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Results for “Generation mean analysis”

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PubMed1994

Evaluation of a new slide-based laser scanning cytometer for DNA analysis of tumors. Comparison with flow cytometry and image analysis.

DNA measurements generated by a new automated slide-based cytometer, the laser scanning cytometer (LSC), were compared with those produced by commercial flow cytometry (FCM) and image analysis (IA) devices. Laser scanning-cytometric analysis was performed by scanning alcohol-fixed, propidium iodide-stained tumor imprints with a 5-microns spot laser beam. Fifty-three malignant tumors (51 breast carcinomas and 2 lung carcinomas) were studied. Ploidy concordance rates for FCM versus LSC, IA versus LSC, and FCM versus IA were 96%, 91%, and 91%, respectively. Statistically significant agreement between methods was determined by linear regression analysis of DNA indices. Synthesis-phase fractions generated by FCM and LSC also were comparable, as demonstrated by linear regression (r = .83). Mean coefficients of variation for the LSC compared favorably with those for FCM and IA. The few discrepancies in ploidy status between methods could be explained by sampling error, the presence of possible near-diploid aneuploid populations that could not be effectively resolved by one or another modality, and the visual selection bias with IA when small aneuploid cell populations were present. The LSC shares many useful features with FCM, including automation, accuracy of quantitation, rapidity, and generation of reliable information regarding cell proliferation (synthesis-phase fraction). In addition, it has some of the advantages of IA, such as minimal tissue requirement, no need for special preparation, and the potential for visual selection of the cells measured. The LSC holds great promise for use in the clinical laboratory because of these combined characteristics.

Breast Neoplasms↗

PubMed2000

Measurement of striatal and extrastriatal dopamine D1 receptor binding potential with [11C]NNC 112 in humans: validation and reproducibility.

To evaluate the postulated role of extrastriatal D1 receptors in human cognition and psychopathology requires an accurate and reliable method for quantification of these receptors in the living human brain. [11C]NNC 112 is a promising novel radiotracer for positron emission tomography imaging of the D1 receptor. The goal of this study was to develop and evaluate methods to derive D1 receptor parameters in striatal and extrastriatal regions of the human brain with [11C]NNC 112. Six healthy volunteers were studied twice. Two methods of analysis (kinetic and graphical) were applied to 12 regions (neocortical, limbic, and subcortical regions) to derive four outcome measures: total distribution volume, distribution volume ratio, binding potential (BP), and specific-to-nonspecific equilibrium partition coefficient (k3/k4). Both kinetic and graphic analyses provided BP and k3/k4 values in good agreement with the known distribution of D1 receptors (striatum > limbic regions = neocortical regions > thalamus). The identifiability of outcome measures derived by kinetic analysis was excellent. Time-stability analysis indicated that 90 minutes of data collection generated stable outcome measures. Derivation of BP and k3/k4 by kinetic analysis was highly reliable, with intraclass correlation coefficients (ICCs) of 0.90+/-0.06 (mean +/- SD of 12 regions) and 0.84+/-0.11, respectively. The reliability of these parameters derived by graphical analysis was lower, with ICCs of 0.72+/-0.17 and 0.58+/-0.21, respectively. Noise analysis revealed a noise-dependent bias in the graphical but not the kinetic analysis. In conclusion, kinetic analysis of [11C]NNC 112 uptake provides an appropriate method with which to derive D1 receptor parameters in regions with both high (striatal) and low (extrastriatal) D1 receptor density.

Adult↗

PubMed2005

Comparison of predictive accuracy for pathologically organ confined clinical stage T1c prostate cancer using human glandular kallikrein 2 and prostate specific antigen combined with clinical stage and Gleason grade.

