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PubMed1985

Digital signal and image processing in echocardiography. The American Society of Echocardiography.

Digital signal and image processing techniques are acquiring an increasingly important role in the generation and analysis of cardiac images. This is particularly true of 2D echocardiography, in which image acquisition, manipulation, and storage within the echocardiograph, as well as quantitative analysis of echocardiographic data by means of "off-line" systems, depend upon digital techniques. The increasing role of computers in echocardiography makes it essential that echocardiographers and technologists understand the basic principles of digital techniques applied to echocardiographic instrumentation and data analysis. In this article, we have discussed digital techniques as applied to image generation (digital scan conversion, preprocessing, and postprocessing) as well as to the analysis of image data (computer-assisted border detection, 3D reconstruction, tissue characterization, and contrast echocardiography); a general introduction to off-line analysis systems was also given. Experience with other cardiac imaging methods indicates that digital techniques will likely play a dominant role in the future of echocardiographic imaging.

Echocardiography↗

PubMed2005

Comments on selected fundamental aspects of microarray analysis.

Microarrays are becoming a ubiquitous tool of research in life sciences. However, the working principles of microarray-based methodologies are often misunderstood or apparently ignored by the researchers who actually perform and interpret experiments. This in turn seems to lead to a common over-expectation regarding the explanatory and/or knowledge-generating power of microarray analyses. In this note we intend to explain basic principles of five (5) major groups of analytical techniques used in studies of microarray data and their interpretation: the principal component analysis (PCA), the independent component analysis (ICA), the t-test, the analysis of variance (ANOVA), and self organizing maps (SOM). We discuss answers to selected practical questions related to the analysis of microarray data. We also take a closer look at the experimental setup and the rules, which have to be observed in order to exploit microarrays efficiently. Finally, we discuss in detail the scope and limitations of microarray-based methods. We emphasize the fact that no amount of statistical analysis can compensate for (or replace) a well thought through experimental setup. We conclude that microarrays are indeed useful tools in life sciences but by no means should they be expected to generate complete answers to complex biological questions. We argue that even well posed questions, formulated within a microarray-specific terminology, cannot be completely answered with the use of microarray analyses alone.

Computational Biology↗

PubMed2006

Genomewide scan in Ashkenazi Jewish families demonstrates evidence of linkage of ocular refraction to a QTL on chromosome 1p36.

UNLABELLED: The development of refractive error is mediated by both environmental and genetic factors. We performed regression-based quantitative trait locus (QTL) linkage analysis on Ashkenazi Jewish families to identify regions in the genome responsible for ocular refraction. We measured refractive error on individuals in 49 multi-generational American families of Ashkenazi Jewish descent. The average family size was 11.1 individuals and was composed of 2.7 generations. Recruitment criteria specified that each family contain at least two myopic members. The mean spherical equivalent refractive error in the sample was -3.46D (SD=3.29) and 87% of individuals were myopic. Microsatellite genotyping with 387 markers was performed on 411 individuals. We performed multipoint regression-based linkage analysis for ocular refraction and a log transformation of the trait using the statistical package Merlin-Regress. Empirical genomewide significance levels were estimated through gene-dropping simulations by generating random genotypes at each of the 387 markers in 200 replicates of our pedigrees. Maximum LOD scores of 9.5 for ocular refraction and 8.7 for log-transformed refraction (LTR) were observed at 49.1 cM on chromosome 1p36 between markers D1S552 and D1S1622. The empirical genomewide significance levels were P=0.065 for ocular refraction and P<0.005 for LTR, providing strong evidence for linkage of refraction to this locus. The inter-marker region containing the peak spans 11 Mb and contains approximately 189 genes. CONCLUSION: We found genomewide significant evidence for linkage of refractive error to a novel QTL on chromosome 1p36 in an Ashkenazi Jewish population.

Alleles↗

PubMed2006

Additive genetic variation of transcriptional regulation: metallothionein expression in the soil insect Orchesella cincta.

