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PubMed2002

Precise Monte Carlo simulation of gamma-ray response functions for an NaI(Tl) detector.

Three widely used methods to calculate the response functions for NaI(TI) detectors were investigated. The methods were Berger-Seltzer's method (Nucl. Instrum. Methods 104 (1972) 317), general Monte Carlo (MC) programs, such as EGS4 (The EGS4 code system, Stanford Linear Accelerator Center, 1985) and MCNP4B (MCNP-a general Monte Carlo N-particle transport code, Los Alamos National Laboratory Report, LA-12625-M, 1997), and special MC programs. The pulse height spectra in a 3" x 3" NaI(Tl) detector due to several gamma-ray sources have been measured to verify the calculated results of these methods. The energies of the sources ranged from 0.4118 to 7.11 MeV. The spectra generated by Berger-Seltzer's method and the general MC programs did not agree well with the experimental data. PETRANS 1.0, the special MC program developed in house, was fairly accurate since it also considered the scintillation efficiency and the single escape peak shift.

Journal Article↗
PubMed1962

The routine fitting of kinetic data to models: a mathematical formalism for digital computers.

A mathematical formalism is presented for use with digital computers to permit the routine fitting of data to physical and mathematical models. Given a set of data, the mathematical equations describing a model, initial conditions for an experiment, and initial estimates for the values of model parameters, the computer program automatically proceeds to obtain a least squares fit of the data by an iterative adjustment of the values of the parameters. When the experimental measures are linear combinations of functions, the linear coefficients for a least squares fit may also be calculated. The values of both the parameters of the model and the coefficients for the sum of functions may be unknown independent variables, unknown dependent variables, or known constants. In the case of dependence, only linear dependencies are provided for in routine use. The computer program includes a number of subroutines, each one of which performs a special task. This permits flexibility in choosing various types of solutions and procedures. One subroutine, for example, handles linear differential equations, another, special non-linear functions, etc. The use of analytic or numerical solutions of equations is possible.

Biophysical Phenomena↗
PubMed2001

Effects of linear, irrigated-tip radiofrequency ablation in porcine healed anterior infarction.

INTRODUCTION: Radiofrequency (RF) catheter ablation for ventricular tachycardia (VT) in healed infarction is modestly successful. More extensive, anatomically based procedures and irrigated RF delivery may improve outcome. However, limited data exist regarding the characteristics of irrigated RF lesions in infarcted myocardium. This study addresses this shortcoming. METHODS AND RESULTS: Linear lesions were created at the medial border of a healed anterior infarct in eight pigs using irrigated RF energy guided by sinus rhythm electroanatomic voltage mapping and intracardiac echocardiography (ICE). Lesion morphology and effects on ventricular function were assessed with ICE imaging and pathologic analysis (n = 5). The response to programmed stimulation also was determined before and after linear lesions (n = 6). A mean of 9.4 +/- 1.3 RF applications created linear lesions 37.0 +/- 10.6 mm long, 5 to 12 mm wide, and 4 to 8 mm deep. Thrombus formation was not observed. Lesion delivery resulted acutely in increased local wall thickness at the RF site (26.9% +/- 27.5%; P < 0.0001) and transient systolic dysfunction in adjacent normal myocardium (fractional shortening -38% +/- 34%; P < 0.01). Uniform sustained VT (cycle length 232 +/- 41 msec) was induced in 4 of 6 pigs before ablation, but sustained VT could not be induced afterward. CONCLUSION: Irrigated RF energy produced relatively large lesions in infarcted myocardium without thrombus formation. Changes in tissue thickness and echo density observed with ICE verify irrigated RF lesion delivery. Temporary left ventricular dysfunction is consistently observed in the normal myocardium adjacent to the linear lesion.

Animals↗
PubMed2004

Application of a mixed model approach for assessment of interventions and evaluation of programs.

