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A basis for a visual language for describing, archiving and analyzing functional models of complex biological systems.

BACKGROUND: We propose that a computerized, internet-based graphical description language for systems biology will be essential for describing, archiving and analyzing complex problems of biological function in health and disease. RESULTS: We outline here a conceptual basis for designing such a language and describe BioD, a prototype language that we have used to explore the utility and feasibility of this approach to functional biology. Using example models, we demonstrate that a rather limited lexicon of icons and arrows suffices to describe complex cell-biological systems as discrete models that can be posted and linked on the internet. CONCLUSIONS: Given available computer and internet technology, BioD may be implemented as an extensible, multidisciplinary language that can be used to archive functional systems knowledge and be extended to support both qualitative and quantitative functional analysis.

Animals↗

Ethical and legal risks associated with archival research.

Mental health facilities and practitioners commonly permit resarchers to have direct access to patients' records for the purposes of archival research without the informed consent of patient-participants. Typically these researchers have access to all information in such records as long as they agree to maintain confidentiality and remove any identifying data from subsequent research reports. Changes in the American Psychological Association's Ethical Principles (American Psychological Association, 1992) raise ethical and legal issues that require consideration by practitioners, researchers, and facility Institutional Review Boards. This article addresses these issues and provides recommendations for changes in ethical standards as well as alternative avenues for conducting research using archival mental health records.

Behavioral Research↗

The quality of DNA recovered from the archival tissues of atomic bomb survivors is good enough for the single nucleotide polymorphism analysis in spite of the decade-long preservation in formalin.

It is well known that the yield of DNA recovered form tissues preserved in formalin is inversely proportional to the stored duration. How is the quality? We tested the quality of DNA from archival tissues of atomic-bomb survivors stored in formalin for decades with the parameters of gene amplification efficiency by a polymerase chain reaction. All of the DNA extracted from the tissues preserved in formalin for 30 years amplified the 54- and 61-base pairs of the DNA fragments successfully. The direct sequencing of the PCR products confirmed the accurate amplification of the target sequence. A further trial to amplify the longer sequence of 111 base pairs succeeded in 20% of the samples tested. From these results, we propose a new utility of archival samples for the analysis of single nucleotide sequence polymorphism of genes, no matter how long the samples have been preserved in formalin.

Animals↗

Author! author!: creating a digital archive of publications in a hospital library setting.

Baptist Hospital of Miami has been honoring its staff authors annually during National Library Week since 1979, at the time the library was relocated. Upon "doing the math" and realizing that twenty-five years had passed, a special event was planned to celebrate the occasion in 2004. A merger of four hospitals in 1995 to form Baptist Health South Florida, and an addition of a fifth hospital in 2003 added into the complexity of these publications. Organizing the event led to the conclusion that there had to be a "better way" to manage the publication archive. This paper will include a look back at the event's past, present efforts to develop an archival database, and future plans to make articles available electronically to users, copyright permitting.

Databases, Bibliographic↗

Human papillomavirus typing with hybrid capture II on archived liquid-based cytologic specimens: is HPV typing always reproducible?

Reproducibility of human papillomavirus (HPV) typing on archived ThinPrep (Cytyc, Boxborough, MA) specimens was evaluated repeating Hybrid Capture II (HCII) (Digene, Gaithersburg, MD) testing after 25 to 40 months (mean, 31.3 months; group 1), 6 to 11 months (mean, 8.4 months; group 2), and 0 to 5 months (mean, 3.5 months; group 3). Another ThinPrep slide was prepared to evaluate cellularity and reproducibility of the cytologic diagnosis. The mean residual relative light units (RLU) calculated for each group showed a strong decrease of RLU values at the second typing (group 1, 21.69%; group 2, 26.47%; and group 3, 32.25% of original values). No residual HPV DNA was shown in group 1 in 8 (13%) of 60 cases or in groups 2 and 3 in 2 (3%) of 60 cases each. These cases were associated mostly with poor cellularity and reproducibility of the initial cytologic diagnosis in the final cytologic examination. Intergroup statistical analysis of mean relative percentages for cases with satisfactory residual cellularity revealed a significant difference only between groups 1 and 3 (P < .05). Although mostly reproducible, HPV typing results by HCII on archived specimens are influenced by material consumption. In addition, results might be affected by some DNA degradation after long-term sample storage.

