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Acceptance of genetic testing for hereditary breast ovarian cancer among study enrollees from an African American kindred.

Clinical availability of genetic testing for cancer predisposition genes is generating a major challenge for U.S. health care systems to provide relevant genetic services to underserved populations. Here we present rates of study enrollment and utilization of genetic testing in a research study on BRCA1 testing acceptance in one large kindred. We also present data on baseline access to genetic information as well as enabling and obstructing factors to study enrollment. The study population included female and male members of an African American kindred based in the rural southern United States with an identified BRCA1 mutation. A combination of quantitative and qualitative data were collected and analyzed. Of the 161 living, eligible, and locatable kindred members, 105 (65%) enrolled in the study. Family, personal, and educational motivations were the most commonly endorsed reasons for study participation. The most commonly cited reasons for refusal to participate in the study were: lack of interest, time constraints, and negative experiences with prior participation in genetic research. Eighty three percent of the participants underwent BRCA1 testing. In multiple logistic regression analysis, age 40-49 (odds ratio (OR) = 6.9; 95% confidence interval (CI) = 1.2-39.5), increased perceived risk of being a BRCA1 mutation carrier (OR = 4.1; 95% CI = 1.1-14.6), and high cancer genetics knowledge levels (OR = 1.5; 95% CI = 1.1-2.3) were associated with BRCA1 testing acceptance. The results of this study indicate that cognitive and demographic factors may influence genetic research participation and genetic testing decisions among African Americans who are at increased risk of carrying a deleterious BRCA1 mutation.

Adult↗

Identification of a gene encoding a new Ypt/Rab-like monomeric G-protein in Saccharomyces cerevisiae.

A Saccharomyces cerevisiae sequence cloned by serendipity was found to encode a protein that is a new member of the Ypt/Rab monomeric G-protein family. This sequence shows high homology to the yeast genes SEC4 and YPT1 and, like SEC4 and YPT1, is essential for viability. The sequence was localized to chromosome V based upon hybridization to pulse-field gel-separated yeast chromosomes. The sequence has been deposited in the GenBank data library under Accession Number L17070.

Amino Acid Sequence↗

Biological markers of breast cancer: a review.

This review of biological markers of breast carcinoma has summarized a fairly representative series of studies pertaining to endocrine, carcinoembryonic, tissue-associated, serologic, biochemical, and specific tumor markers, with attention to some of the contributions from genetic engineering techniques applied to this research area. It is meant to be a helpful review with two purposes: those involved in research or clinical studies of breast cancer may wish to use this review as a basis for adding additional references in each category and to refer to the references provided for further study, thought, and synthesis of the data, perhaps to stimulate new associations between pertinent facts; those involved in the general scientific or clinical fields may wish to use it as an overview of biological markers pertaining to a particular form of cancer and perhaps this review will permit faster, more easily accessible synthesis of data, and a better understanding of a variety of parameters which are associated with breast cancer diseases.

Antibodies, Monoclonal↗

Medicare and Medicaid programs; requirements for long term care facilities; nursing services; posting of nurse staffing information. Final rule.

In this rule, we finalize provisions specified in the Medicare, Medicaid, and SCHIP Benefits Improvement and Protection Act of 2000 (BIPA) that establish new data collection, posting, and recordkeeping requirements for skilled nursing facilities (SNFs) and nursing facilities (NFs). It requires that on a daily basis for each shift, SNFs and NFs must post nurse staffing data for the licensed and unlicensed staff directly responsible for resident care in the facility. Facility census information must also be posted. This final rule is also part of a broader communication outreach initiative by CMS to provide beneficiaries, their families, and the public with access to updated data and other information that can assist them in making healthcare decisions.

Forms and Records Control↗

The Ensembl automatic gene annotation system.

