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Functional dynamics of living systems and genetic engineering.

The discussion on Genetically Modified Organisms (GMO's) has been centred mainly on the nature and effects on economy, human health, environment, of the few transgenic plant lines present in the market in the last eight years. On the contrary, the present paper starts with a discussion of some of the relevant changes in our basic knowledge of the structure and dynamics of living systems in the last twenty years. Contemporary Biology is then compared with what may be called the "modern paradigm" of life sciences on which present day GMO's are conceptually based. Technical, environmental, social and economic problems deriving from the unexpected, persistent prevalence of the old fashioned modern vision of life in the "spirit of time" will be thoroughly discussed with a particular attention to the virtualisation process of GMO's and the effects of the prevalence over economic, social, environmental reality of their symbolic values.

Animals↗

Introduction to cancer gene therapy.

Over the past decade, the unprecedented growth in science and technology has fueled the development of novel treatment strategies to combat disease. The creative and innovative efforts of scientists and clinicians to overcome the multitude of unforeseen obstacles to success is no better exemplified than in the field of cancer gene therapy. Since its inception, developers of cancer gene therapy have been charged with the challenge of altering basic tumor biology or, alternatively, the host responses for the purpose of tumor eradication and prevention. Several major therapeutic strategies have emerged from preclinical studies, and results from these early studies hold promise for altering the clinical outcome in a variety of malignancies. These strategies may be broadly subcategorized and range in intent from alteration of the tumor cell phenotype by replacement of defective cellular response genes (e.g., mutated or deleted tumor suppressor genes) to the enhancement of the immunological response to cancer (e.g., amplification of the cell surface antigen signature or modulation of the host response). Not surprisingly, the increasingly intricate nature of tumor biology revealed over the past several years has effectively raised the bar of success for those involved in the development of effective molecular and cancer gene therapy strategies. This, in turn, has led to the development of more complex therapies that frequently draw upon multiple disciplines in an effort to optimize treatment response.

Cancer Vaccines↗

Mucosal T cell response to reovirus.

During the last three decades, immunologists and gastroenterologists have witnessed the formation of mucosal immunology as a discipline in biomedical science, and studies of reovirus infection have substantially contributed to this evolution. We have focused on mucosal T cell responses induced by reovirus in conventional, germfree, nude, and NF-kappaB deficient mice. Several major facets of T cell function in the immune responses to this mucosal pathogen have been examined, including viral selection of oligoclonal-T cells, extrathymic T cell development, and distinct signaling pathways used by CD8 sublineages. In addition, our findings with virus-specific T cells selected in the mucosa have suggested novel mechanisms for the rearrangement, selection, and expansion of TCR genes. With the increasing application of molecular tools, reovirus will continue to be a useful model pathogen to study mucosal immunology and will further our understanding of mucosal immunity in health and disease.

Adult↗

"A mission-driven discipline": the growth of conservation biology.

Conservation biology emerged in the mid-1980s, drawing on established disciplines and integrating them in pursuit of a coherent goal: the protection and perpetuation of the Earth's biological diversity. Opportunistic in its borrowing and application of knowledge, conservation biology had its roots within the established biological sciences and resource management disciplines but has continually incorporated insights from the empirical experience of resource managers, from the social sciences and humanities, and from diverse cultural sources. The Society for Conservation Biology (SCB) has represented the field's core constituency, while expanding that constituency in keeping with the field's integrative spirit. Conservation Biology has served as SCB's flagship publication, promoting research, dialog, debate, and application of the field's essential concepts. Over the last 20 years the field, SCB, and the journal have evolved to meet changing conservation needs, to explore gaps in our knowledge base, to incorporate new information from related fields, to build professional capacity, and to provide expanded opportunities for international participation. In turn, the field, SCB, and journal have prompted change in related fields, organizations, and publications. In its dedication to advancing the scientific foundations of biodiversity conservation and placing that science at the service of society in a world whose variety, wildness, and beauty we care for conservation biology represents both a continuation and radical reconfiguration of the traditional relationship between science and conservation.

