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Towards a medically approved technology for alginate-based microcapsules allowing long-term immunoisolated transplantation.

The concept of encapsulated-cell therapy is very appealing, but in practice a great deal of technology and know-how is needed for the production of long-term functional transplants. Alginate is one of the most promising biomaterials for immunoisolation of allogeneic and xenogeneic cells and tissues (such as Langerhans islets). Although great advances in alginate-based cell encapsulation have been reported, several improvements need to be made before routine clinical applications can be considered. Among these is the production of purified alginates with consistently high transplantation-grade quality. This depends to a great extent on the purity of the input algal source as well as on the development of alginate extraction and purification processes that can be validated. A key engineering challenge in designing immunoisolating alginate-based microcapsules is that of maintaining unimpeded exchange of nutrients, oxygen and therapeutic factors (released by the encapsulated cells), while simultaneously avoiding swelling and subsequent rupture of the microcapsules. This requires the development of efficient, validated and well-documented technology for cross-linking alginates with divalent cations. Clinical applications also require validated technology for long-term cryopreservation of encapsulated cells to maintaining a product inventory in order to meet end-user demands. As shown here these demands could be met by the development of novel, validated technologies for production of transplantation-grade alginate and microcapsule engineering and storage. The advances in alginate-based therapy are demonstrated by transplantation of encapsulated rat and human islet grafts that functioned properly for about 1 year in diabetic mice.

Alginates↗

Physician factors as an indicator of technological device adoption.

This paper analyzes a sample interventional cardiologist's demographic, academic, and professional characteristics to provide an understanding of their technological device adoption styles. The study sample consisted of 15 physicians from two large Midwestern hospitals, one an academic medical center and the other a medium-sized community hospital. Interventional cardiologists were identified through their online physician profile and respective departments. A questionnaire was developed to assess each physician's self-perceived adoption style, their awareness of the new technology, their participation in clinical trials, organizational support, and how various factors influence their adoption of new technology. Lastly, a database of bare metal and drug eluting stents was examined to document the number of stents used by each physician. Pragmatic and observational findings are presented from the questionnaire, physician profile, to database on stent use. The paper concludes with a discussion of the managerial and forecasting implications and methods to promote technology adoption.

Cardiology↗

Comparison of transcript profiling on Arabidopsis microarray platform technologies.

To date there have been few systematic studies comparing the results of transcript profiling from different microarray platform technologies. We evaluated in detail two different Arabidopsis thaliana microarray platforms: our own Genomic Amplicon arrays and the Qiagen long oligonucleotide arrays designed by Operon; furthermore, we cross-validated these arrays against the Affymetrix AG and ATH1 GeneChips. Data were obtained from all three platforms in each of two separate experiments; (1) at 2 h and (2) 8 h following a salicylic acid treatment applied to both wild-type and npr1-3 mutant plants. A total of 20 hybridizations were performed, analyzing the expression of 26,814 unique locus IDs. We demonstrate that intensity rank is a key variable that affects both inter-platform and cross-platform reproducibility. Although general agreement between platform technologies is low, data derived from high signal intensities (90th percentile) can correlate as well between differing platforms as replicates within the same platform (r=0.4-0.7). We also show that the identification of differentially expressed genes by significance analysis of microarrays is influenced by signal intensity and that overlap between significant gene lists from different platform technologies was as high as 67% when low intensity values were removed. Validation of 41 genes by Northern blot hybridization showed that all platform technologies performed well, qualitatively confirming 83-100% of differential gene expression. Our results suggest that the potential for the broad integration of microarray data from different platforms and laboratories is promising.

Arabidopsis↗

Amplicon-plus targeting technology (APTT) for rapid production of a highly unstable vaccine protein in tobacco plants.

