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PubMed2002

AFLP diversity in the common vetch ( Vicia sativa L.) on the world scale.

The Vavilov Institute of Plant Industry (VIR) keeps a living seed collection of about 700 accessions of landraces and local cultivars of common vetch ( Vicia sativa L.) that have been collected over a period of more than 50 years throughout the former USSR. Much of the material is available nowhere else. The collection of this economically important fodder crop is well adapted to the various growing regions of Russia and serves as a basis for the all domestic vetch breeding programs. Using AFLP as a DNA fingerprinting method we investigated 673 accessions from the VIR and compared their genetic variability with that of the worldwide vetch collection of the Institut für Pflanzengenetik und Kulturpflanzenforschung (IPK), 450 accessions. The analysis is a first assessment of the intra-specific diversity of V. sativa stored ex situ on a scale of more than 1,000 accessions. Six primer combinations, which gave clear polymorphic amplification products with 96 test samples, were chosen from 111 primer combinations tested. The selected AFLP primers used to analyse the V. sativa intra-specific diversity resulted in 70 unequivocally recognizable polymorphic fragments. We found that all of the AFLP fragments generated can be detected with varying frequency throughout the entire distribution area of V. sativa. The difference in frequency of some AFLP fragments between the regions may amount to 90%. The arrangement of most of the accessions in all dendrograms reflects their geographical origin, with a differentiation between Russia, Western Europe, Turkey and Bulgaria, and the Mediterranean. The "Russian" genepool stored at the IPK is a limited and biased sample of the available diversity when compared to the material stored at the VIR. Approximately 10-15% of the accessions in each geographical group showed AFLP patterns that clustered with members of other groups. This appreciable overlap raises several questions: (1) to which degree is an AFLP pattern representative of the overall genetic similarity of the samples; (2) to which degree are samples collected at a site adaptively limited to that site? Since our data identify accessions with very similar AFLP patterns from very diverse geographic origins, a comparison of the agronomic performance of these accessions (possibly in the two regions) will provide important information for the utilization of ex situ germplasm collections.

Journal Article↗

PubMedDate not supplied

A searchable database for comparing protein-ligand binding sites for the analysis of structure-function relationships.

The rapid expansion of structural information for protein-ligand binding sites is potentially an important source of information in structure-based drug design and in understanding ligand cross reactivity and toxicity. We have developed a large database of ligand binding sites extracted automatically from the Protein Data Bank. This has been combined with a method for calculating binding site similarity based on geometric hashing to create a relational database for the retrieval of site similarity and binding site superposition. It contains an all-against-all comparison of binding sites and holds known protein-ligand binding sites, which are made accessible to data mining. Here we demonstrate its utility in two structure-based applications: in determining site similarity and in aiding the derivation of a receptor-based pharmacophore model. The database is available from http://www.bioinformatics.leeds.ac.uk/sb/.

Binding Sites↗

PubMed2002

Limitations of inferences from observational databases in amyotrophic lateral sclerosis: all that glitters is not gold.

Data from three observational databases have suggested that survival in patients with ALS who take riluzole is far greater than that reported in randomized controlled studies. This editorial discusses why therapeutic efficacy cannot be inferred from observational databases. Data in these databases cannot control for biases in treatment assignment or for differences in intensity of follow-up or supportive care. The retrospective riluzole data, as presented so far, have not demonstrated comparability between the treated and untreated groups across all known prognostic factors, including vital capacity at the start of the observation period. Furthermore, the similarity of untreated patients to historical cohorts likely reflects adverse selection. Optimization of analysis in retrospective studies may be accomplished by allowing full access to data to all interested parties.

Amyotrophic Lateral Sclerosis↗

PubMedDate not supplied

Lines of evidence on the risks of suicide with selective serotonin reuptake inhibitors.

