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[Impact of caregiving on women's health and quality of life].

BACKGROUND: Informal care currently lies at the heart of the debate on welfare policies since demands for such care are increasing and the future availability of informal caregivers is uncertain. OBJECTIVE: To analyze the distribution of the burden of informal care between men and women and its consequences on health and quality of life. METHODS: Data from Spain and other neighboring countries obtained from several bibliographic databases, publications, and official reports were gathered. In addition, the results of a home survey conducted by the authors on 1.000 male and female informal caregivers in Andalusia (Spain) were used. RESULTS: The studies reviewed demonstrate that women are the main providers of informal care in Spain. Most informal carers are women with a low educational level, without employment and from a low social class. The negative impact of caregiving was noted by a large proportion of carers, especially financial consequences and loss of employment and time. Informal caregiving also has a considerable impact on health, especially on psychological health, and is associated with high levels of burden. CONCLUSIONS: The present study demonstrates the need to reorganize health and social policies and to provide sufficient resources to meet the increasing need for informal care and to mitigate the impact and costs of caregiving on diverse aspects of women's lives.

Caregivers↗

The use of standardized incidence and prevalence rates in epidemiological studies on multiple sclerosis. A meta-analysis study.

OBJECTIVE: To demonstrate whether or not the age and sex adjustment of incidence and prevalence rates in multiple sclerosis (MS) could allow more reliable comparison between epidemiological studies performed in different areas of the world and to establish if the latitude gradient theory could be confirmed after the standardization for age and sex distribution. METHODS: A meta-analysis of population-based incidence and prevalence studies on MS from 1980 through 1998 using the terms 'multiple sclerosis', 'prevalence' and 'incidence' in the bibliographic databases MEDLINE and EMBASE was performed. We included studies that reported the diagnostic criteria, number of cases and the population studied, the date of the study, the latitude, and the age- and sex-specific crude incidence and prevalence rates. According to the inclusion criteria, 69 of 127 papers on prevalence and 22 of 70 papers on incidence were considered for age adjustment and 27 prevalence and 8 incidence studies for sex adjustment. The mean incidence and prevalencerates and the 95% confidence intervals age- and sex-adjusted to the World and the European standard populations were calculated. RESULTS: The Spearman rank correlation and the multiple regression analyses indicated that age adjustment to standard populations could overcome the limitations in comparing the crude prevalence and incidence rates of different epidemiological studies on MS. When the mean crude and age- and sex-adjusted prevalence and age-adjusted incidence rates were stratified by latitude (from south to north), the latitudinal gradient, which was highly significant for the crude rates, became less remarkable for the age- and sex-adjusted prevalence rates and not significant for the age-adjusted incidence rates. CONCLUSIONS: The crude incidence and prevalence rates in epidemiological studies on MS should be age- and sex-adjusted to a common standard population to permit a more reliable comparison among studies performed in different countries. Our findings support the opinion that the latitude does not play a key role in determining the onset of MS. Whenever possible, the crude incidence and prevalence rates should be adjusted to the ethnic origin and migration characteristics.

Adolescent↗

Potential confounding by intermediate phenotypes in studies of the genetics of ischaemic stroke.

BACKGROUND: Family history (FHx) of stroke is perceived to be an important risk factor for ischaemic stroke. However, there are several intermediate phenotypes that are often involved in the aetiology of ischaemic stroke and that have a substantial genetic component themselves. We studied FHx of ischaemic heart disease (IHD), hypertension (HTN) and diabetes mellitus (DM) as risk factors for ischaemic stroke. METHODS: We performed a systematic review of case-control and cohort studies reporting on FHx(IHD), FHx(HTN) or FHx(DM) as risk factors for stroke using bibliographic databases, and by hand searching reference lists and journals. Odds ratios of FHx as a risk factor for stroke were calculated within individual studies. We included unpublished data from two Oxfordshire population-based studies to assess effects on subtypes of ischaemic stroke. RESULTS: We identified 54 studies that investigated the odds of stroke conferred by a positive FHx, 24 of which reported data on FHx of one or more intermediate phenotypes in addition to FHx of stroke. Most studies reported an increased frequency of FHx(IHD) and FHx(HTN) in stroke patients versus controls. The association was significant in 6 out of 14 studies for FHx(IHD) and 4 out of 11 studies for FHx(HTN). In contrast, FHx(DM) was not associated with stroke. FHx(IHD) was particularly associated with large vessel strokes (OR 1.72, CI 1.3-2.2, p = 0.00004). CONCLUSIONS: FHx(IHD) and FHx(HTN) are both risk factors for stroke. It is likely that the apparent heritability of stroke is partly accounted for by heritability of HTN and large vessel atherosclerosis. Analyses of heritability of stroke and candidate gene studies should be adjusted accordingly.

