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PubMed1995

Using data preprocessing and single layer perceptron to analyze laboratory data.

During daily work in hospitals a large amount of clinical data is produced each day. Totally computerized patient records are not yet widely used but a large part of essential information is already stored on computer files. These include laboratory test results, diagnoses, codes for operations, codes of histopathological diagnoses and maybe even the patient's medication. Accordingly, these databases include much clinical knowledge that would be useful for clinicians. Laboratories try to support clinicians by producing reference values for laboratory tests. It is, of course, necessary information but, however, it does not give very much information about the weight of evidence that an abnormal laboratory test will give in special clinical settings. We have developed a software package - DiagaiD - in order to build a smart link between patient databases and clinicians. It utilizes neural network-based machine learning techniques and can produce decision support which meets the special needs of clinicians. From example cases it can learn clinically relevant transformations from original numeric values to logical values. By using data transformation together with a single layer perceptron it is possible to build nonlinear models from a set of preclassified example cases. In this paper, we use two small datasets to show how this scheme works in the diagnosis of acute appendicitis and in the diagnosis of myocardial infarction. Results are compared with those obtained using logistic regression or backpropagation neural networks. The performance of our neuro-fuzzy tool seemed to be slightly better in these two materials but the differences did not reach statistical significance.

Appendicitis↗
PubMed2005

Spontaneous alterations of the corneal topographic pattern.

PURPOSE: To assess whether the type of corneal topographic pattern is stable during a 1-minute pause in blinking in healthy subjects. SETTING: First Department of Ophthalmology, Semmelweis University, Budapest, Hungary. METHODS: Corneal topographic images were recorded 5, 15, 30, and 60 seconds after a complete blink in the right eyes of 36 healthy subjects using the TMS-1 instrument in a prospective observational study. The topographic pattern of each image was assessed from the color-coded topographic map and classified into 5 groups (in order of decreasing regularity: round, oval, symmetric bow-tie, asymmetric bow-tie, and irregular). RESULTS: During the 60-second period, a change in the type of topographic pattern was found in 19 subjects (53%), whereas in 17 subjects (47%) the pattern was stable. The alteration of the topographic pattern was statistically significant (P<.001). CONCLUSIONS: Immediately after blinking, the ocular surface regularity improves, possibly due to the building up of the tear film. This is followed later by the distortion of the ocular surface, which is the precursor of the tear-film break up phenomenon. Because of these changes, even in healthy eyes, the optimization and standardization of the postblink time of topographic image capture are very important, especially for planning refractive surgery.

Adult↗
PubMed2004

Regreening the metropolis: pathways to more ecological cities: keynote address.

Eighty percent of the American population now lives in metropolitan regions whose geographic extent continues to expand even as many core cities and inner-tier suburbs lose middle-class populations, jobs, and tax base. Urban sprawl and the socioeconomic polarizing of metropolitan America have been fostered by public policies including (1) federal subsidies for new infrastructure on the urban fringe; (2) tax policies that favor home ownership over rental properties; (3) local zoning codes; and (4) federal and state neglect of older urban neighborhoods. In the face of diminished access to "nature" outside of metropolitan areas, locally based efforts to protect and restore greenspaces within urban areas seek to make older communities more habitable and more "ecological." Some pathways to more ecological cities include the following: (1) the notion of rus in urbe ("the country in the city"); (2) the "usable outdoors"; (3) garden cities and eco-villages; (4) green buildings and green roofs; (5) urban biodiversity; (6) ecological services; and (7) space, nature, and place.

City Planning↗
PubMed2004

Healthy families of children who are deaf.

Families provide the building blocks for the development of healthy, happy, competent children. The purpose of the present study was to identify and interview healthy families of children who were deaf. The researchers were interested in identifying factors that contribute to families' health as well as in collecting suggestions for other families with children who are deaf and for professionals in the field of deaf education. Nineteen families, all nominated by deaf education professionals, were interviewed. The interviews were transcribed and coded, and responses to each interview question were grouped under recurring themes. A summary of the results, limitations of the study, suggestions for future research, and recommendations for practice are provided.

Adolescent↗
PubMed2005

The origin and evolution of operons: the piecewise building of the proteobacterial histidine operon.