As more genomes are sequenced, there is an increasing need for automated first-pass annotation which allows timely access to important genomic information. The Ensembl gene-building system enables fast automated annotation of eukaryotic genomes. It annotates genes based on evidence derived from known protein, cDNA, and EST sequences. The gene-building system rests on top of the core Ensembl (MySQL) database schema and Perl Application Programming Interface (API), and the data generated are accessible through the Ensembl genome browser (http://www.ensembl.org). To date, the Ensembl predicted gene sets are available for the A. gambiae, C. briggsae, zebrafish, mouse, rat, and human genomes and have been heavily relied upon in the publication of the human, mouse, rat, and A. gambiae genome sequence analysis. Here we describe in detail the gene-building system and the algorithms involved. All code and data are freely available from http://www.ensembl.org.

Animals↗

Validation of in silico-predicted genic SNPs in white clover (Trifolium repens L.), an outbreeding allopolyploid species.

White clover (Trifolium repens L.) is an obligate outbreeding allotetraploid forage legume. Gene-associated SNPs provide the optimum genetic system for improvement of such crop species. An EST resource obtained from multiple cDNA libraries constructed from numerous genotypes of a single cultivar has been used for in silico SNP discovery and validation. A total of 58 from 236 selected sequence clusters (24.5%) were fully validated as containing polymorphic SNPs by genotypic analysis across the parents and progeny of several two-way pseudo-testcross mapping families. The clusters include genes belonging to a broad range of predicted functional categories. Polymorphic SNP-containing ESTs have also been used for comparative genomic analysis by comparison with whole genome data from model legume species, as well as Arabidopsis thaliana. A total of 29 (50%) of the 58 clusters detected putative ortholoci with known chromosomal locations in Medicago truncatula, which is closely related to white clover within the Trifolieae tribe of the Fabaceae. This analysis provides access to translational data from model species. The efficiency of in silico SNP discovery in white clover is limited by paralogous and homoeologous gene duplication effects, which are resolved unambiguously by the transmission test. This approach will also be applicable to other agronomically important cross-pollinating allopolyploid plant species.

Arabidopsis↗

Developing the electronic health record: what about patient safety?

This paper examines the development of electronic health records within the National Health Service (NHS) by an analysis of a series of pilot projects funded by the Electronic Record Development and Implementation Project (ERDIP), one aspect of the work of the NHS Information Authority (NHSIA) (As of 1 April 2005, the NHSIA ceased to operate. Much of its work is continued by Connecting for Health and the Health and Social Care Information Centre.) The focus of the analysis is on the extent to which identifying and correcting error within health records was explored through these projects. The inherent potential for error and resultant impact on patient safety is highlighted, by considering the context of the record, the content of the record and the process of change from paper-based or piecemeal electronic health records to integrated electronic health records. While the process of change highlights issues of data security and access, it is the variability in starting points for different organizations that possibly poses most risk to patient safety. Issues relating to the content of the record can to some extent be minimized by the effective use of technology, but the tension between coding and qualitative data requires further consideration in terms of its impact on patient safety. This paper concludes that the development of electronic health records has to be viewed within the context of governance and patient safety, and the implications articulated.

Diffusion of Innovation↗

Imatinib mesylate, the first molecularly targeted gene suppressor.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and drug-drug and drug-food interactions of imatinib and the economic considerations of imatinib in the treatment of chronic myeloid leukemia (CML). DATA SOURCES: Literature accessed through MEDLINE (January 1970-January 2002), abstracts from the 2001 annual meetings of the American Society of Clinical Oncology and the American Society of Hematology, imatinib product labeling, and additional studies or abstracts identified from the bibliographies of the reviewed literature were used to compile data. Key search terms were allogeneic bone marrow transplant and stem cell transplant, chronic myeloid leukemia, imatinib, interferon, Gleevec, leukemia, gastrointestinal stromal tumors, STI-571, and tyrosine kinase inhibitors. FINDINGS: Imatinib is a distinctively characteristic drug targeted toward inhibition of tyrosine kinase activity. Imatinib is indicated for the treatment of patients with CML who failed interferon (IFN)-alpha therapy and for the treatment of patients with gastrointestinal stromal tumors (GISTs) expressing the tyrosine kinase receptor c-kit. Imatinib produces positive short-term hematologic and cytogenetic responses in patients with CML; short-term positive objective responses have been shown for patients with GISTs. To our knowledge, there are no controlled trials demonstrating long-term safety, improvement in disease-related symptoms, or increased survival with imatinib. Serious adverse effects requiring dosage decreases and/or therapy termination are edema, hepatotoxicity, and hematologic toxicity. Imatinib also has been found to inhibit tyrosine kinases involved in the growth of other malignancies. The role of imatinib in tumors that express a tyrosine kinase is constantly evolving with new research results. CONCLUSIONS: Imatinib therapy should be limited to patients whose tumor growth is related to a genetically defective tyrosine kinase. In cases of CML, imatinib should be further limited to patients who have tried and failed IFN-alpha therapy or who are not candidates for an allogeneic stem cell transplant.

