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Influence of culture site-specific MIC distributions on the pharmacokinetic and pharmacodynamic properties of piperacillin/tazobactam and piperacillin: a data analysis.

BACKGROUND: Investigators who perform pharmacokinetic/pharmacodynamic (PK-PD) modeling with Monte Carlo simulation have historically not stratified microbiological data by culture site. This lack of stratification might be problematic if susceptibility patterns differ among sites and might lead to differences in PK-PD. OBJECTIVE: This study compared the PK-PD of 2 antimicrobial regimens against 5 gram-negative bacterial species form 3 culture sites. METHODS: This data analysis was performed at the Department of Pharmacology, The University of Texas Health Science Center, San Antonio, Texas. Blood, pulmonary (ie, bronchial, endotracheal, lung, respiratory, sputum, and tracheal secretions), and wound distributions of MICs were extracted from the 2002 Intensive Care Unit Surveillance System database. Bacteria included Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The PK properties of piperacillin/tazobactam (3.375 g every 4 hours) and piperacillin (3 g every 4 hours) were obtained from studies in healthy volunteers. Monte Carlo simulation was used in 10,000 patients for each antimicrobial-bacteria-culture site combination. The cumulative fraction of response (CFR) for a free percentage time above the MIC of > or =50% was determined for each combination, and a clinically significant difference was defined a priori as > or =10%. RESULTS: Data from 2408 pulmonary, 490 blood, and 242 wound isolates were included. For piperacillin/tazobactam, the CFR varied <10% by culture site in all 5 bacterial species. Site-specific differences were noted in MIC50 for piperacillin versus E cloacae and E coli and MIC90 for piperacillin/tazobactam versus K pneumoniae and P aeruginosa. Likewise, for piperacillin, the CFR was similar among the 3 culture sites for P aeruginosa. However, the CFR for piperacillin varied by > or =10% for A baumannii (blood > wound), E cloacae (pulmonary > blood), E coli (pulmonary and blood > wound), and K pneumoniae (wound > blood). CONCLUSIONS: The PK-PD models based on PK properties found in healthy humans and site-specific MIC distributions in this study suggest that for piperacillin, culture-site differences subsequently resulted in CFR differences that exceeded a predetermined level of clinical significance. Furthermore, these data suggest that traditional reporting strategies for microbiological data (ie, MIC50 and MIC90) might fail to adequately characterize the MIC population.

Anti-Bacterial Agents↗

Identification of expression patterns associated with hemorrhage and resuscitation: integrated approach to data analysis.

BACKGROUND: Although transcriptional profiling is a well-established technique, its application to systematic studying of various biological phenomena is still limited because of problems with high-volume data analysis and interpretation. This research project's objective was to create a comprehensive summary of changes in gene expression after hemorrhagic shock (HS), reliant and impartial of multiple variables, such as resuscitation treatments, organ analyzed, and time after impact. METHODS: Rat model of severe (40% total blood loss) HS was employed. Hemorrhagic shock was treated with 6 different resuscitation strategies: (1) racemic lactated Ringer's (DL-LR); (2) L-lactated Ringer's (L-LR); (3) ketone Ringer's (KR); (4) pyruvate Ringer's (PR); (5) 6% hetastarch (Hex); (6) 7.5% hypertonic saline (HTS). Nonresuscitated and nonhemorrhaged rats served as controls. Ketone and pyruvate Ringer solutions were identical to the lactated Ringer's solution except for equimolar substitution of lactate with beta-hydroxybutyrate and sodium pyruvate, respectively. Total RNA from liver, lung, and spleen was isolated immediately (0 hour) and 24 hour postresuscitation. Each organ, time point and treatment was profiled using individual cDNA array (1,200 genes), to produce 183 separate data files. Methods of analysis included one-way and unbalanced factorial ANOVA, Sokal-Michener average linkage clustering and contextual mapping. RESULTS: : Unresuscitated HS produced the highest number (56) of upregulated expressions in spleen and lungs. HEX and HTS affected mostly pulmonary genes (22 and 9). Fourteen genes changed in response to combination of all three factors: treatment, organ, and time. Eighteen genes were identified as treatment-specific. Fifteen genes adjusted expression 24 hour post-treatment. The largest number of genes with altered expression (168) responded differently in all three organs. In this study 15 gene clusters were pinpointed. Contextual mapping identified novel and confirmed known pathways contributing to hemorrhage/resuscitation. CONCLUSIONS: We have reliably identified genes and pathways that are affected by HS and are responsive to resuscitation. Gene expression in various organs is affected differentially by HS, which can be further modulated by the choice of resuscitation strategy.

