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PubMed1989

The use of a spreadsheet computer program to expedite TLD reporting.

A method has been devised using an electronic spread sheet that will shorten the data processing time and give a printed report of the results. Lithium Fluoride chips are used in pairs so as to produce the same average response. The raw TL readings along with descriptive comments are entered into the computer. The program then computes the single chip dose, the average dose for each chip pair, applies a non-linearity correction factor and prints out a report with comments and patient data. The program offers several advantages: It is much faster than hand calculations, it provides a precise and accurate conversion of raw data to final data, and outputs an organized display of calibration factors, input data, dosimetry data, patient data and listing of involved personnel. The program is easy to use and can be run on any computer that can support a spreadsheet program.

Calibration↗
PubMed2004

Evaluation of linearity in the clinical laboratory.

CONTEXT: Clinical laboratory assessment of test linearity is often limited to satisfying regulatory requirements rather than integrating this tool into the laboratory quality assurance program. Although an important part of quality control and method validation for clinical laboratories, linearity of clinical tests does not get the attention it deserves. OBJECTIVE: This article evaluates the concepts and importance of linearity evaluations for clinical tests. DESIGN: We describe the theory and procedural steps of each linearity evaluation. We then evaluate the statistical methods for each procedure. RESULTS: Visual assessment, although simple, is subjective. The lack-of-fit error and the 1986 NCCLS EP6-P G test are sensitive to imprecision and assume that the data are first order. Regression analysis, as developed as the polynomial method, is partly based on the experiences of the College of American Pathologists Instrumentation Resource Committee and has proved to be a robust statistical method. CONCLUSIONS: We provide general guidelines for handling non-linear results from a linearity evaluation. Handling linearity data in an objective manner will aid clinical laboratorians whose goal is to improve the quality of the tests they perform.

Clinical Laboratory Techniques↗
PubMed1986

A suitable parameterization of the Michaelis-Menten enzyme reaction.

It is shown here that a suitable form for estimation and inference using the Michaelis-Menten [(1913) Biochem Z. 49, 333-369] model for simple enzymic reactions is one in which the two parameters appear in the denominator of the equation. In this form, convergence to the least-squares estimates using the Gauss-Newton method [see Kennedy & Gentle (1980) Statistical Computing, Marcel Dekker, New York] is virtually ensured, or, as the model in this form is a member of the class of 'generalized linear models', it may be fitted by packages such as those of Rothamsted Experimental Station [(1977) GENSTAT (A General Statistical Program), Rothamsted Experimental Station, Harpenden] and the Numerical Algorithms Group [(1978) GLIM (Generalised Linear Interactive Modeling), Numerical Algorithms Group, Oxford]. Furthermore, the parameters-in-denominator principle is readily extended to more complicated catalytic models. With all parameters in the denominator, the least-squares estimators are close to being unbiased and normally distributed, whereas severe bias and non-normality may result from use of the standard formulations.

Catalysis↗
PubMed2006

Thermoluminescence glow curve deconvolution and its statistical analysis using the flexibility of spreadsheet programs.

Analysing thermoluminescence glow curves involves the solving of a system of non-linear equations. These equations are either differential equations that must be solved numerically or functional approximations for their solution. The current paper presents software with the functions needed for the study of glow curves that is not a stand-alone computer program but an extension of MS Excel. It supplies functions that solve the general one trap model for the thermoluminescence process without the use of approximating functions. Combined with the Solver utility of Excel this gives a very flexible system for the analysis of glow curves. Functions for analysing the statistics of the deconvolution results are included.

Algorithms↗
PubMed1991

Control of the cryosurgical process in nonideal materials.

