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PubMedDate not supplied

The determination of the absolute bioavailability for drug substances with long elimination half-lives (with PC-programs for the method of truncated areas).

A survey is given of the methods for the determination of the absolute bioavailability for drug substances with long elimination half-lives. All methods depend on the assumption of linear pharmacokinetics. Emphasis is laid on Urso and Aarons' regression method of truncated areas-under-the-curve (AUC) to obtain estimates of the absolute bioavailability, F, and the absorption rate constant, ka, without obeying the otherwise general rule of following blood or plasma levels for at least three times the terminal half-life. It is shown by simulation when the linear and when the logarithmic trapezoidal rule is to be used for the calculation of the AUC. Two PC-programs for the regression method of truncated areas are presented: one program (SIMF&KA.EXE) simulates, based on tentative pharmacokinetic parameters, whether a blood sampling scheme, together with the precision of the analytical assay, is adequate to obtain accurate and precise estimates of F and ka; the method is insensitive to large variations in the tentative value of the elimination half-life. The other program (ESTF&KA.EXE) provides estimates of F and ka, with standard deviations of the estimates, from empirical data.

Biological Availability↗
PubMed1998

Evaluation of a cold/flu self-care public education campaign.

The purpose of the study was to evaluate an Ontario Ministry of Health (MOH) cold/flu self-care public education campaign to reduce unnecessary patient visits to doctors. The MOH campaign consisted of an information booklet delivered to every household in an Ontario city, newspaper ads and radio spots. The program ran during January-March 1994. The evaluation consisted of: (1) 2x2 telephone survey in London (experimental area) and Windsor (comparison area), before and during the campaign; and (2) a telephone survey of London family practitioners during the campaign. In addition, data on the incidence of cold/flu visits to three hospital emergency departments and a sample of family physicians' offices were gathered. The data suggest that program rationale may have been questionable because the majority of the surveyed public were knowledgeable and self-reported appropriate doctor visits for cold/flu. Campaign evaluation showed limited impact. Message penetration was low; only one-third of London residents knew of the campaign or read the booklet. Only two of 10 questions showed increases in knowledge in London and no changes were found for beliefs, attitudes, acquisition of new health practices or self-reported visits to the doctor. The physician survey, emergency room and family physician office visit data were consistent with the public survey findings.

Adult↗
PubMed1981

Statistical package for analysis of competition ELISA results.

A computation and analysis program has been assembled to facilitate the use of competition ELISA and similar assays for studies of antigen regulation and turnover. The program fits sigmoidal standard curves using a 4-parameter logistic function, determines amounts of antigen from the equation which defines the standard curve, and calculates specific activities by linear regression of the levels of antigen in varying amounts of total protein. An optional weighting function is provided to adjust for systematic non-uniform variance. Outlying points are identified during the linear regression, and the user may delete them or redefine the acceptable working range of the standard curve. The program provides a complete print-out of the data and optional plots of the fitted standard curve and the regression analysis of the samples, as well as statistics which are useful for quality control. It also provides the option of storing the data points from the standard curve on magnetic diskettes. The package is written in BASIC for a Wang Model 2200 computer equipped with a magnetic diskette drive, line printer, and flat-bed X-Y plotter, but it is readily adaptable to other systems and input/output devices.

Antigens↗
PubMed1995

Distribution of linear antigenic epitopes on GP120 encoded in sibling clones of novel New York HIV-1 subtype B isolates.

