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Corporate intelligence in biotechnology.

'Know thy neighbor' is a critical component of today's biotechnology practice. The industry is extremely rich in science and business information, and the pace of change is dramatic. Successful participation in biotechnology will always depend on good technology, management and money. In addition, an ingredient that needs more attention is competitive information- gathering and analysis. Competitive intelligence can be defined as actionable information that requires the ability to filter and synthesize relevant knowledge for the benefit of the company. Why is this necessary? How can it be done well? What examples are there? These are good questions that are inevitably faced by all biotechnology practitioners, and some answers are provided herein.

Journal Article↗

Evaluating informatics applications--some alternative approaches: theory, social interactionism, and call for methodological pluralism.

A review of evaluation literature concerning CDSSs indicates that randomized controlled clinical trials (RCTs) are the 'gold standard' for evaluation. While this approach is excellent for studying system or clinical performance, it is not well suited to answering questions concerning whether systems will be used or how they will be used. Because lack of use of CDSS has been of concern for some years, other evaluation research designs are needed to address those issues. This paper critiques RCT and experimental evaluation approaches and presents alternative approaches to evaluation that address questions outside the scope of the usual RCT and experimental designs. A wide range of literature is summarized to illustrate the value of evaluations that take into account social, organizational, professional, and other contextual considerations. Many of these studies go beyond the usual measures of systems performance or physicians' behavior by focusing on 'fit' of the system with other aspects of professional and organizational life. Because there is little explicit theory that informs many evaluations, the paper then reviews CDSS evaluations informed by social science theories. Lastly, it proposes a theoretical social science base of social interactionism. An example of such an approach is given. It involves a CDSS in psychiatry and is based on Kaplan's 4Cs, which focus on communication, control, care, and context. Although the example is a CDSS, the evaluation approach also is useful for clinical guideline implementation and other medical informatics applications. Similarly, although the discussion is about social interactionism, the more important point is the need to broaden evaluation through a variety of methods and approaches that investigate social, cultural, organizational, cognitive, and other contextual concerns. Methodological pluralism and a variety of research questions can increase understanding of many influences concerning informatics applications development and deployment.

Attitude↗

Views on HIS development; recommendations of earlier working conferences compared with present challenges.

UNLABELLED: The objective of this paper is to consider the recommendations and expectations of the IMIA WG10 working conferences at Nijmegen (1988) and Göttingen (1991) from the present perspective. The methods: the original task description of WG10 is considered and the main items during the Nijmegen and Gottingen working conferences are addressed. The design and use of a HIS are compared by those for a ship. THE RESULTS: the tasks of WG10 have only partially been completed. However, for several items significant progress has been made. The conclusions: the recommendations of the earlier conferences are to a large extent still valid. A scientific foundation for HIS development has not yet been created, in this respect HIS design and development compares unfavourably with shipbuilding. The choice has to be made: either we consider HIS development as an art or we give priority to the development of a Science of Health Information Processing (SHIP) to found the HIS development.

Congresses as Topic↗

Gene therapy progress and prospects: fetal gene therapy--first proofs of concept--some adverse effects.

Somatic gene delivery in utero is a novel approach to gene therapy for genetic disease based on the hypothesis that prenatal intervention may avoid the development of severe manifestations of early-onset disease, allow targeting of otherwise inaccessible tissues including expanding stem cell populations, induce tolerance against the therapeutic transgenic protein and thereby provide permanent somatic gene correction. This approach is particularly relevant in relation to prenatal screening programmes for severe genetic diseases as it could offer prevention as a third option to families faced with the prenatal diagnosis of a genetically affected child. Most investigations towards in utero gene therapy have been performed on mice and sheep fetuses as model animals for human disease and for the application of clinically relevant intervention techniques such as vector delivery by minimally invasive ultrasound guidance. Other animals such as dogs may serve as particular disease models and primates have to be considered in immediate preparation for clinical trials. Proof of principle for the hypothesis of fetal gene therapy has been provided during the last 2 years in mouse models for Crigler Najjar Disease, Leber's congenital amaurosis, Pompe's disease and haemophilia B showing long-term postnatal therapeutic effects and tolerance of the transgenic protein after in utero gene delivery. However, recently we have also observed a high incidence of liver tumours after in utero application of an early form of third-generation equine infectious anaemia virus vectors with SIN configuration. These findings highlight the need for more investigations into the safety and the ethical aspects of in utero gene therapy as well as for science-based public information on risks and benefits of this preventive gene therapy approach before application in humans can be contemplated.

