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[Introduction and critical comparison of clinical scores for characterizing the degree of morbidity of patients with cystic fibrosis].

Scoring systems for evaluation of the degree of severity in patients with cystic fibrosis are critically evaluated. Cross-sectional comparison of Shwachman's score, Cooperman's score, Taussig-NIH score, Bernese score and Huang score reveals that advantages and disadvantages of each score exist. In early days used as a marker of disease progression, later on integrated in research studies for patients survival, the scoring systems loose their power due to the possibility of computerized data storage of unlimited variables. Computerized networking allows immediate access to all measured data of an individual or of groups of patients with detailed criteria. Analysis of such data are less vulnerable for mistakes than individually scored patients data; scoring systems in cystic fibrosis will probably become an historical measure.

Child↗

Public web-based services from the European Bioinformatics Institute.

The mission of the European Bioinformatics Institute (EBI), an outstation of the European Molecular Biology Laboratory (EMBL) in Heidelberg, is to ensure that the growing body of information from molecular biology and genome research is placed in the public domain and is accessible freely to all parts of the scientific community in ways that promote scientific progress. To fulfil this mission, the EBI provides a wide variety of free, publicly available bioinformatics services. These can be divided into data submissions processing; access to query, analysis and retrieval systems and tools; ftp downloads of software and databases; training and education and user support. All of these services are available at the EBI website: http://www.ebi.ac.uk/services. This paper provides a detailed introduction to the interactive analysis systems that are available from the EBI and a brief introduction to other, related services.

Computational Biology↗

Chicken microchromosomes are hyperacetylated, early replicating, and gene rich.

The chicken karyotype consists of 39 chromosomes of which 33 are classed as microchromosomes (MICs). MICs contain about one third of genomic DNA. The majority of mapped chicken genes are assigned to macrochromosomes (MACs), but a recent study indicated that CpG islands (CGIs), which are associated with most vertebrate genes, map predominantly to MICs. The present work establishes that chicken genes are concentrated on MICs by several criteria. Acetylated (lysine 5) histone H4, which is strongly correlated with the presence of genes, is highly enriched on MICs by immunocytochemistry. In addition, detailed analysis of chicken cosmids shows that CGI-like fragments are approximately six times denser on MICs than on MACs. Published mapping of randomly chosen genes by fluorescent in situ hybridization (FISH) also shows a significant excess of microchromosomal assignments. Finally, the finding that MICs replicate during the first half of S phase is also compatible with the suggestion that MICs represent gene-rich DNA. We use the cosmid data to predict that approximately 75% of chicken genes are located on microchromosomes. [The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AJ001643 and AJ001644.]

Acetylation↗

A software system for data analysis in automated DNA sequencing.

Software for gel image analysis and base-calling in fluorescence-based sequencing consisting of two primary programs, BaseFinder and GelImager, is described. BaseFinder is a framework for trace processing, analysis, and base-calling. BaseFinder is highly extensible, allowing the addition of trace analysis and processing modules without recompilation. Powerful scripting capabilities combined with modularity and multilane handling allow the user to customize BaseFinder to virtually any type of trace processing. We have developed an extensive set of data processing and analysis modules for use with the program in fluorescence-based sequencing. GelImager is a framework for gel image manipulation. It can be used for gel visualization, lane retracking, and as a front end to the Washington University Getlanes program. The programs were designed using a cross-platform development environment, currently allowing them to run in Windows NT, Windows 95, Openstep/Mach, and Rhapsody. Work is ongoing to deploy the software on additional platforms, including Solaris, Linux, and MacOS. This software has been thoroughly tested and debugged in the analysis of >2 million bp of raw sequence data from human chromosome 19 region q13. Overall sequencing accuracy was measured using a significant subset of these data, consisting of approximately 600 sequences, by comparing the individual shotgun sequences against the final assembled contigs. Also, results are reported from experiments that analyzed the accuracy of the software and two other well-known base-calling programs for sequencing the M13mp18 vector sequence. [The sequence data described in this paper have been submitted to the GenBank data library under accession no. AF025422]

Algorithms↗

Genome-wide expression studies of atherosclerosis: critical issues in methodology, analysis, interpretation of transcriptomics data.

