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PubMed1984

Simplified computer programs for search of homology within nucleotide sequences.

Four new computer programs for search of homology within nucleotide sequences are presented. The main scope of the program design is flexibility, independence of sequence length and the capability to be used by any molecular biologist without any prior computer experience. The programs offer a linear search, a search for maximal identity, an alignment along a given sequence and a search based on homology within the amino acid coding capacity of nucleotide sequences. The language is Fortran V. Copies are available on request.

Amino Acid Sequence↗
PubMed1992

Changing patterns in reported sexual practices in the population: multiple partners and condom use.

OBJECTIVE: To determine whether the pattern of change with regard to condom use and multiple sexual partners is influenced by gender or educational level. DESIGN: Findings from data collected from 1987 to 1990 about changes in condom use and multiple-partner activities are presented, based on telephone interviews with 9416 participants aged 18 to 44 years resident in central Scotland, UK. METHODS: Change in patterns over time were modelled in a multivariate logistic regression using a linear interactive modelling program. RESULTS: Several models showing changes in the proportion of multiple-partner respondents and condom users yielded a complicated pattern of behavioural change in educational status and gender. CONCLUSIONS: There is a large difference in reported condom use and multiple sexual partners by gender, but the difference is decreasing over time. Better educated respondents increased their use of condoms while less educated respondents showed a decrease in the proportion of multiple partners.

Adolescent↗
PubMed1992

Evaluation of a dual-channel full dynamic range compression system for people with sensorineural hearing loss.

This article describes an evaluation of an in the ear hearing aid, which applies fast-acting full dynamic range compression independently in two frequency bands. This can compensate for the loudness recruitment typically associated with sensorineural hearing loss. The crossover frequency between the two bands and the gain and compression ratio in each band are programmable to suit the individual patient. Twenty subjects with moderate sensorineural hearing loss were tested in a counterbalanced order using the aid programmed as a linear amplifier (condition L) and as a two-band compressor (condition C). All subjects were fitted binaurally. Subjects were also tested without hearing aids (condition U) and using the hearing aids that they normally wore (condition Own). Speech intelligibility was measured in quiet at three sound levels (50, 65, and 80 dB SPL), and speech reception thresholds (SRTs) in 12-talker babble were measured under monaurally and binaurally aided conditions, with the speech and babble both coincident and spatially separated. In condition C, speech intelligibility in quiet was high at all sound levels. Speech intelligibility at the two lower levels decreased in condition L, and decreased still further in conditions Own and U. Condition C gave, on average, better speech intelligibility in babble (lower SRTs) than conditions L, Own, or U. The advantage of condition C over condition L varied across subjects and was correlated with the dynamic range for tones at high frequencies; small dynamic ranges were associated with greater benefit from compression. A significant advantage for binaural aiding was found both when the speech and noise were spatially separated and when they were coincident. The binaural advantage was similar for the C and L conditions, indicating that the independent compression at the two ears did not adversely affect the use of binaural cues. Questionnaires on the subjects' experiences with the aids in everyday life indicated that they generally preferred condition C over condition L.

Adult↗
PubMed1990

The evaluation of a gastric bile probe.

The purpose of this study was to validate a new technique for measuring duodenogastric bile reflux in the human subject. A custom built cadmium telluride gamma detector (Radiation Monitoring Devices, Mass), small enough to be passed into the oesophagus and stomach, was developed and tested for sensitivity to 99Tcm and 75Se radioisotopes. When immersed in radiolabelled water, the detector was capable of measuring gamma radiation in quantities as low as 0.1 microCi (0.0037 MBq) per ml. Two patients (A and B) with endoscopically proven bile reflux, and three normal volunteers (C, D and E) underwent oesophageal manometry to map the position of the lower oesophageal sphincter (LOS). The gamma probe was passed via the nose, to a position in the gastric fundus, 5 cm below the LOS. Each subject was placed supine under a gamma camera (Siemens LFOV 37 ZLC head), centred on the epigastrium. A 4 mCi (148 MBq) dose of radiolabelled 99Tcm-HIDA was administered intravenously, and simultaneous internal/external scanning was performed for between 45 and 90 min. Internal gamma probe data was transferred by a screened cable to a Memolog 600 portable recorder, using a 5 s counting interval, and from the gamma camera to a Nodecrest Micas III computer, using a 15 s counting interval. Gamma camera counts from a region of interest over the fundus of the stomach were then correlated with counts from the internal probe using a linear regression analysis program on the Nodecrest. The internal gamma probe functioned well at body temperature in the acidic gastric environment. Radiolabelled bile refluxed into the stomach during HIDA scanning in three out of the five subjects (one patient and two normal volunteers). There was a strong correlation between internal and external gamma counts (A, r = +0.79; C, r = +0.53; E, r = +0.54; P greater than 0.01). In the other two cases, there was no bile reflux, but still a significant correlation between internal and external gamma counts (B, r = +0.89; D, r = +0.75; P greater than 0.01). The mean correlation coefficient for the series of five cases was +0.70. We conclude firstly that the newly developed internal gamma detector is capable of measuring the reflux of radiolabelled bile into the human stomach and, secondly, that bile reflux may occur in normal subjects as well as those with upper gastrointestinal pathology.

