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PubMed2002

Neural correlates of the precedence effect in the inferior colliculus: effect of localization cues.

The precedence effect (PE) is an auditory phenomenon involved in suppressing the perception of echoes in reverberant environments, and is thought to facilitate accurate localization of sound sources. We investigated physiological correlates of the PE in the inferior colliculus (IC) of anesthetized cats, with a focus on directional mechanisms for this phenomenon. We used a virtual space (VS) technique, where two clicks (a "lead" and a "lag") separated by a brief time delay were each filtered through head-related transfer functions (HRTFs). For nearly all neurons, the response to the lag was suppressed for short delays and recovered at long delays. In general, both the time course and the directional patterns of suppression resembled those reported in free-field studies in many respects, suggesting that our VS simulation contained the essential cues for studying PE phenomena. The relationship between the directionality of the response to the lead and that of its suppressive effect on the lag varied a great deal among IC neurons. For a majority of units, both excitation produced by the lead and suppression of the lag response were highly directional, and the two were similar to one another. For these neurons, the long-lasting inhibitory inputs thought to be responsible for suppression seem to have similar spatial tuning as the inputs that determine the excitatory response to the lead. Further, the behavior of these neurons is consistent with psychophysical observations that the PE is strongest when the lead and the lag originate from neighboring spatial locations. For other neurons, either there was no obvious relationship between the directionality of the excitatory lead response and the directionality of suppression, or the suppression was highly directional whereas the excitation was not, or vice versa. For these neurons, the excitation and the suppression produced by the lead seem to depend on different mechanisms. Manipulation of the directional cues (such as interaural time and level differences) contained in the lead revealed further dissociations between excitation and suppression. Specifically, for about one-third of the neurons, suppression depended on different directional cues than did the response to the lead, even though the directionality of suppression was similar to that of the lead response when all cues were present. This finding suggests that the inhibitory inputs causing suppression may originate in part from subcollicular auditory nuclei processing different directional cues than the inputs that determine the excitatory response to the lead. Neurons showing such dissociations may play an important role in the PE when the lead and the lag originate from very different directions.

Acoustic Stimulation↗
PubMed2006

The open nucleotide pocket of the profilin/actin x-ray structure is unstable and closes in the absence of profilin.

The open nucleotide pocket conformation of actin in the profilin:actinCaATP x-ray structure has been hypothesized to be a crucial intermediate for nucleotide exchange in the actin depolymerization/polymerization cycle. The requirement for ancillary modification of actin for crystallization leads to ambiguities in this interpretation, however. We have used molecular dynamics simulations to model the thermodynamic properties of the actin x-ray structure, outside the crystal lattice, in an aqueous environment with profilin removed. Our simulations show that the open-nucleotide-pocket, profilin-free structure is actually unstable, and closes. The coordination of actin to the nucleotide in the molecular-dynamics-derived closed structure is virtually identical to that in the closed profilin:actinSrATP x-ray structure. Thus, there is currently no thermodynamically stable structure representing the open-nucleotide-pocket state of actin.

Actins↗
PubMedDate not supplied

Virtual local target method for avoiding local minimum in potential field based robot navigation.

A novel robot navigation algorithm with global path generation capability is presented. Local minimum is a most intractable but is an encountered frequently problem in potential field based robot navigation. Through appointing appropriately some virtual local targets on the journey, it can be solved effectively. The key concept employed in this algorithm are the rules that govern when and how to appoint these virtual local targets. When the robot finds itself in danger of local minimum, a virtual local target is appointed to replace the global goal temporarily according to the rules. After the virtual target is reached, the robot continues on its journey by heading towards the global goal. The algorithm prevents the robot from running into local minima anymore. Simulation results showed that it is very effective in complex obstacle environments.

Algorithms↗
PubMed1982

Environmental modifiers in carcinogenesis.

The natural history of neoplastic development can be divided into at least three distinct stages - initiation, promotion and progression. These stages can be defined by biological experimentation and by histopathological characterization of the lesions involved in the various stages. It is now possible, both in human beings and in experimental animals, to distinguish by morphological techniques all stages from very early 'precursor' lesions to the final malignant state. Although the final stage - progression - of the neoplastic process can be altered by therapeutic intervention, the principal site at which the natural history of neoplastic development can be actually and potentially regulated is that of promotion. Promoting agents that are relatively selective for carcinogenesis in several different tissue types have now been identified both in experimental systems and in human beings. In at least two experimental systems - those of epidermal carcinogenesis and hepatocarcinogenesis - the general characteristics of both initiation and promotion are virtually identical. Such studies have demonstrated that the activity of promoting agents exhibits a threshold level as well as a maximal level and that the action of promoting agents is reversible; the identification of promoting agents in our environment is therefore of considerable importance in understanding the nature of and preventing the development of human cancer. In addition, the interpretation of whole-animal bioassays for carcinogenic agents in the environment must take into account the existence of promoting agents and recognize that their action is distinct from that of complete and incomplete carcinogens, in order rationally to extrapolate to situations of human risk.

