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PubMed2003

Multivariate exploratory tools for microarray data analysis.

The ultimate success of microarray technology in basic and applied biological sciences depends critically on the development of statistical methods for gene expression data analysis. The most widely used tests for differential expression of genes are essentially univariate. Such tests disregard the multidimensional structure of microarray data. Multivariate methods are needed to utilize the information hidden in gene interactions and hence to provide more powerful and biologically meaningful methods for finding subsets of differentially expressed genes. The objective of this paper is to develop methods of multidimensional search for biologically significant genes, considering expression signals as mutually dependent random variables. To attain these ends, we consider the utility of a pertinent distance between random vectors and its empirical counterpart constructed from gene expression data. The distance furnishes exploratory procedures aimed at finding a target subset of differentially expressed genes. To determine the size of the target subset, we resort to successive elimination of smaller subsets resulting from each step of a random search algorithm based on maximization of the proposed distance. Different stopping rules associated with this procedure are evaluated. The usefulness of the proposed approach is illustrated with an application to the analysis of two sets of gene expression data.

Algorithms↗
PubMed2006

VANTED: a system for advanced data analysis and visualization in the context of biological networks.

BACKGROUND: Recent advances with high-throughput methods in life-science research have increased the need for automatized data analysis and visual exploration techniques. Sophisticated bioinformatics tools are essential to deduct biologically meaningful interpretations from the large amount of experimental data, and help to understand biological processes. RESULTS: We present VANTED, a tool for the visualization and analysis of networks with related experimental data. Data from large-scale biochemical experiments is uploaded into the software via a Microsoft Excel-based form. Then it can be mapped on a network that is either drawn with the tool itself, downloaded from the KEGG Pathway database, or imported using standard network exchange formats. Transcript, enzyme, and metabolite data can be presented in the context of their underlying networks, e. g. metabolic pathways or classification hierarchies. Visualization and navigation methods support the visual exploration of the data-enriched networks. Statistical methods allow analysis and comparison of multiple data sets such as different developmental stages or genetically different lines. Correlation networks can be automatically generated from the data and substances can be clustered according to similar behavior over time. As examples, metabolite profiling and enzyme activity data sets have been visualized in different metabolic maps, correlation networks have been generated and similar time patterns detected. Some relationships between different metabolites were discovered which are in close accordance with the literature. CONCLUSION: VANTED greatly helps researchers in the analysis and interpretation of biochemical data, and thus is a useful tool for modern biological research. VANTED as a Java Web Start Application including a user guide and example data sets is available free of charge at http://vanted.ipk-gatersleben.de.

Algorithms↗
PubMed2006

Disparities in HbA1c levels between African-American and non-Hispanic white adults with diabetes: a meta-analysis.

OBJECTIVE: Among individuals with diabetes, a comparison of HbA(1c) (A1C) levels between African Americans and non-Hispanic whites was evaluated. Data sources included PubMed, Web of Science, the Cumulative Index to Nursing and Allied Health, the Cochrane Library, the Combined Health Information Database, and the Education Resources Information Center. RESEARCH DESIGN AND METHODS: We executed a search for articles published between 1993 and 2005. Data on sample size, age, sex, A1C, geographical location, and study design were extracted. Cross-sectional data and baseline data from clinical trials and cohort studies for African Americans and non-Hispanic whites with diabetes were included. Diabetic subjects aged <18 years and those with pre-diabetes or gestational diabetes were excluded. We conducted a meta-analysis to estimate the difference in the mean values of A1C for African Americans and non-Hispanic whites. RESULTS: A total of 391 studies were reviewed, of which 78 contained A1C data. Eleven had data on A1C for African Americans and non-Hispanic whites and met selection criteria. A meta-analysis revealed the standard effect to be 0.31 (95% CI 0.39-0.25). This standard effect correlates to an A1C difference between groups of approximately 0.65%, indicating a higher A1C across studies for African Americans. Grouping studies by study type (cross-sectional or cohort), method of data collection for A1C (chart review or blood draw), and insurance status (managed care or nonmanaged care) showed similar results. CONCLUSIONS: The higher A1C observed in this meta-analysis among African Americans compared with non-Hispanic whites may contribute to disparity in diabetes morbidity and mortality in this population.

Black or African American↗
PubMedDate not supplied

Complementary roles for toxicologic pathology and mathematics in toxicogenomics, with special reference to data interpretation and oscillatory dynamics.

