New technology expands use of radiosurgery.
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Cost-Benefit Analysis↗
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High technology ... struggling to balance the promise of innovation with the reality of affordability.
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Device Approval↗
Blind persons navigate in virtual reality (VR); hearing and feeling communicates "reality".
Can Virtual Reality (VR) developments in audio navigation for blind persons support therapies for all? Working with Crystal River Engineering we are developing navigable Virtual Reality worlds for blind users, using spatialized audio [1], [2]. All persons, however, use specialized channels, such as: visual, aural, and kinetic learning senses. Predominantly visual VR worlds and health informatics models from World Wide Webs, may be downloaded, tailored, augmented, and delivered to each of these learning senses using VR. We are also testing a proof of concept system with Boston Dynamics which downloads 3-dimensional, satellite-derived map models from the World Wide Web, and makes them navigable by "feeling" the terrain using haptic (tactual or force feedback to your hand) robotic interfaces. Ultimately, these multi-sensory VR access methods: sight, localization by audio, and "feeling" of data sets could open up the World Wide Web to individuals with sight impairments. This could also, however, benefit government, businesses, universities, and (elementary) education. It could contribute more powerful communications, education, and medical simulation applications on the World Wide Web. This work is part of government technology transfer to telemedicine, (elementary) education, disabilities access to the Web, and new Internet access and productivity efforts under Vice President Gore's National Performance Review.
Adult↗
Clinical evaluation of a new, above-elbow, body-powered prosthetic arm: a final report.
The AdVAntage Arm is an above-elbow (AE) body-powered arm designed to improve upon, and overcome, some of the major limitations of conventional prostheses. It is the result of research and development (R&D) accomplished at the Center for Engineering Design (CED), University of Utah and Sarcos Research Corporation (SRC), Salt Lake City, UT. The AdVAntage Arm was developed to provide the following main features: lightweight, independent elbow and terminal device (TD) control, and a cable recovery system for full TD actuation at any elbow position. The Department of Veterans Affairs (VA) Rehab R&D Service's Technology Transfer Section (TTS), with collaboration from the VA National Prosthetic and Sensory Aids Service (PSAS), managed a multi-center clinical evaluation of the precommercial AdVAntage Arm (the Arm). The purpose was to objectively assess and affirm the Arm's functional advantages, reliability, clinical application, and commercial readiness. Eleven VA prosthetic services served as evaluation sites with a total of 16 subjects with amputation (14 unilateral and 2 bilateral). Fifteen prosthetists provided their comments. Overall, the results demonstrated that the Arm could be fit for use by persons with transhumeral, and even with forequarter, amputation. Once the learning curve was overcome, the majority of subjects reported that the Arm offered several functional advantages over their conventional prosthesis. Its overall light weight, separation of elbow and TD function, and cable recovery system allowed opening and closure of the TD at any elbow position; resulting in a more fluid manner of use and allowing subjects to perform more activities from waist level and above (especially in the outstretched and overhead positions). At the conclusion of clinical trials, 10 subjects elected to keep the Arm for continued use. The manufacturer is committed to the commercial marketing and technical support of the arm. Based upon the clinical findings, the AdVAntage Arm was recommended for commercial production and availability, upon prescription, to appropriate veteran beneficiaries.
Activities of Daily Living↗
[Transgenic pigs for xenotransplantation for humans].
Transgenic livestock have been generated via microinjection of DNA-constructs into pronuclei of zygotes. However, efficiency is low and only 1-3% transgenic offspring are to be obtained. Integration of the transgene occurs at random and expression is independent from the number of integrated copies but can be affected by the integration site. To overcome the shortage of human organs, transgenic pigs have been generated that express human complement regulatory genes. This approach enables to overcome the hyperacute rejection response as shown by an average survival rate (40-90 days) of the immunosuppressed primate recipients receiving a heart from a transgenic pig. It is expected that transgenic pigs would be available as organ donors in the next 5-10 years. A major prerequisite, however, is the prevention of the potential transfer of pathogenic microorganisms, in particular porcine endogenous retroviruses (PERV). Improvements of the efficiency in the generation of transgenic pigs will be achieved by the use of genetically modified donor cells in nuclear transfer technology (cloning).
Animals↗
New approaches to modify glomerular inflammation.
