Search PubMed⌕ Search

Biomedical subjects

J Hein

Publications and source records attributed to J Hein.

At least 37 records · Page 2Linked to original sources
PubMed1999

Recombination as a point process along sequences.

Histories of sequences in the coalescent model with recombination can be simulated using an algorithm that takes as input a sample of extant sequences. The algorithm traces the history of the sequences going back in time, encountering recombinations and coalescence (duplications) until the ancestral material is located on one sequence for homologous positions in the present sequences. Here an alternative algorithm is formulated not as going back in time and operating on sequences, but by moving spatially along the sequences, updating the history of the sequences as recombination points are encountered. This algorithm focuses on spatial aspects of the coalescent with recombination rather than on temporal aspects as is the case of familiar algorithms. Mathematical results related to spatial aspects of the coalescent with recombination are derived.

Algorithms↗
PubMed1999

Meanings of state hospital nursing. I: Facing challenges.

The purpose of this study was to describe the meaning of work for nurses employed in two state psychiatric hospitals. Nurses at both hospitals participated in designing and carrying out the research. In Phase I, nurses described situations in which they had been observers or participant observers and the way that they understood what was occurring in the situations described. The data from these descriptions were analyzed in collaboration with small groups of nurse co-investigators at each hospital. In Phase II, patterns of meaning identified in Phase I were checked and further refined based on focus groups and interviews with nurses at both hospitals. The interrelated dilemmas faced by nurses are discussed as (1) challenges in clinical decision making, (2) challenges regarding personal control, and (3) challenges of maintaining professional standards. Ways of meeting these challenges, coping, and making meaning are discussed in a companion article, "Meanings of State Hospital Nursing II: Coping and Making Meaning".

Focus Groups↗
PubMed1999

Combining many multiple alignments in one improved alignment.

MOTIVATION: The fact that the multiple sequence alignment problem is of high complexity has led to many different heuristic algorithms attempting to find a solution in what would be considered a reasonable amount of computation time and space. Very few of these heuristics produce results that are guaranteed always to lie within a certain distance of an optimal solution (given a measure of quality, e.g. parsimony). Most practical heuristics cannot guarantee this, but nevertheless perform well for certain cases. An alignment, obtained with one of these heuristics and with a bad overall score, is not unusable though, it might contain important information on how substrings should be aligned. This paper presents a method that extracts qualitatively good sub-alignments from a set of multiple alignments and combines these into a new, often improved alignment. The algorithm is implemented as a variant of the traditional dynamic programming technique. RESULTS: An implementation of ComAlign (the algorithm that combines multiple alignments) has been run on several sets of artificially generated sequences and a set of 5S RNA sequences. To assess the quality of the alignments obtained, the results have been compared with the output of MSA 2.1 (Gupta et al., Proceedings of the Sixth Annual Symposium on Combinatorial Pattern Matching, 1995; Kececioglu et al., http://www.techfak.uni-bielefeld. de/bcd/Lectures/kececioglu.html, 1995). In all cases, ComAlign was able to produce a solution with a score comparable to the solution obtained by MSA. The results also show that ComAlign actually does combine parts from different alignments and not just select the best of them. AVAILABILITY: The C source code (a Smalltalk version is being worked on) of ComAlign and the other programs that have been implemented in this context are free and available on WWW (http://www.daimi.au.dk/ õcaprani). CONTACT: klaus@bucka-lassen.dk; jotun@pop.bio.au.dk;ocaprani@daimi.au.dk

Algorithms↗
PubMed1999

RNA secondary structure prediction using stochastic context-free grammars and evolutionary history.

MOTIVATION: Many computerized methods for RNA secondary structure prediction have been developed. Few of these methods, however, employ an evolutionary model, thus relevant information is often left out from the structure determination. This paper introduces a method which incorporates evolutionary history into RNA secondary structure prediction. The method reported here is based on stochastic context-free grammars (SCFGs) to give a prior probability distribution of structures. RESULTS: The phylogenetic tree relating the sequences can be found by maximum likelihood (ML) estimation from the model introduced here. The tree is shown to reveal information about the structure, due to mutation patterns. The inclusion of a prior distribution of RNA structures ensures good structure predictions even for a small number of related sequences. Prediction is carried out using maximum a posteriori estimation (MAP) estimation in a Bayesian approach. For small sequence sets, the method performs very well compared to current automated methods.

