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Gene expression databases and data mining.

The DNA microarray technology has arguably caught the attention of the worldwide life science community and is now systematically supporting major discoveries in many fields of study. The majority of the initial technical challenges of conducting experiments are being resolved, only to be replaced with new informatics hurdles, including statistical analysis, data visualization, interpretation, and storage. Two systems of databases, one containing expression data and one containing annotation data are quickly becoming essential knowledge repositories of the research community. This present paper surveys several databases, which are considered "pillars" of research and important nodes in the network. This paper focuses on a generalized workflow scheme typical for microarray experiments using two examples related to cancer research. The workflow is used to reference appropriate databases and tools for each step in the process of array experimentation. Additionally, benefits and drawbacks of current array databases are addressed, and suggestions are made for their improvement.

Breast Neoplasms↗

World Health Organization equations have shortcomings for predicting resting energy expenditure in persons from a modern, affluent population: generation of a new reference standard from a retrospective analysis of a German database of resting energy expenditure.

BACKGROUND: Reference standards for resting energy expenditure (REE) are widely used. Current standards are based on measurements made in the first part of the past century in various races and locations. OBJECTIVE: The aim of the present study was to investigate the application of the World Health Organization (WHO) equations from 1985 in healthy subjects living in a modern, affluent society in Germany and to generate a new formula for predicting REE. DESIGN: The study was a cross-sectional and retrospective analysis of data on REE and body composition obtained from 2528 subjects aged 5-91 y in 7 different centers between 1985 and 2002. RESULTS: Mean REE varied between 5.63 and 8.07 MJ/d in males and between 5.35 and 6.46 MJ/d in females. WHO prediction equations systematically overestimated REE at low REE values but underestimated REE at high REE values. There were significant and independent effects of sex, age, body mass or fat-free mass, and fat mass on REE. Multivariate regression analysis explained up to 75% of the variance in REE. Two prediction formulas including weight, sex, and age or fat-free mass, fat mass, sex, and age, respectively, were generated in a subpopulation and cross-validated in another subpopulation. Significant deviations were still observed for underweight and normal-weight subjects. REE prediction formulas for specific body mass index groups reduced the deviations. The normative data for REE from the Institute of Medicine underestimated our data by 0.3 MJ/d. CONCLUSIONS: REE prediction by WHO formulas systematically over- and underestimates REE. REE prediction from a weight group-specific formula is recommended in underweight subjects.

Adolescent↗

Iodised salt for preventing iodine deficiency disorders.

BACKGROUND: Iodine deficiency is the main cause for potentially preventable mental retardation in childhood, as well as causing goitre and hypothyroidism in people of all ages. It is still prevalent in large parts of the world. OBJECTIVES: To assess the effects of iodised salt in comparison with other forms of iodine supplementation or placebo in the prevention of iodine deficiency disorders. SEARCH STRATEGY: We searched the Cochrane Library, Medline, the Register of Chinese trials developed by the Chinese Cochrane Centre, and the Chinese Med Database. We performed handsearching of a number of journals (Chinese Journal of Control of Endemic Diseases, Chinese Journal of Epidemiology, Chinese Journal of Preventive Medicine, and Studies of Trace Elements and Health up to February 2001), and searched reference lists, databases of ongoing trials and the Internet. Date of latest search: November 2001. SELECTION CRITERIA: We included prospective controlled studies of iodised salt versus other forms of iodine supplementation or placebo in people living in areas of iodine deficiency. Studies reported mainly goitre rates and urinary iodine excretion as outcome measures. DATA COLLECTION AND ANALYSIS: The initial data selection and quality assessment of trials was done independently by two reviewers. Subsequently, after the scope of the review was slightly widened from including only randomised controlled trials to including non-randomised prospective comparative studies, a third reviewer repeated the trials selection and quality assessment. As the studies identified were not sufficiently similar and not of sufficient quality, we did not do a meta-analysis but summarised the data in a narrative format. MAIN RESULTS: We found six prospective controlled trials relating to our question. Four of these were described as randomised controlled trials, one was a prospective controlled trial that did not specify allocation to comparison groups, and one was a repeated cross-sectional study comparing different interventions. Comparison interventions included non-iodised salt, iodised water, iodised oil, and salt iodisation with potassium iodide versus potassium iodate. Numbers of participants in the trials ranged from 35 to 334; over 20,000 people were included in the cross-sectional study. Three studies were in children only, two investigated both groups of children and adults and one investigated pregnant women. There was a tendency towards goitre reduction with iodised salt, although this was not significant in all studies. There was also an improved iodine status in most studies (except in small children in one of the studies), although urinary iodine excretion did not always reach the levels recommended by the WHO. None of the studies observed any adverse effects of iodised salt. REVIEWER'S CONCLUSIONS: The results suggest that iodised salt is an effective means of improving iodine status. No conclusions can be made about improvements in other, more patient-oriented outcomes, such as physical and mental development in children and mortality. None of the studies specifically investigated development of iodine-induced hyperthyroidism, which can be easily overlooked if just assessed on the basis of symptoms. High quality controlled studies investigating relevant long term outcome measures are needed to address questions of dosage and best means of iodine supplementation in different population groups and settings.