Analysis of Variance↗

The effect of oxygen administration on visuospatial cognitive performance: time course data analysis of fMRI.

This study investigated the effects of 30% oxygen administration on visuospatial cognitive ability using time course data analysis of fMRI. A visuospatial task was presented while brain images were scanned by a 3T MRI system. The results showed that there was an improvement in performance and also increased BOLD intensity in the parietal lobe in the higher oxygen condition. There was positive relation between behavior performance and BOLD intensity in the right parietal lobe. This result supports the conclusion that the increase in the cognitive processing ability due to highly concentrated oxygen can be explained by the increase in the BOLD intensity.

Adult↗

Microarray data analysis made easy.

DNA microarrays are valuable tools for analyzing global gene expression. Because of the increasing popularity and the large volume of data produced, tools for facile microarray data analysis are essential. FiRe, a recently introduced computer program, has now solved the seemingly insuperable discrepancy between simplicity and evaluation of DNA microarray data. The program is available as a macro for the popular Microsoft Office Excel software and is user-friendly, interactive, versatile and platform-independent, paving the way for a further push in the evaluation of DNA microarrays.

Database Management Systems↗

New data analysis of the stroop matching task calls for a reevaluation of theory.

In Stroop matching tasks, participants indicate whether the color of an object matches the meaning of a color word printed in color. Previously in this journal, Luo (1999) concluded that interference between two incongruent representations of the same attribute (ink color) occurs prior to the response stage. However, this conclusion was based on questionable data analysis. We suggest analyzing the data by separating "same" and "different" responses and then analyzing three congruency conditions within the "different" responses: (a) congruence between word color and word meaning, (b) congruence between word color and object color, and (c) incongruence between word color, word meaning, and object color. In an experiment similar to Luo's, such an analysis revealed that responding was slowest in the first condition. This pattern of results does not fit with previous conclusions regarding this task, but rather indicates that task conflict and response competition contribute to interference. This analysis has implications for matching tasks other than the Stroop matching task.

Color Perception↗

[Characteristics of categorical data analysis].

This work presents characteristics of categorical data, their presentation and possible models of statistical analysis. There are two types of categorical data; nominal, where categories are equally valued (i.e. we can measure them only in terms of whether individual items belong to some distinctively different categories) and ordinal, where categories allow to rank order on some scale of measurement. Categorical data are non-numeric by nature, but could be numerically presented and analyzed anyway. Although the information value of categorical data is well below the respective information value of numerical, practically there's no study where their analysis wouldn't be of importance. Numerically, the categorical data can be presented via frequencies (absolute number of items belonging to the category) or their proportion (percentage) in the sample. Adequate graphical presentation goes with pie charts or percentage stacked bars charts. The statistical analysis of categorical data most often is done on contingency tables. The type of the analysis depends on the relation between samples from which the data are drowning. If the samples are independent, the analysis would be performed using difference of proportion test, chi2 test or Fisher exact test. The limitations and suitability for application of the three is discussed. If the samples are dependent, the choice goes to McNemar chi2 test (2 samples) or Cochrane's Q test 8more than 2 samples). The conclusions from the aforementioned analyses could be drowned only in terms of significant or nonsignificant relations between the rows and columns in the contingency tables. In the need to measure the level of relations between categorical data, two types of measures are defined: relative risk and odds ratio, which can both be calculated only in 2x2 contingency tables. Relative risk is a ratio of two proportions (suitable only in prospective studies), whether odds ratio measures ratio between odds in two groups (could be calculated both in prospective and retrospective studies). All the aforementioned analyses are well documented with calculations on data collected in biomedical studies.

Data Interpretation, Statistical↗

Quantitative data analysis for exploring outcomes in cardiac surgery.