Brain Ischemia↗

Cardiac effects of growth hormone in adults with growth hormone deficiency: a meta-analysis.

BACKGROUND: Growth hormone (GH) treatment may improve morphological and functional cardiac parameters in adults with GH deficiency (GHD). However, clinical trials reported to date involved few patients and yielded variable effects. METHODS AND RESULTS: We systematically reviewed blinded, placebo-controlled, randomized clinical trials of GH treatment in adults with GHD and open studies in patients with GHD before and after GH treatment, evaluating the effects of GH on cardiac parameters assessed by echocardiography. Sixteen trials (9 blinded and 7 open), involving a total of 468 patients, were identified in 3 bibliographic databases. GH dosage, duration of treatment, and study populations varied among the studies. We conducted a combined analysis of effects on left ventricular mass (LVM), interventricular septum thickness (IVS), left ventricular posterior wall (LVPW), left ventricular end-systolic (LVESD) and diastolic (LVEDD) diameters, stroke volume, E/A ratio, isovolumic relaxation time (IRT), and fractional shortening. Overall effect size was used to evaluate significance, and weighted mean difference between GH and control was given to appreciate size of the effect. GH treatment was associated with a significant increase in LVM: +10.8 (SD: 9.3) g (P=0.02); IVS: +0.28 (0.38) mm (P<0.001), LVPW: 0.98 (0.22) mm (P=0.05), LVEDD: +1.34 (1.13) mm (P<0.001), and stroke volume: +10.3 (8.7) mL (P<0.001). A trend toward a difference in fractional shortening was observed: +1.1 (1.1)% (P=0.06). Overall effect sizes were not significant for LVESD, E/A, and IRT. CONCLUSIONS: GH treatment is associated with a significant positive effect on LVM, IVS, LVPW, LVEDD, and stroke volume, as assessed by echocardiography, in adults with GHD.

Adult↗

Oral citicoline in acute ischemic stroke: an individual patient data pooling analysis of clinical trials.

BACKGROUND AND PURPOSE: No single neuroprotective agent has been shown to influence outcome after acute stroke. Citicoline has been studied worldwide in many clinical trials with positive findings, but only 1 trial has obtained significant results in the primary efficacy variables. Our objective was to evaluate the effects of oral citicoline in patients with acute ischemic stroke by a data pooling analysis of clinical trials. The primary efficacy end point chosen was the common evaluation of recovery, combining National Institutes of Health Stroke Scale </=1, modified Rankin Scale score </=1, and Barthel Index >/=95 at 3 months using the generalized estimating equations analysis. METHODS: A systematic search of all prospective, randomized, placebo-controlled, double-blind clinical trials with oral citicoline (MEDLINE, Cochrane, and Ferrer Group bibliographic databases) was undertaken. Individual patient data were extracted from each study and pooled in a single data file. The main inclusion criteria included compatible neuroimaging with ischemic stroke, National Institutes of Health Stroke Scale >/=8, and prior modified Rankin Scale score </=1. Four clinical trials using various doses of oral citicoline (500, 1000, and 2000 mg) were identified. RESULTS: Of 1652 randomized patients, 1372 fulfilled the inclusion criteria (583 received placebo, 789 received citicoline). Recovery at 3 months was 25.2% in citicoline-treated patients and 20.2% in placebo-treated patients (odds ratio [OR], 1.33; 95% CI, 1.10 to 1.62; P=0.0034). The dose showing the largest difference with placebo was 2000 mg, with 27.9% of patients achieving recovery (OR, 1.38; 95% CI, 1.10 to 1.72; P=0.0043). The overall safety of citicoline was similar to placebo. CONCLUSIONS: Treatment with oral citicoline within the first 24 hours after onset in patients with moderate to severe stroke increases the probability of complete recovery at 3 months.