Conservation of Natural Resources↗

Microbial forensics for natural and intentional incidents of infectious disease involving animals.

Microbial forensics is a relatively new scientific discipline dedicated to analysing microbiological evidence from a crime for attribution purposes. It builds on traditional microbiology and epidemiology but within a legal framework. Important motives for forensic investigations include interdiction of criminals, prosecution of justice, and ideally, deterrence of others from committing similar acts. Forensic capabilities in animal health should focus on building capacity for detection and reporting of increases in infectious disease morbidity and mortality among animals that might reflect a covert release of a pathogen. Suspicion should be raised when epidemiological patterns are different from those expected for the animal population and the pathogen in question. Existing capacities for the detection and reporting of epidemic and even endemic diseases should be an international priority for the prevention of catastrophic losses in animal and potentially in human life. The veterinary community needs to be more aware of the legal requirements related to forensic investigations so that veterinarians will be prepared to handle evidence properly within their own fields.

Animal Diseases↗

[The contribution of science to health promotion in the workplace].

An imposing amount of knowledge has been produced during the course of three hundred years of research in the field of occupational medicine and in other specialisations that in the last fifty years developed as branches of this discipline (industrial hygiene, industrial toxicology, respiratory physiopathology, etc). Part of this scientific heritage has been used to the full to plan and carry out prevention measures that have led to improved working conditions in many sectors of industry. Examples are the successes obtained in the prevention of pneumoconioses, aplastic anaemia and leukemia due to benzene, cancer caused by aromatic amines, and diseases occurring in pesticide users and consumers of agricultural products treated with such products. More recently, through original research programmes, with particular reference to the "Clinica del Lavoro" of Milan, a theoretical revision was made of the conception and method for analysing the relationship between organised work and health, resulting in an organic arrangement of the variables and procedures for the analysis of working conditions for the purposes of prevention. Other ways and areas where scientific bio-medical knowledge can be used are: a) planning of prevention measures on a vast social scale; b) variables and indicators for planning and assessing services designed for diagnosis and prevention of occupational risks and diseases; c) development of training programmes. In spite of these positive results, European Community statistics show that still too many occupational accidents and work-related diseases occur all over the world, especially in the developing countries, because the amount of scientific knowledge used is still much smaller than what is already available. The causes of this situation are many, among which those of a cultural nature. The author proposes the setting up of an "International Network for the History of Occupational and Environmental Prevention", and furnishes a detailed illustration of the aims and foreseeable initial actions.

Health Promotion↗

Fever: a concept analysis.

AIM: The purpose of this paper is to critically analyse the current state of the science literature in order to develop an accurate conception of fever. RATIONALE: The measurement of body temperature and treatment of fever have long been considered to be within the domain of nursing practice. What body temperature constitutes 'fever', however, is often not clear from nursing protocols or the literature. METHODS: Literature for this concept analysis was obtained by computerized searches of PubMed, CINAHL and BIOSYS for the years 1980-2004. Additional sources were obtained after reviewing the bibliographies of the literature identified by the initial search. The Wilsonian method of concept analysis provided the framework for the analysis. FINDINGS: Fever has characteristically been recognized as a cardinal sign of illness and has traditionally had negative connotations for patient well-being. Substantive advances over the past 20 years in immunology and neurophysiology have expanded understanding of the process of fever. This new knowledge has shifted the perception of fever as part of the acute-phase response to one of an adaptive nature. This knowledge has yet to be fully translated into changes in the fever management practices of nurses. CONCLUSIONS: Consistent usage of terminology in relation to fever should lead to improved and evidence-based care for patients, and to fever management practices consistent with current research. It is important to use clear language about fever and hyperthermia in discussions and documentation between nurses and among disciplines. By creating clarity in our language, we may help to achieve praxis.

Anxiety↗

Integrating the "new" with the "traditional": an innovative education model.

