SNOMED CT coding variation and grouping for "other findings" in a longitudinal study on urea cycle disorders.

Semantic interoperability requires consistent use of controlled terminologies. However, non-terminology experts (although perhaps experts in a particular domain) are prone to produce variant coding. We examine this problem by investigating SNOMED CT coding variation for other findings reported on case report forms from a clinical research study on urea cycle disorders. The natural language findings from the forms were normalized, and the associated SNOMED CT concept descriptions were compared. The subset of normalized strings associated with two different concept descriptions were further compared to determine the relationship among the associated SNOMED CT concepts. We found 45% of the concept description pairs were associated with two hierarchically related concepts or with the same concept, while 55% were associated with two unrelated concepts. Clearer guidelines for use of SNOMED CT in particular contexts, or structured data entry tools tailored to the needs of non-expert coders, are needed to better manage coding variation.

A comparison of linear, fixed-form computer-based testing versus traditional paper-and-pencil-format testing in veterinary medical education.

Computerized testing has made significant inroads into veterinary education. Traditional paper-and-pencil examination formats are being replaced by computer-based testing (CBT). Computer-administered, fixed-form tests, because they mimic most closely the familiar fixed-response paper-and-pencil test formats, might intuitively seem to be inherently equivalent to their paper-and-pencil counterparts. However, research examining test-mode effects on student performance presents a very mixed picture. Additionally, students often report that they feel their performance is adversely affected by CBT and that their grades on the computer-based exams are lower than they would have been on the more familiar paper-and-pencil format. In order to address student perceptions of negative impact and the mixed nature of the published research results on the topic, a study was conducted to assess whether the transition from paper-and-pencil to equivalent linear CBT exams did, in fact, affect students' examination scores. This study found no evidence for significant test-mode effects on student scores as a result of the introduction of computer-based testing into the veterinary curriculum.

Evidence-based retrieval in evidence-based medicine.

OBJECTIVE: Clinical decisions based on a meta-analysis that is based on an ineffective retrieval strategy may have serious negative consequences for patients. The study objective was to investigate the extent to which meta-analyses report proof of their retrieval strategies' effectiveness. METHODS: The authors examined a random sample (n = 100) of articles in the 1996 to 2002 full-text subset of Ovid MEDLINE indexed as "meta-analysis." We classified the articles in three ways: the article (A) reported both a retrieval strategy in sufficient detail (such that it could be repeated) and with evidence of the strategy's effectiveness, (B) reported a retrieval strategy in sufficient detail but not with evidence of the strategy's effectiveness, or (C) neither reported a strategy in detail nor evidence of the strategy's effectiveness. Articles classified as (A) were further classified according to the level of evidence reported. RESULTS: Of the eighty-nine articles in our final analysis, six (6.7%) were classified as category (A), fifty-seven (64%) as (B), and twenty-six (29%) as (C). Articles in category (A) reported a previously validated search, a published strategy, or strategy based on expert opinion. CONCLUSION: Peer-review standards must be developed that require authors of meta-analyses to report evidence for the effectiveness of their retrieval strategies.

Evidence-based retrieval in E-health.

In this chapter we address the issue of standards for information retrieval to support decision making in e-health. Specifically, we consider the issue of evidence-based retrieval in the e-health domains of the consumer, healthcare practitioner, healthcare researcher, and genomics researcher. We present the results of a preliminary study to assess the current state of evidence-based retrieval in e-health. Within this study, we reviewed articles in e-health and telemedicine to determine the extent to which authors provide details of the information retrieval strategies used, as well as evidence of the effectiveness of those strategies. We also examined the extent to which the associated journals require authors of reviews to explicitly provide details of information retrieval strategies that they used, as well as reporting any evidence for the effectiveness of those strategies.

Expression profiling identifies dysregulation of myosin heavy chains IIb and IIx during limb immobilization in the soleus muscles of old rats.

Aged individuals suffer from multiple dysfunctions during skeletal muscle atrophy. The purpose of this study was to determine differential changes in gene expression in atrophied soleus muscle induced by hindlimb immobilization in young (3-4 months) and old (30-31 months) rats. The hypothesis was that differentially expressed mRNAs with age-atrophy interactions would reveal candidates that induce loss of function responses in aged animals. Each muscle was applied to an independent set of Affymetrix micoarrays, with 385 differentially expressed mRNAs with atrophy and 354 age-atrophy interactions detected by two-factor ANOVA (alpha of 0.05 with a Bonferroni adjustment). Functional trends were observed for 23 and 15 probe sets involved in electron transport and the extracellular matrix, respectively, decreasing more in the young than in the old. Other functional categories with atrophy in both ages included chaperones, glutathione-S-transferases, the tricarboxylic acid cycle, reductions in Z-line-associated proteins and increases in probe sets for protein degradation. Surprisingly, myosin heavy chain IIb and IIx mRNAs were suppressed in the atrophied soleus muscle of old rats as opposed to the large increases in the young animals (16- and 25-fold, respectively, with microarrays, and 61- and 68-fold, respectively, with real-time PCR). No significant changes were observed in myosin heavy chain IIb and IIx mRNA with micoarrays in the atrophied soleus muscles of old rats, but they were found to increase six- and fivefold, respectively, with real-time PCR. Therefore, deficiencies in pre-translational signals that normally upregulate myosin heavy chain IIb and IIx mRNAs during atrophy may exist in the soleus muscle of old animals.

