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Acoustic feedback margin improvements in hearing instruments using a prototype DFS (digital feedback suppression) system.

The properties of a prototype DFS (digital feedback suppression) system have been investigated. 21 ears fitted with behind-the-ear (BTE) hearing instruments and hard acrylic ear-moulds and 4 ears fitted with vented in-the-ear (ITE) hearing instruments were selected for the investigation. Two ITE instruments with different venting were employed to one of the ears. Complex loop gain has been measured in an anechoic room, and from these measurements the improvements in acoustic feedback margin due to the DFS system have been determined. For the BTE group, median values of 13.1 and 10.0 dB of improvement were established for two sets of measurements introducing a 180 degrees phase shift in connection with the last set of measurements. For the ITE group, values from 9.8 to 16.1 dB and from 13.7 to 16.3 dB of improvement were observed for the normal and the 180 degrees phase shift conditions respectively. Beyond this the DFS system may improve the sound quality to some extent, because the amplitude distortion, caused by the external feedback signal, is almost completely eliminated.

Acoustic Stimulation↗

Intracavitary hyperthermia: construction and heat patterns of individualized vaginal prototype applicators.

Patients who have inoperable or previously irradiated cervical recurrences, especially if very confined and alone, pose a challenging problem to the clinician. Low-dose irradiation and hyperthermia seems to be a promising method for salvage treatments in previously treated patients. In order to heat the vaginal apex, individualized prototype applicators utilizing commercial microwave antennas were constructed and tested in muscle equivalent phantom. The technical construction of vaginal applicators followed Pierquin's procedure for gynaecological brachy-therapy moulds: (1) a true negative vaginal print in alginate was made; (2) a positive mould in plaster of Paris was then constructed; (3) a negative vaginal print was produced in plaster of Paris and (4) heat moulding of a 0.1 cm thick sheet of cellulose acetate on the plaster mould was accomplished. Interstitial microwave antennas were inserted within the applicator and kept in place using silk wires or Teflon rings. The external part of the applicator was thermally sealed and protected with silicone. This was particularly useful in cases where an inner cooling system was required. Heat patterns in tissue equivalent phantom materials were determined using non-perturbing probes and infrared thermography. An illustrative clinical case is described.

Carcinoma, Squamous Cell↗

Insonation of fixed porcine kidney by a prototype sector-vortex-phased array applicator.

The sector-vortex applicator, an ultrasound phased array with a geometric focus having multiple sectors and tracks, can directly synthesize, without scanning, diffuse focal patterns useful for hyperthermia. A perfused tissue phantom, consisting of an alcohol-fixed porcine kidney with thermocouples placed in the cortex, is insonated by a prototype sector-vortex applicator with 16 sectors and two tracks at an ultrasound frequency of 750 kHz. Steady-state temperature distributions are measured for a wide range of perfusion rates. Results demonstrate that the radius of the heated region can be controlled effectively by choosing the focal mode of the applicator as it is predicted by theoretical analysis.

Animals↗

On facial composite image prototyping as a descriptive and diagnostic tool.

As long ago as 1878 attempts have been made to define photographically the typical facial characteristics of persons exhibiting particular appearances or afflictions. State-of-the-art numerical computing techniques facilitate definition of highly accurate facial composites. Such images are devoid of ghosting caused by nonalignment of facial features. Composites can help to define the prototypical visual appearance of facial types and as such have applications in visual cognitive psychology and clinical imaging. This article describes the imaging process and discusses how clinical presentation of different diseases can be visualized using physiognomic information and how this has the potential to be developed as a diagnostic tool.

Cockayne Syndrome↗

Microsurgical robotic system for the deep surgical field: development of a prototype and feasibility studies in animal and cadaveric models.