During the past 6 years, gene expression profiling of atherosclerosis has been used to identify genes and pathways relevant in vascular (patho)physiology. This review discusses some critical issues in the methodology, analysis, and interpretation of the data of gene expression studies that have made use of vascular specimens from animal models and humans. Analysis of gene expression studies has evolved toward the genome-wide expression profiling of large series of individual samples of well-characterized donors. Despite the advances in statistical and bioinformatical analysis of expression data sets, studies have not yet fully exploited the potential of gene expression data sets to obtain novel insights into the molecular mechanisms underlying atherosclerosis. To assess the potential of published expression data, we compared the data of a CC chemokine gene cluster between 18 murine and human gene expression profiling articles. Our analysis revealed that an adequate comparison is mainly hindered by the incompleteness of available data sets. The challenge for future vascular genomic profiling studies will be to further improve the experimental design, statistical, and bioinformatical analysis and to make data sets freely accessible.

Animals↗

Granulocyte macrophage-colony stimulating factor and oral mucositis.

OBJECTIVE: To evaluate the effect of granulocyte macrophage-colony stimulating factor (GM-CSF) in patients with oral mucositis. DATA SOURCES: Literature was accessed through MEDLINE (1966-June 2000) and bibliographic searches. DATA SYNTHESIS: Published literature assessing the use of GM-CSF to treat or prevent oral mucositis was analyzed. CONCLUSIONS: Reports of GM-CSF improving mucositis have been published; however, because of limitations in these reports, insufficient evidence confirms the benefits of GM-CSF. These preliminary studies provide a rationale to conduct well-designed, double-blind, randomized trials to evaluate the safety and efficacy of GM-CSF in the treatment and/or prevention of oral mucositis induced by chemotherapy and/or radiotherapy.

Adolescent↗

Microcomputer database management for surgical residents.

Surgical residents must record procedures performed and may choose to keep files of photographic slides, bibliographic references, and a curriculum vitae. Four databases that store this information are produced with an inexpensive and easily obtained microcomputer software program. A surgical procedure database is modeled after the procedure list recommended by surgical boards. This list can be viewed while one enters data, thereby enabling production of accurate and complete records. In the second database, photographic slides are assigned sequence numbers and slide content is designated using both procedure codes and key words, allowing structured and personal recall of data. Data can be printed in many report formats, including that used by the boards of surgery for final submission of reports of residents' operations at the completion of residency. The bibliographic and CV databases contain highly segmented citation data. This structure enables manipulation of data to satisfy the sequence requirements of journals or institutions to which articles or CV are submitted. Database maintenance consumes a few minutes daily and requires a minimum of experience with computers. By providing ease of access to organized data, these databases enhance the potential for critical review of clinical experience by both residents and program directors.

General Surgery↗

New national surveillance system for hemodialysis-associated infections: initial results.

BACKGROUND: Hemodialysis patients have frequent infections, especially of the vascular access site, and often harbor antimicrobial-resistant pathogens. Therefore a voluntary national system was created to monitor and prevent infections in these patients. METHODS: From October 1999 to May 2001, participating centers recorded the number of chronic hemodialysis outpatients that were treated (denominator). Several outcome events, including infections of the vascular access site, were monitored. Data were reported on paper forms or via an Internet-based data entry and analysis system. RESULTS: Among 109 participating centers, the vascular access infection rate per 100 patient-months was 3.2 overall and varied markedly by type of vascular access: 0.56 for native arteriovenous fistulas, 1.36 for synthetic arteriovenous grafts, 8.42 for cuffed catheters, and 11.98 for noncuffed catheters. Among 76 dialysis centers reporting at least 200 patient-months of data, 11 had a significantly low and 14 a significantly high rate of vascular access infection. CONCLUSION: Initial results from the first national project to monitor infections in patients undergoing hemodialysis indicate that vascular access infections were common and that risk varied substantially among different vascular access types and different dialysis centers. These results can be used for quality improvement at individual centers and to help evaluate the efficacy of specific infection control measures.