Many social programs and programs for prevention of drug use are designed to affect a wide variety of targets, including individuals, families and neighborhoods, and organizations such as schools, companies, or hospitals. The nature of the intervention and the design of the particular study determine the choice of the appropriate unit of analysis in assessments of outcome. When the units of assignment and units of observation differ from one another, that is, when clusters of persons rather than persons are assigned at random to treatments, analyses performed at lower levels in the study hierarchy provide inefficient estimates of parameters and often lead to inappropriate significance tests. The present goal was to illustrate the applications of linear mixed models for evaluating statistically the effectiveness of programs.

Alcoholism↗
PubMed1999

Error checking and graphical representation of multiple-complete-digest (MCD) restriction-fragment maps.

Genetic and physical maps display the relative positions of objects or markers occurring within a target DNA molecule. In constructing maps, the primary objective is to determine the ordering of these objects. A further objective is to assign a coordinate to each object, indicating its distance from a reference end of the target molecule. This paper describes a computational method and a body of software for assigning coordinates to map objects, given a solution or partial solution to the ordering problem. We describe our method in the context of multiple-complete-digest (MCD) mapping, but it should be applicable to a variety of other mapping problems. Because of errors in the data or insufficient clone coverage to uniquely identify the true ordering of the map objects, a partial ordering is typically the best one can hope for. Once a partial ordering has been established, one often seeks to overlay a metric along the map to assess the distances between the map objects. This problem often proves intractable because of data errors such as erroneous local length measurements (e.g., large clone lengths on low-resolution physical maps). We present a solution to the coordinate assignment problem for MCD restriction-fragment mapping, in which a coordinated set of single-enzyme restriction maps are simultaneously constructed. We show that the coordinate assignment problem can be expressed as the solution of a system of linear constraints. If the linear system is free of inconsistencies, it can be solved using the standard Bellman-Ford algorithm. In the more typical case where the system is inconsistent, our program perturbs it to find a new consistent system of linear constraints, close to those of the given inconsistent system, using a modified Bellman-Ford algorithm. Examples are provided of simple map inconsistencies and the methods by which our program detects candidate data errors and directs the user to potential suspect regions of the map.

Algorithms↗
PubMed1987

Epidemiologic programs for computers and calculators. Inferences on odds ratios, relative risks, and risk differences based on standard regression programs.

Statistical analyses of the joint effects of several factors (covariates) on the risk of disease, death, or other dichotomous outcomes, are frequently based on a model that relates the effect of the covariates to some function of the probability of the outcome. The odds ratio, relative risk, and the difference in risks are among the simplest candidates for the outcome function. Each can be specified as a special case of the generalized linear model, but their use has been limited to researchers with access to specialized computer programs that are not yet generally available in standard computer packages. The purpose of this communication is to describe how to implement the maximum likelihood estimation procedures and hypothesis testing associated with the generalized linear model using any computer program that can perform weighted least squares analyses. The procedure is applied specifically to models for relative risks, risk differences, and odds ratios. The techniques are illustrated with SAS and SPSSx programs for data sets previously presented.

Computers↗
PubMed1995

SEQPWR and SEQOPR: computer programs for design of maximum information trials based on group sequential logrank tests.

The maximum information trial paradigm for clinical trials with failure time data was recognized and has been investigated. With the maximum information trial paradigm, a study is concluded when a prespecified maximum number of events of interest, thus maximum information, has been accrued if there was no early stopping due to treatment difference or lack thereof. We present two interactive FORTRAN programs for use in designing maximum information trials based on group sequential logrank tests. The program SEQPWR computes the attainable power of group sequential logrank tests given the combinations of the accrual and follow-up durations. The program SEQOPR allows the users to investigate the operating characteristics of the maximum information trial given the information fractions of interim analyses. A clinical trial from the Eastern Cooperative Oncology Group is provided to illustrate the usage and features of the programs.

Algorithms↗
PubMed1997

Estimation of relative bioavailability of nutrients using SAS procedures.