Acute Disease↗

Systematic review of methods and results of studies of the genetic epidemiology of ischemic stroke.

BACKGROUND AND PURPOSE: To design appropriate molecular genetic studies, we first need to understand the genetic epidemiology of stroke. We therefore performed a systematic review of the literature to assess the heritability of stroke according to methodological quality of studies and to determine any heterogeneity in findings between studies and possible publication bias. METHODS: We searched for twin studies and studies of family history of stroke using bibliographic databases and by hand-searching reference lists and journals. Odds ratios (ORs) for family history as a risk factor for stroke were calculated within studies and combined by meta-analysis. Heterogeneity between studies, methodological quality of studies, and the influence of the age at which stroke occurred in both probands and relatives were assessed. RESULTS: We identified 53 independent studies (3 twin, 33 case-control, and 17 cohort). Monozygotic twins were more likely to be concordant than dizygotic twins (OR, 1.65; 95% CI, 1.2 to 2.3; P=0.003). A positive family history was a risk factor for stroke in both case-control (OR, 1.76; 95% CI, 1.7 to 1.9; P<0.00001) and cohort (OR, 1.30; 95% CI, 1.2 to 1.5; P<0.00001) studies. However, there was major heterogeneity between studies (cohort P=0.0001; case-control P<0.00001), with much stronger associations in small studies and methodologically less rigorous studies. Moreover, studies that reported insufficient data to allow meta-analysis tended to have found weaker associations. Family history of stroke was more frequent in studies that were confined to probands or relatives aged <70 years. However, few studies considered the number of affected and unaffected relatives, only 2 studies considered stroke phenotypes in detail, and only 19 studies (38%) adjusted associations for intermediate phenotypes. No twin study, only 5 cohort studies (26%), and 20 case-control studies (61%) differentiated between ischemic and hemorrhagic stroke in the proband. Family history of stroke was more frequent in large- and small-vessel stroke than in cardioembolic stroke. There were very few data on the influence of family history on stroke severity and no data on stroke recovery. CONCLUSIONS: Twin studies suggest a small genetic contribution to stroke, but reliable interpretation of published family history studies is undermined by major heterogeneity, insufficient detail, and potential publication and reporting bias. More detailed large-scale genetic epidemiology is required.

Bias↗

Sample size calculations in acute stroke trials: a systematic review of their reporting, characteristics, and relationship with outcome.

BACKGROUND AND PURPOSE: Only a few randomized controlled trials in acute stroke have shown a treatment-related benefit. Inadequate trial design, especially low sample size, may partly explain this failure. We investigated sample size calculations (SSCs) in a systematic review of acute stroke trials. METHODS: Full reports of nonconfounded randomized controlled trials that recruited patients within 1 week of stroke onset and were published before the end of 2001 were identified from the Cochrane Library and other bibliographic databases. Information on the SSC and outcome event rates was collected for each trial. RESULTS: Of 189 identified trial reports, 57 (30%) reported > or =1 components of the SSC, phase II 14/129 (11%) versus phase III 43/60 (72%) (P<0.001), with 32 (56%) giving all the required parameters. Significance (alpha) was mentioned in 54 (96%) reports; 53 used a significance level of alpha=0.05. And 55 (98%) reports gave the power (1-beta) of the study (median [25th and 75th percentile] 0.80 [0.80, 0.90]). The anticipated percentage of control subjects having a primary outcome event was given in 24 (42%) articles: case fatality 21.8% (11.8%, 23.5%, n=4) and combined death or disability/dependency 55.5% (44.5%, 66.3%, n=20); 25 studies used other outcomes and 8 studies gave insufficient information. Four of the 22 trials achieved a control rate within 5% of their prediction. 49 (86%) reports gave the anticipated treatment effect; case fatality: anticipated 9.5% (1.1%, 12.5%, n=6), achieved -0.3% (-4.1%, +2.4%); combined death or disability/dependency: anticipated 13.0% (10.0%, 16.0%, n=25), achieved 1.8% (-0.5%, +5.4%). The median calculated sample size was 600 (198, 995, n=54). CONCLUSIONS: Too few trial publications report the assumptions underlying their SSC. Most trials were underpowered, ie, power <0.90, used inappropriate assumptions for event rates, and were grossly overoptimistic in their expectation of treatment effect. These deficiencies will together have resulted in trials being far too small and reduced their chance of being able to detect real treatment effects.