High-level expression of transgenes is essential for cost-effective production of valuable pharmaceutical proteins in plants. However, transgenic proteins often accumulate in plants at low levels. Low levels of protein accumulation can be caused by many factors including post-transcriptional gene silencing (PTGS) and/or rapid turnover of the transgenic proteins. We have developed an Amplicon-plus Targeting Technology (APTT), by using novel combination of known techniques that appears to overcome both of these factors. By using this technology, we have successfully expressed the highly-labile L1 protein of canine oral papillomavirus (COPV L1) by infecting transgenic tobacco plants expressing a suppressor of post-transcriptional gene silencing (PTGS) with a PVX amplicon carrying a gene encoding L1, and targeting the vaccine protein into the chloroplasts. Further, a scalable "wound-and-agrospray" inoculation method has been developed that will permit high-throughput Agrobacterium inoculation of Nicotiana tabacum, and a spray-only method (named "agrospray") for use with N. benthamiana to allow large-scale application of this technology. The good yield and short interval from inoculation to harvest characteristic of APTT, combined with the potential for high-throughput achieved by use of the agrospray inoculation protocol, make this system a very promising technology for producing high value recombinant proteins, especially those known to be highly labile, in plants for a wide range of applications including producing vaccines against rapidly evolving pathogens and for the rapid response needed to meet bio-defense emergencies.

Biotechnology↗

A single instrument: engineering and engineering technology students demonstrating competence in ethics and professional standards.

This paper details efforts by the Purdue School of Engineering and Technology at Indiana University Purdue University Indianapolis (IUPUI) to create a single instrument for honors science, technology, engineering and mathematics (STEM) students wishing to demonstrate competence in the IUPUI Principles of Undergraduate Learning (PUL's) and Accreditation Board for Engineering and Technology (ABET) Engineering Accreditation Criterion (EAC) and Technology Accreditation Criterion (TAC) 2, a through k. Honors courses in Human Behavior, Ethical Decision-Making, Applied Leadership, International Issues and Leadership Theories and Processes were created along with a specific menu of activities and an assessment rubric based on PUL's and ABET criteria to evaluate student performance in the aforementioned courses. Students who complete the series of 18 Honors Credit hours are eligible for an Honors Certificate in Leadership Studies from the Department of Organizational Leadership and Supervision. Finally, an accounting of how various university assessment criteria, in this case the IUPUI Principles of Undergraduate Learning, can be linked to ABET outcomes and prove student competence in both, using the aforementioned courses, menu of items, and assessment rubrics; these will be analyzed and discussed.

Accreditation↗

An overview of advanced manufacturing technology.

In recent years there has been a veritable avalanche of information about AMT - advanced manufacturing technology - and, latterly, CIM - computer-integrated manufacturing. But what do these terms mean, and have the associated technologies been entirely successful? The opening section of this paper seeks to answer the first question by describing some of the radical changes currently occurring in manufacturing industry and suggesting possible definitions for both 'AMT' and 'CIM'. It will be shown that there is a steady trend in manufacturing towards 'integration' (of both functions and information) and that integration has progressed furthest in the area of flexible manufacturing systems (FMS). The second question is addressed by an analysis of the results of various surveys into the diffusion of FMS. This analysis indicates particular problems of design and implementation. The authors believe that many of these problems can be attributed to a 'technology-centred' approach to the design of man-machine systems and are common to other elements of AMT/CIM. The paper concludes with a brief description of research being carried out to develop an alternative 'human-centred' approach to the design and implementation of FMS and ultimately CIM. This approach seeks to integrate the design of computer-aided technology and work, in order to make optimal use of both technical and human resources in manufacturing systems.

Journal Article↗

Management of medical technology in developing countries.

To help developing countries to improve their medical use of physical technology, it is essential to study their difficulties and real needs. The greater severity of equipment problems in the third world, relative to the developed countries, indicates the important influence of an established technological culture. Strategies such as the training of technicians cannot succeed in the absence of this culture unless effective national policies to manage technology are implemented. The training of high-level staff in medical technology management must be a priority for international action. Below this level it is necessary to train engineering graduates, rather than technicians, to manage and maintain equipment.

Developing Countries↗

Prospective reimbursement and the diffusion of new technologies in hospitals.

