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PubMed2004

Other people, other drugs: the policy response to petrol sniffing among indigenous Australians.

This paper examines the policy response of Australian governments to petrol sniffing in Indigenous communities from the 1980s until the present. During this period, despite the formation of numerous inquiries, working parties and intergovernmental committees, there has been little accumulation of knowledge about the nature and causes of sniffing, or about the effectiveness of interventions. Policies are fragmentary; programmes are rarely evaluated, and most rely on short-term funding. The paper sets out to explain why this should be so. It draws upon a conceptual framework known as 'analytics of government' to examine the ways in which petrol sniffing comes to the attention of government agencies and is perceived as an issue; the mechanisms deployed by governments to address petrol sniffing; ways in which knowledge about sniffing is generated; and the underlying assumptions about people that inform policy-making. Drawing upon case studies of policy responses, the paper argues that a number of structural factors combine to marginalize petrol sniffing as an issue, and to encourage reliance on short-term, one-off interventions in place of a sustained policy commitment. Four recommendations are advanced to help overcome these factors: (1) agreements should be reached within and between levels of government on steps to be taken to reduce risk factors before the eruption of petrol-sniffing crises; (2) the evidence base relevant to petrol sniffing (and other inhalants) should be improved by funding and directing one or more existing national drug research centres to collate data on inhalant-caused mortality and morbidity, and to conduct or commission research into prevalence patterns, effectiveness of interventions and other gaps in knowledge; (3) the current pattern of short-term, pilot and project funding should be replaced with longer-term, evidence-based interventions that address the multiple risk and protective factors present in communities; and (4) insistence by governments that communities must take 'ownership' of the problem should be replaced by a commitment to genuine partnerships involving governments, non-government and community sectors.

Australia↗

PubMed2003

The current status of therapy for adult T-cell leukaemia-lymphoma in Japan.

More than 25 years have passed since adult T-cell leukaemia-lymphoma (ATLL) was identified as a distinct clinical entity clustered in the southwestern part of Japan. During these years, its causative agent, Human T-cell leukaemia virus type I (HTLV-I), was found, and remarkable clinical variance of this disease was recognized afterward. Because of the regional occurrence of this disease in the world, young medical scientists whose community is not endemic for this disease may have little understanding of it and may think that it a T-lymphoblastic leukaemia-lymphoma of adult-onset. In Nagasaki prefecture in Japan, where HTLV-I carriers account for 3-5% of the population, the incidence of ATLL is almost the same as the incidence of B-cell lymphomas, and hence ATLL is a matter of major concern. In contrast to the vast accumulation of knowledge about the oncogenic role of HTLV-I and molecular biology of ATLL cells, improvement in the prognosis of patients has not been satisfactorily achieved except for some recent progression. Here, we review the current status of therapy for ATLL in Japan and discuss how best to manage this difficult disease at this point and what next step should be taken.

Clinical Trials as Topic↗

PubMed1998

Adaptive Process Control in Rubber Industry.

This paper describes the problems and an adaptive solution for process control in rubber industry. We show that the human and economical benefits of an adaptive solution for the approximation of process parameters are very attractive. The modeling of the industrial problem is done by the means of artificial neural networks. For the example of the extrusion of a rubber profile in tire production our method shows good resuits even using only a few training samples.

extruder mask estimation↗

PubMed1998

Sequence alignment in molecular biology.

Molecular biology is becoming a computationally intense realm of contemporary science and faces some of the current grand scientific challenges. In its context, tools that identify, store, compare and analyze effectively large and growing numbers of bio-sequences are found of increasingly crucial importance. Biosequences are routinely compared or aligned, in a variety of ways, to infer common ancestry, to detect functional equivalence, or simply while searching for similar entries in a database. A considerable body of knowledge has accumulated on sequence alignment during the past few decades. Without pretending to be exhaustive, this paper attempts a survey of some criteria of wide use in sequence alignment and comparison problems, and of the corresponding solutions. The paper is based on presentations and literature given at the Workshop on Sequence Alignment held at Princeton, N.J., in November 1994, as part of the DIMACS Special Year on Mathematical Support for Molecular Biology.

Algorithms↗

PubMed2004

GAPSCORE: finding gene and protein names one word at a time.

MOTIVATION: New high-throughput technologies have accelerated the accumulation of knowledge about genes and proteins. However, much knowledge is still stored as written natural language text. Therefore, we have developed a new method, GAPSCORE, to identify gene and protein names in text. GAPSCORE scores words based on a statistical model of gene names that quantifies their appearance, morphology and context. RESULTS: We evaluated GAPSCORE against the Yapex data set and achieved an F-score of 82.5% (83.3% recall, 81.5% precision) for partial matches and 57.6% (58.5% recall, 56.7% precision) for exact matches. Since the method is statistical, users can choose score cutoffs that adjust the performance according to their needs. AVAILABILITY: GAPSCORE is available at http://bionlp.stanford.edu/gapscore/

Abstracting and Indexing↗

PubMed2005

A precise and scalable method for querying genes in chromosomal banding regions based on cytogenetic annotations.