Animals↗

Convergence of self-report and archival crash involvement data: a two-year longitudinal follow-up.

This study constructively extends Arthur et al. (2001) by assessing the convergence of self-report and archival motor vehicle crash involvement and moving violations data in a 2-year longitudinal follow-up. The relationships among these criteria, conscientiousness, and driving speed were also assessed using both predictive and postdictive criterion-related validation designs. Data were collected from a 2-year follow-up sample of 334 participants. Results suggested a lack of convergence between self-report and archival data at both Time 1 and Time 2. In addition, the predictor/criterion relationships varied across research design and data source. An actual application of our findings is that the interpretation of relationships between specified predictors and crash involvement and moving violations must be made within the context of the criterion-related validation design and criterion data source. Specifically, predictive designs may produce results different from those of postdictive designs (which are more commonly used). Furthermore, self-report data appear to include a broader range of incidents (more crashes and tickets), and thus researchers should consider using self-report data when they are interested in including lower threshold crashes and tickets that may not be reported on state records (e.g., because of the completion of a defensive driving course).

Accidents, Traffic↗

The HIV/AIDS Prevention Program Archive (HAPPA): a collection of promising prevention programs in a box.

This article describes the methods used and findings obtained in establishing the HIV/AIDS Prevention Program Archive (HAPPA), a collection of effective HIV/AIDS prevention programs in a box. The HAPPA collection builds on a previously established collection of 13 effective HIV/AIDS/sexually transmitted disease (STD) prevention programs for adolescents known as PASHA, the Program Archive on Sexuality, Health, & Adolescence. Together, the HAPPA and PASHA collections provide a rich source of 23 promising programs designed to prevent the spread of HIV/AIDS. The HAPPA and PASHA programs are available for use by communities, schools, family planning clinics, STD clinics, mental health centers, and drug rehabilitation centers throughout the country.

Acquired Immunodeficiency Syndrome↗

[Publication trends in quarterly, bimonthly and monthly cycles of publication during the five decades of Brazilian Archives of Cardiology].

OBJECTIVE: To study trends in selected manuscript characteristics of articles published in the Brazilian Archives of Cardiology from March 1948, to February 1998, in the quarterly, bimonthly and monthly cycles of publication. METHODS: A random sample of 25% of all issues of the journal comprised the study sample: 13 issues (11.5%) from the quarterly, 27 (23,5%) from the bimonthly, and 58 (65%) from the monthly publication cycle. We studied the type of manuscript, number of authors, geographical distribution, language of publication and references. RESULTS: A total of 1204 articles were studied, 90 (7.5%) from the quarterly, 238 (19,8%) from the bimonthly, and 876 (72.8%) from the monthly publication cycle. The most frequent published articles were original contributions (353), reviews (350) and case reports (205). No significant difference occurred in the proportion of original articles, reviews and case reports; the number of authors was higher in the monthly period;a geographical concentration of the contributions occurred (72% from three Brazilian States); manuscripts in languages other than Portuguese decreased. The mean number of Brazilian references cited was less than 4.7 and the mean number of international references cited was greater than 16.7. CONCLUSION: The analysis of the trends over five decades of publication revealed the need for further steps to be taken by the Brazilian Archives of Cardiology, to meet international publication standards for biomedical journals as well as authors' and readers' demands.

Bibliometrics↗

Whole transcriptome amplification for gene expression profiling and development of molecular archives.