Toxicogenomics is an emerging multidisciplinary science that will profoundly impact the practice of toxicology. New generations of biologists, using evolving toxicogenomics tools, will generate massive data sets in need of interpretation. Mathematical tools are necessary to cluster and otherwise find meaningful structure in such data. The linking of this structure to gene functions and disease processes, and finally the generation of useful data interpretation remains a significant challenge. The training and background of pathologists make them ideally suited to contribute to the field of toxicogenomics, from experimental design to data interpretation. Toxicologic pathology, a discipline based on pattern recognition, requires familiarity with the dynamics of disease processes and interactions between organs, tissues, and cell populations. Optimal involvement of toxicologic pathologists in toxicogenomics requires that they communicate effectively with the many other scientists critical for the effective application of this complex discipline to societal problems. As noted by Petricoin III et al (Nature Genetics 32, 474-479, 2002), cooperation among regulators, sponsors and experts will be essential for realizing the potential of microarrays for public health. Following a brief introduction to the role of mathematics in toxicogenomics, "data interpretation" from the perspective of a pathologist is briefly discussed. Based on oscillatory behavior in the liver, the importance of an understanding of mathematics is addressed, and an approach to learning mathematics "later in life" is provided. An understanding of pathology by mathematicians involved in toxicogenomics is equally critical, as both mathematics and pathology are essential for transforming toxicogenomics data sets into useful knowledge.

Animals↗
PubMed2005

Amplification of the concept of meaning as the validating principle in psychodynamic science.

In two previous articles by this author, the concept of psyche was given legitimate scientific status insofar as a necessarily new and unique scientific paradigm for psychodynamics was elaborated, stemming from the idea that positivistic science is not appropriate to the subjective data of psychoanalysis. This paradigm includes the idea that the concept of meaning as scientific validation is central to psychodynamic science. The concepts of erroneous meaning, synchronicity, and numinosity were introduced as aspects of this new scientific paradigm. In the present article, the complementary relationship between psychodynamic and traditional science is explored. The concepts of synchronicity, numiosity, and meaning are elaborated, together with discussion of the phenomenon of anxiety as it impinges on these dynamics. The concept of erroneous meaning is in this article separated from the concept of meaning itself through the idea that the activation of anxiety separates the two.

Anxiety↗
PubMed1993

Overlooking ethics in the search for objectivity and misconduct in science.

The author investigates the relationship between the reliability of scientific data and the ethics of the scientist, demonstrates how attention given to misconduct in the biological sciences adversely affects the broader significance of ethics in this field, and extracts from the applications of ethics in medicine perspectives relevant to the biological sciences. As twentieth-century biological scientists applied increasingly powerful methods to diminish bias and to improve the objectivity of their work, including the replication of experimental findings to verify them, they came to believe that these methods would protect their studies from error and misleading conclusions. This assumption has been shown to be unwarranted because it cannot protect scientists from self-conscious or biased selection in reporting evidence. The canons of scientific objectivity must be grounded in something more fundamental--the canon of ethics. In the end, a commitment to the ethical standard of truthfulness, through an understanding of its meaning to science, is essential to enhance objectivity and diminish bias. Unfortunately, the ethos of concern for scientific misconduct continues to dominate the research-ethics movement. This focus is damaging because it turns the attention to seeking and finding wrong-doers and determining punishment rather than discussing generic issues of doing the right thing, preventing harms, seeking benefits, and understanding the right-making and wrong-making characteristics of actions. The focus on scientific misconduct makes ethical issues appear synonymous with legal issues and the search for ethical understanding synonymous with carrying out an investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomedical Research↗
PubMed1999

Chlamydia pneumoniae and atherosclerosis.

OBJECTIVE: To review the literature for evidence that chronic infection with Chlamydia pneumoniae is associated with atherosclerosis and acute coronary syndromes. DATA SOURCES: MEDLINE and Institute of Science and Information bibliographic databases were searched at the end of September 1998. Indexing terms used were chlamydi*, heart, coronary, and atherosclerosis. Serological and pathological studies published as papers in any language since 1988 or abstracts since 1997 were selected. DATA EXTRACTION: It was assumed that chronic C pneumoniae infection is characterised by the presence of both specific IgG and IgA, and serological studies were examined for associations that fulfilled these criteria. Pathological studies were also reviewed for evidence that the presence of C pneumoniae in diseased vessels is associated with the severity and extent of atherosclerosis. DATA SYNTHESIS: The majority of serological studies have shown an association between C pneumoniae and atherosclerosis. However, the number of cases in studies that have reported a positive association when using strict criteria for chronic infection is similar to the number of cases in studies which found no association. Nevertheless, the organism is widely found in atherosclerotic vessels, although it may not be at all diseased sites and is not confined to the most severe lesions. Rabbit models and preliminary antibiotic trials suggest that the organism might exacerbate atherosclerosis. CONCLUSION: More evidence is required before C pneumoniae can be accepted as playing a role in atherosclerosis. Although use of antibiotics in routine practice is not justified, large scale trials in progress will help to elucidate the role of C pneumoniae.