Algorithms↗

Prognostic value of troponin T and I among asymptomatic patients with end-stage renal disease: a meta-analysis.

BACKGROUND: The prognostic usefulness of troponin enzymes in end-stage renal disease (ESRD) patients is controversial. To resolve this uncertainty of troponin as a prognostic tool, we conducted a systematic review to quantify the association between elevated troponin I or T and long-term total mortality among ESRD patients not suspected of having acute coronary syndrome. METHODS AND RESULTS: We conducted an unrestricted search from the MEDLINE, EMBASE, and DARE bibliographic databases to December 2004 using the terms troponin.mp. or exp troponin and exp kidney, exp renal, exp kidney disease exp renal replacement therapy. We also manually searched review articles and bibliographies to supplement the search. Studies were included if they were prospective observational studies, used cardiac-specific troponin assays, and evaluated long-term risk of death or cardiac events for asymptomatic ESRD patients. Two authors independently abstracted data on study and patient characteristics. Studies findings were stratified according to troponin T or I levels. We used a random-effects model to pool study results and tested for heterogeneity using chi2 testing and used funnel-plot inspection to evaluate the presence of publication bias. Data from 28 studies (3931 patients) published between 1999 and December 2004 were included in this review. Patients received dialysis for a median duration of 4 years, with a mean follow-up of 23 months. From the pooled analysis, elevated troponin T (>0.1 ng/mL) was significantly associated with increased all-cause mortality (relative risk, 2.64; 95% CI, 2.17 to 3.20). Although the prognostic effect sizes were all consistent with a positive relationship between troponin T and mortality, there was significant heterogeneity in the magnitude of these effect sizes (P=0.015). The funnel plot showed evidence of publication bias. Elevated troponin T was also strongly associated with increased cardiac death. Studies evaluating troponin I included a wide variety of assays and differing cut points, rendering synthesis of the study findings difficult. CONCLUSIONS: Elevated troponin T (>0.1 ng/mL) identifies a subgroup of ESRD patients who have poor survival and a high risk of cardiac death despite being asymptomatic. These findings suggest that troponin T is a promising risk stratification tool and may help frame therapeutic decisions. The clinical interpretation of elevated troponin I levels, however, remain unclear, largely because of the lack of standardization of assays.

Biomarkers↗

Selection of outcome assessment instruments for inpatients with severe and persistent mental illness.

The purpose of this article is to describe a procedure to assist in selecting outcome measures for inpatients treated at a state psychiatric hospital. The procedure combines evidence-based criteria from the literature, instruments shown to be sensitive to change in clinical trials, and the perspectives of a multidisciplinary team of researchers, administrators, providers, and patient advocates. Recent efficacy and effectiveness studies were used to identify recurrently used outcome instruments. A computerized search of more than 30 bibliographic databases, such as PsycINFO, MEDLINE, Social SciSearch, and ERIC, was conducted for articles published between 1990 and 2002. Comparisons of the most frequently used instruments were made on seven criteria proposed as best-practice indicators, including sensitivity to change and robust psychometrics. The sample produced 110 measures. Rater-completed instruments were represented more often than patient-completed ones. However, considerable variability across both methods was found on the criteria. The limited resources associated with publicly funded inpatient facilities led to a recommendation to select at least one rater-completed and one patient-completed instrument.

Brief Psychiatric Rating Scale↗

Risk of cardiovascular events and celecoxib: a systematic review and meta-analysis.