Ambulatory Care Facilities↗

Development of a data visualization and analysis tool to study the particle dynamics in the coastal zone.

Developing a field experiment to study the different aspects of the marine system involves both the co-operation of research groups from distinct disciplines and the use of various meteorological and oceanographical sensors deployed simultaneously at different locations. The information obtained, stored in voluminous data sets and frequently in various formats, needs to be visualized and analysed in different ways to provide knowledge of the dynamics of the system examined. There is therefore need for tools to be able to: (i) access and retrieve data sets stored in various file formats, and (ii) to allow their visualization and analysis. In this work, a user-friendly visualization and analytical tool was developed for this purpose using the IDL (Interactive Data Language v.5.3). It allows the description, interpretation and analysis of the temporal and spatial variability of both scalar and vector variables. A description of the software is given and an application using data from the High Frequency Flux (HFF) experiment, part of the European MTP II-Mater research project, in the Gulf of Lions is presented.

Automation↗

The JCAHO patient safety event taxonomy: a standardized terminology and classification schema for near misses and adverse events.

BACKGROUND: The current US national discussions on patient safety are not based on a common language. This hinders systematic application of data obtained from incident reports, and learning from near misses and adverse events. OBJECTIVE: To develop a common terminology and classification schema (taxonomy) for collecting and organizing patient safety data. METHODS: The project comprised a systematic literature review; evaluation of existing patient safety terminologies and classifications, and identification of those that should be included in the core set of a standardized taxonomy; assessment of the taxonomy's face and content validity; the gathering of input from patient safety stakeholders in multiple disciplines; and a preliminary study of the taxonomy's comparative reliability. RESULTS: Elements (terms) and structures (data fields) from existing classification schemes and reporting systems could be grouped into five complementary root nodes or primary classifications: impact, type, domain, cause, and prevention and mitigation. The root nodes were then divided into 21 subclassifications which in turn are subdivided into more than 200 coded categories and an indefinite number of uncoded text fields to capture narrative information. An earlier version of the taxonomy (n = 111 coded categories) demonstrated acceptable comparability with the categorized data requirements of the ICU safety reporting system. CONCLUSIONS: The results suggest that the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) Patient Safety Event Taxonomy could facilitate a common approach for patient safety information systems. Having access to standardized data would make it easier to file patient safety event reports and to conduct root cause analyses in a consistent fashion.

Causality↗

A casemix model for estimating the impact of hospital access block on the emergency department.

OBJECTIVE: To determine the ED activity and costs resulting from access block. METHODS: A casemix model (AWOOS) was developed to measure activity due to access block. Using data from four hospitals between 1998 and 2002, ED activity was measured using the urgency and disposition group (UDG) casemix model and the AWOOS model with the purpose of determining the change in ED activity due to access block. RESULTS: Whilst the mean length of stay in ED (admitted patients) increased by 93% between 1998 and 2002, mean UDG activity increased by 0.63% compared to a mean increase in AWOOS activity of 24.5%. The 23.9% difference between UDG and AWOOS activity represents the (unmeasured) increase in ED activity and costs for the period 1998-2002 resulting from access block. CONCLUSION: The UDG system significantly underestimates the activity in EDs experiencing marked access block.

Diagnosis-Related Groups↗

Benefits of the worldwide government computer-based patient record framework.