Expression profiling of clinically obtainable tumor specimens has been hindered by the need for microgram quantities of RNA. In vitro transcription (IVT)-based amplifications are most commonly used to amplify small quantities of RNA for microarray analysis. However, significant drawbacks exist with IVT-based amplification, and the need for alternative amplification methods remains. Herein, we validate whole transcriptome amplification (WTA), an exponential amplification technique that produces cDNA libraries and amplified target in 3 to 4 hours from nanogram quantities of total RNA using a combination of cDNA microarrays and quantitative polymerase chain reaction (PCR). We demonstrate that WTA material can serve as a "molecular archive" because a WTA cDNA library can be faithfully amplified through multiple rounds of PCR amplification, allowing it to serve as a bankable and distributable resource. To demonstrate applicability, WTA was combined with laser capture microdissection to profile frozen prostate tissues. Unlike most IVT-based and exponential amplification techniques, WTA does not depend on the presence of a poly-A tail. Thus, we demonstrate that WTA is compatible with artificially degraded RNA and RNA isolated from formalin-fixed paraffin-embedded tissues. Taken together, WTA represents a versatile approach to profile and archive cDNA from minute tumor samples and is compatible with partially degraded RNA.

Biological Specimen Banks↗

Examination of gene fusion status in archival samples of alveolar rhabdomyosarcoma entered on the Intergroup Rhabdomyosarcoma Study-III trial: a report from the Children's Oncology Group.

Alveolar rhabdomyosarcoma (ARMS) is a soft tissue cancer in which chromosomal translocations generate PAX3-FKHR and PAX7-FKHR gene fusions. To improve the approach for fusion detection in archival samples, we developed a real-time reverse transcriptase-polymerase chain reaction assay for these fusion transcripts. By incorporating consensus primers and gene-specific probes, both presence and subtype of the fusion were determined in one assay. We applied this approach to a convenience sample of 78 formalin-fixed, paraffin-embedded ARMS tumors from the Intergroup Rhabdomyosarcoma Study (IRS)-III clinical trial and obtained satisfactory results in 59 (76%) cases. The distribution of fusion types was 35 (59%) PAX3-FKHR, 11 (19%) PAX7-FKHR, and 13 fusion-negative (22%). In a subsequent clinical analysis, we found that IRS-III ARMS cases analyzed for fusion status had a significantly improved outcome compared to IRS-III ARMS cases that were not available for fusion analysis. The basis of this outcome could not be explained by known prognostic clinical factors, and multivariate analysis confirmed that our convenience sample was not representative of the whole IRS-III cohort. In conclusion, although these robust assays provide new opportunities for correlative studies of archival material, our first application illustrates an important limitation of using a convenience sample for molecular-clinical correlative studies.

Child↗

Postadhesive technique for archival paraffin sections.

We present a postadhesive protocol for adhering paraffin sections of archival material to microscope slides. Appropriately posttreated sections, subsequently processed for immunohistochemistry, remained attached to the slides and were well preserved with no signs of artifacts, such as scratching and shrinkage. The immunohistochemical staining was intense and antigen-specific without nonspecific background. Specific staining intensity was equal to that produced in untreated control sections; however, the latter became partially or fully detached from the slides. The postadhesion protocol may be used with modern techniques and is recommended for reclaiming use of otherwise unsuitable paraffin sections of archival material.

Antigens↗

Immunohistochemical detection of progesterone receptors in archival breast cancer.