We have initiated studies to characterize the predominant subtypes of HIV-1 which account for infections in a defined cohort of intravenous (IV) drug addicts. A region of ENV encoding the C2 to the V5 regions was amplified from the leukocytes of two subjects currently enrolled in a methadone maintenance program at the Addiction Research and Treatment Corporation (ARTC), in Brooklyn, New York. This region of the viral genome encodes the principal neutralizing determinant (PND) located in the V3 loop, the immunogenic CD4-binding site, and six other linear antigenic epitopes in the envelope glycoprotein, gp120. Phylogenetic tree analysis of the nucleotide sequences showed that the sibling clones RT1.4, RT1.15, RT1.17, RT1.21 and RT3.6, RT3.10, RT3.11, RT3.12 and RT3.15 derived from the isolates, RT1 and RT3, respectively, cluster with "group B" viruses at 99% confidence level. Marked intra-patient and inter-patient sequence variation was apparent in the V3 loop. The divergence included the presence of a previously unreported hexapeptide GPWGTF at the cap of the loop in the clones from RT1. The North American consensus hexapeptide, GPGRAF, was identified in the cap of the loop from the clones of RT3. Four of the five sibling clones from RT3 were closely related whereas the other clone, RT3.15, displayed five amino acid mutations downstream of the V3 cap. To assess the effect of sequence variation on the distribution of linear antigenic epitopes, complementary computer software programs, were used to analyze the gp120 residues. Eight analogous antigenic epitopes were identified in the clones from both isolates despite the marked divergence in the primary sequences.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1999

Tai chi practice reduces movement force variability for seniors.

BACKGROUND: The purpose of this study was to examine whether Tai Chi practice can reduce the inconsistency of arm movement force output in older adults. METHODS: Twenty seniors took part in the 8-week-long exercise intervention program (12 in Tai Chi practice, M = 79.3 years, SD = 2.4; and 8 in a locomotor activity group, walking or jogging, M = 79.5 years, SD = 1.9). Linear and curvilinear manual aiming movements were tested at the beginning (pretest), during 4th week (retest), and the end of the exercise program (post-test). The measure of vertical pressure on the surface of a tablet served as the dependent variable. RESULTS: The findings suggest that the Tai Chi participants significantly reduce more pressure variability than the participants in locomotor activity group after 8 weeks of practice. Additionally, seniors produced higher pressure variability in the curvilinear task than in the linear task. CONCLUSIONS: Evidence from this study proposes that Tai Chi practice may serve as a better real world exercise for reducing force variability in older adults' manual performance.

Aged↗
PubMed2002

Quantitative evaluation of proteins in one- and two-dimensional polyacrylamide gels using a fluorescent stain.

The characteristics of protein detection and quantitation with SYPRO Ruby protein gel stain in one- and two-dimensional polyacrylamide gels were evaluated. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analyses of three different purified recombinant proteins showed that the limits of detection were comparable to the limits of detection with ammoniacal silver staining and were protein-specific, ranging from 0.5 to 5 ng. The linearity of the relationship between protein level and SYPRO Ruby staining intensity also depended on the individual protein, with observed linear dynamic ranges of 200-, 500-, and, 1000-fold for proteins analyzed by SDS-PAGE. SYPRO Ruby protein gel stain was also evaluated in two-dimensional electrophoretic (2-DE) analysis of Escherichia coli proteins. The experiment involved analysis of replicates of the same sample as well as dilution of the sample from 0.5 to 50 nug total protein across gels. In addition to validating the 2-DE system itself, the experiment was used to evaluate three different image analysis programs: Z3 (Compugen), Progenesis (Nonlinear Dynamics), and PDQuest (Bio-Rad). In each program, we analyzed the 2-DE images with respect to sensitivity and reproducibility of overall protein spot detection, as well as linearity of response for 20 representative proteins of different molecular weights and pI. Across all three programs, coefficients of variation (CV) in total number of spots detected among replicate gels ranged from 4 to 11%. For the 20 representative proteins, spot quantitation was also comparable with CVs for gel-to-gel reproducibility ranging from 3 to 33%. Using Progenesis and PDQuest, a 1000-fold linear dynamic range of SYPRO Ruby was demonstrated with a single known protein. These two programs were more suitable than Z3 for examining individual protein spot quantity across a series of gels and gave comparable results.

Bacterial Proteins↗
PubMed2001

Transient enlargement of contrast uptake on MRI after linear accelerator (linac) stereotactic radiosurgery for brain metastases.