Acute Disease↗
PubMedDate not supplied

InfVis--platform-independent visual data mining of multidimensional chemical data sets.

The tremendous increase of chemical data sets, both in size and number, and the simultaneous desire to speed up the drug discovery process has resulted in an increasing need for a new generation of computational tools that assist in the extraction of information from data and allow for rapid and in-depth data mining. During recent years, visual data mining has become an important tool within the life sciences and drug discovery area with the potential to help avoiding data analysis from turning into a bottleneck. In this paper, we present InfVis, a platform-independent visual data mining tool for chemists, who usually only have little experience with classical data mining tools, for the visualization, exploration, and analysis of multivariate data sets. InfVis represents multidimensional data sets by using intuitive 3D glyph information visualization techniques. Interactive and dynamic tools such as dynamic query devices allow real-time, interactive data set manipulations and support the user in the identification of relationships and patterns. InfVis has been implemented in Java and Java3D and can be run on a broad range of platforms and operating systems. It can also be embedded as an applet in Web-based interfaces. We will present in this paper examples detailing the analysis of a reaction database that demonstrate how InfVis assists chemists in identifying and extracting hidden information.

Computational Biology↗
PubMed2004

Pediatric trauma in southwestern Ontario: linking data with injury prevention initiatives.

BACKGROUND: Our objective was to provide an epidemiologic description of pediatric trauma in SW Ontario using multiple data sets. Injury prevention (IP) initiatives were linked with predominant injury mechanisms to determine whether IP programs were supported by data. METHODS: Descriptive analysis was undertaken for five pediatric age groups (<1 year, 1-4 years, 5-9 years, 10-14 years, 15-19 years) using the Ontario Trauma Registry's Death Data Set, Comprehensive Data Set (Lead Trauma Hospitals [LTH] patients), and Minimal Data Set (hospital admissions), 1999-2000, for all pediatric patients residing in SW Ontario. National Ambulatory Care Reporting System (NACRS) data from the Children's Hospital of Western Ontario/London Health Sciences Centre were used to capture the Emergency Room (ER) injury data. Information on IP initiatives for children and youth was gathered through an Internet search, supplemented by a survey. RESULTS: Injury in SW Ontario resulted in 13,197 ER visits, 1,616 hospital admissions, 70 severe trauma (ISS > 12) cases treated at a LTH and 47 deaths to children and youth. More males than females were injured, with the sex differential more pronounced as age increased. Falls were the leading mechanism for ER visits (37%) and hospital admissions (26%). Recreational injuries represented approximately 30% of injuries to the 10-14 yr age group. As ISS increased, MVCs emerged as an important mechanism, representing 71% of LTH cases and 53% of pediatric injury deaths in SW Ontario. There were 61 pediatric IP programs identified in SW Ontario. Eighty-four percent of programs (51/61) were supported by data, and were related to one of the predominant injury mechanisms. CONCLUSIONS: Injury is a serious problem for children in SW Ontario. Data can be used to identify modifiable risk factors to develop and implement new IP initiatives with the goal of reducing childhood injury and death. There is a need to integrate and link IP programs in SW Ontario for full coverage of all injury mechanisms.

Accident Prevention↗
PubMed2003

Research contributions in ophthalmology: Australia's productivity.

BACKGROUND: In 2000, the Australian and New Zealand Journal of Ophthalmology (ANZJO) changed title to Clinical and Experimental Ophthalmology. At this time, a review of Australia's contributions to the literature over the previous 21 years appears timely. Bibliometric indicators are used extensively to assess research performance as they offer views of a field that might not otherwise be apparent. The aim of this study was to explore publication output data to construct a picture of ophthalmology that may be of benefit to researchers and ophthalmologists. METHODS: Science Citation Index and Social Sciences Citation Index databases were used to collate data on ophthalmology research literature from 1980 to 2000. Subsequent analysis particularly focused on Australia's contribution to this literature, including publication frequency vis-à-vis the world, collaboration, and the journals in which Australian researchers frequently publish. These data were also compared with other countries of similar scientific stature or language. RESULTS: Since 1980, Australia has ranked in the top 10 nations contributing to world ophthalmology research. Its contribution was close to world average in the 1980s, but increasing numbers of researchers and papers show Australia exceeding the world average during the 1990s. Most ophthalmology research collaboration by Australians is within Australia. Although fewer in number, collaborative papers with overseas researchers include 28 other countries. Data on the journals in which Australians publish show that Australian researchers continue to exhibit a preference for publication in their own regional journals. CONCLUSIONS: This paper, one of a series on the literature of the vision sciences, provides some initial benchmarks on Australia's standing and contribution to the field of ophthalmology research.

