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PubMed1999

Estimating equations for a latent transition model with multiple discrete indicators.

This paper proposes a two-part model for studying transitions between health states over time when multiple, discrete health indicators are available. The includes a measurement model positing underlying latent health states and a transition model between latent health states over time. Full maximum likelihood estimation procedures are computationally complex in this latent variable framework, making only a limited class of models feasible and estimation of standard errors problematic. For this reason, an estimating equations analogue of the pseudo-likelihood method for the parameters of interest, namely the transition model parameters, is considered. The finite sample properties of the proposed procedure are investigated through a simulation study and the importance of choosing strong indicators of the latent variable is demonstrated. The applicability of the methodology is illustrated with health survey data measuring disability in the elderly from the Longitudinal Study of Aging.

Aged↗

PubMed2006

Epigenetic acquisition of inducibility of type III cytotoxicity in P. aeruginosa.

BACKGROUND: Pseudomonas aeruginosa, an opportunistic pathogen, is often encountered in chronic lung diseases such as cystic fibrosis or chronic obstructive pneumonia, as well as acute settings like mechanical ventilation acquired pneumonia or neutropenic patients. It is a major cause of mortality and morbidity in these diseases. In lungs, P. aeruginosa settles in a biofilm mode of growth with the secretion of exopolysaccharides in which it is encapsulated, enhancing its antibiotic resistance and contributing to the respiratory deficiency of patients. However, bacteria must first multiply to a high density and display a cytotoxic phenotype to avoid the host's defences. A virulence determinant implicated in this step of infection is the type III secretion system (TTSS), allowing toxin injection directly into host cells. At the beginning of the infection, most strains isolated from patients' lungs possess an inducible TTSS allowing toxins injection or secretion upon in vivo or in vitro activation signals. As the infection persists most of the bacteria permanently loose this capacity, although no mutations have been evidenced. We name "non inducible" this phenotype. As suggested by the presence of a positive feedback circuit in the regulatory network controlling TTSS expression, it may be due to an epigenetic switch allowing heritable phenotypic modifications without genotype's mutations. RESULTS: Using the generalised logical method, we designed a minimal model of the TTSS regulatory network that could support the epigenetic hypothesis, and studied its dynamics which helped to define a discriminating experimental scenario sufficient to validate the epigenetic hypothesis. A mathematical framework based on formal methods from computer science allowed a rigorous validation and certification of parameters of this model leading to epigenetic behaviour. Then, we demonstrated that a non inducible strain of P. aeruginosa can stably acquire the capacity to be induced by calcium depletion for the TTSS after a short pulse of a regulatory protein. Finally, the increased cytotoxicity of a strain after this epigenetic switch was demonstrated in vivo in an acute pulmonary infection model. CONCLUSION: These results may offer new perspectives for therapeutic strategies to prevent lethal infections by P. aeruginosa by reverting the epigenetic inducibility of type III cytotoxicity.

Bacterial Proteins↗

PubMedDate not supplied

National medical spending attributable to overweight and obesity: how much, and who's paying?

We use a regression framework and nationally representative data to compute aggregate overweight- and obesity-attributable medical spending for the United States and for select payers. Combined, such expenditures accounted for 9.1 percent of total annual U.S. medical expenditures in 1998 and may have been as high as dollar 78.5 billion (dollar 92.6 billion in 2002 dollars). Medicare and Medicaid finance approximately half of these costs.

Cost of Illness↗

PubMed2002

Multidimensional approach for evaluation of system activity of the brain by EEG.

The way of investigation some fundamental properties of integrative brain activity was worked out. Within the framework of the qEEG system for computer diagnostics of EEG NeuroResearcher '2001 (Version 7.5) is created modules for investigation of multivariate neurodynamic systems of the brain on the base of multidimensional spectral EEG and ESCoG analysis. It is intended for doctors and neuroscientists who use mathematical methods (classical correlation and spectral analysis and newest methods of multidimensional analysis of neurodynamic systems of the brain) for quantitative EEG (qEEG) successfully.

Brain↗

PubMed1986

Role of electrical interactions in synchronization of epileptiform bursts.