Field-selected metal tolerance in Orchesella cincta is correlated with overexpression of the single copy cadmium (Cd) inducible metallothionein (mt). Previously, we have demonstrated large phenotypic variation in mt gene expression, and a higher frequency of high-expression phenotypes in a tolerant population. Here, we describe midparent-offspring regression analysis of mt gene expression in a laboratory culture originating from a noncontaminated natural population. Families were either not exposed (n=47) or exposed to 0.5 micromol Cd per gram dry food (n=46). Mean mt gene expressions normalized to 28S rRNA and beta-actin RNA were generated using real-time RT-PCR applied to parents and offspring RNA and subjected to regression analysis. A significant heritability (h2) for mt gene expression was estimated between 0.36 (beta-actin normalized) and 0.46 (28S normalized) in Cd exposed families. Nontreated families did not yield a significant h2 value. Restriction Fragment Length Polymorphism analysis of the metallothionein promoter sequence revealed eight promoter alleles that show structural variation. Three alleles show increased frequencies in families with high mt expression. Another gene, croquemort (isolated from a differential screening for 1 micromole Cd treatment) showed no h2 of gene expression in response to 0.5 micromol Cd. This gene codes for a receptor-protein involved in recognition of apoptotic cells and may participate in the general stress response. The present data suggest that evolution of metal tolerance in O. cincta can occur in the field by selection for high mt expression due to structural changes in mt cis-regulation.

Adaptation, Physiological↗

PubMed2005

Generating words: one approach to teaching clinical writing.

Language is our means of reaching our patients and our means of describing the process of analysis to others. The task of the case history is to show the evolution of consciousness in both analyst and patient. It will be more effective if written in a lively engaging way. The author describes one method of teaching clinical writing, introducing candidates to techniques of fiction writing and poetry. Her class has involved both focused reading and writing exercises; examples are given of both.

Clinical Competence↗

PubMed1985

Neutrophil migration in vivo: analysis of a skin window technique.

The applicability of a skin chamber technique for the quantitation of neutrophil migration in vivo was studied in healthy subjects. Skin lesions were generated on lower abdominal skin by separating epidermis from dermis by suction. In 23 subjects the mean chamber cell count at 24 h was 20.9 X 10(6)/cm2 of skin lesion area, and 97.5% of the cells were neutrophils. An analysis of the variance in up to 8 parallel chambers in 10 subjects supported the use of 4 simultaneous replicates. Reproducibility in consecutive experiments was studied by testing 9 persons twice; the results were found to agree closely. Kinetic studies were performed in 15 subjects. The method is useful for the in vivo study of diseases and medications thought to affect leukocyte function.

Adult↗

PubMed1975

Randomization and the analysis of variance.

This paper attempts to strengthen faith in randomization, first by defining it in general and second by showing how it is the fundamental means, in many experiments, of generating the probability space. It is defined by the natural structure of the experimental units (E.U.'s) not by a particular experimental design imposed on that structure. Three examples are given, with the same design but different E.U. structures and randomizations, to show that models developed from experimental designs are superficial, but that their randomization is fundamental.

Analysis of Variance↗

PubMed2001

Methods for estimating the AIDS incubation time distribution when date of seroconversion is censored.

In most cohort studies on HIV infection and AIDS, data on time from seroconversion to AIDS or death are doubly censored, both at the time origin and at the endpoint of interest. In epidemiological research, the most frequently adopted approach is to restrict the analysis to persons with narrow seroconversion intervals and to impute the midpoint of this interval as date of seroconversion. For many cohort studies, the consequence is that a substantial proportion of the data is not used. We consider four methods that are expected to be less biased when all cohort data are used: two imputation methods, conditional mean and multiple imputation, and two likelihood maximization methods. We derive the likelihood structure of the cohort data and clarify its dependence on study design. All methods are applied to data from the Amsterdam cohort study among injection drug users. In a simulation study the data generation process of this cohort study is imitated. The performance of midpoint, conditional mean and multiple imputation are compared. With midpoint imputation, both an analysis using the full data set, as well as one restricted to the cases with small seroconversion intervals, is performed. Conditional mean imputation comes out as the preferred method. It gives best results with respect to mean squared error. Moreover, when confidence intervals are computed through standard methods that ignore the uncertainty in the imputed date of seroconversion, coverage probabilities are almost correct.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

The state of EMS education research project: characteristics of EMS educators.

