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Exploring spatial patterns of mortality: the new atlas of United States mortality.

The National Center for Health Statistics, CDC, has produced an Atlas of United States Mortality which includes maps of rates for the leading causes of death in the United States for the period 1988-1992. As part of this project, many aspects of statistical mapping have been re-examined to maximize the atlas's effectiveness in conveying accurate mortality patterns to epidemiologists and public health practitioners. Because recent cognitive research demonstrated that no one map style is optimal for answering many different map questions, maps and graphs of several different mortality statistics are included for each cause of death. New mixed effects models were developed to provide predicted rates and improved variance estimates. Results from these models were smoothed using a weighted head-banging algorithm to produce maps of general spatial trends free of background noise. Maps of White female lung cancer rates from the new atlas are presented here to illustrate how this innovative combination of maps and graphs permits greater exploration of the underlying mortality data than is possible from previous single-map atlas designs. Published in 1999 by John Wiley & Sons, Ltd. This article is a U.S. Government work and is in the public domain in the United States.

Adult↗

Comparing diagnostic tests: a simple graphic using likelihood ratios.

The diagnostic abilities of two or more diagnostic tests are traditionally compared by their respective sensitivities and specificities, either separately or using a summary of them such as Youden's index. Several authors have argued that the likelihood ratios provide a more appropriate, if in practice a less intuitive, comparison. We present a simple graphic which incorporates all these measures and admits easily interpreted comparison of two or more diagnostic tests. We show, using likelihood ratios and this graphic, that a test can be superior to a competitor in terms of predictive values while having either sensitivity or specificity smaller. A decision theoretic basis for the interpretation of the graph is given by relating it to the tent graph of Hilden and Glasziou (Statistics in Medicine, 1996). Finally, a brief example comparing two serodiagnostic tests for Lyme disease is presented. Published in 2000 by John Wiley & Sons, Ltd.

Diagnostic Tests, Routine↗

Flow analysis for determination of paraoxon with use of immobilized acetylcholinesterase reactor and new type of chemiluminescent reaction.

A highly sensitive flow analysis method for determination of acetylcholinesterase (AChE) inhibitors like organophosphorous pesticides using a new chemiluminescent reaction was developed and optimized. This method is fast, sensitive, and cheap, because it requires only one enzyme and its substrate. The system incorporates a reactor with immobilized AChE on controlled pore glass (CPG) and a chemiluminometric detector. Variations in enzyme activity due to inhibition are measured from the changes of concentrations of thiocholine produced when the substrate (acetylthiocholine chloride) is pumped before and after the passage of the solution containing the pesticide through the immobilized AChE reactor. Thiocholine is determined by a new chemiluminescent reaction with luminol in the presence of potassium ferricyanide. The percentage inhibition of enzyme activity is correlated to the pesticide concentration. The inhibited enzyme is reactivated by 10 mM pyridine-2-aldoxime methiodide (2-PAM). The experimental conditions were first optimized for activity determination of the effect of pH, flow rates, and Tris concentrations. For the measurement of AChE inhibition, the appropriate concentration of the substrate is selected such that the rate of noninhibited reaction can be considered unchanged and could be used as a reference. For optimization of experimental conditions for inhibition, several parameters of the system are studied and discussed: flow rate, enzyme-pesticide contact time, luminol concentration, ferricyanide concentration, 2-PAM concentration, and configuration of the FIA manifold. Paraoxon, an organophosphorous pesticide was tested. For an inhibition time of 10 min the calibration graph is linear from 0.1 to 1 ppm paraoxon with a relative standard deviation (n = 5) of 4.6% at 0.5 ppm. For an inhibition time of 30 min the calibration graph is linear from 25 to 250 ppb paraoxon.

Acetylcholinesterase↗

Cellular sociology applied to neuroendocrine tumors of the lung: quantitative model of neoplastic architecture.

