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"Thanks to the Internet, researchers now have instant and easy access to reference sources and databases and in many cases, no longer have to pay search fees. Highlighted here are some of the most useful reference sources for population research on the Internet."
UNLABELLED: TRANSPATH is an information system on gene-regulatory pathways, and an extension module to the TRANSFAC database system (Wingender et al., Nucleic Acids Res., 28, 316-319, 2000). It focuses on pathways involved in the regulation of transcription factors in different species, mainly human, mouse and rat. Elements of the relevant signal transduction pathways like complexes, signaling molecules, and their states are stored together with information about their interaction in an object-oriented database. The database interface provides clickable maps and automatically generated pathway cascades as additional ways to explore the data. All information is validated with references to the original publications. Also, references to other databases are provided (TRANSFAC, SWISS-PROT, EMBL, PubMed and others). AVAILABILITY: The database is available over (http://transpath.gbf.de) for interactive perusal. As an exchange format for the data, eXtensible Markup Language (XML) flatfiles and a Document Type Definition (DTD) are provided.
OBJECTIVE: To assess the diversity of research on the management of opioid withdrawal, identify sources of heterogeneity and provide a context for subsequent systematic reviews to establish evidence-based best practice. METHODS: References were identified through searches of multiple electronic databases and handsearching the reference lists of retrieved articles. The principal criterion for inclusion in the literature mapping process was that it be a study of an intervention intended to manage the process of opioid withdrawal. RESULTS: Of 218 references assessed, all participants were dependent on heroin in 41% and on methadone or l-alpha acetyl methadol (LAAM) in 24%. More than 17 different types of treatment approach were identified. Only 42% of references used a rating instrument to assess withdrawal severity and reported sufficient results to indicate the timing and magnitude of the peak and/or duration of withdrawal. The type of rating instrument used and the way in which results were reported varied enormously. A clear parameter for completion of detoxification was used for 37% of references. CONCLUSIONS: The capacity for rigorous systematic reviews of the management of opioid withdrawal is currently limited. There are multiple sources of heterogeneity that will need to be taken into account. IMPLICATIONS: The use of narrative reviews and observational studies are important complements to formal systematic reviews in the establishment of evidence-based practice in any area that combines aspects of psychology, behaviour, social context and medical treatment.
We investigated the association between hormone replacement therapy (HRT), primarily conjugated estrogens with or without medroxyprogesterone acetate, and colon cancer risk in a nested case-control study among women ages 55-79 years enrolled in Group Health Cooperative, a health maintenance organization in Washington state. Cases were diagnosed between 1984 and 1993. We selected controls randomly from enrollment files. HRT use was ascertained from a computerized database containing virtually all prescriptions dispensed since 1977. Among subjects with at least 5 years of pharmacy database information before reference date (1 year before diagnosis date), there were 341 cases of incident colon cancer and 1,679 controls. Estrogen use during the 5 years before reference date was not associated with risk of colon cancer [odds ratio (OR) = 0.85 and 95% confidence interval (CI) = 0.57-1.27 for 1-749 estrogen tablets; OR = 0.97 and 95% CI = 0.68-1.40 for > or =750 estrogen tablets]. An analysis including only women with at least 10 years of pharmacy database coverage found no association with use during the 10 years before reference date [OR = 1.07 (95% CI = 0.61-1.86) for 1-749 estrogen tablets; OR = 1.11 (95% CI = 0.69-1.80) for 750 or more estrogen tablets]. These results do not support the hypothesis that recent HRT use substantially reduces risk of colon cancer.