BACKGROUND: There has been a long-standing controversy about the possibility that selective serotonin reuptake inhibitor (SSRI) antidepressants might induce suicidality in some patients. METHODS: Starting from the clinical studies that gave rise to this issue, this paper reviews an unselected cohort of randomized clinical trials (RCTs), a series of meta-analyses undertaken to investigate aspects of the problem, studies in recurrent brief depressive disorders, epidemiological studies and healthy volunteer studies using SSRIs to shed light on this issue. RESULTS: The original clinical studies produced evidence of a dose-dependent link, present on a challenge, dechallenge and rechallenge basis, between SSRIs and both agitation and suicidality. Meta-analyses of RCTs conducted around this time indicate that SSRIs may reduce suicidal ideation in some patients. These same RCTs, however, yield an excess of suicides and suicide attempts on active treatments compared with placebos. This excess also appears in the best-controlled epidemiological studies. Finally, healthy volunteer studies give indications that SSRIs may induce agitation and suicidality in some individuals. CONCLUSIONS: The data reviewed here, which indicate a possible doubling of the relative risk of both suicides and suicide attempts on SSRIs compared with older antidepressants or non-treatment, make it difficult to sustain a null hypothesis, i.e. that SSRIs do not cause problems in some individuals to whom they are given. Further studies or further access to data are indicated to establish the magnitude of any risk and the characteristics of patients who may be most at risk.

Antidepressive Agents↗

PubMed1999

Street outreach for homeless persons with serious mental illness: is it effective?

OBJECTIVES: This study examined data on case management clients who are homeless and have a severe mental illness to determine how those contacted through street outreach differ in their socio-demographic characteristics, service needs, and outcomes from those clients contacted in shelters and other health and social service agencies. METHODS: As part of the Center for Mental Health Services' Access to Community Care and Effective Services and Supports (ACCESS) program, data were obtained from potential clients over the first 3 years of the program at the time of the first outreach contact (n = 11,857), at the time of enrollment in the case management program (n = 5,431), and 3 months after enrollment (n = 4,587). RESULTS: Clients contacted at outreach on the street, as opposed to being contacted in shelters and service agencies, were generally worse off. They were more likely to be male, to be older, to spend more nights literally homeless before the contact, to have psychotic disorders, and took longer to engage in case management. They expressed less interest in treatment and were less likely to enroll in the case management phase of the project. Subjects contacted on the street who did enroll were more impaired than their street counterparts who did not enroll. Three month outcome data showed that enrolled clients contacted through street outreach showed improvement that was equivalent to those enrolled clients contacted in shelters and other service agencies on nearly all outcome measures. CONCLUSION: Street outreach to homeless persons with serious mental illness is justified as these clients are more severely impaired, have more basic service needs, are less motivated to seek treatment, and take longer to engage than those contacted in other settings. Street outreach is further justified as it engages the most severely impaired among the street population. Street outreach also appears to be effective as the clients reached in this way showed improvement equal to that of other clients in most outcome domains when baseline differences were taken into account.

Adult↗

PubMed2004

Cardiovascular outcomes of pediatric seroreverters perinatally exposed to HAART: design of a longitudinal clinical study.

Seroreverters (uninfected children of HIV-infected mothers) have exhibited left ventricular (LV) dysfunction. Mitochondrial toxicity associated with in utero or postnatal exposure to highly active antiretroviral therapy (HAART) is a possible mechanism. Adult and animal models have demonstrated associations between LV abnormalities, cardiomyopathy, and components of HAART. Yet, outcomes in children are poorly understood. In this study, we explore HAART-associated LV abnormalities in seroreverters exposed to HAART (n = 144) or never exposed (n = 252). Subjects are drawn from the Women and Infants Transmission Study and the Pediatric Pulmonary and Cardiovascular Complications of HIV Study, respectively. Data include (1) echocardiographic studies of LV structure and function and (2) serologic cardiac biomarkers (cardiac troponin, probrain natriuretic peptide, high-sensitivity C reactive protein), both collected during the first month of life, and again at 6, 12, 24, 36, and 48 months postnatally. Planned analyses include several regression models. At this time, we have access to data for all 252 unexposed children, and 53 exposed subjects are enrolled. The cohorts are similar in terms of gender and race and the recruited subjects are representative of all eligible subjects in terms of exposure to HAART. Recruitment will continue into 2006.

Adult↗

PubMed1999

Molecular characterization and in situ localization of a full-length cyclic nucleotide-gated channel in rat brain.