Antineoplastic Agents↗

Nucleotide sequence analysis of a 32,500 bp region of the right arm of Saccharomyces cerevisiae chromosome IV.

We have sequenced a region containing 32.5 kb of the right arm of chromosome IV of Saccharomyces cerevisiae. Twenty open reading frames (ORFs) greater than 100 amino acids could be identified in this region. Six ORFs correspond to known yeast genes, including DOA4, UBC5 and UBC3, the gene products of which are involved in ubiquitin metabolism. UBC5 is preceded by the two tRNA genes tRNA-Arg2 and tRNA-Asp. Six genes were discovered with homologies to non-yeast genes or with homologies to other yeast ORFs. One of these could be identified as ribosomal protein gene RPS13. The putative function of eight ORFs remains unclear because comparison to different DNA or protein databases revealed no significant patterns. The sequence from cosmid 2F21 was obtained entirely by a combined subcloning and walking primer strategy, and has been deposited in the EMBL data library under Accession Number X84162.

Base Composition↗

Columbia University's Informatics for Diabetes Education and Telemedicine (IDEATel) project: technical implementation.

The Columbia University Informatics for Diabetes Education and Telemedicine IDEATel) project is a four-year demonstration project funded by the Centers for Medicare and Medicaid Services with the overall goal of evaluating the feasibility, acceptability, effectiveness, and cost-effectiveness of telemedicine. The focal point of the intervention is the home telemedicine unit (HTU), which provides four functions: synchronous videoconferencing over standard telephone lines, electronic transmission for fingerstick glucose and blood pressure readings, secure Web-based messaging and clinical data review, and access to Web-based educational materials. The HTU must be usable by elderly patients with no prior computer experience. Providing these functions through the HTU requires tight integration of six components: the HTU itself, case management software, a clinical information system, Web-based educational material, data security, and networking and telecommunications. These six components were integrated through a variety of interfaces, providing a system that works well for patients and providers. With more than 400 HTUs installed, IDEATel has demonstrated the feasibility of large-scale home telemedicine.

Case Management↗

Development of a GIS-based, real-time Internet mapping tool for rabies surveillance.

BACKGROUND: Oral rabies vaccination programs have been implemented to control the spread of wildlife rabies in the United States. However, current surveillance systems are inadequate for the efficient management and evaluation of these large scale vaccine baiting programs. With this in mind, a GIS-based rabies surveillance database and Internet mapping application was created. This surveillance system, RabID, provides a new resource for the rapid mapping and dissemination of data on animal rabies cases in relation to unaffected, enzootic, and baited areas where current interventions are underway. RESULTS: RabID is a centralized database for diagnostic and demographic information collected by local, state, and federal agencies involved in rabies surveillance. The geo-referenced database remits data to an Internet-accessible mapping application that displays rabies surveillance data in relation to environmental and geographic features. CONCLUSION: RabID provides a pioneering example of the power of geographically based Internet-accessible, infectious disease surveillance. This surveillance system was developed from existing technology and is readily adaptable to other infectious diseases and may be particularly useful for zoonoses. The development and application of public health informatics technology may enhance the effectiveness of public health interventions and allow better evaluation of public health interventions.

Animals↗

Health care management. A tool for the future.