Animals↗

Blood pressure variability and cardiovascular control mechanisms in hypertension.

Blood pressure variability is the result of a complex interaction between external stimulation and several cardiovascular control mechanisms and is enhanced in all those conditions characterized by an impaired autonomic regulation of circulation. In particular, blood pressure variability is enhanced in hypertension over 24 h and may independently contribute to the cardiovascular complications of this condition. The paper by Mussalo and co-workers in this issue of Clinical Science offers additional information in this field by suggesting that different forms of hypertension are characterized by different patterns of blood pressure variability, and that these differences may reflect variations in the underlying autonomic regulation of the heart and blood vessels.

Autonomic Nervous System↗

Technological advances in renal care.

The first systems for treating kidney failure were developed in the 1940's, when it was found that blood could be successfully cleared of toxins and returned to the body using a relatively simple device based on artificial sausage skin wrapped around a wooden frame. This process was used to replace the function of the kidney, allowing patients to recover from conditions such as poisoning or crush injuries that temporarily stop the kidneys working. In the 1960's, advances in technology made long-term replacement of renal function using haemodialysis machines possible and allowed surgeons to carry out kidney transplants between people who were not identical twins. Long-term peritoneal dialysis became a viable treatment option two decades later. There are now over 1.1 million people world-wide receiving regular dialysis treatment and around 340,000 people living with a donated kidney. This paper reviews the pioneering work in the treatment of kidney failure and looks at some of the recent advances in equipment design, materials science, immunosuppression and information technology that aim to improve the quality of life and the life expectancy for patients living on renal replacement therapy.

Biotechnology↗

Expressed sequence tags from feline uterine library.

Partial nucleotide sequences of 634 cDNAs randomly isolated from a feline uterine cDNA library (Stratagene) were determined by single pass sequencing. Homology search of the sequences to the non-redundant nucleotide databases revealed that 83% of the cDNAs matched registered feline or non-feline genes. Based on the gene identifications, these genes were predicted to be related with immunological, biochemical and regulatory functions in cats. Interestingly, the rest 17% of the cDNAs did not show homology to gene or EST sequence present in the nucleotide and protein databases, suggesting that these cDNAs include novel genes expressed only in the Felidae. This large scale sequencing of uterine cDNA will provide a useful molecular source for research not only towards health and disease conditions in cats but also in different fields of science where genetic information from cats will be of interest.

Animals↗

Can we track the impact of Australian mental health research?

OBJECTIVE: Arguments are being made to increase research and development funding for mental health research in Australia. Consequently, the methods used to measure the results of increased investment require review. This study aimed to describe the status of Australian mental health research and to propose potential methods for tracking changes in research output. Specifically, we describe the research output of nations, Australian states, Australian and New Zealand institutions and Australian and New Zealand researchers using citation rates. METHOD: Information on research output was sourced from two international databases (Institute for scientific information [ISI] Essential Science Indicators and ISI Web of Science) and the ISI list of Highly Cited Researchers. RESULTS: In an international setting, Australia does not perform as well as other comparable countries such as New Zealand or Canada in terms of research output. Within Australia, the scientific performance of institutions apparently relates to the strength of some individual researchers or consolidated research groups. Highly cited papers are evident in the fields of syndrome definition, epidemiology and epidemiological methods, cognitive science and prognostic or longitudinal studies. CONCLUSIONS: Australian researchers need to consider the success of New Zealand and Canadian researchers, particularly given the relatively low investment in health and medical research in New Zealand. Although citation analyses are fraught with difficulties, they can be effectively complemented by other measures of responsiveness to clinical or population needs and community expectations and should be conducted regularly and independently to monitor the status of Australian mental health research.

Australia↗

Population strategies to enhance physical activity: the Minnesota Heart Health Program.

