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M Posch

Publications and source records attributed to M Posch.

31 records · Page 2Linked to original sources
PubMed2000

Interim analysis and sample size reassessment.

This article deals with sample size reassessment for adaptive two-stage designs based on conditional power arguments utilizing the variability observed at the first stage. Fisher's product test for the p-values from the disjoint samples at the two stages is considered in detail for the comparison of the means of two normal populations. We show that stopping rules allowing for the early acceptance of the null hypothesis that are optimal with respect to the average sample size may lead to a severe decrease of the overall power if the sample size is a priori underestimated. This problem can be overcome by choosing designs with low probabilities of early acceptance or by midtrial adaptations of the early acceptance boundary using the variability observed in the first stage. This modified procedure is negligibly anticonservative and preserves the power.

Animals↗
PubMed1999

Characterization of the translation-dependent step during iron-regulated decay of transferrin receptor mRNA.

Iron regulates the stability of the mRNA encoding the transferrin receptor (TfR). When iron is scarce, iron regulatory proteins (IRPs) stabilize TfR mRNA by binding to the 3'-untranslated region. High levels of iron induce degradation of TfR mRNA; the translation inhibitor cycloheximide prevents this. To distinguish between cotranslational mRNA decay and a trans effect of translation inhibitors, we designed a reporter system exploiting the properties of the selectable marker gene thymidine kinase (TK). The 3'-untranslated region of human transferrin receptor, which contains all elements necessary for iron-dependent regulation of mRNA stability, was fused to the TK cDNA. In stably transfected mouse fibroblasts, the expression of the reporter gene was perfectly regulated by iron. Introduction of stop codons in the TK coding sequence or insertion of stable stem-loop structures in the leader sequence did not affect on the iron-dependent regulation of the reporter mRNA. This implies that global translation inhibitors stabilize TfR mRNA in trans. Cycloheximide prevented the destabilization of TfR mRNA only in the presence of active IRPs. Inhibition of IRP inactivation by cycloheximide or by the specific proteasome inhibitor MG132 correlated with the stabilization of TfR mRNA. These observations suggest that inhibition of translation by cycloheximide interferes with the rate-limiting step of iron-induced TfR mRNA decay in a trans-acting mechanism by blocking IRP inactivation.

Animals↗
PubMed1999

Win-stay, lose-shift strategies for repeated games-memory length, aspiration levels and noise.

Win-stay, lose-shift, the principle to retain a successful action is a simple and general learning rule that can be applied to all types of repeated decision problems. In this paper I consider win-stay, lose-shift strategies with diverse memory sizes and strategies that adapt their aspiration levels, i.e. the payoff level considered as "success". I study their evolution for the Prisoner's Dilemma, as well as in a rapidly changing environment, where a randomly selected game is assigned to the players. For win-stay, lose-shift strategies with memory one the average payoffs are computed and their evolutionary stability is discussed. Using computer simulations I show that the win-stay, lose-shift strategies with longer memory are very successful both for the Prisoner's Dilemma, where cooperation dominates even for high noise levels, and the randomly assigned games, where the players achieve nearly the expected Pareto optimal payoffs. I discuss the impact of noise and show that the memory length of the players increases with the noise level. These results indicate that the win-stay, lose-shift principle is a very successful strategy in repeated games with noise.

Animals↗
PubMed1999

The assessment of four different methods to verify tracheal tube placement in the critical care setting.

UNLABELLED: One of the most serious complications of conventional endotracheal intubation is unidentified placement of the tube in the esophagus. The aim of our study was to evaluate four different methods for immediate detection of the tube position: auscultation, capnographic determination of ETCO2, esophageal detection method (EDM) using a self-inflating bulb, and the transillumination method using a lighted stylet (Trachlight; Laerdal, Armonk, NY). Thirty-eight endotracheally intubated patients admitted to our medical intensive care unit were enrolled in the study. A second identical tube was inserted into the esophagus under laryngoscopic control. The endotracheal tube was then disconnected from the ventilator. Two blinded examiners, one experienced, the other inexperienced, determined the tube position within 30 s using one of the four methods. The order of the tubes tested and the methods used were randomized. In 130 of 152 examinations, both examiners correctly diagnosed the position of the tube. The wrong result was obtained by both examiners 4 times; only the experienced examiner was wrong 4 times, and only the inexperienced examiner was wrong 14 times. Using ETCO2, both examiners were correct in all cases. Auscultation showed an obvious relation to the examiner's experience: the experienced examiner was correct in all cases, the inexperienced examiner was correct in only 68% of cases. Using the self-inflating bulb, there were two wrong results of the experienced examiner and one wrong result of the inexperienced examiner. The transillumination technique was associated with a high error rate by both examiners (16% and 13%, respectively). Comparing all four methods showed that capnography is superior to auscultation (P = 0.0005) and to the Trachlight detection method (P = 0.0078). EDM was not statistically superior to auscultation and transillumination. Capnography was the most reliable method for rapid evaluation of tube position, followed by EDM, whereas auscultation and Trachlight did not seem to be of comparable value. Experience was a determining factor for auscultation. IMPLICATIONS: To prevent unidentified esophageal intubation, a serious complication in the critical care setting, four methods for detecting tube position were tested by two examiners (one experienced, the other inexperienced) in endotracheally intubated patients after insertion of a second tube into the esophagus.