Aged↗
PubMed2004

Dose adjustment strategy for oral microemulsion formulation of cyclosporine: population pharmacokinetics-based analysis in kidney transplant patients.

The present study aims to determine the population pharmacokinetic parameters of cyclosporine (CsA) after multiple oral administration of the microemulsion formulation, Neoral, in kidney transplant patients and to propose a limited sampling strategy to predict AUC(0-4h) using them and the Bayesian method. The AUC(0-4h) is a parameter that has recently been recommended as an index for the dose adjustment in therapeutic drug monitoring of CsA. Blood samples were obtained at the trough level and at hourly intervals up to 5 hours from 125 patients (78 male and 47 female) who were receiving Neoral twice daily, and whole-blood concentrations of CsA were measured. The population pharmacokinetic parameters were estimated using the NONMEM computer program and a linear two-compartment model with first-order absorption. The observed AUC0-4h and concentrations at different sampling times were compared with those computer-predicted by the Bayesian method, using the population pharmacokinetic parameters and 2 or 3 concentrations from those at 0 h (C(0)), 1 h (C(1)), and 2 h (C(2)) after administration. Typical values for the absorption rate constant (k(a)), elimination rate constant (k(el)), apparent volume of distribution for the central compartment (Vd/F), and oral clearance (CL/F) calculated by population pharmacokinetic analysis were 2.16 hours(-1), 0.547 hours(-1), 43.3 L, and 23.7 L/h, respectively. The CsA concentrations predicted using either the 2-point or 3-point sampling strategy exhibited an excellent correlation with the observed values (R(2) > 0.81), and accordingly, the predicted AUC(0-4h) values were in excellent agreement with those observed. The best predictability of AUC(0-4h) was found for the 3-point sampling strategy using C(0), C(1), and C(2), closely followed by a 2-point sampling strategy using C(1) and C(2). The present findings suggest that a simplified strategy based on population pharmacokinetics can accurately predict AUC(0-4h) from concentrations at 2 or 3 sampling time points, providing an excellent method for the daily dose adjustment of Neoral in routine clinical use for kidney transplant patients.

Administration, Oral↗
PubMed1983

Influence of race on the predictability of mixed lymphocyte culture identity by HLA-DR matching.

HLA-DR-identical North American individuals of Caucasian, black, and Asian Indian origin were tested in checkerboard mixed lymphocyte cultures (MLCs) and the distribution of negative (weak), intermediate, and positive (strong) MLC reactions was determined using the linear clustering analysis program. Overall, the data show that the frequency of weak MLC reactions is significantly higher when the HLA-DR-identical responder-stimulator pair derives from the same ethnic group than when they are of different ethnic origin. Caucasians responded stronger to blacks than to Asian Indians; blacks responded stronger to Asian Indians than to Caucasians, while Asian Indians responded stronger to blacks than to Caucasians. The fact that the frequency of MLC identity is greater among HLA-DR-identical individuals of similar as opposed to different ethnic origin suggests that the predictability of successful transplants by HLA-DR matching may be also influenced by the ethnic background of the donor.

Black People↗
PubMedDate not supplied

Educating to manage the accelerated change environment effectively: Part 1.

Without appropriate educational preparation, nurse managers may not have the competencies to effectively manage accelerated change that is so pervasive on the front lines of healthcare organizations in transformation. Part 1 of this article describes the findings from an extensive literature review of nursing, business, and higher education literature on the subject of change management. A comprehensive reference list is provided. Part 2 reports the results of a Delphi study from which baccalaureate-prepared nurse manager experts and nurse educator experts in baccalaureate nursing programs validated what linear and nonlinear change management concepts they believed were relevant in managing change in today's dynamic environment. With key roles as organizational change agents, staff development educators and administrators can use the validated concepts to develop educational offerings to promote effective change management.

