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PubMed1989

Statistical evaluation of cell kinetic data from DNA flow cytometry (FCM) by the EM algorithm.

Flow cytometric DNA measurements yield the amount of DNA for each of a large number of cells. A DNA histogram normally consists of a mixture of one or more constellations of G0/G1-, S-, G2/M-phase cells, together with internal standards, debris, background noise, and one or more populations of clumped cells. We have modelled typical DNA histograms as a mixed distribution with Gaussian densities for the G0/G1 and G2/M phases, an S-phase density, assumed to be uniform between the G0/G1 and G2/M peaks, observed with a Gaussian error, and with Gaussian densities for standards of chicken and trout red blood cells. The debris is modelled as a truncated exponential distribution, and we also have included a uniform background noise distribution over the whole observation interval. We have explored a new approach for maximum-likelihood analyses of complex DNA histograms by the application of the EM algorithm. This algorithm was used for four observed DNA histograms of varying complexity. Our results show that the algorithm works very well, and it converges to reasonable values for all parameters. In simulations from the estimated models, we have investigated bias, variance, and correlations of the estimates.

Algorithms↗
PubMed1992

Automatic assessment of the quality of G-banded metaphases. A preliminary study.

Assessment of the quality of cytogenetic preparations is important for 1) a general quality control of the cytogenetic laboratory and 2) for determining the quality of individual cytogenetic analyses. It is generally accepted that good preparations allow a more detailed search for structural abnormalities than poor preparations. As part of a comprehensive study on automated assessment of slide quality we have developed a simple algorithm for automated measurement of metaphase resolution. During semi-automated karyotyping with the Magiscan chromosome analysis system (Joyce-Loebl) three measurements related to resolution are automatically extracted 1) the total number of dark bands of the chromosomes of the metaphase (TB), 2) the normalized average length of the chromosomes (NL), and 3) the average "thickness" of the chromosomes (T). The algorithm TB x NL/T has been tested on 35 metaphases of various quality and compared with visual assessment of the same 35 metaphases. The results indicate that the automatic assessment of metaphase resolution is superior to the visual.

Chromosome Banding↗
PubMed1989

Automatisation of the single-breath nitrogen washout test.

The paper presents a computer-based system for performance and analysis of the single-breath nitrogen washout test (Sb-N2 test). A pneumotachometer and a rapid gas analyser are used for volume flow rate and nitrogen fraction measurements. The data are acquired and analysed by a PDP-11/34 computer. Several sources of measurement errors are considered. An algorithm is proposed to reduce errors in flow measurements due to viscosity variation in respired air. The algorithm for closing volume (CV) detection and calculation of other Sb-N2 parameters is developed from 50 tracings of 18 subjects. The CV is obtained by an iterative linear fitting of the later half of the Sb-N2 curve. Comparisons between computer and hand measurements of three trained readers show good correlations (r = 0.87, 0.93, 0.91). The variability of computer CV measurements was comparable with that of the hand reader with the lowest variance. The coefficient of variation of residual volume and slope of alveolar plateau measurements are apparently reduced. The results demonstrate the adequacy and convenience of using the computer to analyse the Sb-N2 test and indicate that the automation allows for reduction of experimental errors and of test parameter variabilities.

Adult↗
PubMed1992

Assessment of protein coding measures.

A number of methods for recognizing protein coding genes in DNA sequence have been published over the last 13 years, and new, more comprehensive algorithms, drawing on the repertoire of existing techniques, continue to be developed. To optimize continued development, it is valuable to systematically review and evaluate published techniques. At the core of most gene recognition algorithms is one or more coding measures--functions which produce, given any sample window of sequence, a number or vector intended to measure the degree to which a sample sequence resembles a window of 'typical' exonic DNA. In this paper we review and synthesize the underlying coding measures from published algorithms. A standardized benchmark is described, and each of the measures is evaluated according to this benchmark. Our main conclusion is that a very simple and obvious measure--counting oligomers--is more effective than any of the more sophisticated measures. Different measures contain different information. However there is a great deal of redundancy in the current suite of measures. We show that in future development of gene recognition algorithms, attention can probably be limited to six of the twenty or so measures proposed to date.

Algorithms↗
PubMed1989

A theoretical and experimental study of the effects of non-uniform membrane resistance on the shape of single-cell charging curves.