Adult↗
PubMed1997

ENVIRONMENTAL AUDITING: Exceedance of Critical Loads for Lakes inFinland, Norway, and Sweden: Reduction Requirements for AcidifyingNitrogen and Sulfur Deposition

/ The main objectives of this study were to identify the regions inFennoscandia where the critical loads of sulfur (S) and acidifying nitrogen(N) for lakes are exceeded and to investigate the consequences for depositionreductions, with special emphasis on the possible trade-offs between S and Ndeposition in order to achieve nonexceedance. In the steady-state model forcalculating critical loads and their exceedances, all relevant processesacting assinks for N and S are considered. The critical loads of N and S areinterrelated (defining the so-called critical load function), and therefore asingle critical load for one pollutant cannot be defined without makingassumptions about the other. Comparing the present N and S deposition withthe critical load function for each lake allows determination of thepercentage of lakes in the different regions of Fennoscandia where: (1) Sreductions alone can achieve nonexceedance, (2) N reductions alone aresufficient, and (3) both N and S reductions are required but to a certaindegree interchangeable. Secondly, deposition reduction requirements wereassessed by fixing the N deposition to the present level, in this wayanalyzing the reductions required for S, and by computing the percentage oflakes exceeded in Finland, Norway and Sweden for every possible percentdeposition reduction in S and N, in this way showing the (relative)effectiveness of reducing S and/or N deposition. The results showed clearregional patterns in the S and N reduction requirements. In practically thewhole of Finland and the northern parts of Scandinavia man-made acidificationof surface waters could be avoided by reducing S deposition alone. In thesouthern parts of Sweden some reductions in N deposition are clearly neededin addition to those for S. In southern Norway strong reductions are requiredfor both N and S deposition.KEY WORDS: Acidification; Critical load; Exceedance; Sulfur; Nitrogen;Deposition; Lake

Journal Article↗
PubMed1995

Effect of transcription inhibitors on the iron-dependent degradation of transferrin receptor mRNA.

Transferrin receptor (TfR) mRNA expression is tightly linked to intracellular iron levels. Upon iron deprivation, the iron regulatory protein (IRP) stabilizes TfR mRNA by binding to stem-loop structures in its 3'-untranslated region, whereas increased iron levels result in inactivation of the mRNA-binding protein and rapid degradation of TfR mRNA. Although IRP and the regulation of its RNA binding activity have been studied intensively, little is known about the mechanism of TfR mRNA degradation. In order to get more information about factors involved in this process we investigated the in vivo IRP-RNA interaction and the effect of transcription inhibitors on the iron-dependent decay of TfR mRNA. Here we demonstrate that part of the active IRP co-localizes with TfR mRNA to the rough endoplasmic reticulum. High intracellular iron levels led to a drastic reduction of this active RNA-bound IRP in vivo, indicating that IRP dissociates prior to TfR mRNA decay. Furthermore, the transcription inhibitor actinomycin D and translation inhibitor cycloheximide suppressed TfR mRNA degradation but did not interfere with the IRP dissociation step. Other inhibitors of RNA polymerase II had no effect on iron-dependent degradation of TfR mRNA. However, high concentrations of alpha-amanitin known to block transcription by RNA polymerase III interfered with mRNA decay suggesting the involvement of polymerase III transcripts in the degradation pathway.

Animals↗
PubMed1992

Critical loads for Finnish lakes: comparison of three steady-state models.