This paper reports on cellular sociology, which consists of modeling tissular architecture based on graph theory. Voronoi's diagram was chosen to build the models. This diagram derives from a cell neighborhood concept and generates parameters which objectively represent tissue architecture. Minimal spanning tree (MST) is probably the more frequently used among graphs and successfully discriminates different grades of pathological process. However, Voronoi's diagram is more comprehensive and a more complete representation of architecture with the advantage of stability. The lung neuroendocrine tumor classification is far from being consensual, especially for lesions which don't fall in with typical carcinoid and small cell carcinoma groups. By comparing architectural models of 20 neuroendocrine tumors of the lung, this work supports the morphologic spectrum concept of these tumors and also supports the recently proposed concept of large-cell neuroendocrine tumors of the lung. Finally, architectural parameters separate small-cell-lung carcinomas from neuroendocrine non-small-cell lung carcinomas.

Carcinoid Tumor↗

Classification of organelle trajectories using region-based curve analysis.

A method based on analysis of the region of movement and the functioning of the acto-myosin cytoskeleton has been elaborated to quantify and classify patterns of organelle movement in tobacco pollen tubes. The trajectory was dilated to the region of movement, which was then reduced to give a one-pixel-wide skeleton, represented by a graph structure. The longest line in this skeleton was hypothesized to represent the basic track of the organelle along a single actin filament. Quantitative features were derived from the graph structure, direction of movement on the longest skeletal line, and distance between skeletal line and particle. These features corresponded to biological events like the amount of linear movement or the probability of attachment of an organelle to the actin filament. From 81 analyzed organelle trajectories, 17 had completely linear, 17 had completely non-linear, and 47 had alternating linear and non-linear movement. Selected features were employed for classification and ranking of the movement patterns of a representative sample of the population of organelles moving in the cell tip. The presented methods can be applied to any field where analysis and classification of particle motion are intended.

Actin Cytoskeleton↗

Suicide rates and methods in different age groups: Australian data and perceptions.

OBJECTIVES: The two major aims of this study were (1) to assess senior medical students' knowledge of the age pattern of suicides in Australia, and (2) to note changes in the pattern of suicide in recent years. DESIGN: (1) Two groups of medical students were asked to graph the age distribution of Australian male and female suicides. (2) Suicide statistics (up to 1994) were provided by the Australian Bureau of Statistics. RESULTS: (1) Only 40% of the 75 medical students were aware that suicide in Australia is much more frequent among males. Only two of the 75 drew graphs that were similar to the true pattern. (2) The male rate of suicide at age 20-40 years was almost 35 per 100000 in 1989-94; above 80 years it was nearly 40 per 100000. The female suicide rate of all age groups from 20 years to late old age was about 7 per 100000. The most striking changes in method of suicide in Australia in recent years have been the doubling of male rates of suicide by hanging and car exhaust fumes, increases being greater in younger age groups. Elderly females are more likely than younger females to use hanging as a means of suicide. CONCLUSIONS: Male suicide rates peak in young adulthood and (higher) in late old age. Senior medical students were unaware of the true age and sex patterns of suicide in Australia. Treating depressions and preventing suicides of elderly people (as well as of young people) should be top priorities.

Adolescent↗

Statistical analysis of nuclear genome size of plants with flow cytometer data.

BACKGROUND: There is a mismatch between the sophistication of the cytometer and the resulting data, made possible by the computing power of today, and the traditional statistical methods based on the computing power of the early 1930s. The purpose here is to apply modern statistical techniques that similarly take advantage of this computer power. METHODS: Likelihood functions and their graphs are introduced as direct measures of plausibility of the parameters of interest. These methods are valid for samples of any size. They are exemplified on an experimental plant flow cytometer data set with n = 2 replications. RESULTS: The likelihood functions revealed important features of the data that would have been missed by the traditional methods, and in fact would invalidate them. CONCLUSIONS: The likelihood function produced highly informative graphs that allow quantitative comparisons of different aspects of 2C DNA nuclear contents among different groups or varieties of plants.

Analysis of Variance↗

Corticosteroids for preventing relapse following acute exacerbations of asthma.

