluation of the probability (p(i)) of the system being in rotameric state i. The principle of this paper is to obtain an estimate of p(i) from the observed distribution of exposed side-chain rotamers in 50 non-homologous protein crystal structures. However because of limited data we show that for all side-chains except Asn, Asp and Glu the side-chain distribution is independent of burial and accordingly all data were pooled in the calculation of p(i). For Asn, Asp and Glu side-chains with relative accessibility > 60% were used. The scale includes effects due to the symmetry of side-chains such as Phe and the free rotation of side-chain amide, carboxyl and hydroxyl groups. An empirical scale for the loss of side-chain conformational entropy during protein folding is thereby obtained. Values of the change in free energy due to entropy (-T delta S) on burying a side-chain range from 0 for Ala, Gly and Pro to +2.1 kcal/mol for Gln (T = 300 K). We explore the consistency of a simple model for protein folding that includes side-chain entropy, main-chain entropy, hydrophobicity and hydrogen bonding. The stability of site-directed mutations is discussed in terms of conformational entropy.

Models, Chemical↗

Complexity of tissue injury-induced nociceptive discharge of dorsal horn wide dynamic range neurons in the rat, correlation with the effect of systemic morphine.

Persistent discharge of wide dynamic range (WDR) neurons was recorded from lumbar dorsal horn of anesthetized rats following subcutaneous bee venom injection into the receptive field. To quantitatively describe the complexity of this nociceptive activity, we computed the approximate entropy (ApEn) for each sampled interspike interval (ISI) series. A larger value of ApEn indicates higher complexity or less regularity and vice versa. The ApEn value varied across different WDR neurons tested, and for each neuron the ApEn remained constant through the 1-h discharge though the average ISI of the sampled data increased progressively with time (16 neurons). A low dose of intravenous morphine (0.3 mg/kg) depressed the activity of WDR neurons differentially, and the degree of this inhibition showed a significant correlation with the value of ApEn (P<0.001, 27 neurons, Spearman's correlation test). The present results suggest that the complexity feature of WDR neurons is various under tissue injury state, and for each single WDR neuron the complexity feature is relatively independent of the strength of peripheral noxious input and cannot be fully described in terms of average firing rate. Moreover, the response of the nociceptive discharge to analgesics may be related to the nonlinear dynamics feature of nociceptive neurons, which can be quantitatively characterized by the degree of complexity.

Action Potentials↗

Quantitative tools for comparing animal communication systems: information theory applied to bottlenose dolphin whistle repertoires.

Comparative analysis of nonhuman animal communication systems and their complexity, particularly in comparison to human language, has been generally hampered by both a lack of sufficiently extensive data sets and appropriate analytic tools. Information theory measures provide an important quantitative tool for examining and comparing communication systems across species. In this paper we use the original application of information theory, that of statistical examination of a communication system's structure and organization. As an example of the utility of information theory to the analysis of animal communication systems, we applied a series of information theory statistics to a statistically categorized set of bottlenose dolphin Tursiops truncatus, whistle vocalizations. First, we use the first-order entropic relation in a Zipf-type diagram (Zipf 1949 Human Behavior and the Principle of Least Effort) to illustrate the application of temporal statistics as comparative indicators of repertoire complexity, and as possible predictive indicators of acquisition/learning in animal vocal repertoires. Second, we illustrate the need for more extensive temporal data sets when examining the higher entropic orders, indicative of higher levels of internal informational structure, of such vocalizations, which could begin to allow the statistical reconstruction of repertoire organization. Third, we propose using 'communication capacity' as a measure of the degree of temporal structure and complexity of statistical correlation, represented by the values of entropic order, as an objective tool for interspecies comparison of communication complexity. In doing so, we introduce a new comparative measure, the slope of Shannon entropies, and illustrate how it potentially can be used to compare the organizational complexity of vocal repertoires across a diversity of species. Finally, we illustrate the nature and predictive application of these higher-order entropies using a preliminary sample of dolphin whistle vocalizations. The purpose of this preliminary report is to re-examine the original application of information theory to the field of animal communication, illustrate its potential utility as a comparative tool for examining the internal informational structure of animal vocal repertoires and their development, and discuss its relationship to behavioural ecology and evolutionary theory. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗

Resonance assignment of proteins with high shift degeneracy based on 5D spectral information encoded in G2FT NMR experiments.

