Complexity-reduction by first-order approximation of non-linear kinetics

Ecological, toxicological, and pharmacological research is often concerned with the answer to the question of how a substance is processed within a biological system. The exact knowledge of the corresponding kinetic pattern forms the basis for a useful answer. In order to identify non-linear kinetics, a first-order approximation method is proposed for complexity-reduction. A simulation study is presented to investigate the error of the approximation in case of a simple Michaelis-Menten kinetic process. The proposed method shows to give useful results which allow to characterize the underlying kinetic pattern. Furthermore it could be shown that in simulating kinetic processes the applied numerical methods may perform with considerable numerical instabilities

(2005-2006) Assembly Resolution: Resolution against House Resolution 609

Governmen

Serum markers detect the presence of liver fibrosis: a cohort study

BACKGROUND &amp; AIMS: Histologic examination of a liver biopsy specimen is regarded as the reference standard for detecting liver fibrosis. Biopsy can be painful and hazardous, and assessment is subjective and prone to sampling error. We developed a panel of sensitive automated immunoassays to detect matrix constituents and mediators of matrix remodeling in serum to evaluate their performance in the detection of liver fibrosis.METHODS: In an international multicenter cohort study, serum levels of 9 surrogate markers of liver fibrosis were compared with fibrosis stage in liver biopsy specimens obtained from 1021 subjects with chronic liver disease. Discriminant analysis of a test set of samples was used to identify an algorithm combining age, hyaluronic acid, amino-terminal propeptide of type III collagen, and tissue inhibitor of matrix metalloproteinase 1 that was subsequently evaluated using a validation set of biopsy specimens and serum samples.RESULTS: The algorithm detected fibrosis (sensitivity, 90%) and accurately detected the absence of fibrosis (negative predictive value for significant fibrosis, 92%; area under the curve of a receiver operating characteristic plot, .804; standard error, .02; P &lt; .0001; 95% confidence interval, .758-.851). Performance was excellent for alcoholic liver disease and nonalcoholic fatty liver disease. The algorithm performed equally well in comparison with each of the pathologists. In contrast, pathologists' agreement over histologic scores ranged from very good to moderate (kappa = .97-.46). CONCLUSIONS: Assessment of liver fibrosis with multiple serum markers used in combination is sensitive, specific, and reproducible, suggesting they may be used in conjunction with liver biopsy to assess a range of chronic liver diseases.Abbreviations used in this paper: ALD, alcoholic liver disease; AUC, area under the curve; CI, confidence interval; GA, total cohort; GT, test set; GV, validation set; HA, hyaluronic acid; NAFLD, nonalcoholic fatty liver disease; NPV, negative predictive value; PIIINP, N-terminal propeptide of type III collagen; PPV, positive predictive value; ROC, receiver operator characteristic; TIMP-1, tissue inhibitor of matrix metalloproteinase 1 <br/

Rivaroxaban (BAY 59-7939) – an oral, direct Factor Xa inhibitor – has no clinically relevant interaction with naproxen

What is already known about this subjec

More counselling for end-of-life decisions by GPs with own advance directives: A postal survey among German general practitioners

Background: Although general practitioners (GPs) are among the preferred contact persons for discussing end-of-life issues including advance directives (ADs), there is little data on how GPs manage such consultations. Objectives: This postal survey asked German GPs about their counselling for end-of-life decisions. Methods: In 2015, a two-sided questionnaire was mailed to 959 GPs. GPs were asked for details of their consultations on ADs: frequency, duration, template use, and whether they have own ADs. Statistical analysis evaluated physician characteristics associated with an above-average number of consultations on AD. Results: The participation rate was 50.3% (n = 482), 70.5% of the GPs were male; the average age was 54 years. GPs had an average of 18 years of professional experience, and 61.4% serve more than 900 patients per three months. Most (96.9%) GPs perform consultations on living wills (LW) and/or powers of attorney (PA), mainly in selected patients (72.3%). More than 20 consultations each on LWs and PAs are performed by 60% and 50% of GPs, respectively. The estimated mean duration of consultations was 21 min for LWs and 16 min for PAs. Predefined templates were used in 72% of the GPs, 50% of GPs had their ADs. A statistical model showed that GPs with ADs and/or a qualification in palliative medicine were more likely to counsel ≥20 patients per year for each document. Conclusion: The study confirmed that nearly all German GPs surveyed provide counselling on ADs. Physicians with ADs counsel more frequently than those without such documents