Cross-Sectional Studies↗

Library of FT-Raman spectra of pigments, minerals, pigment media and varnishes, and supplement to existing library of Raman spectra of pigments with visible excitation.

Sixty pigments, minerals and media have been analysed by Fourier-transform Raman (FT-Raman) microscopy in order to assemble a database of reference FT-Raman spectra for scientists working at the Arts-Science interface. An earlier library of Raman spectra compiled using visible excitation has been extended by the addition of 22 further reference spectra obtained with 780.0, 647.1, 632.8 and/or 514.5 nm excitation. The relative merits of 1064 nm and visible excitation are discussed.

Databases, Factual↗

Beyond the rhetoric: what do we mean by a 'model of care'?

BACKGROUND: Contemporary health care systems are constantly challenged to revise traditional methods of health care delivery. These challenges are multifaceted and stem from: (1) novel pharmacological and non-pharmacological treatments; (2) changes in consumer demands and expectations; (3) fiscal and resource constraints; (4) changes in societal demographics in particular the ageing of society; (5) an increasing burden of chronic disease; (6) documentation of limitations in traditional health care delivery; (7) increased emphasis on transparency, accountability, evidence-based practice (EBP) and clinical governance structures; and (8) the increasing cultural diversity of the community. These challenges provoke discussion of potential alternative models of care, with scant reference to defining what constitutes a model of care. AIM: This paper aims to define what is meant by the term 'model of care' and document the pragmatic systems and processes necessary to develop, plan, implement and evaluate novel models of care delivery. METHODS: Searches of electronic databases, the reference lists of published materials, policy documents and the Internet were conducted using key words including 'model*', 'framework*', 'models, theoretical' and 'nursing models, theoretical'. The collated material was then analysed and synthesised into this review. RESULTS: This review determined that in addition to key conceptual and theoretical perspectives, quality improvement theory (eg. collaborative methodology), project management methods and change management theory inform both pragmatic and conceptual elements of a model of care. Crucial elements in changing health care delivery through the development of innovative models of care include the planning, development, implementation, evaluation and assessment of the sustainability of the new model. Regardless of whether change in health care delivery is attempted on a micro basis (eg. ward level) or macro basis (eg. national or state system) in order to achieve sustainable, effective and efficient changes a well-planned, systematic process is essential.

Delivery of Health Care↗

ISCORS Catalog of References to Parameter Values and Distributions Used in Environmental Pathway Modeling for Cleanup of Sites Contaminated with Radioactivity.