The article focuses on possibilities of statistical knowledge exploration to predict outcomes of surgical treatments. The outcomes were defined in relation to the measured peri- and intraoperative data, as well as follow-up patient questionnaire. Clinical consequences are expected in terms of a smaller data set with a better ability to predict the surgery outcomes and a better cost performance. The important questions that could discriminate quality of life (QoL) were: Relief from surgery?, Has cardiac surgery effected earlier symptoms? Work capacity? Consultations after the surgery? The performed data analysis proved to be efficient in the complex data set that was collected. Pain relief was identified to be significant, while relations between measured blood laboratory profile and later QoL were weak.

Aged↗

A novel approach for nontargeted data analysis for metabolomics. Large-scale profiling of tomato fruit volatiles.

To take full advantage of the power of functional genomics technologies and in particular those for metabolomics, both the analytical approach and the strategy chosen for data analysis need to be as unbiased and comprehensive as possible. Existing approaches to analyze metabolomic data still do not allow a fast and unbiased comparative analysis of the metabolic composition of the hundreds of genotypes that are often the target of modern investigations. We have now developed a novel strategy to analyze such metabolomic data. This approach consists of (1) full mass spectral alignment of gas chromatography (GC)-mass spectrometry (MS) metabolic profiles using the MetAlign software package, (2) followed by multivariate comparative analysis of metabolic phenotypes at the level of individual molecular fragments, and (3) multivariate mass spectral reconstruction, a method allowing metabolite discrimination, recognition, and identification. This approach has allowed a fast and unbiased comparative multivariate analysis of the volatile metabolite composition of ripe fruits of 94 tomato (Lycopersicon esculentum Mill.) genotypes, based on intensity patterns of >20,000 individual molecular fragments throughout 198 GC-MS datasets. Variation in metabolite composition, both between- and within-fruit types, was found and the discriminative metabolites were revealed. In the entire genotype set, a total of 322 different compounds could be distinguished using multivariate mass spectral reconstruction. A hierarchical cluster analysis of these metabolites resulted in clustering of structurally related metabolites derived from the same biochemical precursors. The approach chosen will further enhance the comprehensiveness of GC-MS-based metabolomics approaches and will therefore prove a useful addition to nontargeted functional genomics research.

Automation↗

Multivariate data analysis of sea waters and mussels in relation to pollution sources of trace elements.

The total concentration of Cu, Zn and Pb in surface sea waters from the Bay of Muggia (Gulf of Trieste, Northern Adriatic Sea) was determined by anodic stripping voltammetry. The association of these trace elements in relation to the known sources of pollution was discussed. The content of eight trace elements (Mn, Co, Ni, Cu, Zn, Cd, Hg, Pb) in the soft part of mussels (Mytilus galloprovincialis Lamarck) is also considered. The wild molluscs were sampled in the harbour of Trieste, in the proximity of an important city sewer. Principal component analysis was used to analyse the correlation matrix obtained from an 8 x 43 data matrix after a logarithmic transformation of the concentration variables. Eight variables were reduced to four principal components, which explained 80% of the total variance. The orthogonally rotated factor matrix shows that Co, Ni, Cd, and Pb are associated with the first principal component, Cu and Zn to the second, Hg to the third and Mn to the fourth principal component. The results of this multivariate data analysis are compared with those already obtained from two sampling sites in the Bay of Muggia and the origin of some trace metals in the soft part of mussels from the Gulf of Trieste is discussed.

Analysis of Variance↗

Stochastic approach to data analysis in fluorescence correlation spectroscopy.

