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At least 1,027 records · Page 57Linked to original sources
PubMed2003

Screening of biomarkers in rat urine using LC/electrospray ionization-MS and two-way data analysis.

Biofluids, like urine, form very complex matrixes containing a large number of potential biomarkers, that is, changes of endogenous metabolites in response to xenobiotic exposure. This paper describes a fast and sensitive method of screening biomarkers in rat urine. Biomarkers for phospholipidosis, induced by an antidepressant drug, were studied. Urine samples from rats exposed to citalopram were analyzed using solid-phase extraction (SPE) and liquid chromatography mass spectrometry (LC/MS) analysis detecting negative ions. A fast iterative method, called Gentle, was used for the automatic curve resolution, and metabolic fingerprints were obtained. After peak alignment principal component analysis (PCA) was performed for pattern recognition, PCA loadings were studied as a means of discovering potential biomarkers. In this study a number of potential biomarkers of phospholipidosis in rats are discussed. They are reported by their retention time and base peak, as their identification is not within the scope of the study. In addition to the fact that it was possible to differentiate control samples from dosed samples, the data were very easy to interpret, and signals from xenobiotic-related substances were easily removed without affecting the endogenous compounds. The proposed method is a complement or an alternative to NMR for metabolomic applications.

Animals↗
PubMed1996

Surrogate data analysis of sleep electroencephalograms reveals evidence for nonlinearity.

We tested the hypothesis of whether sleep electroencephalographic (EEG) signals of different time windows (164 s, 82 s, 41 s and 20.5 s) are in accordance with linear stochastic models. For this purpose we analyzed the all-night sleep electroencephalogram of a healthy subject and corresponding Gaussian-rescaled phase randomized surrogates with a battery of five non-linear measures. The following nonlinear measures were implemented: largest Lyapunov exponent L1, correlation dimension D2, and the Green-Savit measures delta 2, delta 4 and delta 6. The hypothesis of linear stochastic data was rejected with high statistical significance. L1 and D2 yielded the most pronounced effects, while the Green-Savit measures were only partially successful in differentiating EEG epochs from the phase randomized surrogates. For L1 and D2 the efficiency of distinguishing EEG signals from linear stochastic data decreased with shortening of the time window. Altogether, our results indicate that EEG signals exhibit nonlinear elements and cannot completely be described by linear stochastic models.

Adult↗
PubMed2004

Surrogate data analysis for assessing the significance of the coherence function.

In cardiovascular variability analysis, the significance of the coupling between two time series is commonly assessed by setting a threshold level in the coherence function. While traditionally used statistical tests consider only the parameters of the adopted estimator, the required zero-coherence level may be affected by some features of the observed series. In this study, three procedures, based on the generation of surrogate series sharing given properties with the original but being structurally uncoupled, were considered: independent identically distributed (IID), Fourier transform (FT), and autoregressive (AR). IID surrogates maintained the distribution of the original series, while FT and AR surrogates preserved the power spectrum. The ability of the three methods to define the threshold for zero coherence was validated and compared by computer simulations reproducing typical cardiovascular interactions. While the IID threshold depended only on record length and design parameters of the coherence estimator, FT and AR thresholds were frequency-dependent with peaks corresponding to the local maxima of the estimated coherence. FT and AR surrogates were able to compensate spurious coherence peaks due to equal-frequency but independent oscillations in the two series. The benefit of frequency-dependent thresholds was evident for short series with narrow-band oscillations. Thus, surrogates preserving the power spectrum of the original series are recommended to avoid false coupling detections in the presence of oscillations occurring at nearby frequencies but produced by different mechanisms, as may frequently happen in cardiovascular and cardiorespiratory regulation.

Algorithms↗
PubMed2005

Sample size for FDR-control in microarray data analysis.

We consider identifying differentially expressing genes between two patient groups using microarray experiment. We propose a sample size calculation method for a specified number of true rejections while controlling the false discovery rate at a desired level. Input parameters for the sample size calculation include the allocation proportion in each group, the number of genes in each array, the number of differentially expressing genes and the effect sizes among the differentially expressing genes. We have a closed-form sample size formula if the projected effect sizes are equal among differentially expressing genes. Otherwise, our method requires a numerical method to solve an equation. Simulation studies are conducted to show that the calculated sample sizes are accurate in practical settings. The proposed method is demonstrated with a real study.