OBJECTIVES: The preparation of emergency medicine practitioners occurs at a variety of levels, via individuals with various levels of experience and training, and through a variety of oversight organizations. The purpose of this study was to quantify the characteristics of those recognized as prehospital emergency medical services (EMS) educators, the type and amount of infrastructure available to facilitate the learning process, and what attributes and common practices the profession values. METHODS: The respondents (n = 1,691) were generated randomly from a nationwide systematic sample of all known EMS instructors. The sample was adequate to generalize to the 15,000 EMS educators. Face validity and content validity were assured through use of a 24-member focus group of EMS educators, practitioners, and administrators, who reviewed the questionnaire. Reliability estimates were generated via Cronbach's alpha and Kuder-Richardson 20 and 21 and ranged from 0.59 to 0.83, with a grand mean for the seven study constructs of 0.70. Factor analysis with varimax rotation explained 40% to 66% of the respective construct variance, with a grand mean of 56% of the response variance explained. RESULTS: The respondents were satisfied with their teaching experience (98%), expected to continue (80%), and taught because of a perceived dearth of qualified instructors. Only half of the respondents utilized federally generated curricular materials, and approximately 20% were uncomfortable in assessing psychomotor skills. The relationship of testing to assessment and skill performance appeared to be the most significant pedagogic challenge. CONCLUSIONS: The respondents were a senior group of educators committed to the training of new providers who will comprise the foundation of future EMS educational efforts at the national level.

Adult↗

PubMed1987

Nucleic acid-based analyses of non-group A rotaviruses.

Simple genome profile studies on polyacrylamide gels allow all non-group A rotaviruses isolated so far to be recognized by the absence of the tight triplet (7-9) of RNA segments seen in all group A viruses. However, reliance solely on genome profile studies for rotavirus grouping can be misleading and, for virus group definition, additional corroborating nucleic acid and serological studies are essential. Terminal fingerprint analysis was the first generation of nucleic acid-based assays that allowed discrimination between the various rotavirus groups. By means of this technique the clear definition of five rotavirus groups (A-E), correlating exactly with those found by a serological assay, has been possible, with preliminary evidence for at least two additional groups. The technical sophistication of fingerprinting techniques prevents their widespread use in epidemiological studies; the development of a second generation of nucleic acid-based assays is therefore under way. These employ molecularly cloned cDNA probes to the genomes of non-group A viruses which can be widely distributed for use in 'dot-blot' screening of faecal samples and, if expressed as protein in Escherichia coli, should provide a ready source of viral antigen for use in surveying viral prevalence through the screening of serum antibody levels.

DNA↗

PubMed1994

Quantification of intracoronary volume by videodensitometry: validation study using fluid filling of human coronary casts.

Changes in intracoronary volume reflect the hemodynamic significance of progression or regression of diffuse coronary artery disease where intracoronary catheters cannot be applied for direct measurements due to small vessel dimensions. We have validated the videodensitometric measurement of intracoronary volume with epoxy casts of postmortem human coronary arteries. The volume of 31 coronary segments (cross-sectional areas in a range of 2-13 mm2) measured by fluid-filling using a precision dispenser was compared with the respective single plane intracoronary volume assessments obtained by the videodensitometric algorithm of the new generation Cardiovascular Angiography Analysis System (CAAS II). The true and measured values of volume were compared by calculation of the mean of the signed differences +/- standard deviation and by linear regression analysis. Videodensitometric measurement of intracoronary volume correlate well with fluid-filling of human coronary artery casts (correlation coefficient: r = 0.99, y = 1.96 +/- 0.99x, standard error of estimate: SEE = 3.96) with a significant trend towards overestimation of true volume values (mean difference = 1.73 +/- 3.64 mm3, P < 0.05). Intracoronary volume estimations can be used to measure changes of luminal dimensions of coronary arteries and may offer a new approach to assessment of progression or regression of diffuse coronary artery disease.

Coronary Angiography↗

PubMed2005

Characterization of the TE-NORM waste associated with oil and natural gas production in Abu Rudeis, Egypt.

