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PubMedDate not supplied

[Environment and genetics in the etiology of cleft lip and cleft palate with reference to the role of folic acid].

The combined birth prevalence of cleft palate [CP] and cleft lip with or without cleft palate [CL(P)] in Europe is approximately one in 700 with characteristic regional variations. Orofacial clefting (OC) is therefore now one of the most frequent congenital anomalies, with a higher birth prevalence that Down's Syndrome or Neural Tube defects, but still lower than cardiovascular malformation. Babies with OC require a multidisciplinary medical approach, surgery and rehabilitative treatments over time. This means an important effort in terms of social organization as well as economical costs for the health care system. In Italy, the health care costs for approximately 800 children born with orofacial clefting per year has been estimated at around 150 billion Lire (80 million Euros). The etiology of OC is complex and heterogeneous both for isolated and associated defects; causes linked to environment, genetics and gene-environment interaction are known, although there is still a lot to do, especially in clarifying the role of genetics in producing susceptibility to the environment. Four categories of genes for which there are results suggestive of a genetic susceptibility to OCs are: 1) genes expressed in a particular area of the embryo or in a particular period of the palatine arch development, such as the transforming growth factors alpha and beta (TGF alpha, TGF beta 2, TGF beta 3); 2) genes having biological activities linked to the OC's pathogenesis without direct involvement (e.g. the retinoic acid receptor (RARA), the methylenetetrahydrofolate reductase receptor (MTHFR) and the folic acid receptor (FOLR1); 3) genes or locus identified in experimental animals as the homeotic genes MSX-1 and MSX-2; 4) genes involved in the interaction with the xenobiotics metabolism as those in P-450 cytochrome system. Several environmental factors have been implicated in the OC etiology; among those, the folic acid supplementation during the periconceptional period that was found effective in the prevention of neural tube defects. In fact, folic acid deficiency may be responsible for different malformations through a common mechanism that interferes with the embryonic development, depending on the maternal or embryo genotype. Further investigation is required to study in depth how the genotype would modify the role of environmental factors like folic acid. Well-designed and conducted epidemiological studies seem to be able to give worthwhile information. Studies carried out in Europe on these issues are a few, particularly those on gene-environment interaction. Recent results obtained in molecular biology and the availability of wealth of data can allow to perform ad hoc investigations, being important not only for the basic research but also for their public health implications. For this objective a specific scientific network at the European level has been set by the European Science Foundation (ESF), whose first step will be to establish consistent case ascertainment and data collection across Europe and to develop standardized protocols and methods of analysis. It is hoped that in the longer term such multicentre collaborative research will enable combined analysis and lead to the identification of genetic susceptibility to certain environmental factors, including nutrition. Such studies would inform the current debate about the efficacy of folic acid and other nutritional factors in prevention of disease in the developing embryo. Subsequent public health measures targeted according to risk might reduce the prevalence of disorders such as orofacial clefting.

Adult↗
PubMed1975

Library cooperation: wave of the future or ripple?

Little of the literature in library cooperation applies specifically to library service for the health sciences. Based on experience in and observations of the cooperation of health science libraries, this short lecture reviews aspects of general library cooperation, networks, and consortia. The effects on library operation of several cooperative activities are enumerated and cooperation management is discussed briefly.

Cataloging↗
PubMed1994

Immunologic infertility.

The existence of immunologic infertility is well grounded in the theories of humoral and cell-mediated immunology. Both of these immune system arms can theoretically and experimentally be shown to play roles in states of male factor infertility. Although much progress has been made in relating immunopathology to infertility, several problems plague the investigation and diagnosis: the use of multiple, different assay systems; the lack of properly controlled experimental work; a need to oversimplify a tremendously complex immunologic network for clinical purposes; and a dearth of communication between basic science and clinical investigators. Unlike the established role of humoral or antibody-mediated infertility, the way cell-mediated immunity induces reproductive failure is just beginning to be understood. Two active areas of investigation include a delineation of active immunosuppression in the normal testicular environment and the pathologic deficits induced by cytokines in cases of leukospermia. Other research seeks to define functional, sperm-specific antigens to which autoantibodies are directed and to elucidate the mechanisms of antibody-mediated infertility at various sites in the reproductive tract. The diagnosis of immunologic infertility still remains one of exclusion. When the diagnosis is made, it is necessary to define precisely which functional reproductive deficits exist, through an analysis of semen parameters, postcoital tests, sperm penetration assays, and tests of acrosomal reactivity. This is essential because the therapeutic options are broad and can involve significant side effects and expense. Proven modalities include sperm manipulation, direct sperm insemination, donor insemination, systemic immunosuppression, and assisted reproductive techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed2006

The emergence and diffusion of DNA microarray technology.