BACKGROUND: Acute asthma is responsible for many emergency department visits annually. Between 12-16% will relapse to require additional interventions within two weeks of ED discharge. Treatment of acute asthma is based on rapid reversal of bronchospasm and reducing airway inflammation and this review examines the evidence for using systemic corticosteroids to improve outcomes after discharge from the ED. OBJECTIVES: To determine the benefit of corticosteroids (oral, intramuscular, or intravenous) for the treatment of asthmatic patients discharged from an acute care setting (i.e. usually the emergency department) after assessment and treatment of an acute asthmatic exacerbation. SEARCH STRATEGY: The Cochrane Airways Group "Asthma and Wheez* RCT" register was searched using the terms: a) Asthma OR Wheez* b) Glucocorticoid OR Steroid* AND c) Exacerbat* OR Relapse* OR Emerg*. In addition, authors of all included studies were contacted to determine if unpublished studies which met the inclusion criteria were available. Bibliographies from included studies, known reviews and texts were also searched for additional citations. SELECTION CRITERIA: Only randomized controlled trials were eligible for selection. Studies were included in this review if they dealt with the outpatient treatment of asthmatic exacerbations using glucocorticoids at discharge and reported either relapse rate or PFTs. Two independent reviewers first identified potentially relevant studies and then selected articles for inclusion. Methodological quality was assessed independently by two reviewers. Agreement was assessed using kappa (k) statistics. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers; authors were contacted to verify the extracted data and clarify missing information. When author contact was unsuccessful, missing data were estimated from graphs where possible. Sensitivity, sub-group and overall analyses were performed using the Cochrane Review Manager. MAIN RESULTS: A search that yielded 229 references identified 169 (73%) original publications. Reviewers identified 8 studies for potential inclusion (k =0.76); 18 references were added by searching publication reference lists and contact with authors. Of these 26 articles, a total of 7 were included in the overview. Two studies used intramuscular corticosteroids, five studies used oral corticosteroids. Significantly fewer patients in the corticosteroid group relapsed to receive additional care in the first week (odds ratio (OR) 0.35; 95% confidence interval (CI): 0.17, 0.73). This favourable effect was maintained over the first 21 days (OR 0.33; 95% CI: 0.13, 0.82). Patients receiving corticosteroids had less need for beta-agonists (weighted mean difference (WMD) -3.3 activations/day; 95% CI: -5.5, -1.0). Changes in pulmonary function tests (SMD 0.045; 95% CI: -0.47, 0.56) and side effects (SMD 0.03; 95% CI : -0.38, 0.44) in the first 7-10 days, while rarely reported, showed no differences between the treatment groups. Statistically significant heterogeneity was identified for the side effect results; all other outcomes were homogeneous. It appears that IM corticosteroids are similarly efficacious to a 7-10 day tapering course of oral agents. From these results, as few as 13 patients need to be treated to prevent relapse to additional care after an exacerbation of asthma. REVIEWER'S CONCLUSIONS: A short course of corticosteroids following assessment for an acute exacerbation of asthma significantly reduces the number of relapses to additional care and decreases beta-agonist use without an apparent increase in side effects. Intramuscular corticosteroids appear as effective as oral agents.

Acute Disease↗

A [2]catenane and a [2]rotaxane as prototypes of topological and Euclidean molecular "rubber gloves".

A [2]catenane and a [2]rotaxane have been prepared from a C2-symmetric, 2,9-diphenyl-1,10-phenanthroline-based (dpp-based) macrocycle incorporating a 1,5-dioxynaphthalene subunit by means of the transition metal templated technique. In the case of the catenane, this macrocycle is interlocked with a dpp-based macrocycle that is oriented through the location of a p-tolyl substituent in the 4-position of the phenanthroline subunit. In the case of the rotaxane, the C2-symmetric macrocycle is threaded onto an oriented, dumbbell-shaped molecule, based on the same 4-p-tolyl-1,10-phenanthroline subunit, which bears tetraarylmethane stoppers. Both species are chemically achiral molecules, yet they are composed entirely of asymmetric, mirror-image conformations. Conformational enantiomerization processes therefore take place exclusively by chiral pathways, conferring on these molecules the "rubber glove" property. However, while the molecular graph (constitutional formula) of the [2]rotaxane can be deformed into a planar and, hence, rigidly achiral representation, a feature shared by a few other compounds in the literature that have been characterized as "Euclidean rubber gloves", the molecular graph of the [2]catenane cannot be deformed in this way. It therefore has the unique property of being a chemically achiral "topological rubber glove".