MOTIVATION: Staining the human metaphase chromosomes reveals characteristic banding patterns known as cytogenetic bands or cytobands. Using technologies based on metaphase chromosomes, researchers have accumulated much knowledge about the correlations between human diseases and specific cytoband aberrations, indicating the presence of disease-associated genes in those bands. With the progress of human genome project and techniques such as fluorescent in situ hybridization, many genes have been assigned to the cytobands and annotated in public databases, making it possible to find all genes in the disease-related cytobands through database queries. However, finding genes in cytobands remains an imprecise process, partly due to the insufficiency of current methods for cytoband queries, especially for those based on cytogenetic annotations. RESULTS: By transforming the cytoband annotations into numerical segments, a new query method is developed that is able to accurately define any cytogenetic ranges in human chromosomes. A query system (designated cytoband query sys CQS) is implemented using cytogenetic annotations in the public domain. Judged by a performance test, CQS executed as accurately as expected using cytogenetic annotations from NCBI Map Viewer. The new method is scalable and can be applied to genomes from other species. AVAILABILITY: The CQS is freely accessible over the Internet at http://moris.csie.ncku.edu.tw/cqs/ CONTACT: clh9@mail.ncku.edu.tw SUPPLEMENTARY INFORMATION: http://moris.csie.ncku.edu.tw/cqs/

Algorithms↗

PubMed2002

Complexities of cancer research: mouse genetic models.

Cancer susceptibility is a complex interaction of an individual's genetic composition and environmental exposures. Huge strides have been made in understanding cancer over the past 100 yr, from recognition of cancer as a genetic disease, to identification of specific carcinogens, isolation of oncogenes, and recognition of tumor suppressors. A tremendous amount of knowledge has accumulated about the etiology of cancer. Cancer genetics has played a significant role in these discoveries. Analysis of high-risk familial cancers has led to the discovery of new tumor suppressor genes and important cancer pathways. These families, however, represent only a small fraction of cancer in the general population. Most cancer is instead probably the result of an intricate interaction of polymorphic susceptibility genes with the sea of environmental exposures that humans experience. Although the central cadre of cancer genes is known, little is understood about the peripheral genes that likely comprise the polymorphic susceptibility loci. The challenge for cancer genetics is therefore to move forward from the mendelian genetics of the rare familial cancer syndromes into the field of quantitative trait loci, susceptibility factors, and modifier genes. By identifying the genes that modulate an individual's susceptibility to cancer after an environmental exposure, researchers will be able to gain important insights into human biology, cancer prevention, and cancer treatment. This article summarizes the current state of quantitative trait genetic analysis and the tools, both proven and theoretical, that may be used to unravel one of the great challenges in cancer genetics.

Animals↗

PubMed2006

Applications for protein sequence-function evolution data: mRNA/protein expression analysis and coding SNP scoring tools.

The vast amount of protein sequence data now available, together with accumulating experimental knowledge of protein function, enables modeling of protein sequence and function evolution. The PANTHER database was designed to model evolutionary sequence-function relationships on a large scale. There are a number of applications for these data, and we have implemented web services that address three of them. The first is a protein classification service. Proteins can be classified, using only their amino acid sequences, to evolutionary groups at both the family and subfamily levels. Specific subfamilies, and often families, are further classified when possible according to their functions, including molecular function and the biological processes and pathways they participate in. The second application, then, is an expression data analysis service, where functional classification information can help find biological patterns in the data obtained from genome-wide experiments. The third application is a coding single-nucleotide polymorphism scoring service. In this case, information about evolutionarily related proteins is used to assess the likelihood of a deleterious effect on protein function arising from a single substitution at a specific amino acid position in the protein. All three web services are available at http://www.pantherdb.org/tools.

Amino Acid Substitution↗

PubMed2004

Antiretroviral therapy in drug-naive patients infected with human immunodeficiency virus.

A vast amount of knowledge has accumulated since the discovery of the immunodeficiency diseases caused by human immunodeficiency virus-1 (HIV-1) in the early 1980s. An expert panel of HIV researchers and clinicians produced the first set of treatment guidelines in 1997. Since then, these guidelines have been updated based on available clinical information and supplemented by expert opinion when scientific data were incomplete. The latest version of the HIV treatment guidelines are summarized here, with attention focused on the rationale for treatment of asymptomatic as well as symptomatic individuals, including when and what to start as a first regimen of highly active antiretroviral therapy (HAART). Components of initial and follow-up evaluations are detailed, with attention given to available HIV viral load tests and their use. Because adherence to HAART is critical to immune recovery and stabilization, data on predictors of both good and poor medication compliance, as well as strategies to maximize medication adherence are presented. Lastly, recommendations for the use of HIV genotypic and phenotypic resistance testing in antiretroviral naive patients are presented.