In 1998 the Faculty of Pharmacy and Pharmaceutical Sciences at the University of Alberta, Canada, introduced a new elective semester course entitled "The Pain Module" for pharmacy students in their final year of undergraduate training. The aim was to build on the existing theoretical content related to areas such as pharmacology and therapeutics and to generate opportunities for skill and attitude development, including those related to the management of cancer-related pain. Traditional formats such as classroom-based seminars were integrated with innovative methods such as computer-mediated discussions and conferencing (CMC) and academic bus rounds. The CMC component of the course served to provide continuity of discussion between weekly classroom discussions, gave students access to content experts on an ongoing basis and furthered learning initiated in the classroom. Students were given the opportunity to meet palliative care patients being cared for at home and in hospices. A total of 21 students participated in all the course activities. By the end of the course, there appeared to be a greater appreciation for end-of-life care issues. This highlights the need to incorporate end-of-life care into the undergraduate curriculum of disciplines other than medicine and nursing. Evaluation of the course identified several benefits and limitations of CMC. There was increased access to content experts and increased interaction between students. Limitations of CMC included increased time commitments and an open-ended nature that was uncomfortable for some learners. Other benefits and limitations are described further in this article. Future attempts at integrating new instructional technologies should be systematically evaluated.

Computer-Assisted Instruction↗

Whatsoever things are true: ways, means and values in modern psychiatry.

Epistemology and ethics are fundamental disciplines to understanding the nature of the medical enterprise. Values of truth, goodness, faith and love dominate the knowledge and practise of medicine. Each epistemological model of truth (truth as useful, truth as correspondence to fact, and truth as coherence) has strengths and weaknesses in guiding us in the scientific method in medicine. Dialectic skills are also important epistemological tools in exploring truth in relationship to diagnosis and treatment. By dialectic and analogy we approach the good as we explore and debate available technique and desirable goal. All of the doctor's scientific discipline and technical skill must be brought to bear within a relationship. It is here that the medical enterprise becomes intensely concerned with ethics. Most ethicists describe the doctor-patient relationship as a fiduciary relationship in which the doctor commits himself to his patient in faithfulness. The doctor-patient relationship is a special form of the "I-Thou relationship" grounded not only in trust but also in love.

Ethics, Medical↗

[An approach to food consumption in an urban environment. The case of west Africa].

West Africa has undergone rapid economic and political changes during the last 20 years. After the failure of economic policies implemented since independence, programs for structural adjustment have strongly influenced the economy. Food problems affect each country differently. The Sahel has experienced food shortages and starvation whereas in forested countries the food supply has remained stable. Nevertheless, food policies have not succeeded in contributing to urban and rural development. The rate of urbanization in west Africa is generally low but the rate of urban population growth is particularly high, much more than the growth rates of industry and infrastructure. Although metropolitan areas are affected by poverty, they offer more hope and opportunities than rural areas. Urban markets have expanded and diversified as social differences have also increased and contributed to changes in consumption structure. Urban growth has contributed to the increase of imported food: this is indicated by both the strong dependency and the change of food habits towards western food patterns. Recently however, west African urban dwellers are still preferring local items if they are affordable. When imported products are used, they are integrated within a stable meal plan consisting of a single dish with a base and a sauce, which is typical of African food preparation. Surveys of consumption-budgets are still only available on a national scale. These can provide accurate information about food consumption patterns of families, particularly for significant trends. However, they do not provide information about the dynamics of food consumption, neither for urban areas or the individual. Now a significant proportion of individual food consumption occurs outside of the home, mainly with food provided by street vendors. This new consumption habit is a response to the urban food crisis. Consumption of street-vendor-food comprises one component but this cannot be dissociated from in-home food consumption. Despite the growing importance of street-vendor food consumption, it has still not been adequately documented. Theoretically, food consumption is an evolving concept. Single disciplines, such as economics or nutrition, first studied food consumption. More recently, social sciences developed new approaches with various interpretations, which were sometimes contradictory. The evolution of urban food consumption and the numerous related problems support the approach proposed by some authors suggesting a mixed analysis integrating both economics and cultural factors. Operationally, a global and dynamic approach to food styles must consider urban heterogeneity and diversity of situations. For example, food consumption by people maintaining their in-home food habits shows the pertinence of studies focusing on individuals. Therefore, the food course concept may be a useful method for the study of food consumption.