Fluorescence correlation spectroscopy (FCS) has emerged as a powerful technique for measuring low concentrations of fluorescent molecules and their diffusion constants. In FCS, the experimental data is conventionally fit using standard local search techniques, for example, the Marquardt-Levenberg (ML) algorithm. A prerequisite for these categories of algorithms is the sound knowledge of the behavior of fit parameters and in most cases good initial guesses for accurate fitting, otherwise leading to fitting artifacts. For known fit models and with user experience about the behavior of fit parameters, these local search algorithms work extremely well. However, for heterogeneous systems or where automated data analysis is a prerequisite, there is a need to apply a procedure, which treats FCS data fitting as a black box and generates reliable fit parameters with accuracy for the chosen model in hand. We present a computational approach to analyze FCS data by means of a stochastic algorithm for global search called PGSL, an acronym for Probabilistic Global Search Lausanne. This algorithm does not require any initial guesses and does the fitting in terms of searching for solutions by global sampling. It is flexible as well as computationally faster at the same time for multiparameter evaluations. We present the performance study of PGSL for two-component with triplet fits. The statistical study and the goodness of fit criterion for PGSL are also presented. The robustness of PGSL on noisy experimental data for parameter estimation is also verified. We further extend the scope of PGSL by a hybrid analysis wherein the output of PGSL is fed as initial guesses to ML. Reliability studies show that PGSL and the hybrid combination of both perform better than ML for various thresholds of the mean-squared error (MSE).

Computer Simulation↗

Exploratory data analysis of the multilevel anthropogenic copper cycle.

A comprehensive multilevel contemporary cycle for stocks and flows of copper is analyzed by the tools of exploratory data analysis (EDA). The analysis is performed at three discrete spatial levels--country (56 countries or country groups that comprise essentially all anthropogenic stocks and flows of copper), eight world regions, and the planet as a whole. Among the most interesting results are the following: (1) EDA is employable and valuable for use in the analysis of material flows, especially those across multiple spatial levels; (2) All distributions of country-level stock and flow data are highly skewed, a few countries having large magnitudes, many having small magnitudes; (3) Rates of fabrication of copper-containing products for the countries are poorly correlated with rates of extraction, reflecting the fact that many countries that extract copper do not fabricate products from copper to any significant degree and vice versa; (4) Virtually all countries are adding copper to stock (in pipe, wire, etc.); These rates of addition are highly correlated with rates of copper entering use in all regions and are higher in regions under vigorous development; (5) With weak confidence, the rate of copper landfilling by regions is about one-half the rate of copper discarded; (6) The statistical distributions of both country-level and regional-level copper cycle parameters have successively lower standard deviations at later life stages; and (7) Copper flow distributions at different life stages tend to reflect those of lower spatial level extreme values, but Asia's and Europe's regional patterns are much more reflective of country-level distributions as a whole.

Asia↗

Automated pattern ranking in differential display data analysis.

Gene expression analysis by differential display (DD) is limited by the labor-intensive visual evaluation of the electrophoretic data traces. We describe a flexible method for computer-assisted ranking of expression patterns in data from DD experiments. The method is based on a pairwise alignment and comparison of the quantitative trace data with respect to specific expression patterns defined by the investigator. The observed patterns are ranked according to a score value that identifies the most potential findings to be confirmed visually instead of the vast amount of original results. This two-step approach, enabled by the efficient computer algorithm for gene expression pattern comparison, will increase the percentage of true-positive findings chosen for the tedious downstream processing, while minimizing the cost and labor involved in large scale DD data analysis.

Algorithms↗

Dynamic force spectroscopy: optimized data analysis.

The forced rupture of single chemical bonds in biomolecular compounds (e.g., ligand-receptor systems) as observed in dynamic force spectroscopy experiments is addressed. An optimized method of data analysis is proposed. This method significantly outperforms the current standard one when applied to data from an idealized numerical computer simulation of an experiment with realistic parameter values. In particular, the force-free dissociation rate can be inferred with a considerably smaller statistical uncertainty and without the systematic overestimation of about 30%, which is shown to be inherent in the standard method.

Journal Article↗

Comparison of control analysis data using different approaches: modelling and experiments with muscle extract.

Experimental and model studies have been performed to characterize the control properties of hexokinase and phosphofructokinase in muscle glycolysis and to examine the nature of error associated with experimental flux control coefficient determinations. Different approaches of metabolic control analysis, classical titration, co-response analysis and kinetic modelling indicated that flux control coefficients could be reliably estimated experimentally for the upper part of glycolysis. The kinetic parameters applied to construct the mathematical model were determined in muscle extract under similar conditions used for flux studies. If the kinetic parameters of commercial enzymes are introduced into the model the control analysis data cannot be trusted. Co-response analysis can also be successfully applied to determination of the flux control coefficients of the system. However, the involvement of a rapid-equilibrium enzyme, such as glucose 6-phosphate isomerase, could result in estimation errors for the relevant co-response coefficients that are propagated into the elasticity matrix. If the co-response coefficients related to isomerase activity are replaced by the values obtained by kinetic modelling, the values of elasticities are correct. Our data also suggest that in the upper part of glycolysis hexokinase mainly controls the pathway flux whereas phosphofructokinase exerts dominant control on the turnover of internal metabolite stocks inside the system.