Curriculum↗
PubMedDate not supplied

Educating to manage the accelerated change environment effectively: Part 2.

Without appropriate educational preparation, nurse managers may not have the competencies to manage accelerated change effectively. Part 1 of this two-part series provided the condensed findings from an extensive review of nursing, business, and higher education literature. Part 2 describes the results of a Delphi study whereby baccalaureate-prepared nurse manager experts and nurse educator experts in baccalaureate nursing programs validated what linear and nonlinear change management concepts they believed were relevant in managing change in today's dynamic environment. Staff development educators and administrators, as organizational change agents, can use the validated concepts to develop educational offerings to promote effective change management.

Adult↗
PubMed2005

Estimating the genetic component (RGC) in pharmacokinetic variability of the antiretroviral didanosine among healthy Brazilians.

BACKGROUND: We estimate the variance between between- and within-subjects, using mixed effect models, as a way to assess the genetic component in explaining the observed heterogeneity of ddl kinetics among healthy individuals. Our work expands on a previous reported method known as RGC. METHODS: Repeated measurements of ddl concentration in the serum were obtained from 48 healthy adult volunteers enrolled in two bioequivalence study. We use the NONMEM program (Non-linear Mixed Effect Model) to estimate the between- and within-subject variability and the corresponding pharmacokinetic parameters. We assess the genetic contribution to the variability of each pharmacokinetic parameter through the RGC method. RESULTS: Pharmacokinetic parameters, expressed as functions of covariates gender and creatinine clearance (CLCR), were: Oral clearance (CL = 55.1 + 240 * CLCR + 16.6 l/h for male and CL = 55.1 + 240 * CLCR for female), central volume (V2 = 9.82), inter-compartmental clearance (Q = 40.90/h), peripheral volume (V3 = 62.7 + 22.90 for male and V3 = 62.70 for female), absorption rate constant (Ka = 1.51 h(-1)) and duration of the dose administration (D = 0.44 h). The RGC of CL, Q, V3, Ka and D were 0.58, 0.97, 0.60, 0.53 and 0.88, respectively. CONCLUSION: We estimated parameter-specific RGC indices and rank them according to the potential genetic contribution as an explanation for the observed variance. Our study design improved precision by decreasing background noise and, thus, improved the chances that indices such as the RGC are in fact describing genetic variability.

Adult↗
PubMed2000

Interior-point methodology for 3-D PET reconstruction.

Interior-point methods have been successfully applied to a wide variety of linear and nonlinear programming applications. This paper presents a class of algorithms, based on path-following interior-point methodology, for performing regularized maximum-likelihood (ML) reconstructions on three-dimensional (3-D) emission tomography data. The algorithms solve a sequence of subproblems that converge to the regularized maximum likelihood solution from the interior of the feasible region (the nonnegative orthant). We propose two methods, a primal method which updates only the primal image variables and a primal-dual method which simultaneously updates the primal variables and the Lagrange multipliers. A parallel implementation permits the interior-point methods to scale to very large reconstruction problems. Termination is based on well-defined convergence measures, namely, the Karush-Kuhn-Tucker first-order necessary conditions for optimality. We demonstrate the rapid convergence of the path-following interior-point methods using both data from a small animal scanner and Monte Carlo simulated data. The proposed methods can readily be applied to solve the regularized, weighted least squares reconstruction problem.

Algorithms↗
PubMed1978

Quantitation of HLA-D differences.

The predictability of MLC non-reactivity by HTC typing was tested in a single checkerboard experiment which involved 39 unrelated individuals belonging to 12 different groups of HLA-D identical phenotypes. The strength of one-way MLC reactions in all possible responder-stimulator combinations (39 X 39) was quantitated by the Linear Clustering Analysis Program. Individuals who, by HTC typing, were identical for two HLA-D antigens gave 51% negative, 36% intermediate and 13% strong positive MLC responses. Identity for only one HLA-D antigen resulted in 3% negative, 40% intermediate and 57% strong MLC reactions. When no HLA-D antigen was shared, 88% of the reactions were strongly positive. HLA-D antigens behaved as equipotent stimulators in MLC between half-identical pairs. The only exception consisted of the higher frequency of weak responses displayed by the Dw5 positive individuals against stimulators differing by LD107. The same pattern was observed when LD107 homozygous cells were used as stimulators, suggesting that determinants of this specificity might be partially included in Dw5.

Epitopes↗
PubMed1993

Inorganic phosphate compartmentation in the normal isolated canine brain.