Africa, Western↗

Sustainability science and engineering: the emergence of a new metadiscipline.

A case is made for growth of a new metadiscipline of sustainability science and engineering. This new field integrates industrial, social, and environmental processes in a global context. The skills required for this higher level discipline represent a metadisciplinary endeavor, combining information and insights across multiple disciplines and perspectives with the common goal of achieving a desired balance among economic, environmental, and societal objectives. Skills and capabilities that are required to support the new metadiscipline are summarized. Examples of integrative projects are discussed in the areas of sustainability metrics and integration of industrial, societal, and environmental impacts. It is clear that a focus on green engineering that employs pollution prevention and industrial ecology alone are not sufficient to achieve sustainability, because even systems with efficient material and energy use can overwhelm the carrying capacity of a region or lead to other socially unacceptable outcomes. To meet the educational and human resource needs required for this new discipline, the technological and environmental awareness of society must be elevated and a sufficient and diverse pool of human talent must be attracted to this discipline.

Conservation of Natural Resources↗

[A tribute to professor Héctor Croxatto Rezzio: setting up science in Chile. "Nature is always more amazing than our imagination can conceive"].

Héctor R. Croxatto, M.D., has recently celebrated his 90th anniversary, fully active in scientific research and in other academic activities. Along his productive life, he has contributed with original observations on the role of certain peptides in the pathogenesis of arterial hypertension. Furthermore, he has been a leader in the development of biological research in Chile and the mentor or teacher of several prominent disciples who have had, or are having, their own brilliant careers in medicine and in science in Chile and other Latinamerican countries. Although most of his scientific productivity has been published in top journals in the international field, several of his papers have been published in Revista Médica de Chile. In this issue, the journal pays a tribute to this outstanding scholar, his exceptional personality and fruitful academic career. The tribute includes this Editorial, a Letter to the Editor and its reply, and his most recent manuscript, all testifying the exceptional virtues of a great man.

Biological Science Disciplines↗

Emergence of quantification in clinical investigation and the quest for certainty in therapeutics: the road from Hammurabi to Kefauver.

Throughout most of history, medical knowledge was descriptive in nature and derived from the work of individual investigators of independent mind pursuing careful but often chance observations. Using deductive reasoning, these findings were then generalized, authoritatively presented, and dogmatically promulgated. This, coupled with firmly grounded principles of divine determinism, precluded any serious consideration of randomness, even when variations from recorded, but erroneous, statements were actually observed. Although probability remained an integral component of diagnosis and therapy, it was only as an attribute of opinion and not one supported by numbers. The gradual erosion of this edifice began during the scientific revolution of the seventeenth century that led to the burgeoning of the sciences basic to medicine. Although clinicians applauded these contributions, they failed to apply the inductive method of investigation to the study of disease or to therapy. The "numerical method" of Pierre Louis (1787-1872) first introduced systematic quantification into medicine during the first half of the nineteenth century. Analysis of quantifiable data found its principal application in epidemiology, which flourished during the second half of the nineteenth century. The subsequent adoption of probability calculus for the analysis of quantifiable data, during the first half of the twentieth century, refined the process further and led to the gradual emergence of medical statistics, with a distinct role in clinical research. The mathematical precision provided by quantification and statistical analysis established certainty in medicine and ultimately changed the conjectural art of clinical practice into a disciplined science founded on clinical investigation, the very basis of present-day, evidence-based medicine.

History, 15th Century↗

On key lesions and all that: a tribute to Paul Lohman.

