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Cardiac function and Fourier phase data from simulated Wolff-Parkinson-White syndrome in a baboon model.

The diagnostic value of Fourier phase analysis and planar scintigraphy in Wolff-Parkinson-White (WPW) syndrome has been suspect. This study investigates phase analytical data from planar radionuclide ventriculography of six baboons with simulated WPW syndrome by means of implanted electrodes. An electrode in the atrium controlled the heart rate and a subsequent stimulation was delivered by electrodes placed at different sites on the ventricles, delayed to cause the characteristic delta wave of the WPW syndrome. Sensitivity for accurately-localizing variously-situated first points of activation (FPAs) from the Fourier phase images was found highest for premature right ventricular (RV) activation, and for atrioventricular (AV) delays around 125 msec. Other sites were subject to artifacts. Changes in cardiac function, phase delay, and histogram parameters were not statistically meaningful.

Animals↗

Quantitative methods for assessing a synergistic or potentiated genotoxic response.

The problem of assessing chemical interactions in studies of genotoxicity is discussed. Attention is focused on assessing possible synergism or potentiation when the observed genotoxic response is binary (yes-no). Different forms of enhancement are distinguished based upon different assumptions on the genotoxic activity of the experimental treatments. A generalized linear statistical model is considered that links the probability of the binary response to the doses, and data-analytic strategies are described for detecting synergy and potentiation in factorially designed experiments. This approach is illustrated with a series of analyses of various genotoxicity data-sets.

Aminacrine↗

Average volume of alcohol consumption and all-cause mortality in African Americans: the NHEFS cohort.

AIM: To analyze the relationship between average volume of alcohol consumption and all-cause mortality in African Americans. DESIGN: Prospective cohort study--the NHANES Epidemiologic Follow-Up Study (NHEFS)--with baseline data collected 1971 through 1975 as part of the first National Health and Nutrition Examination Survey (NHANES I) and follow-up through 1992. PARTICIPANTS: The analytic data set consisted of 2054 African American men (n = 768) and women (n = 1,286), 25 to 75 years of age, who were followed for approximately 19 years. MEASUREMENT: Alcohol was measured with a quantity-frequency measure at baseline. OUTCOME: All-cause mortality. RESULTS: No J-shaped curve was found in the relationship between average volume of alcohol consumption and mortality for male or female African Americans. Instead, no beneficial effect appeared and mortality increased with increasing average consumption for more than one drink a day. The reason for not finding the J-shape in African Americans may be the result of the more detrimental drinking patterns in this ethnicity and consequently the lack of protective effects of alcohol on coronary heart disease. Taking into account sampling design did not substantially change the results from the models, which assumed a simple random sample. CONCLUSIONS: If this result can be confirmed in other samples, alcohol policy, especially prevention, should better incorporate patterns of drinking into programs.

Adult↗

Proper assessment of the JFK assassination bullet lead evidence from metallurgical and statistical perspectives.

The bullet evidence in the JFK assassination investigation was reexamined from metallurgical and statistical standpoints. The questioned specimens are comprised of soft lead, possibly from full-metal-jacketed Mannlicher-Carcano (MC), 6.5-mm ammunition. During lead refining, contaminant elements are removed to specified levels for a desired alloy or composition. Microsegregation of trace and minor elements during lead casting and processing can account for the experimental variabilities measured in various evidentiary and comparison samples by laboratory analysts. Thus, elevated concentrations of antimony and copper at crystallographic grain boundaries, the widely varying sizes of grains in MC bullet lead, and the 5-60 mg bullet samples analyzed for assassination intelligence effectively resulted in operational sampling error for the analyses. This deficiency was not considered in the original data interpretation and resulted in an invalid conclusion in favor of the single-bullet theory of the assassination. Alternate statistical calculations, based on the historic analytical data, incorporating weighted averaging and propagation of experimental uncertainties also considerably weaken support for the single-bullet theory. In effect, this assessment of the material composition of the lead specimens from the assassination concludes that the extant evidence is consistent with any number between two and five rounds fired in Dealey Plaza during the shooting.

