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A universal molecular method for identifying underground plant parts to species.

As part of a large project to determine rooting depth and resource uptake on the Edwards Plateau of central Texas, we developed a DNA-based technique that allows the below-ground parts of all plants to be identified to the level of genus and usually to species. Identification is achieved by comparing DNA sequences of the internal transcribed spacer (ITS) region of the 18S-26S nuclear ribosomal DNA repeat, derived from below-ground plant material, with a reference ITS region database for plants at a site. The method works throughout plants because the plant ITS region can be PCR amplified using a set of universal primers. Congeneric species can usually be identified because the ITS region evolves relatively rapidly. In our study, all roots were easily identified to the level of genus; most congeneric species were identified solely by ITS sequence differences but some required a combination of ITS sequence data and above-ground surveys of species at a site. In addition to showing the feasibility and efficacy of our technique, we compare it with another DNA-based technique used to identify below-ground plant parts. Finally, we also describe a DNA extraction and purification technique that reliably provides high-quality DNA of sufficient quantity from roots so that PCR can be readily accomplished. Our technique should allow the below-ground parts of plants in any system to be identified and thereby open new possibilities for the study of below-ground plant communities.

Base Sequence↗

Predictive factors for success of neo-adjuvant therapy in upper gastrointestinal cancer.

BACKGROUND: Predicting response to treatment has long been the Holy Grail of clinicians treating patients with upper gastrointestinal malignancy. The widespread use of neoadjuvant therapy for esophageal cancer has provided an added urgency to the issue and at the same time brought success a step closer because accurate response can be determined from analysis of the resected specimen. METHODS: A search was undertaken of the Medline database for text references to neoadjuvant therapy, esophagus, stomach and predicting response. The references of these publications were further scanned for appropriate references in the text and reference lists. RESULTS: Publications describing predictive markers to neoadjuvant therapy for esophageal cancer, which were most likely to be of clinical significance, were selected for inclusion in this report. CONCLUSIONS: The most reliable tissue markers of response based on analysis of pretreatment biopsy specimens include P53, Ki-67, EGFR and the most impressive serum marker for monitoring response are CYFRA 21-1 and CEA. The results, however, are inconsistent, and the markers of relatively low sensitivity and none reliably identifies individual patients who will respond.

Biomarkers↗

Does smoking status influence the prognosis of bladder cancer? A systematic review.

OBJECTIVE: To summarize, in a systematic review, the evidence for the effect of stopping smoking on recurrence, cancer-specific and all cause-mortality among smokers with newly diagnosed bladder cancer. MATERIALS AND METHODS: Two electronic databases and the reference lists of identified primary studies and reviews were searched. Studies were included if a hazard ratio and its confidence intervals could be extracted. A predefined set of study characteristics was extracted which defined whether studies were giving valid prognostic data on the effects of smoking in reasonably homogenous cohorts. The results of studies were synthesized qualitatively. RESULTS: Fifteen relevant studies were identified; former and current smokers were combined in many studies. Many studies produced information on prognosis that was confounded by the mixing of incident and prevalent cases. Only three studies examined the influence of smoking on prognosis in only incident cases, most of whom had superficial disease. Of these, only one was of high quality. These three studies and the other 12 showed suggestive evidence that continued smoking or a lifetime of smoking constitutes a moderate risk factor for recurrence and death, and that stopping smoking could favourably change this. However, the evidence base for this is weak because of the methodological shortcomings and because most studies' results were not statistically significant. A life-table model showed that if stopping smoking altered the prognosis, the size of the benefit would be clinically worthwhile. CONCLUSION: There is suggestive evidence that stopping smoking might favourably alter the course of bladder cancer, but this is insufficient for clinicians to inform patients that doing so will improve their prognosis, and for providing specialized services to assist in stopping smoking to patients with bladder cancer.

Adult↗

Global transcript analysis of rice leaf and seed using SAGE technology.

