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Cultural ergonomics in Ghana, West Africa: a descriptive survey of industry and trade workers' interpretations of safety symbols.

Globalization and technology transfer have led to the diffusion of risk communications to users from cultures that were not initially viewed as the target users. This study examined industry and trade workers' overall impressions of symbols used to convey varying degrees of hazardousness. Six symbols, including symbols from the American National Standards Institute (ANSI) Z535 Standard (ANSI, 1998) and the International Organization for Standardization (ISO) 3864:1984 Standard (ISO, 1984) were selected. With the exception of the SKULL symbol, results showed wide discrepancies between users' perceptions of the symbols and their intended meanings. Implications for cross-cultural research on warning components and risk communications are discussed.

Accidents, Occupational↗

Changing provider practices, program environment, and improving outcomes by transporting multidimensional family therapy to an adolescent drug treatment setting.

Effective interventions for drug abusing adolescents are underutilized. Using an interrupted time series design, this study tested a multicomponent, multi-level technology transfer intervention developed to train clinical staff within an existing day treatment program to implement multidimensional family therapy (MDFT), an evidence-based adolescent substance abuse treatment. The sample included 10 program staff and 104 clients. MDFT was incorporated into the program and changes were noted in the program environment, therapist behavior, and in most (e.g., drug abstinence, and out of home placements) but not all (e.g., drug use frequency) client outcomes. These changes remained after MDFT supervision was withdrawn.

Adolescent↗

An overview of health-related industrial biotechnology in Latin America and the Caribbean.

There is some uncertainty about the extent to which Latin America and the Caribbean have participated in the advances of health-related industrial biotechnology. This article reviews the available literature and seeks to provide an overview of the prevailing situation. In general, national governments and multinational agencies have provided most of the health-related biotechnology investments within this region. Efforts to achieve technology transfers, a subject of prime concern, have been developed by a number of programs including the WHO Special Program for Research and Training in Tropical Diseases, the UNDP/UNESCO/UNIDO Regional Biotechnology Program for Latin America and the Caribbean; PAHO's Program for the Regional Development of Biotechnology as Applied to Health; The PAHO/WHO Expanded Program on Immunization (EPI); and PAHO's Regional System of Vaccines (SIREVA). Regarding current production capacity, some successful efforts have been made to produce a variety of therapeutic products including recombinant and natural interferons, interleukins, insulin, and recombinant streptokinase; but in general the region's current potential in this area is at best incipient and uncertain. However, the region does have a limited ability to make diagnostic products and a well-established capacity for vaccine development. Overall, this picture suggests that the region has the potential to play a small but significant role in health-related biotechnology.

Biological Products↗

Characteristics, beliefs, and practices of community clinicians trained to provide manual-guided therapy for substance abusers.

The successful dissemination of empirically supported addiction therapies to community providers requires an appreciation of the characteristics of those practitioners who might be willing participants in this process of technology transfer. Clinicians (N = 66) from 11 community treatment programs associated with six research-clinic partnerships of the National Drug Abuse Clinical Trials Network volunteered to be trained in Motivational Interviewing or Motivational Enhancement Therapy (MET/MI) and were assessed prior to training. The sample of clinicians was heterogeneous in education and credentials, had a high level of counseling experience, reported using a wide range of counseling techniques and orientations, but had limited prior exposure to MET/MI or to the use of treatment manuals of empirically supported therapies. In general, many of the clinicians reported beliefs and techniques that were consistent with their stated theoretical orientation and recovery status. Relatively few participants reported relying on one dominant orientation or set of techniques.

Adult↗

Tissue engineering via local gene delivery: update and future prospects for enhancing the technology.

This review describes the status of a local plasmid-based gene transfer technology known as the gene activated matrix (GAM). Studies over the past 6 years suggest that GAM may serve as a platform technology for local gene delivery in the wound bed of various tissues and organs. These studies demonstrated that plasmid encoding genes can be delivered to acutely injured tendon, ligament, bone, muscle, skin and nerve. Moreover, direct in vivo transfer of therapeutic plasmid encoding genes in bone, skin and nerve was associated with a significant regenerative response relative to sham controls. The review also describes new technology that should enhance the potential of local gene delivery in a manner consistent with the risk-benefit profile associated with tissue engineering applications.

Biotechnology↗

Getting patients the services they need using a computer-assisted system for patient assessment and referral--CASPAR.