In vivo 31P magnetic resonance spectra of 16 isolated dog brains were studied by using a 9.4-T wide-bore superconducting magnet. The observed Pi peak had an irregular shape, which implied that it represented more than one single homogeneous pool of Pi. To evaluate our ability to discriminate between single and multiple peaks and determine peak areas, we designed studies of simulated 31Pi spectra with the signal-to-noise (S/N) ratios ranging from infinity to 4.4 with reference to the simulated Pi peak. For the analysis we used computer programs with a linear prediction algorithm (NMR-Fit) and a Marquardt-Levenberg nonlinear curve-fit algorithm (Peak-Fit). When the simulated data had very high S/N levels, both methods located the peak centers precisely; however, the Marquardt-Levenberg algorithm (M-L algorithm) was the more reliable at low S/N levels. The linear prediction method was poor at determining peak areas; at comparable S/N levels, the M-L algorithm determined all peak areas relatively accurately. Application of the M-L algorithm to the individual experimental in vivo dog brain data resolved the Pi peak into seven or more separate components. A composite spectrum obtained by averaging all spectral data from six of the brains with normal O2 utilization was fitted using the M-L algorithm. The results suggested that there were eight significant peaks with the following chemical shifts: 4.07, 4.29, 4.45, 4.62, 4.75, 4.84, 4.99, and 5.17 parts per million (ppm). Although linear prediction demonstrated the presence of only three peaks, all corresponded to values obtained using the M-L algorithm. The peak indicating a compartment at 5.17 ppm (pH 7.34) was assigned to venous pH on the basis of direct simultaneous electrode-based measurements. On the basis of earlier electrode studies of brain compartmental pH, the peaks at 4.99 ppm (pH 7.16) and 4.84 ppm (pH 7.04) were thought to represent interstitial fluid and the astrocyte cytoplasm, respectively.

Adenosine Triphosphate↗
PubMed1990

Evaluation of protein binding effect on local disposition of oxacillin in rat liver by a two-compartment dispersion model.

The effect of protein binding upon the hepatic uptake of oxacillin was evaluated in the rat isolated perfused liver, based on the two-compartment dispersion model by means of the fast inverse Laplace transform (FILT). The perfusion experiment was carried out using the perfusates without and with bovine serum albumin (BSA, 40 g L-1). Oxacillin was injected as a pulse through the portal vein, and the outflow concentration-time course of oxacillin was fitted to the dispersion model using the non-linear least squares program MULTI(FILT). The partition ratio (k'), which is the measure of the extent of the reversible distribution into the hepatic tissue, was 0.163 +/- 0.041 (s.d.) in the presence of BSA, and 0.095 +/- 0.018 in the absence of BSA, which suggests interaction of the albumin-bound drug with the hepatic tissue. The elimination rate constant (ke) from the perfusate in the absence of BSA was 8.0 +/- 0.55 min-1 and that in the presence of BSA was 3.3 +/- 1.4 min-1 while the unbound fraction of the drug in the presence of 40 g L-1 BSA was 0.282. The hepatic elimination rate of oxacillin was not proportional to the unbound concentration of drug suggesting hepatic uptake of the bound fraction.

Animals↗
PubMed1997

Study of the effective dose of a topical antifungal agent, omoconazole nitrate, on the basis of percutaneous pharmacokinetics in guinea-pigs and mice.

The clinically useful optimum dose of omoconazole nitrate, a topical antifungal agent, has been examined by analysing the percutaneous pharmacokinetics of the drug to assess its pharmacological activity in an in-vivo study. Creams containing omoconazole nitrate were prepared on a pilot basis. The therapeutic effect of the omoconazole nitrate creams was examined in an in-vivo pharmacological dermatophytosis infection model in guinea-pigs. Creams containing 0.25% or higher concentrations of omoconazole nitrate resulted in significant inhibition compared with no treatment and with vehicle-treated controls. In the mycological examination no growth of dermatophytes was observed for creams containing 1% or higher concentrations. In an in-vitro hairless mouse skin-permeability test a non-linear least squares program based on a fast inverse Laplace transform algorithm was used to calculate the partition and diffusion parameters of omoconazole nitrate in the stratum corneum and viable epidermis. The time-course of drug concentrations in the skin of the guinea-pig, estimated on the basis of these parameters, led to predictions that percutaneous drug concentrations on the guinea-pig would require 10 or more days to reach equilibrium in the skin; that drug concentrations in the corneum-viable epidermis border, where dermatophytes are considered to grow, would exceed the minimum effective concentration when 0.1% higher concentration creams were used; and that for binding to keratin drug concentrations would reach the practical minimum effective concentration when creams containing 0.5% or more omoconazole nitrate were used. These results show that partition and diffusion parameters obtained from in-vitro skin permeation studies can be used to predict in-vivo percutaneous pharmacokinetics and to estimate therapeutically effective concentrations.