Algorithms↗
PubMed1987

[An information system for hospital hygiene. III. Exploratory data analysis of the dynamic aspects in the pathogen spectra of patient specimens from two intensive care units at a Berlin university hospital].

For the 18-months period ending June 1986 the computerised database of the institutes of medical microbiology and of hygiene at Berlin Free University showed about 12,200 specimens from 1,236 intensive care patients. In addition to a traditional tabulation of pathogens by site (urine, wound, bronchial secretion and blood) and service (multidisciplinary post-operative, 4,628 isolates and internal medicine, 1,813 isolates) resulting in a time aggregated assessment of the patients at both intensive care units (ICU) the same data were analysed to detect dynamic variations using 3 different approaches: (1) Medians of the sampling time span (STS) from first specimen of the same patient to follow-up specimens were analysed for 8 pathogens. In specimens from the bronchial tract S. aureus, Klebsiella spp., enterococci and P. aeruginosa showed the same sequence of STS-medians at both ICUs. (2) Dynamic modelling of sequential batches of 100 specimens from the bronchial tract using 3RSSH smoothing showed only poor variation in the proportion of E. coli and enterococci, but demonstrated substantial variation in S. aureus and P. aeruginosa. (3) The negative exponential model was used to fit frequency distributions of STS data. The model suggests a STS half life of 8 days before the first P. aeruginosa is reported from specimens of the bronchial tract of patients mostly with respirators. Periodical reporting of these indicators provides quantitative reference and enables the clinician to better relate individual information from his patients to the epidemiological outcome of his unit.

Bacteria↗
PubMed2007

Promoter profiling and coexpression data analysis identifies 24 novel genes that are coregulated with AMPA receptor genes, GRIAs.

We identified a set of transcriptional elements that are conserved and overrepresented within the promoters of human, mouse, and rat GRIAs by comparing these promoters against a collection of 10,741 gene promoters. Cells regulate functional groups of genes by coordinating the transcriptional and/or posttranscriptional mRNA levels of interacting genes. As such, it is expected that functional groups of genes share the same transcriptional features within their promoters. We found 47 genes whose promoters contain the same combination of transcriptional elements that are overrepresented within the promoters of the GRIA gene family. Coexpressed genes may be transcriptionally coregulated, which in turn suggests that these genes may play complementary roles within a particular functional context. Using microarray expression data, we found 24 (of the 47) genes that share not only a similar promoter profile with GRIAs but also a well-correlated gene expression profile and, thus, we believe these to be coregulated with GRIAs.

Animals↗
PubMed2006

Elucidating the digital control mechanism for DNA damage repair with the p53-Mdm2 system: single cell data analysis and ensemble modelling.

Recent experimental evidence about DNA damage response using the p53-Mdm2 system has raised some fundamental questions about the control mechanism employed. In response to DNA damage, an ensemble of cells shows a damped oscillation in p53 expression whose amplitude increases with increased DNA damage--consistent with 'analogue' control. Recent experimental results, however, show that the single cell response is a series of discrete pulses in p53; and with increase in DNA damage, neither the height nor the duration of the pulses change, but the mean number of pulses increase--consistent with 'digital' control. Here we present a system engineering model that uses published data to elucidate this mechanism and resolve the dilemma of how digital behaviour at the single cell level can manifest as analogue ensemble behaviour. First, we develop a dynamic model of the p53-Mdm2 system that produces non-oscillatory responses to a stress signal. Second, we develop a probability model of the distribution of pulses in a cell population, and combine the two with the simplest digital control algorithm to show how oscillatory responses whose amplitudes grow with DNA damage can arise from single cell behaviour in which each single pulse response is independent of the extent of DNA damage. A stochastic simulation of the hypothesized control mechanism reproduces experimental observations remarkably well.

Cell Physiological Phenomena↗
PubMed2004

Prescriber intent, off-label usage, and early discontinuation of antidepressants: a retrospective physician survey and data analysis.