The General Linear Models procedure (PROC GLM) in SAS/STAT software can be programmed to perform the standard statistical analyses used for relative bioavailability studies. The first steps are validity checks to test for statistical validity (linearity), fundamental validity (intersection of regression lines at 0 supplemental level), and equality of the basal diet mean to the point of intersection. The CLASS variable capabilities of PROC GLM can be exploited to expedite these tests. After the validity checks, the GLM procedure can be used to obtain parameter estimates for calculation of relative bioavailability. Optional output provides an inverse matrix to calculate standard errors of slopes and slope ratios. Logarithmic and other transformations of the dependent variable to reduce variance heterogeneity or achieve linearity for subsequent calculation of appropriate bioavailability values also can be accomplished within the SAS System. When nonlinear regression models are more appropriate than linear models, the NLIN procedure can be used.

Animals↗
PubMed1999

A kinematic study of progressive apraxia with and without dementia.

BACKGROUND: Prehension is an ideationally simple, cued movement requiring proximal (transport) and distal (manipulation) limb control. Patients with this syndrome of progressive apraxia are unable to perform many activities of daily living that require prehension. There is little known about how this syndrome kinematically disrupts such movements or whether concurrent dementia might play a critical role. OBJECTIVES: Using prehension as a paradigm for an ideationally simple, cued functional movement, we sought to (1) characterize the kinematic features of progressive apraxia in general, and (2) contrast the kinematic differences between apraxic patients with and without dementia. METHODS: Eight patients with the syndrome of progressive apraxia (including five without dementia, one of whom had autopsy-confirmed corticobasal ganglionic degeneration, and three with dementia, one of whom had autopsy-confirmed Alzheimer's disease) were compared with eight age-matched normal control subjects on a prehension task using an Optotrak camera system. RESULTS: Compared with control subjects, apraxic subjects had slowed reaction time, slowed transport and manipulation kinematics, greater lateral deviation from the linear prehension trajectory, greater intermanual asymmetry, motor programming disturbances, and mild transport-manipulation uncoupling. There were minor differences between the apraxia subgroups such as greater intermanual differences and impaired grip aperture velocity in the nondemented group, and overall slower movement in the demented group. CONCLUSIONS: There are major kinematic differences between apraxic and control subjects on a prehension task. The differences between clinical-pathologic subgroups are more subtle, and the movement disorder itself rather than concurrent dementia is the greatest determinant of motor disability.

Aged↗
PubMed1993

Bumetanide binding to normal albumins and to albumin in renal failure.

Binding of bumetanide, a loop diuretic, to partially purified albumins from renal failure patients (RF-HA), and healthy subjects (N-HA), human serum albumin (HSA) and defatted-HSA (D-HSA), was studied with equilibrium dialysis at a constant albumin concentration and various ligand concentrations. Binding parameters (n and K) were estimated from Scatchard plots and with a non-linear two-binding site model computer program, assuming two classes of independent sites. The binding capacities (n1K1) decreased in the order N-HA > RF-HA > D-HSA > HSA. Computer estimates of K1 for the partially purified albumin preparations were not markedly different. However, the graphical estimate of K1 for N-HA was greater than that for RF-HA. When the degree of binding (r) was plotted as a function of the logarithm of the free bumetanide concentration, an asymptotic plateau was not observed, indicating that the protein binding sites were not saturated. Consequently, the calculated binding estimates may not adequately describe the binding of bumetanide.

Albumins↗
PubMed2005

Alcohol intake in adolescence and mammographic density.

Adolescent exposures may be important in the development of breast cancer later in life. We examined the association of adolescent alcohol consumption and adult mammographic density, a strong risk factor for breast cancer. Women within the Minnesota Breast Cancer Family Cohort with detailed mammogram and risk factor information (n = 1,893) formed our sample. Breast cancer cases were excluded. Adolescent alcohol consumption (before age 18) was solicited through a mailed questionnaire. Percent density (PD) was estimated using the computer-assisted thresholding program, Cumulus. Statistical analyses were performed using linear mixed effect models. Women who reported ever drinking alcohol before age 18 (n = 390; 21%) had a higher unadjusted PD than women who never drank during adolescence (mu(unadj) = 26.5% vs. 22.2%), but this difference disappeared with adjustment for risk factors for mammographic density (mu(adj) = 21.0% vs. 21.2%, p = 0.94). Adult PD was not associated with age at initiation, amount of alcohol consumed at one sitting or frequency of alcohol use before age 18. The lack of differences was seen across strata of menopausal status. There was suggestion of higher PD among heavy and more frequent drinkers (24.0%, 95% CI 21.1-26.8%) compared to lighter (21.3%, 95% CI 20.3-22.3%) and never drinkers (21.4%, 95% CI 20.9-21.9%) and also among regular adolescent drinkers who were daily or weekly adult drinkers (25.0%, 95% CI 23.0-27.0%) compared to less regular drinkers in these 2 time periods (23.0-23.4%). However, these associations were not statistically significant (p = 0.27 and p = 0.22, respectively). In summary, there was no evidence that adolescent alcohol use was associated with large and persistent effects on adult PD.