As a result of increasing health care costs in the U.S., the skilled, knowledgeable occupational health nurse can implement a plan to reduce these costs with benefits personnel. Using accepted business principles such as the Deming/Shewart cycle, health data can be obtained from the provider, trends can be analyzed, and strategies can be planned for the population. Health and subsequent costs can be managed through the use of the natural history of disease, the three levels of prevention, occupational health nurses' relationships with people, and their access to confidential data. Short-term strategies should include catastrophic and intermediate case management. These systems ensure results in terms of quality and cost.

Accidents, Occupational↗

[Cause of death registry--an important data source for medical research].

Statistics on mortality and cause of death are of crucial importance to epidemiological research. The Cause of Death Register kept by Statistics Norway is the only national register including information on cause of death for all deceased persons registered as residents in Norway at their time of death, whether death occurred in Norway or abroad. This article presents historical information and guidelines for research access to individual data on cause of death.

Cause of Death↗

A model for the interim analysis process: a case study.

To evaluate data from a clinical trial before its completion, researchers routinely perform interim analyses. However, if not performed carefully, interim analyses can compromise the integrity of a clinical trial. In the last 10-15 years, regulatory authorities and the pharmaceutical industry have developed procedures and guidelines to allow trial sponsors access to unblinded data in an ongoing clinical trial without affecting the outcome. In December 1996, Abbott Laboratories was codeveloping a drug for treatment of an autoimmune disease. The pivotal phase II/III trial for the new drug application was very expensive, large, long term, and slow-accruing. The trial was initiated with a great deal of uncertainty concerning the safety and efficacy of the proposed treatment. An interim analysis was a logical part of the trial design. Two interim analyses were performed; the second analysis resulted in early termination of the trial. This article describes the interim analysis, including the process used for planning and execution and the lessons learned from the experience. In addition, the methodology for performing an interim analysis and the roles and responsibilities of involved members are discussed.

Clinical Trials Data Monitoring Committees↗

Collecting behavioural data using the world wide web: considerations for researchers.

OBJECTIVE: To identify and describe advantages, challenges, and ethical considerations of web based behavioural data collection. METHODS: This discussion is based on the authors' experiences in survey development and study design, respondent recruitment, and internet research, and on the experiences of others as found in the literature. RESULTS: The advantages of using the world wide web to collect behavioural data include rapid access to numerous potential respondents and previously hidden populations, respondent openness and full participation, opportunities for student research, and reduced research costs. Challenges identified include issues related to sampling and sample representativeness, competition for the attention of respondents, and potential limitations resulting from the much cited "digital divide", literacy, and disability. Ethical considerations include anonymity and privacy, providing and substantiating informed consent, and potential risks of malfeasance. CONCLUSIONS: Computer mediated communications, including electronic mail, the world wide web, and interactive programs will play an ever increasing part in the future of behavioural science research. Justifiable concerns regarding the use of the world wide web in research exist, but as access to, and use of, the internet becomes more widely and representatively distributed globally, the world wide web will become more applicable. In fact, the world wide web may be the only research tool able to reach some previously hidden population subgroups. Furthermore, many of the criticisms of online data collection are common to other survey research methodologies.

Behavioral Research↗

Use of in vivo genetic toxicity data for risk assessment.