The present study was conducted to characterize the Technically Enhanced Naturally Occurring Radioactive Materials (TE-NORM) waste generated from oil and gas production. The waste was characterized by means of dry screening solid fractionation, X-ray analysis (XRF and XRD) and gamma-ray spectrometry. Sediment of the TE-NORM waste was fractionated into ten fractions with particle sizes varying from less than 100 microm to more than 3 mm. The results showed that the TE-NORM waste contains mainly radionuclides of the 238U, 235U and 232Th series. The mean activity concentrations of 226Ra (of U-series), 228Ra (of Th-series) and 40K in the waste samples before fractionation (i.e. 3 mm) were found to amount to 68.9, 24 and 1.3 Bq/g (dry weight), respectively. After dry fractionation, the activity concentrations were widely distributed and enriched in certain fractions. This represented a 1.48 and 1.82-fold enrichment of 226Ra and 228Ra, respectively, in fraction F8 (2.0-2.5 mm) over those in bulk TE-NORM waste samples. The activity ratios of 238U/226Ra, 210Pb/226Ra, 223Ra/226Ra and 228Ra/224Ra were calculated and evaluated. Activity of the most hazardous radionuclide 226Ra was found to be higher than the exemption levels established by IAEA [International Atomic Energy Agency, 1994. International Basic Safety Standards for the Protection against Ionizing Radiation and for the Safety of Radiation Sources. GOV/2715/94, Vienna]. The radium equivalent activity (Ra-eq), radon (222Rn) emanation coefficient (EC) and absorbed dose rate (Dgammar) were estimated and these are further discussed.

Egypt↗

PubMed1989

Effects of normalization errors on size distributions obtained from dynamic light scattering data.

This paper presents a study of the influence of normalization errors on size distributions obtained from the analysis of intensity fluctuations by photon correlation spectroscopy. The effects of these errors are demonstrated by means of computer-generated autocorrelation functions simulating light scattered from a monomodal Schulz distribution of small, spherical, unilamellar lipid vesicles. The calculations show that even small errors in the baseline, modifying the data upon normalization systematically, will cause serious errors in the estimated size distribution. As it turns out this is due to the peculiar characteristics of normalization errors in data of the first order autocorrelation function. The errors introduced there are described in parts by functions of the delay time having positive exponents. Such components are not considered in the integral equations commonly used to analyze the measured data. The error's property to be a function of delay time in turn enables us to obtain the relative baseline error from the inversion of the data. The new method for its determination is described in some detail. Here, it has been realized with a modified version of the size distribution algorithm CONTIN.

Light↗

PubMed1997

Analysis of the forces developed during obturation: warm vertical compaction.

The aim of this work was to measure and analyze the forces applied by endodontists during an obturation. This was achieved by devising a system of force transducers linked to acquisition software. The software allowed us to study the obturation forces in real time or to store them. In this initial study, the forces developed by endodontists and students during a warm vertical compaction were analyzed. The vertical and frontware backware horizontal direction forces were first stored. Graphs of the compaction forces were then generated, permitting the analysis of the obturation method. Indeed, two cases of obturation failure were analyzed from these graphs. The mean values for the vertical forces applied by the endodontists and students were, respectively, 2.5 +/- 0.4 kg and 1.9 +/- 0.9 kg; the mean values for the lateral forces were, respectively, 0.85 +/- 0.2 kg and 1.4 +/- 0.6 kg. This device permits the analysis of compaction forces and may thus be highly useful in obtaining improvements in obturation techniques.

Analysis of Variance↗

PubMedDate not supplied

Clinical usefulness of iodine 123-labeled fatty acid imaging in patients with acute myocardial infarction.

BACKGROUND: Iodine 123-labeled 15-(p-iodophenyl)-3R,S-methylpentadecanoic acid (BMIPP) has recently been developed, since normal myocardium metabolizes free fatty acids. This study investigated the clinical usefulness of BMIPP imaging in patients with acute myocardial infarction (MI), particularly in the detection of stunned myocardium in patients who underwent acute coronary revascularization. METHODS: The subjects were 41 patients with acute MI who had undergone emergency coronary revascularization. Both BMIPP and thallium-201 images at rest were obtained during the subacute phase. The myocardial distribution of radiotracers was quantified by generating circumferential count-distribution profile analysis. Initial 201Tl imaging, delayed 201Tl imaging, and BMIPP imaging were performed, and the mean count densities in the infarct region (initial 201Tl images [TL1], delayed 201Tl images [TL2], and BMIPP images in the infarct region [BM], respectively) were obtained. The differences between mean count densities (TL1-BM: BM subtracted from TL1; TL2-BM: BM subtracted from TL2) were also calculated. RESULTS: BM showed a higher correlation with wall motion data by echocardiography (WM) in the acute phase than other nuclear imaging tests, whereas TL2 showed the highest correlation with WM in the chronic phase. Acute to chronic WM improvement showed a good correlation with TL2-BM. CONCLUSION: Single photon emission computed tomography imaging with BMIPP is a candidate for providing the "memory image" of ischemic damage, whereas TL2 reflects all viable tissue. The mismatch between the tracers can serve as an indicator of myocardial stunning.