PURPOSE: Previously human glandular kallikrein 2 (hK2) has been implicated to predict pathologically organ confined prostate cancer (PCa) in patients with stage T2 disease. Now we evaluated the usefulness of hK2, as measured by 2 entirely different immunoassay designs, to enhance the discrimination of pathologically organ from nonorgan confined clinical stage T1c PCa. MATERIALS AND METHODS: A consecutive series of pretreatment serum from 148 men with clinical stage T1c PCa was used in 2 equally sensitive and specific methods to measure total hK2 with independent reagents and entirely different assay designs. Total prostate specific antigen (tPSA) and free PSA (fPSA) were measured and percent fPSA was calculated. We determined the algorithm, hK2*tPSA/fPSA, from data generated by each hK2 assay, calculated means, medians and ranges for each analyte and algorithm, and calculated the significance of differences on univariate analysis. Using pretreatment PSA, clinical stage and biopsy Gleason grade we then developed a multivariate logistic regression base model to predict organ confined cancer and we compared predictions of the base model supplemented by the different hK2 measurements. RESULTS: hK2 and hK2 based algorithms obtained by each hK2 assay were significantly different for pT2a/b vs pT3a or greater PCa (p = 0.034 to 0.0001) compared to tPSA (p = 0.06), fPSA (p = 0.90) or percent fPSA (p = 0.059). However, AUC (0.67 to 0.70) calculated by ROC analysis of the 4 models containing hK2 derived information was not significantly larger than that of the base model (AUC = 0.64, p = 0.52). CONCLUSIONS: The current data confirm that hK2 alone or hK2*tPSA/fPSA measured by 2 immunoassays is significantly lower in men with pT2a/b vs pT3a or greater PCa compared to tPSA, fPSA or percent fPSA on univariate analysis of a validation set of clinical stage T1c prostate cancer treated at an American center of excellence for prostate cancer surgery. However, the incorporation of preoperative hK2 into multiparameter predictive models for pT2 cancers did not increase predictive accuracy in this cohort of men.

Adult↗

PubMed1998

Assessment of presystemic factors on the oral bioavailability of rifampicin following multiple dosing.

This study was carried out to elucidate the possible mechanism(s) responsible for reduced oral rifampicin bioavailability after multiple dosing. In addition to autoinduction, the relative contribution of the two possible controlling factors, e.g., intestinal metabolism and microbial degradation, was investigated using a rat model. Pharmacokinetic studies were carried out to assess the absolute rifampicin bioavailability by both oral and intravenous drug administration before and after 8 daily doses of 25 mg/kg. To estimate the possible involvement of microbial degradation, rifampicin kinetics were also assessed in rats on day 8 after receiving multiple oral dosing and concurrent administration of nonabsorbable triple antibiotics for gut sterilization 3 days prior to the study day. Pharmacokinetic parameters were generated by noncompartmental analysis. The results revealed a significant decrease in rifampicin levels for rats after multiple exposure, compared to single dosing; the mean clearance determined by intravenous dosing increased by 43% from 3.7 ml/min/kg and the half-life decreased by 24% from 238 min. However, the extent of decrease in rifampicin exposure following multiple dosing was substantially greater for rats dosed orally than intravenously; estimated absolute oral bioavailability decreased by 15% from 0.89 on day 1 to 0.76 on day 8. No apparent alterations in any of the pharmacokinetic parameters were observed after gut sterilization, suggesting minimal contribution of microbial degradation to the reduction in oral rifampicin absorption after multiple dosing. In addition to hepatic enzyme autoinduction, these results strongly suggest the involvement of enhanced intestinal metabolism as a contributing factor to the decrease in oral rifampicin bioavailability following prolonged exposure.

Absorption↗

PubMed2001

The concept of priority as it relates to a community mental health team.

This article illustrates how a concept clarification exercise can provide evidence to inform local policy development. Based on the framework developed in Walker and Avant's (1995) concept clarification theory, the concept of priority is examined in the context of a team of community mental health nurses. Themes of risk, multidisciplinary working, resources, and nursing role are identified as key areas for consideration, and the difficulties existing between government policy directives towards the severely mentally ill and health promotion are discussed. The article highlights how nursing theory can integrate the concept analysis of priority in planning client care. This is presented using Peplau's (1952) model as a guide to further enhance meaning of generated priorities to nursing practice.

Community Health Nursing↗

PubMed2006

Developing optimum sample size and multistage sampling plans for Lobesia botrana (Lepidoptera: Tortricidae) larval infestation and injury in northern Greece.