PURPOSE/OBJECTIVE: With the increasing number of patients successfully treated with stereotactic radiosurgery for brain metastases, decision making after therapy based on follow-up imaging findings becomes more and more important. Magnetic resonance imaging (MRI) is the most sensitive means for follow-up studies. The objective of this study was to investigate the treatment outcome of our radiosurgery program and to describe the response of brain metastases to contrast-enhanced MRI after linear accelerator (linac) stereotactic radiosurgery and identify factors to distinguish among local control and local failure. METHODS AND MATERIALS: Using serial MRI, we followed the course of 87 brain metastases in 48 consecutive patients treated between September 1996 and November 1997 with linac-based radiosurgery with 15-MV photons. Treatment planning was performed on an MR data cube. For spherical metastases, radiosurgery was delivered using a 9 noncoplanar arc technique with circular-shaped collimators. For irregularly shaped targets, radiosurgery was delivered using a manually driven multi-leaf collimator with a leaf width of 1.5 mm projected to the isocenter. Median radiosurgery dose was 20 Gy prescribed to the 80% isodose. Together with whole brain radiotherapy (20 x 2 Gy, 5/w), a median radiosurgical dose of 15 Gy was delivered. Median follow-up was 8 (range 2--36) months. Factors influencing local control and survival rates were analyzed with respect to MRI response, and Kaplan-Meier curves were calculated. RESULTS: Actuarial local tumor control was 91% at one and two years. Patient survival at one and two years was 30% and 18%. Median survival was 9 months. During follow-up in 70 (81%) of the 87 treated metastases, the contrast-enhancing volumes on T1W images were stable or disappeared partly or completely. A transient enlargement of contrast-enhancing volumes was observed in 11 (12%) of the 87 lesions treated, while a progressive enlargement due to local treatment failure was observed in 6 (7%) of the 87 treated metastases. Younger age, early contrast onset after radiosurgery, and previous chemotherapy were associated with this transient enlargement of contrast-enhancing lesion volume. CONCLUSIONS: Linac-based radiosurgery is an effective, noninvasive, and safe treatment option for patients with brain metastases. A marked enlargement of the contrast-enhancing volume on T(1)-weighted MR images after radiosurgery is a sensitive predictor for, but not equivalent with, local failure. In as many as two-thirds of the cases with contrast enlargement in MRI follow-up, the contrast enlargement is transient with no need for further treatment. While some MRI findings are more likely if transient enlargement is present, a clear decision cannot be made based on MRI, and ultimately the clinical status dictates further action.

Analysis of Variance↗
PubMed1993

Profile sequence analysis and database searches on a transputer machine connected to a Macintosh computer.

An implementation of Profilesearch (a technique to search for relationships between a protein sequence and multiply aligned sequences) for a parallel computer is described. The number-crunching machine, consisting of 21 T800 transputers, is connected to a Macintosh IIcx host computer. The program utilizes a standard Macintosh application as its user-interface, resulting in a transparent and user-friendly environment for addressing the parallel computer. The program is independent of the number of available processors and exceeds the speed of a VAXstation 3200 with only one transputer in operation, thus allowing cheap and fast database searches with a PC front-end. For a larger number of processors, the speed increase is approximately linear with no obvious symptoms of saturation with the available maximum of 21 transputers. The program and environment are useful to search quickly and easily for similarities between a single sequence or sequence set and individual sequences contained in a large database. The alignment is determined by typical dynamic programming techniques.

Amino Acid Sequence↗
PubMed2004

Adplot: detection and visualization of repetitive patterns in complete genomes.