OBJECT: To enhance the surgeon's dexterity and maneuverability in the deep surgical field, the authors developed a master-slave microsurgical robotic system. This concept and the results of preliminary experiments are reported in this paper. METHODS: The system has a master control unit, which conveys motion commands in six degrees of freedom (X, Y, and Z directions; rotation; tip flexion; and grasping) to two arms. The slave manipulator has a hanging base with an additional six degrees of freedom; it holds a motorized operating unit with two manipulators (5 mm in diameter, 18 cm in length). The accuracy of the prototype in both shallow and deep surgical fields was compared with routine freehand microsurgery. Closure of a partial arteriotomy and complete end-to-end anastomosis of the carotid artery (CA) in the deep operative field were performed in 20 Wistar rats. Three routine surgical procedures were also performed in cadavers. The accuracy of pointing with the nondominant hand in the deep surgical field was significantly improved through the use of robotics. The authors successfully closed the partial arteriotomy and completely anastomosed the rat CAs in the deep surgical field. The time needed for stitching was significantly shortened over the course of the first 10 rat experiments. The robotic instruments also moved satisfactorily in cadavers, but the manipulators still need to be smaller to fit into the narrow intracranial space. CONCLUSIONS: Computer-controlled surgical manipulation will be an important tool for neurosurgery, and preliminary experiments involving this robotic system demonstrate its promising maneuverability.

Anastomosis, Surgical↗

Biocidal activity of ozone versus formaldehyde against poultry pathogens inoculated in a prototype setter.

Ozone was evaluated as an alternative hatchery disinfectant to replace formaldehyde in the event that the Environmental Protection Agency regulates the use of formaldehyde under the Toxic Substances Control Act. Cultures of Staphylococcus, Streptococcus, and Bacillus species previously isolated from poultry hatcheries and selected culture collections of Escherichia coli, Pseudomonas fluorescences, Salmonella typhimurium, Proteus species, and Aspergillus fumigatus were spread-plated on open petri plates and independently fumigated with ozone or formaldehyde in a prototype laboratory poultry setter. Ozone (1.52% to 1.65% by weight) resulted in bacterial reductions of greater than 4 to 7 log10 and fungal reductions of greater than 4 log10, whereas formaldehyde achieved reductions of greater than 7 log10 and greater than 5 log10, respectively, after 8 min of exposure to either disinfectant. Potential mutagenic effects were observed in ozonated E. coli colonies resulting in decreased superoxide dismutase activity and increased catalase activity when compared with nonozonated control colonies. In this study ozone reduced microorganism counts but not as much as formaldehyde. Ozone may be used as a disinfectant against selected microorganisms, although further testing under actual hatchery conditions is needed before making recommendations to the industry.

Animals↗

[Self-evaluation of the quality of life of children aged 6 to 12 years old: analysis of the concept and development of a prototype tool].

The objective of this work was to assess the quality of life of children aged 6 to 12 years old. The authors present the different conceptual and operational steps which lead to the construction of a prototype tool. It was a generic tool composed of 63 items which covered the classically described areas of life. Its originality was due to the method of construction used which included children's involvement, to the pictorial representation of real-life situations for children, and to its adaptation for gender. The evaluation of this tool showed a good level of acceptability but statistical analysis revealed some metrological inadequacies leading to the reconsideration of the initial concepts and their methods of exploration. Therefore a new tool was constructed whose validation is presented in a second article in the next issue.

Child↗

Multi-course sequential learning as a model for content integration: ethics as a prototype.

Multi-course sequential learning (MCSL), a model for integrating content throughout the curriculum, is described using ethics education as a prototype. In this model, content is presented via a vertical course, with units embedded in existing courses across various levels of the nursing program, which is designed to provide coherent organization of content, visibility, and accountability, and to prevent gaps and unnecessary duplication. This article describes the process of developing an Ethics MCSL, which is being implemented and evaluated with support from a three-year grant from the Fund for the Improvement of Postsecondary Education (FIPSE).

Curriculum↗

Activation/division of lymphocytes results in increased levels of cytoplasmic activation/proliferation-associated protein-1: prototype of a new family of proteins.