The purpose of this research was to quantify the spatial pattern and develop a sampling program for larvae of Lobesia botrana Denis and Schiffermüller (Lepidoptera: Tortricidae), an important vineyard pest in northern Greece. Taylor's power law and Iwao's patchiness regression were used to model the relationship between the mean and the variance of larval counts. Analysis of covariance was carried out, separately for infestation and injury, with combined second and third generation data, for vine and half-vine sample units. Common regression coefficients were estimated to permit use of the sampling plan over a wide range of conditions. Optimum sample sizes for infestation and injury, at three levels of precision, were developed. An investigation of a multistage sampling plan with a nested analysis of variance showed that if the goal of sampling is focusing on larval infestation, three grape clusters should be sampled in a half-vine; if the goal of sampling is focusing on injury, then two grape clusters per half-vine are recommended.

Analysis of Variance↗

PubMed1995

Granulocyte margination in bone marrow: comparison with margination in the spleen and liver.

The kinetics of radiolabelled granulocytes in the reticuloendothelial system were studied in order to evaluate granulocyte margination in bone marrow. A total of 34 patients took part in a two-part study. In the first part, bone marrow uptake of indium-111-labelled granulocytes was retrospectively analysed in early (3-h) and late (24-h) images in 26 patients, 13 with bronchiectasis and 13 with enclosed abdominal abscesses. The ratios between early and late counts from the bone marrow, spleen, liver and inflammatory lesion were used to quantify granulocyte margination in bone marrow, postulating that if the lesion to bone marrow ratio at 24 h exceeds the value at 3 h, then the "excess" bone marrow counts on the early images would represent margination. In the second part, this suggestion was prospectively tested using Rutland-Patlak graphical and deconvolution analysis of dynamic data, acquired in 8 patients undergoing routine scanning with technetium-99m HMPAO-labelled granulocytes. In the first part of the study, it appeared that the bone marrow is a regional site of granulocyte margination, like the spleen, with at least one-half of the 3-h marrow signal arising from marginated granulocytes, compared with about two-thirds from the spleen. In the second part, it was found that the gradient of the Patlak plot, based on spleen and marrow, continuously decreased, consistent with bi-directional movement of cells between these organs and the blood. Granulocyte pooling in the marrow was confirmed with deconvolution analysis, which generated biphasic retention functions for marrow and spleen. These curves were also consistent with two-way granulocyte exchange, and gave mean cell transit times in both organs of about 12 min and probabilities of extraction on each pass of 5-10%. We conclude that granulocytes marginate in bone marrow to an extent similar to that in the spleen.

Abdominal Abscess↗

PubMed1983

Model testing in radioligand/receptor interaction by Monte Carlo simulation.

Monte Carlo simulations have been applied for evaluating the reliability of parameter estimates as well as for testing models in radioligand saturation binding experiments. Scatchard analysis was compared to the nonlinear least-square curve fitting method for one-site saturation binding curves. It was found that linear regression analysis from the transformed data in the Scatchard plot yielded generally less accurate parameter estimates than nonlinear regression analysis of untransformed data. The advantage of the nonlinear least-squares curve fitting method was especially pronounced in cases where the scatter and number of data points, as well as the radioligand concentration range, were chosen similar to less optimal experimental conditions. Under such circumstances, several KD and Bmax values derived by Scatchard analysis led to physically impossible negative values whereas the same data analyzed by nonlinear regression yielded reasonable parameter estimates. Furthermore, it was found that for both means of analysis, KD and Bmax correlated positively. In another set of Monte Carlo experiments, saturation binding curves involving two receptor sites were generated and subsequently analyzed according to both a one-site and a two-site model. The confidence with which one is able to distinguish the two-site model from nonlinear least-squares curve fitting was then estimated for optimal, as well as for, less ideal experimental conditions.

Models, Biological↗

PubMed1989

[Bone metabolism in thalassemic children with multiple transfusions. Compartmental analysis of 99mTc-Sn-MDP kinetics].

