Accentuate the positive. A display system for clinical laboratory data.
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Clinical Laboratory Techniques↗
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A measure of association for assessing prediction accuracy that is a generalization of non-parametric ROC area.
There is a need for a measure of prediction accuracy that generalizes non-parametric receiver operating characteristic (ROC) area to polytomous ordinal patient state. We describe such a measure, prediction probability PK derived from Kim's measure of association. We show that the value of PK equals the value of non-parametric ROC area for dichotomous patient state and is a meaningful generalization of non-parametric ROC area for polytomous state.
Anesthesia↗
Cardiorespiratory effects of O-isobutyl S-[2-(diethylamino)-ethyl] methylphosphonothioate -- a structural isomer of VX.
O-Isobutyl S-[2-(diethylamino)ethyl]methylphosphonothioate (VR) is a structural isomer of a more well-known chemical warefare agent, O-ethyl S-[2(diisopropylamino)ethyl]methylphosphonothioate (code designation VX). In this study, cardiorespiratory and central nervous system (CNS) effects of VR (2LD50 or 22.6 microg kg(-1); s.c.) were evaluated in urethane-anesthetized (Group 1) and unanesthetized (Group 2) guinea pigs instrumented for concurrent recordings of electrocorticogram (ECoG) and a variety of cardiorespiratory activities. The first sign of intoxication was a state of progressive bradycardia, vascular hypotension and arrhythmia (Group 1, approximately 13 min post-VR; Group 2, approximately 6 min post-VR). Bradypnea, excessive salivation and compensatory changes in blood pressure typically did not emerge until 3-5 min prior to apnea (Group 1, approximately 28 min post-VR; Group 2, approximately 15 min post-VR). An idioventricular rhythm, which signalled a failing myocardium, appeared at the same time or shortly after the development of a bradypneic profile. Another notable toxicity component of VR, based on arterial pH, pO2/pCO2 and bicarbonate (HCO3-) level data, was a state of combined hypercapnia, acidemia and hypoxemia during the development of bradypnea. Taken together, findings from this study indicated that changes in medullary respiratory unit activity and ECoG data displayed little, if any, notable signs of CNS perturbation prior to the terminal stage (approximately 1 min prior to respiratory failure). Thus, in addition to displaying a greater sensitivity to perturbation by VR, the peripheral cardiorespiratory system components also appeared to play a more important role in precipitating a progressively dysfunctional cardiorespiratory status that ultimately led to collapse of central respiratory mechanisms and death.
Acidosis↗
Application of self-organizing maps for the detection and classification of human blood plasma lipoprotein lipid profiles on the basis of 1H NMR spectroscopy data.
Efficient and relevant classification of clinical findings, i.e. diagnostic decision making, poses a major challenge in medicine. In relation to biomedical NMR spectroscopy the problem of classification is often accompanied by complex, heavily overlapping information. Self-organizing map (SOM) analysis has been successfully applied in many areas of research and was thus also considered as a potential tool for NMR data analysis. In this paper we demonstrate how SOM analysis can be used for automated NMR data classification. Our goal was analysis of plasma lipoprotein lipids, a complex but biochemically well understood and specified system. The results illustrate that clinically relevant lipid classifications can be obtained from the SOM analysis of 1H NMR spectral information alone. The resulting maps were calibrated using independent biochemical lipid analyses and were found to produce excellent clustering of the plasma samples into clinically useful groups: normal, type IIa, IIb and IV hyperlipidaemias. In addition to this traditional classification, we also present results from SOM analysis in which the reference vectors of the map were calibrated for plasma total cholesterol and triglycerides and high and low density lipoprotein C; the plasma lipid parameters that are currently considered as the most useful indicators of coronary heart disease risk. In all, the present results indicate that SOM analysis can cope well with complex NMR spectral information and is thus likely to have an independent role in the area of biomedical NMR data analysis.
Cholesterol↗
Echo-planar magnetic resonance myocardial perfusion imaging: parametric map analysis and comparison with thallium SPECT.