PURPOSE: This article provides the foundation for a series of literature reviews that critically examine the effectiveness of worksite health promotion programs. This issue reviews the exercise, health risk appraisal, nutrition and cholesterol, and weight control literatures; a future issue will review the alcohol, HIV/AIDS, multicomponent program, seat belt, smoking, and stress management literatures. METHODS: The literature search used a four-step process that included a computerized database search, a reference search, a manual search of relevant health promotion journals, and the writing of the review by a recognized expert in the area being searched. The databases were searched from 1968 through 1994 and included Medline, Aidsline, Psychological Abstracts, Combined Health Information Database, Employee Benefits Infosource, National Prevention Evaluation Research Collection, National Resource Center on Worksite Health Promotion, National Technical Information Service, and the Substance Abuse Information database. A total of 288 articles were identified by the search, not including the 37 articles in the hypertension literature. Authors of each review were requested to incorporate additional studies not identified by the search, provide a research rating for each individual article, and a rating for the overall literature for their respective area. The authors reviewed 316 studies. FINDINGS: The overall ratings for the reviews reported in this issue were suggestive for exercise, weak for health risk appraisals, suggestive/indicative for both nutrition and cholesterol, and indicative for weight control. The ratings for the other reviews will be reported in the subsequent issue. CONCLUSIONS: Research reported in these reviews suggests the effectiveness of worksite health promotion programs, however, additional research is required to provide conclusive evidence of their impact.
GeneTag is a novel expression profiling method that allows the visualization, quantification and identification of expressed genes-whether known or novel-in any species, tissue or cell type, independent of knowledge of the underlying sequence. Here we describe the application of this method to determine variation of gene expression in individual human liver samples and the identification of tissue-specific genes by comparing expression patterns across several human organs. Expression data are stored in a database for future reference and data analysis relies on proprietary software, which allows complex comparisons to be performed. Differentially expressed genes are quickly identified through a link to a sequence database. The results from our study underscore the importance of knowledge of individual variation of gene expression for the design and interpretation of transcript profiling experiments in the context of any biological question.
MOTIVATION: There have been several endeavours to address the problem of annotating sequence data computationally, but the task is non-trivial and few tools have emerged that gather useful information on a given sequence, or set of sequences, in a simple and convenient manner. As more genome projects bear fruit, the mass of uncharacterized sequence data accumulating in public repositories grows ever larger. There is thus a pressing need for tools to support the process of automatic analysis and annotation of newly determined sequences. With this in mind, we have developed PRECIS, which automatically creates protein reports from sets of SWISS-PROT entries, collating results into structured reports, detailing known biological and medical information, literature and database cross-references, and relevant keywords.
Polymerase chain reaction (PCR) was applied to detect and establish provisional identity of begomoviruses through amplification of a approximately 575 bp fragment of the begomoviral coat protein gene (CP), referred to as the 'core' region of the CP gene (core CP). The core CP fragment contains conserved and unique regions, and was hypothesized to constitute a sequence useful for begomovirus classification. Virus relationships were predicted by distance and parsimony analyses using the A component (bipartite viruses) or full genome (monopartite viruses), CP gene, core CP, or the 200 5'-nucleotides (nt) of the CP. Reconstructed trees and sequence divergence estimates yielded very similar conclusions for all sequence sets, while the CP 5'-200 nt was the best strain discriminator. Alignment of the core CP region for 52 field isolates with reference begomovirus sequences permitted provisional virus identification based on tree position and extent of sequence divergence. Geographic origin of field isolates was predictable based on phylogenetic separation of field isolates examined here. A 'closest match' or genus-level identification could be obtained for previously undescribed begomoviruses using the BLAST program to search a reference core CP database located at our website and/or in GenBank. Here, we describe an informative molecular marker that permits provisional begomovirus identification and classification using a begomoviral sequence that is smaller than the presently accepted, but less accessible CP sequence.
Either of these programs will accomplish the task of storing and organizing a personal bibliography. Reference Manager is more widely used, but more costly. Although it contains more input formats than Papyrus, most of the common formats used in medicine are supported by both programs. Importing is the best way to establish a personal database with many references, since it avoids manually typing the data. The import interface in Reference Manager is simpler to use at first, and faster than Papyrus's, but either program accomplishes the task with relative ease. The authors of Papyrus are receptive to updating import formats and adding new formats to their libraries as requested by users. Why not use MEDLINE alone instead of downloading and maintaining a personal reference list? These programs are more useful than MEDLINE in their output formatting capabilities. The most useful output feature is the generation of bibliographies for manuscripts, and both programs accomplish this task nicely. Papyrus includes fewer specific journal formats than Reference Manager, but both programs permit the user to add detailed output specifications to their personal journal lists.