A study of a controlled cryosurgical process is presented. This study is based on the energy equations describing the probe response and the phase change occurring in the medium. First-order nonlinear differential equations (state equations) are obtained by applying the integral-solution method. In order to obtain maximal cell destruction, it is desired to control a specific cooling rate at the solid-liquid interface. This cooling rate defines the desired trajectories of the state variables through the state equations. In order to satisfy the cooling rate condition on the freezing front, a closed-loop is designed to control the probe temperature program. A simple analysis of the system stability employed linearization at several points along the desired trajectories. Ranges of stability were obtained for a system containing a proportional-integral controller. It was demonstrated that these stability ranges depend mainly on the selected sampling time of the discrete control loop and that the phase-change process does not significantly affect the stability results. A complete study of the nonlinear equations was performed by a computer simulation program which enables the selection of the final values of the controller parameters, in order to minimize the error and to ensure stability. In addition, the simulation program gives information about the effects of the A/D and D/A converters accuracy on the performance of the control loop. An A/D converter accuracy of 12 bits was found necessary in order to reduce the oscillations in probe temperature to acceptable values. The simulation also yields a complete calculated temperature field in the tissue during the controlled process. From these simulated results it can be seen that oscillations of +/- 0.5 degrees C in the desired probe temperature do not significantly affect the desired cooling rate at the freezing front. An initial overshoot of 1.5 degrees C in the desired probe temperature was obtained both experimentally and theoretically from the simulation. When this initial overshoot occurs at the beginning of the freezing process, it causes an error in freezing front velocity and consequently in ice-front position. From the numerical simulation, it can be deduced that the cooling rate obtained at the front deviates from the desired value by approximately 1%. The probe-temperature error increases at two instants: a) during the super-cooling effect and the subsequent sudden crystallization, and b) when the probe temperature is below -80 degrees C and unstable boiling of the cooling medium causes oscillations.

Cryosurgery↗
PubMed1994

A pharmacodynamic approach to the estimate of carbamazepine autoinduction.

Population-based pharmacokinetic prediction algorithms have been developed for several medications. A fundamental assumption has been that the kinetics remain constant over time. Carbamazepine (CBZ), however, induces its own metabolism in a concentration- and time-dependent manner. A Bayesian estimation program is presented that models the changing catabolic enzyme activity, linearly related to hepatic microsomal enzyme concentration, along with the serum drug concentration. An Emax model is used for enzyme formation with respect to drug concentration: elimination of enzyme activity is modeled as a first-order process. This program was tested in 22 drug-naive outpatients begun on CBZ monotherapy. The 1 week concentrations were used to prospectively predict concentrations at 1 month of therapy and were very close to actual measurements: prediction bias (mean error of prediction) = -0.1 micrograms/mL and precision (median absolute error of prediction) = 1.2 micrograms/mL. Comparison estimates, made by assuming a constant concentration/dose ratio, had bias = 2.6 micrograms/mL (p < 0.001) and precision = 2.2 micrograms/mL (p = 0.01). We conclude that (1) CBZ autoinduction is not complete after 1 week of therapy and (2) the methodology permits accurate estimation of CBZ pharmacokinetics.

Adult↗
PubMed1995

Algorithms for protein structural motif recognition.

The identification of protein sequences that fold into certain known three-dimensional (3D) structures, or motifs, is evaluated through a probabilistic analysis of their one-dimensional (1D) sequences. We present a correlation method that runs in linear time and incorporates pairwise dependencies between amino acid residues at multiple distances to assess the conditional probability that a given residue is part of a given 3D structure. This method is generalized to multiple motifs, where a dynamic programming approach leads to an efficient algorithm that runs in linear time for practical problems. By this approach, we were able to distinguish (2-stranded) coiled-coil from non-coiled-coil domains and globins from nonglobins. When tested on the Brookhaven X-ray crystal structure database, the method does not produce any false-positive or false-negative predictions of coiled coils.

Algorithms↗
PubMed2002

Longitudinal investigation of soft palate and nasopharyngeal airway relations in different rotation types.