The two goals of this technology transfer study were to: (1) increase the number and appropriateness of services received by substance abuse patients, and thereby (2) give clinical meaning and value to research-based assessment information. A software-based Resource Guide was developed to allow counselors to easily identify local resources for referral of their patients to additional clinical and social services. Two hours of training were provided on the use of the guide. It was hoped that this software and training would provide the counselors with a concrete method of linking the Addiction Severity Index (ASI) assessment information on patient problems to appropriate, available community services. We expected improved treatment planning, increased problem services matching, better patient-counselor rapport/satisfaction and better patient-performance during treatment. Data were analyzed from 131 patients of 33 counselors from 9 treatment programs, randomly assigned to 2 groups--Standard Assessment (SA) or Enhanced Assessment (EA). Patients of counselors in the EA group (1) had treatment plans that were better matched to their needs, (2) received significantly more and better-matched services than patients in the SA group, and (3) were less likely to leave treatment against medical advice and more likely to complete the full course of treatment than patients of counselors in the SA group. They did not have higher levels of patient satisfaction or helping alliance scores. These findings are discussed with regard to integrating empirically supported procedures into contemporary, community-based substance abuse treatment.

Computers↗

Review of North-South and South-South cooperation and conditions necessary to sustain research capability in developing countries.

The paper extracted pertinent aspects of 21 years (1981-2001) of scientific cooperation among Zimbabwe's Blair Research Laboratory (BRL), the Biomedical Research and Training Institute (BRTI), and the Danish Bilharziasis Laboratory (DBL). DBL supported the building of research capacity at BRL through PhD-level training and short courses on research training organized by BRTI. The BRL-BRTI-DBL cooperation involved institutional support, scientific training, joint research programmes, and technology transfer, and forms a basis for the discussion of North-South and South-South collaboration in this paper. As the collaboration matured, DBL researchers began cooperating with their counterparts at BRL in internationally funded research programmes and partnerships based on mutual interests and responsibilities. Several research projects were formulated under co-principal investigators from the two institutions and later extended to other European and US institutions. An impressive outturn (18 PhDs) of postgraduate students undertaking field-based PhD work was accomplished from 1990 to 2001. As the socioeconomic situation in Zimbabwe deteriorated from 1999, significant attrition of senior scientists began to affect some of BRL's core functions in support of the Ministry of Health's programmes. In solidarity with BRL, DBL and BRTI jointly implemented a management-strengthening project to reduce deterioration of research productivity by retaining mid-level research managers. BRTI, able to respond rapidly to research needs in the Southern Africa Development Community (SADC), is not in competition with national research institutions and universities. An advisory committee of SADC stakeholders sets its priorities. The framework for South-South cooperation is research training to facilitate national scientists to attract resources from local and international funding agencies. It has established a National Institutes of Health-accredited ethical review board that provides ethical assurance for BRTI and non-BRTI-administered projects. Over the last eight years, BRTI has established regional and international legitimacy, and many funding agencies accept the role of the organization in 'Third Country Training for South-South Cooperation'. The article concludes by identifying essential conditions for sustaining research capability at BRL and similar institutions in developing countries. In rolling out a new ethos for research, great expectation is placed on the success of the New Partnership for Africa Development.

Communicable Disease Control↗

Somatic gene therapy in gastroenterology: approaches and applications.

Somatic gene therapy represents a new approach for treating a variety of genetic and acquired diseases and has many potential applications in gastroenterology. Somatic gene therapy is based on the ability to transfer recombinant genes efficiently into somatic tissues, such as the liver or intestine, and achieve expression of the recombinant gene product. Gene transfer could be used to replace genetically defective gene functions or prevent the progression of acquired or multifactorial diseases. The therapeutic application of gene transfer technologies requires development of methods for achieving efficient transfer and expression of recombinant gene products, research directed at developing strategies for altering the course of disease, and clinical research aimed at assessing both the technical feasibility and therapeutic efficacy of this approach.

Ethics, Medical↗

Low-volume jet injection for efficient nonviral in vivo gene transfer.

The transfer of naked deoxyribonucleic acid (DNA) represents an alternative to viral and liposomal gene transfer technologies for gene therapy applications. Various procedures are employed to deliver naked DNA into the desired cells or tissues in vitro and in vivo, such as by simple needle injection, particle bombardment, in vivo electroporation or jet injection. Among the various nonviral gene delivery technologies jet injection is gaining increasing acceptance because it allows gene transfer into different tissues with deeper penetration of the applied naked DNA. The versatile hand-held Swiss jet injector uses pressurized air to force small volumes of 3 to 10 microL of naked DNA into targeted tissues. The beta-galactosidase (LacZ) reporter gene construct and tumor necrosis factor alpha gene-expressing vectors were successfully jet injected at a pressure of 3.0 bar into xenotransplanted human tumor models of colon carcinoma. Qualitative and quantitative expression analysis of jet injected tumor tissues revealed the efficient expression of these genes in the tumors. Using this Swiss jet-injector prototype repeated jet injections of low volumes (3-10 microL) into one target tissue can easily be performed. The key parameters of in vivo jet injection such as jet injection volume, pressure, jet penetration into the tumor tissue, DNA stability have been defined for optimized nonviral gene therapy. These studies demonstrate the applicability of the jet injection technology for the efficient and simultaneous in vivo gene transfer of two different plasmid DNAs into tumors. It can be employed for nonviral gene therapy of cancer using minimal amounts of naked DNA.

