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Prolonged persistence of substantial volumes of potentially viable brain tissue after stroke: a correlative PET-CT study with voxel-based data analysis.

BACKGROUND AND PURPOSE: The existence in humans of brain tissue at risk for infarction but potentially viable (eg, the penumbra) remains unproven. One retrospective operational definition of such tissue includes its final infarction despite a relatively preserved or even normal cerebral metabolic rate of oxygen (CMRO2) in the early hours after stroke onset. Although previous positron emission tomography (PET) studies identified tissue whose CMRO2 declined from the acute to the subacute stage, in principle compatible with deteriorating penumbra, they all lacked a coregistered CT scan mapping of final infarct and an objective three-dimensional PET data analysis, while many patients were studied in the subacute (up to 48 hours) phase. We have evaluated whether tissue with CMRO2 ranging above a threshold for presumably irreversible damage in the first 18 hours of middle cerebral artery territory stroke, but below it in the chronic stage, could be retrospectively identified within the final infarct volume. METHODS: Our data bank comprises 30 consecutive patients with first-ever middle cerebral artery territory stroke prospectively studied with PET within the first 18 hours after clinical onset; the 15O equilibrium method was used to measure cerebral blood flow and CMRO2. All survivors with the following criteria were eligible for the present study: (1) technically adequate chronic-stage PET performed in the same stereotaxic conditions, (2) coregistered CT scan also performed in the chronic stage, and (3) an infarct of sufficient dimension (>16mm diameter) on late CT. Corresponding CT scan cuts and PET slices were exactly realigned, and the outlines of CT hypodensities were superimposed on the corresponding CMRO2 matrix. Infarcted voxels with CMRO2 values less than or greater than 1.40 mL/100 mL per minute (ie, the generally accepted threshold for irreversible damage) were automatically identified and projected on matrices of all other PET parameters and for both PET studies. RESULTS: Eight patients (mean age, 78 Years) were eligible for the present study. The acute-stage PET study was performed 7 to 17 hours after stroke onset and the chronic-stage PET 13 to 41 days later. Within the final infarct, mean CMRO2 fell significantly from the acute- to the chronic-stage PET study (P<.001). Eventually infarcted voxels with acute-stage CMRO2 values above the threshold were found in each of these eight patients; they were most often situated near the infarct borders and constituted 10% to 52% (mean, 32%) of the final infarct volume. The acute-stage CMRO2 in these voxels ranged up to 4.13 mL/100 mL per minute but fell below 1.40 mL/100 mL per minute in 93% of them at the chronic-stage PET. in 7 of 8 patients the acute-stage mean cerebral blood flow ranged from 10 to 22 mL/100 mL per minute, and the mean oxygen extraction fraction was markedly increased (>0.70) in these voxels, consistent with a penumbral state. CONCLUSION: In a strictly homogeneous sample of prospectively studied patients, we have identified, up to 17 hours after stroke onset, substantial volumes of tissue with CMRO2 well above the assumed threshold for viability that nevertheless spontaneously evolved toward necrosis. This tissue exhibited penumbral ranges of both cerebral blood flow and oxygen extraction fraction and thus could represent the part of penumbra that might be saved with appropriate therapy.

Aged↗

Signal peptide amino acid sequences in Escherichia coli contain information related to final protein localization. A multivariate data analysis.

With few exceptions, the signal peptides from proteins inserted into, or translocated through, the membranes of gram-negative bacteria or the endoplasmic reticulum of eukaryotes have no sequence homologies. Therefore these signal peptides have not been considered to contain information related to the different final localizations of the proteins. In this study, 43 signal peptide amino acid sequences from proteins with different final localizations in Escherichia coli have been subjected to a multivariate data analysis. Each amino acid residue was characterized by 20 physico-chemical properties, yielding a multivariate property profile for each peptide. The similarities/dissimilarities in the property profiles for the signal peptides from different classes were compared with each other by generating few-dimensional partial least squares (PLS) discriminant plots. With this approach, signal peptides from proteins localized to the periplasmic space (PS), the outer membrane (OM), and the extracellular surroundings (excreted proteins), were separated into distinct groups. Signal peptides from pili proteins were not separated from the OM signal peptides and only partly from the PS signal peptides, but were clearly different from the signal peptides of the excreted proteins. Signal peptides from inner membrane proteins were similar to those of the PS peptides. The size and the hydrophobicity of different peptide segments were responsible for the separation of the signal peptide classes. For example, the hydrophobicity of the N-terminal segment of the signal peptides increased with an increased distance from the cytoplasm of the final localization for the corresponding proteins. Thus, many signal peptides from proteins with different final localizations in E. coli have different discernible physico-chemical profiles.