Animals↗

Diabetic autonomic neuropathy--Part I. Autonomic nervous system data analysis by a computerized central unit in a multicenter trial.

To determine the feasibility of utilizing a central, computerized unit to analyze autonomic nervous system function tests for a 10-year, multicenter, clinical trial, the Autonomic Nervous System Reading Center was established. The Reading Center selected and standardized testing methods, designed the testing protocol, developed testing equipment, computerized data analysis, and instituted measures to monitor data quality. Three cardiovascular testing methods, RR-variation, Valsalva maneuver, and postural testing, were selected because each is a simple, non-invasive, quantitative, sensitive, and reproducible test. Furthermore, a hierarchy of sensitivity has been established with these cardiovascular autonomic nervous system measurements: RR-variation, Valsalva maneuver, and finally postural testing. Confounding variables were minimized by prescribing eligibility criteria. Testing equipment, designed to record time between RR intervals in a form easily read into a computer, has been in 21 clinics for three years and a total of 54 technicians have been trained. Over 85 percent of the autonomic nervous system tests performed have been usable at initial testing. A central reading center is an efficient and necessary means of collecting and analyzing data for a multicenter clinical trial.

Autonomic Nervous System Diseases↗

An integrated Arabidopsis annotation database for Affymetrix Genechip data analysis, and tools for regulatory motif searches.

Genome-scale sequencing projects have provided the essential information required for the construction of entire genome chips or microarrays for RNA expression studies. The Arabidopsis and rice genomes have been sequenced and whole-genome oligonucleotide arrays are being manufactured. These should soon become available to researchers. Expression studies using genomic-scale expression arrays are providing us with a vast quantity of information at a rapid pace. The rate-limiting step in this type of experiments is not the data generation step but rather the data analysis component of experiments. We report improvements that should facilitate the analysis of Affymetrix Genechip expression data.

Arabidopsis↗

A wavelet, fourier, and PCA data analysis pipeline: application to distinguishing mixtures of liquids.

Using a new optical engineering technique for the "fingerprinting" of beverages and other liquids, we study and evaluate a range of features. The features are based on resolution scale, invariant frequency information, entropy, and energy. They allow mixtures of beverages to be very precisely placed in principal component plots used for the data analysis. To show this we make use of data sets resulting from optical/near-infrared and ultrasound sensors. Our liquid "fingerprinting" is a relatively open analysis framework in order to cater for different practical applications, in particular, on one hand, discrimination and best fit between fingerprints, and, on the other hand, more exploratory and open-ended data mining.

Journal Article↗

[Evaluation of the efficiency of primary care centers. Application of data analysis].

BACKGROUND: One of the major difficulties in evaluating the efficiency of Primary Medical Centres is that of integrating quantitative and qualitative data. METHODS: This study applies the Involved Data Analysis (DEA) for the purpose of evaluating the efficiency of Primary Medial Centres located in the Province of Zaragoza (Spain). DEA is a lineal programming technique that provides information on the relative efficiency of each unit, as compared to all other units. Output such as doctors and nursing services as well as variables relating to the quality of service, and input (personnel and pharmaceutical expenses) referring to 1994, were obtained from Area Management. RESULTS: Without taking qualitative variables into account, only 13 Primary Medical Centres reached maximum efficiency level 1. with a range of 0.53 to 1. Taking quality variables into account, 24 units reached optimum efficiency, with a range of 0.61 to 1. CONCLUSIONS: DEA is a useful tool for both qualitative and quantitative overall evaluation of input and output and identifies units that are inefficient as compared to others. Despite the difficulties involved, the method appears to be beneficial for management as a complementary aid to currently used techniques.

Data Interpretation, Statistical↗