[CME in Germany--the voluntary CME-certification of the Chambers of Physicians].
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Certification↗
Biomedical subjects
J Engelbrecht
Publications and source records attributed to J Engelbrecht.
[More power for patients: the patients' forum--a joint platform for the medical profession and patient self-help groups].
New ways of cooperation between doctors and representatives of patients are followed with the help of the patients' forum which was founded on the initiative of the German Medical Association. Members of the German Association 'Help for the Handicapped People', the 'Forum of the Chronic Ill and Handicapped People' of the 'Equal Charitable Organisation' (Paritätischer Wohlfahrtsverband), the 'German Association of Self-Help Groups' as well as representatives of the committees and the management of the German Medical Association and the National Association of Statutory Health Insurance Physicians form the patients' forum. The major aim of this cooperation is to discuss the possibilities and the ways to improve the quality in health care. A direct participation of patients' representatives is for the moment planned in the evaluation of the quality of medical information for the lay public. In cooperation with the Agency for Quality in Medicine--a joint institution of the German Medical Association and the National Association of Statutory Health Insurance Physicians--the quality of information on health care that is published in the internet should be examined. The patients' information service which was developed by the Agency for Quality in Medicine and is found under www.patienten-information.de is the basis for this examination.
Chronic Disease↗
Mining of assembled expressed sequence tag (EST) data for protein families: application to the G protein-coupled receptor superfamily.
The availability of large expressed sequence tag (EST) databases has led to a revolution in the way new genes are identified. Mining of these databases using known protein sequences as queries is a powerful technique for discovering orthologous and paralogous genes. The scientist is often confronted, however, by an enormous amount of search output owing to the inherent redundancy of EST data. In addition, high search sensitivity often cannot be achieved using only a single member of a protein superfamily as a query. In this paper a technique for addressing both of these issues is described. Assembled EST databases are queried with every member of a protein superfamily, the results are integrated and false positives are pruned from the set. The result is a set of assemblies enriched in members of the protein superfamily under consideration. The technique is applied to the G protein-coupled receptor (GPCR) superfamily in the construction of a GPCR Resource. A novel full-length human GPCR identified from the GPCR Resource is presented, illustrating the utility of the method.
Amino Acid Sequence↗
Cardiac mechanoenergetics replicated by cross-bridge model.
The aim of this work is to reproduce the experimentally measured linear dependence of cardiac muscle oxygen consumption on stress-strain area using a model, composed of a three-state Huxley-type model for cross-bridge interaction and a phenomenological model of Ca2+-induced activation. By selecting particular cross-bridge cycling rate constants and modifying the cross-bridge activation model, we replicated the linear dependence between oxygen consumption and stress-strain area together with other important mechanical properties of cardiac muscle such as developed stress dependence on the sarcomere length and force-velocity relationship. The model predicts that (1) the amount of the "passenger" cross bridges, i.e., cross bridges that detach without hydrolyzing ATP molecule, is relatively small and (2) ATP consumption rate profile within a beat and the amount of the passenger cross bridges depend on the contraction protocol.
Actomyosin↗
Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites.
We have developed a new method for the identification of signal peptides and their cleavage sites based on neural networks trained on separate sets of prokaryotic and eukaryotic sequence. The method performs significantly better than previous prediction schemes and can easily be applied on genome-wide data sets. Discrimination between cleaved signal peptides and uncleaved N-terminal signal-anchor sequences is also possible, though with lower precision. Predictions can be made on a publicly available WWW server.
Algorithms↗
Splice site prediction in Arabidopsis thaliana pre-mRNA by combining local and global sequence information.