Glomerulonephritis remains the leading cause of end-stage renal failure and treatments for these conditions remain non-specific and with significant side effects. The cellular and molecular basis of acute and chronic inflammation is increasingly understood and the work in a number of animal models of nephritis demonstrates the potential of specific molecular interventions. These include preventing the migration of inflammatory cells by inhibiting the effects of chemokines or blocking endothelial/leucocyte adhesion interactions. Within damaged tissue it is possible to decrease the activity of pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor (TNF) by using their natural antagonists, namely interleukin-1 receptor antagonist (IL-1ra) and soluble TNF receptors. In addition the behaviour of macrophages can be altered by the effects of anti-inflammatory cytokines including interleukin-4 (IL-4), interleukin-13 (IL-13), interleukin-10 (IL-10), interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta). By deactivating the inflammatory response of macrophages these cytokines can favour resolution of disease. The ability to use these approaches in clinical practice remains elusive, however the prospect of using gene transfer technology to deliver anti-inflammatory factors directly to the site of inflammation and our increasing understanding of the complexity of the control of inflammation bring such therapies closer.
Animals↗
Genetic testing for patients with renal disease: procedures, pitfalls, and ethical considerations.
The Human Genome Project is rapidly producing insights into the molecular basis of human genetic disorders. The most immediate clinical benefit is the advent of new diagnostic methods. Molecular diagnostic tools are available for several genetic renal disorders and are in development for many more. Two general approaches to molecular diagnosis are linkage-based testing and direct mutation detection. The former is used when the gene has not been cloned but has been mapped in relation to polymorphic loci. Linkage-based testing is also helpful when a large diversity of mutations makes direct detection difficult. Limitations include the need to study multiple family members, the need for informative polymorphisms, and genetic heterogeneity. Direct mutation detection is limited by genetic heterogeneity and the need to distinguish nonpathogenic allelic variants from pathogenic mutations. Molecular testing raises a number of complex ethical issues, including those associated with prenatal or presymptomatic diagnosis. In addition, there are concerns about informed consent, privacy, genetic discrimination, and technology transfer for newly developed tests. Health professionals need to be aware of the technical and ethical implications of these new methods of testing, as well as the complexities in test interpretation, as molecular approaches are increasingly integrated into medical practice.
Ethics, Medical↗
Betting on the future: the virtues of contingent contracts.
It happens all the time. Two parties with common interests fail to reach an agreement--about a sale, a merger, a technology transfer--because they have different expectations about the future. They are both so confident in their prediction, or so suspicious of the other side's motives, that they refuse to compromise. Such impasses are hard to break through. Fortunately, they can often be avoided altogether by using a straightforward but frequently overlooked type of agreement called a contingent contract. The terms of a contingent contract are not finalized until the uncertain event in question--the contingency--takes place. In some areas of business, such as compensation, contingent contracts are common: a CEO's pay is tied to the company's stock price, for instance. But in many business negotiations, contingent contracts are either ignored or rejected out of hand. That's mistake, according to the authors. In an increasingly uncertain world, flexible contingent contracts can actually be more rational and less risky than rigid, traditional ones. In particular, contingent contracts offer six benefits: they enable a difference of opinion to become the basis of an agreement, not an obstacle to it; they cancel out the biases of negotiators; they level the playing field by reducing the impact of asymmetric information; they provide a means of uncovering deceitful dealings; they reduce risk by sharing it among parties; and they motivate parties to fulfill their promises. While contingent contracts are not appropriate in all instances, they are much more broadly applicable than managers may think.
Contract Services↗
Telemetry as a new concept in long term monitoring of SIDS-risk infant.
Sudden Infant Death Syndrome (SIDS) is the most frequent cause of infant death within the period of 2 to 12 months in western countries. It has been found that a suit similar to that worn by the astronauts during the execution of experiments on the Spacelab Mission D-2 is a very simple and useful means to carry the sensors required to monitor vital signs of babies at risk. A small baby-suit has been developed with the same technology used for the Spacelab Mission. The baby s suit is equipped with similar sensors to record thoracic and abdominal respiratory movements as its big -space travel brother-. This is a typical example of a successful technology transfer from medical aerospace activities into fields of daily clinical routine. In addition to the above described sensors, ECG-electrodes were integrated, as well as sensors to record vascular oxygen saturation and the corresponding pulse curve, and the baby s movements. All these vital signs are registered by a medical monitor, and permanently stored and automatically analysed online. In case of a life-threatening situation the system alerts simultaneously the personal at hospital and the parents at home. The requisite software algorithms have been developed by DLR in Cooperation with the pediatricians of the Pediatric Hospital in Köln-Porz, Cologne. When the system registers an alteration of the parameters above described -as a signal of a change in the baby s health condition- all vital signs are transfered in real-time to the supervising hospital via radio data transmission devices, mobile phone or a fixed network phone. The parents are also alerted by the device, and they can carry out the necessary reanimation procedures in case of an emergency. Parents will be trained in such actions when newborns must to be monitored. But nevertheless, they are guided and tele-assisted by an expert via telephone during the action. A clinical field trial, that will start in December 1999 at the Pediatric Hospital in Köln-Porz, Cologne, will evaluate the benefits of teleprotection by home monitoring of SIDS risk-babies.
