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A kinetic method for glucose that is insensitive to variations in temperature and enzyme activity.

We have adapted for glucose determination a new approach to kinetic analyses [Anal. Chem. 50, 1611 (1978)]; it is 50-fold less dependent upon some experimental variables than is a more conventional rate method. Modification of a commercially available hexokinase/glucose-6-phosphate dehydrogenase reagent system for glucose provides that the rate of production of NADH be first-order in total glucose concentration within about 30 s after sample and reagent are mixed. In the kinetic method, absorbance vs. time data recorded after 30 s and a multiple-linear-regression program are used to compute the absorbance change that would occur if the reaction were monitored to completion. Results demonstrate a linear relationship between glucose concentration and computed absorbance change. Application of the method to 51 human sera without rigorous control of either temperature or reagent composition yielded a regression equation of y = 1.01x -0.3 when kinetic results (y) were compared with equilibrium results (x) for the same samples analyzed in a hospital laboratory.

Blood Glucose↗

Impact of reporting delay and reporting error on cancer incidence rates and trends.

BACKGROUND: Cancer incidence rates and trends are a measure of the cancer burden in the general population. We studied the impact of reporting delay and reporting error on incidence rates and trends for cancers of the female breast, colorectal, lung/bronchus, prostate, and melanoma. METHODS: Based on statistical models, we obtained reporting-adjusted (i.e., adjusted for both reporting delay and reporting error) case counts for each diagnosis year beginning in 1981 using reporting information for patients diagnosed with cancer in 1981-1998 from nine cancer registries that participate in the Surveillance, Epidemiology, and End Results (SEER) program. Joinpoint linear regression was used for trend analysis. All statistical tests are two-sided. RESULTS: Initial incidence case counts (i.e., after the standard 2-year delay) accounted for only 88%-97% of the estimated final counts; it would take 4-17 years for 99% or more of the cancer cases to be reported. The percent change between reporting-adjusted and unadjusted cancer incidence rates for the 1998 diagnosis year ranged from 3% for colorectal cancers to 14% for melanoma in whites and for prostate cancer in black males. Reporting-adjusted current incidence trends for breast cancer and lung/bronchus cancer in white females showed statistically significant increases (estimated annual percent change [EAPC] = 0.6%, 95% confidence interval [CI] = 0.1% to 1.2%) and 1.2%, 95% CI = 0.7% to 1.6%, respectively), whereas trends for these cancers using unadjusted incidence rates were not statistically significantly different from zero (EAPC = 0.4%, 95% CI = -0.1% to 0.9% and 0.5%, 95% CI = -0.1% to 1.1%, respectively). Reporting-adjusted melanoma incidence rates for white males showed a statistically significant increase since 1981 (EAPC = 4.1%, 95% CI = 3.8% to 4.4%) in contrast to the unadjusted incidence rate, which was most consistent with a flat or downward trend (EAPC = -4.2%, 95% CI = -11.1% to 3.3%) after 1996. CONCLUSIONS: Reporting-adjusted cancer incidence rates are valuable in precisely determining current cancer incidence rates and trends and in monitoring the timeliness of data collection. Ignoring reporting delay and reporting error may produce downwardly biased cancer incidence trends, particularly in the most recent diagnosis years.

Adult↗

A minicomputer program for automatic saccade detection and linear analysis of eye movement systems using sine wave stimulus.

A FORTRAN IV program is described, which may be run interactively or in batch and which allows a user to obtain the frequency response amplitude ratio and phase resulting from the linear analysis of an eye movement system using sine wave stimuli. The response (eye position) signal may contain components contributed by the saccadic eye movements. The program can digitize analog signals and store data on a magnetic tape. With the aid of digital filters, the program can detect saccades without requiring any input parameters from the user. The program interpolates the saccade interval using a method of least square curve fitting with a sine wave. The interpolation is relatively noise immune and works well regardless of the stimulus frequencies and the width of a saccade interval. Moreover, the program can handle long duration of signals such as 90 min of data which covers about 5 cycles of a 0.001 Hz sine wave signal. Sample runs for the cases of 0.001 and 0.1 Hz are given. The resident driver and the overlayable segments of the program have been implemented on a DEC (Digital Equipment Corp.) LAB-11 minicomputer (PDP 11/20).