Federal and state regulatory agencies that are concerned with issues of environmental management have adopted approaches toward policy-making that are dose- and risk-informed. To that end they (and others) have developed environmental models and computer codes to mimic the transport of contaminants along air, water, food-chain, and related pathways for estimating potential exposures, doses, and risks to individuals, populations, and ecosystems. Their calculations commonly find application in the planning of remediation, and thereafter in the demonstration of compliance with federal and state cleanup standards. As the models and codes have become more sophisticated, so also have requirements on the accuracy and level of detail of the numerical point values and probability distributions of environmental transfer factors and other parameters that serve as input parameters to them. In response to this growing need, the federal Interagency Steering Committee On Radiation Standards (ISCORS) and the Argonne National Laboratory have developed an on-line, national repository of information on parameter values and distributions of known provenance and demonstrated utility. The ISCORS Catalog of References to Parameter Values and Distributions Used in Environmental Pathway Modeling for Cleanup of Sites Contaminated with Radioactivity is a web-based, indexed compilation of references, compendia, databases, and other sources of peer-reviewed information on parameters. It does not itself contain numerical point values or distributions for any particular parameter, but rather it provides links or directions to sites or other published materials where such information can be obtained. Designed to be user-friendly, easily searchable, and readily up-dateable, the Catalog is being filled, after some initial priming, mainly through on-line submissions of proposed references by the Catalog users themselves. The relevant information on a proposed reference is submitted to ISCORS in a simple, standardized format; it is vetted (with acceptance criteria such as publication in a peer-reviewed technical journal, or appearance in a formally-issued federal agency report) and then added semi-automatically to the Catalog. Built around a relational database, the system offers subject- and text-search capabilities, provides information on parameter definitions and methods of measurement, on transport/exposure pathways, and on standard models and codes. The Catalog is intended for use by (and being populated by) the professionals, managers, and others involved or interested in the application of pathway modeling to estimate doses and risks associated with sites contaminated with radioactive or other hazardous materials.

Databases as Topic↗

An implementation study of the PDRD primary care computerized guidelines.

OBJECTIVE: To study the implementation of electronic guidelines designed for general practitioners (GPs). DESIGN: A descriptive 3-year follow-up study. SUBJECTS: All new subscribers to Physician's Desk Reference and Database (PDRD) in 1992. SETTING: Locations of computers, where PDRD software was installed for the first time in 1992. MAIN OUTCOME MEASURES: Expectations of the program and changes in attitudes towards it, getting started with the system, frequency and continuity of use and estimated usefulness of the program. RESULTS: The guidelines were expected to enhance diagnostic accuracy (60% of subscribers), save time (45%), and reduce costs (11%). After 1 year's use, the opinions of the users on these topics had become slightly more positive. Technical problems delayed starting to use the program in 27%. After 1 year 72% were using the program at least weekly. Using frequency was associated with having the computer in the office. The subscribers who renewed their subscription after one year often became regular users. CONCLUSIONS: The study provides insight into the implementation phase of computer-based guidelines in a population of early adopters. Technical support was essential to overcome the barriers associated with computer technology. The perceived need for information was independent of the age and experience of the physicians.

Adult↗

Clinical and cost-effectiveness of electroconvulsive therapy for depressive illness, schizophrenia, catatonia and mania: systematic reviews and economic modelling studies.

OBJECTIVES: To establish the clinical effectiveness and cost-effectiveness of electroconvulsive therapy (ECT) for depressive illness, schizophrenia, catatonia and mania. DATA SOURCES: Electronic bibliographic databases. The reference lists of relevant articles and health services research-related resources were consulted via the Internet. REVIEW METHODS: Identified studies were examined to ascertain whether they met the inclusion criteria for the review. The study quality of relevant articles was assessed using standard checklists and data were abstracted using standardised forms into a database. Where relevant, results from studies were pooled for meta-analysis. Two economic models were developed primarily based on evidence from the clinical effectiveness analysis and limited quality of life studies. RESULTS: Two good-quality systematic reviews of randomised evidence of the efficacy and safety of ECT in people with depression, schizophrenia, catatonia and mania were identified. Four systematic reviews on non-randomised evidence were also identified, although only one of these could be described as good quality. There was no randomised evidence of the effectiveness of ECT in specific subgroups including older people, children and adolescents, people with catatonia and women with postpartum exacerbations of depression or schizophrenia. The economic modelling results for depression did not demonstrate that any of the scenarios had a clear economic benefit over the others, mainly because of the uncertainty surrounding the clinical effectiveness of the different treatments and the quality of life utility gains. Sensitivity analysis surrounding the cost of ECT and the quality of life utility values had little effect on the overall results. The results of the model for schizophrenia adapted to include ECT suggest that clozapine is a cost-effective treatment compared with ECT. For patients who fail to respond to clozapine, ECT treatment may be preferred to the comparative treatment of haloperidol/chlorpromazine. CONCLUSIONS: Real ECT is probably more effective than sham ECT, but as stimulus parameters have an important influence on efficacy, low-dose unilateral ECT is no more effective than sham ECT. ECT is probably more effective than pharmacotherapy in the short term and limited evidence suggests that ECT is more effective than repetitive transcranial magnetic stimulation. Tricyclic antidepressants (TCAs) may improve the antidepressant effect of ECT during the course of treatment. Continuation pharmacotherapy with TCAs combined with lithium in people who have responded to ECT reduces the rate of relapses. Overall, gains in the efficacy of the intervention depending on the stimulus parameters of ECT are achieved only at the expense of an increased risk of cognitive side-effects. Limited evidence suggests these effects do not last beyond 6 months, but there is no evidence examining the longer term cognitive effects of ECT. There is little evidence of the long-term efficacy of ECT. ECT either combined with antipsychotic medication or as a monotherapy is not more effective than antipsychotic medication in people with schizophrenia. More research is needed to examine the long-term efficacy of ECT and the effectiveness of post-ECT pharmacotherapy, the short-term and longer term cognitive side-effects of ECT, and the impact of ECT on suicide and all-cause mortality. Further work is needed to examine the information needs of people deciding whether to accept ECT and how their decision-making can be facilitated. More research is also needed on the mechanism of action of ECT. Finally, the quality of reporting of trials in this area would be vastly improved by strict adherence to the Consolidated Standards of Reporting Trials recommendations. Economic analysis may identify areas in which research would be best targeted by identifying parameters where reducing the level of uncertainty would have the most effect in helping to make the decision on whether ECT is a cost-effective treatment.