Animals↗

Technology assessment and transfer in district health systems.

Initially reviewing the concepts of a district health system and technologies, the article develops into a discussion on health technologies and the process of their transnational diffusion, as well as their impact on district health systems in developing countries. Finally, the paper points to the need for assessment and quality assurance in a managed transfer of technologies.

Developing Countries↗

Transfer of medical technology from a developed to a developing country.

Medical care is increasingly dependent on technology, but what are the problems involved in the transfer of technology from a developed to a developing country? What are the administrative, personnel and engineering problems? We address these questions in the context of our experience of transferring the medical technology and knowledge necessary for the development of nuclear medicine facilities in Kuwait.

Biomedical Engineering↗

Gene-based cancer vaccines: an ex vivo approach.

The application of gene transfer techniques to immunotherapy has animated the field of gene-based cancer vaccine research. Gene transfer strategies were developed to bring about active immunization against tumor-associated antigens (TAA) through gene transfer technology. A wide variety of viral and nonviral gene transfer methods have been investigated for immunotherapeutic purposes. Ex vivo strategies include gene delivery into tumor cells and into cellular components of the immune system, including cytotoxic T cells and dendritic cells (DC). The nature of the transferred genetic material as well as the gene transfer method has varied widely depending on the application. Several of these approaches have already been translated into clinical gene therapy trials. In this review, we will focus on the rationale and types of ex vivo gene-based immunotherapy of cancer. Critical areas for future development of gene-based cancer vaccines are addressed, with particular emphasis on use of DC and on the danger-tolerance hypothesis. Finally, the use of gene-modified DC for tumor vaccination and its prospects are discussed.

Animals↗

A comparison of established and new approaches in ovine and bovine nuclear transfer.

Several breakthroughs in nuclear transfer research were first achieved in sheep, although cattle soon became the main livestock species of interest. However, sheep still offer significant advantages both in basic and applied research. With increased interest in cloning of livestock, new approaches have been developed for both sheep and cattle nuclear transfer technology. These include methods for zona-free nuclear transfer that can be performed with or without the use of micromanipulator. Here we describe four different nuclear transfer methods including the traditional micromanipulation-assisted method in sheep, zona-free method in sheep in which the order of enucleation and nucleus delivery have been reversed ("reverse-order" cloning) and zona free manual cloning methods ("hand-made cloning") for embryonic and somatic cloning in cattle. The purpose of this paper is to encourage people to familiarize themselves with these different methods available and to help them choose and test the method most suitable for their particular circumstances.

Animals↗

Biological barriers to cellular delivery of lipid-based DNA carriers.

Although lipid-based DNA delivery systems are being assessed in gene therapy clinical trials, many investigators in this field are concerned about the inefficiency of lipid-based gene transfer technology, a criticism directed at all formulations used to enhance transfer of plasmid expression vectors. It is important to recognize that many approaches have been taken to improve transfection efficiency, however because of the complex nature of the formulation technology being developed, it has been extremely difficult to define specific carrier attributes that enhance transfection. We believe that these optimization processes are flawed for two reasons. First, a very defined change in formulation components affects the physical and chemical characteristics of the carrier in many ways. As a consequence, it has not been possible to define structure/activity relationships. Second, the primary endpoint used to assess plasmid delivery has been transgene expression, an activity that is under the control of cellular processes that have nothing to do with delivery. Gene expression following administration of a plasmid expression vector involves a number of critical steps: (i) DNA protection, (ii) binding to a specific cell population, (iii) DNA transfer across the cell membrane, (iv) release of DNA into the cytoplasm, (v) transport through the cell and across the nuclear membrane as well as (vi) transcription and translation of the gene. The objective of this review is to describe lipid-based DNA carrier systems and the attributes believed to be important in regulating the transfection activity of these formulations. Although membrane destabilization activity of the lipid-based carriers plays an important role, we suggest here that a critical element required for efficient transfection is dissociation of lipids bound to the plasmid expression vector following internalization.

Journal Article↗

Improvement of nonviral gene therapy by Epstein-Barr virus (EBV)-based plasmid vectors.