Journal Article↗

Micellar electrokinetic capillary chromatography for the determination of Viagra and its metabolite (UK-103,320) in human serum.

Micellar electrokinetic capillary chromatography (MEKC) was investigated for the determination of Viagra (sildenafil citrate, SC) and its metabolite (UK-103,320) in human serum in a concentration range of clinical interest. For MEKC, human serum samples spiked with SC and UK were obtained directly after elution with methanol from a tC18 cartridge. The extract was evaporated and regenerated in a solution 1 mM of phosphate buffer (pH 12.3) which contained a methanol percentage of 20% that was analyzed using phosphate buffer (pH 12.3, 10 mM) containing 30 mM sodium dodecyl sulfate (SDS) as separation electrolyte and a fused-silica capillary. This method gave satisfactory interday precision with respect to migration times relative standard deviation (RSD < 1%) and linear responses for the concentration ranges investigated (0.50-3.50 mg L(-1) for the compound SC and 0.90-4.60 mg L(-1) for UK). An intraday RSD (n = 5 graphs) between the slopes of the calibration graphs was acceptable (6.40%) for SC and (3.37%) for UK. A satisfactory interday precision between slopes was also obtained (RSD 4.10% for SC and a RSD 2.72% for UK) which demonstrated the ruggedness of this method. Detection limits (S/N = 3) were about 200 ng/mL for both compounds in human serum. MEKC was shown as a good method with regards to simplicity, precision and sensitivity.

Electrophoresis, Capillary↗

CAMPS: computer-automated metacarpophalangeal profile system.

The metacarpophalangeal profile (MCP) pattern has been proven useful in describing individuals with genetic and nongenetic syndromes. However, the measurement of the 19 bone lengths is a tedious procedure requiring use of hand vernier calipers, detailed normative data to be looked up in extensive tables, hand calculator, and manual graphing techniques. Presently there are no reports of microcomputer-automated systems for the accurate measurement, recording, analysis, and graphing of MCP profiles. We describe a computer-automated metacarpophalangeal profile system (CAMPS) that will assist in the derivation of the MCP profile. This program allows the user to select different program routines that perform the functions necessary for MCP profile construction. The "data acquisition module" (DAM) assists in bone length measurement from contact prints of hand radiographs and stores the 19 measurements on a floppy disk. The "standardization analysis module" (SAM) then compares the 19 measurements to age- and sex-matched normal data and converts the raw data to z-score values. The "Pearson product-moment correlation module" (PPM) generates a correlation coefficient describing the degree of similarity between the two hands measured and graphically illustrates the resulting scatterplot. The "MCP plotting module" (MCPM) provides a graphic plot of the 19 bones in either transverse rows or phalangeal rays on a dot-matrix printer or X-Y plotter.

Bone and Bones↗

The prenatal growth of the human body determined by the measurement of bones and organs by ultrasonography.

This paper presents the ultrasonographic analysis of the growth of two groups of human fetuses, one longitudinal and the other cross-sectional. Measurements of all the long bones were taken, as well as measurements of the following diameters: Biparietal, occipitofrontal, thoracic and abdominal anterior/posterior and transverse, spinal canal width, arm, forearm, thigh and leg transverse. The bladder and the stomach were also measured. The pregnancies analyzed covered the period between the 8th and 38th week of gestation. Centiles (3rd-97th) were calculated for each structure and week. All pregnancies known or suspected to be abnormal were removed from the study. The values obtained were tested in 102 pregnancies (test group); the expected values (from the graphs) did not deviate from the values obtained from this group of fetuses, demonstrating the reliability of the values presented in these graphs. All structures measured showed linear growth. There was no significant difference between the longitudinal and cross-sectional groups.