A suite of novel (5,3)D G2FT triple resonance NMR experiments encoding highly resolved 5D spectral information is presented for sequential resonance assignment of proteins exhibiting high chemical shift degeneracy. Efficient resonance assignment is achieved by separate joint sampling of (i) chemical shifts which solely serve to provide increased resolution and (ii) shifts which also provide sequential connectivities. In these G2FT experiments, two G-matrix transformations are employed. Peaks are resolved along a first GFT dimension at both Omega(15N) + Omega(13C') and Omega(15N) - Omega(13C'), or at Omega(15N) + Omega(13Calpha) and Omega(15N) - Omega(13Calpha), to break backbone 15N,1HN chemical shift degeneracy. Sequential connectivities are established along a second GFT dimension by measuring intraresidue and sequential correlations at 2Omega(13Calpha), Omega(13Calpha + 13Cbeta), and Omega(13Calpha - 13Cbeta), or at Omega(13Calpha + 1Halpha) and Omega(13Calpha - 1Halpha), to resolve 13Calpha/beta,1Halpha chemical shift degeneracy. It is demonstrated that longitudinal proton relaxation optimization of out-and-back implementations suitable for deuterated proteins and nonlinear data sampling combined with maximum entropy reconstruction further accelerate G2FT NMR data acquisition speed. As a result, the spectral information can be obtained within hours, so that (5,3)D G2FT experiments are viable options for high-throughput structure determination in structural genomics. Applications are presented for 17 kDa alpha-helical protein YqbG and 13.5 kDa protein rps24e, targets of the Northeast Structural Genomics consortium, as well as for 9 kDa protein Z-domain. The high resolving power of the G2FT NMR experiments makes them attractive choices to study alpha-helical globular/membrane or (partially) unfolded proteins, thus promising to pave the way for NMR-based structural genomics of membrane proteins.

Fourier Analysis↗

Optimized mixed Markov models for motif identification.

BACKGROUND: Identifying functional elements, such as transcriptional factor binding sites, is a fundamental step in reconstructing gene regulatory networks and remains a challenging issue, largely due to limited availability of training samples. RESULTS: We introduce a novel and flexible model, the Optimized Mixture Markov model (OMiMa), and related methods to allow adjustment of model complexity for different motifs. In comparison with other leading methods, OMiMa can incorporate more than the NNSplice's pairwise dependencies; OMiMa avoids model over-fitting better than the Permuted Variable Length Markov Model (PVLMM); and OMiMa requires smaller training samples than the Maximum Entropy Model (MEM). Testing on both simulated and actual data (regulatory cis-elements and splice sites), we found OMiMa's performance superior to the other leading methods in terms of prediction accuracy, required size of training data or computational time. Our OMiMa system, to our knowledge, is the only motif finding tool that incorporates automatic selection of the best model. OMiMa is freely available at 1. CONCLUSION: Our optimized mixture of Markov models represents an alternative to the existing methods for modeling dependent structures within a biological motif. Our model is conceptually simple and effective, and can improve prediction accuracy and/or computational speed over other leading methods.

Algorithms↗

The relationship between 24-hour growth hormone secretion and insulin-like growth factor I in patients with successfully treated acromegaly: impact of surgery or radiotherapy.