We have compiled two comprehensive gene expression profiles from mature leaf and immature seed tissue of rice (Oryza sativa ssp. japonica cultivar Nipponbare) using Serial Analysis of Gene Expression (SAGE) technology. Analysis revealed a total of 50 519 SAGE tags, corresponding to 15 131 unique transcripts. Of these, the large majority (approximately 70%) occur only once in both libraries. Unexpectedly, the most abundant transcript (approximately 3% of the total) in the leaf library was derived from a type 3 metallothionein gene. The overall frequency profiles of the abundant tag species from both tissues differ greatly and reveal seed tissue as exhibiting a non-typical pattern of gene expression characterized by an over abundance of a small number of transcripts coding for storage proteins. A high proportion ( approximately 80%) of the abundant tags (> or = 9) matched entries in our reference rice EST database, with many fewer matches for low abundant tags. Singleton transcripts that are common to both tissues were collated to generate a summary of low abundant transcripts that are expressed constitutively in rice tissues. Finally and most surprisingly, a significant number of tags were found to code for antisense transcripts, a finding that suggests a novel mechanism of gene regulation, and may have implications for the use of antisense constructs in transgenic technology.

Journal Article↗

Hierarchical cluster analysis as an approach for systematic grouping of diet constituents on basis of fatty acid, energy and cholesterol content: application on consumable lamb products.

The role of dietary fat in the etiology of chronic diseases is both a qualitative and a quantitative issue. The dietary fat intake is largely influenced by behavioral and social influences on food choice. Ongoing scientific research has led to dietary recommendations with main concerns being the percentage of saturated, essential fatty acids and cholesterol with respect to total energy intake. However, the compositional complexity of food choice constituting the diet is a critical concept complicating the interpretation of epidemiologic, clinical and laboratory evidence to define the role of dietary fat in the etiology of diseases. This study was conducted on the observation of the need to better systematically classify consumable food based on complex composition and lamb meat is randomly selected as a non-specific subset for application of hierarchical cluster analysis method to obtain the dendogram using average linkage. Data on fat composition of consumable lamb prepared by different methods was obtained from USDA Nutrient Database for Standart Reference. Using agglomerative hierarchical cluster analysis lamb meat was grouped into two main clusters among which one divided into two families of which each was subdivided into two subfamilies based on fatty acids, cholesterol and energy composition. Present work may be considered as a leading study to systematically classify larger food sets. As high fat foods are rich in flavor and overall palatability, the outcome of this study may lead to behaviorally more acceptable but healthier dietary replacements. Besides future use of the results obtained may reveal the effect of complex compositional dietary influences on health and disease and may have superiority to studies questioning individual dietary items. Furthermore, hieararchial cluster analysis may be used to cluster food including other compositional data in food items like amino acids, vitamins, carbohydrates, as well.

Animals↗

Cryotherapy after ACL reconstruction: a meta-analysis.

Cryotherapy is a common treatment modality after orthopedic surgery procedures. Single institutional randomized clinical trials have evaluated the efficacy of cryotherapy after arthroscopically-assisted anterior cruciate ligament (ACL) reconstruction. Most of these studies were, however, underpowered to detect clinically relevant outcomes differences. This meta-analysis assessed the combined scientific evidence of studies evaluating the effectiveness of cryotherapy after arthroscopically-assisted ACL reconstruction. Electronic databases and bibliographic references of relevant articles were used to identify all relevant randomized clinical trials comparing cryotherapy to a placebo group after ACL reconstruction. Outcomes under investigation were postoperative drainage, range of motion, and pain. Random-effects models were used to combine the findings of the randomized controlled trials. Seven randomized clinical trials were included in the meta-analysis. Postoperative drainage (P=.23) and range of motion (P=.25) were not significantly different between cryotherapy and control group. However, cryotherapy was associated with significantly lower postoperative pain (P=.02). This meta-analysis showed that cryotherapy has a statistically significant benefit in postoperative pain control, while no improvement in postoperative range of motion or drainage was found. As the cryotherapy apparatus is fairly inexpensive, easy to use, has a high level of patient satisfaction, and is rarely associated with adverse events, we believe that cryotherapy is justified in the postoperative management of knee surgery.

Anterior Cruciate Ligament↗

Andrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy.

Acute respiratory infections represent a significant cause of over-prescription of antibiotics and are one of the major reasons for absence from work. The leaves of Andrographis paniculata (Burm. f.) Wall ex Nees (Acanthaceae) are used as a medicinal herb in the treatment of infectious diseases. Systematic literature searches were conducted in six computerised databases and the reference lists of all papers located were checked for further relevant publications. Information was also requested from manufacturers, the spontaneous reporting schemes of the World Health Organisation and national drug safety bodies. No language restrictions were imposed. Seven double-blind, controlled trials (n = 896) met the inclusion criteria for evaluation of efficacy. All trials scored at least three, out of a maximum of five, for methodological quality on the Jadad scale. Collectively, the data suggest that A. paniculata is superior to placebo in alleviating the subjective symptoms of uncomplicated upper respiratory tract infection. There is also preliminary evidence of a preventative effect. Adverse events reported following administration of A. paniculata were generally mild and infrequent. There were few spontaneous reports of adverse events. A. paniculata may be a safe and efficacious treatment for the relief of symptoms of uncomplicated upper respiratory tract infection; more research is warranted.

