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At least 1,639 records · Page 91Linked to original sources
PubMed1994

Design of dosage regimens: a multiple model stochastic control approach.

This paper presents a general stochastic control framework for determining drug dosage regimens where the sample times, dosing times, desired goals, etc., occur at different times and in an asynchronous fashion. In the special case of multiple models with linear dynamics and quadratic cost (MMLQ), it is shown that the optimal open-loop stochastic control with linear control/state constraints can be solved exactly and efficiently as a quadratic program. This provides a simple and flexible method for computing open-loop feedback designs of drug dosage regimens. An implementation of the MMLQ adaptive control approach is demonstrated on a Lidocaine infusion process. For this example, the resulting MMLQ regimen is more effective than the MAP Bayesian regimen at reducing interpatient variability and keeping patients in the therapeutic range.

Drug Administration Schedule↗
PubMed1987

A programmable-delay line.

A relatively simple circuit is described which delays audio signals in 5 microseconds steps from 0 microsecond to 4000 microseconds. Delays are programmed via twelve TTL-level data lines. The magnitude response is flat and the phase response is linear from DC to 5 kHz. The gain of the circuit is fixed and independent of the selected delay. Delays are accurate to within 1 microsecond of the programmed value. The device is a nice alternative to other methods which have diverse shortcomings.

Acoustic Stimulation↗
PubMed1983

Capillary GLC assay for carbinoxamine and hydrocodone in human serum using nitrogen-sensitive detection.

Capillary gas chromatography using an open tubular fused silica column and NP-FID was applied to the simultaneous analysis of the antihistamine, carbinoxamine, and the antitussive, hydrocodone, in human serum. Carbinoxamine and hydrocodone were extracted into methylene chloride-2-propanol (9:1) under alkaline conditions along with their respective internal standards, brompheniramine and N-ethylhydrocodone. The basic drugs were back-extracted into 0.1 N sulfuric acid and reextracted into benzene after making the aqueous phase alkaline with potassium hydroxide. The benzene extracts were evaporated to dryness and the residues were reconstituted with 40 microliter of n-nonyl alcohol-methanol (19:1). Samples (1-2 microliter) were injected onto the capillary column in the splitless mode (solvent effect) at 185 degrees and the temperature programmed to 250 degrees. Calibration curves using spiked serum standards were linear to at least 20 ng/ml for both drugs. Coefficients of variation averaged +/- 6.1% for carbinoxamine and +/- 5.0% for hydrocodone in the 2-15 ng/ml range. Sensitivity was estimated to be approximately 0.2 ng/ml for a 2-ml serum sample. Serum levels of carbinoxamine and hydrocodone were determined in a human volunteer administered these drugs.

Administration, Oral↗
PubMed1995

Computerized consensus diagnosis: a classification strategy for the robust analysis of MR spectra. I. Application to 1H spectra of thyroid neoplasms.

We introduce and apply a new classification strategy we call computerized consensus diagnosis (CCD). Its purpose is to provide robust, reliable classification of biomedical data. The strategy involves the cross-validated training of several classifiers of diverse conceptual and methodological origin on the same data, and appropriately combining their outcomes. The strategy is tested on proton magnetic resonance spectra of human thyroid biopsies, which are successfully allocated to normal or carcinoma classes. We used Linear Discriminant Analysis, a Neural Net-based method, and Genetic Programming as independent classifiers on two spectral regions, and chose the median of the six classification outcomes as the consensus. This procedure yielded 100% specificity and 100% sensitivity on the training sets, and 100% specificity and 98% sensitivity on samples of known malignancy in the test sets. We discuss the necessary steps any classification approach must take to guarantee reliability, and stress the importance of fuzziness and undecidability in robust classification.

Adenocarcinoma, Follicular↗
PubMed2005

Association of free-prostate specific antigen subfractions and human glandular kallikrein 2 with volume of benign and malignant prostatic tissue.

BACKGROUND: We investigated the association of different subfractions of prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2), such as total PSA (tPSA), complexed PSA (cPSA), free PSA (fPSA), "single-chain Intact fPSA" (fPSA-I), "multi-chain nicked fPSA" (fPSA-N), and total hK2 with volumes of total prostate gland, transition zone (tz), and prostate cancer (PCa) tissue in patients with benign and malignant prostatic disease. METHODS: Serum samples were collected from men with negative biopsy (n=164) and PCa (n=252). Total and fPSA were measured using a commercially immunoassay. We measured hK2 and fPSA-I by previously reported in-house research assays specific for hK2 and single-chain, non-cleaved fPSA, respectively. Levels of fPSA-N (=fPSA-fPSA-I) and cPSA (=tPSA-fPSA) were calculated. Total prostate and tz volume were measured using transrectal ultrasound (TRUS); PCa volume was calculated using a computer assisted volumetric program. Association with tz and cancer volumes (CaVols) was performed by linear regression analysis. RESULTS: All PSA subfractions and hK2 were associated with tz volume in multivariable linear regression analysis. Only hK2, fPSA, and fPSA-N were significantly associated with CaVol in multivariable analysis, fPSA-I seemed to be cancer related. CONCLUSIONS: The multi-chain fPSA-N subfractions of fPSA may be a valuable predictor of both benign prostate hyperplasia (BPH) and CaVol that is likely to be more useful in predicting tz volumes than CaVols. fPSA-I may provide information on cancer without being influenced by the presence of BPH.