Carcinoma, Hepatocellular↗
PubMed1998

Economic and clinical impact of filmless operation in a multifacility environment.

The transition from conventional film-based to filmless operation at the Baltimore Veterans Affairs (VA) Medical Center has resulted in a large number of clinical and economic benefits. The integration of the Department of VA hospitals in Maryland into the VA Maryland Health Care System has resulted in the opportunity to establish a "virtual" radiology and nuclear medicine department. This integrated department is based on a wide area network in which outlying medical centers use a central hospital information system/radiology information system (HIS/RIS) and a central commercial picture archiving and communication system (PACS), as well as a VA-developed image management and communication system. The creation of this virtual radiology/nuclear medicine department has resulted in additional savings and improvements in clinical care. The benefits of the PACS are made possible, to a large extent, by the high level of integration of the PACS and medical modalities with the hospital information and transcription systems. Our experience suggests that it is absolutely essential to integrate the PACS into the patient's electronic medical record to maximize efficiency and clinical effectiveness of the system.

Computer Communication Networks↗
PubMed1997

A flexible and extensible object-oriented 3D architecture: application in the development of virtual anatomy lessons.

"Anatomic VisualizeR" represents the first application to be developed using a 3D architectural framework created at the University of California, San Diego, School of Medicine. This application combines 3D anatomic models (based on the Visible Human dataset) with supporting 2D media (e.g., diagnostic imagery, surgical videos, etc.) to establish a comprehensive learning environment for anatomy. "Guided lessons" are being created to address complex curricular and learning objectives. Faculty expertise is represented in these preconfigured lessons, in part through the specification of appropriate content and the incorporation of activities to enhance visualization. These lessons are an intellectual framework which ensures that clinically-relevant issues and ancillary learning opportunities are available. The curricular exercises are non-sequential and can be interrupted at any time; users are encouraged to freely explore the environment. At the core of Anatomic VisualizeR's object-oriented architecture is the ability to identify, access, view, and manipulate heterogeneous content. The capacity to query a database gateway to retrieve specified resources has been built into the application. Encapsulation of individual elements to form 3D display objects ("blocks") enables Anatomic VisualizeR to efficiently manage 3D models, 2D images, text, sound, and video. The "block" paradigm also allows Anatomic VisualizeR to associate contextually appropriate display characteristics and behaviors with the various content elements. For example, the anatomic model block provides the capability to "link" and "unlink" the anatomic models and to alter their transparencies. The anatomic models can be displayed concurrently with other blocks to facilitate structural comparisons. Anatomic VisualizeR marks a major milestone in our developmental efforts. While lessons and database content are still not complete, we are confident that it will become the first tangible realization of our vision.

Anatomy↗
PubMed2000

The MuPSi project--a learning environment for multiprofessional collaboration.

Students studying for different professions within the field of health care need to practice both multiprofessional collaboration and use of HIS and EPR software. The MuPSi concept utilizes computer-mediated communication to provide students access to a EPR software to enable the students to act collaboratively as members of a virtual health care team. The students are given a fictive patient case and use the EPR software to plan and document the care they provide. In order to achieve a higher grade of authenticity the case is presented as segments--the teachers direct the simulation by recording events that change the situation into the patient record.

Computer Simulation↗
PubMed2006

Infant's brain responses to live and televised action.

Whether human infants perceive televised stimuli in the same way to live stimuli largely remains unknown. Action observation, which has been extensively confirmed to elicit activation of internal motor representation, provides a promising framework for investigating this issue. This 'mirror-matching' property has been found in the monkey premotor cortex as well as the premotor and primary motor cortices in human adults. Although larger activation in observing a live action compared to a televised action in adult subjects has been reported, it is unknown whether the same neural response is obtained from human infants. To address this issue, we first measured the activity of motor areas in adult subjects while viewing either a live or televised action of other people by using near-infrared spectroscopy. The motor areas that were activated when the subject themselves performed an action were also activated during action observation in the live setting, while this was not evident in the TV setting. We then conducted qualitatively the same experiment with 6- to 7-month-old infants. The infant's motor areas were significantly activated when observing a live person performing an action. Although we also found activation in the same area during action observation in the TV setting, the difference in activity between action observation and object-motion observation was significant only in the live setting. Our results are the first to demonstrate activation in motor areas during action observation in human infants. We suggest that human brain responds differently to the real world and the virtual world.