Famous Persons↗

[Psychiatric care research--an instrument for planning health care needs].

The planning of health care is primarily an administrative task. Service research supports the health administration in this task by supplying empirical data to objectify the need for care and ways to cater for that need. In this, service research on the one hand draws on descriptive and analytical data of epidemiological studies. On the other hand, indices of social structure provide information about factors influencing the utilisation of health services. Apart from this, different types of service utilisation data are used for the analysis of needs. None of the methods mentioned is sufficient on its own. Only the integration of the different levels of analysis allows sufficiently competent statements on health care needs.

Epidemiologic Studies↗

Interstitial lung disease related to dermatomyositis. Comparative study with patients without lung involvement.

OBJECTIVE: To compare clinical and histopathological data and outcome of patients with dermatomyositis (DM) with and without interstitial lung disease (ILD). METHODS: Patients diagnosed with definite DM were prospectively evaluated. Clinical and analytical data were recorded and muscle biopsies were performed. In patients with respiratory symptoms an extensive pulmonary evaluation was done. RESULTS: 104 patients were diagnosed with idiopathic inflammatory myopathy, 63 with DM. Eight of the patients with DM (13%) also had associated ILD. Arthralgia and fever were more frequently seen in the ILD group and there was no associated malignant condition. Either atypical or nonspecific cutaneous lesions were more frequently seen in ILD patients. Anti Jo-1 antibodies were positive in 75% of the patients with ILD and in 3% of patients with DM without ILD (p < 0.001). Bronchoalveolar lavage measured for cell count showed an increased lymphocyte count in 3/5 cases in which this data was recorded. Lung biopsies showed interstitial pneumonitis in 2 cases and desquamative interstitial pneumonitis in one. All patients achieved complete remission of muscular involvement. With respect to lung disease, 4/8 obtained complete remission, and the other 4 showed partial improvement. No significant statistical differences in terms of survival were found between the 2 groups. CONCLUSION: ILD associated with DM represents a subgroup of DM with clinical and biological differences. However, such patients do not have poorer prognosis than patients without ILD if they are managed aggressively with immunosuppressive drugs.

Aged↗

Biostatistical consultation for dental research.

Dental science researchers do not really need a detailed, ready-at-hand knowledge of statistics to design and perform high quality scientific research. Although the acquisition and utilization of such knowledge by dental researchers is not discouraged, it is proposed that it is more important for dental researchers to be committed to developing and maintaining a long term, ongoing, interactive consulting relationship with a biostatistician. The nature of this relationship will depend in large part on the complexity of the dental research being conducted. While the statistical consultant will assist in interpreting analytic results for the dental researcher, the latter will need to provide extensive input in assisting in the estimation of sample size and power, and for expressing scientific hypotheses in statistical terms so that the appropriate data analytic methodology can be specified.

Analysis of Variance↗

Screening for and validated quantification of amphetamines and of amphetamine- and piperazine-derived designer drugs in human blood plasma by gas chromatography/mass spectrometry.

The classical stimulants amphetamine, methamphetamine, ethylamphetamine and the amphetamine-derived designer drugs MDA, MDMA ('ecstasy'), MDEA, BDB and MBDB have been widely abused for a relatively long time. In recent years, a number of newer designer drugs have entered the illicit drug market. 4-Methylthioamphetamine (MTA), p-methoxyamphetamine (PMA) and p-methoxymethamphetamine (PMMA) are also derived from amphetamine. Other designer drugs are derived from piperazine, such as benzylpiperazine (BZP), methylenedioxybenzylpiperazine (MDBP), trifluoromethylphenylpiperazine (TFMPP), m-chlorophenylpiperazine (mCPP) and p-methoxyphenylpiperazine (MeOPP). A number of severe or even fatal intoxications involving these newer substances, especially PMA, have been reported. This paper describes a method for screening for and simultaneous quantification of the above-mentioned compounds and the metabolites p-hydroxyamphetamine and p-hydroxymethamphetamine (pholedrine) in human blood plasma. The analytes were analyzed by gas chromatography/mass spectrometry in the selected-ion monitoring mode after mixed-mode solid-phase extraction (HCX) and derivatization with heptafluorobutyric anhydride. The method was fully validated according to international guidelines. It was linear from 5 to 1000 micro g l(-1) for all analytes. Data for accuracy and precision were within required limits with the exception of those for MDBP. The limit of quantification was 5 micro g l(-1) for all analytes. The applicability of the assay was proven by analysis of authentic plasma samples and of a certified reference sample. This procedure should also be suitable for confirmation of immunoassay results positive for amphetamines and/or designer drugs of the ecstasy type.