Amino Acid Sequence↗

Climatic variables and transmission of malaria: a 12-year data analysis in Shuchen County, China.

OBJECTIVE: The objective of this study was to explore the impact of climate variability on the transmission of malaria, a vector-borne disease, in a county of China and provide suggestions to similar regions for disease prevention. METHODS: A time-series analysis was conducted using data on monthly climatic variables and monthly incidence of malaria in Shuchen County, China, for the period 1980-1991. RESULTS: Spearman's correlation analysis showed that monthly mean maximum and minimum temperatures, two measures of monthly mean relative humidity, and monthly amount of precipitation were positively correlated with the monthly incidence of malaria in the county. Regression analysis suggested that monthly mean minimum temperature and total monthly rainfall, with a one-month lagged effect, were significant climatic variables in the transmission of malaria in Shuchen County. Seasonality was also significant in the regression model and there was a declining secular trend in the incidence of malaria. CONCLUSION: The results indicate that climatic variables should be considered as possible predictors for regions with similar geographic, climatic, and socioeconomic conditions to those of Shuchen County.

China↗

Risk factors associated with pressure ulcer development at a major western Australian teaching hospital from 1998 to 2000: secondary data analysis.

OBJECTIVE: The purpose of this study was to identify risk factors associated with the presence of pressure ulcer development in adult patients at an acute care teaching hospital. DESIGN: The database was established by combining the results from 3 annual cross-sectional pressure ulcer prevalence studies conducted between 1998 and 2000. SETTING AND SAMPLE: The sample consisted of all medical and surgical patients who were inpatients on the day of the pressure ulcer surveys. The sample includes a total of 1394 patients. METHODS: This study undertook secondary data analysis with use of logistic regression and descriptive statistics. RESULTS: Overall pressure ulcer prevalence was calculated at 15.9%, with this figure decreasing slightly to 12.7% when pressure ulcers present on admission were excluded. Initial analysis identified several variables as significant risk factors for pressure ulcer development (age, Braden Scale risk category, and admission type and specialty). However, when entered into a final multivariate model, only 2 factors, age and Braden Scale risk category, were found to be significant. The odds ratio matrix revealed a consistent trend toward increasing odds ratios with increasing Braden Scale risk category within each age group. The magnitude of this trend was more pronounced in the younger age groups, highlighting the importance of undertaking Braden Scale assessments of younger patients, some of whom may be at greater risk of having a pressure ulcer develop than would otherwise be expected. CONCLUSION: Pressure ulcer prevalence in this acute care setting is high when compared with other Australian data. However, comparisons of pressure ulcer prevalence across studies are difficult to interpret because of different reporting methods. Although predictor variables for pressure ulcers have been identified in a number of studies, longitudinal studies are needed to identify the cause-and-effect relationships for potential predictor variables. In addition, more sophisticated statistical analyses such as the use of the odds ratio matrix may help guide further research into interaction effects between predictor variables and how these might affect the psychometric properties of risk assessment tools such as the Braden Scale. Pressure ulcer interventions should be targeted at the sacrum and heel, because these appear to be the most frequently observed locations for pressure ulcers.

Adolescent↗

Using other people's data: the ins and outs of secondary data analysis.

BACKGROUND AND OBJECTIVES: A variety of types of data ranging from administrative data sets to large-scale surveys have been collected for one purpose but can be accessed and used to address new questions of relevance to primary care. For many research questions, primary data collection isn't necessary because the data already exists. Although relatively few researchers consider analyzing existing data sets, there are a variety of advantages to secondary analysis. This paper introduces the practical aspects of performing secondary analysis. We review the types of questions that can addressed, where and how to access data, and the steps involved in preparing data for analysis.

Data Collection↗

Potentially inappropriate medication use in elderly patients receiving home health care: a retrospective data analysis.