BACKGROUND: Many patients discontinue antidepressant therapy long before the 6-month minimum duration recommended for the treatment of major depression and many other diagnoses. We explore various possibilities, including prescriber intent and patient diagnosis, to explain some of this early discontinuation. METHOD: Patients from a single health maintenance organization who filled at least 1 prescription for an antidepressant during the first 4 months of 2001 and who did not fill an antidepressant prescription in the 6 months prior were identified retrospectively. Prescribers of those patients' antidepressants were surveyed for patient diagnosis and length of intended treatment with antidepressant medication. Actual length of treatment was then obtained from pharmacy data and correlated with survey data and other variables. RESULTS: Prescriber surveys were returned for 51% (485/951) of the patients identified. Surveys indicated that for 34% of initial antidepressant prescriptions, < 6 months of treatment was intended. Important determinants of the length of antidepressant therapy included prescriber specialty area, number of prescribers, prescriber intent, diagnosis, specific antidepressant used, and concomitant benzodiazepine use. CONCLUSIONS: Prescriber intention to treat many patients with short courses of antidepressants, often for off-label, non-mental health indications, was correlated with early discontinuation and needs further study of both its rationale and efficacy. Although less prevalent, short-term treatment of mental health disorders, including depression, was also intended by psychiatrists and other prescribers. The widespread practice of intended short-term treatment with antidepressants needs to be understood better, since it results in guideline-incompatible, early antidepressant discontinuation.

Adolescent↗
PubMed2000

Current state of automated crystallographic data analysis.

A goal of structural biology--and of structural genomics in particular--is to improve the underlying methodology for high-throughput determination of three-dimensional structures of biological macromolecules. Here we address issues related to the development, automation and streamlining of the process of macromolecular X-ray crystal structure solution.

Automation↗
PubMed1994

Effects of bladder resorption on pharmacokinetic data analysis.

In modern pharmacokinetic analysis, the urinary bladder is usually viewed as a nonreturning compartment or storage site for renally excreted compounds. Our previous studies have indicated appreciable bladder resorption of drugs. The present study used computer simulations to evaluate the quantitative importance of several potential determinants of bladder resorption, namely the bladder resorption rate constant (ka), interval between bladder voiding (delta tvoid), ratio of renal elimination rate constant to overall elimination rate constant (ex:kel ratio), and kel or t1/2. The data identified ka, delta tvoid, and kex:kel ratio as the three most important determinants of the rate and extent of bladder resorption. We further examined the errors introduced in the derived pharmacokinetic parameters due to omission of bladder resorption. Plasma concentration-time profiles and urinary excretion-time profiles were generated by simulations using different values of ka, delta tvoid, and kex:kel ratio. These profiles were used to derive the pharmacokinetic parameters, including the renal clearance (CLrenal), total body clearance (CLtotal), nonrenal clearance (CLnonrenal), t1/2, mean residence time (MRT), amount and fraction of dose excreted in urine (Aex and fe), and volume of distribution at steady state (Vdss). Data show that resorption of drug from the bladder into the systemic circulation increased the area under the plasma concentration-time profile, MRT and t1/2, but decreased CLrenal, CLtotal, Aex, and Fe. Vdss was relatively unchanged. Overestimation of MRT and t1/2 was dependent on ka, kex:kel ratio, and delta tvoid. Underestimation in CLrenal), Aex, and fe was not dependent on the Kex:kel ratio, but was affected by changes in ka and delta tvoid. CLrenal and fe were the most sensitive pharmacokinetic parameters, with a > or = 50% underestimation at a ka value that we reported previously, for the bladder absorption of antipyrine in rats with intact urothelium. In summary, these data indicate (i) alteration in the plasma concentration-time profiles and urinary excretion-time profiles due to bladder resorption, and (ii) substantial over- or underestimation in the derived pharmacokinetic parameters due to erroneous omission of bladder resorption.

Computer Simulation↗
PubMed2004

[Development of software for data analysis by therapeutic drug monitoring of teicoplanin, a glycopeptide antibiotic].