Ion channels gated directly by cyclic nucleotides are required for the transduction of sensory signals in photoreceptor cells and olfactory cells. Cyclic nucleotide-gated (CNG) channels may also be expressed in the central nervous system because partial transcripts that share homology with CNG channels have been found therein. We have now isolated and cloned a full-length CNG channel cDNA from adult rat brain. The sequence is identical to that of the alpha-subunit originally found in the olfactory epithelium (CNCalpha3). In situ hybridization, using probes specific for the CNCalpha3 mRNA, suggest that this channel is expressed widely in the rat brain, albeit mostly at relatively low levels. Certain neuronal populations, however, such as deep cerebellar nuclei, olfactory bulb mitral cells and cerebellar Purkinje neurons, appeared specially enriched. The study demonstrates for the first time that a full-length CNG channel mRNA is expressed in the brain, supporting the possibility that CNG channels are involved in central neural communication and plasticity. The sequence reported in this paper has been deposited in the GenBank data base (accession no. AF126808).

Animals↗

PubMed1999

Peripheral database module for clinical management and research in sleep medicine.

Hospital-wide information systems may provide economical solutions for communication processes or for documentation by means of centralized digital medical records. Within a large university hospital, however, there may be too many diverse subspecialties and too many special medical procedures to be supported comprehensively by a single database information system. A peripheral modular system has been tailored to the specific needs of a sleep disorder clinic as an adjunct to the main clinical information system. The client server application allows for automatic data acquisition by on-line devices and by a graphical user interface. It supports administrative tasks for patient management, specific encounter interactions and data retrieval for research. Performance and acceptance of the system was assessed during clinical use, revealing positive response by the users, also with respect to significant time savings. Our experience suggests that the concept of peripheral database modules as "satellites" to a main clinical system provides flexibility in design and implementation of the specialized databases while providing access to data of more general relevance via the main database.

Database Management Systems↗

PubMed2000

Family practice research networks. Experiences from 3 countries.

Access to data about the clinical problems, patients, and processes that characterise family practice is essential for the development of this specialty. Practice-based research networks (PBRNs) play an increasing role in obtaining these data. We compared 3 PBRNs: one in Wisconsin in the United States, one in Wessex in the United Kingdom, and one in Nijmegen in the Netherlands. We organized our data into 4 key areas for review: the mission of the network, its contribution to the evidence base of family medicine, the management of the network, and the financing of the network infrastructure. Extending the evidence base of family practice is the overriding objective of these networks, and their main focus is on common morbidities. They provide access to unselected patient populations, but there are differences in their size. There are aspects of PBRNs that are common in countries with different health care systems, despite the fact that local circumstances--the research mission or the characteristics of the health care system under which they operate--determine their form and structure. Networks develop over time and their focus and activities may evolve. Financial support for these networks continues to be a problem.

Family Practice↗

PubMed1996

The incidence and prevalence of AIDS and prevalence of other severe HIV disease in England and Wales for 1995 to 1999: projections using data to the end of 1994.

