Optimal data analysis using transmitted light intensities in analytical ultracentrifuge.
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BACKGROUND: Benzodiazepines are treatment mainstays for several disorders, but there is often concern about dependency and addiction. In January 1989, New York implemented regulations requiring physicians to order benzodiazepines using state-monitored triplicate prescription forms. OBJECTIVE: The purpose of this study was to assess the effects of the triplicate prescription program (TPP) on changes in use of benzodiazepines and other psychoactive drugs in clinically vulnerable Medicaid populations. METHODS: Using an interrupted time series with comparison series design, psychoactive medication use was examined in the New York (intervention) and New Jersey (control) Medicaid programs before and after implementation of the New York benzodiazepine TPP among community-dwelling Medicaid beneficiaries aged >/=19 years continuously enrolled from January 1988 through December 1990 in New York or New Jersey with diagnoses of schizophrenia, schizophreniform disorder, schizoaffective disorder, schizoid personality disorder, or schizotypal personality disorder; bipolar disorder; epilepsy; and/or panic disorder, agoraphobia without history of panic disorder, social phobia, or specific phobia. RESULTS: A total of 125,837 New York and 139,405 New Jersey Medicaid beneficiaries were continuously enrolled and met the study inclusion criteria. Of these, there were 6054 Medicaid enrollees in New York and 6875 enrollees in New Jersey who were clinically vulnerable patients with >/=1 of the specified diagnoses. New York Medicaid patients with any of these diagnoses experienced a -48.1% relative change (95% CI, -50.0% to -46.2%) in benzodiazepine use at 6 months after TPP implementation, with no decline in use in New Jersey patients. The largest reduction in benzodiazepine use was seen among patients with seizure disorder (-59.9% at 6 months; 95% CI, -63.9% to -55.9%). Although use of substitute drugs increased slightly in New York after the TPP, it did not offset reductions in benzodiazepine use. The effects of TPP were sustained for 7 years of follow-up and had the greatest impact on nonproblematic benzodiazepine use. CONCLUSIONS: During the time period studied in this analysis, the New York TPP reduced benzodiazepine use among chronically ill patients for whom these agents represent effective treatment. Our findings suggest that many patients previously receiving benzodiazepines did not receive any pharmacologic intervention.
PURPOSE: To evaluate the performance of three linear discriminant functions (LDFs) and the Moorfields Regression Analysis (MRA) in classifying optic disc topography images obtained with the Heidelberg Retina Tomograph (HRT) from patients with open-angle glaucoma and normal controls. Furthermore, to investigate whether the classification of glaucomatous eyes is related to the severity of visual field loss or to optic disc size. DESIGN: Prospective comparative observational case series. PARTICIPANTS: One eye of 104 patients with a diagnosis of open-angle glaucoma (mean age, 63.2; range, 30-88 years) and 48 normal controls (mean age, 52.4; range, 33-75 years). TESTING: Subjects were examined with the HRT. MAIN OUTCOME MEASURES: Diagnostic performance was calculated for the LDFs published by Mikelberg et al (LDF1), Burk (LDF2), and Bathija et al (LDF3) and for the MRA. RESULTS: Large differences in sensitivity and specificity were found among the different analyses when using the originally suggested cutoff criteria. When specificity was equalized to 90%, the sensitivities were more similar (LDF1, 55%; LDF2, 61%; and LDF3, 67%). At 95% specificity, the sensitivities decreased further (LDF1, 39%; LDF2, 55%; LDF3, 44%). When treating the "borderline" outcomes as test positives, MRA sensitivity and specificity were 78% and 81%, respectively. When treating the "borderline" outcomes as test negatives, the MRA gave a sensitivity of 58%, with a specificity of 96%. In glaucoma patients, the correlation between the severity of visual field damage, as measured by the mean deviation index, and the outcome of the classification systems was low to moderate (Spearman's r between 0.26 and 0.39). When the entire sample was stratified into equal thirds on the basis of optic disc size, large discs (area > 2.10 mm(2)) tended to be classified with a higher sensitivity but lower specificity than small discs (area < 1.73 mm(2)) with all methods except LDF3. Using a multiple regression model controlling for mean deviation, LDF1, and LDF2, but not LDF3, were significantly influenced by disc size. CONCLUSIONS: The 4 methods of analysis had similar sensitivities once their specificities were equalized. In this sample, the LDFs and MRA generally did not discriminate between glaucoma patients and controls as well as reported in the original respective studies that described the methods.