The nonviral gene transfer technologies include naked DNA administration, electrical or particle-mediated transfer of naked DNA, and administration of DNA-synthetic macromolecule complex vectors. Each method has its advantage, such as low immunogenicity, inexpensiveness, ease in handling, etc., but the common disadvantage is that the transfection efficiency has been relatively poor as far as conventional plasmid vectors are involved. To improve the nonviral gene transfer systems, Epstein-Barr virus (EBV)-based plasmid vectors (also referred to EBV-based episomal vectors) have been employed. These vectors contain the EBNA1 gene and oriP element that enable high transfer efficiency, strong transgene expression and long term maintenance of the expression. In the current article, I review recent preclinical gene therapy studies with the EBV plasmid vectors conducted against various diseases. For gene therapy against malignancies, drastic tumor suppression was achieved by gancyclovir administrations following an intratumoral injection with an EBV plasmid vector encoding the HSV1-TK suicide gene. Equiping the plasmid with carcinoembryonic antigen (CEA) promoter sequences enabled targeted killing of CEA-positive tumor cells, which was not accomplished by conventional plasmid vectors without the EBV genetic elements. Transfection with an apoptosis-inducing gene was also effective in inhibiting tumors. Interleukin (IL)-12 and IL-18 gene transfer, either local or systemic, induced therapeutic antitumoral immune responses including augmentation of the cytotoxic T lymphocyte (CTL) and natural killer (NK) activities, while an autologous tumor vaccine engineered to secrete Th1 cytokines via the EBV system also induced growth retardation of tumors. Non-EBV conventional plasmids were much less effective in eliciting these therapeutic outcomes. Intracardiomuscular transfer of the beta-adrenergic receptor gene induced a significant elevation in cardiac output in cardiomyopathic animals, suggesting the usefulness of the EBV system in treating heart failure. The EBV-based nonviral delivery also worked as genetic vaccine that triggered prophylactic cellular and humoral immunity against acute lethal viral infection. All the nonviral delivery vehicles so far tested showed an improved transfection rate when combined with the EBV-plasmids. Collectively, the EBV-based plasmid vectors may greatly contribute to nonviral gene therapy against a variety of disorders, including malignant, congenital, chronic and infectious diseases.

Animals↗

Advances in biotechnology: new tools in future pig production for agriculture and biomedicine.

Biotechnology in livestock comprises an arsenal of reproductive biotechniques and molecular genetics. While molecular genetics are poorly developed in swine, reproductive techniques are more advanced and applied under field conditions. This review describes three selected examples of our own research to illustrate the implication of biotechnology in future pig reproduction. Sperm sexing technology is now available and can be used to generate piglets of the desired sex by IVF and ICSI. First studies also indicate satisfactory success rates following intrauterine insemination with sexed spermatozoa. Cloning technique and production of transgenic pigs require information about the regulation and time course of gene expression during in vitro production and pre-implantation development. Information on gene expression is scare in porcine embryos. With the exception of transcripts for the oestrogen receptor gene, no mRNA's from the activated porcine genome have been identified. Recent development of cDNA arrays might help to identify a larger amount of genes in single embryos. Remarkable progress has been made in organ transplantation technology. As the demand for human organs is increasing rapidly, the pig might serve as donor of xenotranplants, provided the transmission of zoonoses from the donor animal to the human recipient is prevented, donor organ anatomy and function are compatible, and immunological rejections (HAR, VAR MAC) can be overcome. The most promising strategy is the synthesis of human complement regulatory proteins in the pig. Transgenic pigs have been generated for hDAF or hCD 46 and their hearts have been transplanted into non human primates for up to 90 days. HCD 59 driven by CMV promotor provides significant protection against HAR at least under in vitro and in vivo conditions. Current studies indicate a temporary use in patients within the next 3-5 years. As the microinjection technology to produce transgenic offspring is time consuming and very expensive, nuclear transfer technology provides a possibility for multiplication without going through the germ line with recombination effects. A functional nuclear transfer system will be crucial for xenotransplantation as it is anticipated that the expression of several transgenes will be required.

Agriculture↗

Commercial applications of nuclear transfer cloning: three examples.

Potential applications of cloning go well beyond the popularly envisioned replication of valuable animals. This is because targeted genetic modifications can be made in donor cells before nuclear transfer. Applications that are currently being pursued include therapeutic protein production in the milk and blood of transgenic cloned animals, the use of cells, tissues and organs from gene-modified animals for transplantation into humans and genetically modified livestock that produce healthier and safer products in an environmentally friendly manner. Commercial and social acceptance of one or more of these early cloning applications will lead to yet unimagined applications of nuclear transfer technology. The present paper summarises progress on three additional applications of nuclear transfer, namely the development of male livestock that produce single-sex sperm, the transfer of immune responses from animals to their clones to permit the production of unlimited supplies of unique polyclonal antibodies, and the generation of genetically modified animals that accurately mimic human diseases for the purpose of developing new therapies. However, the myriad applications of cloning will require appropriate safeguards to ensure safe, humane and responsible outcomes of the technology.

Animals↗