BACKGROUND: Previous medication management research has focused on hospital and long-term care facility settings, where drug-utilization reviews are used to reduce medication errors. Patients receiving home health care (HHC) are without the benefit of systematic drug-utilization reviews. OBJECTIVE: The purpose of this study was to review medication use in elderly patients receiving HHC to identify the prevalence of potentially inappropriate medication (PIM) use, dangerous drug interactions (DDIs), and other patterns of medication use. METHODS: This retrospective chart review was conducted using data from Medicare recipients aged > or =65 years who were patients of Scott & White Memorial Hospital and Clinic, Scott, Sherwood and Brindley Foundation, Temple, Texas, in 2002. Pharmacists compiled medication profiles based on admissions data. PIM use was identified using the Beers criteria. DDIs were identified using the Multidisciplinary Medication Management Project criteria. Polyphsarmsacy was identified in patients receiving > or =9 medications. RESULTS: Data from 786 patients were included (mean [SD] age, 78 [7] years [range, 65-100 years; median, 78 years]; 36% men; 86% white; and 53% admitted to HHC after a hospital stay). The mean (SD) number of medications was 8.0 (3.7), with 39% of patients receiving polypharmacy. PIM use was identified in 31% of patients. DDIs were identified in 10% of patients, with a significantly higher prevalence in men (P < 0.01). Rates of PIM use and DDIs were 37% and 20%, respectively, in patients receiving polypharmacy. CONCLUSION: In this retrospective data analysis in this population of elderly patients receiving HHC in 2002, PIM and DDI were prevalent, and polypharmacy was associated with increased rates of PIM use and DDIs.

Aged↗

[Improvement of resolution of positron annihilation radiation energy spectrum measurement by data analysis (author's transl)].

Recently much attention is being paid to positron annihilation radiation energy spectrum measurement as a simple method that gives information about the momentum distribution of an annihilating pair. However, this method has a disadvantage that it is sensitive to drifts of the measuring system and the resolution is still insufficient. We have succeeded to reduce the influence of the drifts to a negligibly small degree by using, in addition to the necessary procedure for a temperature control and stabilizing of AC power lines, a compensation technique in data analysis. We have further attempted to improve the resolution by deconvolution processing. By these procedures, we have been able to separate a narrow component which has not otherwise been resolved directly from the spectrum. The resolution attained by this way is 0.43 keV (FWHM), and is two- or three-fold superior to those ever reported.

Models, Theoretical↗

Web-based tissue microarray image data analysis: initial validation testing through prostate cancer Gleason grading.

Tissue microarray technology promises to enhance tissue-based molecular research by allowing improved conservation of tissue resources and experimental reagents, improved internal experimental control, and increased sample numbers per experiment. Organized, well-validated collection and analysis of the voluminous image data produced by tissue microarray technology is critical to maximize its value. Web-based technology for visual analysis and searchable storage of microarray image data could provide optimal flexibility for research groups in meeting this goal, but this approach has not been examined scientifically. Toward this goal, a prostate tissue microarray block containing 432 tissue cores (0.6 mm diameter) was constructed. Moderately compressed (200 kb).jpg images of each tissue spot were acquired and were saved using a naming convention developed by the SPORE Prostate Tissue Microarray Collaborative Group. Four hundred three tissue array spot images were uploaded into a database developed for this study and were converted to.fpx format to decrease Internet transmission times for high-resolution image data. In phase I of the image analysis portion of the study, testing and preliminary analysis of the Web technology was performed by 2 pathologists (M.A.R. and G.S.B.). In phase II, 2 pathologists (J.I.E. and T.M.W.) with no previous exposure to this technology and no knowledge of the structure of the study were presented a set of 130 sequential tissue spot images via the Web on their office computers. In phase III, the same pathologists were presented a set of 193 images, including all 130 from phase II and 63 others, with image presentation order randomized. With each zoomable tissue spot image, each pathologist was presented with a nested set of questions regarding overall interpretability of the image, presence or absence of cancer, and predominant and second most frequent Gleason grade. In phases II and III of the study, 319 of 323 (99%) image presentations using this Web technology were rated interpretable. Comparing the 2 pathologists' readings in phases II and III, Gleason grade determinations by each pathologist were identical in 179 of 221 (81%) determinations and were within 1 point of each other in 221 of 221 (100%) determinations, a performance rate similar to if not better than that previously reported for direct microscopic Gleason grading. Interobserver comparison of Gleason score determinations and intraobserver comparisons for Gleason grade and score also showed a pattern of uniformity similar to those reported in direct microscope-based Gleason grading studies. Interobserver (7.5%) and intraobserver (5% and 3%) variability in determining whether diagnosable cancer was present point out the existence of a "threshold effect" that has rarely been studied but may provide a basis for identification of features that are most amenable to improved diagnostic standardization. In summary, storage and analysis of tissue microarray spot images using Web-based technology is feasible and practical, and the quality of images obtained using the techniques described here appears adequate for most tissue-based pathology research applications. HUM PATHOL 32:417-427.