The G-CPR organization composed of the DoD, VA, IHS, and the LSUMC presents an opportunity to facilitate the exchange of clinical data across existing healthcare information systems with new business practices. The organization's ability to reengineer existing healthcare delivery processes through the G-CPR framework will improve the sharing of information and will ultimately provide for better-quality healthcare, improved access to care, greater cost efficiencies, and enhanced medical readiness of the DoD healthcare beneficiaries. The projected benefits that are by-products of the organization sharing effort tend to be focused in two broad categories: improving access to clinical data and creating a mechanism to gather information across large clinical populations. Both of the two categories include various benefits that accrue to members of the organization relative to their ability to use the G-CPR framework as a business reengineering tool. As information management processes are refined through reengineering initiatives, benefits will be observed at multiple program levels--from the DoD enterprise level down to the operational level at individual treatment facilities. Using comprehensive data to quantify precise benefits and ROI strategies is difficult because the development of the G-CPR framework is still in its early stage. Formal performance-based outcome studies are envisioned to demonstrate these results once the G-CPR framework attains greater functional definition. Through the future development of benefits performance metrics, these benefits can be shown to have substantial impact on achieving the strategic goals of the MHS and the organization while helping to improve the cost and quality of healthcare, access to care, and the medical readiness posture within the DoD.

Computer Communication Networks↗

Crystal structure of reverse gyrase: insights into the positive supercoiling of DNA.

Reverse gyrase is the only topoisomerase known to positively supercoil DNA. The protein appears to be unique to hyperthermophiles, where its activity is believed to protect the genome from denaturation. The 120 kDa enzyme is the only member of the type I topoisomerase family that requires ATP, which is bound and hydrolysed by a helicase-like domain. We have determined the crystal structure of reverse gyrase from Archaeoglobus fulgidus in the presence and absence of nucleotide cofactor. The structure provides the first view of an intact supercoiling enzyme, explains mechanistic differences from other type I topoisomerases and suggests a model for how the two domains of the protein cooperate to positively supercoil DNA. Coordinates have been deposited in the Protein Data Bank under accession codes 1GKU and 1GL9.

Adenosine Triphosphate↗

[Experiences in scientific use of data from cancer registries].

Epidemiological cancer registries have now been established in all federal states of Germany. Though some are still in an initial phase and completeness has not yet generally been achieved, the use of the data for scientific purposes appears feasible. The examples presented in this paper demonstrate that scientific projects have already been conducted or are ongoing. However, the experiences also demonstrate that lack of completeness and partially the legal regulations on access to the data may hamper the use considerably. Efforts must now focus on (a) achieving completeness, e. g., by making the reporting system more efficient and (b) harmonizing the legal regulations on cancer registration among the federal states and fitting them to practice.

Adolescent↗

The pH-dependence of the non-specific esterase activity of carboxypeptidase A.

The hydrolysis of the following 6 esters by bovine pancreatic carboxypeptidase A (peptidyl-L-amino-acid hydrolase, EC 3.4.12.2) has been investigated over the range pH 5--10 at 25 degrees C, ionic strength 0.2: CH3CO2CHRCO2H (R = C6H5 (ester 3), C6H5CH2 (ester 4), 4-NO2C6H4CO2CHRCO2H (R = C6H5 (ester 5), C6H5CH2 (ester 6), CH3(CH2)2 (ester 7)), CH3CH2CO2CH(CH2C6H5)-CO2H (ester 9). For each ester the pH dependence of kcat/Km indicates that substrate binding is controlled by an acid of pKEH = 9.2 +/- 0.2 in the free enzyme, and although kcat/Km decreases in acidic solutions no simple dependence on an enzymic ionization is apparent. For esters 3, 5 and 7 the dependence of kcat on pH is 'bell-shaped' and is controlled by pKEH2S = 6.73, 6.72, 6.23, respectively and pKEHS = 9.3 +/- 0.2 for each ester. For esters 4 and 6 the 'bell-shaped' kcat (pKEH2S = 7.38, 6.28, respectively) is modified by a significant increase in kcat in the vicinity of pH 10. This latter phenomenon is also shown by ester 9, although data are only accessible over the range pH 7--10 for this latter ester due to pronounced product inhibition in acidic solutions. The common pH-dependences observed for the enzymic hydrolyses of these nonspecific ester substrates are compared with literature data for specific ester and peptide substrates, and possible assignments for the various enzymic pKa values are discussed.