Magnetic resonance (MR) perfusion FLASH imaging has been used for assessing coronary artery disease (CAD). Echo-planar MR techniques have advantages in speed and in making MR perfusion imaging results more clinically accessible through parametric maps, but have not been previously assessed. We implemented a spin-echo, echo-planar MR technique and applied it at rest and during adenosine stress in 26 patients with CAD and abnormal thallium single-photon-emission computed tomography (SPECT), and analyzed the results by using a newly developed parametric map analysis of time to peak, peak intensity, and slope of contrast washin. The results were compared with the results of conventional visual analysis of the perfusion cine series. For detecting abnormal coronary territories, MR and SPECT were comparable for sensitivity, specificity, and accuracy (thallium, 70%, 78%, and 73%; MR, 79% 83%, and 80%; P = NS). There was good agreement between thallium and MR during stress (kappa = 0.49), but defects were larger by MR (2.4 vs. 3.1 segments for slope; P < 0.01). Additional segments were detected at rest by MR (58 for slope vs. 25 for thallium), which correlated with areas that became abnormal with stress in the thallium (sensitivity, 100%; specificity, 63%). The parametric maps were easier and faster to interpret than review of the original first-pass series of images (chi2 = 10.8; P < 0.04). The diagnostic performance of echo-planar perfusion MR and SPECT was similar, and combining the results with parametric mapping was useful for interpretation and considerably improved data display for clinical interpretation. MR, however, was faster and yielded images of higher resolution with no radiation burden. In multislice mode, these new MR techniques may have clinical value.
Aged↗
Disposable polymeric high-density nanovial arrays for matrix assisted laser desorption/ionization-time of flight-mass spectrometry: I. Microstructure development and manufacturing.
In order to meet the expected enormous demand for mass spectrometry (MS) throughput as a result of the current efforts to completely map the human proteome, this paper presents a new concept for low-cost high-throughput protein identification by matrix assisted laser desorption/ionization-time of flight-(MALDI-TOF)-MS peptide mapping using disposable polymeric high-density nanovial MALDI target plates. By means of microfabrication technology precision engineered nanovial arrays are fabricated in polymer substrates such as polymethylmethacrylate (PMMA) and polycarbonate (PC). The target plate fabrication processes investigated were precision micromilling, cold embossing and injection moulding (work in progress). Nanovial dimensions were 300, 400 or 500 microm. Typical array densities were 165 nanovials/cm2, which corresponds to 3,300 vials on a full Applied Biosystems MALDI target plate. Obtained MALDI data displayed equal mass resolution, accuracy, signal intensity for peptide standards as compared to high-density silicon nanovial arrays previously reported by our group [7], as well as conventional stainless steel or gold targets.
Disposable Equipment↗
Retrospective follow-up study of foundry and engine plant workers.
A retrospective follow-up study of 21,013 workers employed at a foundry and two engine manufacturing plants was conducted to determine if these workers had an unusual mortality experience. A total of 2,235 deaths occurred during the follow-up period of 1970-1987. Mortality from all causes was lower than expected. Men experienced a 6-13% excess of lung cancer deaths, depending on the choice of the comparison group. The data displayed evidence of a positive trend between lung cancer mortality and increasing duration of employment (p = 0.008). White men experienced a statistically significant excess of deaths from stomach cancer (standardized mortality ratio [SMR] = 158; 95% confidence interval [CI] = 101-234). Black men had increased mortality from pancreatic cancer, especially among engine plant workers (SMR = 303; CI = 121-624), and an excess of prostate cancer, concentrated among foundry workers (SMR = 234; CI = 112-430).
Adult↗
Characterizing aquatic bacteria according to population, cell size, and apparent DNA content by flow cytometry.