Preliminary clinical studies suggest that spiral computed tomography (CT) of the lungs can improve early detection of lung cancer in high-risk individuals. More clinical studies are needed, however, before public health recommendations can be proposed for population-based screening. Spiral CT generates large-volume data sets and thus poses problems in terms of implementation of efficient and cost-effective screening methods. Image processing algorithms such as computer assisted diagnostic (CAD) methods have the potential to assist in lesion (eg, nodule) detection on spiral CT studies. CAD methods may also be used to characterize nodules by either assessing the stability or change in size of lesions based on evaluation of serial CT studies, or quantitatively measuring the temporal parameters related to contrast dynamics when using contrast material-enhanced CT studies. CAD methods therefore have the potential to enhance the sensitivity and specificity of spiral CT lung screening studies. Lung cancer screening studies now under investigation create an opportunity to develop an image database that will allow comparison and optimization of CAD algorithms. This database could serve as an important national resource for the academic and industrial research community that is currently involved in the development of CAD methods. The National Cancer Institute request for applications (RFA) (CA-01-001) has already been announced (April 2000) to establish and support a consortium of academic centers to develop this database, the consortium to be referred to as the Lung Image Database Consortium (LIDC). This RFA is now closed. Five academic sites have been selected to be members of the LIDC, the first meeting of this consortium is planned for spring of 2001, and a public meeting is to be held in 2002. This report is abstracted from the previously published RFA to serve as an example of how an initiative is developed by the National Cancer Institute to support a research resource. For specific details of the RFA, please access the following Internet site: http://www. nci.nih.gov/bip/NCI-DIPinisumm.htm#a11.
This article summarizes the various problems and pitfalls in using clinical databases for epidemiologic research, with particular reference to an HIV clinical database. The combined population of HIV-infected individuals attending the Chelsea and Westminster Hospital, the Charing Cross Hospital, and the Victoria Clinic in London is the largest cohort of HIV-positive individuals in the U.K. A computerized database was developed in the mid-1980s and was adapted into a clinically oriented observational database for approximately 6,653 HIV-1-positive registered patients from three hospital-based clinics within the Riverside Health Authority in London, U.K.: Chelsea and Westminster Hospital Clinic (n = 5,000); Charing Cross Hospital (n = 500); and the Victoria Clinic (n = 500). The majority (83%) of HIV-infected patients registered at these sites are homosexual or bisexual men. Of 2,078 patients seen within the last 6 months, 22% are asymptomatic and 33% have AIDS; 30% have a CD4 cell count of less than 100 cells/mm3 and 17% have a CD4 cell count of greater than 500 cells/mm3. Dates of seroconversion are known for approximately 285 patients. For each patient, information on demographic characteristics, clinical symptoms, and HIV-related diagnoses, outpatient pharmacy prescriptions, day care treatments and procedures, and enrollment into clinical trials is routinely collected at outpatient clinic visits and entered into the database. Inpatient diagnoses and treatments were integrated into the database in September 1995. Unused serum samples from routine AIDS antibody or antigen testing are stored in a local specimen repository. The main purpose of the HIV database is to provide a multipurpose resource for use by physicians, researchers, and managers for administration, clinical care, and research. The specific functions of the database are the following: to enhance patient management by providing access to a clinical summary sheet detailing up-to-date information; to serve as a research tool for clinical and epidemiologic research; to aid in the identification of patients eligible for planned or ongoing clinical trials; to provide a facility for local and regional AIDS surveillance and reporting; and to provide a facility for administration and resource management of HIV services. The major limitations of this database in the conduct of clinical research have been losses to follow-up and incomplete information about clinical outcomes, because physicians have failed to update the clinical information.