OBJECTIVES: To examine whether the increased risk of cardiovascular events with rofecoxib represents a class effect of cyclooxygenase-2 (COX-2) specific inhibitors. DESIGN: Systematic review and meta-analysis of randomized double-blind clinical trials of celecoxib of at least 6 weeks' duration and presented data on serious cardiovascular thromboembolic events. Data sources included six bibliographic databases, the relevant files of the United States Food and Drug Administration, and pharmaceutical company websites. MAIN OUTCOME MEASURES: Pooled fixed effects estimates of the odds ratios for risk of cardiovascular events with celecoxib compared with comparator treatment were calculated using the inverse variance weight method. The main outcome measure was myocardial infarction. RESULTS: Four placebo-controlled trials with 4422 patients were included in the primary meta-analysis comparing celecoxib with placebo. The odds ratio of myocardial infarction with celecoxib compared to placebo was 2.26 (95%confidence interval 1.0 to 5.1). For composite cardiovascular events [odd ratio 1.38 (95% CI 0.91 to 2.10)], cardiovascular deaths [OR 1.06 (95% CI 0.38 to 2.95)] and stroke [OR 1.0(95% CI 0.51 to 1.84)] there was no significant increase in risk with celecoxib. The secondary meta-analysis which included a total of six studies (with placebo, diclofenac, ibuprofen, and paracetamol as comparators) of 12 780 patients, showed similar findings with a significant increased risk with celecoxib for myocardial infarction [OR 1.88 (95% CI 1.15 to 3.08)] but not other outcome measures. CONCLUSION: The available data indicate an increased risk of myocardial infarction with celecoxib therapy, consistent with a class effect for COX-2 specific inhibitors.

Cardiovascular Diseases↗

Where do UK health services researchers publish their findings?

Health services research has emerged as the third vital requirement for understanding and improving health care, alongside basic science and clinical research. This has coincided with more stringent management of research, in particular by funding bodies. The latter are seeking to use bibliographic databases to aid the monitoring of the output of their investments. The principal source of data in the UK is the Research Outputs Database (ROD) set up by the Wellcome Trust primarily to monitor basic and clinical research. Health services researchers' output is difficult to monitor in view of the large number and wide variety of journals in which they publish. In addition, nearly half the journals (representing 35% of the articles) are not currently covered by the ROD. Funding bodies will underestimate the quantity of health services researchers' output unless they take these findings into account.

Clinical Medicine↗

Optimizing the benefits and minimizing the risks of enteral nutrition in the critically ill: role of small bowel feeding.

BACKGROUND: Strategies that maximize the delivery of enteral nutrition while minimizing the associated risks have the potential to improve the outcomes of critically ill patients. By delivering enteral feeds in the small bowel, beyond the pylorus, the frequency of regurgitation and the risk of aspiration is thought to be decreased while at the same time, nutrient delivery is maximized. The purpose of this paper is to systematically review those studies that compare gastric with small bowel feeding. METHODS: We searched computerized bibliographic databases, personal files, and relevant reference lists to identify eligible studies. Only randomized, clinical trials of critically ill patients that compared small bowel and gastric feedings were included in this review. In an independent fashion, relevant data on the methodology and outcomes of primary studies were abstracted in duplicate. RESULTS: There were 10 studies that met the inclusion criteria for this review. In 1 study, small bowel feeding was associated with a reduction in gastroesophageal regurgitation and a trend toward reduced pulmonary aspiration. Several studies document that small bowel feeding was associated with an increase in protein and calories delivered and a shorter time to target dose of nutrition. Compared with gastric feeding, when the results of 7 randomized trials were aggregated statistically, small bowel feeding was associated with a reduction in pneumonia (relative risk, 0.76; 95% confidence intervals, 0.59, 0.99). There was no difference in mortality rates between the 2 groups. CONCLUSIONS: Small bowel feeding may be associated with a reduction in gastroesophageal regurgitation, an increase in nutrient delivery, a shorter time to achieve desired target nutrition, and a lower rate of ventilator-associated pneumonia.

Critical Illness↗

The challenges of searching for and retrieving qualitative studies.