The progesterone receptor (PR) is an important marker of response to endocrine agents in breast cancer. Immunohistochemical demonstration of PR in formalin fixed tissue has previously proved difficult, and heat pretreatment is considered necessary to retrieve the antigen. There are few data on the effectiveness of autoclaving in unmasking PR, however, and it is not known whether all PR epitopes are equally unmasked. The objectives of this study were to compare the efficacy of autoclaving and microwaving to retrieve PR antigen in archival breast tumors, to determine whether there is an epitope-dependent variability in the pretreatment required, and to examine different slide types and adhesives to reduce the problem of section loss frequently associated with these procedures. Paraffin embedded sections were cut at 2 or 4 microm, mounted onto various slide types with or without the addition of adhesive, and heat pretreated prior to immunoperoxidase staining. Whereas PR immunoreactivity was clearly demonstrated in tissue after both autoclaving and microwaving, autoclaving produced a significantly stronger staining intensity under the conditions used in this study. The duration of autoclaving required to reveal PR fully differed for different epitopes examined. In the absence of heat pretreatment, PR was not detected. Section retention was improved by the use of adhesives and by cutting tissue at 2 microm. Maximum retention was obtained using positively charged slides coated with Mayer albumen adhesive. We conclude that for maximal tissue preservation autoclave pretreatment is the preferred method of PR antigen retrieval from archival breast tumors, that there is epitope-dependent variability in pretreatment required, and that section loss during this procedure can be minimized by choice of slide type, the use of adhesive, and by cutting sections at 2 microm.

Adhesives↗

Assessment of Helicobacter pylori clarithromycin resistance mutations in archival gastric biopsy samples.

AIM: First, to assess the clarithromycin resistance (Cla(R)) rate 1) in patients with persistent Helicobacter pylori (H. pylori) infection after eradication,2) in patients with untreated infection and 3) in patients with successful status post eradication. Second, to evaluate the techniques sequencing and line probe hybridisation INNO-LipA for resolution of uniform and mixed populations in archival gastric biopsy samples. METHODS: The genomic 2142/43 23s rRNA mutations of the 50S ribosomal subunit conferring Cla(R) were detected by PCR-based assays. RESULTS: A total of 130 patients were investigated. Out of 21 patients of a first series with persistent infection after eradication, 19 (90%; CI (95%): 67-99%) exhibited point mutations at position 2142/43. In the second series of untreated patients, primary resistance was observed in 8 out of 93 patients (9%; CI: 4-16%). In a third series of 16 successfully eradicated patients, pure wild type populations (WT; for loci 2142/43) without any minimal mutated part were found (resistance rate 0%; CI: 0-21%). Further, in all 24 biopsies with uniform mutated and in 8 of 11 biopsies with mixed populations the two molecular biological methods yielded concordant results (100%; CI: 86-100% and 73%; CI: 39-94%, respectively). CONCLUSION: In the Baden region of Switzerland, most clarithromycin resistant H. pylori strains harbour mutations at position 2142/43. The primary resistance rate is below 10%. Mixed populations, even with minor mutated part, cannot become successfully eradicated. The two investigated techniques are equally valid for resolution of uniform mutated or mixed H. pylori populations in archival biopsy material.

Anti-Bacterial Agents↗

A distributed medical record on a Holter-ECG archiving and analysis system.

At the Department of Cardiology of the Technical University of Munich and the Deutsches Herzzentrum München cardiac disease patients are treated in close co-operation. In order to support the collaborative treatment as well as cardiological studies a distributed medical record (DMR) has been implemented on the basis of a Holter-ECG archiving and analysis system. Architecture, experiences and major benefits of the solution are reported in the paper. Between January 1995 and December 1997 6500 Holter-ECGs have been archived and analysed. The DMR is in routine operation since January 1996 for all heart catheter patients.

Attitude to Computers↗

Comparative polymerase chain reaction analysis of c-myc amplification on archival breast fine-needle aspiration materials.