Adolescent↗

PubMed2000

Medical information privacy and the conduct of biomedical research.

Profound changes in the health care delivery system, the increasing pervasiveness of information technology, and dramatic advancements in research in human genetics are intensifying public concerns about the privacy of medical information. The author argues that some of these concerns, such as the fear that medical data could be used to deny health insurance or employment, are "pragmatic" and can be dealt with through the political process. But other, "ideologic" concerns tend to generate strong emotions and political positions that impede rational discourse and confound attempts to seek workable compromises. He stresses that the progress of medicine has long depended on studies of collections of empirical data about individuals, and discusses the federal oversight of research involving human subjects, including provisions in place to protect their privacy and maintain the confidentiality of data while at the same time permitting necessary access to data for research. He suggests that since every individual benefits from the accumulated medical knowledge base, everyone should contribute to the ongoing expansion and renewal of that base. The author then states nine principles crafted at the Association of American Medical Colleges to guide its thinking and advocacy efforts regarding medical-information privacy issues. (For example, "the free flow of identifiable medical information within the boundaries of the health care system is essential to the optimum provision of patient care and its payment.") He acknowledges that the flows and uses of identifiable patient information within our complex health care and research systems are bewildering and hard to explain to the public, which is deeply concerned about privacy in general, and especially medical information privacy. How to address this concern and at the same time protect the completeness, accuracy, and integrity of the medical record? The author offers no specific answers beyond those embodied in the AAMC principles, but maintains that a satisfactory solution will come only from carefully crafted federal legislation that creates a comprehensive, uniform, and effective system of workable protections of the confidentiality of medical information, while protecting the access needed to puruse the nation's ambitious agenda in health research.

Confidentiality↗

PubMed1992

Determination of insulin sensitivity: methodological considerations.

During the past decade, it became obvious that in contrast to defective insulin secretion in type I diabetes, defective insulin action (insulin resistance) is the most pertinent feature of type II diabetes. In addition, it has been known for a long time that obesity and insulin resistance are closely linked. Recently, hypertension also has been shown to often coincide with insulin resistance, although any causal relationships are still hypothetical. Last, several widely used pharmacological drugs such as diuretics, adrenergic blockers, and angiotensin-converting enzyme inhibitors may influence insulin sensitivity. Therefore, growing interest has emerged to most accurately measure insulin sensitivity. Although considerable knowledge has accumulated as to the actual mechanisms of insulin-dependent glucose transport, the signal transduction pathway of insulin remains poorly understood. When insulin sensitivity is measured, it is the overall glucose uptake that is quantified under controlled conditions. Other actions of insulin, such as the transport of ions, (e.g., sodium and potassium), synthesis of insulin-like growth factor-binding proteins, translocation of transporter proteins, and regulation of enzyme activities, are much more difficult to quantify. Of the many approaches used to quantify insulin action, the euglycemic hyperinsulinemic clamp technique has emerged as the most reliable tool, fulfilling clinical and scientific demands equally. In combination with tracer methodology and calorimetry, a detailed view into the quantitative aspects of insulin action at different target cells is possible. Whether insulin resistance extends to other known actions of insulin in addition to those on glucose metabolism remains open to debate.

Animals↗

PubMed1997

Genetic factors in human hypertension.

The advancement of molecular biomedical techniques has allowed solutions to the problem of finding a genetic linkage to hypertension. This is now being approached by limiting study to a select number of genetic factors possibly influencing a particular physiologic dysfunction or structural defect. Analysis of chromosomal abnormalities or regions bearing a particular mutation have been greatly influenced by the ability to produce artificial chromosomes or to identify closely linked markers. Rapid accumulation of knowledge of the genetic map has led to a number of these gene/disease linkages. Perhaps the unraveling of some of the polygenic influences in hypertension may lead to even better treatment protocols to minimize the disease complications of elevated blood pressure.

Alleles↗

PubMed2000

Interorgan amino acid exchange.

This review is concerned with the status of our current research related to the exchange of amino acids across organs. Accumulation of knowledge regarding how amino acid pools are maintained within the body remains a work in progress. In recent years, the use of organ balance measurement techniques in combination with isotopic tracers has much increased our understanding of the role of the kidney and splanchnic organs in amino acid metabolism, and in kidney and liver gluconeogenesis from amino acids. An interorgan cooperation between the kidney and splanchnic organs for leucine-ketoisocaproate metabolism has also been demonstrated.