This paper presents new evidence on the effects of prospective hospital reimbursement on the diffusion of new medical technologies in American hospitals. The probability, speed, and extent of adoption of five specific new technologies in six states, three with prospective reimbursement and three without, are examined using the results of a hospital survey conducted by the American Hospital Association for this study in 1980. The analysis demonstrates the influence of prospective reimbursement on the diffusion of new technologies. It is clear as well that these effects depend upon the specific attributes of the prospective reimbursement program and the characteristics of the technologies themselves.

Capital Expenditures↗

Future technological implications of demographic changes into the 21st century.

Throughout history there has been a constant interaction between the presence or absence of technological developments and demography. Technology in general and health technologies in particular have contributed to substantial changes in the demographic situation to the extent that even the morbidity and mortality patterns have adapted to technological progress. It is speculated that the demographic imperative will, during the third millennium, shift the centre of gravity of our world towards the Pacific basin. This in turn may influence our norms, values and practice of health care to the same extent as colonialism permeated the African, Asian and American health systems during the period of colonialism.

Demography↗

Decision to adopt new medical technology: a case study of thrombolytic therapy.

New medical technologies are adopted by practising physicians at varying rates. Thrombolytic therapy is an example of a technological advance that many physicians have seemed reluctant to employ. A random sample of board certified internists was surveyed by mail to study factors that influence decisions to use thrombolytic agents. Variables important in predicting use were identified by discriminant analysis. In general users and non-users had similar assumptions about the risks and benefits of this technology. Among the important predictor variables were a perception of having patients suitable for treatment, availability of the agents and self-rating of knowledge about this therapy. Among questions related to type of practice and education, only subspecialization and textbook reading were important discriminators. These results suggest that decisions to adopt new technologies do not follow simply from risk-benefit assessments.

Adult↗

Information for decision makers at hospital laboratory level: an example of a graphical method of representing costs and effects for a replacement automated technology in a haematology laboratory.

The costs and effects on patient management following the introduction of a fully automated blood count analyser have been evaluated for a hospital haematology laboratory in England, during 1985. In the case of the relatively high throughput observed in the laboratory studied, the automated technology was judged to be cheaper if considering laboratory-centred costs alone. But this was no longer necessarily the case once wider costs, including extra medical workload generated for hospital and community physicians, were included. Effects on patient management were measured for all types of patient, including hospital in-patients, out-patients and general practice patients. A graphical method allowing comparison of the costs and effects of the replacement automated system, termed a Technology MAP (Management Awareness Profile) is presented in the paper. MAPs provide a flexible information display which can be tailored to an individual laboratory's situation producing an overall picture of expected costs and effects on patient management following the introduction of a new technology--a full value-in-use assessment. The authors argue that there is a need for a central source of such value-in-use assessments, especially for new medium-priced diagnostic technologies which are likely to become widely spread in Britain.

Blood Cell Count↗

Evaluation of new technology in the clinical microbiology laboratory.

Technology capable of significantly influencing the practice of clinical microbiology is evolving at an ever-accelerating rate. During their early developmental years, it is difficult to predict which evolving technologies will prove amenable for use in hospital laboratory settings. With the considerable and increasing cost constraints placed on our medical institutions and the resulting budgetary pressures exerted on clinical laboratories, evaluation of developing technology is essential. The Clinical Laboratory Improvement Act of 1988 mandates correlation studies by clinical laboratories as part of the evaluation of all new assays to compare their sensitivities and specificities with those obtained using established methodologies. With shrinking numbers of technologists available for such evaluations, however, the mechanism with which this will be accomplished promises to pose a significant challenge. Factors that demand consideration in any such evaluation include (but are not restricted to) utility, accuracy, prospective time savings, cost of related instrumentation and reagents, and potential for diverse applications. Specific current examples that exemplify the need for such evaluations include the emergence of gene-based techniques such as the polymerase chain reaction as clinical tools, availability of new blood culture systems based on divergent sensor systems, and varying techniques for the the detection of antibodies and antigens for the serodiagnosis of infectious diseases. We as clinical microbiologists have the opportunity to approach the challenges confronting us regarding evaluation of developing technologies with responsible innovation and insight. Only by embracing these responsibilities can we hope to influence the impact of health care reform in the hospital laboratory setting.