Projections of the future incidence of AIDS cases are needed for planning purposes, to help set research priorities, and to describe the most likely pattern of transmission of HIV infection in the past that underlies the observed and projected incidence of AIDS. Earlier reports of projections for England and Wales were published in 1988, 1990, and 1993. During 1995 a group of experts has worked, using AIDS case reports to the end of December 1994, to make new projections to the end of 1999. The expert group concludes that, after adjustment for underreporting, there will be between 1840 and 2300 new cases of AIDS in England and Wales in 1997, and between 1760 and 2455 new AIDS cases in 1999. For planning purposes, a figure of 2025 new AIDS cases is projected for 1997, and 2010 for 1999. The planning projections for new AIDS cases in 1997 and 1999 among the main exposure categories, after adjustment for underreporting, are as follows: homo/bisexual males 1305 and 1235, people exposed heterosexually 490 and 525, and injecting drug users 140 and 155. Between 1995 and 1999, it is expected that new AIDS cases may fall by 7% in homo/bisexual males, and rise by 25% in the heterosexual exposure category and by 29% in injecting drug users. The incidence of AIDS in the children of mothers infected with HIV is expected to rise steadily from 30 new cases in 1994 to 45 in 1997 and 55 in 1999. New cases in recipients of contaminated blood or blood factors are expected to fall to 35 in 1997 and 30 in 1999, compared with a peak 10 years earlier of over 70 new cases each year. It is projected that 4010 AIDS cases will be alive in England and Wales at the end of 1999, and that the same number of people will be alive with other forms of severe HIV disease. Since 1989 the proportion of reported AIDS cases who live in the NHS Thames regions has remained constant at between 70% and 75%. We expect this concentration of AIDS cases in the south east, particularly within London, to remain unchanged. Compared with the report published in June 1993, the planning projections for 1997 are 37% lower for cases acquired heterosexually, and the upper boundary of the range in this exposure category has fallen from 1140 to 495. The reduction in the planning projection has resulted from a substantial decline in the rate of increase in the number of new AIDS cases arising each year from heterosexual exposure. The range of uncertainty has narrowed largely because more extensive seroprevalence data are now available. For homo/bisexual males, the planning projection for 1997 has fallen by 3%, because the 1993 report presented an over optimistic view of the extent to which patients received treatment and prophylaxis before the onset of AIDS, since such management became available in 1988. Unlike the 1993 working group, the 1995 working group has access to data from several years on the uptake of treatment and prophylaxis given before the diagnosis of AIDS. It is estimated that about 21,900 adults (range 20,400 to 23,400) were infected with HIV in England and Wales at the end of 1993. This total includes 12,350 who had been infected through male homosexual exposure, 2050 men and women infected through injecting drug use, 6800 men and women infected through heterosexual exposure, and about 3000 adults alive with AIDS. Various data indicate that HIV transmission among homo/bisexual men has been substantial since 1989. Use of data from the unlinked anonymous HIV prevalence monitoring programme suggest that between 500 and 1000 HIV infections due to homosexual male exposure occurred each year in 1992 and 1993. Should HIV transmission continue at this level, a high incidence of AIDS within the homo/bisexual male community will be inevitable for many more years. Most HIV infections and AIDS cases due to heterosexual exposure are thought to have been acquired abroad. The future of the epidemic in this exposure category is therefore unclear.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Crystal structure of the outer membrane protease OmpT from Escherichia coli suggests a novel catalytic site.

OmpT from Escherichia coli belongs to a family of highly homologous outer membrane proteases, known as omptins, which are implicated in the virulence of several pathogenic Gram-negative bacteria. Here we present the crystal structure of OmpT, which shows a 10-stranded antiparallel beta-barrel that protrudes far from the lipid bilayer into the extracellular space. We identified a putative binding site for lipopolysaccharide, a molecule that is essential for OmpT activity. The proteolytic site is located in a groove at the extracellular top of the vase-shaped beta-barrel. Based on the constellation of active site residues, we propose a novel proteolytic mechanism, involving a His-Asp dyad and an Asp-Asp couple that activate a putative nucleophilic water molecule. The active site is fully conserved within the omptin family. Therefore, the structure described here provides a sound basis for the design of drugs against omptin-mediated bacterial pathogenesis. Coordinates are in the Protein Data Bank (accession No. 1I78)

Amino Acid Sequence↗

PubMed2002

From asthma to AirBeat: community-driven monitoring of fine particles and black carbon in Roxbury, Massachusetts.

Asthma is an ongoing environmental justice concern in Roxbury, an urban neighborhood of Boston, Massachusetts. Residents, especially local youth, were the first to investigate the potential links between high asthma rates and air pollution, particularly from diesel buses and trucks. A youth-led march for clean air and community air monitoring projects drew governmental and media attention to these problems. In 1998, a collaboration of environmental justice, government, and research groups came together to develop a real-time air pollution monitoring system known as AirBeat. This community-based participatory research project was designed to answer community questions about whether there are pollution "hot spots" in Roxbury and the degree to which diesel emissions are contributing to health problems. AirBeat measures and reports levels of PM2.5 (particulate matter with a mass median aerodynamic diameter < or= to 2.5 microm), ozone, and black carbon on an hourly basis. These data are accessible via a website, telephone hotline, and a flag warning system. AirBeat is successful because community residents and organizations participate as equal partners with an equitable share of funding. The project also promotes a community sense of ownership and pride. Dozens of youth have developed leadership and scientific skills. The media have extensively covered the project as a community victory. The data support the claim that Dudley Square in Roxbury is a hot spot for air pollution. This information is now being used to advocate for alternative fuel transit buses and other clean air measures. Finally, this project has strengthened community partnerships with research and governmental institutions.