Andrographis↗

Breast-feeding and the risk of bronchial asthma in childhood: a systematic review with meta-analysis of prospective studies.

BACKGROUND: The protective effect of breast-feeding on the development of childhood asthma remains a matter of controversy. We conducted a systematic review of prospective studies that evaluated the association between exclusive breast-feeding during the first 3 months after birth and asthma. STUDY DESIGN: We searched the 1966-1999 MEDLINE database and reviewed reference lists of relevant articles to identify 12 prospective studies that met pre-stated inclusion criteria. Methodological aspects of the studies, duration and exclusivity of breast-feeding, and outcomes were assessed. Effect estimates were abstracted by the investigators, using a standardized approach. RESULTS: The summary odds ratio (OR) for the protective effect of breast-feeding was 0.70 (95% CI 0.60 to 0.81). The effect estimate was greater in studies of children with a family history of atopy (OR = 0.52) than in studies of a combined population (OR = 0.73). CONCLUSIONS: Exclusive breast-feeding during the first months after birth is associated with lower asthma rates during childhood. The effect, caused by immunomodulatory qualities of breast milk, avoidance of allergens, or a combination of these and other factors, strengthens the advantage of breast-feeding, especially if a family history of atopy is present.

Asthma↗

Neurocognitive dysfunction after coronary artery bypass surgery: a systematic review.

OBJECTIVE: Substantial, albeit scattered, evidence suggests that coronary artery bypass grafting may impair cognitive function. As methods and definitions differ greatly across studies, the reported incidence of cognitive decline after coronary bypass surgery varies widely as well. The aim of the present study was to systematically review those studies on cognitive decline that are relatively comparable and meet with certain quality criteria. METHODS: Four electronic databases and the references of several abstract books and earlier reviews were used to identify relevant literature. Stringent criteria, based in part on the 1994 consensus meeting on assessment of neurobehavioral outcomes after cardiac surgery, were used to assess the studies that were found. In total, 256 different titles were found, of which 23 met with the formulated selection criteria. RESULTS: Twelve cohort studies and eleven intervention studies were evaluated. A pooled analysis of six highly comparable studies yielded a proportion of 22.5% (95% confidence interval, 18.7%-26.4%) of patients with a cognitive deficit (a decrease of at least 1 standard deviation in at least two of nine or ten tests) 2 months after the operation. CONCLUSIONS: Neurocognitive dysfunction is a frequently occurring complication of coronary artery bypass grafting. The etiologic contribution of cardiopulmonary bypass to this complication will remain unclear until a randomized trial that directly compares off-pump and on-pump bypass surgery is carried out.

Cardiopulmonary Bypass↗

Comparative economic analyses of minimally invasive direct coronary artery bypass surgery.

OBJECTIVE: This study was undertaken to assess the degree to which published cost comparisons of minimally invasive direct coronary artery bypass through a thoracotomy versus conventional coronary artery bypass grafting, off-pump bypass surgery through a sternotomy, or angioplasty with or without stenting adhered to existing guidelines for performing economic analyses. METHODS: We used minimally invasive direct coronary artery bypass (MIDCAB), off-pump bypass surgery, cost-effectiveness, economic analysis, and related keywords to search MEDLINE, other literature databases and article reference lists for English-language economic analyses of minimally invasive direct coronary artery bypass procedures versus other procedures that were published from 1990 to February 2002. We critically appraised article adherence to a 10-item methodologic checklist modified to address issues particularly relevant to minimally invasive direct coronary artery bypass evaluations. Assessment discordance was reconciled by consensus. RESULTS: Ten articles published from June 1997 to March 2001 compared costs and (generally) outcomes of minimally invasive direct coronary artery bypass with those of other procedures. All were nonrandomized comparisons, generally of concurrent intrainstitutional clinical series. Stated results generally favored minimally invasive direct coronary artery bypass, angioplasty, or off-pump bypass surgery through a sternotomy relative to conventional coronary artery bypass grafting. Studies adequately addressed an average of only 24% of applicable checklist items (range 0%-67%). Few studies adequately ensured the comparability of treatment groups, clearly performed intent-to-treat analyses, comprehensively and credibly measured costs that were considered, or clearly addressed costs and results of preprocedural angiography or postprocedural imaging. Only 1 study compared success of revascularization between minimally invasive direct coronary artery bypass and competing alternatives. No studies specified the cost-analysis perspective or included costs of physician or physician assistant care. CONCLUSIONS: Most published comparative economic analyses of minimally invasive direct coronary artery bypass have failed to adequately address issues crucial to such evaluations. Future studies should more closely follow well-described principles of clinical epidemiology and cost-effectiveness analysis.