Flow cytometry offers a rapid method for characterizing aquatic populations according to the properties of individual cells. This technology has been extended to aquatic bacteria by using high-intensity UV excitation, condensing the laser beam onto a small area, using blemish-free flow cells, optimizing organism staining protocol, segregating the optical signal produced with high-transmittance optical filters, collecting the signal with sensitive photomultipliers, and expanding the range of data displayed from individual samples with calibrated circuitry. Bacteria could be counted according to event frequency, and populations agreed with direct counts by epifluorescence microscopy. Forward scatter intensity was a linear function of volume for bacterial cells between 1.3 and 0.25 micron 3 as calibrated by Coulter impedance. Plastic spheres down to 0.014 micron 3, 0.3 micron in diameter, were resolved. Aquatic bacteria 0.05 micron 3 in volume were clearly resolved according to DNA content by staining with DAPI. The observed signal was DNA-dependent because DNase treatment eliminated most fluorescence. These procedures are suitable for direct analysis of the bacteria in marine and freshwater samples without interference from algae, sediment, or most DNA-free organic particles. Cytograms indicated one or more clearly resolved subpopulations of bacteria of substantially smaller size and DNA content than the laboratory organisms typically classified.
Bacteria, Anaerobic↗
The early origins and development of the scatterplot.
Of all the graphic forms used today, the scatterplot is arguably the most versatile, polymorphic, and generally useful invention in the history of statistical graphics. Its use by Galton led to the discovery of correlation and regression, and ultimately to much of present multivariate statistics. So, it is perhaps surprising that there is no one widely credited with the invention of this idea. Even more surprising is that there are few contenders for this title, and this question seems not to have been raised before. This article traces some of the developments in the history of this graphical method, the origin of the term scatterplot, the role it has played in the history of science, and some of its modern descendants. We suggest that the origin of this method can be traced to its unique advantage: the possibility to discover regularity in empirical data by smoothing and other graphic annotations to enhance visual perception.
Animals↗
Morphology of the gastrointestinal tract in primates: comparisons with other mammals in relation to diet.
Three categories of dietary adaptation are recognized--faunivory, frugivory, and folivory--according to the distinctive structural and biochemical features of animal matter, fruit, and leaves respectively, and the predominance of only one in the diets of most species. Mammals subsisting mainly on animal matter have a simple stomach and colon and a long small intestine, whereas folivorous species have a complex stomach and/or an enlarged caecum and colon; mammals eating mostly fruit have an intermediate morphology, according to the nature of the fruit and their tendency to supplement this diet with either animal matter or leaves. The frugivorous group are mostly primates: 50 of the 78 mammalian species, and 117 of the 180 individuals included in this analysis are primates. Coefficients of gut differentiation, the ratio of stomach and large intestine to small intestine (by area, weight, and volume), are low in faunivores and high in folivores; the continuous spread of coefficients reflects the different degrees of adaptation to these two dietary extremes. Interspecific comparisons are developed by allowing for allometric factors. In faunivores, in which fermentation is minimal, the volume of stomach and large intestine is related to actual body size, whereas these chambers are more voluminous in larger frugivores and mid-gut fermenting folivores; fore-gut fermenters show a marked decrease in capacity with increasing body size. Surface areas for absorption are related to metabolic body size, directly so in frugivores; area for absorption is relatively less in larger faunivores and more in large folivores, especially those with large stomachs. Indices of gut specialization are derived from these regressions by nonlinear transformation, with references to the main functional features of capacity for fermentation and surface area for absorption. These are directly comparable with the dietary index, derived from quantitative feeding data displayed on a three-dimensional graph, with all species within a crescentic path from 100% faunivory through 55--80% frugivory to 100% folivory, perhaps illustrating, at least for primates, the evolutionary path from primitive insectivorous forms through three major ecological grades.
Animals↗
Ultrastructural qualitative and quantitative data on the sporogenesis of the protozoan Abelspora portucalensis (Microspora, Abelsporidae): a different approach to the study of microsporidia.
The sporogenesis of the microsporidium Abelspora portucalensis was studied with electron microscopy. In qualitative terms, new aspects of the cytoplasmic ultrastructure of the schizont, sporont, and sporoblast are described: the presence of microtubules, of aggregates of small opaque vesicles, and of dispersed larger vesicles with clear matrix. The hypothesis that the opaque vesicles may represent the Golgi apparatus and the clear vesicles may correspond to the smooth endoplasmic reticulum is discussed. The use of standard stereological and statistical techniques gives us a new perspective on the development of this microsporidium. The most relevant quantitative data display that the amount of rough endoplasmic reticulum (either in relative or absolute terms) presents significant differences among the three stages, with the sporont showing the highest values; that the absolute (but not the relative) volume of the large vesicles significantly changes during sporogenesis with the highest values presented by the sporont; that the surface-to-volume ratio of the schizont and sporont cells is similar and significantly greater than that of the sporoblast cell; that the surface density of the nucleus in relation to soma remains constant in the three stages (on the contrary, the surface-to-volume ratio of the nucleus increases and its volumetric density diminishes); and finally, that the nucleolus decreases its relative and absolute volumes. The functional significance of these results is analyzed and the application of similar methodology in quantifying the effects of drugs upon microsporidia is suggested.