Aged↗
PubMed1984

Coupled transcription--translation in extracts of Streptomyces lividans.

A coupled transcription-translation system has been developed using extracts of Streptomyces lividans. Analysis by polyacrylamide gel electrophoresis revealed that proteins of the expected sizes were produced in systems programmed by pBR 322 or the Streptomyces plasmid pIJ 350. Also, linear forms of these plasmids retained template activity with no apparent loss of fidelity.

Bacterial Proteins↗
PubMed2002

Use of DRYLAB to compare octadecylsilane and carbon supports for reversed-phase chromatography of triazine herbicide test solutes.

One of the most important aspects of method development in reversed-phase high-performance liquid chromatography (RPLC) is the accurate prediction of the resolution as one or more experimental variables (usually the mobile-phase composition) are changed. By use of commercially available computer simulation programs, e.g. Drylab 2000, data from a few initial experimental runs are used to predict how the separation will vary with composition so that a computer program can then rapidly locate the optimum conditions. Assumption of a linear relationship between log k' (retention factor) and phi (volume fraction of organic modifier in the element) minimizes the number of initial runs required for a separation and is usually adequate when the range of phi is not large. In this work the linearity of plots of log k' against phi for octadecylsilane-coated silica (ODS) and carbon-coated zirconia (C-ZrO(2)) columns were compared and the plots were used to determine whether prediction of the separation of triazine herbicides was adequate. Analysis of the slopes and intercepts of such plots are presented for both types of columns.

Chromatography, High Pressure Liquid↗
PubMed2005

A clinical evaluation of the image quality computer program, CoCIQ.

To provide an objective way of measuring image quality, a computer program was designed that automatically analyzes the test images of a contrast-detail (CD) phantom. The program gives a quantified measurement of image quality by calculating an Image Quality Figure (IQF). The aim of this work was to evaluate the program and adjust it to clinical situations in order to find the detectable level where the program gives a reliable figure of the contrast resolution. The program was applied on a large variety of images with lumbar spine and urographic parameters, from very low to very high image qualities. It was shown that the computer program produces IQFs with small variations and there were a strong linear statistical relation between the computerized evaluation and the evaluation performed by human observers (R2= 0.98). This method offers a fast and easy way of conducting image quality evaluations.

Data Display↗
PubMed1983

Microprocessor assisted handling of oestrogen receptor assays.

The use of an Apple II microcomputer equipped with a light-pen for interactive analysis of steroid receptor data is described. Processing times have been reduced to less than 5 minutes per patient from around 45-60 minutes by the manual method. Graphical outputs using full and part data sets with derived results are printed for subsequent verification by the Consultant Medical Biochemist. Data processing backlogs have been completely eliminated by this system. The program has, of course, general applicability to any analyses producing a linear correlation between the x and y parameters, and its use in oestrogen receptor analysis is detailed principally because of a considerable and increasing demand for such assays in our department.

Biopsy↗
PubMed1992

A personal computer-based spike detector and sorter: implementation and evaluation.

Many studies of neuronal activity require isolation of the extracellular wave form (spike) of a single neuron from the potentials generated by nearby cells. A variety of methods for spike sorting exists, but most are expensive and require specialized hardware and software. Moreover, there is no easy and objective way for evaluating and comparing the performance of spike sorting devices. We describe here a system for on-line spike sorting that is implemented on an IBM PC/AT computer using commercially available hardware and C-language software. Spikes are detected after crossing an amplitude threshold and are sorted or rejected by template matching. The templates are constructed in a learning phase, using a fast manual sorting of all detected spikes. Later, each detected spike is matched against all defined templates. A detected spike which does not match any template, or matches more than one, is rejected. A continuous display of the wave forms of the last 256 sorted, double-matched, and rejected spikes is used as the main tool for parameter adjustment and error detection. Also described is a new and highly versatile tool for generating appropriate wave forms for critical evaluation of sorter performance. Using the same hardware and software tools, a simulation program mimics the extra-cellular activity of several neurons by linear combination of two vectors and added random noise. The size, shape and the variability of the action potential, as well as its firing pattern, can be adjusted. Comparison of the sorter output with the known simulated activity is used to examine the sorter performance and limitations.