In patients with treated acromegaly, improved survival is associated with serum GH concentrations below 2 microgram/L (5 mU/L). A principal aim of therapy in acromegaly is to achieve a GH level less than 2 microgram/L, as such levels are thought to be "safe." However, such GH levels do not always equate with normalization of plasma insulin-like growth factor I (IGF-I), although epidemiological data linking survival or morbidity to IGF-I levels are at present lacking. The aims of this study were 1) to further define the nature of GH release in those acromegalic patients who achieve mean GH concentrations below 2 microgram/L post therapy, 2) to examine the effect of different therapeutic interventions on the 24-h GH profile (surgery alone or radiotherapy), and 3) to determine the relationship between the various characteristics of the 24-h GH profile and IGF-I production in acromegalic subjects who have achieved GH below 2 microgram/L. Spontaneous 24-h GH secretion was measured using both a conventional immunoradiometric assay (limit of detection, 0.4 microgram/L) and an ultrasensitive assay (limit of detection, 0.002 microgram/L). The GH data have been analyzed by several methods: 1) the pulse detection algorithm Cluster, 2) a distribution method for detection of peak [the observed concentration 95%, i.e. the threshold at or below which GH concentrations are assessed to be 95% of the time, as calculated by probability analysis (OC 95%)] and trough (OC, 5%) GH activity, 3) deconvolution analysis, and 4) approximate entropy analysis. GH was sampled every 20 min for 24 h, along with basal IGF-I and IGF-binding protein-3, in 21 treated acromegalic patients with a mean GH below 2 microgram/L [ACR; 9 women and 12 men; median age (range), 49 (31-76) yr] and 16 healthy controls [C; 6 women and 10 men; age, 50 (30-75) yr]. Mean 24-h serum GH concentrations were [median (range)]: ACR, 1.1 (0.04-1.5) microgram/L; C, 0.4 (0.02-3.3) microgram/L (P = 0.28). GH pulse frequency was: ACR, 11 (1-14)/24 h; C, 10 (8-18)/24 h (P = 0.41). In the GH profiles the mean heights of the GH peaks were: ACR, 1.2 (0.05-2.8) microgram/L; C, 0.8 (0.02-5.1) microgram/L (P = 0.91), and the mean GH valley nadirs were: ACR, 0.65 (0.03-1.1) microgram/L; C, 0.09 (0.01-1.8) microgram/L (P < 0.02). The OC 95% was: ACR, 1.0 (0.04-3.8) microgram/L; C, 1.0 (0.02-10) microgram/L (P = 0.65), and the OC 5% was: ACR, 0.09 (0.01-0.6) microgram/L; C, 0.01 (0.001-0.4) microgram/L (P < 0.001). The median IGF-I was: ACR, 227 (100-853) microgram/L; C, 156 (89-342) microgram/L (P < 0.005). Approximate entrophy values were: ACR, 1.06 (0.35-1.45); and C, 0.57 (0.27-1.19); P < 0.05. In the acromegaly group a significant positive correlation was found between IGF-I and the calculated GH secretory burst amplitude in the radiotherapy subset (r = 0.85; P < 0.0005) as well as between IGF-I and both the mean GH valley nadir (r = 0.60; P < 0.004) and the trough (OC 5%) GH activity for the acromegalic patients as a whole (r = 0.55; P < 0.02). We conclude that in treated acromegaly (GH, <2 microgram/L), 1) IGF-I (by approximately 50%) and basal GH secretion (by 5-fold) remain significantly elevated compared with control values despite similar mean 24-h GH concentrations; 2) the calculated GH secretory pulse amplitude, mean GH valley nadir, and OC 5% correlate positively with IGF-I; 3) the greater mean GH valley nadir and OC 5% in acromegalic patients compared with controls may account for the raised IGF-I; and 4) radiotherapy is unlikely to normalize the GH secretory pattern, which underlies the persisting elevated IGF-I levels.

Acromegaly↗

Improved proton affinity measurements for proline and modified prolines using triple quadrupole and ion trap mass spectrometers.

Proton affinity (PA) of compounds such as proline, cis-3-methylproline, cis-3-ethylproline, cis-3-isopropylproline and cis-3-isopentanylproline was determined by kinetic method with amines as the reference bases. The effective temperatures determined using ion trap and triple quadrupole mass spectrometers were found to be significantly different. In the case of the triple quadrupole instruments, the effective temperature depends significantly on the collision energy. The influence of the apparent basicity (GBapp) on the effective temperature may be used to estimate the difference in protonation entropy (DeltaDeltaS degrees) between the sample and reference compounds. In case of the ion trap mass spectrometer, the variation of the effective temperature as a function of the excitation amplitude is small, so it is difficult to account for the contribution of the entropy effects to the proton affinity value. A better estimation of the PA and DeltaDeltaS degrees values for the investigated molecules is obtained by combining the GBapp and Teff data pairs that are obtained from both the mass spectrometers.

Kinetics↗

Sex differences in circulating human leptin pulse amplitude: clinical implications.