This paper is a tribute to Paul Lohman at the occasion of his retirement from the position of Professor in the Medical Faculty at the Leiden University in The Netherlands and as Director of its Department of Radiation Genetics and Chemical Mutagenesis. Paul's contributions to the science of genetic toxicology are discussed in the context of more recent insights as to how mammalian cells process DNA damage, and how this may lead to cancer and, possibly, aging. Starting with his work on the characterization of UV-induced DNA repair in cultured cells from xeroderma pigmentosum patients and the development of methodology for monitoring the removal of UV-induced lesions in human cells, the concept of the key lesion is introduced. Among the myriad of DNA lesions that can be induced in DNA as a consequence of exposure to a range of natural or synthetic mutagens, key lesions are the ones responsible for subsequent adverse effects, for example, because they give rise to mutation. The development of methods using immunofluorescence microscopy to detect and identify such key lesions and quantitate them at the single cell level, is one of the highlights of Paul's career. Based on the perceived need to evaluate mutational end points in vivo in relation to specific lesions identified by his immunofluorescence methods, Paul subsequently made crucial contributions to the development of the first transgenic mouse model to measure mutations in chromosomally integrated reporter genes. In parallel to his experimental work, Paul greatly contributed to genetic toxicology at the theoretical level by his work on the development and evaluation of methods for assessment or prediction of risks of exposure to environmental mutagens. Finally, Paul has served the discipline of genetic toxicology in a more administrative role in various ways, both locally as one of the founders of the Medical Genetics Center South-West Netherlands and internationally by playing a prominent role in organizations such as ICPEMC. Here, his numerous contributions to the journal Mutation Research, both as author on many papers and as Executive Managing Editor should not go unmentioned.

Genetics↗

Radiation risk and human space exploration.

Radiation protection is essential to enable humans to live and work safely in space. Predictions about the nature and magnitude of the risks posed by space radiation are subject to very large uncertainties. Prudent use of worst-case scenarios may impose unacceptable constraints on shielding mass for spacecraft or habitats, tours of duty of crews on Space Station, and on the radius and duration of sorties on planetary surfaces. The NASA Space Radiation Health Program has been devised to develop the knowledge required to accurately predict and to efficiently manage radiation risk. The knowledge will be acquired by means of a peer-reviewed, largely ground-based and investigator-initiated, basic science research program. The NASA Strategic Plan to accomplish these objectives in a manner consistent with the high priority assigned to the protection and health maintenance of crews will be presented.

Aerospace Medicine↗

Communication in ecosystem management: a case study of cross-disciplinary integration in the assessment phase of the interior Columbia Basin Ecosystem Management Project.

Effective communication is essential to the success of collaborative ecosystem management projects. In this paper, we investigated the dynamics of the Interior Columbia Basin Ecosystem Management Project's (ICBEMP) cross-disciplinary integration process in the assessment phase. Using a case study research design, we captured the rich trail of experience through conducting in-depth interviews and collecting information from internal and public documents, videos, and meetings related to the ICBEMP. Coding and analysis was facilitated by a qualitative analysis software, NVivo. Results include the range of internal perspectives on barriers and facilitators of cross-disciplinary integration in the Science Integration Team (SIT). These are arrayed in terms of discipline-based differences, organizational structures and activities, individual traits of scientists, and previous working relationships. The ICBEMP organization included a team of communication staffs (CT), and the data described the CT as a mixed group in terms of qualifications and educational backgrounds that played a major role in communication with actors external to the ICBEMP organization but a minor one in terms of internal communication. The data indicated that the CT-SIT communication was influenced by characteristics of actors and structures related to organizations and their cultures. We conclude that the ICBEMP members may not have had a sufficient level of shared understanding of central domains, such as the task at hand and ways and timing of information sharing. The paper concludes by suggesting that future ecosystem management assessment teams use qualified communications specialists to design and monitor the development of shared cognition among organization members in order to improve the effectiveness of communication and cross-disciplinary integration.

Communication↗

1995 Volvo Award in basic sciences. The use of an osteoinductive growth factor for lumbar spinal fusion. Part II: Study of dose, carrier, and species.