The authors' purpose in this article is to report the results of their search and retrieval efforts to date in an ongoing study to develop the procedural, analytic, and interpretive techniques to conduct qualitative meta-synthesis projects, using studies on women with HIV infection as the method case. For researchers conducting qualitative meta-synthesis projects, the ideal goal is to retrieve all of the relevant studies in a field--not simply a sample of them. Bates's model of berrypicking is used as the framework to describe the techniques used to conduct these searches. The authors discuss, in particular, the challenges of working with bibliographic databases, including choosing which databases to search, learning about the idiosyncrasies of working with each database, developing a list of search terms, and refining inclusion criteria regarding which studies to include in the meta-synthesis. Recommendations are given for searchers and writers of qualitative research.

Databases, Factual↗

Management of otitis media with effusion in young children.

OBJECTIVE: To summarize and critique the Agency for Health Care Policy and Research (AHCPR) Clinical Practice Guideline for the management of otitis media with effusion (OME) in children. DATA SOURCES: The AHCPR Clinical Practice Guideline, Otitis Media with Effusion in Young Children; the Quick Reference Guide for Clinicians, Managing Otitis Media with Effusion in Young Children; and the Parent Guide, Middle Ear Fluid in Young Children, were the primary data sources. The AHCPR developed the Guideline based on a comprehensive literature review from multiple bibliographic databases, including the National Library of Medicine. Data were also collected during open hearings and from unpublished sources derived from a call in the Federal Register. Additional citations from the biomedical literature were used for supporting evidence. STUDY SELECTION: Peer-reviewed reports of controlled, randomized studies were preferred, but other study designs were considered. Over 3000 abstracts were identified, of which 378 articles were used for data extraction, and an additional 100 articles were included from bibliography review and panel recommendations. An expert panel reviewed the data and incorporated clinical expertise into the development of consensus statements. DATA EXTRACTION: Data were extracted to apply to a base case with OME to narrow the scope of the Guideline. The base case was defined as a child who is 1-3 years old, is otherwise healthy, and has no underlying craniofacial, neurologic, or sensory conditions. Multiple meta-analyses were done to help the panel come to conclusions on several issues. DATA SYNTHESIS: The Guideline documents carefully outlined treatment algorithms for the management of OME in otherwise healthy children. The main areas that need to be further clarified are the role of more aggressive identification of causative pathogens, when antimicrobial therapy should be initiated, and which antimicrobial agents are preferred for the treatment of OME. There are many vague areas in the Guideline that allow for multiple interpretations. Data regarding the use of corticosteroids were influenced heavily by the expert opinion of the panel rather than the literature-based evidence and potential cost implications. The Guideline provided specific recommendations for the surgical management of OME. Confounding patient factors that would affect decisions on management of OME, such as underlying disease states and physical or mental abnormalities, were not addressed in the Guideline. CONCLUSIONS: The documents were well organized and provide detailed explanation of the recommendations. The Guideline provides specific criteria for the surgical management of OME, but is vague in its recommendations on the medical management of OME with antibiotics, corticosteroids, and the use of invasive tympanocentesis in the evaluation of OME in otherwise healthy children.

Anti-Bacterial Agents↗

Does gender bias exist in the use of specialist health care?

OBJECTIVES: To investigate the evidence for the existence of gender bias (defined as care provided independently of clinical need) in the use of specialist services by critically appraising the literature. METHODS: A computer-assisted search of the bibliographic databases PubMed, Medline, EMBASE, Healthstar and Social Science Citation Index for English language papers published from 1966 until May 1999. In addition, four journals were handsearched and the reference lists of identified papers were explored. Retrospective studies were only used when there were insufficient prospective studies. RESULTS: One hundred and thirty-eight studies were identified covering five major topics: coronary artery disease; renal transplantation; human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS); mental illness; and other (mainly invasive) procedures. The majority (94) examined coronary artery disease. It appears that men are more likely to undergo non-invasive investigations than women, but that subsequent investigation and treatment shows no clear evidence of gender differences. Men are more likely to undergo renal transplantation and, for those with HIV and AIDS, to receive azidothymidine (zidovudine, AZT) than women. There are some indications that disparities in favour of men also occur for those suffering from cardiac arrhythmias and cerebrovascular disease, and for those undergoing vascular surgery, hip replacement and heart transplantation. In contrast, women are more likely to undergo liver transplantation and cataract surgery. Mental health services may be provided differently for men and women. All these findings are limited by a lack of accurate denominator information and insufficient ability to adjust for prognostic factors. CONCLUSIONS: Differences in health care use can be due to demand factors (e.g. differences in the prevalence and severity of disease or in patient preferences), supply factors (particularly clinical judgement), or both. There is a need to examine these explanations thoroughly for gender inequalities in order to ensure that equity (lack of bias) is achieved. There is also a need for higher quality studies if differences are to be attributed conclusively to bias or not.