Three simple steady-state water-chemistry models are used to calculate critical loads of sulfur for lakes in Finland. Because of the high concentrations of organic matter in Finnish lakes, the influence of organic anions on the calculation of critical loads has been given special attention. The first two methods are well known ion-balance methods which have been used in many previous lake-acidification studies. The third method, developed for this study, includes the numerical solution of equilibrium equations for organic anions, inorganic carbon species and inorganic monomeric aluminum. The original pH and aluminum concentration of the lakes are estimated with this model, and a method to estimate the original acid neutralizing capacity (ANC) by simulating a Gran-titration is also tested on the lake data. Uncertainty in the predictions is estimated by varying the most critical model parameters.

Journal Article↗
PubMed1987

Several mediators appear to interact in neurogenic inflammation.

Plasma protein extravasation was studied in the rat abdominal skin. Substance P (SP), neurokinin A (NKA) and B (NKB) were found to induce extravasation with a threshold dose of about 1 pmol. Calcitonin gene-related peptide (CGRP) caused no or little extravasation alone but it potentiated the action of SP, NKA, NKB, and physalaemin. The potentiation of the SP-induced extravasation was unaffected by pretreatment with capsaicin, indomethacin or compound 48/80, it was reduced by neuropeptide Y or pretreatment with mepyramine plus cimetidine, and was abolished in streptozotocin diabetic rats. CGRP augmented extravasation induced by histamine, reduced the effect of ATP or adenosine and did not alter extravasation by serotonin, bradykinin or neurotensin. These results indicate that in addition to SP the novel mammalian tachykinins NKA and NKB may be considered as mediator candidates for neurogenic plasma extravasation. CGRP is a possible mediator of antidromic vasodilation. Furthermore, CGRP potentiates the extravasation caused by coexisting tachykinins and could thereby augment neurogenic inflammation. The diverse interactions of CGRP with other inflammatory mediators suggest multiple sites of action.

Animals↗
PubMed1983

Cooperative effects in the interaction between melittin and phosphatidylcholine model membranes. Studies by temperature scanning densitometry.

The interaction between the peptide melittin from bee venom with multilamellar liposomes of dipalmitoylphosphatidylcholine or egg yolk phosphatidylcholine has been studied by the method of temperature scanning densitometry, yielding information on the specific volume of the association products and on the changes during the thermotropic transition of the lipids. The effects of the interaction were found to be biphasic with respect to melittin concentration; below 10(-3) mol per mol of phospholipid, an increase in transition temperature, abolition of the pretransition, a reduction in the transition volume of the lipids by about 25%, and a nonadditive increase in apparent specific volume of the complexes were observed. Only minor changes in these parameters could be detected between molar ratios of 10(-3) and 10(-2). Above 1 mol % melittin, the transition temperature decreased and the transition volume approached zero around 10 mol %. Since the effects in the low concentration range cannot be accounted for only by local perturbations around the actual sites of interaction, it is concluded that the interaction involves long range effects of melittin affecting several hundreds of phospholipid molecules. The results are discussed in terms of a phospholipid cluster model, whereby the interaction with melittin leads to a cooperative transition of entire clusters to a state of expanded volume. It is suggested that this transition may be important to the activating effect of melittin on membrane enzymes and to enhanced membrane permeability and lysis.

Bee Venoms↗
PubMedDate not supplied

[Translation and psychometric testing of the Western Ontario Rotator Cuff Index (WORC) for use in Germany].

AIM: At the moment a specific subjective measurement tool for evaluation of German-speaking patients with a pathology of the rotator cuff is lacking. Following international guidelines, the German translation and the psychometric testing of the 21-item, multidimensional Western Ontario Rotator Cuff Index (WORC) is the aim of the study. METHOD: After translation and cross-culture adaptation of the English original, the reliability, validity, practicability and the acceptance of the German version of the WORC were tested on 102 patients with an impingement syndrome. Additionally the SF-36, the Constant and UCLA score were evaluated. RESULTS: The Pearson correlation coefficient showed with 0.96 an excellent result for the test-retest reliability. The internal consistency showed a high homogeneity with a Cronbach alpha coefficient of 0.96. A Pearson correlation coefficient between 0.66-0.81 registered a high correlation with the physical subscales of the SF-36, the Constant and the UCLA score. The mean time required for filling out the WORC was 7.5 minutes, the mean time required for evaluation was 10 minutes. The acceptance and the understanding were very high. CONCLUSION: After successful translation and psychometric testing of the German version of the Western Ontario Rotator Cuff Index (WORC), a patient-based measurement tool for evaluating the quality of life of German-speaking patients with pathology of the rotator cuff is available.

Adult↗