STUDY DESIGN: Efficacy of a bovine-derived osteoinductive growth factor was studied in a rabbit model and in a nonhuman primate model of posterolateral lumbar spinal fusion. OBJECTIVES: To determine the minimum effective dose of growth factor and the influence of different carrier material on the outcome of intertransverse process lumbar fusion. SUMMARY OF BACKGROUND DATA: Bone morphogenetic proteins and related growth factors are becoming increasingly available in purified extract or genetically engineered forms and are capable of inducing new bone formation in vivo. Osteoinductive growth factors to enhance lumbar spinal infusion have not been well studied in models of posterolateral intertransverse process fusion. Because of the diminished potential of bone regeneration in primates (including humans) compared with phylogenetically lower animals, extrapolations regarding dose and efficacy cannot be made directly from results obtained in experiments performed on phylogenetically lower animals. Experiments on non-human primates are a critical step before attempting to use these growth factors on humans. METHODS. One hundred fifteen adult New Zealand white rabbits and 10 adult rhesus macaques underwent single level posterolateral intertransverse process lumbar spinal arthrodesis to evaluate different doses and carrier materials for a bovine-derived osteoinductive bone protein extract. Rabbit fusion masses were evaluated 5 weeks after arthrodesis by manual palpation, radiography, biomechanical testing, and light microscopy. Monkey fusion masses were evaluated 12 weeks after arthrodesis by radiography and light microscopy. RESULTS: Successful posterolateral intertransverse process spinal fusions were achieved in the rabbit models using an osteoinductive growth factor with three different carriers (autogenous iliac bone, demineralized allogeneic bone matrix, and natural coral). There was a dose-dependent response to the osteoinductive growth factor in the rabbit model, indicating that a threshold must be overcome before bone formation is induced. The methodology for biologic enhancement of spinal fusion developed in the rabbit model transferred successfully to the rhesus monkey, where the use of the osteoinductive growth factor with a demineralized bone matrix carrier resulted in spinal fusion in 12 weeks. CONCLUSION: These experiments provide an essential building block in the understanding of the biology of spinal fusion and the use of osteoinductive growth factors to enhance a posterolateral intertransverse process spinal fusion. The achievement of posterolateral spinal fusion in the rhesus monkey using an osteoinductive growth factor is a significant step toward the biologic enhancement of spinal fusion in humans.

Animals↗

Symptom experiences of children and adolescents with cancer.

This paper examines nursing research focused on the symptom experiences of children and adolescents with cancer, and the extent to which the perspective and methods of developmental science have been used in this research. CINALH, MEDLINE, and PSYCHLIT were searched for publications between 1990 and 2002. The researcher or research team had to include a nurse or developmentally oriented researchers from other disciplines. Studies focused exclusively on pain were excluded because of recent published reviews. While nurse researchers have contributed influential knowledge related to symptom experiences and symptom distress in children and adolescents with cancer, this research is still in a formative but exciting stage. Two nurse researchers and their teams laid the foundation for this research through their individual studies and collaborative multisite studies. In general, children and adolescents from 10 through 18 years of age were primarily studied; few studies focused on preschool children. Given the fact that these are rare populations, sample sizes were generally small, limiting power and generalizability. Gender, ethnicity, and socioeconomic status were rarely considered in analyses. Most studies used cross-sectional designs, although several included short-term longitudinal or repeated measure designs. To date, longitudinal designs focused on long-term outcomes have not been conducted. There were only a few qualitative studies. There was limited use of conceptual models or theories, and inadequate attention was paid to broader ecological perspectives in the children's lives. Studies included a focus on global symptoms and on individual symptoms, particularly pain and fatigue. Few focused on nausea and vomiting. Operationalization of symptom distress generally involved adapting instruments designed for adults. A more explicit employment of a developmental science perspective in future studies would call for more longitudinal designs that conceptualize the symptom experience from the perspective of the child and that view their responses as complex and multidimensional in nature. This would necessitate measuring clusters of symptoms at multiple levels (e.g., emotional, behavioral, and biophysiological) using developmental data collection methods. Furthermore, attention needs to be paid in conceptualizing studies to ecological factors related to families, social networks, communities, and ethnicity, as well as to the ecology of the health care system, which likely influences the symptom experience of children.

Adolescent↗