Leptin, a product of fat cells, provides a signal of nutritional status to the central nervous system. Leptin concentrations have ultradian and diurnal fluctuations. We conducted this study to assess sex differences in the levels of organization of frequently sampled leptin concentrations in healthy, normal weight women and men. Leptin levels were sampled every 7 min for 24 h in 14 healthy, normal weight individuals (6 women and 8 men). The 14 leptin time series containing a total of 2898 leptin measurements were assessed by 1) algorithms that characterize statistically significant pulsatility, 2) Spectral (Fourier) analysis, 3) analysis of time intervals and variability, and 4) approximate entropy. We found that frequently sampled plasma leptin concentrations have a 24-h profile that is numerically more than twice as high in women as in men, and leptin pulse amplitude is likewise more than twice as high in women. However, healthy men and women have nearly identical concentration-independent and frequency-related 24-h and ultradian patterns. Leptin concentrations have nonrandom fluctuations over 24 h, independent of their absolute value and underlying 24-h periodicity, that are similar in men and women. Ultradian periodicities detected by Fourier time series have similar values in men and women. The strongest distinction between the sexes in the level of organization of leptin concentration is not at the level of pulse organization or oscillation frequency, but, rather, in the mass or amount of leptin released (or removed) per unit time, indicating that women might be more resistant to the effects of leptin than men. Because leptin is clinically relevant to the regulation of body weight, future studies should examine whether the relative leptin resistance exhibited by women might contribute to their increased susceptibility to disorders whose pathophysiology involves dysregulation of food intake and body weight.

Adult↗

Electroencephalogram approximate entropy correctly classifies the occurrence of burst suppression pattern as increasing anesthetic drug effect.

BACKGROUND: Approximate entropy, a measure of signal complexity and regularity, quantifies electroencephalogram changes during anesthesia. With increasing doses of anesthetics, burst-suppression patterns occur. Because of the high-frequency bursts, spectrally based parameters such as median electroencephalogram frequency and spectral edge frequency 95 do not decrease, incorrectly suggesting lightening of anesthesia. The authors investigated whether the approximate entropy algorithm correctly classifies the occurrence of burst suppression as deepening of anesthesia. METHODS: Eleven female patients scheduled for elective major surgery were studied. After propofol induction, anesthesia was maintained with isoflurane only. Before surgery, the end-tidal isoflurane concentration was varied between 0.6 and 1.3 minimum alveolar concentration. The raw electroencephalogram was continuously recorded and sampled at 128 Hz. Approximate entropy, electroencephalogram median frequency, spectral edge frequency 95, burst-suppression ratio, and burst-compensated spectral edge frequency 95 were calculated offline from 8-s epochs. The relation between burst-suppression ratio and approximate entropy, electroencephalogram median frequency, spectral edge frequency 95, and burst-compensated spectral edge frequency 95 was analyzed using Pearson correlation coefficient. RESULTS: Higher isoflurane concentrations were associated with higher burst-suppression ratios. Electroencephalogram median frequency (r = 0.34) and spectral edge frequency 95 (r = 0.29) increased, approximate entropy (r = -0.94) and burst-compensated spectral edge frequency 95 (r = -0.88) decreased with increasing burst-suppression ratio. CONCLUSION: Electroencephalogram approximate entropy, but not electroencephalogram median frequency or spectral edge frequency 95 without burst compensation, correctly classifies the occurrence of burst-suppression pattern as increasing anesthetic drug effect.

Adult↗

Reproducibility and efficiency testing of two sampling methods for image analysis in cytology.

OBJECTIVE: Quantitative nuclear DNA analyses and nuclear morphometry have become a widely used tool in pathology. Nevertheless, studies done by different observers utilizing the same methods very often have shown different results. One of the reasons could be that different sampling methods were used. In this study two selection methods for image analyses (the consecutive selection method and the random selection method) were tested for reproducibility and efficiency. STUDY DESIGN: Using an interactive imaging analysis system, 10 cases (5 breast adenocarcinomas, 3 prostatic cancers, 1 sarcoma, 2 prostatic hyperplasias) were measured twice by using each sampling method. Median nuclear area and entropy (i.e., a statistical descriptor of DNA histograms) were the parameters calculated. RESULTS: The results showed that using the consecutive selection method, the number of individual nuclei in a cytologic sample that should be measured to obtain reproducible results was 150 for nuclear area and 110 for entropy. The corresponding figures using random systematic selection method were 80 for assessment of nuclear area and 100 for assessment of entropy. CONCLUSION: Both methods showed high reproducibility and a good correlation with each other. The mathematical idea of "plateau values," which was used to estimate the number of measurements needed, was considered a good contribution to increasing the efficiency of both methods.

Breast Neoplasms↗