Algorithms↗
PubMed1999

The ancestry of a sample of sequences subject to recombination.

In this article we discuss the ancestry of sequences sampled from the coalescent with recombination with constant population size 2N. We have studied a number of variables based on simulations of sample histories, and some analytical results are derived. Consider the leftmost nucleotide in the sequences. We show that the number of nucleotides sharing a most recent common ancestor (MRCA) with the leftmost nucleotide is approximately log(1 + 4N Lr)/4Nr when two sequences are compared, where L denotes sequence length in nucleotides, and r the recombination rate between any two neighboring nucleotides per generation. For larger samples, the number of nucleotides sharing MRCA with the leftmost nucleotide decreases and becomes almost independent of 4N Lr. Further, we show that a segment of the sequences sharing a MRCA consists in mean of 3/8Nr nucleotides, when two sequences are compared, and that this decreases toward 1/4Nr nucleotides when the whole population is sampled. A measure of the correlation between the genealogies of two nucleotides on two sequences is introduced. We show analytically that even when the nucleotides are separated by a large genetic distance, but share MRCA, the genealogies will show only little correlation. This is surprising, because the time until the two nucleotides shared MRCA is reciprocal to the genetic distance. Using simulations, the mean time until all positions in the sample have found a MRCA increases logarithmically with increasing sequence length and is considerably lower than a theoretically predicted upper bound. On the basis of simulations, it turns out that important properties of the coalescent with recombinations of the whole population are reflected in the properties of a sample of low size.

Genome, Human↗
PubMed1999

Predictors of cognitive test patterns in autism families.

In a case-control study of cognitive performance, tests of intelligence, reading, spelling, and pragmatic language were administered to the parents and siblings of 90 community-ascertained probands with autism (AU group) and to the parents and siblings of 40 similarly ascertained probands with trisomy 21 Down syndrome (DS group). The two samples were comparable for age and parents' education; both groups were well-educated and had above-average intelligence. AU parents scored slightly but significantly lower on the WAIS-R Full Scale and Performance IQ, on two subtests (Picture Arrangement and Picture Completion), and on the Word Attack Test (reading nonsense words) from the Woodcock-Johnson battery. There were no differences between AU and DS siblings. As in earlier studies, AU parents, more often than DS parents, reported a history of early language-related cognitive difficulties; we were not able to replicate this in siblings. AU parents who reported such difficulties scored significantly lower on Verbal IQ, spelling, and the nonsense reading test. AU parents without a history of early language-related cognitive difficulties often had a Verbal IQ that exceeded Performance IQ by more than one standard deviation. AU siblings with early language-related difficulties had similar findings: lower Verbal IQ, poorer spelling, and poorer reading scores, compared to AU siblings without such a history. Parents with a positive history also scored worse on a measure of pragmatic language,the Pragmatic Rating Scale, but not on measures of social-related components of the broader autism phenotype. We propose that cognitive differences in a subset of autism family members are manifestations of the language-related component of the broader autism phenotype, and separate from the social-related component. This is consistent with the hypothesis that there are several genes that may interact to cause autism which segregate independently and have distinguishable manifestations in family members. The hypothesis would be further supported by finding different patterns of genetic loci linked to autism in families where one or both parents has language difficulties.

Adolescent↗
PubMed1998

[Short-term triple therapy with pantoprazole, amoxicillin and metronidazole in Helicobacter pylori infection].

BACKGROUND: The present study was conducted to investigate the efficacy and tolerability of a 7-day treatment with pantoprazole, amoxicillin and metronidazole for the eradication of Helicobacter pylori (H. pylori) infection. PATIENTS AND METHODS: Fifty patients (26 male, 24 female, age 18 to 86, mean 54 years) with an active duodenal (n = 25) or gastric ulcer (n = 25) were recruited into the study, 48 patients being H. pylori positive at the study start. Patients were treated with pantoprazole (40 mg bid), amoxicillin (1 g bid) and metronidazole (500 mg bid) for 7 days and for another 21 days with pantoprazole (40 mg/od). Four weeks after the end of study medications the patients were re-examined endoscopically and their H. pylori status was re-assessed using urease test, histology and 13C-urea-breath test. RESULTS: In 39 of 48 intention to treat patients, H. pylori infection was cured, according to 81% (95%-CI = 67 to 91%). In the per protocol population in 35 of 41 patients H. pylori was eradicated, which results in an eradication rate of 85% (95%-CI = 71 to 94%). Ulcer healing was endoscopically confirmed in 45 of 48 patients (94%; 95%-CI = 83 to 99%) after 8 weeks. Six of 50 patients (12%) reported mild to moderate probable side-effects of the study medication. Cure of the infection was associated with a distinct reduction of the gastritis grade and activity. CONCLUSION: A 7-day triple therapy using pantoprazole, amoxicillin and metronidazole is an effective and cost-effective alternative to regimens including clarithromycin for the treatment of H. pylori infection.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