Animals↗
The staging of childhood acute lymphoblastic leukemia: strategies of the Childrens Cancer Study Group and a three-dimensional technic of multivariate analysis.
In childhood acute lymphoblastic leukemia, univariate analyses have identified more than thirty clinical and laboratory prognostic factors. Multivariate analysis is used to sort out the most independent and predictive of these factors, but the methods used are mathematically and conceptually complex. In this report, we depict the interactions between multiple variables graphically using 3-dimensional data displays. This approach helps conceptualize the multivariate process and provides an alternative method. We applied the method to the 2,987 children in the CCG-160 series of studies, and specifically to the "high-risk" subgroups: initial white cell count (WBC) greater than 50,000/microliter; white count greater than 50,000/microliter in conjunction with a mediastinal mass; age at diagnosis less than 1 year; and, central nervous system (CNS) leukemia at diagnosis. Analyzed in this fashion, T-cell immunophenotype, the presence of a large mediastinal mass, CNS leukemia, and the lymphomatous pattern lose their prognostic value when outcome is stratified by age and WBC. The 3-dimensional method confirms the mathematical analyses and provides graphic evidence for the conclusions.
Age Factors↗
The application of depth-pulse localized 31P NMR spectroscopy to monitor tumor metabolism and response to chemotherapy in the rat kidney.
To illustrate the spatial variations in metabolism within tumors, 31P spectral data are presented from a predefined, depth-pulse localized region of a rat kidney impregnated with Walker sarcoma cells. These data display the changes in energy metabolism during infiltration of the kidney by the tumor and during treatment of the tumor with cyclophosphamide.
Animals↗
Single heartbeat cardiac tagging for the evaluation of transient phenomena.
Many cardiac abnormalities are of a transient nature, creating a beat-to-beat variation in myocardial function. This work presents the cardiac imaging technique for the measurement of regional function during transient cardiac phenomena. All information necessary for the reconstruction of a cine loop is acquired within a single heartbeat, avoiding the temporal blurring introduced by segmented imaging due to the assumption of cardiac cycle periodicity. This method incorporates a gradient-optimized, high-efficiency EPI-SSFP sequence and TSENSE parallel imaging. For acquisitions with readout resolutions of 128,160, 192, and 256 points, the technique produced images with average temporal resolution of 35, 39, 43, and 52 ms and average spatial resolutions of 2.65, 2.12, 1.77, and 1.32 mm in the readout direction, respectively, and 2.88 and 2.08 mm in the phase encode direction for acceleration rates of 3 and 4, respectively. Local apparent strains in the single slice and measurements of ventricular end-systolic and end-diastolic areas were used as quantitative measures to validate the single heartbeat technique. To demonstrate the utility of the sequence, movie loops were acquired for multiple heartbeats in non-breath-held acquisitions as well as during a Valsalva maneuver. A heartbeat-interleaved acquisition allowed for the reconstruction of nonaccelerated images from R contiguous heartbeats. Images reconstructed from such data displayed tag blurring and reduced tag persistence due to motion and inter-heartbeat variability. Images acquired during the Valsalva maneuver demonstrated apparent beat-to-beat variability, visible both in the images and as changing strain patterns and ventricular volumes.
Adult↗
Testing normality of fetal DNA concentration in maternal plasma at 10-12 completed weeks' gestation: a preliminary approach to a new marker for genetic screening.