The structure and organization of 470 histidine biosynthetic genes from 47 different proteobacteria were combined with phylogenetic inference to investigate the mechanisms responsible for assembly of the his pathway and the origin of his operons. Data obtained in this work showed that a wide variety of different organization strategies of his gene arrays exist and that some his genes or entire his operons are likely to have been horizontally transferred between bacteria of the same or different proteobacterial branches. We propose a "piecewise" model for the origin and evolution of proteobacterial his operons, according to which the initially scattered his genes of the ancestor of proteobacteria coded for monofunctional enzymes (except possibly for hisD) and underwent a stepwise compacting process that reached its culmination in some gamma-proteobacteria. The initial step of operon buildup was the formation of the his "core," a cluster consisting of four genes (hisBHAF) whose products interconnect histidine biosynthesis to both de novo synthesis of purine metabolism and that occurred in the common ancestor of the alpha/beta/gamma branches, possibly after its separation from the epsilon one. The following step was the formation of three mini-operons (hisGDC, hisBHAF, hisIE) transcribed from independent promoters, that very likely occurred in the ancestor of the beta/gamma-branch, after its separation from the alpha one. Then the three mini-operons joined together to give a compact operon. In most gamma-proteobacteria the two fusions involving the gene pairs hisN-B and hisI-E occurred. Finally the gamma-proteobacterial his operon was horizontally transferred to other proteobacteria, such as Campylobacter jejuni. The biological significance of clustering of his genes is also discussed.

Databases, Nucleic Acid↗
PubMed1992

Regulation of the Escherichia coli lac operon expressed in human cells.

We have investigated the use of various Epstein-Barr virus (EBV)-based vectors bearing the two components of the Escherichia coli lac operator-repressor (lacO, lacI) complex. Our aim was to develop a model system of gene expression by looking at the transcription of the bacterial beta-galactosidase coding gene (lacZ) in 293 human embryonic kidney cells. Several vectors have been built carrying different promoters upstream of the lacI and lacZ genes and in which natural or synthetic operator sequences were inserted in the 5' part of the lacZ gene. In transient expression assays we achieved efficient lacZ gene repression which could be released by the specific inducer isopropyl beta-D-thiogalactoside (IPTG). A stable transformed cell line carrying two EBV-derived plasmids with the building blocks of the lac operator/repressor system was established. This cell line allowed us to achieve a wide range of lacZ gene regulation. In this cell line IPTG alone could remove the repression to trigger a 5-fold increase of lacZ expression. Heavy metal ions, which induced the mouse metallothionein I promoter located upstream of the lacZ gene, added together with IPTG gave rise to a 40-fold induction of lacZ expression.

Base Sequence↗
PubMedDate not supplied

Understanding the scientific issues embedded in the generic drug approval process.

OBJECTIVE: To review the major scientific issues embedded in the generic drug approval process. DATA SOURCES: Articles indexed initially under terms such as generic medications, generic drugs, bioequivalence, and bioinequivalence. These terms were used to search indexing services such as MEDLINE, International Pharmaceutical Abstracts, CINAHL (a database of nursing and allied health literature), and Science Citation Index. Additional data sources included the Code of Federal Regulations and regulatory guidances from the Food and Drug Administration (FDA) Center for Drug Evaluation and Research. STUDY SELECTION: Performed by the authors. DATA EXTRACTION: Not applicable. DATA SYNTHESIS: Despite the fact that regulations regarding bioequivalence have been in place for more than 20 years, controversies over bioequivalence continue to arise. Consensus on many of these issues is driving the development of new FDA guidances regarding bioequivalence. Still, despite the issuance of new guidance and consensus building among scientists, many clinicians and consumers remain uninformed regarding the scientific basis for establishing bioequivalence and the generic drug approval process in general. Although some have suggested that the generic drug approval process is flawed, overall, it appears that the process works. CONCLUSION: Understanding the generic drug approval process and the issues surrounding bioequivalence is of paramount importance to both clinicians and scientists.

Drug Approval↗
PubMed1994

Transients in the inhibitory driving of neurons and their postsynaptic consequences.