A population-wide, community-based program in cardiovascular disease prevention, the Minnesota Heart Health Program (MHHP), has been designed to promote more frequent and vigorous physical activity in North American communities, along with improved eating and smoking patterns. The physical activity component of this broad-based education strategy is based on the facilitation which physical activity provides to lowering of other risk characteristics for heart disease and its enhancement of other healthy behaviors and on the potential for prevention of elevated risk in the first place. The rationale for a population strategy to complement medical approaches to prevention is that exercise patterns are largely socially learned and culturally determined. The MHHP Physical Activity Program is implemented through three major education strategies: direct education, community organization, and mass communications. Early results from this 10-year project indicate that it is feasible to enter U.S. communities and to involve their leadership actively in MHHP activities of health promotion. Moreover, attitudes, knowledge, awareness, participation, and behaviors related to exercise and eating patterns appear to be changed by the program. Nevertheless, there are problems in the design, implementation, analysis and interpretation of population changes in physical activity and other health behaviors in community demonstration programs. These issues, along with their solutions, should provide useful information for medical science and for the public health about population strategies of disease prevention and health promotion.

Adolescent↗

The biochemical approach to mental handicap: 30 years of achievements and disappointments.

In the past half century, biochemistry has emerged as an independent discipline that provides essential and fundamental information for medical science. It has an increasingly important role in various branches of medicine and the biochemist is frequently called upon to apply his expertise to the solution of clinical problems, amongst them the role of biochemical disturbances in the aetiology of disorders associated with mental handicap, and the investigation of factors affecting their severity and clinical course. The expectation has been that the understanding of biochemical defects will lead promptly to the suggestion of remedies.

Brain Diseases, Metabolic↗

Future role of micronutrients on immune functions.

The future is bright in the field of micronutrients and immunity. New advances in technology now permit the design of many new research studies, and an increased application of the findings to clinical and public health practices. More investigators will need to be trained in the fundamentals of both nutritional and immunological sciences. More basic information will be needed in both fields, but the scientific and clinical values of merging these two fields are already well established. The development of additional animal models will be needed to dissect out the role of each essential micronutrient and its potential importance in each step of the immune response. Based on future studies, new RDAs must be formulated and applied widely in medical and public health practices and in public education.

Animals↗

Digital tomosynthesis of hand joints for arthritis assessment.

The two principal forms of hand arthritis, rheumatoid arthritis (RA) and osteoarthritis (OA) have large clinical and economic costs. Radiography has been shown to be a useful tool to assess the condition of the disease. A hand radiograph, however, is a two-dimensional projection of a three-dimensional object. In this report we present the results of a study that applied digital tomosynthesis to hand radiography in order to extract three-dimensional outcome measures that should be more sensitive to arthritis progression. The study was performed using simulated projection radiographs created using micro computed tomography (microCT) and a set of five dry-bone hand skeletons. These simulated projection images were then reconstructed into tomographic slices using the matrix inversion tomosynthesis (MITS) algorithm. The accuracy of the tomosynthesis reconstruction was evaluated by comparing the reconstructed images to a gold standard created using the microCT data. A parameter from image registration science, normalized mutual information, provided a quantifiable figure of merit. This study examined the effects of source displacement, number of reconstructed planes, number of acquisitions, noise added to the gray scale images, and errors in the location of a fiducial marker. We also optimized the reconstruction as a function of two variables k and alpha, that controlled the mixing of MITS with conventional shift-and-add tomosynthesis. A study using hand delineated joint margins demonstrated that MITS images provided a better measurement of average joint space width. We found good agreement between the MITS slices and the true planes. Both joint margins and trabecular structure were visible and the reconstructed slices showed additional structures not visible with the standard projection image. Using hand-delineated joint margins we compared the average joint space width of the gold standard slices to the MITS and projection images. A root-mean square deviation (RMSD), calculated for this comparison, gave RMSDproj = 0.18 mm and RMSDMITS = 0.14 mm for the projection and MITS images, respectively. We have demonstrated the potential of digital tomosynthesis for imaging of the hand to assess arthritic changes. We have also developed a methodology that can be used to optimize the technique and have studied the issues that will control the feasibility of clinical implementation.