Adolescent↗
PubMed2001

Adsorption on Heterogeneous Regular Surfaces.

Quantifying the role of surface shape and physicochemical surface conditions on the interfacial reactivity of particles and substrates is fundamental to a multitude of natural and engineered surface adsorption phenomena. We consider continuum/jump regime adsorption at the gas or liquid interface of arbitrary regular solid surfaces with heterogeneous surface features. In particular, the 3-D boundary value problem (based on Laplace's diffusion equation) is converted into a 2-D integral equation for the adsorbate concentration at the particle surface. This accommodates numerical descretization via the implementation of 2-D Gauss-Legendre quadratures on an arrangement of high- and low-adsorption patch trace sites constructed to completely cover the particle surface. A generalized computer program is developed to solve the resulting linear algebra problem for the unkown local adsorption current densities. We investigate the role of various distributions of high- and low-adsorption sites for a generalized class of spheres which includes the DNA-like shaped twisted spheres. The biological implications of the role of surface curvature on interfacial adsorption/reactivity at particle surfaces are also discussed. Copyright 2001 Academic Press.

Journal Article↗
PubMed1980

Kinetic analysis of the fate of methyl parathion in the dog.

Methyl parathion (1, 3, 10 and 30 mg.kg-1) was injected intravenously in dogs and the serum concentrations were followed in function of time. For each dose the serum level data were fitted to a two- or tri-exponential equation by means of a non-linear least-squares regression analysis computer program. During the first hours after injection a rapid and important decrease of the serum levels was observed, whereas afterwards the levels decreased more slowly with a harmonic mean terminal half-life of 7.2 h (range 6.6-8.8 h) for the 10 mg.kg-1 dose. Simulations using the kinetic parameters obtained for the dose of 10 mg.kg-1 show that elimination of methyl parathion from the body is fast (5 h after injection only 30% of the dose is still present in the body) and that the fraction remaining is mainly located in the peripheral compartments.

Animals↗
PubMed1981

Wiener kernels determination in the cats lateral geniculate nucleus as a function of velocity of a sinusoidal grating: preliminary results.

The aim of this work was to develop a mathematical model which could describe information collected in the lateral geniculate body in response to the movement of a specific stimulus in an animal's visual field. To do this, a visual stimulation technique was developed, as well as a group of computer programs for processing the information recorded during the experiments. This group of programs is a method of non-linear identification based on the Wiener Kernels method, with the speed of an image's motion in the visual field as the systems entry variable. Preliminary results have shown that non-linearities in visual information processing would also be involved in speed coding. Thus a further utilization of the Wiener method seems useful and could contribute a great deal to visual system analysis.

Animals↗
PubMed1986

Effects of exercise-training on the thermic effect of food and body fatness of adult women.