Angioplasty, Balloon, Coronary↗

Visualization, reconstruction, and integration of neuronal structures in digital brain atlases.

Brain atlases are used in neuroanatomy to define the spatial layout of neuronal structures. Their digital variant can serve as a database and common reference frame for integrating data from different biological experiments. This article presents an overview of methods for three-dimensional visualization of neuroanatomical image data, reconstructing neuronal structures from image data, creating digital brain atlases, and registering data in an atlas. This enables analysis of spatial relations between individual structures imaged in different experiments as well as between these structures and the atlas.

Animals↗

Consolidation therapy for adult acute myeloid leukemia: a systematic analysis according to evidence based medicine.

Post-remission therapy in acute myeloid leukemia (AML) remains problematic. It has been demonstrated that younger patients can maintain longer complete remissions (CR) with aggressive post-remission therapies after induction treatment: allogeneic (allo), autologous (auto) stem cell transplantation (SCT), or intensive chemotherapy (ICC). The purpose of our study was to identify the most important randomized and controlled studies comparing these three therapeutic options, in order to draw conclusions and possible suggestions for post-remission therapy of AML, according to the evidence based medicine (EBM) rules. We performed an exhaustive analysis of the literature, searching either in electronic databases or among the references of the identified articles (hand searching). We searched the MEDLINE computer database for reports from 1985 through January 2005 and selected for analysis the clinical trials conducted over adults affected by newly diagnosed AML aged less than 65 years. The study design had to satisfy strict methodological criteria and must consider global mortality and/or disease free survival as primary outcomes. Overall we found 7750 papers; by using the limits "clinical trial" as publication type, "all adults 19+ years", we were able to select 344 papers. Among these, a further selection was made, based on two main clinical queries: 1) is auto-SCT superior to ICC/no other therapy in improving DFS and/or OS in adult AML patients in first CR? 2) is allo-SCT superior to auto-SCT/other therapeutic options in improving DFS and/or OS in adult AML patients in first CR? Concerning the first query, a possible advantage of auto-SCT over ICC was not clearly supported by data from clinical trials; there is no evidence that auto-SCT is superior in terms of OS to chemotherapy. Nevertheless, the reported TRM has been significantly reduced within the past years. Thus, the percentage of patients suitable for auto-SCT in CR has increased. Moreover, the scarce data concerning the comparison between auto-SCT and chemotherapy in different subsets of patients are unable to suggest a differentiated approach in patients with high-risk, standard-risk or low-risk AML. Data from the literature show that patients with unfavorable risk disease are more often addressed to allo-SCT and patients with low-risk disease receive more often intensive consolidation chemotherapy. Concerning the second query, interpretation of data from the main prospective studies about the role of allo-SCT in previously untreated AML is not easy. The first problem is the lack of real randomized clinical trials; in fact, according to the reported studies, AML patients generally receive allo-SCT on the basis of donor availability (the so called "genetic randomization"). The second problem is the frequent absence of intention to treat analysis. Despite methodological limitations, it was possible to compare allo-SCT with auto-SCT on a donor versus no-donor analysis and within risk groups. No overall benefit of allo-grafting on survival was demonstrated by any trial. In conclusion, the EBM approach highlighted the limitations observed in the published studies concerning consolidation therapy in AML; some suggestions, emerging from non-randomized, as well as randomized studies, are adequate, but not conclusive. This point, coupled with the intrinsic complexity to study AML biological heterogeneity, is probably a major obstacle to draw conclusive evidences for consolidation therapy in AML. These observations should plan to address new randomized studies on AML therapy; however, due to the emergence of genetic subgroups and new drugs targeting specific abnormalities, these trials should probably be designed directly focusing on the single entities. In this way, the cure of AML could eventually become the cure of each specific AML subset with its peculiar biological, molecular and prognostic features.

Adult↗

Physostigmine as a treatment for gamma-hydroxybutyrate toxicity: a review.