Amphetamines↗

On parametric empirical Bayes methods for comparing multiple groups using replicated gene expression profiles.

DNA microarrays provide for unprecedented large-scale views of gene expression and, as a result, have emerged as a fundamental measurement tool in the study of diverse biological systems. Statistical questions abound, but many traditional data analytic approaches do not apply, in large part because thousands of individual genes are measured with relatively little replication. Empirical Bayes methods provide a natural approach to microarray data analysis because they can significantly reduce the dimensionality of an inference problem while compensating for relatively few replicates by using information across the array. We propose a general empirical Bayes modelling approach which allows for replicate expression profiles in multiple conditions. The hierarchical mixture model accounts for differences among genes in their average expression levels, differential expression for a given gene among cell types, and measurement fluctuations. Two distinct parameterizations are considered: a model based on Gamma distributed measurements and one based on log-normally distributed measurements. False discovery rate and related operating characteristics of the methodology are assessed in a simulation study. We also show how the posterior odds of differential expression in one version of the model is related to the ratio of the arithmetic mean to the geometric mean of the two sample means. The methodology is used in a study of mammary cancer in the rat, where four distinct patterns of expression are possible.

Animals↗

High-throughput method development approaches for bioanalytical mass spectrometry.

A rational approach to the development and optimization of solid-phase extraction (SPE) methods is described. The semiautomated scheme allows for the simultaneous testing of multiple chemistries using a custom multiple-sorbent 96-well method development plate. Optimized extraction conditions for up to five analytes are determined in a single 2.5-h experiment. The experiment can be tailored to determine SPE conditions (including wash protocols) for related analytes. Data obtained by liquid chromatography-atmospheric pressure ionization-mass spectrometry allows the quantitation of absolute recovery and selection of the best extraction conditions for approximately 100 analytes of diverse structure. Optimized extraction protocols yielding at least 80% recovery are determined for 81% of the analytes. For 96% of the analytes screened, extraction conditions resulting in recoveries of > or = 60% are determined. The most generic set of SPE conditions consist of either C8 or C18 sorbent with an eluent composition of acetonitrile with 5mM nitric acid added.

Acetonitriles↗

Partitioning of Zn, Pb and Cd in river sediments from a lead and zinc mining area using the BCR three-step sequential extraction procedure.

The extent of pollution was investigated in sediments collected along the course of the river Meza and its tributaries in the lead and zinc mining area of the Mezica valley (Slovenia). In order to evaluate the heavy metal burden, total concentrations of Zn, Pb and Cd were determined and the partitioning of these metals between the easily and sparingly soluble sediment fractions was performed by the use of the slightly modified BCR sequential extraction procedure. The quality of analytical data was checked with Certified Reference Material CRM 601. Good agreement between the determined and certified or indicative metal concentrations was obtained. In order to estimate the natural and anthropogenic inputs of Zn, Pb and Cd in the sediments, normalisation to Al was applied. The results of the partitioning study indicate that Zn prevails in the most sparingly soluble fraction and is distributed between organic matter and sulfides, while a smaller proportion is found in the easily soluble fraction. Pb is distributed mainly between organic matter and sulfides, whereas Cd is predominantly associated with the most sparingly soluble fraction. Data from the normalisation procedure indicate that the anthropogenic inputs of Zn, Pb and Cd correlate with the very high total metal concentrations determined in sediments. The highest total Zn, Pb and Cd concentrations (16.3. 9.3 and 0.13 g kg(-1), respectively) were found in the sediment of the Helena rivulet, arising from former mining activities. In spite of the relatively low easily soluble metal fractions in the sediment, the concentrations of metals in these fractions are high, owing to the extremely high total metal concentrations. These data indicate severe pollution of the terrestrial and aquatic environment.