Animals↗

Linear circuits for neural networks and affective computing.

Biological phenomena are often modeled with software on digital computers, even though the events may be analog in nature. The author describes the use of linear circuitry in two areas of biological simulation: artificial neural networks and affective computing. The operational amplifier, with the assistance of some new analog chips and simple digital microcontrollers, is featured prominently in these linear designs.

Computer Simulation↗

Identification of human gene structure using linear discriminant functions and dynamic programming.

Development of advanced technique to identify gene structure is one of the main challenges of the Human Genome Project. Discriminant analysis was applied to the construction of recognition functions for various components of gene structure. Linear discriminant functions for splice sites, 5'-coding, internal exon, and 3'-coding region recognition have been developed. A gene structure prediction system FGENE has been developed based on the exon recognition functions. We compute a graph of mutual compatibility of different exons and present a gene structure models as paths of this directed acyclic graph. For an optimal model selection we apply a variant of dynamic programming algorithm to search for the path in the graph with the maximal value of the corresponding discriminant functions. Prediction by FGENE for 185 complete human gene sequences has 81% exact exon recognition accuracy and 91% accuracy at the level of individual exon nucleotides with the correlation coefficient (C) equals 0.90. Testing FGENE on 35 genes not used in the development of discriminant functions shows 71% accuracy of exact exon prediction and 89% at the nucleotide level (C = 0.86). FGENE compares very favorably with the other programs currently used to predict protein-coding regions. Analysis of uncharacterized human sequences based on our methods for splice site (HSPL, RNASPL), internal exons (HEXON), all type of exons (FEXH) and human (FGENEH) and bacterial (CDSB) gene structure prediction and recognition of human and bacterial sequences (HBR) (to test a library for E. coli contamination) is available through the University of Houston, Weizmann Institute of Science network server and a WWW page of the Human Genome Center at Baylor College of Medicine.

Algorithms↗

Symbolic programs for structural identification of linear pharmacokinetic systems.

Most parameter estimation techniques implicitly assume that it is possible to determine the parameters of the system uniquely if there were no noise in the output. In practice, this is not always the case. Whether or not this assumption is true for a given input-output experiment is the problem of structural identification. Two programs utilizing symbolic matrix calculus are presented which aid in solving this problem for linear systems. Pharmacokinetic examples are given.

Computers↗

Predictive estimation of protein linear epitopes by using the program PEOPLE.

A single small segment (sequence recognition) or domain (conformation recognition) of a protein could act as an antigen (antigenic determinant) vs an antibody. Epitopes of the first kind being a continuous segment along the sequence (linear), generally bent with a typical non-ordered structure (turns and/or loops), can be predicted from the only knowledge of the primary structure. After reviewing the different algorithms, we present PEOPLE (Predictive Estimation Of Protein Linear Epitopes) which uses combined prediction methods, taking into account the basic fundamental properties corresponding to what should be an ideal epitope: bent (secondary structure mainly beta-turns), surface accessible, hydrophilic and mobile and/or flexible. Four classes of basic biophysical parameters are considered for the determination of an antigenic index AG - secondary structure; hydrophilicity; surface accessibility; flexibility. The AG index is finally defined as a linear combination of the four class profiles. Typical applications are presented.

Animals↗

Genetic programming over context-free languages with linear constraints for the knapsack problem: first results.

In this paper, we introduce genetic programming over context-free languages with linear constraints for combinatorial optimization, apply this method to several variants of the multidimensional knapsack problem, and discuss its performance relative to Michalewicz's genetic algorithm with penalty functions. With respect to Michalewicz's approach, we demonstrate that genetic programming over context-free languages with linear constraints improves convergence. A final result is that genetic programming over context-free languages with linear constraints is ideally suited to modeling complementarities between items in a knapsack problem: The more complementarities in the problem, the stronger the performance in comparison to its competitors.

Combinatorial Chemistry Techniques↗

The growth of palliative care programs in United States hospitals.