The isolated Muller glial cell of the neotenous tiger salamander retina is used as an experimental model for studying the effects of non-uniform membrane conductance on the shape of charging curves in response to step current inputs. A simple cable model of the Muller cell is formulated and used to interpret the experimental data. The Muller cell model is completely described by three parameters: (a) electrotonic length L; (b) the membrane time constant tau m; and (c) the percentage of the total membrane conductance accounted for by the endfoot S. Model analysis indicates that increasing S produces monotonic decreases in the rise time of charging curves. This effect is greatest when L is small. In such cases charging curve rise time can be substantially faster than that of a semi-infinite cable. When S greater than 0, the first time constant obtained by fitting the late exponential tail of the charging curve is not the membrane time constant (as is the case when S = 0), but is instead an equalizing time constant equal to the membrane time constant times a scale factor in the range of 0 to 1. This scaling factor becomes quite small as S approaches 100%. We describe a convergent numerical procedure for generating unique estimates of all three model parameters from charging curves. Application of the algorithm to experimentally measured Muller cell charging curves confirms Newman's finding that a large fraction of membrane conductance in these cells is accounted for by the endfoot (greater than 90%). The model prediction that charging curve rise time may be substantially faster than that of the semi-infinite cable when S greater than 0 is also confirmed. The error that results from misinterpreting the first equalizing time constant tau l as the membrane time constant tau m can have a significant effect on estimates of specific membrane resistance and capacitance. The algorithm described in this paper provides a means for obtaining direct estimates of the membrane time constant and will make possible more accurate estimates of specific membrane resistance and capacitance in Muller glial cells. The fact that the estimation procedure is based on a simple electrophysiological measurement suggests that it may be useful for studying asymmetry of membrane conductance in glial and neural elements of the intact nervous system.

Animals↗
PubMed1991

DEXA measurement of spine density in the lateral projection. I: Methodology.

Bone mineral content and bone mineral density (BMC in g and BMD in g/cm2) were measured using dual-energy X-ray absorptiometry (DEXA). DEXA scans in the lateral decubitus position required about 12 minutes for the L2-L4 sequence at 0.75 mA (dose 5 mrem) and 4 minutes at 4.75 mA (7 mrem). The former scans were done with the Lunar DPX densitometer and the latter with the Lunar DPX-L. One test of the algorithms used for measurement is the equality of BMC in both AP and lateral projections. BMC in the lateral projection averaged about 1% lower than in the AP projection in phantoms and for L2 + L3 in 8 subjects, but the difference was not significant. Additional tests were done on the effects of tissue thickness and position from the tabletop. There was little or no influence of tissue thickness from 18 to 30 cm on BMD results, but there was a small influence of thickness below 18 cm (0.01 g/cm2; P = 0.01) and of distance from the tabletop at extremes of positioning (0.02 g/cm2; P = 0.06). The precision in vivo was similar for both 4- and 12-minute scans; the standard deviation of repeat measurements was about 0.02 g/cm2, which was about 2% relative to the mean BMD for a region within the vertebral body. The latter region included half the BMC of the body, or 24% of the entire vertebra. Results of 4-minute scans on the DPX and 12-minute scans on the DPX-L in 9 subjects were highly correlated (r = 0.98; P less than 0.001).

Absorptiometry, Photon↗
PubMedDate not supplied

Real-time measurement of microvascular dimensions using digital cross-correlation image processing.

A real-time automatic digital image-processing algorithm was developed for measuring microvascular dimensions. Using video microscopic images of the vasculature, the video images are digitized and analyzed using contrast enhancement, frame averaging, and pattern recognition, rather than edge detection. Performance of the algorithm was evaluated for second- and third-order vessels surrounded by the complex interfering features of in vivo skeletal muscle. Graded diameter changes and vasomotion were induced with pharmacological agents. Data obtained by auto-tracking agreed with data obtained by traditional manual methods of measurement. These findings indicate that a pattern recognition algorithm based on cross-correlation analysis provides a highly accurate method for real-time automatic tracking of microvessel diameters.

Animals↗
PubMedDate not supplied

Similarity searching in databases of three-dimensional molecules and macromolecules.

This paper discusses algorithmic techniques for measuring the degree of similarity between pairs of three-dimensional (3-D) chemical molecules represented by interatomic distance matrices. A comparison of four methods for the calculation of 3-D structural similarity suggests that the most effective one is a procedure that identifies pairs of atoms, one from each of the molecules that are being compared, that lie at the center of geometrically-related volumes of 3-D space. This atom mapping method enables the calculation of a wide range of types of intermolecular similarity coefficient, including measures that are based on physicochemical data. Massively-parallel implementations of the method are discussed, using the AMT Distributed Array Processor, that achieve a substantial increase in performance when compared with a sequential implementation on a UNIX workstation. Current work involves the use of angular information and the extension of the method to field-based similarity searching. Similarity searching in 3-D macromolecules is effected by the use of a maximal common subgraph (MCS) isomorphism algorithm with a novel, graph-based representation of the tertiary structures of proteins. This algorithm is being used to identify similarities between the 3-D structures of proteins in the Brookhaven Protein Data Bank; its use is exemplified by searches involving the NAD-binding fold motif.

Algorithms↗
PubMedDate not supplied

Automatic derivation of initial match points for paired digital images of skin.