We developed a new software named TEICTDM based on the Bayesian estimation utilized in the therapeutic drug monitoring (TDM) of teicoplanin, a glycopeptide antibiotic, for the estimation of individual pharmacokinetic parameters. Therefore, it is necessary to input more than one plasma concentration(s) determined in individual patient. Individual pharmacokinetic parameters were calculated by a least squares methods, MULTI2 (BAYES). Two-compartment model was applied to determine individual pharmacokinetic parameters in male healthy volunteers in Japan, and the relationship between clearance of teicoplanin and creatinine clearance in adult patients with various degrees of renal impairment in Europe was used. A series of work from data input to graph drawing or printing of results could efficiently carried out with the best of use of this software, suggesting that this software is now available in clinical practice.

Adult↗
PubMed2004

[Experimental investigation on the reproducibility of ensemble-averaged electromyographic gait analysis data in the area of experimental and clinical orthopaedics].

With suitable application and signal processing methods, surface electromyography is a comparatively simple instrument for investigating the temporal pattern of the muscular activity of a walking subject. The influence of changes both in the external experimental conditions (e.g. orthopedic shoe design) and in the human locomotor system (due to disease or therapy) on the individual muscular gait characteristics can be documented in this way. The usefulness of this kind of investigation is basically limited by the reproducibility of the gait analytical findings of the subject, who is examined at different times with unchanged bodily state and under identical experimental conditions unchanged. In our experiments we observed that the reproducibility of electromyographic activity curves obtained by ensemble averaging over a sufficiently high number of full strides differs for different muscles and in different subjects. Within the same experimental session it is very high and considerably better than in experiments done on different days. In examinations done on different days the basic characteristics of the activity curves are reproduced better than the absolute height of the amplitudes. In view of these findings the differences observed in the gait analysis of patients in the course of operative or conservative therapy have to be interpreted very carefully as to their true origin.

Algorithms↗
PubMed1980

[Validity of retro- and prospective data analysis (authors' translation)].

Retrospective chart analysis of 88 operated patients with bronchial carcinoma showed grave deficiencies. In 15% the reason for admission to hospital was not available and the exact smoking habits of 74% were not known. Retrospective TNM-classification was possible in only 59%. It was known in 67% whether a radiotherapy and in 17% whether a cytostatic therapy was additionally performed. Only 13 of the 20 surviving patients participated in the follow-up. In contrast with these figures, a prospective collection of data (44 patients) has an effectiveness of 95% or more for all parameters.

Bronchial Neoplasms↗
PubMed2006

The effects of celeration lines on visual data analysis.

Previous visual analysis research reported that the overall agreement between visual analysis and statistical analysis was poor. In response, some researchers suggested the use of celeration lines to improve the accuracy and reliability of visual analysis. However, subsequent research reported little or no improvement in accuracy with such lines. The present study presented 5 board-certified behavior analysts with a series of behavioral graphs. The participants were asked to answer questions similar to those posed in previous studies but were also asked to talk aloud as they viewed each graph. Results indicate that the participants made accurate decisions for only 72% of the graphs and that celeration lines did not improve overall accuracy. The verbal protocol analysis suggests that participants were as likely to attend to trend when celeration lines were absent as they were when they were present, with the most differences attributable to varying participant competencies and not graph (i.e., celeration line) characteristics.

Behavior Therapy↗
PubMed1997

Effect of antihypertensive treatment in patients having already suffered from stroke. Gathering the evidence. The INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) Project Collaborators.

BACKGROUND AND PURPOSE: Drug treatment of high blood pressure has been shown to reduce the associated cardiovascular risk. Stroke represents the type of event more strongly linked with high blood pressure, responsible for a high rate of death or invalidity, and with the highest proportion of events that can be avoided by treatment. Hypertensive patients with a history of cerebrovascular accident are at particularly high risk of recurrence. Specific trials of blood pressure lowering drugs in stroke survivors showed inconclusive results in the past. METHODS: We performed a meta-analysis using all available randomized controlled clinical trials assessing the effect of blood pressure lowering drugs on clinical outcomes (recurrence of stroke, coronary events, cause-specific, and overall mortality) in patients with prior stroke or transient ischemic attack. RESULTS: We identified 9 trials, including a total of 6752 patients: 2 trials included 551 hypertensive stroke survivors; 6 trials of hypertensive patients included a small proportion of stroke survivors (536 patients); 1 trial included stroke survivors, whether hypertensive or not (5665 patients). The recurrence of stroke, fatal and nonfatal, was significantly reduced in active groups compared with control groups consistently across the different sources of data (relative risk of 0.72, 95% confidence interval: 0.61 to 0.85). There was no evidence that this intervention induced serious adverse effect. CONCLUSIONS: Blood pressure lowering drug interventions reduced the risk of stroke recurrence in stroke survivors. Available data did not allow to verify whether such benefit depends on initial blood pressure level. More data are needed before considering antihypertensive therapy in normotensive patients at high cerebrovascular risk.