BACKGROUND: Palliative care programs are becoming increasingly common in U.S. hospitals. OBJECTIVE: To quantify the growth of hospital based palliative care programs from 2000-2003 and identify hospital characteristics associated with the development of a palliative care program. DESIGN AND MEASUREMENTS: Data were obtained from the 2001-2004 American Hospital Association Annual Surveys which covered calendar years 2000-2003. We identified all programs that self-reported the presence of a hospital-owned palliative care program and acute medical and surgical beds. Multivariate logistic regression was used to identify characteristics significantly associated with the presence of a palliative care program in the 2003 survey data. RESULTS: Overall, the number of programs increased linearly from 632 (15% of hospitals) in 2000 to 1027 (25% of hospitals) in 2003. Significant predictors associated with an increased likelihood of having a palliative care program included greater numbers of hospital beds and critical care beds, geographic region, and being an academic medical center. Compared to notfor- profit hospitals, VA hospitals were significantly more likely to have a palliative care program and city, county or state and for-profit hospitals were significantly less likely to have a program. Hospitals operated by the Catholic Church, and hospitals that owned their own hospice program were significantly more likely to have a palliative care program than non- Catholic Church-operated hospitals and hospitals without hospice programs respectively. CONCLUSIONS: Our data suggest that although growth in palliative care programs has occurred throughout the nation's hospitals, larger hospitals, academic medical centers, not-for-profit hospitals, and VA hospitals are significantly more likely to develop a program compared to other hospitals.

Data Collection↗

A computer program for the analysis of structural identifiability and equivalence of linear compartmental models.

A FORTRAN program based on the sufficient and necessary algebraic condition for structural identifiability is presented. In the case of an unidentifiable model the program generates all identifiable submodels that are structurally equivalent to the original model in the given input--output experiment. The parametrization vector of the model may include first-order and zero-order transport rate coefficients, unknown distribution volumes and initial conditions, as well as unknown elements of input and output matrices. Any a priori constraint imposed upon the parameters may be taken into account. An attempt is made to reduce input data requirements preserving generality of the program.

Computers↗

Practical aspects on the estimation of the parameters in Coale's model for marital fertility.

This paper demonstrates the estimation of the parameters in the Coale model for marital fertility by the maximum likelihood method, under the assumption of a simple Poisson process model. The necessary calculations are easily performed in the statistical computer program package GLIM, and the necessary commands are noted. Without access to GLIM, or any equivalent, it is still possible to fit the model approximately by the use of any weighted linear regression program. In both cases, goodness of fit tests are available.

Adult↗

The exponential-Gompertzian tumor growth model: data from six tumor cell lines in vitro and in vivo. Estimate of the transition point from exponential to Gompertzian growth and potential clinical implications.

The published growth data were examined for six tumor cell lines (FSA, Line 1, MCA-11, EMT6/RO, MGH-U1, MLS) grown in vivo and in vitro as monolayer cultures and as multicell spheroids cultured under different experimental conditions. Serial estimates of tumor sizes were fitted by Gompertzian equations obtained with a non-linear computerized program. When the growth equations of the same tumor growing in different experimental conditions were compared, the Gompertzian parameters alpha 0 (initial specific growth rate) and beta (retardation factor) showed a strong linear correlation in all the examined lines, with no exception. This occurrence supports the exponential-Gompertzian growth model, where an early exponential phase (which is virtually not influenced by exogenous factors) is followed by a Gompertzian phase, the characteristics of which are greatly dependent on environmental conditions. The transition between the two phases was estimated to occur when tumor size reached 10(2)-10(4) cells, depending on the cell line. This kinetic change in tumor growth may be clinically relevant as regards cytotoxic treatments. It could explain some consequences of delays in adjuvant (postoperative) chemotherapy observed in clinical trials on primary breast cancer.

Animals↗

Determination of flavonoids in Hypericum perforatum by HPLC analysis.

AIM: To establish an HPLC method for simultaneous determination of four flavonoids in Hypericum perforatum L., ruitn, hyperin, avicularin and quercetin. METHODS: C18 column was used, the chromatography was carried out with a linear gradient program. The mobile phase was A: H2O (pH 3.0-3.5 adjusted with phosphoric acid) and B: acetonitrile, at flow rate of 1.0 mL.min-1, peaks were detected at 254 nm. RESULTS: The linear range of rutin was 1.376-8.256 micrograms.mL-1 (gamma = 0.9999), hyperin 3.160-18.960 micrograms.mL-1 (gamma = 0.9996), avicularin 0.968-5.808 micrograms.mL-1 (gamma = 0.9998) and quercetin 0.776-4.656 micrograms.mL-1 (gamma = 0.9993). The average recovery of rutin was 97.8%, RSD 4.8% (n = 3), hyperin 100.7%, RSD 3.7% (n = 3), avicularin 97.3%, RSD 0.8% (n = 3) and quercetin 100.5%, RSD 4.4% (n = 3). All of RSDs of precision were less than 2% (n = 5), reproducibilities less than 3%. CONCLUSION: The method is simple, effective and feasible. It can be used to determine flavonodis in Hypericum perforatum.