Databases, Factual↗

Some practical issues of experimental design and data analysis in radiological ROC studies.

Receiver operating characteristic (ROC) analysis has been used in a broad variety of medical imaging studies during the past 15 years, and its advantages over more traditional measures of diagnostic performance are now clearly established. But despite the essential simplicity of the approach, workers in the field often find--sometimes only after an ROC study is under way--that a number of subtle issues related to experimental design and data analysis must be confronted in practice. Many of these issues have not been discussed in the literature in detail, and most are not well known. The purposes of this paper are to make users of ROC methodology in medical imaging aware of potential problems that should be confronted before an ROC study is begun and to indicate, at least broadly, how those problems may be dealt with, given the present state of the art. Some of the issues raised here can be addressed adequately by easily prescribed techniques, whereas others remain difficult and will be resolved fully only by new methodologic developments.

ROC Curve↗

Dichotic listening performance of articulatory-impaired children: directed attention, severity, and data analysis.

The present study compared the performance of articulatory-impaired and non-articulatory-impaired children on a dichotic word task. The dichotic words were presented under three listening conditions: free recall, directed right, and directed left. In addition, different methods for analyzing ear preferences were computed and compared. Children between 5 and 9 years of age participated. Results indicated no significant differences between articulatory-impaired and non-impaired groups on ear preferences. The directed left condition failed to produce a significant difference between right and left ear scores for both groups. Data analysis showed similarities, except with the use of the phi coefficient. No correlations were established between the number and type of articulation errors and dichotic ear preferences.

Articulation Disorders↗

The actigraph data analysis software: I. A novel approach to scoring and interpreting sleep-wake activity.

Decades of empirical observations have established the validity of actigraphy primarily in individuals without sleep disorders. Methodological problems encountered thus far coupled with the widespread use of actigraphy signal the need for concentrated efforts to establish a consensus regarding scoring procedures. Currently available scoring methods show less reliability in clinical populations. To address these issues two validation studies were conducted: one for individuals without sleep disorders and the other for patients diagnosed with insomnia. The results of these two studies using the Actigraph Data Analysis Software as the scoring method have shown that the described system is fairly precise. It can be used for actigraphs with different features and mode of operation and is applicable to individuals with insomnia. These findings corroborate previous research showing that actigraphy is a valid instrument for assessment of sleep and wakefulness.

Calibration↗

In vivo relationship between compositional and mechanical imaging of coronary arteries. Insights from intravascular ultrasound radiofrequency data analysis.

OBJECTIVE: We sought to explore in vivo the relation between mechanical and compositional properties of matched cross sections (CSs) using novel catheter-based techniques. BACKGROUND: Intravascular ultrasound (IVUS) palpography allows the assessment of local mechanical tissue properties. Spectral analysis of IVUS radiofrequency data (IVUS-VH) is a tool to assess plaque morphology and composition. METHODS AND RESULTS: Palpography analysis defined high- and low-strain regions. One hundred twenty-three CSs (27 vessels) were colocalized. The mean strain value was higher in CSs with necrotic core (NC) in contact with the lumen than in CSs with no NC contact with the lumen (1.03 +/- 0.5 vs 0.86 +/- 0.4, P = .06). Mean relative calcium (1.61 +/- 2.5% vs 0.25 +/- 0.7%, P = .001) and NC (15.64 +/- 10.6% vs 2.8 +/- 3.9%, P < .001) content were significantly higher in the CSs with NC in contact with the lumen, whereas the inverse was seen for the fibrotic component of the plaque (64.16 +/- 11.6% vs 75.75 +/- 13.7, P < .001). The sensitivity, specificity, positive predictive value, and negative predictive value of IVUS-VH to detect high strain were 75.0%, 44.4%, 56.3%, and 65.1%, respectively. A significant inverse relationship was present between calcium and strain levels (r = -0.20, P = .03). After adjusting for univariate predictors, the contact of NC with the lumen was identified as the only independent predictor of high strain (OR 5.0, 95% CI 1.7-14.1, P = .003). CONCLUSION: In the present study, IVUS-VH showed an acceptable sensitivity to detect high strain. In turn, the specificity was low. Of interest, a significant inverse relationship was present between calcium and strain levels.