OBJECTIVES: To test the distribution of fetal DNA in maternal plasma expressed as gen/eq in a population of normal pregnancies. METHODS: Peripheral blood samples were obtained from 63 women (85% > or =35 years of age at delivery) bearing a euploid male fetus. Each patient underwent chorionic villus sampling (CVS) for karyotype analysis and/or beta thalassemia screening. Ultrasound scanning was used to determine gestational age. At 10-12 weeks' gestation, a peripheral blood sample was collected followed by CVS. To detect the Y chromosome specific sequences (SRY) quantitative polymerase chain reaction (PCR) analysis was used. Normal distribution of the data was tested by means of the Kolmogorov-Smirnov (KS) test. A Symmetry test (reliability p>0.05) was used to evaluate the reliability of the median. RESULTS: Only after natural logarithmic transformation did the data display a normal distribution. The median value of fetal DNA was 23.3 gen/eq (range 2.08-195), interquartile range 18.57-45.4. A Pearson test showed a significant correlation between gestational age and fetal DNA concentration (r=0.25, p=0.045). CONCLUSION: The present finding is a preliminary step towards a possible integration of fetal DNA with other variables (biochemical and/or ultrasound). It may serve to improve the discrimination of the screening for genetic diseases in the first trimester. Because of the relatively high dispersion, adjustments for possible covariates would appear to be necessary in further studies.
Chorionic Villi Sampling↗
An improved thin-layer chromatography/mass spectrometry coupling using a surface sampling probe electrospray ion trap system.
A combined surface sampling probe/electrospray emitter coupled with an ion trap mass spectrometer was used for the direct read out of unmodified reversed-phase C18 thin-layer chromatography (TLC) plates. The operation of the surface sampling electrospray ionization interface in positive and negative ionization modes was demonstrated through the direct analysis of TLC plates on which a commercial test mix comprised of four dye compounds viz., rhodamine B, fluorescein, naphthol blue black, and fast green FCF, and an extract of the caffeine-containing plant Ilex vomitoria, were spotted and developed. Acquisition of full-scan mass spectra and automated collection of MS/MS product ion spectra while scanning a development lane along the surface of a TLC plate demonstrated the advantages of using an ion trap in this combination. Details of the sampling system, benefits of analyzing a developed lane in both positive ion and negative ion modes, levels of detection while surface scanning, surface scan speed effects, and the utility of three-dimensional data display, are also discussed.
Amido Black↗
Kaplan-Meier, marginal or conditional probability curves in summarizing competing risks failure time data?
In the context of competing risks the Kaplan-Meier estimator is often unsuitable for summarizing failure time data. We discuss some alternative descriptive methods including marginal probability and conditional probability estimators. Two-sample test statistics are also presented.
Bone Marrow Transplantation↗
Low-resolution structure of the proteolytic fragments of the Rapana venosa hemocyanin in solution.
Rapana venosa hemocyanin (Hc) is a giant oxygen-binding protein consisting of different subunits assembled in a hollow cylinder. The polypeptide chain of each subunit is believed to be folded in several oxygen-binding functional units of molecular mass 50 kDa, each containing a binuclear copper active site. Limited proteolysis with alpha-chymotrypsin of native R. venosa hemocyanin allows the separation of three functional proteolytic fragments with molecular masses of approximately 150, 100, and 50 kDa. The functional fragments, purified by combining gel filtration chromatography and ion-exchange FPLC, were analyzed by means of small-angle X-ray scattering (SAXS). The gyration radius of the 50-kDa Rapana Hc fraction (2.4 nm) agrees well with that calculated on the basis of the dimensions determined by X-ray crystallography for one functional unit of Octopus Hc (2.1 nm). Independent shape determination of the 50- and 100-kDa proteolytic fragments yields consistent low-resolution models. Simultaneous fitting of the SAXS data from these fragments provides a higher-resolution model of the 100-kDa species made of two functional units tilted with respect to each other. The model of the 150-kDa proteolytic fragment consistent with the SAXS data displays a linear chain-like aggregation of the 50-kDa functional units. These observations provide valuable information for the reconstruction of the three-dimensional structure of the minimal functional subunit of gastropod hemocyanin in solution. Furthermore, the spatial relationships among the different functional units within the subunit will help in elucidation of the overall quaternary structure of the oligomeric native protein.
Animals↗