The presynaptic fiber at an inhibitory synapse on a pacemaker neuron was forced to generate transients, defined here as spike trains with a trend, unceasingly accelerating or slowing. Experiments were on isolated crayfish stretch receptor organs. Spike train analyses used tools and notions from conventional point processes and from non-linear dynamics. Pre- and postsynaptic discharges contrasted clearly in terms of rates and interspike intervals. The inhibitory train evolved monotonically and smoothly, following tightly the simple prescribed curves; it was uniform, exhibiting throughout a single and simple discharge form (i.e. interval patterning). The inhibited postsynaptic train alternately accelerated and slowed, not following tightly any simple curve; it was heterogeneous, exhibiting in succession several different and often complex discharge forms, and switching abruptly from one to another. The inhibited trains depended on the inhibitory transient's span, range and average slope. Accordingly, transients separated (not cuttingly) into categories with prolonged spans (over 1 s) and slow slopes (around 1/s2) and those with short spans (under 1 s) and fast slopes (around 30/s2). Special transients elicited postsynaptic discharges that reproduced it faithfully, e.g. accelerated with the transient and proportionately; no transient elicited postsynaptic discharges faithful to its mirror image. Crayfish synapses are prototypes, so these findings should be expected in any other junction, as working hypotheses at least. Implications involve the operation of neural networks, including the role of distortions and their compensation, and the underlying mechanisms. Transients have received little attention, most work on synaptic coding concentrating on stationary discharges. Transients are inherent to the changing situations that pervade everyday life, however, and their biological importance is self-evident. The different discharges encountered during a transient had strong similarities to the stationary forms reported for different pacemaker drivings that are called locking, intermittency, erratic and stammering; they were, in fact, trendy versions of these. Such forms appear with several synaptic drivings in the same order along the presynaptic rate scale; they may constitute basic building blocks for synaptic operation. In terms of non-linear science, it is as if the attractors postulated for stationary drivings remained strongly influential during the transients, though affected by the rate of change.

Animals↗
PubMed2005

Unusual usage of AGG and TTG codons in humans and their viruses.

Prior analysis on human protein-coding DNA sequences has identified local base composition as the primary predictor of synonymous codon usage. However, in many organisms, codon usage is influenced by natural selection, particularly for efficient expression of functional gene products. Because viruses are expected to evolve codon usage in the context of their host's molecular machinery, their genomes provide another window into the forces that guide their host's molecular evolution. Factor analysis was performed on codon usage of 16,654 genes annotated in Build 34 of the human genome, and the primary factor was correlated strongly with local base composition. However, two codons, AGG and TTG, rose in frequency as all other C- and G-ending codons decreased in frequency. These two codons were the only C- or G-ending codons with usages that negatively correlated with gene expression. Variation among viruses in codon usage also strongly reflects variation in base composition and, again, AGG and TTG decrease in frequency as all other C- and G-ending codons increase in frequency. It appears that usages of these two codons can not be explained by local compositional biases, implying a more direct role of natural selection on codon usage in humans.

Amino Acids↗
PubMed2005

Heroin and HIV risk in Dar es Salaam, Tanzania: youth hangouts, mageto and injecting practices.

HIV risk through needle sharing is now an emerging phenomenon in Africa. This article describes the practices that heroin users are producing as they establish the rules and organization surrounding their drug use. Their practices and interactions reveal the ways that they become initiated into its use, how they progress to injecting, and the important role of local neighbourhood hangouts in facilitating this process. Their practices, interactions and narratives also provide insights into what may be the most appropriate HIV-prevention interventions. Semi-structured interviews were conducted during the months of February and July 2003 with 51 male and female injectors residing in 8 neighbourhoods in the Dar es Salaam, Tanzania. Interviews were content coded and codes were collapsed into emergent themes around hangout places, initiation of heroin use, and progression to injecting. Interviews reveal that Dar es Salaam injectors begin smoking heroin in hangout areas with their friends, either because of peer pressure, desire, or trickery. One hangout place in particular, referred to as the 'geto' (ghetto) is the main place where the organization and rules governing heroin use are produced. Three main types of heroin 'ghettoes' are operating in Dar es Salaam. As users build a tolerance for the drug they move along a continuum of practices until they begin to inject. Injecting heroin is a comparatively recent practice in Africa and coincides with: (1) Tanzania transitioning to becoming a heroin consuming community; (2) the growing importance of youth culture; (3) the technical innovation of injecting practices and the introduction and ease of use of white heroin; and (4) heroin smokers, sniffers, and inhalers perceived need to escalate their use through a more effective and satisfying form of heroin ingestion.

Female↗
PubMed2004

[Study on the molecular epidemiology of beta-lactamase TEM gene in isolated Streptococcus pneumoniae].

OBJECTIVE: To investigate the beta-lactamase TEM gene of isolated Streptococcus pneumoniae (Sp) in Suzhou area. METHODS: Twenty-three strains of Sp were collected from respiratory tract secretions of children with respiratory diseases in Nov 2002 to Apr 2003 at Children's Hospital of Suzhou University (reference strain ATCC49619) to build TEM polymerase chain reaction (PCR) system (reference strain E. coli. 9-j53R1 with TEM gene) TEM gene of 23 strains was detected to comparo the sequences with published TEM gene sequences in GenBank for analyzing TEM gene model. RESULTS: Twenty-one strains had TEM gene with a positive rate of 91.3% (21/23). TEM-129 gene were confirmed from No.17 (SR017, penicillin resistance) TEM sequence. New discovered TEM-129 sequence had a modification (ATG[M]-->ATA[I]) at No.182 code and published (GenBank: www.ncbi.nlm.nih.gov/nucleotide, AY452662). TEM-1 genes were confirmed from other TEM sequences. New discovered TEM-1 gene of isolated Sp had been published (GenBank: www.ncbi.nlm.nih.gov/nucleotide, AY392531) too. CONCLUSION: Isolated Sp had TEM gene (TEM-129, EM-1 genotype) with a positive rate of 91.3%. The result enriched the understanding of isolated Sp with penicillin resistance.