Australia↗
PubMed2005

Mining parasite data using genetic programming.

Genetic programming is a technique that can be used to tackle the hugely demanding data-processing problems encountered in the natural sciences. Application of genetic programming to a problem using parasites as biological tags demonstrates its potential for developing explanatory models using data that are both complex and noisy.

Algorithms↗
PubMed1996

Analysis of paired ordered categorical data in a factorial design.

In clinical trials and behavioral sciences, there exist situations where paired responses are obtained from each subject on an ordinal scale. Existing methods for analyzing such data in a factorial design are reviewed and new methods are developed with a special emphasis on pre- and post-treatment responses. The distribution of a square table is decomposed into successively independent pairs of discordant vectors, and assuming a logistic model, a statistics is computed to measure the shift in the marginal distributions. The approach is similar to McCullagh's approach (1). Two other criteria are proposed, one based on a Lehmann alternative used for comparing two distribution functions and the other based on a proportional odds model. These criteria are applied to the marginal distributions of a square table. For each case, a statistic measuring lack of marginal homogeneity and its variance are computed for each independent square table of a factorial design. Given such statistics, one can estimate a set of linear contrasts and compute its dispersion matrix for making inference. A numerical example is given.

Double-Blind Method↗
PubMed2002

Using a course-long theme for inquiry-based laboratories in a comparative physiology course.

I developed an inquiry-based laboratory model that uses a central theme throughout the semester to develop in undergraduate biology majors the skills required for conducting science while introducing them to modern and classical physiological techniques. The physiology laboratory uses a goal-oriented approach, with students working cooperatively in small groups to answer basic biological questions. The student teams work to develop skills associated with experimental design, data analysis, written and oral communication, science literacy, and critical thinking. The laboratory curriculum is a research-based model that offers the advantage of students asking open-ended questions by use of a variety of techniques. For the students and instructor alike, this presents an exciting and challenging approach for learning physiology and basic biological principles. Another advantage of this laboratory model is that it is flexible and adaptable; the central theme can be any that the instructor chooses, and the goals and techniques developed are based on student and instructor needs and interests. Students who have completed this model at Loyola College in Maryland have become equipped with the skills essential for any area of the biological sciences and, most importantly, showed elevated excitement and commitment to learning.

Cooperative Behavior↗
PubMed1991

DNA single locus profiles: tests for the robustness of statistical procedures within the context of forensic science.

We describe a series of experiments, carried out on data from DNA profiles, which have been designed specifically to test the validity of the statistical procedures currently used in the Home Office Forensic Science Service. The tests address issues which have been the subject of topical debate, in particular those of representativeness and band independence. The results confirm the confidence which had already been placed in the established procedures. We recommend that all practitioners in the forensic field should carry out similar testing on their own data collections.

DNA Fingerprinting↗
PubMedDate not supplied

[To the history of organisation and development of cardiac anesthesiology in the A. N. Bakulev Research Center of Cardiovascular Surgery of the Russian Academy of Medical Sciences: the start of activities (1956-1965)].

The authors present data on the development and introduction of anesthetic techniques during cardiac surgery at the Institute of Thoracic Surgery, USSR Academy of Medical Sciences, in 1956-1960 and after its reorganization to the Institute of Cardiovascular Surgery, USSR Academy of Medical Sciences, in 1961-1965. It is shown that in the years of introduction of closed operations on the heart, the methods of one- and many component inhalational anesthesia were mastered, its techniques were developed, anesthesia apparatuses and an anesthesia schedule were designed, cardiac anesthesiological studies were conducted, training of physicians from the country's regions was initiated, and the first guidelines for general anesthesia were published. In these years, the firm foundation was laid for the development of cardiac anesthesia. Later on the Institute developed and introduces all basic types of inhalational anesthesia during operations on the open heart under both extracorporeal circulation and hypothermia. The gained experience allowed the laboratory staff to defend several dissertations, to issue two monographs, and to analyze errors and risks of general anesthesia in patients with cardiovascular diseases at surgery.

Academies and Institutes↗