Aged↗

Combining fold recognition and exploratory data analysis for searching for glycosyltransferases in the genome of Mycobacterium tuberculosis.

Fold recognition was applied to the systematic analysis of the all sequences encoded by the genome of Mycoplasma tuberculosis H37Rv in order to identify new putative glycosyltransferases. The search was conducted against a library composed of all known crystal structures of glycosyltransferases and some related proteins. A clear relationship appeared between some sequences and some folds. It appears necessary to complete the fold recognition approach with a statistical approach in order to identify the relevant data above the background noise. Exploratory data analysis was carried out using several methods. Analytical methods confirmed the validity of the approach, while predictive methods, although very preliminary in the present case, allowed for identifying a number of sequences of interest that should be further investigated. This new approach of combining bioinformatics and chemometrics appears to be a powerful tool for analysis of newly sequenced genomes. Its application to glycobiology is of great interest.

Computational Biology↗

Prevalence survey of infection in a Hong Kong hospital using a standard protocol and microcomputer data analysis.

A 1-day prevalence survey of hospital infection was performed in June 1985 at a new general teaching hospital in Hong Kong. The 1980 British national survey protocol was used, and the results were analysed by microcomputer. The major part of the survey was carried out by nine people over a period of 3 days and was completed within 6 weeks. The rate of hospital-acquired infection was 8.9% and of community-acquired infection was 16.5%. Antibiotics were mainly used in infected patients. The British protocol is suitable for Hong Kong hospitals, and with microcomputer data analysis such surveys can be completed quickly and accurately even with limited resources.

Adolescent↗

Ischemic cerebral tissue response to subventricular zone cell transplantation measured by iterative self-organizing data analysis technique algorithm.

To investigate the changes of the ischemic lesion in rat brain after subventricular zone (SVZ) cell transplantation and the influence of the grafted cells on the appearance of angiogenesis, SVZ cells, superparamagnetically labeled, were intracisternally transplanted into the rat brain 48 h after onset of embolic stroke. A complete set of magnetic resonance (MR) images was acquired for all animals with (n=8) and without (n=3) cell grafting at approximately 24 h, 72 h, and weekly for 6 weeks after stroke. Transplanted cells were tracked by high-resolution three-dimensional gradient-echo images and the interaction between the cells and ischemic lesion was detected by ISODATA (Iterative Self-Organizing Data Analysis Technique Algorithm) calculated from T(1), T(2) and T(1sat) maps. Tissue status from ISODATA was characterized by a specific signature, which represents the deviation from normal tissue in the feature space. Transplanted SVZ cells selectively migrated towards the ischemic side of the rat brain and approached the lesion boundary within 1-week after grafting. Cell treated rats exhibited a significant reduction of average lesion size compared with control rats (P<0.05). A significant reduction of tissue signature (P<0.001) induced by cell transplantation was localized to the position of grafted cells, and these sites exhibited stably restored cerebral blood flow (CBF) (approximately 85% of normal CBF). Angiogenesis was present in sites either immediately adjacent to or surrounded by the grafted cells. Our data indicate that map-ISODATA accurately and dynamically characterizes the ischemic lesion and its response to cell therapy.

Algorithms↗

Capillary electrophoresis enhanced by automatic two-way background correction using cubic smoothing splines and multivariate data analysis applied to the characterisation of mixtures of surfactants.