INTRODUCTION: Gamma-hydroxybutyrate is a potent sedative-hypnotic agent and a popular drug of abuse. In the United States, gamma-hydroxybutyrate is a Schedule I controlled substance (sodium oxybate) with orphan drug status for the treatment of narcolepsy within approved clinical studies. Physostigmine is a carbamate inhibitor of acetylcholinesterase that is reported to attenuate the sedative effects of a number of drugs, including gamma-hydroxybutyrate. We reviewed the literature that pertains to the use of physostigmine to treat gamma-hydroxybutyrate-induced sedation. METHODS: A structured literature search was performed to identify articles in which physostigmine and gamma-hydroxybutyrate were mentioned. Keywords were used to identify relevant articles in the Medline database, and the reference sections of articles identified by this method were hand-checked to identify additional articles. Those articles that presented original evidence pertaining to the use of physostigmine to treat gamma-hydroxybutyrate-induced sedation were included in this review; those that did not were rejected. RESULTS: The literature search identified 22 articles, six of which did not pertain to the subject matter. Of the 16 articles which remained, 12 were rejected because they offered opinions without presenting original evidence. Of the four articles that presented original evidence, there were no in vitro studies and no animal studies. There were two small case series in which physostigmine was given to treat acute gamma-hydroxybutyrate toxicity in an emergency department setting, and two larger series in which physostigmine was given to attenuate the sedation induced by gamma-hydroxybutyrate in a more structured anesthesia setting. Although these references report that physostigmine attenuates gamma-hydroxybutyrate-induced sedation, there are methodological flaws and confounding factors that limit the scope of the conclusions that can be drawn from them. CONCLUSIONS: There is currently insufficient scientific evidence to support the routine use of physostigmine in the treatment of gamma-hydroxybutyrate toxicity. Further studies are needed to determine the role, if any, for physostigmine in this setting.

Cholinesterase Inhibitors↗

Use of vancomycin-containing lock or flush solutions for prevention of bloodstream infection associated with central venous access devices: a meta-analysis of prospective, randomized trials.

BACKGROUND: Prolonged exposure to central venous access devices carries significant risk of device-associated bloodstream infection (BSI), which is associated with morbidity, added health care costs, and attributable mortality. We aimed to determine the efficacy of vancomycin-heparin lock or flush solution in preventing BSI in patients being treated with long-term central venous intravascular devices (IVDs). METHODS: We collected data from January 1966 to January 2006 from multiple computerized databases and compiled reference lists of identified articles. We identified prospective, randomized controlled trials comparing a vancomycin-heparin lock or flush solution with heparin alone for prevention of BSI associated with long-term central venous IVDs. Using a standardized form, we abstracted data regarding study quality, patient characteristics, and incidence of BSI. RESULTS: Seven randomized, controlled trials involving a total of 463 patients being treated with IVDs met the inclusion criteria; 5 studies were conducted among patients with cancer, 1 among a critically ill neonatal population, and 1 among patients with cancer or who required parenteral nutrition. We could not detect publication bias. The summary risk ratio with a vancomycin heparin-lock solution for IVD-associated BSI was 0.49 (95% confidence interval [CI], 0.26-0.95; P = .03). Results of the test for heterogeneity were statistically significant; however, when a single study was removed from the analysis, heterogeneity was no longer present. Use of vancomycin as a true lock solution--instilling it for a defined period, rather than simply flushing it directly through the device--conferred a much greater benefit, with a risk ratio of 0.34 (95% CI, 0.12-0.98; P = .04). The 2 studies that performed prospective surveillance cultures to identify colonization or infection by vancomycin-resistant organisms did not find an increased risk. CONCLUSIONS: Use of a vancomycin lock solution in high-risk patient populations being treated with long-term central IVDs reduces the risk of BSI. The use of an anti-infective lock solution warrants consideration for patients who require central access but who are at high risk of BSI, such as patients with malignancy or low-birthweight neonates.

Adult↗

The intensive care unit as a research laboratory: developing strategies to prevent antimicrobial resistance.