Cadmium↗

Consideration of some taphonomic variables of relevance to forensic palynological investigation in the United Kingdom.

Palynology is a long established and respected branch of environmental science that has been applied to criminal investigation in a meaningful way only in recent years. It has proved to be remarkably versatile in many kinds of criminal enquiry. It is not, however, an absolute science; palynological data are on a par with the suites of symptoms which allow medical practitioners to make diagnoses. Taphonomic variability is the main factor complicating interpretation of forensic palynological data. Palynological taphonomy may be defined as "all the factors that influence whether a palynomorph (pollen, spore, or other microscopic entity) will be found at a specific place at a specific time". If taphonomic variability is anticipated, and regularly tested, palynology will continue to keep its place in the armoury of useful forensic methods. Some assumptions made by palynologists engaged in palaeoecology and archaeology have been shown to be untenable in the forensic context. Palynological and botanical profiling of crime scenes has demonstrated anomalies which challenge received wisdoms. It has proved impossible to obtain palynological population data because every site is unique - expectations of any palynological profile can only be crude. The palynological status of any place must be tested every time. Without a body of analytical data from the actual crime scene, it is difficult to see how any palynologist can hope to present credible arguments under cross-examination. The statements made in this paper relate mainly to work carried out in the United Kingdom.

Automobiles↗

Stability of rearrangement measures in the comparison of genome sequences.

We present data-analytic and statistical tools for studying rates of rearrangement of whole genomes and to assess the stability of these methods with changes in the level of resolution of the genomic data. We construct datasets on the numbers of conserved syntenies and conserved segments shared by pairs of animal genomes at different levels of resolution. We fit these data to an evolutionary tree and find the rates of rearrangement on various evolutionary lineages. We document the lack of clocklike behavior of rearrangement processes, the independence of translocation and inversion rates, and the level of resolution beyond which translocations rates are lost in noise due to other processes.

Animals↗

The effects of whole-body vibration on human biodynamic response.

The objective of vibration research at the Armstrong Laboratory includes the expansion and improvement of the measurement, quantification, analysis, and modeling of human vibration response. The driving-point impedance and transmissibility techniques have been expanded and are rigorously applied in the research efforts. Driving-point impedance is defined as the ratio between the transmitted force and input velocity at the point of load application. Transmissibility is typically defined as the ratio between the acceleration level measured at some location on the body and the input acceleration at the seat. These two ratios are used to assess the magnitude and frequency location of resonance behaviors where maximum motions occur in the body. From these data, analytical models are developed which can simulate the motions and coupling behaviors, and predict the stiffness and damping characteristics of the affected anatomical structures. The ultimate goal of the research is to provide new and improved data and modeling capability for revising exposure standards and for developing equipment design guidelines and criteria for improving tolerance and reducing physiological consequences. This paper describes the results of recent studies conducted to identify the biodynamic behavior of major anatomical structures affected by seated whole-body vibration, to develop an analytical model for simulating human vibration response, and to apply the model to evaluate the effects of seat cushion materials on the transmission/attenuation pathways.

Acceleration↗

Characterization of elemental pollution and its variations in sediments and suspended particulate matter from the River Elbe via multi-element analysis combined with chemometric data evaluation.