Base Sequence↗
PubMed2005

The significance of cognitive modeling in building healthcare interfaces.

BACKGROUND: Although there are many reasons that widespread adoption of healthcare information systems has not transpired, one reason is a failure to take into account the cognitive needs of the users. AIM: To understand the cognitive needs of nurses and physicians and determine how these needs should influence the design of healthcare interfaces. DESIGN OF STUDY: A qualitative and quantitative study that compares how nurses and physicians comprehend patient information. SETTING: Twenty-four registered nurses and twenty-four physicians working in the specialties of gastrointestinal or internal medicine. METHODS: Each clinician reviewed two mock electronic medical records and summarized the cases using a think-aloud protocol. All verbalizations were coded for medical and conceptual information. RESULTS: The nurses included a larger mean proportion (p<0.001) of recalls than did the physicians. As compared to the nurses, the physicians included a statistically significant (p<0.001) larger mean proportion of inferences, conditional statements, and interventions. The nurses concentrated on functional problems, whereas the physicians focused on diagnosis, treatment, and management. CONCLUSION: The main cognitive differences between the physicians and the nurses are explained through the differences in their practice models. Therefore, healthcare IT must develop separate interfaces for each discipline to address their unique needs.

Adult↗
PubMed2001

An object-oriented framework for dynamic ecosystem modeling: application for integrated risk assessment.

Ecological risk assessment requires the integration of a wide range of data on anthropogenic processes, ecological processes and on processes related to environmental fate and transport. It is a major challenge to assemble a simulation system that can successfully capture the dynamics of complex ecological systems and an even more serious challenge to be able to adapt such a simulation to shifting and expanding analytical requirements and contexts. The dynamic information architecture system (DIAS) is a flexible, extensible, object-based framework for developing and maintaining complex simulations. DIAS supports simulations in which the real-world entities that make up ecological systems are represented as software 'entity objects'. The object-oriented integrated dynamic landscape analysis and modeling system (OO-IDLAMS) provides a good example of how DIAS has been used to build a suite of models for the purpose of assessing the ecological impacts of military land use and land management practices. OO-IDLAMS is a prototype conservation modeling suite that provides military environmental managers and decision-makers with a strategic, integrated and adaptive approach to natural resources planning and ecosystem management. The OO-IDLAMS prototype used Fort Riley, Kansas as a case study to demonstrate DIAS' capabilities to offer flexibility, interprocess dynamics and cost-effective reuse of code for ecosystem modeling and simulation. DIAS can also readily lend itself to other applications in ecological risk assessment. It has great potential for the integration of ecological models (associated with biological uptake and effects) with environmental fate and transport models. A DIAS ecological risk assessment application could be used to predict the magnitude and extent of ecological risks and evaluate remedy effectiveness in a timely and cost-effective manner.

Animals↗
PubMed2002

Arabidopsis A BOUT DE SOUFFLE, which is homologous with mammalian carnitine acyl carrier, is required for postembryonic growth in the light.

The degradation of storage compounds just after germination is essential to plant development, providing energy and molecules necessary for the building of a photosynthetic apparatus and allowing autotrophic growth. We identified à bout de souffle (bou), a new Arabidopsis mutation. Mutant plants stopped developing after germination and degraded storage lipids, but they did not proceed to autotrophic growth. Neither leaves nor roots developed in the mutant. However, externally added sugar or germination in the dark could bypass this developmental block and allowed mutant plants to develop. The mutated gene was cloned using the transposon Dissociation as a molecular tag. The gene coding sequence showed similarity to those of the mitochondrial carnitine acyl carriers (CACs) or CAC-like proteins. In animals and yeast, these transmembrane proteins are involved in the transport of lipid-derived molecules across mitochondrial membranes for energy and carbon supply. The data presented here suggest that BOU identifies a novel mitochondrial pathway that is necessary to seedling development in the light. The BOU pathway would be an alternative to the well-known glyoxylate pathway.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2006

Shifts in doctor-patient communication between 1986 and 2002: a study of videotaped general practice consultations with hypertension patients.