Resting metabolic rate (RMR), thermic effect of food (TEF), aerobic capacity (VO2max), body fat, and food intake were measured in 10 healthy women before and after a 10 week graded exercise program of jogging. Pretraining TEF was a linear function of VO2max. Following exercise training, the women showed a significant increase (20%) in VO2max and loss (10.4%) of body fat; body weight did not change. Fat loss was directly related to changes in VO2max and RMR. The women showed a wide variation of changes in RMR (-21 to +2%) and TEF (-32 to +66%) from their pretraining levels. The changes in RMR and TEF were significantly positively correlated with improvements in VO2max. Analyses using multiple regression techniques, indicated that the changes in RMR and TEF accounted for 96.2% of the total variation in the changes of VO2max. Analyses of food intake indicated that diet composition (but not caloric intake) was highly related to the changes in VO2max, RMR, TEF and body fatness. Present results support further our hypothesis, that VO2max is an important physiological index of dietary thermogenesis and fat loss of individuals of normal body weight and fatness. Possible nutritional and physiological factors that may explain the wide variation in RMR and TEF of the women are discussed.

Adipose Tissue↗
PubMed1995

Investigation of the inhibition of leukotriene A4 hydrolase.

In an effort to better understand the favorable binding interactions between the reversible picomolar inhibitor 3-(4-benzyloxyphenyl)-2-(R)-amino-1- propanethiol (1) and leukotriene A4 (LTA4) hydrolase (EC 3.3.2.6), we prepared a number of derivatives of 1-L and other related structures, and assayed their inhibition of LTA4 hydrolase-catalyzed hydrolysis of L-alanine-p-nitroanilide. The inhibition data was analyzed using a weighted non-linear least-squares curve fitting computer program developed for this purpose to fit data derived under the non-Michaelis-Menten condition of [I]t < [E]t. The free thiol is necessary for sub-micromolar binding and the enzyme prefers the R enantiomer over the S enantiomer, in contrast to the stereoselectivity displayed towards bestatin, an inhibitor of somewhat similar structure. Substitution of acid moieties around the periphery of the benzyloxyphenyl portion of 1-L leads to substantially decreased binding, suggesting that this group resides within a large hydrophobic pocket when bound to the enzyme. Possible LTA4 binding modes in the active site of LTA4 hydrolase, including a possible direct role for the carboxylic acid of LTA4 in the enzyme-catalyzed hydrolysis of leukotriene A4, are discussed.

Computer Graphics↗
PubMed2003

Cardiomyocytes derived from embryonic stem cells resemble cardiomyocytes of the embryonic heart tube.

OBJECTIVE: After formation of the linear heart tube a chamber-specific program of gene expression becomes active that underlies the formation of the chamber myocardium. To assess whether this program is recapitulated in in vitro differentiated embryonic stem cells, we performed qualitative and quantitative analyses of cardiogenesis in vivo and in vitro. METHODS: Gene expression profiles were made by in situ hybridisation and real-time PCR and electrophysiological profiles by patch clamp analyses of cardiomyocytes derived from time series of differentiating HM1 mouse embryonic stem cells and from embryonic and adult mouse hearts. RESULTS: In embryoid bodies the in situ patterns of expression of alpha-myosin heavy chain, myosin light chain 2a and sarcoendoplasmic reticulum calcium ATPase 2a were similar to that of the heart muscle-specific marker gene cardiac troponin I. Myosin light chain 2v was expressed in part of the cardiac troponin I-expressing area, indicating heterogeneity within the cardiac cell population. Atrial natriuretic factor expression, indicative of the chamber-type program, could only very occasionally be detected by in situ hybridisation. Quantitative reverse transcriptase PCR showed that all cardiac genes, most notably atrial natriuretic factor, were expressed at relatively low levels, similar to those in embryonic hearts at embryonic day 8.75-9. Analysis of the electrophysiological characteristics of embryonic stem cell-derived cardiomyocytes showed an increase of the upstroke velocity and a shorter duration of the action potential during prolonged differentiation in vitro. When embryonic mouse heart compartments of embryonic day 12.5 were used as a reference, the electrophysiological characteristics of a substantial part of the embryonic stem cell-derived cardiomyocytes were most reminiscent to those observed in the embryonic outflow tract. CONCLUSION: Together, these data suggest that most cardiomyocytes acquired by differentiation of embryonic stem cells maintain a phenotype reminiscent of that of the cardiomyocytes of the primary heart tube, and hardly any myocytes develop a chamber myocardial phenotype.

Action Potentials↗