UNLABELLED: The network model of innovation widely adopted among researchers in the economics of science and technology posits relatively porous boundaries between firms and academic research programs and a bi-directional flow of inventions, personnel, and tacit knowledge between sites of university and industry innovation. Moreover, the model suggests that these bi-directional flows should be considered as mutual stimulation of research and invention in both industry and academe, operating as a positive feedback loop. One side of this bi-directional flow--namely; the flow of inventions into industry through the licensing of university-based technologies--has been well studied; but the reverse phenomenon of the stimulation of university research through the absorption of new directions emanating from industry has yet to be investigated in much detail. We discuss the role of federal funding of academic research in the microarray field, and the multiple pathways through which federally supported development of commercial microarray technologies have transformed core academic research fields. RESULTS AND CONCLUSION: Our study confirms the picture put forward by several scholars that the open character of networked economies is what makes them truly innovative. In an open system innovations emerge from the network. The emergence and diffusion of microarray technologies we have traced here provides an excellent example of an open system of innovation in action. Whether they originated in a startup company environment that operated like a think-tank, such as Affymax, the research labs of a large firm, such as Agilent, or within a research university, the inventors we have followed drew heavily on knowledge resources from all parts of the network in bringing microarray platforms to light. Federal funding for high-tech startups and new industrial development was important at several phases in the early history of microarrays, and federal funding of academic researchers using microarrays was fundamental to transforming the research agendas of several fields within academe. The typical story told about the role of federal funding emphasizes the spillovers from federally funded academic research to industry. Our study shows that the knowledge spillovers worked both ways, with federal funding of non-university research providing the impetus for reshaping the research agendas of several academic fields.

Journal Article↗
PubMed2005

Science and the British Empire.

The last few decades have witnessed a flowering of interest in the history of science in the British Empire. This essay aims to provide an overview of some of the most important work in this area, identifying interpretative shifts and emerging themes. In so doing, it raises some questions about the analytical framework in which colonial science has traditionally been viewed, highlighting interactions with indigenous scientific traditions and the use of network-based models to understand scientific relations within and beyond colonial contexts.

Colonialism↗
PubMed1993

A service-oriented information sources database for the biological sciences.

Researchers in the biological sciences require access to a variety of information sources located in various places on different computer networks. In order to satisfy the information needs of a researcher, appropriate information sources must be selected and access to these information sources and the computing services supporting them must be provided in a way that does not distract the researcher from problems of real interest. At the University of Missouri-Columbia a service-oriented information sources database is being developed as a key component of a layered-model design of an intelligent system which will provide a research environment appropriate to the needs of researchers in the biological sciences.

Artificial Intelligence↗
PubMed2005

From single genes to co-expression networks: extracting knowledge from barley functional genomics.

The paper reports an 'in silico' approach to gene expression analysis based on a barley gene co-expression network resulting from the study of several publicly available cDNA libraries. The work is an application of Systems Biology to plant science: at the end of the computational step we identified groups of potentially related genes. The communities of co-expressed genes constructed from the network are remarkably characterized from the functional point of view, as shown by the statistical analysis of the Gene Ontology annotations of their members. Experimental, lab-based testing has been carried out to check the relationship between network and biological properties and to identify and suggest effective strategies of information extraction from the network-derived data.

Computational Biology↗
PubMed1978

Fees for information services to hospitals: a California experience.

The project was directed toward planning, developing, and implementing a subregional biomedical information network among the forty-three health care facilities (hospitals) of the four-county area served by Loma Linda University's health sciences library. The project coordinator contacted administrators and health care professionals in the forty-three institutions to present a plan for the network. The health care facilities were encouraged to support the continuation of the network through contract fees. The availability of specific information services was assured through contractual agreements. It was anticipated that the subregional network would be self-supporting after the twelve-month project period (December 1, 1976-November 30, 1977). The working territory (40,429 square miles) encompassed Mono, Inyo, Riverside, and San Bernardino counties. The project resulted in nine of the forty-three hospitals signing annual contracts for library services. It is recommended that projects of this kind extend beyond a year's duration in order to educate health professionals concerning the value of access to biomedical literature in improving patient care.

California↗
PubMed2002

An eigenvector method for estimating item parameters of the dichotomous and polytomous Rasch models.