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An autonomous evolutionary algorithm for constructing decision trees is presented. The algorithm requires no or minimal human interaction and shows some interesting properties when used on different medical datasets. The algorithm uses a non-standard implicit fitness evaluation in the selection phase of a co-evolving environment. Together with self-adaptation of evolution parameters and with some other improvements it can monitor and adjust its own behavior. The algorithm's capability to self-adapt to a given problem is used as a measure to predict if some dataset is just difficult or impossible to analyze. The autonomous algorithm on average produces very general solutions or gives no solution if the dataset is prone to the overfitting problem.
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The force-distance cycle mode of the atomic force microscope (AFM) allows for detection of interaction forces between the AFM-tip and a substrate (probe). This can either be a direct tip-sample interaction or an interaction between molecules coupled to the tip and probe, respectively. The interaction forces are typically in the range of a few pN to some hundred pN. In this article we describe algorithms for the analysis of force-distance cycles, to quantify interaction forces between tip and probe. Both, the direct tip-probe interaction as well as the interaction between specifically bound molecules are analyzed. The molecules bound to tip and probe have to be either long and flexible or have to be bound via a flexible cross linker. The algorithms are exemplified on direct tip-probe interactions and on unbinding events of cadherins which are bound via PEG-spacers to the AFM-tip and to the probe.
Carbon monoxide is a well-known toxic component in fire atmospheres. However, the importance of hydrogen cyanide as a toxic agent in fire causalities is under discussion. A tragic polyurethane mattress fire provoked death of 35 convicts in a prison (Unit I, Olmos, Penitenciary Service of Buenos Aires Province, Argentina), in 1990. There is no report of any investigation carried out with such a large amount of victims in Argentina. Carboxihemoglobin (COHb) and hydrogen cyanide (HCN) were quantified in victims blood to elucidate the cause of the death. Saturation of COHb ranged between 4 and 18%, and HCN 2.0-7.2mg/l. These latter values were higher than the lethal levels reported in literature. Other toxic components routinely measured (ethanol, methanol, aldehydes and other volatile compounds) gave negative results on the 35 cases. Neither drugs of abuse nor psychotropics were detected. Statistical chi(2) analysis was applied to find differences between HCN and COHb concentrations. Saturation of COHb and HCN in blood were not independent variables (chi(2)=8.25). Moreover, the ratio COHb/HCN was constant (0.47+/-0.04). In order to evaluate the contribution of each toxic to the diagnosis, a lethal index was defined for each toxic (LI(CO) and LI(HCN)). The most probable cause of death could be inferred by a suitable plot of both indexes. The results indicated that death in the 35 fire victims was probably caused by HCN, generated during the extensive polyurethane decomposition provoked by a rapid increase of temperature.
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Peptide mass fingerprinting (PMF) is a powerful tool for identification of proteins separated by two-dimensional electrophoresis (2-DE). With the increase in sensitivity of peptide mass determination it becomes obvious that even spots looking well separated on a 2-DE gel may consist of several proteins. As a result the number of mass peaks in PMFs increased dramatically leaving many unassigned after a first database search. A number of these are caused by experiment-specific contaminants or by neighbor spots, as well as by additional proteins or post-translational modifications. To understand the complete protein composition of a spot we suggest an iterative procedure based on large numbers of PMFs, exemplified by PMFs of 480 Helicobacter pylori protein spots. Three key iterations were applied: (1) Elimination of contaminant mass peaks determined by MS-Screener (a software developed for this purpose) followed by reanalysis; (2) neighbor spot mass peak determination by cluster analysis, elimination from the peak list and repeated search; (3) re-evaluation of contaminant peaks. The quality of the identification was improved and spots previously unidentified were assigned to proteins. Eight additional spots were identified with this procedure, increasing the total number of identified spots to 455.
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