Selected Contribution: Identification of differentially expressed genes between young and old rat soleus muscle during recovery from immobilization-induced atrophy.

After cessation of hindlimb immobilization, which resulted in a 27-37% loss in soleus mass, the atrophied soleus muscle of young but not old rats regrows to its mass before treatment. We hypothesized that during remobilization the mRNA levels of growth potentiating factor(s) would be present in the soleus muscle of young (3- to 4-mo-old) but absent in old (30- to 31-mo-old) Fischer 344 x Brown Norway rats or that mRNAs for growth inhibitory factor(s) would be absent in young but present in old. Gene expression levels of >24,000 transcripts were determined by using Affymetrix RGU34A-C high-density oligonucleotide microarrays in soleus muscles at 3, 6, 10, and 30 days of remobilization after cessation of a 10-day period of hindlimb immobilization. Each muscle sample was applied to an independent set of arrays. Recovery-related differences were determined by using a three-factor ANOVA with a false discovery rate-adjustment of P = 0.01, which yielded 64 significantly different probe sets. Elfin, amphiregulin, and clusterin mRNAs were selected for further confirmation by real-time PCR. Elfin mRNA levels were less in old than in young rats at 6, 10, and 30 days of remobilization. Amphiregulin expression exhibited a unique spike on the 10th day of successful regrowth in young rats but remained unchanged old. Clusterin mRNA was unchanged in young muscles but was elevated on the 3rd, 6th, and 10th days of recovery in old soleus muscles. The mRNAs identified as differentially expressed between young and old recovery may modulate muscle growth that could highlight new candidate mechanisms to explain the failure of old soleus muscle to recover lost muscle mass.

Transcriptional profiling identifies extensive downregulation of extracellular matrix gene expression in sarcopenic rat soleus muscle.

The direction of change in skeletal muscle mass differs between young and old individuals, growing in young animals and atrophying in old animals. The purpose of the experiment was to develop a statistically conservative list of genes whose expression differed significantly between young growing and old atrophying (sarcopenic) skeletal muscles, which may be contributing to physical frailty. Gene expression levels of >24,000 transcripts were determined in soleus muscle samples from young (3-4 mo) and old (30-31 mo) rats. Age-related differences were determined using a Student's t-test (alpha of 0.05) with a Bonferroni adjustment, which yielded 682 probe sets that differed significantly between young (n = 25) and old (n = 20) animals. Of 347 total decreases in aged/sarcopenic muscle relative to young muscles, 199 were functionally identified; the major theme being that 24% had a biological role in the extracellular matrix and cell adhesion. Three themes were observed from 213 of the 335 total increases in sarcopenic muscles whose functions were documented in databases: 1) 14% are involved in immune response; 2) 9% play a role in proteolysis, ubiquitin-dependent degradation, and proteasome components; and 3) 7% act in stress/antioxidant responses. A total of 270 differentially expressed genes and ESTs had unknown/unclear functions. By decreasing the sample sizes of young and old animals from 25 x 20 to 15 x 15, 10 x 10, and 5 x 5 observations, we observed 682, 331, 73, and 3 statistically different mRNAs, respectively. Use of large sample size and a Bonferroni multiple testing adjustment in combination yielded increased statistical power, while protecting against false positives. Finally, multiple mRNAs that differ between young growing and old, sarcopenic muscles were identified and may highlight new candidate mechanisms that regulate skeletal muscle mass during sarcopenia.

Gene indexing: characterization and analysis of NLM's GeneRIFs.

We present an initial analysis of the National Library of Medicine's (NLM) Gene Indexing initiative. Gene Indexing occurs at the time of indexing for all 4600 journals and over 500,000 articles added to PubMed/MEDLINE each year. Gene Indexing links articles about the basic biology of a gene or protein within eight model organisms to a specific record in the NLM's LocusLink database of gene products. The result is an entry called a Gene Reference Into Function (GeneRIF) within the LocusLink database. We analyzed the numbers of GeneRIFs produced in the first year of GeneRIF production. 27,645 GeneRIFs were produced, pertaining to 9126 loci over eight model organisms. 60% of these were associated with human genes and 27% with mouse genes. About 80% discuss genes with an established MeSH Heading or other MeSH term. We developed a prototype functional alerting system for researchers based on the GeneRIFs, and a strategy to find all of the literature related to genes. We conclude that the Gene Indexing initiative adds considerable value to the life sciences research community.

A prototype system for retrieval of gene functional information.

Microarrays allow researchers to gather data about the expression patterns of thousands of genes simultaneously. Statistical analysis can reveal which genes show statistically significant results. Making biological sense of those results requires the retrieval of functional information about the genes thus identified, typically a manual gene-by-gene retrieval of information from various on-line databases. For experiments generating thousands of genes of interest, retrieval of functional information can become a significant bottleneck. To address this issue, we are currently developing a prototype system to automate the process of retrieval of functional information from multiple on-line sources.