OBJECTIVE: To assemble the available clinical data on the prevention of antimicrobial resistance in the intensive care unit (ICU) setting. DATA SOURCE: A MEDLINE database search and references from identified articles were employed to obtain the literature relating to the prevention of antimicrobial resistance in the ICU. CONCLUSIONS: The ICU presents a unique environment for the conduct of clinical research. The closed physical space with centralized patient management and efficient data recovery allows important clinical questions to be evaluated in a timely manner. Antimicrobial resistance has emerged as an important determinant of mortality for patients in the ICU. Additionally, there is currently a limited pipeline of new agents for the treatment of emerging bacteria with new resistance genes that pose an increasing threat to the ICU patient. Effective strategies for the prevention of antimicrobial resistance within ICUs are available and should be implemented aggressively. These strategies can be divided into non-pharmacologic infection- control strategies (e.g., routine hand hygiene, infection-specific prevention protocols) and antibiotic management strategies (e.g., shorter courses of appropriate antibiotics, narrowing of the antimicrobial spectrum on the basis of culture results). Additional studies conducted in ICUs are needed urgently to identify the optimal approaches for the management of antibiotics in order to balance the need for efficacy with the ability to minimize resistance.

Anti-Bacterial Agents↗

The risk of dementia with increased body mass index.

BACKGROUND: identification of modifiable risk factors is crucial in the prevention of dementia, given its limited treatment options. Studies on increased body mass index (BMI) as a risk factor for dementia show conflicting results. METHODS: we systematically retrieved and reviewed longitudinal population-based studies on increased BMI and dementia using a standard protocol. We searched Medline (1966-2006), Ageline (1978-2006), PsychInfo (1966-2006), CINAHL (1982-2006), and other relevant databases, including the reference lists of the eligible articles for review. Included studies were subjected to a quality assessment protocol. RESULTS: we identified eight studies that met our selection criteria. These studies covered 1,688 cases of dementia from 28,697 participants. After adjustment for age, smoking, comorbidities, and other confounders, four studies presented significantly increased risk of dementia with elevated BMI. CONCLUSION: this systematic review supports the hypothesis that increased BMI is independently associated with increased risk of dementia. Long-term studies to examine the mechanisms underlying the relationship between obesity and dementia are needed.

Adult↗

Accuracy of carbohydrate-deficient transferrin in the detection of excessive alcohol consumption: a systematic review.

AIMS: Excessive alcohol consumption is a common problem in society and medical practice. There is a need for a diagnostic tool with both high sensitivity and specificity for the detection of excessive alcohol consumption in unselected medical populations. Therefore, we evaluated the diagnostic accuracy of carbohydrate-deficient transferrin (CDT) in the detection of excessive alcohol consumption. METHODS: Computerised literature searches in Medline, Embase and Current Contents databases (01/1966-06/2003) and reference checking. Articles on the detection of excessive alcohol consumption reporting CDT levels and self-reported alcohol consumption as a reference test were selected (n = 101). Studies concerning treatment, relapse detection and traffic offenders were excluded. Quality assessment and data-extraction was done by two reviewers independently. Only studies scoring positive on core validity criteria by Lijmer were eligible for quantitative analysis (n = 29). RESULTS: Only two CDT-assays (CDTect and CDTriTIA) were evaluated in more than two high validity studies fulfilling the criteria for inclusion in the statistical analysis. Sensitivity of CDTect (14 data points) ranged from 20 to 85%, whereas specificity ranged from 77 to 95%. A summary ROC curve was computed for CDTect. Sensitivity of CDTTriTIA (4 data points) ranged from 10 to 67%, and specificity ranged from 90 to 100%. No summary measure could be computed for CDTTriTIA. The heterogeneity of results could not be explained clinically. CONCLUSIONS: The validity of CDT as a diagnostic tool is still questionable. If the higher values for sensitivity that some studies report can be confirmed by others it is a useful diagnostic tool in unselected populations. However, more methodologically sound, comparable studies need to be performed before firm conclusions can be drawn.

Alcoholism↗

Finding regulatory modules through large-scale gene-expression data analysis.

MOTIVATION: The use of gene microchips has enabled a rapid accumulation of gene-expression data. One of the major challenges of analyzing this data is the diversity, in both size and signal strength, of the various modules in the gene regulatory networks of organisms. RESULTS: Based on the iterative signature algorithm [Bergmann,S., Ihmels,J. and Barkai,N. (2002) Phys. Rev. E 67, 031902], we present an algorithm-the progressive iterative signature algorithm (PISA)-that, by sequentially eliminating modules, allows unsupervised identification of both large and small regulatory modules. We applied PISA to a large set of yeast gene-expression data, and, using the Gene Ontology database as a reference, found that the algorithm is much better able to identify regulatory modules than methods based on high-throughput transcription-factor binding experiments or on comparative genomics.

Algorithms↗