[Eating before of an unselected student population of the 7th to 10th grade in a Berlin school].

In 1990 a study of 32 girls and 44 boys in Grades 7 to 10 in a former "East Berlin" school in the borough of Prenzlauer Berg was carried out in continuation of an "East-West Berlin Study on Eating Disorders in Adolescents" which we had initiated in the mid-eighties. The Eating Attitudes Test (EAT), Eating Disorder Inventory (EDI), State of Comfort Scale (SCS) were used in a one-step study design together with complementary clinical and sociodemographic data, including body weight, height and BMI. On the whole, all students were well aware of their own body measurements and had definite ideas about their ideal body weight. Boys were less sure about their real weight, while girls showed some insecurity in defining their ideal weight. Regardless of weight parameters, girls were more strongly preoccupied with issues specific to eating disorders, such as dissatisfaction with their own body, the quest for a slim figure and diet. They were more severely affected by perceptions of insufficiency. 44% of all girls and 4% of the boys said they had problems with their body weight. These students' intensive preoccupation with issues specific to eating disorders was dependent on their actual body weight. They exhibited more clearly pronounced psychological characteristics of eating disorders. Eating-related and psychological characteristics of eating disorders were significantly more pronounced in girls with irregular menstruation. The correlation between irregular menstruation and individually perceived weight problems was significant. These results are discussed in greater detail with due consideration of the need for understanding the specific dynamics of eating attitudes in the general population.

Adolescent↗
PubMed1997

On the number of ancestors to a DNA sequence.

If homologous sequences in a population are not subject to recombination, they can all be traced back to one ancestral sequence. However, the rest of our genome is subject to recombination and will be spread out on a series of individuals. The distribution of ancestral material to an extant chromosome is here investigated by the coalescent with recombination, and the results are discussed relative to humans. In an ancestral population of actual size 1.3 million a minority of <6.4% will carry material ancestral to any present human. The estimated actual population size can be even higher, 5 million, reducing the percentage to 1.7%.

DNA↗
PubMed1996

The Cincinnati Payer Initiative.

In 1991, four companies (Procter & Gamble, General Electric, Cincinnati Bell, and Kroger) located in Cincinnati, OH, decided to cooperate in a collaborative partnership with hospitals and a health care data consulting firm to get more information about the health care options available in their community. The Cincinnati Quality Initiative was formed with the goal of stimulating competition around quality and value in the health care market place. The 14 hospitals in the Cincinnati area were invited to participate in a 3-year program of investigation and analyses. The Initiative implemented the investigation in order to gather information that could be used to make health care choices for their employees. Hospitals that performed well over the 3-year period-those that improved over time-would then be selected by the Initiative. However, this selection process did not occur. Nevertheless, the 3-year evaluation proved useful because it generated valuable information about the health care options in Cincinnati and spurred competition among the hospitals. It also led to a dramatic reduction in health care costs for those hospitals that agreed to participate in the investigation.

Cost Control↗
PubMed1996

[Urticaria vasculitis].

Fifteen cases with suspected urticarial vasculitis which were seen during the last ten years at the Department of Dermatology in Hamburg were reviewed. The cases were reevaluated after strict formulation of criteria for vasculitis (fibrin in and around small vessels, leukocytoclasis of neutrophilic granulocytes, extravasation of erythrocytes) and discussed in the context of the international literature on urticarial vasculitis. The conclusion of our study is that urticarial vasculitis is often overdiagnosed clinically if persistent urticarial lesions occur that show some erythematous changes or a hint of hemorrhage. Furthermore, urticarial vasculitis is often overdiagnosed histopathologically because some cases of urticaria were found that presented with heavy infiltration of small vessel walls with neutrophilic granulocytes. In these cases extravasation of erythrocytes, fibrin in and around vessels and leukocytoclasis is always absent. In summary urticarial vasculitis seems to be a variation of leukocytoclastic vasculitis with less extravasation of erythrocytes and not, as frequently stated, and entity of its own.