Administration, Topical↗
PubMed1998

Evaluation of a diode detector array for use as a linear accelerator QC device.

A series of tests were conducted to evaluate the accuracy of a diode detector array in measuring flatness and symmetry of x-ray and electron energies, and the ability to determine change in beam energy. The results show the diode detector array accurately measures flatness and symmetry and can accurately measure or detect change in beam energy. The evaluation also demonstrates the utility of using this model detector system in a linear accelerator QC program.

Biophysical Phenomena↗
PubMed1995

Convergent evolution within the V3 loop domain of human immunodeficiency virus type 1 in association with disease progression.

Phylogenetic analysis was used to study in vivo genetic variation of the V3 region of human immunodeficiency virus type 1 in relation to disease progression in six infants with vertically acquired human immunodeficiency virus type 1 infection. Nucleotide sequences from each infant formed a monophyletic group with similar average branch lengths separating the sets of sequences. In contrast to the star-shaped phylogeny characteristic of interinfant viral evolution, the shape of the phylogeny formed by sequences from the infants who developed AIDS tended to be linear. A computer program, DISTRATE, was written to analyze changes in DNA distance values over time. For the six infants, the rate of divergence from the initial variant was inversely correlated with CD4 cell counts averaged over the first 11 to 15 months of life (r = -0.87, P = 0.024). To uncover evolutionary relationships that might be dictated by protein structure and function, tree-building methods were applied to inferred amino acid sequences. Trees constructed from the full-length protein fragment (92 amino acids) showed that viruses from each infant formed a monophyletic group. Unexpectedly, V3 loop protein sequences (35 amino acids) that were found at later time points from the two infants who developed AIDS clustered together. Furthermore, these sequences uniquely shared amino acids that have been shown to confer a T-cell line tropic phenotype. The evolutionary pattern suggests that viruses from these infants with AIDS acquired similar and possibly more virulent phenotypes.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Gas exchange and lactate anaerobic thresholds: inter- and intraevaluator agreement.

Twenty-four coded graph sets of gas exchange variables and blood lactate concentration (LA) plotted against time at 15-s intervals were analyzed by nine evaluators who determined the gas exchange (ATGE) and LA (ATLA) anaerobic thresholds. In addition, ATGE and ATLA were determined by a linear regression computer program. Agreement between ATGE and ATLA was poor; the median intraclass correlation coefficient (ri) was 0.53. Among evaluators, ATLA agreement (median ri = 0.81) was better than ATGE agreement (median ri = 0.70). In general, the ability of any evaluator to choose similar values from duplicate plots for either ATGE (median ri = 0.97) or ATLA (median ri = 0.995) was good. There was better agreement between the mean ATLA of the evaluators and the computer ATLA (ComLA) (ri = 0.88) than between the mean ATGE of the evaluators and the computer ATGE (ComVE), (ri = 0.58). Agreement between ComVE and ComLA was poor (ri = 0.29). These results suggest that ATGE does not accurately predict ATLA and that different evaluators choose different thresholds from the same data. Further assessment of the validity and precision of ATGE based on breath-by-breath and minute-by-minute data is needed.

Adult↗
PubMed2006

Optimal vaccination schemes for epidemics among a population of households, with application to variola minor in Brazil.

This paper is concerned with stochastic models for the spread of an epidemic among a community of households, in which individuals mix uniformly within households and, in addition, uniformly at a much lower rate within the population at large. This two-level mixing structure has important implications for the threshold behaviour of the epidemic and, consequently, for both the effectiveness of vaccination strategies for controlling an outbreak and the form of optimal vaccination schemes. A brief introduction to optimal vaccination schemes in this setting is provided by presenting a unified treatment of the simplest and most-studied case, viz. the single-type SIR (susceptible -->infective --> removed) epidemic. A reproduction number R*, which determines whether a trace of initial infection can give rise to a major epidemic, is derived and the effect of a vaccination scheme on R* is studied using a general model for vaccine action. In particular, optimal vaccination schemes which reduce R* to its threshold value of one with minimum vaccination coverage are considered. The theory is illustrated by application to data on a variola minor outbreak in São Paulo, which, together with other examples, is used to highlight key issues related to vaccination schemes.

Brazil↗