Adolescent↗

A comprehensive database for the small nucleolar RNAs from Saccharomyces cerevisiae.

Small nucleolar RNAs (snoRNAs) are involved in cleavage of rRNA, modification of rRNA nucleotides and, perhaps, other aspects of ribosome biogenesis in eukaryotic cells. Scores of snoRNAs have been discovered in recent years from various eukaryotes, and the total number is predicted to be up to 200 different snoRNA species per individual organism. We have created a comprehensive database for snoRNAs from the yeast Saccharomyces cerevisiae which allows easy access to detailed information about each species known (almost 70 snoRNAs are featured). The database consists of three major parts: (i) a utilities section; (ii) a master table; and (iii) a collection of tables for the individual snoRNAs. The utilities section provides an introduction to the database. The master table lists all known S. cerevisiae snoRNAs and their major properties. Information in the individual tables includes: alternate names, size, family classification, genomic organization, sequences (with major features identified), GenBank accession numbers, occurrence of homologues, gene disruption phenotypes, functional properties and associated RNAs and proteins. All information is accompanied with appropriate literature references. The database is available on the World Wide Web (http://www.bio.umass. edu/biochem/rna-sequence/Yeast_snoRNA_Database/snoRNA_ DataBase.html), and should be useful for a wide range of snoRNA studies.

Cell Nucleolus↗

Reliability and adequacy of discharge diagnosis databases in the production of reference values.

Discharge diagnoses provide a possibility to select patients individually and then to establish reference values for both "pathological" and control groups. Currently, the available diagnostic information is still at its infancy and should be carefully evaluated before the reference values based on those groups are utilized. It is anticipated that electronic storage of diagnostic and therapeutic information will be applied more commonly in the future as the development of computers makes it easier. The advanced utilization of laboratory data challenges physicians both in the clinical and laboratory side to participate in this development in order to make the information systems serve their actual needs more closely.

Clinical Laboratory Information Systems↗

Improvements to the GDB Human Genome Data Base.

Version 6.0 of the Human Genome Data Base introduces a number of significant improvements over previous releases of GDB. The most important of these are revised data representations for genes and genomic maps and a new curatorial model for the database. GDB 6.0 is the first major genomic database to provide read/write access directly to the scientific community, including capabilities for third-party annotation. The revised database can represent all major categories of genetic and physical maps, along with the underlying order and distance information used to construct them. The improved representation permits more sophisticated map queries to be posed and supports the graphical display of maps. In addition the new GDB has a richer model for gene information, better suited for supporting cross-references to databases describing gene function, structure, products, expression and associated phenotypes.

Animals↗

Therapies for depression in Parkinson's disease.