Diagnosis, Differential↗
PubMed1995

A maximum-likelihood approach to analyzing nonoverlapping and overlapping reading frames.

A model is presented for sequence evolution on the basis of which one can analyze combinations of noncoding, singly coding, and multiply coding regions of aligned homologous DNA sequences. It is a generalization of Kimura's (J. Mol. Evol. 16:111-120, 1980) and Li et al.'s (J. Mol. Evol. 36:96-99, 1985) transition-transversion models with selection on replacement substitutions. Based on a hierarchy of hypotheses, one will be able to estimate selection factors and transition and transversion distances for different combinations of regions ranging from many regions, each with their private set of parameters, to one set of parameters for all regions. The method is demonstrated on two aligned HIV1 retroviruses.

Amino Acid Sequence↗
PubMed1995

Low resolution DNA typing of the HLA-B5 cross-reactive group by nested PCR-SSP.

We have established a DNA typing system for the HLA-B5 serologically cross-reactive group (CREG) by means of a two-step PCR amplification with nested sequence-specific primers (nPCR-SSP). The present study provides a low resolution definition of the HLA-B5 CREG, i.e. identifying polymorphism equivalent to serology. Two different primer combinations allow group-specific amplification of all HLA-B5 CREG alleles and other related HLA class I alleles from genomic DNA. The amplified DNA is subjected to a second amplification step using eleven nested primer pairs. This assay permits the detection of the HLA-B5 CREG specificities B35, B51, B52, B53, and B7801 in all homozygous and heterozygous combinations. Sensitivity and specificity as judged by a blind quality control study investigating a reference panel (n = 50) is 100%. Extension of this approach should allow rapid DNA typing of all serologically defined HLA-B specificities by nPCR-SSP.

Alleles↗
PubMed1994

An algorithm combining DNA and protein alignment.

An algorithm is presented that aligns two DNA sequences minimizing the overall amount of evolution that the associated proteins have experienced. It is generalized to minimizing a weighted average of protein and DNA evolution.

Algorithms↗
PubMed1994

Antibody response of rabbits and cystic fibrosis patients to an alginate-specific outer membrane protein of a mucoid strain of Pseudomonas aeruginosa.

The aim of this work was to study the immunogenicity of an outer membrane (OM) protein (AlgE; 54 kDa) which is produced solely by mucoid, i.e. alginate-producing strains of P. aeruginosa. The source of AlgE used for our study was the mucoid strain CF3/M1 originally isolated from sputum of a cystic fibrosis (CF) patient. The purified non-denatured protein served as antigen to raise polyclonal monospecific anti-AlgE antibodies in rabbits and to assay sera from 41 cystic fibrosis (CF) patients for anti-AlgE antibodies. According to clinical protocols the sputa of 22 CF patients were positive for P. aeruginosa, 18 were negative and one case was unknown. Our ELISA studies showed that high titers of anti-AlgE antibodies (IgG) corresponded well with the infection status of the CF patients. None of 23 control sera derived from healthy volunteers contained significant levels of anti-AlgE antibodies. Thus the ELISA should be considered as a sensitive diagnostic tool for the early detection of mucoid P. aeruginosa infections in CF patients. Furthermore, we suggest to include AlgE in a multicomponent experimental vaccine for potential protection of non-colonized CF patients from colonization with mucoid P. aeruginosa.

Animals↗
PubMed1994

Genomic alignment.

As sequencing techniques become increasingly efficient, the average length of a sequence is bound to grow. Traditional sequence-comparison algorithms can either compare DNA or protein, but not a mixture, which is actually a common situation. Most obtained DNA sequences contain coding regions, and it is more reliable to compare the coding regions as protein than just as DNA. A heuristic algorithm is presented that can compare DNA with both coding and noncoding regions, but that also can compare multiple reading frames and determine which exons are homologous. A program, GenA1 (Genomic Alignment), was developed that implements the algorithm. Its use is demonstrated on two retroviruses.

Algorithms↗