Angioplasty, Balloon, Coronary↗

PubMed2005

A sensitivity analysis of bias in relative risk estimates due to disinfection by-product exposure misclassification.

We conducted a sensitivity analysis of relative risk estimates using local area mean disinfection by-product exposures. We used Monte Carlo simulations to generate data representing 100 towns, each with 100 births (n=10,000). Each town was assigned a mean total trihalomethane (TTHM) exposure value (mean=45, SD=28) based on a variable number of sampling locations (range 2-10). True maternal TTHM exposure was randomly assigned from a lognormal distribution using that town's true mean value. We compared the effect of a 20 microg/l increase in TTHM exposure on the risk of small-for-gestational age infancy using the true maternal exposure compared to various weighting measures of the town mean exposures. The exposure metrics included: (1) unweighted town mean, (2) town mean weighted by the inverse variance of the town mean, (3) town mean weighted by the inverse standard deviation of the town mean, (4) town mean weighted by 1-(standard deviation of sites per town/mean across all towns), and (5) a randomly selected value from one of the sites within the town of residence. To estimate the magnitude of misclassification bias from using the town mean concentrations, we compared the true exposure odds ratios (1.00, 1.20, 1.50, and 2.00) to the mean exposure odds ratios from the five exposure scenarios. Misclassification bias from the use of unweighted town mean exposures ranged from 19 to 39%, increasing in proportion to the size of the true effect estimates. Weighted town mean TTHM exposures were less biased than the unweighted estimates of maternal exposure, with bias ranging from 0 to 23%. The weighted town mean analyses showed that attenuation of the true effect of DBP exposure was diminished when town mean concentrations with large variability were downweighted. We observed a trade-off between bias and precision in the weighted exposure analyses, with the least biased effects estimates having the widest confidence intervals. Effect attenuation due to intrasystem variability was most evident in absolute and relative terms for larger odds ratios.

Adult↗

PubMed2000

Electronic data collection by trainee anaesthetists using palm top computers.

The Royal College of Anaesthetist requires that trainees wishing to specialise in Anaesthesia register with the College and keep a logbook documenting their experience and training in clinical anaesthesia. There are a number of advantages if such logbooks are kept in an electronic format. For the first time in the United Kingdom, we have evaluated the usefulness in a district general hospital of introducing a computerized system of record keeping based on a portable palm top computer. This has enabled the careful analysis of the individual work load of each trainee in the department by means of a specific program designed to generate a comprehensive report after the information from each individual has been downloaded on to a standard desk top computer. We have found a number of interesting and unexpected results and have highlighted ways in which the system may be improved.

Anesthesiology↗

PubMed2001

Confirmation of a gene locus for medullary cystic kidney disease (MCKD2) on chromosome 16p12.

BACKGROUND: Autosomal-dominant medullary cystic kidney disease (MCKD) is an interstitial nephropathy characterized by structural renal tubular defects that result in salt wasting and a reduction in urinary concentration. The condition has clinical and morphological similarities to autosomal-recessive juvenile nephronophthisis. Two genes predisposing to MCKD have been localized. MCKD1 on chromosome 1q21 was localized in two Cypriot families, and MCKD2 on chromosome 16p12 was localized in a single Italian family. We have evaluated a large Welsh MCKD family for linkage at these two loci. METHODS: Clinical data and DNA samples were collected from affected family members. Polymorphic microsatellite markers spanning the critical regions on chromosome 1 and chromosome 16 that encompass MCKD1 and MCKD2 were analyzed. Two-point and multipoint LOD scores were calculated. RESULTS: The family fulfilled previously published criteria for the diagnosis of MCKD, but hyperuricemia and gout were not prominent features. Twenty-one affected individuals were identified. Mean age at death or end-stage renal disease was 47 years (37 to 60). Linkage and haplotype analysis generated strongly negative results at MCKD1 on chromosome 1q21 (two-point LOD score = -5.32). Strong evidence of linkage to MCKD2 was generated with a maximum multi-point LOD score of 3.75. CONCLUSION: These results provide the first independent confirmation of a gene predisposing to MCKD on chromosome 16p12 and indicate that mutation of this gene is not restricted to a single family or population. The absence of hyperuricemia and gout in our family indicates that these are not obligatory features of MCKD2 mutations.

Adult↗