BACKGROUND: Depression is one of the most common neuropsychiatric disturbances in Parkinson's disease. 40% of observed variation in quality of life is due to depression. However, there is little hard evidence of the efficacy and safety of antidepressant therapies in Parkinson's disease. OBJECTIVES: To assess the efficacy and safety of antidepressant therapies in idiopathic Parkinson's disease. Safety refers to both the direct side-effects of the therapy and also the therapy's interactions with the symptoms of Parkinson's disease and with the antiparkinsonian medications. SEARCH STRATEGY: Relevant clinical trials were identified by electronic searches the Cochrane Controlled Trials Register (the Cochrane Library Issue 3, 2001), MEDLINE(1996-2001), EMBASE (1974-2001), PsychLit (1800's-2001), CINAHL (1982-2001) databases. The reference list of all trial reports and reviews were examined. Queries were sent out to all manufacturers and distributors of antidepressants within the UK requesting information on any relevant clinical trials. SELECTION CRITERIA: Randomised controlled trials (RCT) examining licensed oral antidepressants, electroconvulsive therapy (ECT) or behavioural therapy in the treatment of depression in idiopathic Parkinson's disease. DATA COLLECTION AND ANALYSIS: Data was extracted and assessed independently by three of the authors. Disagreements were resolved by discussion. MAIN RESULTS: Three randomised controlled trials were found examining oral antidepressant medications in Parkinson's disease in a total of 106 patients. No eligible trials of ECT or behavioural therapy were found. In the first arm of the crossover trial by Andersen 1980 (n=22) patients in the nortriptyline group showed a larger improvement than placebo group in median depression score in a self-made 31-item depression rating scale after 16 weeks of treatment but statistical significance was not calculated. A parallel group trial by Wermuth 1998 (n=37) did not show any statistically significant difference between the citalopram and placebo groups in the Hamilton Depression Scale after 52 weeks of treatment. The third study by Rabey 1996 (n=47) was a randomised open-label trial to compare fluvoxamine versus amitriptyline. Similar numbers of patients in amitriptyline and fluvoxamine groups (60% vs 55%) had a 50% reduction of Hamilton score after 16 months of treatment. However, further assessment of this trial was not possible because only summary results were available from an abstract and attempts to contact the authors failed. Visual hallucinations or confusion had been reported in patients with fluvoxamine and amitriptyline. Otherwise, no other major side effects were found in the other two trials. REVIEWER'S CONCLUSIONS: Insufficient data on the effectiveness and safety of any antidepressants therapies in Parkinson's disease are available on which to make recommendations for their use. Further large scale randomised controlled trials are urgently required in this area.

Antidepressive Agents↗

A skeletal gene database.

Systematic organization of documented data coupled with ready accessibility is of great value to research. Catalogs and databases are created specifically to meet this purpose. The Skeletal Gene Database evolves as part of the Skeletal Genome Anatomy Project (SGAP), an ongoing multi-institute collaborative effort, to study the functional genome of bone and other skeletal tissues. The primary objective of the Skeletal Gene Database is to create a contemporary list of skeletal-related genes, offering the following information for each gene: gene name, protein name, cellular function, disease(s) caused by mutation of the corresponding gene, chromosomal location, LocusLink number, gene size, exon/intron numbers, messenger RNA (mRNA) coding region size, protein size/molecular weight, Online Mendelian Inheritance in Man (OMIM) number of the gene, UniGene assignment, and PubMed reference. The database includes genes already known and published in the literature as well as novel genes not yet characterized but known to be expressed in skeletal tissue. It will be posted on the web for easy access and swift referencing. The data will be updated in tempo with current and future research, thereby providing an invaluable service to the scientific community interested in obtaining information on bone-related genes.

Bone and Bones↗

Computer-aided craniofacial surgical planning implemented in CAD software.

Accurate presurgical planning is imperative for successful cranial surgery. This article introduces a simulation program developed in a computer-aided design environment. The neurocranium is introduced as a mathematical surface, since this is the part on which the actual operation will be performed. The viscerocranium, which serves as reference, is visualized using small triangular surfaces. The development of the program commenced with a classification of the different surgical techniques mentioned in the literature into six basic actions. The use of mathematically described surfaces has the advantage that the program can simulate actions which change the shape of a surface and perform an on-line estimation of the fracture risk during bending. Three-point bending tests were carried out to provide the necessary data to perform the mathematical check, as these data are not available in the literature. A database with reference distances was introduced to guide the surgeon to obtain the best possible results. During one clinical trial, the computer was taken into the operating room so that the surgical plan developed with the simulation program could be applied to the actual operation.