MOTIVATION: Repetitive DNA sequences are abundant in genomes and efficient mining of significant repeats is important as the first step of repetitive sequence research. Although many computational tools for the purpose, either automatic or visualization ones, have been developed, detection and analysis of approximate repeats are still non-trivial task. RESULTS: Auto Dot PLOT (Adplot), a dotplot-like repetitive pattern visualization program with a window filtering based on iid Bernoulli trials, is developed and applied to yeast chromosomes and human T cell receptor locus sequence. Typical examples found in yeast chromosomes 1 and 10 and a tandem repeat of periods longer than 10,000 bp in human T cell receptor locus are presented. A complex structure composed of both direct and palindromic repeats found in yeast chromosome 10 is also visualized as specific dot pattern. Computational time measured by a Pentium 3 PC for each yeast auto chromosome with a standard parameter setting is linearly scaled and below 10 s per one chromosome, indicating efficiency of the program. From the examples, it is shown that Adplot can visualize approximate local repeat structures and give us a diagnosis power for inferring a duplicational history of repeats. AVAILABILITY: Adplot can be obtained by an e-mail request.

Algorithms↗
PubMed2005

Nuclear re-organisation of the Hoxb complex during mouse embryonic development.

The spatial and temporal co-linear expression of Hox genes during development is an exquisite example of programmed gene expression. The precise mechanisms underpinning this are not known. Analysis of Hoxb chromatin structure and nuclear organisation, during the differentiation of murine ES cells, has lent support to the idea that there is a progressive 'opening' of chromatin structure propagated through Hox clusters from 3'to 5', which contributes to the sequential activation of gene expression. Here, we show that similar events occur in vivo in at least two stages of development. The first changes in chromatin structure and nuclear organisation were detected during gastrulation in the Hoxb1-expressing posterior primitive streak region: Hoxb chromatin was decondensed and the Hoxb1 locus looped out from its chromosome territory, in contrast to non-expressing Hoxb9, which remained within the chromosome territory. At E9.5, when differential Hox expression along the anteroposterior axis is being established, we found concomitant changes in the organisation of Hoxb. Hoxb organisation differed between regions of the neural tube that had never expressed Hoxb [rhombomeres (r) 1 and 2], strongly expressed Hoxb1 but not b9 (r4), had downregulated Hoxb1 (r5), expressed Hoxb9 but not Hoxb1 (spinal cord), and expressed both genes (tail bud). We conclude that Hoxb chromatin decondensation and nuclear re-organisation is regulated in different parts of the developing embryo, and at different developmental stages. The differential nuclear organisation of Hoxb along the anteroposterior axis of the developing neural tube is coherent with co-linear Hox gene expression. In early development nuclear re-organisation is coupled to Hoxb expression, but does not anticipate it.

Animals↗
PubMedDate not supplied

A new approach to optimizing urea clearances in hemodialysis and continuous ambulatory peritoneal dialysis.

Recent studies suggest that the relationship of the net normalized protein catabolic rate (which is the normalized protein equivalent of nitrogen appearance [nPNA]) to the weekly clearance of urea normalized to total body water (Kt/V urea) in patients on continuous ambulatory peritoneal dialysis (CAPD) is curvilinear, rather than linear, as has been thought. The authors have reexamined the relationship of nPNA to weekly Kt/V urea in a CAPD population by cross-sectional analysis to see if the curvilinear definition of the relationship is as good as or better than the usual linear description. They also examined this relationship in the hemodialysis populations at the Dialysis Clinics Inc. in Columbia, Missouri, and in the Renal Kidney Disease Program in Minneapolis, Minnesota. It seems obvious that there should be a plateau of nPNA in each therapy because extension of linear regressions would predict protein intakes of normal individuals exceeding 8 g/kg/body weight/day. The authors compared their findings to other published results. Intuitively and analytically, the curvilinear relationships seem likely. The authors observed that the nPNA plateau is achieved at lower Kt/V in patients on CAPD than in those on hemodialysis, which is compatible with the peak concentration hypothesis. Asymptotes for CAPD and hemodialysis are similar. Weekly Kt/V urea requirements to achieve nPNA values at 95% of the asymptote are greater than those usually delivered. However, such nearly complete elimination of uremic appetite suppression may not be practical or necessary for achieving acceptable nutritional status and long-term survival in most patients. Optimum therapy may be well above adequate therapy relative to minimizing appetite suppression by uremia.