Animals↗

Translating traditional principles of system development into a process for designing clinical information systems.

Traditional software development methodologies enhanced by a clinical component result in information systems that support the practice of nursing. This paper describes the clinical informatics model used to develop and evaluate a mobile computer assessment tool. Data entry of atomic-level elements, with storage in a relational database, allows the synthesis and analysis by multiple disciplines to aid in real-time decision making. The system is designed to improve the recording and accessibility of patient data and nursing observations on a geriatric unit at the Salt Lake VA Medical Center.

Clinical Medicine↗

Factors that affect postdialysis rebound in serum urea concentration, including the rate of dialysis: results from the HEMO Study.

Previous studies have suggested that postdialysis urea rebound is related to K/V, the rate of dialysis, but a systematic analysis of factors that affect rebound has not been reported. With the use of 30-min and, in a subset, 60-min postdialysis samples, postdialysis urea rebound was measured to (1) determine how well previously proposed equations based on the rate of dialysis (K/V) predict rebound in a large sample of patients with varying characteristics, (2) determine whether other factors besides K/V affect rebound, and (3) estimate more precise values for coefficients in prediction equations for rebound. Rebound was calculated relative to both immediate and 20-s postdialysis samples to study early components of rebound unrelated to access recirculation. The equilibrated Kt/V (eKt/V) computed by fitting the two-pool variable volume model to the 30-min postdialysis sample agreed well with eKt/V based on the 60-min postdialysis sample. Using the pre-, post-, and 30-min postdialysis samples for 1245 patients with arteriovenous (AV) accesses, the median intercompartmental mass transfer coefficient (Kc) was 797 ml/min for rebound computed relative to the 20-s postdialysis samples and 592 ml/min relative to the immediate postdialysis samples. K/V was the strongest predictor of rebound among 22 factors considered. Other factors associated with greater rebound for 1331 patients using AV accesses or venous catheters included access type, black race, male gender, absence of congestive heart failure, greater age, ultrafiltration rate, and low predialysis or intradialysis systolic BP. Equations of the form eKt/V = single-pool Kt/V - B x (K/V) were fit to the data. With AV access, the optimum values for the slope term (B) were 0.39 and 0.46 (in h(-1)) for single-pool Kt/V calculated based on 20-s postdialysis or immediate postdialysis samples, respectively. For patients using venous catheters, the respective values for B were 0.22 and 0.29. Postdialysis urea rebound can be predicted with acceptable accuracy from a postdialysis sample using a zero-intercept, K/V-based rate equation. Several patient or treatment-specific factors predict enhanced or reduced rebound. Rate equation slope coefficients for K/V of 0.39 (AV access) and 0.22 (venous access) are proposed when a 15- to 20-s slow-flow method is used to draw the postdialysis blood. Slightly higher K/V slope coefficients (0.46 and 0.29, respectively) should be used if a shorter (e.g., 10 s) slow-flow period is used.

Female↗

A web access script language to support clinical application development.

This paper describes the development of a script language to support the implementation of decentralized, clinical information applications on the World Wide Web (Web). The goal of this work is to facilitate construction of low overhead, fully functional clinical information systems that can be accessed anywhere by low cost Web browsers to search, retrieve and analyze stored patient data. The Web provides a model of network access to data bases on a global scale. Although it was originally conceived as a means to exchange scientific documents, Web browsers and servers currently support access to a wide variety of audio, video, graphical and text based data to a rapidly growing community. Access to these services is via inexpensive client software browsers that connect to servers by means of the open architecture of the Internet. In this paper, the design and implementation of a script language that supports the development of low cost, Web-based, distributed clinical information systems for both Inter- and Intra-Net use is presented. The language is based on the Mumps language and, consequently, supports many legacy applications with few modifications. Several enhancements, however, have been made to support modern programming practices and the Web interface. The interpreter for the language also supports standalone program execution on Unix, MS-Windows, OS/2 and other operating systems.

Computer Communication Networks↗