Humans↗
Availability of Japanese subsidies for international telemedicine projects.
In this article, the authors report the methods for obtaining subsidies for overseas telemedicine projects from Japanese sources based on their own personal experiences. The Japanese Government is already subsidizing such specialized NGOs (Non-Governmental Organizations) as the Telemedicine Society of Japan and Basic Human Needs and, Japanese trading companies are also hiring telemedicine experts. Prospective methods for obtaining subsidies are outlined as under the following headings: Assistance without compensation, Technology transfer, Grass-roots grant assistance, the Telecommunications Advancement Organization, Postal Savings for International Voluntary Aid, Venture business development funds provided by the Ministry of International Trade and Industry, Mission demonstration satellites by the National Space Development Agency of Japan, the Sasakawa Pacific Island Nations Fund, and International Communications Foundation. Key points of the applications are noted under (1) Degree of contribution to local residents, (2) Significance of project continuation and (3) Novelty and economic impact.
Humans↗
Use of transgenic mice to study the role of apolipoprotein E in lipid metabolism and atherosclerosis.
Insight into the role of apolipoprotein (apo) E in lipoprotein metabolism and atherosclerosis has increased dramatically with the generation and analysis of novel transgenic, knockout and knockin mouse models. Moreover, the recent development and application of somatic gene and cell transfer technologies which can express (or delete) apoE in specific tissues of virtually any mouse model have further added to this increase in knowledge. It is now well established that apoE plays a role in virtually every step in the metabolism of very low-density lipoproteins and in the efflux of cholesterol from macrophages. In this review we will discuss recent insights into the role of apoE in these processes with particular emphasis on the specific effects of variation in apoE structure and quantity.
Animals↗
Sensory capacity of the royal college of surgeons rat.
PURPOSE: To apply noninvasive tests for examining visual and other sensory functions of pigmented Royal College of Surgeons (RCS) rats compared with pigmented and albino control animals. METHODS: Rats aged 3 and 7 months were tested with a general neurologic examination that assessed visual, auditory, tactile, and whisker displacement responses. Photophobic responses and visual discrimination were also measured. RESULTS: Dystrophic RCS rats failed the visual presentation tests, even at 3 months of age, and showed diminished performance on tactile tests. Auditory and whisker displacement performances were normal. Albino rats also showed diminished performance on the visual test, particularly to stimuli presented in the upper visual field. Photophobic responses were diminished in the dystrophic RCS rats compared with the pigmented control animals. Albino animals showed heightened photophobia. The dystrophic rats failed to reach criterion levels of performance on the visual discrimination test even with gratings of 0.045 cyc/deg. CONCLUSIONS: The tests used discriminate deteriorated complex visual functions in RCS rats at ages when some simple reflexes can still be demonstrated. As such, they provide easily executed tests for screening for the effects of reparative treatments such as transplantation, administration of growth factors, and gene transfer technology. The integrity of whisker and auditory function are important when using tests requiring polysensory inputs. The somatosensory defect is surprising but may be useful in searching for the gene locus of the retinal disorder. The aberrations seen in the albino rats may be attributable to the effects of light damage and unfiltered light.
Animals↗
Intellectual property law and genetic health care.
This article provides a basic analysis of intellectual property law, the treatment of genetic information under Title 35 of the United States Code, the controversies surrounding patenting of genetic sequences and related products, and the effects that restriction of information may have on the quality of health care in the United States. In addition, this piece addresses technology transfer and historical developments in public policy that have influenced patent trends. The intended product is not a rigorous review of the scientific or legal literature, as the included cases have been cited elsewhere to accentuate the same points. However, the compact format of the material should be especially valuable for physicians and health personnel who might not have been exposed to these issues as part of their formal professional training.
Genetic Therapy↗
[Immune response induced by hepatitis B DNA vaccine pCI-S-IRES- ProT alpha].