Artificial neural networks have been combined with a rule based system to predict intron splice sites in the dicot plant Arabidopsis thaliana. A two step prediction scheme, where a global prediction of the coding potential regulates a cutoff level for a local prediction of splice sites, is refined by rules based on splice site confidence values, prediction scores, coding context and distances between potential splice sites. In this approach, the prediction of splice sites mutually affect each other in a non-local manner. The combined approach drastically reduces the large amount of false positive splice sites normally haunting splice site prediction. An analysis of the errors made by the networks in the first step of the method revealed a previously unknown feature, a frequent T-tract prolongation containing cryptic acceptor sites in the 5' end of exons. The method presented here has been compared with three other approaches, GeneFinder, Gene-Mark and Grail. Overall the method presented here is an order of magnitude better. We show that the new method is able to find a donor site in the coding sequence for the jelly fish Green Fluorescent Protein, exactly at the position that was experimentally observed in A.thaliana transformants. Predictions for alternatively spliced genes are also presented, together with examples of genes from other dicots, monocots and algae. The method has been made available through electronic mail (NetPlantGene@cbs.dtu.dk), or the WWW at http://www.cbs.dtu.dk/NetPlantGene.html
Algorithms↗
Defining a similarity threshold for a functional protein sequence pattern: the signal peptide cleavage site.
When preparing data sets of amino acid or nucleotide sequences it is necessary to exclude redundant or homologous sequences in order to avoid overestimating the predictive performance of an algorithm. For some time methods for doing this have been available in the area of protein structure prediction. We have developed a similar procedure based on pair-wise alignments for sequences with functional sites. We show how a correlation coefficient between sequence similarity and functional homology can be used to compare the efficiency of different similarity measures and choose a nonarbitrary threshold value for excluding redundant sequences. The impact of the choice of scoring matrix used in the alignments is examined. We demonstrate that the parameter determining the quality of the correlation is the relative entropy of the matrix, rather than the assumed (PAM or identity) substitution mode. Results are presented for the case of prediction of cleavage sites in signal peptides. By inspection of the false positives, several errors in the database were found. The procedure presented may be used as a general outline for finding a problem-specific similarity measure and threshold value for analysis of other functional amino acid or nucleotide sequence patterns.
Algorithms↗
Protein structure and the sequential structure of mRNA: alpha-helix and beta-sheet signals at the nucleotide level.
A direct comparison of experimentally determined protein structures and their corresponding protein coding mRNA sequences has been performed. We examine whether real world data support the hypothesis that clusters of rare codons correlate with the location of structural units in the resulting protein. The degeneracy of the genetic code allows for a biased selection of codons which may control the translational rate of the ribosome, and may thus in vivo have a catalyzing effect on the folding of the polypeptide chain. A complete search for GenBank nucleotide sequences coding for structural entries in the Brookhaven Protein Data Bank produced 719 protein chains with matching mRNA sequence, amino acid sequence, and secondary structure assignment. By neural network analysis, we found strong signals in mRNA sequence regions surrounding helices and sheets. These signals do not originate from the clustering of rare codons, but from the similarity of codons coding for very abundant amino acid residues at the N- and C-termini of helices and sheets. No correlation between the positioning of rare codons and the location of structural units was found. The mRNA signals were also compared with conserved nucleotide features of 16S-like ribosomal RNA sequences and related to mechanisms for maintaining the correct reading frame by the ribosome.
Amino Acid Sequence↗
Prediction of O-glycosylation of mammalian proteins: specificity patterns of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase.
The specificity of the enzyme(s) catalysing the covalent link between the hydroxyl side chains of serine or threonine and the sugar moiety N-acetylgalactosamine (GalNAc) is unknown. Pattern recognition by artificial neural networks and weight matrix algorithms was performed to determine the exact position of in vivo O-linked GalNAc-glycosylated serine and threonine residues from the primary sequence exclusively. The acceptor sequence context for O-glycosylation of serine was found to differ from that of threonine and the two types were therefore treated separately. The context of the sites showed a high abundance of proline, serine and threonine extending far beyond the previously reported region covering positions -4 through +4 relative to the glycosylated residue. The O-glycosylation sites were found to cluster and to have a high abundance in the N-terminal part of the protein. The sites were also found to have an increased preference for three different classes of beta-turns. No simple consensus-like rule could be deduced for the complex glycosylation sequence acceptor patterns. The neural networks were trained on the hitherto largest data material consisting of 48 carefully examined mammalian glycoproteins comprising 264 O-glycosylation sites. For detection neural network algorithms were much more reliable than weight matrices. The networks correctly found 60-95% of the O-glycosylated serine/threonine residues and 88-97% of the non-glycosylated residues in two independent test sets of known glycoproteins. A computer server using E-mail for prediction of O-glycosylation sites has been implemented and made publicly available. The Internet address is NetOglyc@cbs.dtu.dk.