Blood↗

The socioeconomic aspects of information technology for health care with emphasis on radiology.

RATIONALE AND OBJECTIVES: Information technology is the key to cost effective and error free medical care in the United States and the only problem is that there is not enough of it yet. During the past 15 years, billions of dollars have been spent on information technology for health care with very little benefit but significant adverse effects on patients, physicians, and nurses. The truth about health care information technology (HIT) probably lies somewhere between these extreme statements, representing technophile and skeptical views, respectively. MATERIALS AND METHODS: There is no doubt that computer and communication hardware has reached a state of sophistication and availability in which any and all necessary information can be generated, stored, and distributed to health care workers in support of their patient care tasks. The barriers to rapid and widespread development and diffusion of cost effective and practically useful HIT are exclusively related to human factors. RESULTS: This article explores some of the organizational, cultural, cognitive, and economic forces that interact to influence success of HIT initiatives in health care organizations. A key point to be recognized is that the intrinsically handcrafted nature of health care work combined with high degrees of complexity and contingency make it impossible to "computerize" with the same ease and completeness of other industries. The major thrust of the argument is that designers of information systems and health care informatics managers must meet needs of patients and care providers. The software they create and implement should promote, support, and enhance the existing processes of health care rather than seeking to dictate how direct care providers should do their work. CONCLUSIONS: Instead of looking for "buy in" from physicians and nurses, the informatics community must return the authority over functional specification of patient care information systems to them--where it belonged in the first place. This same lesson about computer technology and organizational politics is also being learned in the business community, where executives are reclaiming responsibility for mission critical informatics decisions.

Decision Support Techniques↗

Exosome Display technology: applications to the development of new diagnostics and therapeutics.

Exosome Display is a novel methodology enabling the manipulation of exosome protein content. This technology stems from the identification of addressing domains that mediate the specific distribution of proteins on exosomes. More particularly, Lactadherin expressed in non-mammary gland tissue has been found to localize to exosomes via binding of its C1C2 domain to exosome lipids. Exosome Display of soluble antigens and extracellular domains of membrane proteins that are not naturally found on exosomes occurs upon fusion of proteins with the Lactadherin C1C2 domain. Exosome Display of native full-length membrane proteins can also be achieved by non-restricted expression or sampling of membrane proteins on exosomes. These novel findings enable us to manipulate exosome composition and tailor exosomes with new desirable properties. The Exosome Display technology is very versatile since soluble, membrane-bound, trans-membrane or multimeric antigens that are not naturally found on exosomes can now be efficiently expressed at their surface in a native conformation. The technology was applied to the generation of antibodies against tumor biomarkers such as HLA/peptide complex. This antibody method called ExoMAb can be used to generate antibodies against any drug target candidates, notably including G-protein coupled receptors. The potential of Exosome Display technology for developing a broad range of novel diagnostics and therapeutics is discussed.

Antibodies↗

Microsystem technology as a road from macro to nanoworld.

Tremendous progress of microelectronic technology observed within last 40 years is closely related to even more remarkable progress of technological tools. It is important to note however, that these new tools may be used for fabrication of diverse multifunctional structures as well. Such devices, called MEMS (Micro-Electro-Mechanical-System) and MOEMS (Micro-Electro-Opto-Mechanical-System) integrate microelectronic and micromechanical structures in one system enabling interdisciplinary application, with most interesting and prospective being bio-medical investigations. Development of these applications requires however cooperation of multidisciplinary team of specialists, covering broad range of physics, (bio) chemistry and electronics, not mentioning medical doctors and other medical specialists. Thus, dissemination, of knowledge about existing processing capabilities is of key importance. In this paper, examples of various applications of microelectronic technology for fabrication of Microsystems which may be used for medicine and chemistry, will be presented. Besides, information concerning a design and technology potential available in poland and new, emerging opportunities will be given.