Computerized matching of skin images has been suggested as a means of screening for changes indicative of malignant melanoma. Matching or "registering" each lesion in a pair of images plays an important role in this process. Point-pattern matching algorithms based upon correlation or geometric transformations of the image pairs have been shown to be effective for this registration but require knowledge of one or more "initial match" points which are known to be the same on both images. A method is described for automatically finding these initial match points with a high degree of success. Our algorithm uses the so-called "Gabriel graph" representation of the paired images to select sets of probable matching points. Performance of the algorithm has been measured in realistic trials, using images of patients with large numbers of pigmented lesions. Results show that the single best match chosen is correct greater than 99% of the time, while over 93% of the first three consecutive matches will be chosen correctly. It is likely that these results can be improved through the use of additional nonpositional information or additional image processing.

Algorithms↗
PubMed1979

Utilization of cross-plane rays for three-dimensional reconstruction by filtered back-projection.

Present popular computed tomography (CT) algorithms reconstruct an object from the ray measurements lying on a set of parallel planes. This paper presents an algorithm that can also utilize "cross-plane" rays (i.e., rays that cross through many planes) to reconstruct the object. In this reconstruction algorithm, the ray measurements are grouped into two-dimensional projections, filtered, and stored. The filtered projections can then be back-projected onto a three-dimensional matrix or any plane through the three-dimensional volume. General theoretical aspects are presented and then applied to the special case in which ray measurements have been made in all directions. The algorithm is tested using computer-generated data. Expressions for the noise power spectrum and the variance in the reconstruction are derived. It is shown that the noise-to-signal ratio per detected photon for this reconstruction method is close to a theoretical limit, as it also is for normal CT. The ability to use ray measurements that cross many planes is especially useful in emission CT, where order-of-magnitude improvements in image quality per unit dose can be achieved.

Computers↗
PubMed1990

Negligible effects of previous moderate physical activity and changes in environmental temperature on whole body electrical impedance.

Several studies have shown that the predictive power of various linear combinations of anthropometric data (body weight, height, sex, age, etc.) to estimate fat free mass is improved after inclusion of measurements of electrical impedance (see eg Khaled et al., 1988). Published algorithms are based on measurements performed under fairly standardized conditions with the subjects at stationary conditions of rest, of environmental temperature and of body fluids. Use of the method under less standardized conditions raises the question of possible effects of deviations from these standard conditions. Hydration and dehydration by 1-2 l of fluid increased or decreased, respectively, the electrical resistance by about 14 per cent and the effects persisted for more than 1 h (Khaled et al., 1988). A change in environmental temperature by 21 degrees C from 35 degrees C to 14 degrees C (with almost constant relative humidity) during 90 min caused an increase in the resistance of about 9 per cent (Caton et al., 1988). The perturbations used in the studies quoted above are fairly drastic and not likely to occur under reasonably controlled field conditions. Therefore, we report here results of measurements of whole body electrical impedance before, during and after a period of 10 degrees C increased environmental temperature and before and after a 5-min period of light to moderate physical exercise.

Electric Conductivity↗
PubMed1990

Application of new calculation algorithms to oxygenation parameters of cirrhotic patients. A comparison between calculated and measured data.

Oxygen status from both arterial and mixed venous blood was analyzed by reliable methods in 39 cirrhotic patients. These measured data were checked with computed oxygen parameters by new calculation algorithms. Calculated oxygen contents were higher than directly measured values but there was a highly significant correlation between them. Calculated and measured 2,3-DPG mean values were not significantly different but there was no correlation between them. A large difference was observed between measured and computed evaluation of oxygen-hemoglobin affinity without correlation between P50. In hyperkinetic patients, no correlation was observed between 'compensation factor' and the increase of cardiac index. So, in these patients the new iterative equations were not valid to determine traditional oxygen parameters from only Po2 and So2 arterial measurements. Moreover the new oxygenation parameters appeared frankly inadequate.

2,3-Diphosphoglycerate↗
PubMed1992

Results obtained by using a computerized image analysis system designed as an aid to diagnosis of cutaneous melanoma.

Results obtained using a computerized image analysis system as an aid to clinical diagnosis of melanoma are reported. The system comprises a colour television camera connected through a digitizing board to a 386 personal computer. By means of original algorithms able to measure the shape, the colours and texture of a pigmented lesion of the skin, the system provides eight on/off indicators that are matched with the histological diagnosis to identify benign and malignant pigmented lesions. The chances that a given lesion is malignant increase with the increasing number of positive indicators. The training field of the system was constituted of images and data of 169 cutaneous lesions in 165 patients. Taking two positive indicators as the threshold between pigmented benign and malignant lesions, the efficiency of the system is 0.98, the positive predictive value is 0.45 and the negative predictive value is 0.95. These values were confirmed in a series of 44 pigmented lesions, 10 of which were melanoma, that constitute the present test series. The authors conclude that this computerized image analysis system should be regarded as a useful aid to diagnosis for a non-expert clinician. The system limit is transformation within a naevus.