Appetite↗
PubMed1994

Effects of a statewide antismoking campaign on mass media messages and smoking beliefs.

BACKGROUND. In 1985, The Minnesota Legislature initiated a long-term and broad-based program to deter adolescent tobacco use. The initiative was funded by higher taxes on tobacco products and combined school-based programming, mass-media campaigns, and local community grants. The Minnesota-Wisconsin Adolescent Tobacco-Use Research Project was designed to evaluate this effort by monitoring adolescent tobacco use and related factors in Minnesota and Wisconsin from 1986 to 1990. The results presented in this paper indicate that the Minnesota initiative dramatically increased Minnesota schoolchildren's reported exposure to the anti-smoking messages in the mass media but had little effect on smoking-related beliefs or smoking behaviors. CONCLUSIONS. These results, together with the findings from other recent studies, suggest that even dramatic increases in exposure to anti-tobacco messages in the mass-media, in the absence of a substantial and sustained school-based tobacco prevention measures, may be insufficient to generate reductions in adolescent tobacco use.

Adolescent↗
PubMed2001

Effect of a developmental program on motor performance in infants born preterm.

A randomised controlled trial was conducted to evaluate the effect of a motor developmental program in improving motor performance in Thai infants born preterm. Eighty-four preterm born infants were randomly assigned to either a control or intervention group. Additionally, 27 low-risk preterm infants were included forming a comparative group for this study. From term equivalent age to four months adjusted age, all infants had their motor performance assessed monthly with the Test of Infant Motor Performance by one of the physiotherapist research assistants blind to group assignment and infants' adjusted age. In addition, the intervention infants received a developmental program at each monthly visit. Motor performance for each group plotted against age revealed linear trends of progression. The intervention group showed the greatest improvement. Two-way repeated measures ANOVA revealed significant differences across age and among groups. Scheffé comparisons indicated that the mean differences between each pair of the three groups were significant and supported the finding of greater improvement of the intervention infants over the control group. Thus the results suggest that the intervention program is likely to have beneficial effects when offered to a similar population of preterm born infants.

Child Development↗
PubMed1990

Searching for and predicting the activity of sites for DNA binding proteins: compilation and analysis of the binding sites for Escherichia coli integration host factor (IHF).

An analysis of the sequence information contained in a compilation of published binding sites for E. coli integration host factor (IHF) was performed. The sequences of twenty-seven IHF sites were aligned; the base occurrences at each position, the information content, and an extended consensus sequence were obtained for the IHF site. The base occurrences at each position of the IHF site were used with a program written for the Apple Macintosh computers in order to determine the similarity scores for published IHF sites. A linear correlation was found to exist between the logarithm of IHF binding and functional data (relative free energies) and similarity scores for two groups of IHF sites. The MacTargsearch program and its potential usefulness in searching for other sites and predicting their relative activities is discussed.

Bacterial Proteins↗
PubMed2003

Job satisfaction among program directors in obstetrics and gynecology: a national portrait.

OBJECTIVES: The purpose of this study was to determine job satisfaction among program directors in obstetrics and gynecology with the use of a validated tool and to identify specific sources of dissatisfaction that might lead to job change. STUDY DESIGN: The program director satisfaction and a global job satisfaction survey were sent to all program directors in the United States. Motivators for seeking a job change were assessed. The chi(2) test, Kruskal-Wallis test, correlation analysis, and multiple linear regression were used. RESULTS: Seventy percent of 254 surveys were completed. Global job satisfaction (minimum, 4; maximum, 16) was 11.9+/-2.9; mean program director satisfaction score was 135+/-25.8 (minimum, 54; maximum, 200). Job satisfaction was highest in chairs, full professors, those whose age was >50 years, and those with >5 years of experience (P=.02) and in facets that were related to work with residents, colleagues, and patients. Dissatisfaction was highest with regard to salary, promotion opportunities, and resources. Forty-six percent of those who responded were considering a job change in 3 years; the most common reason for a job change that was cited was administrative hassles. CONCLUSION: Although job satisfaction is high among program directors, administrative hassles may lead to high rate of rapid turnover.