Four general mechanisms can hypothetically contribute to or mediate localized synchronization of neuronal activity: (a) recurrent excitatory chemical synapses, (b) electrotonic coupling via gap junctions, (c) electrical field effects (ephaptic interactions), and (d) changes in the concentration of extracellular ions (e.g., K+). It has generally been believed that synchronization of epileptiform bursts derives primarily, if not exclusively, from recurrent excitatory chemical synapses. Dual intracellular recordings from the CA3 area of the hippocampus have been used to demonstrate the existence of recurrent synaptic excitation, and computer simulations have provided a theoretical framework for the idea that relatively sparse interactions through recurrent excitatory chemical synapses can generate synchronized bursting after inhibitory pathways are blocked with convulsant agents. Additional experimental studies have supported the hypothesis that a model for seizure discharge, the penicillin-induced paroxysmal depolarization shift (PDS), is associated with a large increase in excitatory synaptic conductance. However, recent studies have suggested that electrical interactions are also likely to play an important role in spike synchronization during epileptic discharges. Several research groups have used in vitro preparations to show that afterdischarges and spontaneous bursts of population spikes (which represent synchronized action potentials) can occur after chemical synaptic transmission has been blocked in solutions containing low [Ca2+]. Although this result was first observed in the CA1 area, it has recently been confirmed in other regions of the hippocampus. These experiments indicate that mechanisms other than chemical synaptic transmission are capable of synchronizing action potentials in the hippocampus. In this chapter, two forms of electrical interaction that could mediate synchronization will be considered: (a) electrotonic coupling through gap junctions and (b) electrical field effects through extracellular space. Changes in the concentration of extracellular ions are another mechanism not involving chemical synapses. However, it seems unlikely that ionic changes act on the rapid time scale of electrical interactions, and their contribution is discussed elsewhere in this volume. We review evidence for the existence of electrotonic coupling and electrical field effects in the hippocampus and neocortex, and discuss their possible involvement in the synchronization of epileptiform events.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1998

A software architecture to support a large-scale, multi-tier clinical information system.

A robust software architecture is necessary to support a large-scale multi-tier clinical information system. This paper describes our mechanism for enterprise distribution of applications and support files, the consolidation of data-access functions and system utilities stored on the data access tier, and an application framework which implements a coherent clinical computing environment. The software architecture and systems described in this paper have been robust through pilot testing of our applications at Massachusetts General Hospital.

Computer Security↗

PubMed2006

Interplay of water, extra-framework cations and framework atoms in the structure of low-silica zeolites: the case of the natural zeolite Goosecreekite as studied by computer simulation.

Computational methods are described that model accurately the structure of hydrated Ca-bearing zeolites. Using Goosecreekite as a model system we probe the influence of framework ordering, cation siting and hydration of pores on the structure and its stability. We develop a methodology which allows the location of Al within the framework to be determined together with the position of extra-framework cations, in a stepwise fashion, progressing from an anhydrous model, via a dielectric continuum model, to finally, a fully atomistic model of the water in the intrazeolite pore space. Our methods reveal the complex interplay of short- and long-range interactions on the optimal structure of such materials.

Cations↗

PubMed2006

E-learning for healthcare students: developing the communities of practice framework.

AIM: This paper presents research considering whether healthcare students were able to develop characteristics of communities of practice when engaged in an online module. BACKGROUND: Little is known about whether the communities of practice framework can be applied to online learning, with no previous consideration of its potential use within healthcare education. METHODS: Using a case study approach the research, completed in 2004, had two phases. A questionnaire was administered to a group of 109 healthcare students to gain information on which to base sampling for the subsequent phase. Phase 2 employed three strands of data collection: five students completed an online diary, the online interactions of seven students were captured on a discussion board and three students were interviewed. Data were analysed using a form of pattern matching. FINDINGS: Students were able to develop essential elements of communities of practice: mutual engagement, joint enterprise and shared repertoire, though this was not uniformly seen. Particular issues emerged for the online community, including enabling access to the online environment to support mutual engagement. The development of trust was also threatened by difficulties of presenting identities online. Joint enterprise was hampered by the online situation, although the virtual classroom proved essential for supporting endeavour. Not all students were committed to their groups. There was some evidence of group members developing shared repertoire, as routines of group working emerged. Professional understanding and computer skills were also enhanced. CONCLUSION: The framework can be applied to supporting online learning internationally amongst students and has applicability to professional groups. Those intending to employ the framework should ensure that students can gain access to the community and have the computer skills to engage. Course design should be considered to ensure support for developing the essential components of communities of practice.

Adult↗

PubMed2006

Temperature dependence of the Casimir-like force in free-standing smectic films.

The thermal Casimir-like force in free-standing liquid crystal films close to the smectic-A-nematic transition temperature is computed using a quadratic functional approach. In the framework of a microscopic mean-field model of free-standing smectic-A films, the temperature dependence of the order parameter profiles is computed and later used to estimate the elastic coupling variability in the vicinity of first- and second-order bulk smectic-A-nematic phase transitions. The strong nonuniformity of the coupling constant profiles promotes a significant increase of the fluctuation-induced force over three orders of magnitude, especially in thin films. This result reinforces the possible predominance of the thermal Casimir force as compared to the standard van der Waals interaction in thin smectic-A liquid crystal films.