Brain↗

Increasing prevalence of HIV-1 protease inhibitor-associated mutations correlates with long-term non-suppressive protease inhibitor treatment.

Treatment of human immunodeficiency virus type 1 with protease inhibitors (PIs) is associated with the emergence of resistance-associated mutations. Treatment-characterized datasets have been used to identify novel treatment-associated protease mutations. In this study, we utilized two large reference laboratory databases (>115,000 viral sequences) to identify non-established resistance-associated protease mutations. We found 20 non-established protease mutations occurring in 82% of viruses with a PI resistance score of 4-7, 62% of viruses with a resistance score of 1-3, and 35% of viruses with no predicted PI resistance. We correlated mutational prevalence to treatment duration in a treatment-characterized dataset of 2161 patients undergoing non-suppressive PI therapy. In the non-suppressed dataset, 24 mutations became more prevalent and three mutations became less prevalent after more than 48 months of non-suppressive PI-therapy. Longer durations of non-suppressive treatment correlated with higher PI resistance scores. Mutations at eight non-established positions that were more common in viruses with the longest duration of non-suppressive therapy were also more common in viruses with the highest PI resistance score. Covariation analysis of 3036 protease amino acid substitutions identified 75 positive and nine negative correlations between resistance associated positions. Our findings support the utility of reference laboratory datasets for surveillance of mutation prevalence and covariation.

Amino Acid Sequence↗

GlycoSuiteDB: a curated relational database of glycoprotein glycan structures and their biological sources. 2003 update.

GlycoSuiteDB is an annotated and curated relational database of glycan structures reported in the literature. It contains information on the glycan type, core type, linkages and anomeric configurations, mass, composition and the analytical methods used by the researchers to determine the glycan structure. Native and recombinant sources are detailed, including species, tissue and/or cell type, cell line, strain, life stage, disease, and if known the protein to which the glycan structures are attached. There are links to SWISS-PROT/TrEMBL and PubMed where applicable. Recent developments include the implementation of searching by 2D structure and substructure, disease and reference. The database is updated twice a year, and now contains over 7650 entries. Access to GlycoSuiteDB is available at http://www.glycosuite.com.

Animals↗

Specificity of ICD-9-CM coding practices for stroke rehabilitation.

Designed for acute care classification, the 9th version of the International Classification of Disease, Clinical Modification (ICD-9-CM) is also used to describe the principal diagnosis in medical rehabilitation. ICD-9-CM (ICD-9) coding practices for all stroke cases found in two nationally representative databases were examined (sample sizes over 17,000 and over 2,000). Of the more than 100 codes selected, four were indicated for 67% and 72% of stroke cases in the two data sets, respectively. Codes 436 and 438 distinguish acute from late stroke effects; whereas code 434.9 identifies stroke, but not its duration. The most frequently used code in the larger database, 342.9, refers to the manifestation of hemiplegia rather than to diagnosis, and thus is not specific to stroke. Other less frequently selected ICD-9 codes are more specific to the underlying pathophysiology (e.g., thrombosis, embolus or hemorrhage). Results emphasize the need for more precise selection of etiologic ICD-9 codes for stroke rehabilitation so that they describe specific pathology.

Cerebrovascular Disorders↗

YPL.db2: the Yeast Protein Localization database, version 2.0.

The Yeast Protein Localization database (YPL.db(2)) is an archive of microscopic image data of protein localization patterns in the yeast Saccharomyces cerevisiae. The current version of YPL.db(2) harbours 500 sets of image data derived from high-resolution microscopic analyses of proteins tagged with the green fluorescent protein (GFP). Major functional improvements in YPL.db(2) over a previous release are a web-based experiment and image submission interface, facilitating standardized data entry by remote users through the Internet. The image display page provides image gallery and image scrolling features. In addition, fluorescence and transmission images can be superimposed, allowing image fading for precise correlation of the protein's localization in the cellular context. The reference structure database displaying 'prototypic' localization patterns was extended, and a feature to display and manipulate 3D-image datasets, using a freely available VRML plug-in, was included. Access to the Yeast Protein Localization database version 2.0 (YPL.db(2)) is available through http://YPL.uni-graz.at.

Databases, Protein↗