The kinetics of 99mTc(Sn) methylene diphosphonate [99mTc(Sn)MDP] were evaluated by means of compartmental analysis in 5 normal children and 17 thalassemic subjects. Blood and urine activity were analyzed with a computer program which generates intercompartmental rate constants by an iterative least-square method providing a best-fit to the input data. The amount of tracer in each compartment (corrected for decay) was determined as a function of time. The transfer rate of 99mTc(Sn)MDP from blood to extracellular fluid and lamellar bone (K1-3) was about 20% higher in thalassemic subjects than in normal children. The transfer rate of 99mTc(Sn)MDP from blood to woven bone (K1-4) was about 57% higher in thalassemic subjects. A faster rate of spread into woven bone appears to be the major cause of higher bone uptake of 99mTc(Sn)MDP in thalassemic subjects, which suggests that in these patients bone tissue reoccupies the space previously replaced by hyperplastic marrow. Moreover, the increased bone extraction rate revealed a correlation between anemia and bone metabolic activity.

Adolescent↗

PubMed1987

Interlaboratory proficiency-testing programs: a computer model to assess their capability to correctly characterize intralaboratory performance.

We developed a computer model of an interlaboratory survey program to study the ability of proficiency testing (PT) programs to detect intralaboratory errors (total, random, and systematic). It uses a base interlaboratory PT population of 400 laboratories and one test laboratory each with uniquely defined intralaboratory characteristics, i.e., mean, standard deviation (SD), and bias. A gaussian random-number generator uses these parameters to simulate 401 test results analogous to the analysis of one PT sample by each laboratory. The test laboratory's intralaboratory error is expressed as various combinations of bias and coefficient of variation (CV); its simulated survey result is evaluated by a performance criterion derived from the group statistics. To eliminate statistical artifacts, the computer model repeats the complete simulation process 400 times and determines the percentage of the test laboratory's results that fail to meet a specified performance criterion. The computer model can use assigned values or actual intralaboratory data.

Computer Simulation↗

PubMed1996

[Optimal protocol for 99mTc-tetrofosmin myocardial SPECT imaging with exercise or dipyridamole stress test and the characteristics of bullseye normal file].

To determine optimal protocol for 99mTc-tetrofosmin SPECT imaging, 30 normal volunteers underwent treadmill or dipyridamole stress test with 770 MBq of tetrofosmin injection. Anterior planar images were acquired every 10-15 minutes for calculating heart/liver ratio. SPECT images were also obtained every 30 minutes for generating Bullseye normal files. In analysis of spatial tracer distribution among normal files, myocardium in Bullseye plot was divided in 9 areas, where mean values of % tracer uptake were calculated and compared by analysis of variance (ANOVA). In those 9 areas, mean values of SD (SD mean) were also compared for predicting artificial blackout in the Bullseye plot among 3 standard normal files: dipyridamole-201Tl, dipyridamole-tetrofosmin (60 min post-injection), and treadmill-tetrofosmin (30 min post-injection). In planar image analysis, high initial uptake in the liver and its acceptable clearance were noted in dipyridamole stress test. Adequate heart/liver ratio was accomplished immediately after treadmill, but 40 minutes later after dipyridamole stress test. ANOVA analysis showed no statistical difference in the spatial % tracer uptake among normal files, irrespective of time after acquisition, data collection time, or difference of tracer. However, SD means in inferior and lateral area of treadmill-tetrofosmin file were significantly small compared to that of dipyridamole-201Tl normal file (p < 0.02 by ANOVA). Thus, we conclude that optimal timing for tetrofosmin SPECT imaging is immediately after treadmill, but at least 40 minutes after dipyridamole stress test. In addition, we should also keep in mind that unexpected blackout may appear in inferior and lateral area, when applying our normal files for reference.

Analysis of Variance↗

PubMed1997

[Cost-benefit evaluation of medical rehabilitation by social security pensions and effects of the growth and occupational rehabilitation regulation (WFG)].

The retirement insurers, within the scope of their responsibility for health care, have already adopted the standard that calls for quality control, cost-efficiency, and outcome-focusing. For a start, the BfA (Federal Insurance Agency for Salaried Employees) has compiled a pilot evaluation presented here, based solely on its own costs and returns on costs. This evaluation demonstrates that rehabilitation "pays off". With regard to the WFG, this means that cost-saving in rehabilitation generates significant cost increases through loss of premium payments and necessary early-retirement outlays. The analysis presented shows that future investment in rehabilitation is required to ensure positive returns for the RV.