Action Potentials↗
PubMed1985

Computational statistics for cell survival curves. I. Evaluation of the colony-forming ability of a single cell strain by the APL function CFALINE.

An interactive program for the statistical analysis of cell survival curves by a linear regression approach is described. It allows for the computational determination of the linear part of a cell survival curve and the determination of a common slope estimate in the presence of repeated experiments for a particular cell strain with the appropriate variance estimates and confidence intervals.

Biometry↗
PubMed1993

Radiation resistance of primary clonogenic blasts from children with acute lymphoblastic leukemia.

PURPOSE: Detailed comparative analyses of the radiation sensitivity of primary clonogenic blasts from children with acute lymphoblastic leukemia (ALL) were performed to achieve a better understanding of clinical radiation resistance in ALL. METHODS AND MATERIALS: The radiation sensitivity of primary clonogenic blasts from 74 children with newly diagnosed acute lymphoblastic leukemia (ALL) was analyzed using leukemic progenitor cell (LPC) assays. Primary bone marrow blasts from all 74 patients were exposed to ionizing radiation and subsequently assayed for LPC-derived blast colony formation. Radiation survival curves of primary clonogenic blasts (i.e., LPC) were constructed for each of the newly diagnosed patients using computer programs for the single-hit multitarget as well as the linear quadratic models of cell survival. RESULTS: A marked interpatient variation in intrinsic radiation sensitivity was observed between LPC populations. The SF2 values ranged from 0.01 to 1.00 (median: 0.36; mean +/- SE = 0.40 +/- 0.03), and the alpha values ranged from 0.00 Gy-1 to 3.27 Gy-1 (median: 0.280 Gy-1; mean +/- SE = 0.43 +/- 0.09 Gy-1). Patients were divided into groups according to their sex, age, WBC at diagnosis, cell cycle distribution of leukemic blasts, and immunophenotype. Only immunophenotype provided a significant correlation with the intrinsic radiation sensitivity of LPC. Patients with B-lineage ALL had higher SF2 (0.47 +/- 0.04 vs. 0.31 +/- 0.05, p < 0.05) and smaller alpha values (0.43 +/- 0.09 Gy-1 vs. 0.65 +/- 0.10 Gy-1, p < 0.05) than T-lineage ALL patients, consistent with greater intrinsic radiation resistance at the level of LPC. Notably, 43% of B-lineage ALL cases, but only 27% of T-lineage ALL cases had LPC with SF2 > or = 0.5. Similarly, 66% of B-lineage ALL cases, but only 37% of T-lineage ALL cases had LPC with alpha values < or = 0.4 Gy-1. Combining the two indicators of radiation resistance, we found that only 34% of the B-lineage ALL patients had none of the two parameters in the respective critical regions (alpha < or = 0.4 Gy-1; SF2 > or = 0.5), while 63% of the T-lineage patients had none (p < 0.05). In multivariate analyses, the immunophenotypic B-lineage affiliation was the only significant predictor of radiation resistance at the level of LPC. Whether alone or in combination, none of the other variables examined, including sex, age, WBC, in vitro plating efficiency, S-phase index, and proliferation index were significantly correlated with the radiation sensitivity or resistance of LPC. CONCLUSION: These results offer unprecedented evidence for an association between composite immunophenotype (viz., B-lineage ALL vs T-lineage ALL) and radiation resistance that may form a basis for modifying radiation conditioning regimens.

Adolescent↗
PubMed2003

Aged-related differences in the attentional cost of pointing movements.

The aim of the present study was to analyze, in children aged 6, 8 and 11, the developmental trend of the attentional cost related to the programming and execution of pointing movements, using a dual-task paradigm. Our results showed that the attentional cost associated to the programming and the first phase of the pointing movement decreased non linearly with age, in particular a plateau between 8 and 11 was observed. This confirmed that the developmental trend of the control of pointing movements is characterized by a no monotonic evolution in which feedforward processes were predominantly used in the younger children, feedback processes were predominantly used in older children (since age 8), and one-line over feedforward processes were used in adults.

Adult↗
PubMed1997

Quantification of the neuromuscular blocking agent rocuronium and its putative metabolite 17-desacetylrocuronium in heparinized plasma by capillary gas chromatography using a nitrogen sensitive detector.