The work of a researcher in epidemiology is based on studying literature, planning studies, gathering data, analyzing data and writing results. Therefore he has need for performing, more or less, simple calculations, the need for consulting or quoting literature, the need for consulting textbooks about certain issues or procedures, and the need for looking at a specific formula. There are no programs conceived as a workstation to assist the different aspects of researcher work in an integrated fashion. A hypertextual system was developed which supports different stages of the epidemiologist's work. It combines database management, statistical analysis or planning, and literature searches. The software was developed on Apple Macintosh by using Hypercard 2.1 as a database and HyperTalk as a programming language. The program is structured in 7 "stacks" or files: Procedures; Statistical Tables; Graphs; References; Text; Formulas; Help. Each stack has its own management system with an automated Table of Contents. Stacks contain "cards" which make up the databases and carry executable programs. The programs are of four kinds: association; statistical procedure; formatting (input/output); database management. The system performs general statistical procedures, procedures applicable to epidemiological studies only (follow-up and case-control), and procedures for clinical trials. All commands are given by clicking the mouse on self-explanatory "buttons". In order to perform calculations, the user only needs to enter the data into the appropriate cells and then click on the selected procedure's button. The system has a hypertextual structure. The user can go from a procedure to other cards following the preferred order of succession and according to built-in associations. The user can access different levels of knowledge or information from any stack he is consulting or operating. From every card, the user can go to a selected procedure to perform statistical calculations, to the reference database management system, to the textbook in which all procedures and issues are discussed in detail, to the database of statistical formulas with automated table of contents, to statistical tables with automated table of contents, or to the help module. he program has a very user-friendly interface and leaves the user free to use the same format he would use on paper. The interface does not require special skills. It reflects the Macintosh philosophy of using windows, buttons and mouse. This allows the user to perform complicated calculations without losing the "feel" of data, weight alternatives, and simulations. This program shares many features in common with hypertexts. It has an underlying network database where the nodes consist of text, graphics, executable procedures, and combinations of these; the nodes in the database correspond to windows on the screen; the links between the nodes in the database are visible as "active" text or icons in the windows; the text is read by following links and opening new windows. The program is especially useful as an educational tool, directed to medical and epidemiology students. The combination of computing capabilities with a textbook and databases of formulas and literature references, makes the program versatile and attractive as a learning tool. The program is also helpful in the work done at the desk, where the researcher examines results, consults literature, explores different analytic approaches, plans new studies, or writes grant proposals or scientific articles.
PhosphoBase contains information about phosphorylated residues in proteins and data about peptide phosphorylation by a variety of protein kinases. The data are collected from literature and compiled into a common format. The current release of PhosphoBase (October 1998, version 2.0) comprises 414 phosphoprotein entries covering 1052 phosphorylatable serine, threonine and tyrosine residues. The kinetic data from peptide phosphorylation assays for approximately 330 oligopeptides is also included. The database entries are cross-referenced to the corresponding records in the Swiss-Prot protein database and literature references are linked to MedLine records. PhosphoBase is available via the WWW at http://www.cbs.dtu. dk/databases/PhosphoBase/
A proteomics approach was used to identify the proteins potentially implicated in the cellular response concomitant with elevated production levels of human growth hormone in a recombinant Chinese hamster ovary (CHO) cell line following exposure to 0.5 mM butyrate and 80 microM zinc sulphate in the production media. This involved incorporation of two-dimensional (2-D) gel electrophoresis and protein identification by a combination of N-terminal sequencing, matrix-assisted laser desorption/ionisation-time of flight mass spectrometry, amino acid analysis and cross species database matching. From these identifications a CHO 2-D reference map and annotated database have been established. Metabolic labelling and subsequent autoradiography showed the induction of a number of cellular proteins in response to the media additives butyrate and zinc sulphate. These were identified as GRP75, enolase and thioredoxin. The chaperone proteins GRP78, HSP90, GRP94 and HSP70 were not up-regulated under these conditions.