Mutagenicity studies have been used to identify specific agents as potential carcinogens or other human health hazards; however, they have been used minimally for risk assessment or in determining permissible levels of human exposure. The poor predictive value of in vitro mutagenesis tests for carcinogenic activity and a lack of mechanistic understanding of the roles of mutagens in the induction of specific cancers have made these tests unattractive for the purpose of risk assessment. However, the limited resources available for carcinogen testing and large number of chemicals which need to be evaluated necessitate the incorporation of more efficient methods into the evaluation process. In vivo genetic toxicity testing can be recommended for this purpose because in vivo assays incorporate the metabolic activation pathways that are relevant to humans. We propose the use of a multiple end-point in vivo comprehensive testing protocol (CTP) using rodents. Studies using sub-acute exposure to low levels of test agents by routes consistent with human exposure can be a useful adjunct to methods currently used to provide data for risk assessment. Evaluations can include metabolic and pharmacokinetic endpoints, in addition to genetic toxicity studies, in order to provide a comprehensive examination of the mechanism of toxicity of the agent. A parallelogram approach can be used to estimate effects in non-accessible human tissues by using data from accessible human tissues and analogous tissues in animals. A categorical risk assessment procedure can be used which would consider, in order of priority, genetic damage in man, genetic damage in animals that is highly relevant to disease outcome (mutation, chromosome damage), and data from animals that is of less certain relevance to disease. Action levels of environmental exposure would be determined based on the lowest observed effect levels or the highest observed no effect levels, using sub-acute low level exposure studies in rodents. As an example, the known genotoxic effects of benzene exposure at low levels in man and animals are discussed. The lowest observed genotoxic effects were observed at about 1-10 parts per million for man and 0.04-0.1 parts per million in subacute animal studies. If genetic toxicity is to achieve a prominent role in evaluating carcinogens and in characterizing germ-cell mutagens, minimal testing requirements must be established to ascertain the risks associated with environmental mutagen exposure. The use of the in vivo approach described here should provide the information needed to meet this goal.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Sequencing of a 17.6 kb segment on the right arm of yeast chromosome VII reveals 12 ORFs, including CCT, ADE3 and TR-I genes, homologues of the yeast PMT and EF1G genes, of the human and bacterial electron-transferring flavoproteins (beta-chain) and of the Escherichia coli phosphoserine phosphohydrolase, and five new ORFs.

A 17.6 kb DNA fragment from the right arm of chromosome VII of Saccharomyces cerevisiae has been sequenced and analysed. The sequence contains twelve open reading frames (ORFs) longer than 100 amino acids. Three genes had already been cloned and sequenced: CCT, ADE3 and TR-I. Two ORFs are similar to other yeast genes: G7722 with the YAL023 (PMT2) and PMT1 genes, encoding two integral membrane proteins, and G7727 with the first half of the genes encoding elongation factors 1gamma, TEF3 and TEF4. Two other ORFs, G7742 and G7744, are most probably yeast orthologues of the human and Paracoccus denitrificans electron-transferring flavoproteins (beta chain) and of the Escherichia coli phosphoserine phosphohydrolase. The five remaining identified ORFs do not show detectable homology with other protein sequences deposited in data banks. The sequence has been deposited in the EMBL data library under Accession Number Z49133.

Amino Acid Sequence↗

Strengthening capacity in developing countries for evidence-based public health: the data for decision-making project.

Public health officials and the communities they serve need to: identify priority health problems; formulate effective health policies; respond to public health emergencies; select, implement, and evaluate cost-effective interventions to prevent and control disease and injury; and allocate human and financial resources. Despite agreement that rational, data-based decisions will lead to improved health outcomes, many public health decisions appear to be made intuitively or politically. During 1991-1996, the US Centers for Disease Control and Prevention implemented the US Agency for International Development funded Data for Decision-Making (DDM) Project. DDM goals were to: (a) strengthen the capacity of decision makers to identify data needs for solving problems and to interpret and use data appropriately for public health decisions; (b) enhance the capacity of technical advisors to provide valid, essential, and timely data to decision makers clearly and effectively; and (c) strengthen health information systems (HISs) to facilitate the collection, analysis, reporting, presentation, and use of data at local, district, regional, and national levels. Assessments were conducted to identify important health problems, problem-driven implementation plans with data-based solutions as objectives were developed, interdisciplinary, in-service training programs for mid-level policy makers, program managers, and technical advisors in applied epidemiology, management and leadership, communications, economic evaluation, and HISs were designed and implemented, national staff were trained in the refinement of HISs to improve access to essential data from multiple sources, and the effectiveness of the strategy was evaluated. This strategy was tested in Bolivia, Cameroon, Mexico, and the Philippines, where decentralization of health services led to a need to strengthen the capacity of policy makers and health officers at sub-national levels to use information more effectively. Results showed that the DDM strategy improved evidence-based public health. Subsequently, DDM concepts and practices have been institutionalized in participating countries and at CDC.

Bolivia↗