Mixtures of the surfactant classes coconut diethanolamide, cocamido propyl betaine and alkylbenzene sulfonate were separated by capillary electrophoresis in several media containing organic solvents and anionic solvophobic agents. Good resolution between both the surfactant classes and the homologues within the classes was achieved in a BGE containing 80 mM borate buffer of pH 8.5, 20% n-propanol and 40 mM sodium deoxycholate. Full resolution, assistance in peak assignment to the classes (including the recognition of solutes not belonging to the classes), and improvement of the signal-to-noise ratio was achieved by multivariate data analysis of the time-wavelength electropherograms. Cubic smoothing splines were used to develop an algorithm capable of automatically modelling the two-way background, which increased the sensitivity and reliability of the multivariate analysis of the corrected signal. The exclusion of significant signals from the background model was guaranteed by the conservativeness of the criteria used and the safeguards adopted all along the point selection process, where the CSS algorithm supported the addition of new points to the initially reduced background sample. Efficient background modelling made the application of multivariate deconvolution within extensive time windows possible. This increased the probability of finding quality spectra for each solute class by orthogonal projection approach. The concentration profiles of the classes were improved by subsequent application of alternating least squares. The two-way electropherograms were automatically processed, with minimal supervision by the user, in less than 2 min. The procedure was successfully applied to the identification and quantification of the surfactants in household cleaners.

Electrophoresis, Capillary↗

Primer on medical genomics. Part III: Microarray experiments and data analysis.

Genomics has been defined as the comprehensive study of whole sets of genes, gene products, and their interactions as opposed to the study of single genes or proteins. Microarray technology is one of many novel tools that are allowing global and high-throughput analysis of genes and gene products. In addition to an introduction on underlying principles, the current review focuses on the use of both complementary DNA and oligodeoxynucleotide microarrays in gene expression analysis. Genome-wide experiments generate a massive amount of data points that require systematic methods of analysis to extract biologically useful information. Accordingly, the current educational communication discusses different methods of data analysis, including supervised and unsupervised clustering algorithms. Illustrative clinical examples show clinical applications, including (1) identification of candidate genes or pathological pathways (ie, elucidation of pathogenesis); (2) identification of "new" molecular classes of diseases that may be relevant in disease reclassification, prognostication, and treatment selection (ie, class discovery); and (3) use of expression profiles of known disease classes to predict diagnosis and classification of unknown samples (ie, class prediction). The current review should serve as an introduction to the subject for clinician investigators, physicians and medical scientists in training, practicing clinicians, and other students of medicine.

Breast Neoplasms↗

Multivariate data analysis of organochlorines and brominated flame retardants in Baltic Sea guillemot (Uria aalge) egg and muscle.

Concentrations of organochlorines (OCs) and brominated flame-retardants (BFRs) were determined in guillemot (Uria aalge) eggs from the island of Stora Karlsö in the Baltic Sea where 10 eggs/year were collected in the years 2000, 2001 and 2002. The dominating contaminant in egg was p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) with a geometric mean (GM) concentration of 18200 ng/g lipid weight (lw). The GM concentration in egg of hexabromocyclododecane (HBCD) of 140 ng/glw, was significantly higher than that of polybrominated diphenyl ether (summation operatorPBDE) of 77 ng/glw. For the evaluation of the data multivariate data analysis techniques namely principal components analysis (PCA), partial least squares regression (PLS), soft independent modelling of class analogy (SIMCA classification), and PLS discriminant analysis (PLS-DA), were used. We investigated whether the eggs' biological characteristics co-varied with egg concentrations of OCs and BFRs, and found e.g., significant negative correlations between egg weight and concentrations of HCB and p,p'-DDE. A PLS model with analyzed BFRs as the Y matrix and OCs as the X matrix could, with varying accuracy, calculate the concentrations of BFRs in the individual egg from their concentrations of OCs (e.g., R(2)Y of 0.89 for BDE47, and of 0.50 for HBCD). Lastly, we compared the contaminant concentrations in the eggs to those in previously analyzed pectoral muscles from adult guillemots from Stora Karlsö, from the year 2000. A PLS-DA model, showed that some of the contaminants (e.g., HBCD and CB28) had significantly higher concentrations in egg than in muscle, although 7 of the 14 contaminants showed no difference in concentrations between the two matrices.

Animals↗