Calibration↗

A methodology for speciation of methyltins in mammalian tissues.

Exposure to methyltin compounds results in morphologically detectable damage to several mammalian organ systems. Although reliable dose-response relationships have been described, a fast method for quantitating levels of various methyltin species in target organs has been unavailable. It has been possible to measure organotins as total tin using atomic absorption spectrometry, but speciation of methyltins has proved difficult. We present a rapid method for quantitative analysis and speciation of methyltins, direct from mammalian tissues. Methyltin compounds (monomethyltin trichloride, dimethyltin dichloride, trimethyltin chloride, and tetramethyltin) are purged from freshly homogenized mouse kidney and brain tissues using NaBH4. The volatile organotin hydrides produced are cryogenically trapped on the head of a gas chromatographic column (at -40 degrees C) and eluted using a linear temperature program (15 degrees C/min to 190 degrees C). The compounds are detected using selected ion monitoring in a Hewlett Packard 5985-B mass spectrometer. Quantitation is achieved by integration of the areas of the chromatographic peaks. Linear response is obtained over the range of 1 ng to 30 micrograms for each compound. Recoveries of methyltins spiked into tissues are greater than 85%.

Animals↗

A Brownian dynamics program for the simulation of linear and circular DNA and other wormlike chain polyelectrolytes.

For the interpretation of solution structural and dynamic data of linear and circular DNA molecules in the kb range, and for the prediction of the effect of local structural changes on the global conformation of such DNAs, we have developed an efficient and easy way to set up a program based on a second-order explicit Brownian dynamics algorithm. The DNA is modeled by a chain of rigid segments interacting through harmonic spring potentials for bending, torsion, and stretching. The electrostatics are handled using precalculated energy tables for the interactions between DNA segments as a function of relative orientation and distance. Hydrodynamic interactions are treated using the Rotne-Prager tensor. While maintaining acceptable precision, the simulation can be accelerated by recalculating this tensor only once in a certain number of steps.

Biophysics↗

KINFIT: a non linear least-squares computer program for the estimation of pharmacokinetic parameters after intravenous administration.

KINFIT is a nonlinear least-squares computer program designed to allow pharmacokinetic modeling of experimental data and to obtain pertinent parameter estimates based on the derived values. It is written in Visual BASIC for the Microsoft Windows graphical environment. Drug concentrations in blood, plasma, or serum with time following intravenous administration are input and a linear or semi-logarithmic plot of the data appears on the display. On command, polyexponential coefficients and exponents are computed and a non linear curve is fitted through the data set. Results from statistical tests are printed to determine goodness of fit. Commonly calculated pharmacokinetic parameters are also calculated and appear on the output. The execution of KINFIT is demonstrated for time courses of ampicillin in man. KINFIT was compared with the widely available ESTRIP and RSTRIP computer programs and gave parameter estimates that were very similar, although not identical.

Ampicillin↗

Comparing light sensitivity, linearity and step response of electronic cameras for ophthalmology.

PURPOSE: To develop and test a procedure to measure and compare light sensitivity, linearity and step response of electronic cameras. METHODS: The pixel value (PV) of digitized images as a function of light intensity (I) was measured. The sensitivity was calculated from the slope of the P(I) function, the linearity was estimated from the correlation coefficient of this function. To measure the step response, a short sequence of images was acquired. During acquisition, a light source was switched on and off using a fast shutter. The resulting PV was calculated for each video field of the sequence. RESULTS: A CCD camera optimized for the near-infrared (IR) spectrum showed the highest sensitivity for both, visible and IR light. There are little differences in linearity. The step response depends on the procedure of integration and read out.

Equipment Design↗