The purpose of this paper is to describe a technique for obtaining item parameters of the Rasch model, a technique in which the item parameters are extracted from the eigenvector of a matrix derived from comparisons between pairs of items. The technique can be applied to both dichotomous and polytomous data. In application to a previously published data set, it is shown that the technique provides item parameter estimates comparable to those produced by joint maximum likelihood estimation, and for the most difficult items, the technique appears to produce superior estimates. This method has several advantages. It easily accommodates missing data, and makes transparent the basis for item parameter estimation in the presence of missing data. Furthermore, the method provides a link to other methods in the social sciences and, in particular, provides the framework for application of graph theory to the analysis of assessment networks. Finally, it exploits several characteristics that are unique to the Rasch model.

Algorithms↗
PubMed2026

Comparative Efficacy of Different AI Systems for Polyp Detection by Size During Colonoscopy: Systematic Review and Network Meta-Analysis.

BACKGROUND: Colorectal cancer remains a leading cause of death despite being largely preventable through polypectomy. AI systems designed to enhance polyp detection during colonoscopy have shown promise, but the extent to which they improve detection of different-sized polyps remains unclear. OBJECTIVE: This study compared the size-stratified efficacy of AI-assisted colonoscopy vs standard colonoscopy using the Hartung-Knapp-Sidik-Jonkman (HKSJ) method, and generated exploratory rankings while acknowledging all cross-platform comparisons are indirect. METHODS: This systematic review and network meta-analysis (NMA) searched PubMed, Embase, Cochrane CENTRAL, and Web of Science from inception to July 25, 2026, supplemented by citation searching. We included randomized controlled trials (RCTs) comparing AI-assisted vs standard colonoscopy in adults (≥18 years of age), reporting mean polyp detection counts stratified by size (≤5 mm, 6-9 mm, and ≥10 mm). Two reviewers screened studies, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2.0. We conducted frequentist NMA using the HKSJ method with restricted maximum likelihood estimation, calculated 95% prediction intervals (PIs), and assessed heterogeneity using I2 and τ2. Certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. RESULTS: A total of 13 RCTs (4156 participants) compared 8 AI systems to standard colonoscopy, forming a network without direct AI comparisons. For diminutive polyps (≤5 mm), AI showed a modest advantage (standardized mean difference [SMD] 0.21, 95% CI 0.07 to 0.35, 95% PI -1.12 to 1.54), but substantial heterogeneity (I2=86.6%) and wide PI crossing the null indicated high uncertainty. EndoScreener showed the most consistent evidence (SMD 0.36, 95% CI 0.18-0.54). For small and large polyps, effects were minimal (SMD 0.02, 95% CI -0.02 to 0.06, 95% PI -0.03 to 0.07; SMD 0.01, 95% CI 0.00-0.02, 95% PI -0.01 to 0.03). GRADE certainty was very low for diminutive polyps and low for small and large polyps. Sensitivity analysis excluding Tianjin YuJin did not materially change findings. CONCLUSIONS: AI may modestly enhance diminutive polyp detection, but effects on small and large polyps are minimal, with no platform superiority. Given very low to low certainty, findings are hypothesis-generating. This exploratory NMA provides size-stratified comparisons that can inform future head-to-head trial design. Unlike prior reviews aggregating all polyp sizes, we show the overall AI benefit is driven by diminutive polyp detection, providing a framework for targeted deployment-prioritizing AI for diminutive polyp screening, with limited value for larger lesions. Head-to-head trials are urgently needed. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD420251266932; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251266932.

Colonoscopy↗
PubMed1991

Designing a neural network simulator--the MENS modelling environment for network systems: I.

During recent years, the field of neural network research has increasingly attracted the interest of workers from a large number of different disciplines. Current research topics include aspects as different as detailed simulations in brain physiology, predictions of protein structure in biochemistry, database organization in computer science, or various technical applications. The common scheme behind these different approaches is the use of distributed networks of simple computational elements that communicate with each other by means of weighted links. Computer simulations of neural networks require an appropriate software environment. Due to the computational similarities of many classes of such networks, simulation software can be structured into modular components that, to a large degree, are independent of specific applications. The aim of this and the following paper is to discuss some of the design considerations concerning software for neural network simulations. The aspects presented are interesting for both the development of new simulation software and the efficient use and modification of existing programs. Therefore, the general user as well as the software designer may hopefully benefit from this material. This paper briefly introduces some of the basic principles of neural networks. After a short discussion of different approaches to software design, two simple example applications are presented in order to demonstrate a conceptual framework common to many network simulations. The transfer of these considerations to the design of simulation software is then shown by example of the MENS network simulator developed in the Max-Planck-Institute for Brain Research. The paper gives a general introduction to the layout of data structures and different software components. Using the two introductory examples some aspects of network analysis are demonstrated. The following paper then considers further details of the design of a neural network simulator with respect to performance, implementation, and testing.