We purified from activated T lymphocytes a novel, highly conserved, 116-kDa, intracellular protein that occurred at high levels in the large, dividing cells of the thymus, was up-regulated when resting T or B lymphocytes or hemopoietic progenitors were activated, and was down-regulated when a monocytic leukemia, M1, was induced to differentiate. Expression of the protein was highest in the thymus and spleen and lowest in tissues with a low proportion of dividing cells such as kidney or muscle, although expression was high in the brain. The protein was localized to the cytosol and was phosphorylated, which is consistent with a previous report that the Xenopus laevis ortholog was phosphorylated by a mitotically activated kinase (1 ). The cDNA was previously mischaracterized as encoding p137, a 137-kDa GPI-linked membrane protein (2 ). We propose that the authentic protein encoded by this cDNA be called cytoplasmic activation/proliferation-associated protein-1 (caprin-1), and show that it is the prototype of a novel family of proteins characterized by two novel protein domains, termed homology regions-1 and -2 (HR-1, HR-2). Although we have found evidence for caprins only in urochordates and vertebrates, two insect proteins exhibit well-conserved HR-1 domains. The HR-1 and HR-2 domains have no known function, although the HR-1 of caprin-1 appeared necessary for formation of multimeric complexes of caprin-1. Overexpression of a fusion protein of enhanced green fluorescent protein and caprin-1 induced a specific, dose-dependent suppression of the proliferation of NIH-3T3 cells, consistent with the notion that caprin-1 plays a role in cellular activation or proliferation.

Amino Acid Sequence↗

Prototype Alzheimer's disease vaccine using the immunodominant B cell epitope from beta-amyloid and promiscuous T cell epitope pan HLA DR-binding peptide.

Immunization of amyloid precursor protein transgenic mice with fibrillar beta-amyloid (Abeta) prevents Alzheimer's disease (AD)-like neuropathology. The first immunotherapy clinical trial used fibrillar Abeta, containing the B and T cell self epitopes of Abeta, as the immunogen formulated with QS21 as the adjuvant in the vaccine. Unfortunately, the clinical trial was halted during the phase II stage when 6% of the participants developed meningoencephalitis. The cause of the meningoencephalitis in the patients that received the vaccine has not been definitively determined; however, analysis of two case reports from the AN-1792 vaccine trial suggest that the meningoencephalitis may have been caused by a T cell-mediated autoimmune response, whereas production of anti-Abeta Abs may have been therapeutic to the AD patients. Therefore, to reduce the risk of an adverse T cell-mediated immune response to Abeta immunotherapy we have designed a prototype epitope vaccine that contains the immunodominant B cell epitope of Abeta in tandem with the synthetic universal Th cell pan HLA DR epitope, pan HLA DR-binding peptide (PADRE). Importantly, the PADRE-Abeta(1-15) sequence lacks the T cell epitope of Abeta. Immunization of BALB/c mice with the PADRE-Abeta(1-15) epitope vaccine produced high titers of anti-Abeta Abs. Splenocytes from immunized mice showed robust T cell stimulation in response to peptides containing PADRE. However, splenocytes from immunized mice were not reactivated by the Abeta peptide. New preclinical trials in amyloid precursor protein transgenic mouse models may help to develop novel immunogen-adjuvant configurations with the potential to avoid the adverse events that occurred in the first clinical trial.

Alzheimer Disease↗

The role of TLR2 in vivo following challenge with Staphylococcus aureus and prototypic ligands.

Based on a wealth of in vitro macrophage studies, immunity to Staphylococcus aureus cell wall-derived peptidoglycan (PGN) and lipoteichoic acid has been attributed to TLR2. We investigated whether the in vitro paradigm of TLR2 dominance would hold true in vivo. Using an experimental peritonitis model, we challenged mice with PGN or lipoteichoic acid and found that only PGN resulted in significant leukocyte (primarily neutrophil) accumulation in the peritoneum at 4 h. PGN-mediated leukocyte recruitment was P-/E-selectin dependent but only partially TLR2 dependent, and also involved the C5aR. Concomitant inhibition of TLR2 and C5aR resulted in a further reduction in PGN-induced peritonitis. Peritoneal neutrophilia was partially mast cell dependent; however, the defect could not be reconstituted with TLR2(-/-) or C5aR(-/-) mast cells. Interestingly, macrophage-deficient mice did not have defective neutrophil recruitment. By 24 h, the response to PGN involved primarily monocytes and was TLR2 and C5aR independent. Finally, we challenged mice with live S. aureus and found a similar degree of TLR2 involvement in leukocyte recruitment to that observed with PGN. Most importantly, bacterial clearance from the spleen and peritoneum was not altered in TLR2(-/-) mice vs wild-type mice. Morbidity was only significantly increased in S. aureus-infected mice treated with a blocking Fab against C5aR. Taken together, these studies indicate that in vivo responses to prototypic TLR2 ligands do not necessarily recapitulate the absolute necessity for TLR2 observed in vitro, and additional receptors contribute, in a significant manner, to PGN and S. aureus-mediated immune responses.