We have developed a sensitive and specific capillary GC (cGC) assay for the quantification of the quarternary aminosteroidal compound rocuronium (roc), a neuromuscular blocking agent, and its putative metabolite 17-desacetylrocuronium (17OH-roc), using 3-desacetylvecuronium (3OH-vec) as an internal standard (I.S.). This novel method has been applied to a pharmacokinetic study with roc, monitoring sixty patients who were classified according to four different body mass index (BMI) groups. The isolation of these drugs from plasma was carried out using a dichloromethane liquid-liquid extraction after ion-pairing of the positively charged ammonium compounds with iodide. To achieve thermal stability, tert.-butyldimethylsilyl-ethers were formed at the 3OH- and 17OH-steroidal positions by reaction with N-methyl-N-(tert.-butyldimethylsilyl)-trifluoroacetamide at 70 degrees C overnight. An automated cGC system fitted with a nitrogen sensitive detector with a specially prepared glass phase bead and a computer controlled data handling system was used to analyze and quantify the compounds, which were separated on a DB1 capillary column with helium as the carrier gas and a temperature program ranging from 120 to 300 degrees C. The method is linear for 50-6400 ng/ml for roc and 80-6400 ng/ml for 17OH-roc. The detection limits were 10 ng/ml for roc and 50 ng/ml for 17OH-roc. The lower limit of quantification was 50 ng/ml for roc and 80 ng/ml for 17OH-roc. Intra-assay coefficients of variation (C.V.s) were 10% and 15% and the inter-assay C.V.s 8-18% and 16-21% for roc and 17OH-roc, respectively.

Androstanols↗
PubMed1997

Prediction of distribution coefficient from structure. 1. Estimation method.

A method has been developed for the estimation of the distribution coefficient (D), which considers the microspecies of a compound. D is calculated from the microscopic dissociation constants (microconstants), the partition coefficients of the microspecies, and the counterion concentration. A general equation for the calculation of D at a given pH is presented. The microconstants are calculated from the structure using Hammett and Taft equations. The partition coefficients of the ionic microspecies are predicted by empirical equations using the dissociation constants and the partition coefficient of the uncharged species, which are estimated from the structure by a Linear Free Energy Relationship method. The algorithm is implemented in a program module called PrologD.

Algorithms↗
PubMed2004

A method for material parameter determination for the human mandible based on simulation and experiment.

In cranio-maxillofacial surgery planning and implant design, it is important to know the elastic response of the mandible to load forces as they occur, e.g., in biting. The goal of the present study is to provide a method for a quantitative determination of material parameters for the human jaw bone, whose values can, e.g., be used to devise a prototype plastic model for the mandible. Non-destructive load experiments are performed on a cadaveric mandible using a specially designed test bed. The identical physiological situation is simulated in a computer program. The underlying mathematical model is based on a two component, linear elastic material law. The numerical realization of the model, difficult due to the complex geometry and morphology of the mandible, is via the finite element (FE) method. Combining the validated simulation with the results of the tests, an inverse problem for the determination of Young's modulus and the Poisson ratio of both cortical and cancellous bone can then be solved.

Algorithms↗
PubMedDate not supplied

Combined effects in toxicology--a rapid systematic testing procedure: cadmium, mercury, and lead.

A testing procedure is described for the assessment of the toxicological response (e.g., acute toxicity or mutagenicity) of any combination and number of chemical, physical, and biological agents, with no more effort for a particular combination than for a single agent. The method provides a simple, sensitive, and quantitative index of synergism, antagonism, and additivity, and it has been demonstrated experimentally in rats by determining the acute lethality of combinations of cadmium, mercury, and lead salts. In a combination of two metal salts, the dose of one metal of the pair was fixed at or near the no-effect level while the dose of the second metal was increased until the entire dose-response curve was obtained. To evaluate interactions of the three metals, the previous pair of metals were kept fixed at their combined extrapolated LD1 level, and the third metal was increased. The statistical treatment of the data employed a computer program that did not involve probit transformations, but rather the approximate linear relationship between the fractional response and the logarithm of the dose. A particular combination could be synergistic, antagonistic, or additive, depending on the relative doses employed. Generally, a combination was synergistic when the most toxic member was present at or near its LD1 dose in the presence of the much less toxic member; the same combination was protective when the least toxic member was present at or near its LD1 dose. The results clarify apparently contradictory reports regarding the biological effects of metal combinations. The application of the testing procedure to combinations of mutagens is described, and an example is cited involving, for a particular bacterial mutagen, a combination of N-methyl-N'-nitro-N-nitrosoguanidine with ethylmethanesulfonate.

Animals↗
PubMed1984

A gas and vapor generation system with programmed automatic cyclic output.

This paper describes a gas and vapor generation system that can be programmed to produce contaminant concentrations that are variable with time and that are repeatable. The system utilizes an electromechanical programmer designed to vary a potentiometer in accordance with variations in a program curve manually etched in the surface of a special program card. The output of this programmer is interfaced with a linear mass flow controller which will control either the contaminant stream or the dilution air stream to achieve the desired range of contaminant concentrations. The results of some experiments with carbon monoxide and toluene show repeatability of one to three percent for periodically repeated cycles, and demonstrate the flexibility of the system.

Air Pollutants↗