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PubMed2006

Agents in bioinformatics, computational and systems biology.

The adoption of agent technologies and multi-agent systems constitutes an emerging area in bioinformatics. In this article, we report on the activity of the Working Group on Agents in Bioinformatics (BIOAGENTS) founded during the first AgentLink III Technical Forum meeting on the 2nd of July, 2004, in Rome. The meeting provided an opportunity for seeding collaborations between the agent and bioinformatics communities to develop a different (agent-based) approach of computational frameworks both for data analysis and management in bioinformatics and for systems modelling and simulation in computational and systems biology. The collaborations gave rise to applications and integrated tools that we summarize and discuss in context of the state of the art in this area. We investigate on future challenges and argue that the field should still be explored from many perspectives ranging from bio-conceptual languages for agent-based simulation, to the definition of bio-ontology-based declarative languages to be used by information agents, and to the adoption of agents for computational grids.

Artificial Intelligence↗
PubMed2000

Resolution of the phase-ambiguity problem in the centrosymmetric P [1] space group by Monte Carlo methods.

Simulated-annealing methods have been used to resolve the phase-ambiguity problem in the centrosymmetric P¿bar¿1¿ space group. First, an energy function based on the Sayre equation is introduced and a formal comparison with classical spin systems is drawn. The energy landscape is studied in detail and the validity of several energy criteria thoroughly tested. Classical Monte Carlo methods proved to be successful using a multistart optimization of the Sayre score, along with the additional monitoring of other energetic criteria. These involved the Terwilliger map quality index in reciprocal space in the absence of envelope information, and an envelope score if the shape of the molecule is known. The inherent phase-ambiguity problem of the P¿bar¿1¿ space group was therefore technically solved by Monte Carlo methods. The method should also work to resolve phase ambiguity in the SIR method of protein crystallography.

Computer Simulation↗
PubMed1999

ICH-harmonised guidances on genotoxicity testing of pharmaceuticals: evolution, reasoning and impact.

The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) has convened an expert working group which consisted of the authors of this paper and their respective committees, consulting groups and task forces. Two ICH guidances regarding genotoxicity testing have been issued: S2A, 'Guidance on Specific Aspects of Regulatory Genotoxicity Tests' and S2B, 'Genotoxicity: A Standard Battery for Genotoxicity Testing of Pharmaceuticals.' Together, these guidance documents now form the regulatory backbone for genotoxicity testing and assessment of pharmaceuticals in the European Union, Japan, and the USA. These guidances do not constitute a revolutionary new approach to genotoxicity testing and assessment, instead they are an evolution from preexisting regional guidelines, guidances and technical approaches. Both guidances describe a number of specific criteria as well as a general test philosophy in genotoxicity testing. Although these guidances were previously released within the participating regions in their respective regulatory communiqués, to ensure their wider distribution and better understanding, the texts of the guidances are reproduced here in their entirety (see Appendix A) and the background for the recommendations are described. The establishment of a standard battery for genotoxicity testing of pharmaceuticals was one of the most important issues of the harmonisation effort. This battery currently consists of: (i) a test for gene mutation in bacteria, (ii) an in vitro test with cytogenetic evaluation of chromosomal damage with mammalian cells or an in vitro mouse lymphoma tk assay, (iii) an in vivo test for chromosomal damage using rodent hematopoietic cells. A major change in testing philosophy is the acceptance of the interchangeability of testing for chromosomal aberrations in mammalian cells and the mouse lymphoma tk assay. This agreement was reached on the basis of the extensive review of databases and newly generated experimental data which are in part described in this publication. The authors are fully aware of the fact that some of the recommendations given in these ICH guidances are transient in nature and that the dynamic qualities and ongoing evolution of genetic toxicology makes necessary a continuous maintenance process that would serve to update the guidance as necessary.

Animals↗
PubMed2006

Evaluation of ZAP-70 expression by flow cytometry in chronic lymphocytic leukemia: A multicentric international harmonization process.