The relationship between the soft palate and the nasopharyngeal airway in different mandibular growth rotation models was investigated. A total of 72 lateral cephalograms were obtained three years longitudinally from 24 individuals. The subjects had a mean age of 10.7 +/- 1.2 years and showed a normal (n = 8), posterior (n = 8), and anterior (n = 8) mandibular rotation pattern. Linear and angular measurements of the soft palate and nasopharyngeal airway were recorded by using PORDIOS computer program and were examined by means of descriptive statistics and paired t-tests. A linear increase in the soft palate length (SPL) was observed in all groups, with the posterior mandibular rotation group showing the largest increase within the observation period (28.56 +/- 4.83 to 34.98 +/- 2.87; P < .01). According to the paired t-test, palatal plane (ANS-PNS)/soft palate tip (SPT) angle showed a statistically significant decrease in the posterior rotation group (P < .01). The ratio between SPL and superior nasopharyngeal space (SPS) did not show a statistically significant difference among the groups. Although various amounts of soft palate and nasopharyngeal airway growth occurred in the different mandibular rotation types, the ratio between SPL and SPS (SPL/SPS), which plays an indispensable role in velopharyngeal functions, did not show a statistically significant difference in the groups. This assured velopharyngeal closure throughout the active growth period.

Cephalometry↗
PubMed2001

Health insurance and health services utilization in Ireland.

The numbers buying private health insurance in Ireland have continued to grow, despite a broadening in entitlement to public care. About 40% of the population now have insurance, although everyone has entitlement to public hospital care. In this paper, we examine in detail the growth in insurance coverage and the factors underlying the demand for insurance. Attitudinal responses reveal the importance of perceptions about waiting times for public care, as well as some concerns about the quality of that care. Individual characteristics, such as education, age, gender, marital status, family composition and income all influence the probability of purchasing private insurance. We also examine the relationship between insurance and utilization of hospital in-patient services. The positive effect of private insurance appears less than that of entitlement to full free health care from the state, although the latter is means-tested, and may partly represent health status.

Attitude to Health↗
PubMedDate not supplied

The absolute bioavailability of oral theophylline in patients with spinal cord injury.

The absolute bioavailability of oral theophylline in five tetraplegic, five paraplegic and three control (intact neuraxes) subjects was studied. All were healthy nonobese males between 20 and 60 years of age, with normal renal and hepatic function. More than 1 year had elapsed from the date of injury in all of the patients with spinal cord injury. None of the study subjects was taking medications known to interfere with theophylline metabolism or the analytic methodology. Each received theophylline in an equivalent amount orally, and by intravenous infusion on 2 occasions separated by not less than 2 weeks. The time course of serum theophylline concentration was followed for up to 24 hours and the area under each oral and intravenous curve extrapolated to infinity (AUC male infinity) was compared using a linear, least-squares, best-fit BASIC program (ESTRIP). A statistically significant difference between means and variances of the absolute bioavailability of oral theophylline, AUCoral male infinity/AUCIV male infinity, (AUCratio +/- SD) was demonstrated in the tetraplegic subjects who showed decreased bioavailability (AUCratio = 0.67 +/- 0.04, range 0.63-0.73) as compared to the paraplegic (AUCratio = 0.95 +/- 0.09, range 0.84-1.08) and control subjects (AUCratio = 0.90 +/- 0.12, range 0.78-1.02). A decrease in the bioavailability of oral theophylline in tetraplegic subjects has not previously been described and may be caused by impaired gastric emptying, which frequently characterizes high myelopathy. Diminished bioavailability could result in underestimation of loading and maintenance doses in tetraplegic humans.

Administration, Oral↗
PubMed2000

Chamber formation and morphogenesis in the developing mammalian heart.