Animals↗

Comparison of chlorine and a prototype produce wash product for effectiveness in killing Salmonella and Escherichia coli O157:H7 on alfalfa seeds.

Outbreaks of Salmonella and Escherichia coli O157:H7 infections associated with alfalfa and other seed sprouts have occurred with increased frequency in recent years. This study was undertaken to determine the efficacy of a liquid prototype produce wash product (Fit), compared with water and chlorinated water, in killing Salmonella and E. coli O157:H7 inoculated onto alfalfa seeds. We investigated the efficacy of treatments as influenced by seeds from two different lots obtained from two seeds suppliers and by two methods of inoculation. The efficacy of treatments was influenced by differences in seed lots and amount of organic material in the inoculum. Significant (alpha = 0.05) reductions in Salmonella populations on seeds treated with 20,000 ppm of chlorine or Fit for 30 min ranged from 2.3 to 2.5 log10 CFU/g and 1.7 to 2.3 log10 CFU/g, respectively. Reductions (alpha = 0.05) in E. coli O157:H7 ranged from 2.0 to 2.1 log10 CFU/g and 1.7 to more than 5.4 log10 CFU/g of seeds treated, respectively, with 20,000 ppm of chlorine or Fit. Compared with treatment with 200 ppm of chlorine, treatment with either 20,000 ppm of chlorine or Fit resulted in significantly higher reductions in populations of Salmonella and E. coli O157:H7. None of the treatments eliminated these pathogens as evidenced by their detection on enrichment of treated seeds. Considering the human health and environmental hazards associated with the use of 20,000 ppm of chlorine, Fit provides an effective alternative to chlorine as a treatment to significantly reduce bacterial pathogens that have been associated with alfalfa seeds.

Chlorine↗

Acclimatization resistance of a Pseudomonas aeruginosa prototype strain to imipenem.

A prototype sensitive strain of Pseudomonas aeruginosa (IRs) was acclimatized in vitro to imipenem by serial transfers in broth containing increasing concentrations of the antibiotic up to 32 micrograms/ml. Serial subculture of the resistant progeny (IR1r) in antibiotic-free solid media resulted in a "revertant" progeny (IR2r) that retained resistance to imipenem. Acclimatization resistance to imipenem and the attempted reversion procedure affected colony morphology, growth rate, pigment production, growth at 42 degrees C and glucose oxidation. SDS-PAGE analysis of the outer membrane proteins revealed in strain IR1r a complete loss of 6 proteins that were present in IRs (85 kdaltons, 46 kdaltons or porin D1, 45.5 kdaltons or porin D2, 43 kdaltons or porin E, 21 kdaltons or protein H1 and 20.5 kdaltons or lipoprotein H2) and in strain IR2r a complete loss of 3 proteins (46 kdaltons, 43 kdaltons, 20.5 kdaltons), while three others were found only in trace amounts (75 kdaltons, 45.5 kdaltons and 21 kdaltons). In the outer membranes of strains IR1r and IR2r an acquisition of a 56-kdalton protein was noted. Lipopolysaccharide chemical analysis revealed a marked, partially reversible increase in 2-keto-3-deoxyoctonate, total hexose and heptose constituents; readily extractable lipid chemical analysis and TLC, revealed a marked, partially reversible, increase in the phospholipid content of the outer membrane. Acclimatization resistance to imipenem was accompanied by cross-resistance to gentamicin, by partially reversible cross-resistance to moxalactam, carbenicillin and ticarcillin and by fully reversible cross-resistance to aztreonam. Sensitivity to azlocillin and polymyxin B remained unaltered. To explain this type of resistance to imipenem, an irreversible, non-inducible "loss" mutation mechanism, working in concert with a partially reversible mechanism, is proposed.

Cell Membrane Permeability↗

The hepatitis knowledge base. A prototype information transfer system.