The clinical course of patients with chronic lymphocytic leukemia (CLL) is heterogeneous with some patients requiring early therapy whereas others will not be treated for years. The evaluation of an individual CLL patient's prognosis remains a problematic issue. The presence or absence of somatic mutations in the IgVH genes is currently the gold-standard prognostic factor, but this technique is labor intensive and costly. Genomic studies uncovered that 70 kDa zeta-associated protein (ZAP-70) expression was associated with unmutated IgVH genes and ZAP-70 protein expression was proposed as a surrogate for somatic mutational status. Among the available techniques for ZAP-70 detection, flow cytometry is most preferable as it allows the simultaneous quantification of ZAP-70 protein expression levels in CLL cells and residual normal lymphocyte subsets. However, several factors introduce variability in the results reported from different laboratories; these factors include the anti-ZAP-70 antibody clone and conjugate, the staining procedure, the gating strategy, and the method of reporting the results. The need for standardization of the approach led to the organization of an international working group focused on harmonizing all aspects of the technique. During this workshop, a technical consensus was reached on the methods for cell permeabilization and immunophenotyping procedures. An assay was then designed that allowed comparison of two clones of anti-ZAP-70 antibody and the identification of the expression of this molecule in B, T, and NK cells identified in a four multicolor analysis. This procedure was applied to three stabilized blood samples, provided by the UK NEQAS group to all participating members of this study, in order to minimize variability caused by sample storage and shipment. Analysis was performed in 20 laboratories providing interpretable data from 14 centers. Various gating strategies were used and the ZAP-70 levels were expressed as percentage positive (POS) relative to isotype control or normal B-cells or normal T-cells; in addition the levels were reported as a ratio of expression in CLL cells relative to T-cells. The reported level of ZAP-70 expression varied greatly depending on the antibody and the method used to express the results. The CLL/T-cell ZAP-70 expression ratio showed a much lower interlaboratory variation than other reporting strategies and is recommended for multicenter studies. Stabilization results in decreased expression of CD19 making gating more difficult and therefore stabilized samples are not optimal for multicentric analysis of ZAP-70 expression. We assessed the variation of ZAP-70 expression levels in fresh cells according to storage time, which demonstrated that ZAP-70 is labile but sufficiently stable to allow comparison using fresh samples distributed between labs in Europe. These studies have demonstrated progress toward a consensus reporting procedure, and further work is underway to harmonize the preparation and analysis procedures.

Antibodies, Monoclonal↗
PubMed1991

[Theoretical surgery and making a clinical decision].

Theoretical surgery--if available in departments of surgery--participates in clinical decisions as a supportive system with concepts, structures, and methods of formal (statistical) and heuristic (problem-solving, individual) decision making. Decision making for groups of patients and for individual subjects is not identical, but also not mutually exclusive. Decision support is realized in terms of a defined instrument: the permanent, integrated working team of surgeons, theoretical surgeons, technical staff, and medical students. Hence the process and progress of decision support is determined by the effectiveness of these working groups.

Diagnosis↗
PubMed1991

Hemodynamic monitoring: a technology assessment. Technology Subcommittee of the Working Group on Critical Care, Ontario Ministry of Health.

OBJECTIVE: To review catheterization of the right side of the heart according to technical capability, diagnostic accuracy, range of possible uses, therapeutic impact, benefit to patient outcome and impact on health care workers. DATA SOURCES: MEDLINE was searched for English-language articles published since 1962. Additional references were selected from the bibliographies of identified articles. STUDY SELECTION: Nonrandomized trials and retrospective reviews were included because of a paucity of randomized controlled trials. DATA EXTRACTION AND SYNTHESIS: After a review of the data on hemodynamic monitoring by the subcommittee members, guidelines were developed through the use of the nominal group and Delphi consensus-gathering techniques. CONCLUSIONS: The use of catheterization of the right side of the heart for hemodynamic monitoring should be reserved for tertiary and secondary care hospitals, which are adequately staffed by physicians and nurses well versed in the use of such monitoring. Future research should be directed at determining whether the use of hemodynamic monitoring will improve outcomes among patients, especially those with myocardial infarction, septic shock or pulmonary edema.

Cardiac Catheterization↗
PubMed1975

[Urinary excretion of hippuric acid in workers exposed to toluene. Recommendation for a group biological standard (mac) (author's transl].

Four groups of workers of the rotogravure, shoe and plastic industries, all exposed to toluene, were studied by the authors. Hippuric acid was measured by a colorimetric method, on urines collected at the end of the work shift. From the obtained results, the authors believe that the biological standard (MAC) for an homogeneous working group could be 1100 mg/liter. Such a threshold, which could however be further revised, ought not to be exceeded; higher toluene concentrations will require technical changes of the working environment.

Adult↗
PubMedDate not supplied

[Magnetoencephalography: a new functional diagnostic technique for the neurosciences].

INTRODUCTION AND OBJECTIVES: We present a review on the technical, methodological and clinical advances in the functional study of the brain by means of magneto-encephalography. We look back the milestones of its historical development, through the work of the major research groups on this field and through our group's works and database (including doctoral thesis). Discussion on the neurophysiological and biomagnetism basis is provided as well as description of technical developments in superconducting detectors (SQUID, Superconducting Quantum Interference Device), signal processing, enhancement of noise-signal ratio and dipole modeling. DEVELOPMENT: The need for brain functional studies has led to newer imaging procedures (functional magnetic resonance, PET, SPECT, etc.). Their spatial and temporal resolution and invasivity are compared to that of magneto-encephalography. Current equipment, up to 306 whole-head channels, may accurately detect cortical and subcortical activity. Apart from the physiological activity, it may be applied to a number of conditions: epilepsy (ictal, interictal and presurgical); dementia, movement disorders, stroke, eloquent cortex delimitation prior to tumour or lesion resection; learning disabilities and foetal studies. CONCLUSIONS: Magnetoencephalography provides with an excellent temporal, very good spatial resolution, acquires in real-time, without references and minimal interference. It entails a great advance in the diagnostic approach in neurosciences.