Adult↗
PubMedDate not supplied

Yield of the screening review of systems: a study on a general medical service.

STUDY OBJECTIVE: To determine the usefulness of screening reviews of the cardiopulmonary and gastrointestinal systems during medical admissions. DESIGN: Case series. SETTING: General internal medicine ward of a university hospital. PATIENTS: 550 consecutive medical patients were initially screened at admission. The authors excluded 265 patients with life-limiting medical conditions, and they studied 98 patients with no known cardiopulmonary disease and 207 patients with no known gastrointestinal disease. INTERVENTIONS: Positive responses to screening systems review questions were evaluated using a standardized testing algorithm. MAIN OUTCOME MEASURES: Numbers of new diagnoses; potential for patient benefit. MAIN RESULTS: The authors made 26 new diagnoses for 25 patients (95% confidence limits, 16 to 37 patients), two of whom may have gained years of life as a result. CONCLUSIONS: The absolute yield of the screening cardiopulmonary and gastrointestinal reviews of systems of 550 patients admitted to an internal medicine service of a university hospital was a new diagnosis in about 5% of patients. An estimate of the cost-effectiveness compares favorably with those of other accepted screening practices.

Adult↗
PubMed1991

Noninvasive cerebral optical spectroscopy for monitoring cerebral oxygen delivery and hemodynamics.

OBJECTIVE: To present an algorithm for noninvasive measurement of cerebral oxygen saturation (cerebral oximetry) and cerebral hemodynamics with near infrared spectroscopy. DESIGN: In vitro correlation of oximetry measurements with reference measurements; illustrative cases of hemodynamic and oximetric recordings. SETTING: Tertiary care neuroscience ICU. PATIENTS: Brain-injured patients with a prolonged, decreased level of consciousness chosen as illustrative examples. INTERVENTIONS: Two-channel multiple wavelength diffuse infrared transmission spectroscopy was interfaced with the scalp using adhesive. Transmission data were collected with gross superficial-to-deep spatial resolution. Saturation calculation based on the deep signal was observed longitudinally in the patient. With the same technology, arterial input and cerebral response functions, generated by iv tracer bolus, were deconvoluted to measure mean cerebral transit time. MEASUREMENTS AND MAIN RESULTS: A positive linear regression fit between diffuse transmission oximetry and measured blood oxygen saturation over the range 23% to 99% (r2 = .98, p less than .001) was noted. CONCLUSIONS: The approach used overcomes previously identified difficulties with cerebral oximetry, and demonstrates excellent in vitro correlation. The technique can be performed clinically without difficulty. A simultaneous measure of mean cortical transit time is possible.

Brain↗
PubMed1989

Estimating lung mechanics of dogs with unilateral lung injury.

Extended least-squares algorithms using transpulmonary pressure and airway flow data from ventilatory waveforms were studied for their ability to track parameters of one- and two-compartment models of lung mechanics. A recursive extended least-squares algorithm with discounted measures estimated parameters of discrete-time models during synchronized intermittent mandatory ventilation. In tests on seven dogs developing oleic acid-induced unilateral hemorrhagic pulmonary edema, the one-compartment estimator responded rapidly and appropriately to changes in mechanics: compliance fell to 0.55 +/- 0.15 of its initial value and resistance rose by a factor of 1.8 +/- 0.5 in 3 h following injection of oleic acid. One-compartment parameter estimates revealed a difference between the airway resistance of inspiration and expiration. Two-compartment estimates were seldom physiologically plausible. The difference between inspiratory and expiratory resistance may have caused the two-compartment estimator to fail when applied to data from the entire respiratory cycle; when only expiratory data were used for estimation, the two-compartment estimates were meaningful. These estimates demonstrated increasing lung inhomogeneity after oleic acid was injected; at the end of 3 h, the ratio of the time constants of the two compartments ranged from 5 to 20 in six of the seven dogs. We conclude that the one- and two-compartment estimates may be combined to provide a meaningful assessment of lung mechanics.

Animals↗
PubMed1991

Structural interpretation of fluorescence resonance-energy transfer measurements.

Fluorescence resonance-energy transfer (FRET) has been widely used to determine distance information in macromolecular systems. However, little has been written about methods for combining FRET distances into coherent structural models. I argue that the methods used so far are inappropriate. This paper describes an algorithm specifically tailored for finding structures from FRET measurements. This algorithm finds structures which fit the experimentally measured parameter, the efficiency of energy transfer, rather than derived distances. The algorithm was implemented in Mathematica and applied to FRET distances obtained for the contractile protein actin. The approach used is applicable to other experimental techniques which measure distances between a relatively small number of loci.

Energy Transfer↗