Microchemistry↗

Overview of marker vaccine and differential diagnostic test technology.

Recent advances in molecular biology, immunology, microbiology, genetics and microbial pathogenesis have lead to the development of a wide variety of new approaches for developing safer and more effective vaccines based on designs such as subunit vaccines, gene deleted vaccines, live vectored vaccines, and DNA mediated vaccines. Technology tools can be as basic as identifying naturally occurring strains with deletions that support differentiating infected from vaccinated animal (DIVA) needs or be based on higher technology developments such as improved protein expression and purification methods, transgenic plant- and plant virus-based antigen production, and novel adjuvants that target specific immune responses. These new approaches, when applied to the development of marker vaccines and companion diagnostic test kits hold tremendous potential for developing improved tools for eradication and control programs. Marker vaccines and companion diagnostic test kits must meet the established licensing requirements for purity, potency, safety and efficacy. Efficacy claims are based on evaluation of the level of protection demonstrated in host animal trials and may range from "prevents infection with (a specific agent)", to "for use as an aid in the reduction of disease due to (a specific agent)." The differences in claims and recommendations are a function of the variation in protection elicited by various vaccines. For designing effective eradication programs, vaccine efficacy characteristics such as for reducing susceptibility to infections and spread of infections must be well defined; similarly, diagnostic test performance characteristics (efficacy) must be determined. In addition to data to support efficacy claims, it is imperative that safety of production and use of vaccines be evaluated. During the design of marker vaccines and diagnostic tests, it is important to consider the application of appropriate technologies to improve the safety of these products. Use of recombinant technologies for production of vaccines and/or diagnostic test antigens can reduce the biosafety concerns during production and during use, including human exposure to zoonotic pathogens during production and use, and potential spread of foreign animal disease agents due to loss of biocontainment. In addition, vaccines may induce adverse reactions. It is important to determine the frequency of adverse events and to reduce the likelihood of induction of adverse reactions through proper design.

Animals↗

Genomic and proteomic technologies for individualisation and improvement of cancer treatment.

The development of microarray-based technologies for characterising tumours, both at the genomic and proteomic levels, has had a significant impact on the field of oncology. Gene expression profiling of various human tumour tissues has led to the identification of expression patterns related to disease outcome and drug resistance, as well as to the discovery of new therapeutic targets and insights into disease pathogenesis. Protein microarray technologies, such as reverse-phase protein arrays, provide the unique opportunity to profile tissues and assess the activity of signalling pathways within isolated cell populations. This technology can be used to identify patients likely to benefit from specific treatment modalities and also to monitor therapeutic response in samples obtained during and after treatment. Routine application of genomic and proteomic microarray technologies in clinical practice will require significant efforts to standardise the techniques, controls and reference standards, and analytical tools used. Extensive, independent validation using large, statistically-powered datasets will also be necessary. Inclusion of concomitant genomic and proteomic-based molecular profiling techniques into clinical trial protocols will bring us closer to the reality of patient-tailored therapy.

Gene Expression Profiling↗

Digital technologies and quality improvement in cancer surgery.

Telecommunications, multimedia and computer technologies will introduce marked changes in the management of cancer. New modalities in the representation of patient's medical records using computer technology products and services allow unlimited cross-sharing of information. Education taught through multimedia methods, and through the Internet, is available anywhere and any time just like surgical simulation, robotics and virtual reality. Thanks to computer and IT technologies, surgeons will be able to acquire, assess and validate new surgical procedures or concepts from any geographical location. Live demonstrations shared via videoconferencing facilitate mental development through the acquisition of the cognitive aspects of surgical procedures. Virtual reality is a major improvement in the processing of medical imaging. As a result, the interpretation and the simulation of therapeutic approaches to patients with cancer are facilitated through transparency, navigation and manipulation. The Internet eventually offers uninterrupted communication links between healthcare providers (teaching, training or multidisciplinary telementoring included). Computer and IT technologies will undoubtedly contribute to standardized cancer treatment modalities and determined guidelines for good clinical practice worldwide.

Computer-Assisted Instruction↗