Brain↗
PubMed1997

Open architecture for health care systems: the European RICHE experience.

Groupe RICHE is bringing to the market of health IT the Open Systems approach allowing a new generation of health information systems to arise with benefit for patients, health care professionals, hospital managers, agencies and citizens. Groupe RICHE is a forum for exchanging information, expertise around open systems in health care. It is open to any organisation interested by open systems in health care and wanting to participate and influence the work done by its user, marketing and technical committees. The Technical Committee is in charge of the maintenance of the architecture and impact the results of industrial experiences on new releases. Any Groupe RICHE member is entitled to participate to this process. This unique approach in Europe allows health care professionals to benefit from applications supporting their business processes, including providing a cooperative working environment, a shared electronic record, in an integrated system where the information is entered only once, customised according to the user needs and available to the administrative applications. This allows Hospital managers to satisfy their health care professionals, to smoothly migrate from their existing environment (protecting their investment), to choose products in a competitive environment, being able to mix and match system components and services from different suppliers, being free to change suppliers without having to replace their existing system (minimising risk), in line with national and regional strategies. For suppliers, this means being able to commercialise products well fitted to their field of competence in a large market, reducing investments and increasing returns. The RICHE approach also allows agencies to define a strategy, allowing to create a supporting infrastructure, organising the market leaving enough freedom to health care organisations and suppliers. Such an approach is based on the definition of an open standard architecture. The RICHE esprit project defined in 1993 the three layered architecture, with four main components and their services of which the main principles have recently been adopted by the CEN TC251 as a european pre-standard. From this architecture specifications various implementations have been completed including the IMS DHE, the GESI DHE and the REFERENCE Kernel. However putting into practice this approach on a large scale is not so easy. Interesting lessons have been learned in the last years in different countries.

Computer Communication Networks↗
PubMed2003

Global health improvement and WHO: shaping the future.

A world torn by gross health inequalities is in serious trouble. The global health community can do much to reduce suffering and death among vulnerable groups. WHO is changing its way of working, alongside member states and financial and technical partners, to reach key national health goals and strengthen equity. The most urgent objectives include the health-related Millennium Development Goals, the 3 by 5 target in HIV/AIDS treatment (to provide 3 million people in developing regions with access to antiretroviral treatment by the end of 2005), and addressing the growing epidemics of non-communicable diseases. The key to achieving these objectives is strengthening of health systems guided by the values of Health For All.

Anti-Retroviral Agents↗
PubMed1976

PCBs and environmental contamination.

A survey is given on reported PCB-residues and accumulation in various environmental media including water and aquatic environment, flora, animals, food, and humans. Model studies with technical PCB, as well as with pure individual components, are presented from various working groups. As examples, metabolic studies and photochemical experiments are discussed. According to our present knowledge, a major metabolic pathway in animals and plants is hydroxylation, often followed by methylation or conjugation. By UV-irradiation, however, oxygenation, dechlorination and chlorination, polymerization and isomerization may occur.

Animals↗
PubMed1978

[Network for the epidemiological survey of the enteroviruses in sewage (author's transl)].

Poliomyelitis still occurs each year in France: 27 cases in 1973, 21 cases in each of 1974 and 1975, 8 cases in 1976. Because of the risk, a survey of the spread of poliovirus in healthy populations and in sewage was organized by the Ministry of Health according to the departmental note DGS/HP/1st/250, 9-2-73. The Laboratoire d'Epidémiologie Virale of the Laboratoire National de la Santé was in charge of the technical aspects of the survey. A preliminary questionnaire was sent to each D.D.A.S.S. (Direction Départementale de l'Action Sanitaire et Sociale) in order to find out the local possibilities for sampling and preliminary treatment of the sewage samples. In 1974, all the samples were sent to the Laboratoire d'Epidémiologie Virale. Since 1975, samples have been sent to a local virology laboratory when available. The sewage samples were concentrated according to SHUVAL's or LUND's methods depending on the local conditions. Both methods tested in our laboratory were found equally efficient. In order to improve their technical laboratory methods, the virologists collaborating in this survey joined together in a working group "Virus et Eaux". For isolating the enteroviruses, we recommend the inoculation of each concentrated sample into primary monkey kidney cells grown in vials; an overlay of agar is added after inoculation. This plaque method allowed us to isolate several strains from one sample. It was possible to demonstrate that polioviruses differing in serotypes and thermosensitivity might be detectable in the same sample. Few of the isolated polioviruses (11/272) showed the same thermoresistance as did the wild strains. Certain enterovirus serotypes are known to be responsible for epidemics of meningitis and neurological disorders. It was of interest to identify non-poliomyelitic enteroviruses isolated from sewage. The study of enterovirus spread in sewage in comparison with that in healthy children is in progress.