Aged↗

PubMed1986

Design and analysis considerations in evaluating the chemiluminescence response of mouse spleen cells.

Chemiluminescence is the result of the respiratory burst generated by phagocytic cells after stimulation by antigen. The measurement of chemiluminescence represents a sensitive means for detecting antigenic stimulation and immune cell function. Although the kinetics of chemiluminescence reactions have been described, appropriate statistical methods for the evaluation of data from chemiluminescence assays have not been reported. Based on examination of data from several studies in which the chemiluminescence response of spleen cells was investigated after stimulation with the particulate antigen zymosan, recommendations are made for the design and statistical evaluation of such studies. Three parameters were used in assessing the chemiluminescence response; peak intensity of the emitted light, time to peak, and the area under the intensity-time curve. The data indicated that peak intensity alone provides an adequate characterization of the chemiluminescence response. Since percent change in response upon treatment is of interest, analysis on the log scale is appropriate, and the statistical procedure of choice in evaluating data of this type is a trend analysis. The need for a balanced allocation of treatments to avoid potential bias is demonstrated. The methods proposed are illustrated with data from two studies in which the effect of preincubation with low concentrations of ketoconazole, an antifungal agent, on the chemiluminescence response of BALB/cBY spleen cells was examined.

Analysis of Variance↗

PubMed2004

Analysis of histamine release assays using the Bootstrap.

The data from several types of bioassays is usually presented as a quotient as an intuitive parameter and a means of comparing results between experiments. For the example we considered here, we look at experiments with an experiment-wide negative control used to generate percent activity quotients from each experimental group. We asked if there was a valid means to statistically evaluate the transformed rather than the raw data. The experimental system chosen was a dose response of the agonist compound 48/80, which causes release of histamine from mast cells, thus providing test data from replicates of n=24. Descriptive statistics, the Ryan-Joiner test for normality of distribution of data, and normal probability plots confirm the normality of the distribution of data at each dose level. In parametric analysis, when the control group was treated as an errorless constant, there was a distinct consistent bias in the standard error of the data of 10% or less, which was not present if the control group's mean was treated as a variable with experimental error. This would be of minor interest in qualitative studies and might be safely ignored, but might be of considerable importance in quantitative assessments of activity using confidence intervals. When using Bootstrap estimates of standard error and probability plots of the bootstrap samples, the transformed data does not deviate significantly from normality. The standard, bias-corrected percentile limits (BCa), and empirical percentile methods gave very similar results when using resampling statistics to generate the transformed data from groups of n=6. Sample size can be as low as n=4 and still provide useful results. Thus, we have shown that resampling (i.e., bootstrap, Monte Carlo method, computer-intensive methods) can produce the data transform as well as provide confidence intervals using this type of raw data in small groups (n=4 to 6), giving improved statistical analysis of the transformed data (ratio estimates) without accepting a bias from methodology ignoring variation in the control group.

Animals↗

PubMed1987

A multivariate solution for cyclic data, applied in modelling locomotor forces.

The variability in dependent biological data (measured as forces at the human foot during pedalling) was reduced, by principal components analysis, to two major components which, combined, accounted for 46% of the variability observed in sets of 26 observations per cycle. On the basis of weightings over the cycle, the components were interpreted as due to Power Production and to Phase Switch from power-generation to recovery. Force measurements were made for three frequencies of leg pedalling (1.00, 1.66, and 2.33 Hz at 10 N ergometer resistance). For each principal component, the mean (or summed) deviation over 75 consecutive cycles was found to increase linearly (p less than 0.05) with velocity of leg movement, by 7% and 85% respectively. Analysis of autocorrelations over cycles of movement showed that, in contrast to the strong interconnections of force measures within a cycle of movement, between-cycle dependence was very low. The statistical technique described provides a useful descriptive and inferential method for analyzing dependent cyclic data. The resulting model of the locomotor forces generated at the foot implies that control of power output is substantially for one cycle of a limb and that variability of force increases at the point when the leg switches from power-generation to recovery.

Analysis of Variance↗

PubMed2004

Analysis of dynamic labeling data.