Air Pollutants↗

PubMed1990

MediNet: Singapore's nationwide medical network.

MediNet is Singapore's nationwide computer network for the medical and health care community. This paper presents the case for MediNet and discusses the five high-priority applications which would be implemented by 1993. These 5 pilot applications focus on the processing of claims in hospital bills, electronic procurement of medical and surgical supplies, the transmission of notifications to government agencies, a national patient master index and access to local and foreign databases. MediNet will be able to link the computer systems of all participants in the healthcare delivery system. These include the Ministry of Health, Central Provident Fund (CPF) Board, government, restructured and private hospitals and general practice clinics. By connecting their computers (personal computers, minicomputers and mainframes) to MediNet, these organisations will be able to communicate, exchange data and access common applications on the network.

Computer Communication Networks↗

PubMedDate not supplied

Visualizing 3D data obtained from microscopy on the Internet.

The Internet is a powerful communication medium increasingly exploited by business and science alike, especially in structural biology and bioinformatics. The traditional presentation of static two-dimensional images of real-world objects on the limited medium of paper can now be shown interactively in three dimensions. Many facets of this new capability have already been developed, particularly in the form of VRML (virtual reality modeling language), but there is a need to extend this capability for visualizing scientific data. Here we introduce a real-time isosurfacing node for VRML, based on the marching cube approach, allowing interactive isosurfacing. A second node does three-dimensional (3D) texture-based volume-rendering for a variety of representations. The use of computers in the microscopic and structural biosciences is extensive, and many scientific file formats exist. To overcome the problem of accessing such data from VRML and other tools, we implemented extensions to SGI's IFL (image format library). IFL is a file format abstraction layer defining communication between a program and a data file. These technologies are developed in support of the BioImage project, aiming to establish a database prototype for multidimensional microscopic data with the ability to view the data within a 3D interactive environment.

Animals↗

PubMed1997

HOSEpipe--a WWW-hosted data management and analysis system for STS content mapping projects.

We have developed a data management system, 'HOSEpipe' (High Output STS Evaluation pipeline) to aid sample tracking and data analysis in STS content mapping projects. The system is based around a World Wide Web (WWW) server that provides a number of pages including forms for sample processing and data entry accessible via a standard WWW browser application. The system is split into two main modules: firstly, a sequence evaluation and annotation module that takes de novo sequence for a potential STS, screens it against existing STSs and DNA sequence databases, followed by appropriate primer sequence design; secondly, a module that handles YAC library STS screening and includes facilities for both sample tracking and experimental data analysis. We present the design and rationale of the HOSEpipe system and its development to support a whole chromosomal physical mapping project. This software and design approach is potentially applicable to physical mapping projects of varying sizes and resolution and to similar projects, such as sample sequencing and the construction of sequence-ready maps.

Animals↗

PubMed2004

Making medical research clinically friendly: a communication-based conceptual framework.

CONTEXT: It often takes a long time before the results of medical research are actually used by health care practitioners in day-to-day clinical settings. This problem, referred to as "the evidence-to-practice gap", has significant implications for patient health care. Practitioners have difficulty keeping up with the latest information in part because it is reported in hundreds of journals that may not be easily accessed and understood. APPROACH: This essay conceptualizes the evidence-to-practice gap as a communication problem and suggests how academic research can be translated into messages that are easier for practitioners to access, comprehend and incorporate into their medical practice. A "translation framework" shows the importance of targeting messages to specific audiences and provides a communication-based conceptual approach for summarizing research for clinicians. PRACTICAL IMPLICATIONS: Targeting the results of academic research to practitioners will decrease the time it takes for patients to benefit from the latest medical evidence. Translation guidelines can help health researchers write more effectively for both academic and practitioner audiences. Since the evidence-to-practice gap is a systemic problem that begins with how we train our health researchers, educators should consider addressing this topic in the health professions classroom. The framework presented here can serve as the basis for an instructional unit on interpreting and reporting research findings. Finally, information technology can play a much larger role in the communication process because of the enormous advantages of quick access and data organization that computers and the Internet provide. Practitioner-targeted research summaries could be made available on government or not-for-profit sponsored websites as well as by journals themselves. Funding opportunities exist for research that focuses on how technology can help improve health care, and so the time is right for health researchers to investigate ways of making their studies more accessible and quickly usable via web-based distribution. The potential of medical science should not be limited by an information delivery system that we have the knowledge, expertise and resources to improve.