Amino Acids↗

PubMed2006

Evidence-based overview of ophthalmic disorders in deaf children: a literature update.

BACKGROUND: Deaf children are heavily reliant on the sense of vision in order to develop efficient communication skills and explore the world around them. Any ophthalmic disorder may thus negatively impact on this process, especially if it is unrecognised in the early years of life. These disorders may be correctable (such as myopia) or treatable (such as cataract), and their early identification is of the utmost importance to optimise language development (spoken or sign, or both) and develop social cognition. Those children with non-correctable and non-treatable visual disorders, like retinitis pigmentosa in Usher syndrome, require multiple environmental adaptations and appropriate support services and information. AIM: : To review the accumulated scientific knowledge on ophthalmic disorders in deaf children and assess the quality of evidence published in the literature in order to contribute to better diagnosis and management of these conditions. MATERIAL AND METHODS: The project reviewed more than 1000 published papers and other sources. 191 papers complied with the aims of the study and were used in the project. From these studies, 95% were based on type III or IV evidence (mainly descriptive studies or case reports). Only 3% were based on type II evidence and 2% on type I evidence. RESULTS-CONCLUSIONS: The main conclusions of this project are: a) the overall quality of evidence in the literature concerning deaf children and their ophthalmic problems is very low, b) the prevalence of ophthalmic problems in deaf children is very high (approximately 40% to 60%) and these problems may remain undetected for years although they may have a serious impact on children's acquisition of communication skills, c) screening for ophthalmic problems in deaf children should be encouraged and specialist ophthalmic examination should be carried out as soon as the diagnosis of deafness is confirmed irrespective of age, and may need to be repeated at intervals following diagnosis, d) families should be informed about the nature of the screening process in discussion with the relevant professionals and appropriate information should be available in a range of formats and in different community languages, e) professionals administering the tests should be familiar with the needs of deaf children with ophthalmic problems and should be sensitive to the communication needs of the child, especially undertaking behavioural testing where their collaboration is needed, f) while orthoptists can perform the majority of psychophysical tests (visual and stereo acuity tests, ocular motility tests, etc.) a comprehensive opthalmologic assessment by slit lamp biomicroscopy, streak retinoscopy, direct and indirect ophthalmoscopy, intraocular pressure measurement etc is required. Electrophysiologic testing to help identification of Usher syndrome may also be required, and finally g) serial hearing assessments of children with dual sensory deficits are needed to monitor hearing thresholds, to optimise hearing aid use and to ensure timely referral for cochlear implantation for those who need it.

Child↗

PubMed1983

Chemical structure and biological activity of the diazepines.

Since the introduction of chlordiazepoxide and diazepam many diazepines have been developed. Use of these drugs is increasing and considerable knowledge has accumulated about their mechanisms of action. The structural and pharmacological properties of these drugs are surveyed briefly.

Acetylcholine↗

PubMed1994

Making research useful to the practising nurse.

This paper examines the problem of developing research in nursing and the challenge of establishing its relevance and usefulness to the practising nurse. It is accepted that considerable progress has been made worldwide in recent years in the development of nursing research but nurses remain generally remote from the intellectual challenge of an evolving research-based profession. The publication of research reports is examined in the light of the acknowledged need for dissemination of research findings and differences in their presentation are noted as evidence of an apparent discouragement of the practising nurse from sharing in the accumulated nursing knowledge through research. It is argued that learning about research should be brought into the centre of basic nursing education and the growth in clinical research should be encouraged as a means of demonstrating the usefulness of research to the practising nurse.

Clinical Competence↗

PubMed1994

Historical and epistemological perspectives on research and nursing.

This paper examines four main themes with respect to some problematic issues concerning the discipline of nursing, nursing scholarship and the social sciences. First, attention is directed to the controversial issues concerning nursing's search for a knowledge base. Second, a historical context is provided by drawing attention to some key developments between the quantitative and qualitative approaches to research in nursing. Third, the issue of the fundamental and attested difficulties in the application of qualitative methodologies is addressed. Finally, it is submitted that in the interest of nursing's future as a scholarly endeavour, the discipline should focus polemic attention on the body of knowledge already accumulated.

Australia↗

PubMed1996

The value to nursing research of Gadamer's hermeneutic philosophy.

In recent years there has been an increasing awareness in nursing research of the importance of accumulation of knowledge related particularly to the art of nursing. Because of this, nurses are endeavouring to understand more comprehensively the meanings given to central phenomena such as caring, comfort and reassurance, and also to research them with methodologies in such a way that these meanings are not destroyed, distorted or decontextualized. Gadamer's hermeneutic philosophy may prove to be a valuable approach in enabling nurses to gain a deeper and fuller understanding of these phenomena which are central to nursing practice.

History, 20th Century↗