The Hepatitis Knowledge Base is a prototype computerized information-transfer system aimed at supporting the health practitioner's day-to-day diagnosis, prognosis, and treatment decisions concerned with viral hepatitis. An overview of information-transfer problems in biomedicine is presented and issues pertinent to the knowledge-base concept are discussed. The following research activities are described: selection and organization of the content of the initial draft of the complete Hepatitis Knowledge Base; the method for consensus development by a nationally distributed panel of collaborating experts on the subject matter; methods for updating the knowledge base and maintaining its currency over time; use of a computer conferencing network as the principal medium of communication among the geographically dispersed experts and the project staff; support of on-line access to the knowledge-base contents; and formative evaluation of the above methods and limited field testing of the access system.

Hepatitis, Viral, Human↗

Virtual design prototyping applied to medical facilities.

Over the past five years, MITRE has developed rapid 3D modeling and immersive environment capabilities that supports the application of virtual environment technology to many traditional and non-traditional domains [1]. This paper provides background information on these capabilities and describes the application of this technology to the experimental design prototyping of operating rooms of the future and to the design and retrofit of existing or proposed medical facilities. These capabilities employ contemporary commercial hardware and software and exploit stereoscopic projection displays and headsets. A unique user interface facilitates object manipulation within these immersive environments and addresses two key areas: 1) Visualization of the contents on the model server or library in a catalog form; and 2) Natural interaction and immersion of the user with the visualized catalog and selected visualized objects in a 3D synthetic environment. A brief discussion of two developing applications of this technology will be presented. In one application example, the modeling environment can be used to synthesize physical replicas (potentially full stereo scale) of actual surgical rooms used for training of medical personnel. Alternatively, it can be employed as the infrastructure for a new form of collaborative interactive visualization, namely, telesurgery. In another example, the rapid modeling capability provides designers, architects and medical personnel with a means of rapidly developing synthetic renderings of (potentially interactive and remotely operative) proposed medical facilities prior to construction. We also discuss key issues needing to be resolved for successful model interchange.

Computer Simulation↗

The EUROMEDIES EDI prototype system.

EDI is expected to be the dominant form of business communication between organisations moving to the Electronic Commerce era of 2000. The healthcare sector is already using EDI in the hospital supply function as well as in the clinical area and the reimbursement process. In this paper, we examine the use of EDI in the healthcare administration sector and move specifically its application to the Medical Devices Vigilance System. At a first place, the potential of this approach is examined, after an initial brief presentation of the EDI concept and its application in healthcare. This presentation is followed by an overall description of the EDI prototype system, which was developed in the context of the EUROMEDIES Concerted Action, in order to facilitate the requirements definition phase.

Computer Communication Networks↗

Implementing security on a prototype hospital database.

This paper describes the methodology used and the experience gained from the application of a new secure database design approach and database security policy in a real life hospital environment. The applicability of the proposed database security policy in a major Greek general hospital is demonstrated. Moreover, the security and quality assurance of the developed prototype secure database is examined, taking into consideration the results from the study of the user acceptance.

Computer Security↗

Oleamide: an endogenous sleep-inducing lipid and prototypical member of a new class of biological signaling molecules.

Oleamide is an endogenous fatty acid primary amide that accumulates in the cerebrospinal fluid under conditions of sleep deprivation and induces physiological sleep in animals. A review covering its discovery, its implications, and the emerging biology surrounding its discovery is presented. Consistent with its role as a prototypical member of a new class of biological signaling molecules, enzymatic regulation of endogenous concentrations of oleamide have been characterized or proposed. Fatty acid amide hydrolase (FAAH) is an integral membrane protein that degrades oleamide and potent inhibitors with physiological sleep-inducing properties have been disclosed. The characterization, cloning, and neuronal distribution of FAAH have been detailed and the enzyme was found to possess the ability to hydrolyze a range of fatty acid amides including anandamide which serves as the endogenous ligand for the cannabinoid receptor. An additional endogenous substance with REM sleep-inducing properties, 2-octyl gamma-bromoacetoacetate, was characterized as a potent FAAH inhibitor. Oleamide has been shown to modulate serotonergic neurotransmission and inhibit intercellular gap junction communication and detailed studies of its well defined and selective structural features required for activity have been disclosed.

Animals↗