Journal Article↗

PubMed1999

The hydraulic system of trees: theoretical framework and numerical simulation

Empirical studies pose the problem of the physiological integration of the tree organism, which is also important on the scale of ecosystems. Recently, spatially distributed models emerged, which approach this problem by reflecting the close linkage between physiological processes and the structures of trees and tree stands. In the case of water flow, the tree organism can be regarded as hydraulic system and the branched tree architecture as hydraulic network. Previous models of the hydraulic system either did not take into account the network structure, or they had shortcomings regarding the translation of the underlying physiological assumptions by the discrete computation method. We have developed a theoretical framework which takes the form of a numerical simulation model of tree water flow. A discrete initial boundary value problem (IBVP) combines the phenomena of Darcy flow, water storage and conductivity losses in the hydraulic network. The software HYDRA computes the solution of the IBVP. The theoretical derivation and model tests corroborate the consistent translation of the physiological assumptions by the computational method. Simulation studies enabled us to formulate hypotheses on the following points: (1) differences in the hydraulic segmentation between Picea abies and Thuja occidentalis, (2) responses of the hydraulic system to rapid transpiration changes and to a scenario of drought stress, and (3) how these responses depend on architectural quantities of the trees. The simulation studies demonstrated our possibilities of deriving theoretically well-founded hypotheses about the functioning of the hydraulic system and its relation to system structure. The numerical simulation model is designed as a tool for structure-function studies, which is able to treat tree architecture as independent variable. The model supports the integration of data on tree level, and it can be used for computer experiments which quantify the dynamics of the hydraulic system according to the concepts of system theory. Copyright 1999 Academic Press.

Journal Article↗

PubMed1995

Disulfide stabilization of antibody Fv: computer predictions and experimental evaluation.

Using molecular modeling technology we have recently identified positions in conserved framework regions of Fvs which can be used to stabilize antibody Fvs by an interchain disulfide bond engineered in between the structurally conserved framework positions of the variable domains of heavy (VH) and light (VL) immunoglobulin chains (disulfide-stabilized Fv; dsFv). The computer model indicated the existence of other potential sites in the framework regions that might be suitable for disulfide bond formation between VH and VL. The possibility of obtaining dsFvs using these positions is evaluated here experimentally by constructing dsFv immunotoxins in which the Fv moiety is fused to a truncated form of Pseudomonas exotoxin. We analyzed the extent of dsFv formation and the activity of the resulting dsFv immunotoxins, and compared various dsFv molecules with the scFv immunotoxin. Our results demonstrate that position H44-L105 is the only one which gives high production yields of active dsFv. All other positions gave either low yields and activity or completely failed to produce active dsFv. With one exception, the formation and activities of the dsFvs corresponded to the C alpha-C alpha distance between the VH and VL positions, with an optimal distance of 5.7 A producing the best dsFv. Distances of 6.0-6.9 A resulted in a low yield of protein that was still capable of binding antigen, whereas distances > 7.0 A resulted in molecules in which dsFv formation was not obtained.

Amino Acid Sequence↗

PubMed2000

"Computer addiction": a critical consideration.

Problems related to intemperate Internet use are examined within the conceptual framework of addiction. It is argued that empirical support for the construct validity of computer addiction has yet to emerge, that defining the construct as a unique psychiatric disorder is therefore premature, and that, in most cases, excessive computer use may be symptomatic of other, more primary disorders. Greater caution and rigor are urged in investigating and treating problems related to intemperate computer use.

Behavior, Addictive↗

PubMed1996

Toward a model for nursing informatics.

PURPOSE: To propose a new model for the development of nursing informatics based on historical precedent. SIGNIFICANCE: Nursing informatics is expanding rapidly. The proposed model aids in understanding the areas of research, relating them to each other, and it shows areas where work is missing or should be extended. ORGANIZING FRAMEWORK: Nursing informatics as the interaction of cognitive science, computer science, and information science resting on a base of nursing science. IMPLICATIONS: As this model is tested, it can act as an organizing framework to understand and relate studies of nursing informatics and give organization for future research, education, and development.

Computer Communication Networks↗

PubMedDate not supplied

Quantitative computer-aided computed tomography analysis of sphenoid sinus anatomical relationships.