Administrative Personnel↗
PubMed2007

Progressive segmented health insurance: Colombian health reform and access to health services.

Equal access for poor populations to health services is a comprehensive objective for any health reform. The Colombian health reform addressed this issue through a segmented progressive social health insurance approach. The strategy was to assure universal coverage expanding the population covered through payroll linked insurance, and implementing a subsidized insurance program for the poorest populations, those not affiliated through formal employment. A prospective study was performed to follow-up health service utilization and out-of-pocket expenses using a cohort design. It was representative of four Colombian cities (Cendex Health Services Use and Expenditure Study, 2001). A four part econometric model was applied. The model related medical service utilization and medication with different socioeconomic, geographic, and risk associated variables. Results showed that subsidized health insurance improves health service utilization and reduces the financial burden for the poorest, as compared to those non-insured. Other social health insurance schemes preserved high utilization with variable out-of-pocket expenditures. Family and age conditions have significant effect on medical service utilization. Geographic variables play a significant role in hospital inpatient service utilization. Both, geographic and income variables also have significant impact on out-of-pocket expenses. Projected utilization rates and a simulation favor a dual policy for two-stage income segmented insurance to progress towards the universal insurance goal.

Colombia↗
PubMed2003

Problem-based learning: effects on standard outcomes.

Dental students at the Harvard School of Dental Medicine (HSDM) participate fully in the first two years of the curriculum with the Harvard Medical School (HMS) while also taking parallel dental classes. HSDM students were first exposed to problem-based learning (PBL) in 1987 when the "New Pathway" curriculum was introduced at HMS in the first two years of the medical school curriculum (the HSDM courses remained traditional lecture-based classes). In 1994, HSDM incorporated PBL into the first, second, and third (clinical year) year dental courses, and the curriculum shifted from a five-year curriculum to a four-year curriculum. The purpose of this study was to evaluate the effect of PBL and program length on measurable outcomes for dental education: NBDE Part I scores, attrition and graduation rates, and percentage of graduates entering postdoctoral training programs. This study was designed as a retrospective analysis of outcomes data from 1980 to 2002. Univariate linear regressions were computed for each measure against each outcome. Subsequent bivariate regression analyses revealed that the implementation of PBL has markedly affected NBDE Part I scores, graduation rates, attrition rates, entrance into postdoctoral plans, and percentage of graduates entering GPR/AEGD programs, while program length has had an effect on graduation rates, attrition rates, entrance into postdoctoral programs, and percentage of graduates entering GPR/AEGD programs. The findings of this report suggest that the implementation of PBL combined with a change in program length has been successful for all outcomes measured and that PBL alone has contributed to the rise in NBDE Part I scores among HSDM graduates.

Boston↗
PubMed2001

Identifying determinants of nations' wetland management programs using structural equation modeling: an exploratory analysis.

Integrated management and policy models suggest that solutions to environmental issues may be linked to the socioeconomic and political characteristics of a nation. In this study, we empirically explore these suggestions by applying them to the wetland management activities of nations. Structural equation modeling was used to evaluate a model of national wetland management effort and one of national wetland protection. Using five predictor variables of social capital, economic capital, environmental and political characteristics, and land-use pressure, the multivariate models were able to explain 60% of the variation in nations' wetland protection efforts based on data from 90 nations, as defined by level of participation in the international wetland convention. Social capital had the largest direct effect on wetland protection efforts, suggesting that increased social development may eventually lead to better wetland protection. In contrast, increasing economic development had a negative linear relationship with wetland protection efforts, suggesting the need for explicit wetland protection programs as nations continue to focus on economic development. Government, environmental characteristics, and land-use pressure also had a positive direct effect on wetland protection, and mediated the effect of social capital on wetland protection. Explicit wetland protection policies, combined with a focus on social development, would lead to better wetland protection at the national level.

Agriculture↗