Sediments and suspended particulate matter taken from about 100 sampling sites along the River Elbe from the source to the mouth during the period 1992 and 1998 have been analyzed for the concentrations of more than 60 elements in each sample. The analytical data were subsequently processed by means of multivariate statistics in order to characterize the charge of the River Elbe with inorganic pollutants to elucidate pollution trends. Using factor analysis 18 elements were found to be enriched by human activities. By means of cluster analysis--using the 18 anthropogenically influenced elements as variables--the sampling sites were aggregated into groups having similar element distributions. Thus, the entire stretch of the River Elbe was divided into three sections of characteristic elemental pollution. Finally, the trends in anthropogenic pollution within the characteristic regions since the early nineties were assessed. It turned out that most of the anthropogenically influenced elements showed a decrease in the upper and middle parts of the river, whereas no decrease could be verified in the estuary region.

Environmental Monitoring↗

Retrospective data collection and analytical techniques for patient safety studies.

To enhance patient safety, data about actual clinical events must be collected and scrutinized. This paper has two purposes. First, it provides an overview of some of the methods available to collect and analyze retrospective data about medical errors, near misses, and other relevant patient safety events. Second, it introduces a methodological approach that focuses on non-routine events (NRE), defined as all events that deviate from optimal clinical care. In intermittent in-person surveys of anesthesia providers, 75 of 277 (27%) recently completed anesthetic cases contained a non-routine event (98 total NRE). Forty-six of the cases (17%) had patient impact while only 20 (7%) led to patient injury. In contrast, in the same hospitals over a two-year period, we collected event data on 135 cases identified with traditional quality improvement processes (event incidence of 0.7-2.7%). In these quality improvement cases, 120 (89%) had patient impact and 74 (55%) led to patient injury. Preliminary analyses not only illustrate some of the analytical methods applicable to safety data but also provide insight into the potential value of the non-routine event approach for the early detection of risks to patient safety before serious patient harm occurs.

Anesthesiology↗

Quality assurance in pathology. Cytologic and histologic correlation.

In this study we used a computerized program to compare the cytologic and histologic diagnoses made in a three-year period with the aim of evaluating the data obtained as an index of the diagnostic accuracy of cytology in a pathology quality assurance program. Concordance between the cytologic and histologic diagnoses was observed in 83.2% of the cases. In 1.2% the cytologic diagnosis was suspected malignancy, and 78.4% of these cases were positive for tumor at histologic examination. Analysis of the data must be performed in accordance with the anatomic site involved, and discordance must be investigated by a pathologist, especially in view of the different modalities of cytologic and histologic sampling. Analytic data on the breast, bladder and lung are presented.

Cell Biology↗

Heterogeneous cell response to topotecan in a CFSE-based proliferation test.

BACKGROUND: Carboxyfluorescein diacetate succinimidyl ester (CFSE) is currently used to investigate migration and proliferation of hemopoietic cells. In principle, CFSE is retained by the cells and is shared by the daughter cells at each division, resulting in multimodal flow cytometric CFSE histograms, with each cell generation clustering around half the fluorescence intensity of the previous one. However, intercell variability of CFSE loading results in overlapping peaks, thereby limiting its use with cancer cell lines. METHODS: We used IGROV1 ovarian cancer cells loaded with CFSE at the time of seeding; 24 h later cells were treated with an anticancer drug (topotecan). Potential pitfalls of the analysis were examined, and a procedure of evaluation of CFSE efflux was applied to fix the peak positions with good approximation in advance. Histograms were fitted by a series of gaussians, with each representing cells in a given generation. RESULTS: Effects of topotecan on IGROV1 cells were analyzed in terms of the time course of the percentage of cells that remained undivided or entered the second, third, and subsequent division cycles. A simple algorithm, which combined flow cytometric data with the absolute cell number independently measured by Coulter counter, provided an estimate of the 96-h outcome of the starting cell population by quantifying cells that remained undivided, those able to divide at least once, or those that had died. CONCLUSIONS: We assessed experimental and data analytic procedures for a CFSE-based measurement of antiproliferative activity of drugs in cancer cell lines. A quantitative level was achievable but required a strict procedure for control of the experimental data, which was not straightforward.

Antineoplastic Agents↗