In this study we challenge the generally accepted view that cardiac chambers form from an array of segmental primordia arranged along the anteroposterior axis of the linear and looping heart tube. We traced the spatial pattern of expression of genes encoding atrial natriuretic factor, sarcoplasmic reticulum calcium ATPase, Chisel, Irx5, Irx4, myosin light chain 2v, and beta-myosin heavy chain and related these to morphogenesis. Based on the patterns we propose a two-step model for chamber formation in the embryonic heart. First, a linear heart forms, which is composed of "primary" myocardium that nonetheless shows polarity in phenotype and gene expression along its anteroposterior and dorsoventral axes. Second, specialized ventricular chamber myocardium is specified at the ventral surface of the linear heart tube, while distinct left and right atrial myocardium forms more caudally on laterodorsal surfaces. The process of looping aligns these primordial chambers such that they face the outer curvature. Myocardium of the inner curvature, as well as that of inflow tract, atrioventricular canal, and outflow tract, retains the molecular signature originally found in linear heart tube myocardium. Evidence for distinct transcriptional programs which govern compartmentalization in the forming heart is seen in the patterns of expression of Hand1 for the dorsoventral axis, Irx4 and Tbx5 for the anteroposterior axis, and Irx5 for the distinction between primary and chamber myocardium.

Animals↗
PubMed1990

Population pharmacokinetics of phenytoin in Singapore Chinese.

The pharmacokinetics of phenytoin was studied in 66 epileptic Chinese children and adults. The data were analysed by the population approach, using the non-linear mixed effect model, in the MULTI (ELS) program. There was no age or gender-related effect on either the apparent maximum elimination rate (kmax) or Michaelis-Menten constant (KM). Kmax was related to body weight 0.656. The population pharmacokinetics was similar in children and adults. Kmax and KM were estimated to be 30.72 mg.kg-0.656 day-1 and 2.307 mg.l-1, respectively. Kmax was higher than reported values, and KM was comparable to that reported in a study in Japanese, but was much lower than that reported in studies of European patients. The inter-individual variability of KM (CV 65.58%) was substantially higher than that of kmax (CV 28.49%), and the residual (intra-individual) variability was found 21.33% (CV).

Adolescent↗
PubMed1984

D-propoxyphene kinetics in man: significance of a deep third compartment.

Data from a previously published single dose study of d-propoxyphene 65 mg given i.v. to 8 healthy subjects have been subjected to non linear regression analysis by a curve-fitting program to test the applicability of a 2- and a 3-compartment open model. Analysis of residuals (difference between observed and computed concentrations) revealed similar systematic deviations in all 8 subjects when the 2-compartment model was used (5-10 h negative residuals, after 13 h positive residuals). In contrast, curve-fit by a 3-compartment model (with two parallel peripheral compartments) was good with no systematic deviations. The data show that a terminal monoexponential decline in d-propoxyphene concentrations cannot be expected until 15-30 h after single dose administration, and that the determination of the corresponding half-life is rather inaccurate. Accordingly, precise steady state level predictions may be difficult to obtain from conventional single dose studies with d-propoxyphene.

Adult↗
PubMed1992

Motor control of voluntary arm movements. Kinematic and modelling study.

The motor control of pointing and reaching-to-grasp movements was investigated using two different approaches (kinematic and modelling) in order to establish whether the type of control varies according to modifications of arm kinematics. Kinematic analysis of arm movements was performed on subjects' hand trajectories directed to large and small stimuli located at two different distances. The subjects were required either to grasp and to point to each stimulus. The kinematics of the subsequent movement, during which subject's hand came back to the starting position, were also studied. For both movements, kinematic analysis was performed on hand linear trajectories as well as on joint angular trajectories of shoulder and elbow. The second approach consisted in the parametric identification of the black box (ARMAX) model of the controller driving the arm movement. Such controller is hypothesized to work for the correct execution of the motor act. The order of the controller ARMAX model was analyzed with respect to the different experimental conditions (distal task, stimulus size and distance). Results from kinematic analysis showed that target distance and size influenced kinematic parameters both of angular and linear displacements. Nevertheless, the structure of the motor program was found to remain constant with distance and distal task, while it varied with precision requirements due to stimulus size. The estimated model order of the controller confirmed the invariance of the control law with regard to movement amplitude, whereas it was sensitive to target size.

Adult↗
PubMed1982

Pharmacokinetics of adriamycin in patients with breast cancer: correlation between pharmacokinetic parameters and clinical short-term response.