Adult↗
PubMed2000

Redundancy of aerobic respiratory chains in bacteria? Routes, reasons and regulation.

Bacteria are the most remarkable organisms in the biosphere, surviving and growing in environments that support no other life forms. Underlying this ability is a flexible metabolism controlled by a multitude of environmental sensors and regulators of gene expression. It is not surprising, therefore, that bacterial respiration is complex and highly adaptable: virtually all bacteria have multiple, branched pathways for electron transfer from numerous low-potential reductants to several terminal electron acceptors. Such pathways, particularly those involved in anaerobic respiration, may involve periplasmic components, but the respiratory apparatus is largely membrane-bound and organized such that electron flow is coupled to proton (or sodium ion) transport, generating a protonmotive force. It has long been supposed that the multiplicity of pathways serves to provide flexibility in the face of environmental stresses, but the existence of apparently redundant pathways for electrons to a single acceptor, say dioxygen, is harder to explain. Clues have come from studying the expression of oxidases in response to growth conditions, the phenotypes of mutants lacking one or more oxidases, and biochemical characterization of individual oxidases. Terminal oxidases that share the essential properties of substrate (cytochrome c or quinol) oxidation, dioxygen reduction and, in some cases, proton translocation, differ in subunit architecture and complement of redox centres. Perhaps more significantly, they differ in their affinities for oxidant and reductant, mode of regulation, and inhibitor sensitivity; these differences to some extent rationalize the presence of multiple oxidases. However, intriguing requirements for particular functions in certain physiological functions remain unexplained. For example, a large body of evidence demonstrates that cytochrome bd is essential for growth and survival under certain conditions. In this review, the physiological basis of the many phenotypes of Cyd-mutants is explored, particularly the requirement for this oxidase in diazotrophy, growth at low protonmotive force, survival in the stationary phase, and resistance to oxidative stress and Fe(III) chelators.

Bacteria, Aerobic↗
PubMed2002

Virtual center for renal support: technological approach to patient physiological image.

The patient physiological image (PPI) is a novel concept which manages the knowledge of the virtual center for renal support (VCRS), currently being developed by the Biomedical Engineering Group of the University of Seville. PPI is a virtual "replica" of the patient, built by means of a mathematical model, which represents several physiological subsystems of a renal patient. From a technical point of view, PPI is a component-oriented software module based on cutting-edge modeling and simulation technology. This paper provides a methodological and technological approach to the PPI. Computational architecture of PPI-based VCRS is also described. This is a multi-tier and multi-protocol system. Data are managed by several ORDBMS instances. Communications design is based on the virtual private network (VPN) concept. Renal patients have a minimum reliable access to the VCRS through a public switch telephone network--X.25 gateway. Design complies with the universal access requirement, allowing an efficient and inexpensive connection even in rural environments and reducing computational requirements in the patient's remote access unit. VCRS provides support for renal patients' healthcare, increasing the quality and quantity of monitored biomedical signals, predicting events as hypotension or low dialysis dose, assisting further to avoid them by an online therapy modification and easing diagnostic tasks. An online therapy adjustment experiment simulation is presented. Finally, the presented system serves as a computational aid for research in renal physiology. This is achieved by an open and reusable modeling and simulation architecture which allows the interaction among models and data from different scales and computer platforms, and a faster transference of investigation models toward clinical applications.

Aged↗
PubMed2006

[Long-term care services in Spain: an overview].

To date, both in Spain and virtually all the other European Union (EU) countries, dependency has been seen to be a fundamentally private problem to be dealt with by the family concerned. In this way, whether through informal carers or contracted professionals, in the domestic environment or in care homes, it is the dependent person themselves and their families who currently bear the majority of the costs. In light of this, current concern lies in the social change that is coming on, mainly the accelerated aging process and the increased participation of middle-aged women in the labour market, which heighten the need for collective organisation of that which until now has been resolved within family circles. In this context, at the same time that the Government announces to issue a < > by the end of 2005, our paper briefly analyzes what we consider the four crucial issues in this area: the current scope of dependency problems and its possible future evolution, the characteristics of the current spanish long-term care system and its main problems; the role that health services should have in the dependency issue; and finally, the benefits and drawbacks of the main alternatives that the Administration could manage in case it intends to increase its involvement in this field.

Aged↗
PubMed1985

Agonist-induced redistribution of beta-adrenergic receptors on intact human mononuclear leukocytes: redistributed receptors are nonfunctional.