BACKGROUND: This study describes a novel computer-generated anatomic symmetry plane as a framework for the quantitative description of sphenoid sinus anatomy. The aim of this study was to (1) determine relationships and distances between a midline sphenoid reference point (called the central sphenoid point [CSP]) and lateral sphenoid wall structures and (2) assess the incidence of anterior clinoid process (ACP) pneumatization and pterygoid recess (PR) pneumatization. METHODS: Axial computed tomography (CT) scans (1-mm slice thickness) were obtained on a VolumeZoom CT scanner (Siemens Medical, Erlangen, Germany). Mathematically derived anatomic symmetry planes were created using custom postprocessing software. A standardized review of each CT scan using surgical planning software (CBYON Suite version 2.6; CBYON, Mountain View, CA) was performed. The CSP was defined as a reference point in the midline sagittal plane at the intersection of the vertical sellar face and the horizontal sellar floor. RESULTS: A total of 128 sides in 64 cadaveric specimens were available for review. The incidences of ACP pneumatization and PR pneumatization were 23.4 and 37.5%. The mean distances from the CSP to the left optic canal midpoint, the left ACP entrance point, and the left PR lateral wall were 17.2, 15.6, and 27.6 mm, respectively. The corresponding distances from the CSP on the right side were 17.3, 15.8, and 28.0 mm, respectively. Measurements from the maxillary spine to the optic canal midpoint, ACP entrance point, and PR lateral wall on each side were performed also. CONCLUSION: This approach provides both quantitative and qualitative understanding of sphenoid osteology and may be coupled with intraoperative surgical navigation to reduce the risks of sphenoid surgery. Both PR and ACP pneumatization are surprisingly common. Because the CSP-derived relationships may be referenced during endoscopic surgical navigation, they may provide greater clinical utility than traditional alternatives. This paradigm may facilitate a greater understanding of sphenoid anatomy and enhance surgical safety and precision.

Adult↗

PubMed2001

A methodology for web-enabling a computer-based patient record with contributions from cognitive science.

Cognitive science is a rich source of insight for creative use of new Web technologies by medical informatics workers. I outline a project to Web-enable an existing computer-based patient record (CPR) in the context of ideas from philosophy, linguistics, artificial intelligence, and cognitive psychology. Web prototypes play an important role (a) because Web technology lends itself to rapid prototype development, and (b) because prototypes help team members bridge among disparate medical, computing, and business ontologies. Six Web-enabled CPR prototypes were created and ranked. User scenarios were generated using a user communication matrix. Resulting prototypes were compared according to the degree to which they satisfied medical, computing, and business constraints. In a different organization, or at different time, candidate prototypes and their ranking might have been different. However, prototype generation and comparison are fundamentally influenced by factors usefully understood in a cognitive science framework.

Cognitive Science↗

PubMed2004

The neural representation of time.

This review summarizes recent investigations of temporal processing. We focus on motor and perceptual tasks in which crucial events span hundreds of milliseconds. One key question concerns whether the representation of temporal information is dependent on a specialized system, distributed across a network of neural regions, or computed in a local task-dependent manner. Consistent with the specialized system framework, the cerebellum is associated with various tasks that require precise timing. Computational models of timing mechanisms within the cerebellar cortex are beginning to motivate physiological studies. Emphasis has also been placed on the basal ganglia as a specialized timing system, particularly for longer intervals. We outline an alternative hypothesis in which this structure is associated with decision processes.

Basal Ganglia↗

PubMed1995

Protein docking combining symbolic descriptions of molecular surfaces and grid-based scoring functions.

With the growing number of known 3D protein structures, computing systems, that can predict where two protein molecules interact with each other is becoming of increasing interest. A system is presented, integrating preprocessing like the computation of molecular surfaces, segmentation, and searching for complementarity in the general framework of a pattern analyzing semantic network (ERNEST). The score of coarse symbolic computations is used by the problem independent control strategy of ERNEST to guide a more detailed analysis considering steric clash and judgements based on grid-based surface representations. Successful examples of the docking system are discussed that compare well with other approaches.

Binding Sites↗

PubMed1993

A constraint logic programming framework for constructing DNA restriction maps.

Restriction mapping is an important computational problem in molecular biology, particularly in genetic engineering and DNA sequencing. It is different in that it is not only a purely computational problem but involves an interaction between experimental data collection procedures and the mapping algorithms. Consequently, the problem is loosely defined and in practice requires a flexible and versatile algorithm. We describe a framework for solving many restriction mapping problems in the constraint logic programming language CLP (R) which takes advantage of the declarative and powerful features of constraint logic programming. A CLP (R) algorithm is developed for solving a simple restriction mapping problem. The algorithm is the extended to handle more complex variations of restriction mapping such as fragments with errors, circular maps, multiple enzymes and partial digests. The mapping variants are integrated within the same framework and differ in the constraints required to define the kind of map consistency. Various search heuristics and control strategies to improve the search process are also incorporated as constraints.

Algorithms↗