Adolescent↗

The spectrum of hippocampal sclerosis: a quantitative magnetic resonance imaging study.

One hundred patients with intractable temporal lobe epilepsy and 22 control subjects were scanned on a 1.5-T Siemens SP63 Magnetom scanner. A combination of hippocampal T2 mapping, hippocampal volume measurement corrected for intracranial volume, and inspection of hippocampal morphology on a hippocampal volume distribution graph compared with a control graph revealed previously undetected forms of bilateral hippocampal sclerosis and four false-positive diagnoses of hippocampal sclerosis made on visual inspection of the scans. A physiological asymmetry in the position of the hippocampi in 41% of control subjects and focal hippocampal atrophies in patients made measurement of the whole length of the hippocampus mandatory. The extent of hippocampal damage in patients with hippocampal sclerosis correlated with the number of secondary generalized seizures during a patient's lifetime. In contrast to patients with unilateral hippocampal sclerosis, patients with severe bilateral hippocampal sclerosis had no history of febrile convulsions. Twenty-six patients with intractable temporal lobe epilepsy had normal hippocampal magnetic resonance imaging measures and as a group were significantly older at the onset of habitual epilepsy than were patients with hippocampal sclerosis. In conclusion, a combination of quantitative magnetic resonance imaging techniques revealed a spectrum of hippocampal sclerosis and optimally defined boundaries of hippocampal normality. The spectrum of hippocampal sclerosis is related to the etiology, the number of secondary generalized seizures, and the age at onset of habitual epilepsy.

Adolescent↗

Simultaneous determination of glucose, 1,5-anhydro-d-glucitol and related sugar alcohols in serum by high-performance liquid chromatography with benzoic acid derivatization.

A new, simple and sensitive pre-column high-performance chromatographic method for the determination of diabetes marker d-glucose, 1,5-anhydro-d-glucitol and related compounds is reported. Sugars (d-glucose, d-galactose, d-mannose, sucrose and arabinose) were derivatized with benzoic acid (BA) at 80 degrees C for 60 min. l-Fucose, fructose, d-lactose, l-rhamnose, arabinose and ascorbic acid were not reacted. Sugar alcohols (xylitol, erythritol, mannitol, sorbitol myo-inositol) were also derivatized with BA at 80 degrees C for 60 min. The fluorescence derivatives were separated on a TSK amide 80 column (4.6 mm i.d. x 250 mm, 5 microm) with acetonitrile-50 mm acetate buffer (pH 5.6; 4:96, v/v) as the mobile phase. The detection wavelength of beizoic acid derivatives was lambda(ex) 275 nm and lambda(em) 315 nm. The detection limits of sugars were 10-80 microg/mL. The calibration graphs were linear up to 10 mg/mL. The relative standard deviations of 500 microg/mL sugars were 7.0-7.3%. The proposed method was compared with the enzymatic photometric glucose analysis method (Glucose B-Test II Wako). The correlation coefficient was 0.83 (n = 20) and y = 0.82x + 5.91, where y and x are concentrations in microg/mL obtained by the proposed pre-column HPLC and enzyme-photometric method, respectively. The detection limits of sugar alcohols were 100-1000 ng/mL. The calibration graphs were linear to 50 microg/mL and relative standard deviations of 10 microg/mL were 7.2-8.2%. The 1,5-AG data by the proposed method was also compared with the enzymatic photometric 1,5-AG analysis method (Rana AG 1,5-AG determination kit, Nihon Kayaku) and good correlation (r = 0.91, n = 20) was also obtained. The proposed method was applied to the simultaneous determination of d-glucose, 1,5-AG and related sugar alcohols in serum from healthy males.