Female↗

The Molecular Pages of the mesotelencephalic dopamine consortium (DopaNet).

BACKGROUND: DopaNet http://www.dopanet.org is a Systems Biology initiative that aims to investigate precisely and quantitatively all the aspects of neurotransmission in a specific neuronal system, the mesotelencephalic dopamine system. The project should lead to large-scale models of molecular and cellular processes involved in neuronal signaling. A prerequisite is the proper storage of knowledge coming from the literature. METHODS: DopaNet Molecular Pages are highly structured descriptions of quantitative parameters related to a specific molecular complex involved in neuronal signal processing. A Molecular Page is built by maintainers who are experts in the field, and responsible for the quality of the page content. Each piece of data is identified by a specific ontology code, annotated (method of acquisition, species, etc.) and linked to the relevant bibliography. The Molecular Pages are stored as XML files, and processed through the DopaNet Web Service, which provides functionalities to edit the Molecular Pages, to cross-link the Pages and generate the public display, and to search them. CONCLUSIONS: DopaNet Molecular Pages are one of the core resources of the DopaNet project but should be of widespread utility in the field of Systems Neurobiology.

Animals↗

Using co-occurrence network structure to extract synonymous gene and protein names from MEDLINE abstracts.

BACKGROUND: Text-mining can assist biomedical researchers in reducing information overload by extracting useful knowledge from large collections of text. We developed a novel text-mining method based on analyzing the network structure created by symbol co-occurrences as a way to extend the capabilities of knowledge extraction. The method was applied to the task of automatic gene and protein name synonym extraction. RESULTS: Performance was measured on a test set consisting of about 50,000 abstracts from one year of MEDLINE. Synonyms retrieved from curated genomics databases were used as a gold standard. The system obtained a maximum F-score of 22.21% (23.18% precision and 21.36% recall), with high efficiency in the use of seed pairs. CONCLUSION: The method performs comparably with other studied methods, does not rely on sophisticated named-entity recognition, and requires little initial seed knowledge.

Algorithms↗

MILANO--custom annotation of microarray results using automatic literature searches.

BACKGROUND: High-throughput genomic research tools are becoming standard in the biologist's toolbox. After processing the genomic data with one of the many available statistical algorithms to identify statistically significant genes, these genes need to be further analyzed for biological significance in light of all the existing knowledge. Literature mining--the process of representing literature data in a fashion that is easy to relate to genomic data--is one solution to this problem. RESULTS: We present a web-based tool, MILANO (Microarray Literature-based Annotation), that allows annotation of lists of genes derived from microarray results by user defined terms. Our annotation strategy is based on counting the number of literature co-occurrences of each gene on the list with a user defined term. This strategy allows the customization of the annotation procedure and thus overcomes one of the major limitations of the functional annotations usually provided with microarray results. MILANO expands the gene names to include all their informative synonyms while filtering out gene symbols that are likely to be less informative as literature searching terms. MILANO supports searching two literature databases: GeneRIF and Medline (through PubMed), allowing retrieval of both quick and comprehensive results. We demonstrate MILANO's ability to improve microarray analysis by analyzing a list of 150 genes that were affected by p53 overproduction. This analysis reveals that MILANO enables immediate identification of known p53 target genes on this list and assists in sorting the list into genes known to be involved in p53 related pathways, apoptosis and cell cycle arrest. CONCLUSIONS: MILANO provides a useful tool for the automatic custom annotation of microarray results which is based on all the available literature. MILANO has two major advances over similar tools: the ability to expand gene names to include all their informative synonyms while removing synonyms that are not informative and access to the GeneRIF database which provides short summaries of curated articles relevant to known genes. MILANO is available at http://milano.md.huji.ac.il.

Algorithms↗