The oncogene c-myc is a key regulator of cell cycle progression (from G1 to S phase). The amplification of c-myc can either induce cell proliferation or apoptosis. As a part of our ongoing effort to develop methods for multiple tumor marker analysis, this study was carried out to determine whether biomarkers such as c-myc amplification could be analyzed on genetic materials collected from archival fine-needle aspiration (FNA) smears. A novel comparative PCR analysis was used to analyze c-myc amplification semiquantitatively. Genomic DNA was prepared using cells obtained from archival FNA materials that had undergone quantitative fluorescence image analysis (QFIA) for other biomarkers. Of the 72 cases selected from 1995 for this study, 53 had an adequate amount of DNA for analysis. A novel comparative PCR analysis was used to analyze c-myc amplification quantitatively. For each batch of experiments, DNA from the high c-myc expressing cells, HL-60, and DNA from the low expressing cells, K562, were served as positive and negative controls, respectively. c-myc amplification was observed in 16 (94.1%) of 17 malignant lesions, 5 (41.7%) of 12 proliferative breast diseases with nuclear atypia, and 4 (16.7%) of 24 other benign lesions (fibroadenoma or fibrocystic disease). The overall difference of c-myc expression among these groups was highly significant by chi2 analysis (P = 0.0002). We conclude that multiple phenotypic markers and genotypic markers may be combined in a risk assessment biomarker profile on small FNA samples that can be obtained on multiple occasions relatively noninvasively from the patient. The results of this study suggest that c-myc amplification may be a biomarker of breast cancer risk. However, additional large, prospective studies are needed to confirm the current observation.

Adult↗

The Cooperative Breast Cancer Tissue Resource: archival tissue for the investigation of tumor markers.

Investigators continue to search for reliable markers of prognosis of breast cancer. For many analyses, laboratory techniques permit the use of archival paraffin-embedded tissue collected years previously and readily linked to clinical and follow-up information. Laboratory investigators have often expressed the need for such a tissue resource. We have developed a publicly available resource of archival breast cancer specimens. The pathological material has been collected and reviewed by investigators at four institutions and currently includes breast cancer specimens from more than 9300 cases. Institutional pathologists reviewed slides and blocks using a common protocol and coding scheme. Clinical information and details of follow-up came from data routinely collected by the institutions' cancer registries. Coded data are maintained centrally in a single database. A subset of the data may be searched on the World Wide Web to determine the availability of cases with specified characteristics. The material collected by this Cooperative Breast Cancer Tissue Resource is generally representative of breast cancer diagnosed in community hospital settings in the United States. Seventy-two percent of the living cases have been followed for at least 5 years, and follow-up status is updated regularly. Interested laboratory investigators may apply to the Resource for the use of these tissues. This Resource is proving valuable to laboratory investigators who require large numbers of specimens for validation studies of prognostic markers of breast cancer.

Adult↗

[Archives of environmental health digital maps and their delivery by the Internet].

Geographic Information System is becoming a very important tool for environmental health research. We have produced various digital maps for different scales for different purposes. The burst of E. Coli O-157, distribution of hazadarous chemicals in East Asia, and coastal resin pellets are some examples. It now becomes a problem how to archive these digital maps and how to retrieve these maps according to user's request. We have developed a computer system that can store various types of digital maps and can retrieve them from WWW client machines. The key concept of this archive system is to classify every digital maps according to their region of interest.

Environmental Health↗

[An integrated medical image network of patient records: experience of the Picture Archiving and Communication System (PACS) of the Gustave-Roussy Institute].

The PACS (Picture Archiving and Communication System) is a central radiologic image archiving system coupled with an information system which allows rapid access to these images. It permits rapid access of the entire file of radiologic images of a patient for radiologists and clinicians. After installation of an MRI and CT scan unit at the IGR, a PACS system was installed in July, 2000. The preparation phase and characteristics of the PACS system at the IGR are described here. The data in the literature and the short experience of the PACS system at the IGR show benefits of this system at several levels: improved efficiency (for technicians, radiologists, and secretaries), improved image quality and interpretation, improved clinical management of patients resulting from more timely image interpretation and execution of clinical decisions, increased ease of image transfer for tele-imagery, and improved teaching and publication possibilities. The PACS significantly modifies work habits since the interpretation and consultation of images is done exclusively at the console and progressively obviates the need for actual films.

Computer Systems↗