OBJECTIVE: To investigate immune response in mice inoculated with DNA vaccine. METHODS: pCI-S and pCI-S-IRES- ProT alpha were constructed by gene technology, transferred into cell line NIH-3T3 mediated by lipofectamine. Mice were inoculated with these plasmids too. HBsAg and HBsAb were detected by ELISA, and transcriptions of these plasmids were detected by RT-PCR. RESULTS: pCI-S -IRES- ProT alpha, and pCI-S were effectively expressed in cultured cells and vaccinated animals. Humoral immune and specific T-cell proliferative responses were stronger in pCI-S-IRES group than pCI-S group. CONCLUSIONS: Plasmids coexpression of prothymosin alpha and hepatitis B surface antigen can improve immune responses significantly.
Animals↗
Vaccine and gene therapy of renal cell carcinoma.
The concept of tumor vaccines is not new. However, advances in gene transfer technology, tumor immunology, molecular biology, and methods of monitoring antitumor response, have allowed for novel, more specific vaccine approaches. For example, first-generation tumor vaccines were composed of whole inactivated cancer cells, or tumor lysates (Tuly) given together with immune adjuvants like bacillus Calmette-Guerin (BCG). Current strategies include tumor cells modified with genes encoding molecules necessary to stimulate a cytotoxic T cell response, such as cytokine genes, foreign HLA genes, tumor-associated antigen (TAA) genes, and even costimulatory molecules. Activation of cellular immunity requires at least three synergistic signals including presentation of specific tumor antigens, costimulatory signals (B7 molecules), and propagation of the immune response via cytokine release. In general, tumor cells often fail to demonstrate any of these immunostimulatory properties. Dendritic cell-based vaccines are gaining popularity as these cells can properly present TAA to the immune system, thus circumventing the poor antigen-presenting qualities of tumor cells. Dendritic cells can be "loaded" with TAA or other molecules either by their natural endocytotic capabilities, or by genetic modification.
Carcinoma, Renal Cell↗
Full-scale application of the IAWQ ASM No. 2d model.
In the framework of the EU-funded TTP-UPM project (Technology Transfer Project--Urban Pollution Management) the waste water treatment plant (WWTP) of Tielt was modelled with the recently issued IAWQ ASM No. 2d model. Up to 41 % of the total COD load is originating from a textile industry. A measurement campaign was conducted during a period with industrial discharge and a period with only domestic sewage. The stop of the industrial discharge resulted in a highly dynamic response of the system. Based on an expert-approach the calibration was obtained changing only four parameters (anaerobic hydrolysis reduction factor etafe, reduction factor for denitrification etaNO3, the decay rate of autotrophs bAUT and the decay rate of the bio-P organism building blocks bPAO, bPHA, bPP). Influent fractionation remains a critical step within the model calibration. A proven procedure to characterise the influent determinants by standard physical chemical analysis failed to assess the influent COD fractions when the textile waste water is discharged to the WWTP. Selected bench-scale experiments, instead, succeeded in providing the adequate influent characterisation accuracy. For characterising the readily biodegradable COD fraction respirometry is to be preferred.
Bacteria, Anaerobic↗
Recombinant adeno-associated virus vectors for cystic fibrosis gene therapy.
Cystic fibrosis (CF) is an autosomal recessive inherited disorder that affects approximately 30,000 North Americans. Defects in the CF transmembrane conductance regulator (CFTR) gene lead to altered secretions from exocrine glands and the pulmonary airways, to a heightened susceptibility to airway infections with Pseudomonas aeruginosa, and to severe airway inflammation. Early attempts to develop a genetic therapy for CF have not met with great clinical success, but these efforts have driven the development of viral gene transfer technology for in vivo gene delivery. The recombinant adeno-associated virus (rAAV) system has proven to be safe for in vivo gene delivery in the airways of experimental animals and CF patients, although potential barriers to delivery have been identified. These barriers may limit the transduction efficiency of this vector, especially in the context of the inflamed airways of adolescent and adult CF patients. We anticipate that the use of alternative rAAV serotype capsids and other vector alterations, along with targeting the lungs of CF patients in the earlier stages of their disease, might eventually allow for these potential limitations to be overcome.
Animals↗
Technology innovation.
Technology is the way dentistry is practiced--the materials and methods, characteristics of the dentist and staff, and nature and values of patients. Innovation is a conscious process of improving that technology. Dentists, not researchers or manufacturers, are the source of most innovation in dentistry. Characteristics such a innate curiosity, sophistication, discretionary income, and practice isolation contribute to innovativeness. Innovation diffusion has a characteristic S-shape, with few early and late adopters and a rapid spread in the middle phase. Much is known regarding the personality and behavior of early and late adopters and those types of innovations that are likely to diffusion rapidly.
Dentists↗