Animals↗
PubMed2001

Challenges in harmonising controls on the radioactivity of building materials within the European Union.

Possibilities for harmonising controls on the radioactivity of building materials within the European Union are being discussed in a Working Party on Natural Radiation Sources established by the Article 31 Group of Experts (Euratom Treaty). The Working Party is preparing a document to aid the Article 31 Expert Group and the European Commission in considering possible recommendations and technical guidance to the Member States for the implementation of the new Basic Safety Standards Directive concerning the radioactivity of building materials. The discussions in the working party have demonstrated several challenges in the possible harmonisation of controls, many of them arising from some significant differences in national circumstances.

Air Pollutants, Radioactive↗
PubMed1991

[Risk factors related with occupational and environmental exposure to organochlorine insecticides in the state of Bahia, Brazil, 1985].

In the cacao-growing region in the southern part of the state of Bahia, the organochlorine insecticides, mainly gamma-benzene hexachloride (BHC) and dichlorodiphenyltrichloroethane (DDT), have been used for about 40 years on cacao crops and in public health programs for control of the insect vectors of different diseases, especially malaria. This paper presents the results of tests performed on 127 persons, all males, between the ages of 15 and 52 years, divided into eight groups as follows: three groups consisted of persons occupationally exposed to 1.5% BHC, that is, technical hexachlorocyclohexane (HCH); two groups consisted of individuals who had had occasional contact with the products or worked in areas near those in which they were used; two groups were appliers of DDT, and the last group--the control group--consisted of 50 individuals who had had no history of occupational exposure to insecticides. All the participants underwent testing to determine the parameters of biochemistry, hematology, and organochlorine insecticide residues in the blood. It was found that improper handling of the products and failure to use individual protective equipment, together with longer time of exposure, significantly increased the rates of GOT and GPT in the appliers of DDT and technical HCH, and in the latter the rates of alkaline phosphatase, albumin, and cholesterol were also found to be higher. In view of the high morbidity among pesticide appliers in agriculture and public health campaigns, it is important to institute programs to teach these workers to avoid contamination of their persons and of the environment by developing good hygiene habits, using individual protective equipment, and correctly handling the products. Rural workers and public health authorities must become aware of the importance of protective equipment, periodic health examinations, and reduced environmental pollution in order to lessen occupational risks of field workers and promote improved conditions of life for the rural population at large.

Adolescent↗
PubMed2005

[Venezuelan Virology Network].

In November 2004, sponsored by the World Bank, the Venezuelan Foundation of Science, Technology and Innovation (Fonacit) and the Venezuelan Institute of Scientific Research (IVIC), delegates from the different virology research groups of the country, met in Caracas-Venezuela, with the aim to establish the "Venezuelan Virology Network". The symposium entitled "Molecular biology applied to virus of health importance in Venezuela", was divided into three areas, including human and animals viruses related to public health: 1) Dengue, others arboviruses and Hemorrhagic Fevers; 2) diarrhea-related and others veterinary viruses and 3) Hepatitis, HIV and others sexually transmitted viruses. This symposium allowed the delegates to evaluate the current strengths, weaknesses and needs of the different laboratories, becoming evident the necessity of developing collaborative work between the groups that share the same interests or lines of research; and also their need to exchange technical resources, human and bibliographical material and consequently, avoiding the duplication of efforts and the unnecessary cost of resources. One of the main strengths of Venezuelan virology is the presence, in most laboratories, of researchers with studies of fourth level and multidisciplinary teams of work. We aspire to achieve the raised objectives in the event, to the benefit of our virology and even more important, of our people.

Computer Communication Networks↗
PubMed1984

Closed medullary nailing for fractured shaft of the femur--a comparison between the Küntscher and the AO techniques.

A retrospective review was made of 97 cases of fractured shaft of the femur treated with closed medullary nailing. A comparison was made between the Küntscher and the AO techniques with respect to union of the fracture, rehabilitation, complication and functional results. Patients treated with AO nails enjoyed more rapid recovery: 88 per cent of the fractures united in 12 weeks, 62 per cent walked with full weight bearing in 8 weeks and 78 per cent returned to work within 6 months. However, the functional results in both groups were comparable. The special technical considerations and complications in each group are discussed.

Adolescent↗