The pharmacokinetics of adriamycin was evaluated in the plasma of 12 patients with breast cancer after injection of an i.v. bolus. The patients were suffering from a locally advanced tumor, were free of metastases and had received no prior treatment. They received a chemotherapy consisting in adriamycin (50 mg/m2) on day 1, vincristine (1 mg/m2) on day 2 and methotrexate (6 mg/m2) on days 3, 4 and 5. The response to chemotherapy was assessed as the percentage of reduction of the palpable tumoral mass. Plasma samples were collected at various times after injection of the drug. Adriamycin and its metabolites were extracted using an original column purification technique and were evaluated by high-performance liquid chromatography with fluorometric detection. Pharmacokinetic parameters were calculated with a computer program based upon an algorithm of non-linear function minimization. The three successive half-lives presented little individual variations and were 4.75 min, 0.822 hr and 18.9 hr. On the other hand, the A, B and C parameters were highly scattered. The total plasma clearance of the parent drug ranged from 28.3 to 98.7 1/hr. A highly significant correlation was observed between parameter A and the short-term clinical response. Moreover, a mild correlation exists between the half-life of the 1st phase and the short-term clinical response. We can therefore assume that the efficacy of the drug may be dependent upon its distribution in the organism. Such a relationship may allow the development of new protocols of chemotherapy in order to obtain an optimal distribution of the drug in every patient.

Adult↗
PubMed2005

Drink driving enforcement and publicity campaigns: are the policy recommendations sensitive to model specification?

Since their implementation, the drink driving enforcement and publicity campaigns in the Australian State of Victoria have been extensively evaluated and the mixed results obtained have generated much public debate. Using the same data from previous studies, this paper re-evaluated the effectiveness of the campaigns and tested several model assumptions and specifications. In general, the results obtained were robust and showed that the campaigns were effective in reducing serious crashes during high alcohol hours.

Accidents, Traffic↗
PubMed2006

Weight gain in children with hypertonia of cerebral origin receiving intrathecal baclofen therapy.

OBJECTIVE: To identify the pattern of weight change in children receiving intrathecal baclofen (ITB) therapy. DESIGN: A retrospective medical chart review was conducted to identify weight status before and after ITB pump implantation. SETTING: Tertiary care children's hospital and academic medical center. PARTICIPANTS: All children and adolescents with hypertonia of cerebral origin who were younger than 19 years of age at the time of pump placement and followed in our pediatric baclofen pump program. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A linear mixed model was used to examine the rate of change in weight (weight-gain velocity) before and after surgery. Weight change was adjusted for age, sex, functional level determined by the Gross Motor Functional Classification System, tube feeding, dystonia, and other comorbidities. RESULTS: The average weight-gain velocity was 2.32 kg/y presurgery and 2.93 kg/y postsurgery, adjusted for potential confounders. The 0.61 kg/y increase in weight-gain velocity attained statistical significance (P = .028). CONCLUSIONS: Although excessive weight gain is not a common problem in children with cerebral origin spasticity, increased weight-gain velocity is prevalent in children receiving ITB therapy. Health care providers may anticipate a welcome weight gain in the underweight child. This consequence should be considered when managing children receiving ITB therapy, and health care providers must appropriately intervene to prevent excessive weight gain. Further studies exploring the reasons for the increased weight-gain velocity are warranted.

Adolescent↗
PubMed2005

Absorbed dose estimates at the cellular level for 131I.

Microdosimetric calculations of 131I have been evaluated for a single cell and for cell clusters. A VsBasic program has been used to calculate stopping power, linear energy transfer, range values and deposited energies per decay for beta particles, Auger and conversion electrons of 131I. The chemical composition of the cell has been taken into account in this model; results were compared with water medium. Besides, total absorbed doses have been calculated for the radionuclides distributed randomly within the cell and clusters. Cross-fire irradiation has been considered for clusters of cells. In this case, absorbed doses per cell within a cluster were found to be significantly higher than absorbed doses per single cell, depending on the cluster size. Results showed that 131I is a promising radionuclide for therapy of tumors from millimeter to centimeter dimensions.

Iodine Radioisotopes↗