Incubation of human mononuclear leukocytes (MLN) with isoproterenol rapidly desensitizes beta-adrenergic receptors, i.e. isoproterenol-stimulated cAMP accumulation decreases. This desensitization is accompanied by a redistribution of the receptor into a cellular environment to which hydrophilic compounds have limited access. We found that the total number of beta-receptors [defined as binding of [3H]dihydroalprenolol (DHA) inhibited by 1 microM propranolol] was unchanged in the desensitized MNL. In control MNL, virtually all DHA binding was inhibited by 1 microM CGP-12177, suggesting that all of these receptors are on the cell surface, whereas in desensitized cells, only 33 +/- 2% (mean +/- SEM) of the DHA binding was inhibited by CGP-12177. We quantitated the sequestered receptors by subtracting the number of surface receptors from the total number of receptors. The sequestered receptors were homogeneous, with an affinity for DHA identical to that of surface receptors (Kd, 0.66 +/- 0.12 vs. 0.62 +/- 0.08 nM). The time courses of desensitization and sequestration were identical. The functional status of the sequestered receptors was assessed using the agonist zinterol, which (unlike catecholamines) is quite hydrophobic. Zinterol competed for DHA binding to both sequestered and surface receptors, whereas isoproterenol only competed for binding to the surface receptors. However, cAMP accumulation in desensitized MNL was reduced to the same extent regardless of whether isoproterenol or zinterol was used as the agonist. These results demonstrate that desensitization of intact cells to beta-agonists cannot be attributed to limited accessibility of the sequestered receptors to catecholamines, but, rather, that the sequestered receptors are not functionally coupled to adenylate cyclase.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Multiple-drug resistant enterococci: the nature of the problem and an agenda for the future.

Enterococci, leading causes of nosocomial bacteremia, surgical wound infection, and urinary tract infection, are becoming resistant to many and sometimes all standard therapies. New rapid surveillance methods are highlighting the importance of examining enterococcal isolates at the species level. Most enterococcal infections are caused by Enterococcus faecalis, which are more likely to express traits related to overt virulence but--for the moment--also more likely to retain sensitivity to at least one effective antibiotic. The remaining infections are mostly caused by E. faecium, a species virtually devoid of known overt pathogenic traits but more likely to be resistant to even antibiotics of last resort. Effective control of multiple-drug resistant enterococci will require 1) better understanding of the interaction between enterococci, the hospital environment, and humans, 2) prudent antibiotic use, 3) better contact isolation in hospitals and other patient care environments, and 4) improved surveillance. Equally important is renewed vigor in the search for additional drugs, accompanied by the evolution of new therapeutic paradigms less vulnerable to the cycle of drug introduction and drug resistance.

Anti-Bacterial Agents↗
PubMed2001

Blueprint for discovery in academic medicine: plans, process and outcomes.

By the end of the decade, we had fully implemented most of the recommendations of the Molinoff Report. Our programmatic analysis is summarized in Table 11. While the space needs identified in the Molinoff Report were met by BRB I, II, and III (289,000 nsf as compared [table: see text] to 276,000 nsf as planned), it was possible to provide additional, somewhat unanticipated, research space (111,000 nsf) prior to the end of the decade. The faculty has now developed a research plan for the next decade. It is also important to emphasize that the total faculty grew by 41% [table: see text] over the decade and most of that growth occurred with faculty spending a substantial part of their time in clinical practice. Hence, the dramatic improvement in research funding of over 200% was due largely to the enhanced productivity of our faculty. By taking an organized planning approach deeply seated in the faculty, consistent with Trustee directives and with measurable outcomes, we were successful in growing the research programs within the School of Medicine of the University of Pennsylvania. We believe this particular approach, taken with a focus on multidisciplinary research, [table: see text] was the right one for the 1990s. In the final analysis, it is abundantly clear that outstanding faculty, working in an exciting supportive environment, was the most important factor for success. We are not certain what the right approach will be for the future. Clearly, with the important advances in genomics and information technology, the importance of the team, even if a virtual one world-wide, cannot be overstated. While research is only one mission of the School of Medicine, clearly, our visible success in research played an important role in the overall improvement in the School of Medicine as measured by others. For example, the ranking of the School of Medicine by U.S. News & World Report, perhaps the most widely used ranking by the lay press, went from 10th to 3rd behind only Harvard and Johns Hopkins during the period of the 90s (Table 12).

Academic Medical Centers↗
PubMed2005

Green-blue water system innovations for upgrading of smallholder farming systems--a policy framework for development.