Algorithms↗
Analysis of eukaryotic promoter sequences reveals a systematically occurring CT-signal.
A general data study of eukaryotic promoter sequences from widely different species is presented. Mammalian promoters with known transcription initiation sites represented the largest subclass of the data, and for this group neural network algorithms were trained to predict the location of the initiation site in a test set. The prediction accuracy of this local method was higher than what could be expected from the known non-local structure of eukaryotic promoters. Subsequent analysis revealed, besides the consensus of the two known important subregions: the TATA-box TATAAA and the Cap-signal CA, a CT-signal positioned on the average seven nucleotides downstream of the transcription initiation site. The consensus of the CT-signal is CTNCNG. The details of this core promoter element were disclosed using multiple alignment and have earlier only been described in a few isolated examples.
Algorithms↗
Investigations of Escherichia coli promoter sequences with artificial neural networks: new signals discovered upstream of the transcriptional startpoint.
In this paper we present a novel method for using the learning ability of a neural network as a measure of information in local regions of input data. Using the method to analyze Escherichia coli promoters, we discover all previously described signals, and furthermore find new signals that are regularly spaced along the promoter region. The spacing of all signals correspond to the helical periodicity of DNA, meaning that the signals are all present on the same face of the DNA helix in the promoter region. This is consistent with a model where the RNA polymerase contacts the promoter on one side of the DNA, and suggests that the regions important for promoter recognition may include more positions on the DNA than usually assumed. We furthermore analyze the E. coli promoters by calculating the Kullback Leibler distance, and by constructing sequence logos.
Base Sequence↗
Periodic sequence patterns in human exons.
We analyse the sequential structure of human exons and their flanking introns by hidden Markov models. Together, models of donor site regions, acceptor site regions and flanked internal exons, show that exons--besides the reading frame--hold a specific periodic pattern. The pattern, which has the consensus: non-T(A/T)G and a minimal periodicity of roughly 10 nucleotides, is not a consequence of the nucleotide statistics in the three codon positions, nor of the well known nucleosome positioning signal. We discuss the relation between the pattern and other known sequence elements responsible for the intrinsic bending or curvature of DNA.
Base Sequence↗
[Mandatory continued medical education and continuing education accreditation--contributions to quality assurance in medicine?].
Continuing education is seen as one of the most important instruments of medical quality assurance. Therefore, the duty of continuing medical education was put down in the professional rules of German physicians in 1976. It has been demonstrated many times that most of the physicians keep this professional duty. However, it has been repeatedly discussed whether the physician's motivation for continuing education is sufficient or whether it is necessary to introduce a compulsory proof of CME. It is analyzed in this article how the efficacy of compulsory and compulsory proof of is verified scientifically. Further, different tools are introduced which may help to admit a greater obligation. The discussion is based on data from Medline search using the keywords 'Continuing medical education' and 'Quality assurance' for the years 1984-1993. Studies reporting experiences with compulsory CME and considerations of standards were chosen. Further, presentations of the 'European Academy of Medical Education' (EAMF), Cologne March 4-March 5, 1994 as well as the publications of the German Medical Association regarding quality assurance of CME from the years 1993 to 1995 have been taken into account.
Accreditation↗
Steroid sparing activity of tenidap in patients with polymyalgia rheumatica: a multicenter double blind randomized placebo controlled study.