Animals↗
PubMed1975

The Twin Cities biomedical consortium.

Twenty-eight health science libraries in the St. Paul-Minneapolis area formed the Twin Cities Biomedical Consortium with the intention of developing a strong network of biomedical libraries in the Twin Cities area. Toward this end, programs were designed to strengthen lines of communication and increase cooperation among local health science libraries; improve access to biomedical information at the local level; and enable the Consortium, as a group, to meet an increasing proportion of its members' needs for biomedical information. Presently, the TCBC comprises libraries in twenty-two hospitals, two county medical societies, one school of nursing, one junior college, and two private corporations.

Information Services↗
PubMed2002

The construction of community participation: village family planning groups and the Indonesian state.

Indonesia's family planning program has been one of the most effective in the developing world in promoting contraceptive use and contributing to fertility transition. In evaluating why the program has worked, analysts have given much credit to a network of village family planning groups that developed from the 1970s to the 1990s and that blanketed the archipelago. These groups, composed primarily of female volunteers, made contraception available to women in even the most remote parts of the country, and acted as agents of family planning motivation. They have been labeled by the Indonesian state family planning agency as an example of effective community participation on a national scale. In this paper, I investigate this claim and find it to be simplistic. I provide extensive evidence that the creation of this network was orchestrated by the Indonesian state. On the other hand, I show that these groups are not fully state entities, as they have several characteristics that mark them as socially embedded institutions. They are best labeled as unusual state-society hybrids. In my investigation I draw on one of the newest paradigms in the discipline of political science--the state-society approach--to uncover the odd nature of this family planning network. More deeply, I argue that the state-society approach ought to be adopted in family planning analysis on a comprehensive basis. The traditional organizational and social-demographic approaches that have dominated the field offer only limited understanding of the nature of family planning programs in developing countries. The state-society approach is ideally suited to identifying how family planning programs are institutions of a political nature, embedded in states and societies, and transformed by and transformative of each.

Community Health Planning↗
PubMed2002

On the number of experiments required to find the causal structure of complex systems.

The need to capture the complexity of biological systems in a simpler formalism is the underlying impetus of biological sciences. Understanding the function of many biological complex systems, such as genetic networks or molecular signalling pathways, requires precise identification of the interactions between their individual components. A number of questions in the study of complex systems are then important-in particular, what can be inferred about the interactions in a complex system from an arbitrary set of experiments, and, what is the minimum number of experiments required to characterize the system? This paper shows that the problem of finding the minimal causal structure of a system based on a set of observations is computationally intractable for even moderately sized systems (it is NP-hard), but a reasonable approximation can be found in a relatively short (polynomial) time. Next, it is shown that the number of experiments required to characterize a complex system grows exponentially with the upper bound on the number of immediate upstream influences of each element, but only logarithmically with the number of elements in the system. This makes it possible to study biological systems with extremely large number of interacting elements and relatively sparse interconnections, such as gene regulatory and cell signalling networks. Finally, the construction of a randomized experimental sequence which achieves this bound is discussed.

Animals↗
PubMed1996

Learning and Forgetting in Generalized Brain-state-in-a-box (BSB) Neural Associative Memories.

We propose learning and forgetting techniques for the generalized brain-state-in-a-box (BSB) based associative memories. A generalization of the BSB model allows each neuron to have its own bias and the synaptic weight matrix does not have to be symmetric. A pattern is learned by a memory if its noisy or an incomplete version presented to the memory is mapped back to this pattern. A pattern, previously stored, is forgotten or deleted from the memory if a stimulus that is a perturbed version of the pattern, when presented to the memory, is not mapped back to this pattern. In this paper we propose "on-line" memory storage and deletion methods using an iterative method of computing the pseudo-inverse of a given matrix. The proposed methods allow one to "add" or "delete" a memory pattern by updating, rather than recomputing from scratch, the current synaptic weight matrix in a single step. We first analyze the desired characteristics of neural network associative memories. After that, we review the existing methods for design of neural associative memories. Then we discuss the generalized BSB neural model and its possible function as an associative memory and proffer arguments in support of using such models for neural associative memories. In particular, the generalized BSB type models are easier to analyze, synthesize, and implement than other neural networks. The results obtained are illustrated by numerical examples. Copyright 1996 Elsevier Science Ltd

Journal Article↗