BACKGROUND: Departing from the hypotheses that over the past decades patients have become more active participants and physicians have become more task-oriented, this study tries to identify shifts in GP and patient communication patterns between 1986 and 2002. METHODS: A repeated cross-sectional observation study was carried out in 1986 and 2002, using the same methodology. From two existing datasets of videotaped routine General Practice consultations, a selection was made of consultations with hypertension patients (102 in 1986; 108 in 2002). GP and patient communication was coded with RIAS (Roter Interaction Analysis System). The data were analysed, using multilevel techniques. RESULTS: No gender or age differences were found between the patient groups in either study period. Contrary to expectations, patients were less active in recent consultations, talking less, asking fewer questions and showing less concerns or worries. GPs provided more medical information, but expressed also less often their concern about the patients' medical conditions. In addition, they were less involved in process-oriented behaviour and partnership building. Overall, these results suggest that consultations in 2002 were more task-oriented and businesslike than sixteen years earlier. CONCLUSION: The existence of a more equal relationship in General Practice, with patients as active and critical consumers, is not reflected in this sample of hypertension patients. The most important shift that could be observed over the years was a shift towards a more businesslike, task-oriented GP communication pattern, reflecting the recent emphasis on evidence-based medicine and protocolized care. The entrance of the computer in the consultation room could play a role. Some concerns may be raised about the effectiveness of modern medicine in helping patients to voice their worries.

Adult↗
PubMed2001

FLEXGene repository: from sequenced genomes to gene repositories for high-throughput functional biology and proteomics.

The vast amount of information generated by the human genome sequencing project and related projects has given rise to a new paradigm in experimental biology. This new paradigm invokes the experimentation and data analysis at genome-wide scales, as well as the generation of new technologies and resources that take full advantage of the available sequence information. The Institute of Proteomics at Harvard Medical School is building a comprehensive, characterized, arrayed and flexible gene repository that will allow full exploitation of the genomic information by enabling functional genomics as well as protein expression, purification and analysis at genome wide scale. The FLEXGene repository (Full Length EXpression-ready) will contain clones representing the complete set of open reading frames (ORFs) of different organisms including H. sapiens and several pathogens and model organisms. The clones are constructed using recombination-based cloning technology so that hundreds or thousands of coding regions can be transferred into any expression vector in a parallel and timely mode, allowing the broadest variety of experiments to be carried out.

Animals↗
PubMed1991

Principles of the molecular construction of multienzyme templates for peptide biosynthesis in integrated reaction sequences.

The amino acid sequences of the genes coding for four multienzyme peptide synthetases, operating by the thiotemplate mechanism are compared, to show underlying principles in the biosynthetic mechanism. Alignment with other carboxylic acid activating enzymes shows the sequences. LAY(V/I)I(Y/F)TSGT(T/S)GxPKGV and GELx(L/I)GGxG(V/I) to be involved in MgATP2-binding and adenylate formation, and two other sequences, one containing the element FxLGG(H/D)S(I/L) to be involved in covalent binding of the amino acid. As a general rule, 1000 amino acid building blocks are responsible for the incorporation of one amino acid into the nascent peptide.

Amino Acid Sequence↗
PubMed1994

An improved system for exon recognition and gene modeling in human DNA sequences.

A new version of the GRAIL system (Uberbacher and Mural, 1991; Mural et al., 1992; Uberbacher et al., 1993), called GRAIL II, has recently been developed (Xu et al., 1994). GRAIL II is a hybrid AI system that supports a number of DNA sequence analysis tools including protein-coding region recognition, PolyA site and transcription promoter recognition, gene model construction, translation to protein, and DNA/protein database searching capabilities. This paper presents the core of GRAIL II, the coding exon recognition and gene model construction algorithms. The exon recognition algorithm recognizes coding exons by combining coding feature analysis and edge signal (acceptor/donor/translation-start sites) detection. Unlike the original GRAIL system (Uberbacher and Mural, 1991; Mural et al., 1992), this algorithm uses variable-length windows tailored to each potential exon candidate, making its performance almost exon length-independent. In this algorithm, the recognition process is divided into four steps. Initially a large number of possible coding exon candidates are generated. Then a rule-based prescreening algorithm eliminates the majority of the improbable candidates. As the kernel of the recognition algorithm, three neural networks are trained to evaluate the remaining candidates. The outputs of the neural networks are then divided into clusters of candidates, corresponding to presumed exons. The algorithm makes its final prediction by picking the best canadidate from each cluster. The gene construction algorithm (Xu, Mural and Uberbacher, 1994) uses a dynamic programming approach to build gene models by using as input the clusters predicted by the exon recognition algorithm. Extensive testing has been done on these two algorithms.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