OBJECTIVE: To determine whether tenidap treatment would allow reduction or replacement of systemic corticosteroid treatment in patients with polymyalgia rheumatica (PMR). METHODS: A 15-week double blind, randomized, multicenter, placebo-controlled study of tenidap sodium (120 mg/day) in patients with symptomatically controlled PMR receiving 10 mg/day prednisone was conducted. After receiving study drug for 3 weeks, prednisone dose was reduced by 2.5 mg/day every 3 weeks. The lowest clinically effective dose of prednisone was recorded as 10, 7.5, 5, 2.5 or 0 mg/day. RESULTS: Thirty-two patients were randomized to tenidap or placebo. As prednisone was reduced more placebo patients experienced an exacerbation of PMR symptoms, elevation of erythrocyte sedimentation rate and increased serum C-reactive protein. Twice as many placebo patients (10 of 16) as tenidap patients (5 of 16) discontinued due to lack of efficacy. The lowest effective dose of prednisone could be determined in 27 of the 32 patients, 11 receiving tenidap and 16 placebo. A significantly (p = 0.027) greater proportion of patients receiving tenidap (5 of 11) than placebo (1 of 16) were able to discontinue prednisone without experiencing a symptomatic flare. CONCLUSION: As prednisone was reduced, symptoms of PMR were controlled better by tenidap than by placebo. Forty-five percent of evaluable patients receiving tenidap were able to discontinue prednisone without a disease flare compared to 6% for placebo.
Aged↗
[Participation in continuing education by German physicians--exemplified by the Schleswig-Holstein study].
In order to evaluate the CME behaviour of the physicians in the state of Schleswig-Holstein, the State Society of Physicians questioned all its members (n = 10,326 and 10,698) regarding the participation in CME activities during the previous year using the same questionnaire in 1991 and 1993. Answers were obtained from 6,329/6,904 physicians where 40.2/42.2% (1991/1993) worked in free practice, 46.9 (44.6)% in hospitals, 6.2 (6.9) % in administrative and scientific institutions, 5.2 (2.9)% in various medical occupations, and 1.6 (3.3)% without medical professions. CME activities were identical in 1990 and 1992, where the study of literature was the most relevant activity (99%). Mean reading time was 5.8/5.6 hours per week (physicians in practice: 5.3/5.3 hpw, in hospital 6.4/6.6 hpw), average of read journals: 3.9/3.9 (practice: 4.3/4.3 hospital: 3.6/3.6). Video-CME was documented with 41.7/44.2% in total (practice: 50.5/52.3%-hospital: 37.2/39.9%). Regarding CME courses and conferences, traditional class-room CME was used most frequently (total: 71.9/72.6%-practice: 69.7/71%-hospital: 73.9/74.9%), followed by workshops (total: 50.3/47.9%-practice: 56.4/54.1%-hospital: 45.6/54.1%) and training in small groups (total: 16.6%-practice: 20.9/19.2%-hospital: 13.2/12%). Physicians participated in CME courses and conferences usually in the evenings (7.6/7.2 times a year), followed by halfdays courses (1.4 times), weekend courses (1.4 times) and conferences lasting several day (1.2/1.3-practice: 0.8/0.9-hospital: 1.6/1.6). This study about CME activities firstly demonstrated both the representativity of systematic questionnaires based on the rules of the medical profession, as well as the continuity of the CME behaviour in Germany. The results proof that repeated questionnaires are of little influence on the answering behaviour of physicians.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Emergency service course manual--a contribution to quality assurance in emergency medicine education].
For the purpose of comparison and quality control for the acquisition of the subspeciality in emergency medicine, a committee of experts in the area of emergency medicine developed the first curriculum (course book Emergency medicine) valid in all states of Germany. The requirements for the development of this curriculum were derived from the experts' experiences and from the requirements of the medical society for the quality of medical training.
Curriculum↗
Neural network model of the genetic code is strongly correlated to the GES scale of amino acid transfer free energies.
A neural network trained to classify the 61 nucleotide triplets of the genetic code into 20 amino acid categories develops in its internal representation a pattern matching the relative cost of transferring amino acids with satisfied backbone hydrogen bonds from water to an environment of dielectric constant of roughly 2.0. Such environments are typically found in lipid membranes or in the interior of proteins. In learning the mapping between the codons and the categories, the network groups the amino acids according to the scale of transfer free energies developed by Engelman, Goldman and Steitz. Several other scales based on internal preference statistics also agree reasonably well with the network grouping. The network is able to relate the structure of the genetic code to quantifications of amino acid hydrophobicity-hydrophilicity more systematically than the numerous attempts made earlier. Due to its inherent non-linearity, the code is also shown to impose decisive constraints on algorithmic analysis of the protein coding potential of DNA.
Amino Acid Sequence↗
[Work environment. Slavery or art of living].
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Attitude to Health↗