The approach of the Joint Meeting on Pesticide Residues to the establishment of the acute reference dose for pesticides is presented and related issues are discussed. Three main points seem relevant when discussing the acute reference dose: (1) what compounds should have an acute reference dose, (2) what toxicological database is required for the establishment of an acute reference dose; (3) what safety factors are to be used. It is concluded that (1) groups of compounds that need an acute reference dose can be identified, whereas general rules for identifying groups not requiring an acute reference dose cannot be easily given; (2) studies from the standard toxicological database can often be used to allocate an acute reference dose and the usefulness of refinements (by requesting specific studies) should be evaluated after intake assessment; general rules on study requirements cannot be easily given; (3) more thought should be given to what safety factors apply in certain circumstances.
A proteomics approach was used to investigate global protein changes in rat sensory ganglia exposed to pro-inflammatory stimuli. Inflammation was provoked in vivo by injecting selected facial areas with Freunds Complete Adjuvant (FCA), or by stimulating freshly isolated trigeminal ganglia ex vivo with pro-inflammatory mediators (interleukin-1 beta, tumor necrosis factor-alpha, interferon-gamma). Following two-dimensional gel electrophoresis, silver staining and mass spectrometry, a protein reference map and database was generated for rat trigeminal ganglia, which to our knowledge is the first to be reported. Sixty-seven out of 85 selected protein spots were successfully identified using matrix-assisted laser desorption/ionization mass spectrometry. This reference map was used to monitor changes in the ganglia proteome induced during inflammation in vivo and ex vivo. In vivo we found that FCA treatment specifically induced differential protein expression of two unidentified protein spots and, to a lower extent, of beta-tubulin. Image analysis of ganglia treated ex vivo with the cocktail of cytokines indicated that some of the changes in the protein population were also observed in vivo after FCA treatment. If the cytokine stimulation was performed in the presence of acetaminophen (paracetamol), the drug seemed to reverse the effects of cytokine treatment for at least some protein spots, restoring the same protein pattern observed in control samples.
A drawback of current open-path Fourier transform infrared (OP/FT-IR) systems is that they need a human expert to determine those compounds that may be quantified from a given spectrum. In this work, multilayer feed-forward neural networks with one hidden layer were used to automatically recognize compounds in an OP/FT-IR spectrum without compensation of absorption lines due to atmospheric H2O and CO2. The networks were trained by fast-back-propagation. The training set comprised spectra that were synthesized by digitally adding randomly scaled reference spectra to actual open-path background spectra measured over a variety of path lengths and temperatures. The reference spectra of 109 compounds were used to synthesize the training spectra. Each neural network was trained to recognize only one compound in the presence of up to 10 other interferences in an OP/FT-IR spectrum. Every compound in a database of vaporphase reference spectra can be encoded in an independent neural network so that a neural network library can be established. When these networks are used for the identification of compounds, the process is analogous to spectral library searching. The effect of learning rate and band intensities on the convergence of network training was examined. The networks were successfully used to recognize five alcohols and two chlorinated compounds in field-measured controlled-release OP/FT-IR spectra of mixtures of these compounds.
A protein class (ProClass) database is developed as a "value-added" "second-generation" database organized according to family relationships. The database collects non-redundant protein sequence entries from SwissProt and PIR databases, and classifies them in families defined collectively by the ProSite protein groups and PIR superfamilies. The major objectives of the database are to maximize family information retrieval, to provide speedy family identification, and to help organizing existing protein sequence databases. The database has two sub-databases: PCFam (ProClass Family) to define protein families and provide links to ProSite patterns and PIR superfamilies, and PCSeq (ProClass Sequence) to describe sequence entries and provide links to PCFam, SwissProt, PIR, and ProSite databases. The current ProClass release has a total of 85,165 sequence entries, about half of which are classified in 3072 ProClass families; it also contains 10,431 newly established SwissProt-PIR links. The database can help reveal domain structures of related families, define new ProSite and PIR families, and provide family assignments for unclassified sequence entries. New ProSite and PIR family members are readily identified via database cross-reference, including 9437 SwissProt entries and 8522 PIR entries. False negative family members missed by both ProSite and PIR are detected using a neural network family identification system. The newly identified superfamily memberships are being incorporated into the current PIR database releases in a collaborative effort with the PIR. The ProClass database is accessible through anonymous FTP and on-line search on the World Wide Web.