Arthritis↗

A Bayesian truth serum for subjective data.

Subjective judgments, an essential information source for science and policy, are problematic because there are no public criteria for assessing judgmental truthfulness. I present a scoring method for eliciting truthful subjective data in situations where objective truth is unknowable. The method assigns high scores not to the most common answers but to the answers that are more common than collectively predicted, with predictions drawn from the same population. This simple adjustment in the scoring criterion removes all bias in favor of consensus: Truthful answers maximize expected score even for respondents who believe that their answer represents a minority view.

Bayes Theorem↗

x ray crystallography.

x Ray crystallography is currently the most favoured technique for structure determination of proteins and biological macromolecules. Increasingly, those interested in all branches of the biological sciences require structural information to shed light on previously unanswered questions. Furthermore, the availability of a protein structure can provide a more detailed focus for future research. The extension of the technique to systems such as viruses, immune complexes, and protein-nucleic acid complexes serves only to widen the appeal of crystallography. Structure based drug design, site directed mutagenesis, elucidation of enzyme mechanisms, and specificity of protein-ligand interactions are just a few of the areas in which x ray crystallography has provided clarification.

Algorithms↗

Microbiology of tubercle bacilli.

Based on conventional taxonomic analyses, as well as molecular level studies on DNA and catalases, the tuberculosis complex (M. tuberculosis, M. microti, M. bovis, and M. africanum) appears to consist of a single species. This species does not occur normally free in nature, but depends on host-to-host transmission for its continued existence. Members of the complex are sufficiently distinct genetically from known free-living mycobacteria so that it is unlikely that they would evolve from the free-living species at a significant frequency in nature, although that is presumably how they arose in the first place. Therefore, eradication of tuberculosis seems to be a realistic hope. The technical means now exist for control of the disease; some improvements in diagnostic technology can be expected to accelerate the control efforts. At a basic science level, more information is needed about the ability of M. tuberculosis to survive in a latent state in a host, only to revive years later, if the control of tuberculosis is to progress to eradication.

Bacteriological Techniques↗

The synergistic action of the capsule and the shoulder muscles.

The existence of a reflex arc from the glenohumeral capsule to several muscles crossing the shoulder joint was determined in the feline model. Three branches of the axillary nerve terminating in the glenohumeral capsule were identified and electrically stimulated with supramaximal, 100-microseconds pulses using bipolar hook electrodes. Stimulation of the anterior and the inferior axillary articular nerves elicited electromyographic activity in the biceps, subscapularis, supraspinatus, and infraspinatus muscles. Stimulation of the posterior axillary articular nerve elicited electromyographic activity in the acromiodeltoid muscle. Transection of the three articular nerves just distal to their emergence from the main axillary nerve resulted in the absence of any electromyographic activity in the muscles on stimulation, confirming the afferent nature of the articular branches. The time from application of the stimulus to the appearance of a response in the muscles varied from 2.7 msec in the biceps to 3.1 msec in the supraspinatus. The existence of a reflex arc from mechanoreceptors within the glenohumeral capsule to muscles crossing the joint confirms and extends the concept of synergism between the passive (ligaments) and active (muscles) restraints of the glenohumeral joint. This provides new information in orthopaedic sciences that has direct application in modification of surgical repairs and therapeutic modalities of shoulder injuries.

Animals↗

Drug safety, pharmacoepidemiology, and regulatory decision making.

The safety or risk assessment of a pharmacotherapeutic agent begins early in its development and continues throughout its use cycle. The practice of pharmacoepidemiology is the art of using the sciences and the tools of science to generate information about pharmaceutical outcomes, including associated risks, in the postmarketing environment. A pharmacoepidemiologist must be capable of functioning with a matrix constructed of three components: a knowledge base, a conceptual framework, and an interpretive framework. From this perspective one can establish surveillance schemes, or understand a posed research question, select strategies, apply methodologies, and interpret the results of purposeful investigations. When conveyed to the risk manager, appropriately interpreted results of a properly conducted risk assessment can be used in regulatory decision making. Seven case studies are presented as examples of this approach.

Decision Making↗