Benzoic Acid↗

In vivo measure of average bacterial cell size from a polarized light scattering function.

A particular combination of elements of the Mueller matrix for scattering of polarized light given by (S34 + S14)/(S11 + S13) identical to (S34/S11)++ is measured vs angle at a wavelength of 633 nm for randomly oriented suspensions of several species of bacteria in different stages of growth. (This combination of elements is dominated in the present measurements by the behavior of the normalized S34 matrix element, as is indicated by the notation defined on the right side of the equation.) The resulting graph in each case shows an oscillating function of angle. This function is compressed toward smaller angles when the bacteria are in the exponential phase of growth in comparison with results for a suspension of the same bacteria in the stationary (starving-smaller cells) phase of growth. Microscopic measurements were made to determine, for each case, the average dimensions of the bacterial population. Graphs were then plotted of the peak positions from the Mueller matrix function plots vs either cell length or cell diameter. The function was shown to be strongly correlated with cell diameter under the conditions of this experiment and poorly correlated with cell length. The measurements were shown to have a sensitivity to changes in average diameter of about 20 nm.

Bacillus megaterium↗

Architectural analysis of oral cancer, dysplastic, and normal epithelia.

BACKGROUND: We present a novel, automated, and quantitative approach to evaluate local epithelial tissue architecture based on mathematical graph theory. METHODS: Four hundred forty-one images of three diagnostic classes of oral epithelium (normal, dysplastic, and neoplastic) were analysed. The epithelial compartment was partitioned into exclusive areas associated with each nucleus to approach the theoretical cell extents. The spatial arrangement of cells in neighbourhoods of two sizes was characterised by constructing graph networks based on the cell centroids and recording 29 statistical properties. We analysed 104,627 and 67,590 neighbourhoods of diameters 37.5 and 75 microm, respectively. RESULTS: The discrimination power of the architectural descriptors was evaluated by using discriminant analysis. The best neighbourhood discrimination rate was 75% for normal versus carcinoma. For the pooled data, discrimination into three classes based on largest number of neighbourhoods associated with each class was 100% correct. Case-wise, discrimination rates were 67%, 100%, and 80% correct for normal, premalignant, and malignant. When considering two classes, discrimination rates was 89% (normal) and 100% (malignant) correct, with 71% of premalignant cases assigned to the malignant class. CONCLUSIONS: The results indicate that unbiased and reproducible quantification of tissue architectural features is possible and may provide valuable morphological information for diagnostic purposes.

Cytodiagnosis↗

Radically simplifying the Henry function.

We recently established that every ion has two radii - a geometrical one and an electrokinetic one. Using this principle, and in accordance with Henry's method of determining his function, f(ka), we have discovered that the Henry function can be radically simplified. The graphs of the proposed equation are plotted at different argument values. They are identical with the graphs plotted according to the Henry function.

Ions↗

Development and validation of a robust capillary electrophoresis method for impurity profiling of etomidate including the determination of chiral purity using a dual cyclodextrin system.

An enantioselective CE assay for the simultaneous determination of the enantiomeric purity and of related substances of etomidate has been developed and validated using a binary chiral selector system employing 30 mg/mL beta-CD and 4.6 mg/mL sulfated-beta-CD in a 150 mM potassium phosphate buffer, pH 2.1. The method was validated with respect to specificity, range, linearity, LOQ and LOD, precision and accuracy. The assay allowed the detection and determination of related substances including (S)-etomidate at the 0.05% w/w level, the reporting threshold as defined by the International Conference on Harmonisation guidelines as well as the European Pharmacopoeia. Robustness testing was carried out by an "Augmented Plackett-Burman" design. Quantitation of the compounds was performed by calibration graphs with respect to lidocaine hydrochloride as internal standard and by peak area normalization, the procedure usually applied by pharmacopoeias. Although data obtained from the calibration graphs constructed with the aid of the internal standard were more accurate based on compound recovery, peak area normalization may also be used without significant loss of accuracy and precision.

Cyclodextrins↗