Biomedical Research↗

PubMed1985

[Social disparities in medical consumption].

Our study stems from a micro-economic survey of medical expenditure in the Lyons region carried out within the framework of a research programme organised by the National Centre for Scientific Research. This study is based on a sampling of 3500 households (or 10,000 individuals) taken from the Lyons Institute of Statistics and Economic Studies. Information on individual medical expenditure was taken from Social Security files and from the different hospital establishments involved in the enquiry. The analysis was mainly orientated, on the one hand, towards socio-economic factors whose role in the demand for medical care has only recently been established, and, on the other hand, towards factors of supply whose incidence on individual behaviour still remains insufficiently considered. Our results confirmed that the major criterion of social differentiation was to be found in 'an alternative form' of expenditure. There are significant variations in the type of goods and services in the private sector: in the preferred 'choice' made in favour of either private or public health care; in the nature of the demand for hospitalisation. It is probably, however, in regard to supply, that the data of the Lyonnais enquiry have provided the most interesting conclusions. In private hospital care it was seen that supply could have an autonomous effect on individual medical expenditure in a manner relatively independent of social stratum. As regards hospitalisation, a study on patterns in hospital admission brought to light a polarizing effect on the demand for hospital admission around hospitals and clinics located in the residence area of the inpatients. The phenomenon of 'self-admission' observed operates in a manner relatively independent of the social background of the individual and also very often independently of the public or private nature of the beds at the establishment's disposal. There followed a substitution effect between the public sector on the one hand and the profit-making private sector on the other. Geographical location, however, has no bearing on certain individual choices. In conclusion, it appeared that the logic of social differentiation on the one hand, and the logic of the system of supply on the other, were not absolutely distinct. However, the need for a sound understanding of the complex relations which form between the supply and demand of medical care should necessarily require access to data in individual illness.

Catchment Area, Health↗

PubMed2005

Academic medical centers' standards for clinical-trial agreements with industry.

BACKGROUND: Although industry sponsors provide approximately 70 percent of the funding for clinical drug trials in the United States, little is known about the legal agreements that exist between industry sponsors and academic investigators. We studied institutional standards regarding contractual provisions that restrict investigators' control over trials. METHODS: We used a structured, cross-sectional mail survey of medical-school research administrators responsible for negotiating clinical-trial agreements with industry sponsors. RESULTS: Of 122 institutions approached, 107 participated. There was a high degree of consensus among administrators about the acceptability of several contractual provisions relating to publications. For example, more than 85 percent reported that their office would not approve provisions giving industry sponsors the authority to revise manuscripts or decide whether results should be published. There was considerable disagreement about the acceptability of provisions allowing the sponsor to insert its own statistical analyses in manuscripts (24 percent allowed them, 47 percent disallowed them, and 29 percent were not sure whether they should allow them), draft the manuscript (50 percent allowed it, 40 percent disallowed it, and 11 percent were not sure whether they should allow it), and prohibit investigators from sharing data with third parties after the trial is over (41 percent allowed it, 34 percent disallowed it, and 24 percent were not sure whether they should allow it). Disputes were common after the agreements had been signed and most frequently centered on payment (75 percent of administrators reported at least one such dispute in the previous year), intellectual property (30 percent), and control of or access to data (17 percent). CONCLUSIONS: Standards for certain restrictive provisions in clinical-trial agreements with industry sponsors vary considerably among academic medical centers. Greater sharing of information about legal relationships with industry sponsors is desirable in order to build consensus about appropriate standards.

Academic Medical Centers↗