Comprehensive assessments of the organization and regulation of metabolic pathways cannot be limited to steady-state measurements alone but require dynamic time series data. One experimental means of generating such data consists of radioactively labeling precursors and measuring their fate over time. While labeling experiments belong to the standard repertoire of biological laboratory techniques, corresponding mathematical tools for analyzing the non-linear dynamics of tracers are scarce. The article addresses this issue, using Biochemical Systems Theory as the modeling framework. The description of the dynamics of labeled metabolites alone is difficult, but it is demonstrated that these difficulties are easily overcome by setting up dynamic models in two or three blocks, one for the kinetics of the total pools, the second just for the labeled portions, and the third, optional, block for the remaining unlabeled components. Since the dynamic model is not limited in complexity and can account for linear pathways, converging and diverging branches, cycles, and the various observed modes of regulation, the proposed method of non-linear tracer analysis is rather general and permits simulations of most standard labeling experiments, both at steady state and during transients.

Computer Simulation↗

PubMed1989

Chronic non-specific lung disease and occupational exposures estimated by means of a job exposure matrix: the Zutphen Study.

Information gathered in the Zutphen Study, the Dutch contribution to the Seven Countries Study that started in the 1960s, was used in this study. Of the 1266 men invited to take part in the 1985 survey, 939 (74%) participated. All participants were interviewed according to the BMRC chronic non-specific lung disease (CNSLD) questionnaire and medically examined for CNSLD complaints by a trained physician. The physician also filled in a questionnaire containing questions concerning previous treatments for asthma, bronchitis and emphysema. Exposures were generated by means of a job exposure matrix on the basis of the longest performed job and the gain and grouped into 12 exposure categories. A logistic regression analysis was performed using the occupational exposures as the sector of industry dependent variables in allowing for smoking habits, age and socioeconomic status. For the diagnosis by the physician and treatment for emphysema and or bronchitis, the strongest elevated odds ratios were found, indicating an adverse effect of the occupational exposures. In contrast, the variable 'ever treated for asthma' had odds ratios smaller than one with most of the exposure variables indicating a selection effect. In an analysis in which everyone who was ever treated for asthma was excluded an increase in the odds ratios compared with the first analysis was seen. The relationships between occupational exposures as generated by the job exposure matrix and CNSLD were stronger than those recently reported in the literature.

Aged↗

PubMed1996

Subarachnoid hemorrhage diagnosis: lumbar puncture is still needed when the computed tomography scan is normal.

OBJECTIVES: To determine the sensitivity of third-generation CT scanners for diagnosed nontraumatic subarachnoid hemorrhage (SAH) and to assess the impact of symptom duration on sensitivity. METHODS: A retrospective chart review was performed in a university-affiliated tertiary care hospital with an annual ED volume of > 100,000 patients. The target population was all patients who presented to the ED from January 1991 to September 1994 with symptoms suggestive of SAH and who had a final diagnosis of nontraumatic SAH based on either a positive CT scan or positive spinal fluid analysis. Patients referred from outside facilities were included if they had a CT done at the study site. All CT scans were done using third-generation scanners. Official CT scan reports were used to categorize scans as positive or negative. RESULTS: There were 140 patients identified with SAH, with a mean age of 56 years (range 10-88). The sensitivity of CT in the diagnosis of nontraumatic SAH when performed at or before 12 hours of symptom duration was 100% (80/80), and 81.7% (49/60) after 12 hours of symptom duration (95% CI 95-100% and 69.5-90.4%, respectively; p < 0.0001). Eleven of the 140 patients had a negative CT and positive spinal fluid analysis, yielding an overall sensitivity of 92.1% (129/140). CONCLUSION: The sensitivity of third-generation CT scans for SAH decreases with time from the onset of symptoms. In this sample population, CT was able to detect all patients scanned < or = 12 hours after symptom onset. Although the study demonstrated good sensitivity of CT scan reports for SAH when the scan was performed after < or = 12 hours of symptom onset, additional real-time experience is needed to better define the potential risk of a missed SAH should this population not receive the customary lumbar puncture examination in the setting of a negative CT scan.

Adolescent↗