Aged↗
PubMed2003

[Novel approaches; improved diagnosis and therapy with DNA microarrays. I. Technology and data analysis].

With DNA microarrays it will be possible to refine diagnostics and treatment with the use of genome wide information on a patient's sample. Microarrays are currently applied to unravel gene functions, pathogenetic mechanisms, metabolic routes and the effects of drugs on these, to refine diagnostic classifications and prognostic indexes, and to find new targets for therapy. With genotyping it will be possible to generate risk profiles for certain diseases and to assess the likelihood of a given drug-related side effect. Furthermore, it may accelerate research of mutations in genes for which the normal DNA sequences are already known. The basic principle of DNA microarrays is that thousands of different DNA sequences, each specific for a given gene, are immobilised on a solid surface (for example a microscope slide), arranged in a known order, and are hybridised with a solution of labelled DNA or RNA molecules. The DNA or RNA molecules under investigation bind to complementary base pairs on the slide, and permit us to measure the amount of labelled DNA or RNA hybridised to each gene sequence. Sophisticated software is used to analyse the large amount of data generated. The ultimate aim is to group genes with similar expression patterns across all samples, and then group samples accordingly. Conventional biological or biochemical techniques are required to validate the data obtained with microarrays, and to verify whether the observed associations among genes are biologically relevant.

Diagnostic Techniques and Procedures↗
PubMed2006

Absolute myoglobin quantitation in serum by combining two-dimensional liquid chromatography-electrospray ionization mass spectrometry and novel data analysis algorithms.

To measure myoglobin, a marker for myocardial infarction, directly in human serum, two-dimensional liquid chromatography in combination with electrospray ionization mass spectrometry was applied as an analytical method. High-abundant serum proteins were depleted by strong anion-exchange chromatography. The myoglobin fraction was digested and injected onto a 60 mm x 0.2 mm i.d. monolithic capillary column for quantitation of selected peptides upon mass spectrometric detection. The addition of known amounts of myoglobin to the serum sample was utilized for calibration, and horse myoglobin was added as an internal standard to improve reproducibility. Calibration graphs were linear and facilitated the reproducible and accurate determination of the myoglobin amount present in serum. Manual data evaluation using integrated peak areas and an automated multistage algorithm fitting two-dimensional models of peptide elution profiles and isotope patterns to the mass spectrometric raw data were compared. When the automated method was applied, a myoglobin concentration of 460 pg/microL serum was determined with a maximum relative deviation from the theoretical value of 10.1% and a maximum relative standard deviation of 13.4%.

Algorithms↗
PubMed2004

Estimating treatment effect in the presence of non-compliance measured with error: precision and robustness of data analysis methods.

Non-compliance with the nominal prescribed dosage causes unintended variability in actual drug exposure during clinical trials. In the ideal case that compliance is not a confounder, and it is known--hence actual dosage is known--true dose-response can be validly estimated. Measuring compliance presents a challenge, however. A simulation study of the case that dosage history questionnaires (C(Q)--usually over-optimistic estimates of actual compliance) are available in all subjects enrolled in a clinical trial, but accurate compliance measurements (C--e.g. from electronic medication event monitors), are only available in a (random) fraction of subjects is reported. It reveals that a 'Maximum Penalized Marginal Likelihood' (MPML) method which uses all compliance data, effectively calibrating C(Q) to C, is superior to other methods which use only one compliance measure, or both, or neither (neither = ITT, intention to treat, which assumes actual dosage equals nominal dosage), but do not calibrate. MPML yields the most precise estimates of dose-response over widely varying clinical trial designs, extremes in quality and quantity of compliance information, and a range of drug effect sizes. It is most beneficial when compliance data are sparse and maintains good performance even when its key assumptions are somewhat violated.

Algorithms↗