Rainfed agriculture and other depletion of water by green flows have as yet an untapped potential for improving livelihoods in semi-arid areas through income and food security. A vivid evidence of this is seen in the fact that, although working full time on food production, majority of smallholder farmers are frequently affected by shortage of food or famines. At the same time enough examples exist to show that productivity of labor, water and land under rainfed farming can be doubled or even trebled through proper land management and improved agronomic inputs supported by modest investments to reduce impacts of dry spells. However, these shining examples remain small 'islands of success' across the entire semi-arid areas. Farmers have not adopted these systems due to poor ratio of benefit to costs brought about by inadequate development or complete lack of food trade among the rural areas. This paper argues that there is a need for policy, strategic and programmatic frameworks which facilitate integrated management of land, water and markets. For this kind of strategy to work, a local market for food should be ensured to absorb at competitive prices the surplus produced by farmers in years of good rains. This will promote wealth creation and asset building among the poor in semi-arid areas. A food-exchange "futures" mechanism based on the principle of virtual water trade is proposed as a basis for achieving this objective.

Agriculture↗
PubMed2002

Virtual reality simulators: current status in acquisition and assessment of surgical skills.

Medical technology is currently evolving so rapidly that its impact cannot be analysed. Robotics and telesurgery loom on the horizon, and the technology used to drive these advances has serendipitous side-effects for the education and training arena. The graphical and haptic interfaces used to provide remote feedback to the operator--by passing control to a computer--may be used to generate simulations of the operative environment that are useful for training candidates in surgical procedures. One additional advantage is that the metrics calculated inherently in the controlling software in order to run the simulation may be used to provide performance feedback to individual trainees and mentors. New interfaces will be required to undergo evaluation of the simulation fidelity before being deemed acceptable. The potential benefits fall into one of two general categories: those benefits related to skill acquisition, and those related to skill assessment. The educational value of the simulation will require assessment, and comparison to currently available methods of training in any given procedure. It is also necessary to determine--by repeated trials--whether a given simulation actually measures the performance parameters it purports to measure. This trains the spotlight on what constitutes good surgical skill, and how it is to be objectively measured. Early results suggest that virtual reality simulators have an important role to play in this aspect of surgical training.

Clinical Competence↗
PubMed1984

Plasmid-mediated biodegradative fate of monohalogenated biphenyls in facultatively anaerobic sediments.

The results of these studies have demonstrated that model PCB substrates can be mineralized by indigenous microbial population in contaminated sediments. This catabolic function can be rate limited at the microenvironmental level by physical-chemical processes such as physical partitioning and accumulation. At the biochemical level, this catabolic function is determined by the existence of plasmid borne genes that, under laboratory conditions, can be maintained and expressed in pure or mixed culture. Numerous limitations are encountered in establishing the significance of these biodegradative bacteria and the catabolic plasmids at the environmental level. Relatively little information is available concerning frequencies and stability of the bacteria or the plasmid encoded genes within the community. There is no information on the incompatibility grouping of the isolated plasmid relative to other plasmids maintained within the populations. Such factors will influence the development of gene screening techniques to monitor gene frequency distributions in the sediment community. Although mineralization of 4CBP was observed under moderately reducing conditions, it remains suspect that transient or trace levels of dissolved oxygen may have permitted conventional aerobic metabolism of the substrate. If this is true, demonstrating anaerobic metabolism of environmental contaminants will require strict and tedious cultivation under highly reduced conditions (approximately-300 mV). Large deletions of cryptic DNA observed under laboratory conditions may affect bacterial survival and gene maintenance and transfer under environmental conditions. Little information exists on regulation of catabolic activity of selective pressures required to maintain the degradative genes under environmental conditions. Such limitation encountered in these studies are shared by virtually all attempts to utilize genetically manipulated bacteria or newly isolated strains and plasmids. Perhaps the fundamental question is whether the catabolic genes are maintained and expressed within the community rather than whether the host bacterium can survive in the environment.

Anaerobiosis↗
PubMedDate not supplied

The conquest of "schizophrenia:" Sisyphus revisited.

Despite the fact that the diagnosis of schizophrenia, or dementia praecox, has been in use for over 80 years, there remains a great lack of clarity about the nature of this "disease." An impressive array of clinical and experimental data has been accumulated which pertains to the characteristics of "schizophrenics" but there are virtually no data which are schizophrenia specific. Quite to the contrary, the emerging picture is one of a complex and interacting field of several continuous dimensions or factors. Three underlying factors are suggested in an ad hoc fashion; the internal environment, the physical environment, and the human environment. It is suggested that these basic dimensions and their interactions over time should be the object of further investigation and definition, hopefully developing more adequate and productive description of clinical syndromes, rather than continuing the preoccupation with "schizophrenia" as a diagnostic label.

Environment↗