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Java Web Simulation (JWS); a web based database of kinetic models.

Software to make a database of kinetic models accessible via the internet has been developed and a core database has been set up at http://jjj.biochem.sun.ac.za/. This repository of models, available to everyone with internet access, opens a whole new way in which we can make our models public. Via the database, a user can change enzyme parameters and run time simulations or steady state analyses. The interface is user friendly and no additional software is necessary. The database currently contains 10 models, but since the generation of the program code to include new models has largely been automated the addition of new models is straightforward and people are invited to submit their models to be included in the database.

Computer Simulation↗

The impact of lexical-semantic impairment and of executive dysfunction on the word reading performance of patients with probable Alzheimer dementia.

The influence of lexical-semantic impairment and of executive dysfunction on word naming performance was investigated in a group of patients with probable Alzheimer dementia (AD). The patients, who varied in the severity of the illness, were tested in a word naming task where they had to read aloud Italian three-syllable words with a dominant or subordinate stress pattern. These types of words have been shown to interact with frequency in normal adults [J. Exp. Psychol.: Hum. Percept. Perform. 18 (4) (1992) 987], so that the effect of the subordinate stress pattern (slower reading times) is only apparent for low frequency words. The frequency and stress effects on accuracy increased across dementia severity levels. Regression analyses showed that the impairment in reading low frequency words with subordinate stress depended largely on the level of lexical-semantic impairment, measured by a test of semantic memory and comprehension. Implications for the current reading models are discussed.

Aged↗

The Database of Quantitative Cellular Signaling: management and analysis of chemical kinetic models of signaling networks.

MOTIVATION: Analysis of cellular signaling interactions is expected to pose an enormous informatics challenge, perhaps even larger than analyzing the genome. The complex networks arising from signaling processes are traditionally represented as block diagrams. A key step in the evolution toward a more quantitative understanding of signaling is to explicitly specify the kinetics of all chemical reaction steps in a pathway. Technical advances in proteomics and high-throughput protein interaction assays promise a flood of such quantitative data. While annotations, molecular information and pathway connectivity have been compiled in several databases, and there are several proposals for general cell model description languages, there is currently little experience with databases of chemical kinetics and reaction level models of signaling networks. RESULTS: The Database of Quantitative Cellular Signaling is a repository of models of signaling pathways. It is intended both to serve the growing field of chemical-reaction level simulation of signaling networks, and to anticipate issues in large-scale data management for signaling chemistry. AVAILABILITY: The Database of Quantitative Cellular Signaling is available at http://doqcs.ncbs.res.in. Links to the signaling model simulator, GENESIS/Kinetikit are at http://www.ncbs.res.in/~bhalla/kkit/index.html and are also provided from within the database. The database source code is available under the GNU Public License.

Abstracting and Indexing↗

New challenges, emerging trends, and issues in regulation of migrating nurses.

The delivery of nursing and health care services is increasingly global in nature, largely as the result of international trade and migration. For the delivery of care and services to be safe, international regulation must come into play. Ensuring nurse competency depends on evaluation in three fundamental areas: knowledge and skills, clinical judgment, and language competency. Countries use a variety of regulatory methods, and there is no perfect regulatory model. Each presents its own challenges in the areas of screening, supervision, and testing. Regulation is going international with several regions having developed mutual recognition agreements. The implementation of trade agreements such as General Agreement on Trades in Services may pose new challenges for international regulation in nursing, the basic purpose of which must remain protection of the public.

Developed Countries↗

MD Concept: a model for integrating medical knowledge.

Many integrated clinical information systems depend on large knowledge bases containing dictionary of terms as well as specific information about each term and the relationships between terms. We propose a knowledge base model called MD Concept which is based on a semantic network and uses an object-oriented paradigm and relational tables. A prototype has been developed which integrates the Unified Medical Language System (UMLS) with other databases including the Systematized Nomenclature of Medicine (SNOMED II), the Diagnostic and Statistical Manual of Mental Disorders (DSM-IIIR) and a pharmaceutical database. We demonstrate how a user can easily navigate in this knowledge world using a browser.

Artificial Intelligence↗

Challenges in converting frame-based ontology into OWL: the Foundational Model of Anatomy case-study.

A description logics representation of the Foundational Model of Anatomy (FMA) in the Web Ontology Language (OWL-DL) would allow developers to combine it with other OWL ontologies, and would provide the benefit of being able to access generic reasoning tools. However, the FMA is currently represented in a frame language. The differences between description logics and frames are not only syntactic, but also semantic. We analyze some theoretical and computational limitations of converting the FMA into OWL-DL. Namely, some of the constructs used in the FMA do not have a direct equivalent in description logics, and a complete conversion of the FMA in description logics is too large to support reasoning. Therefore, an OWL-DL representation of the FMA would have to be optimized for each application. We propose a solution based on OWL-Full, a superlanguage of OWL-DL, that meets the expressiveness requirements and remains application-independent. Specific simplified OWL-DL representations can then be generated from the OWL-Full model by applications. We argue that this solution is easier to implement and closer to the application needs than an integral translation, and that the latter approach would only make the FMA maintenance more difficult.

Anatomy↗

The role of automated speech recognition in endoscopic data collection.

Speech recognition technology has developed substantially in the past half decade. Currently, large vocabulary, speaker independent, discrete recognizers are the state-of-the-art. This will change. Moderate sized, continuous recognition systems now exist in research settings. However, it is unlikely that such systems will be widely available until the mid to late 1990's. The accuracy rates of current speech recognition systems are high. Consequently, speech accuracy is not the current limiting aspect of using ASR. The limiting aspect of using ASR technology is the approach to integrating speech functionality into applications. One approach is to use ATNs as models of natural language to support both an input strategy and a text generation system. ATNs provide approaches to both syntactical correctness and semantic richness. This is an approach which plays to the strengths of the discrete nature of current speech technology and also provides a methodology for the capture and archiving of highly detailed information. The ATN approach avoids the natural language parsing problem created by a fully free form dictation interface. Evolving along with the underlying speech technology are standards in the definitions and criteria used in endoscopic practice. There are clear benefits from standards in this area. However, it is likely that this will also take several years and may never yield a universally accepted lexicon. Furthermore, there will be user interface barriers to surmount in any system attempting to use speech as an input modality. Because of the relatively large vocabularies used in medical discourse, the user interface will need to be carefully crafted.(ABSTRACT TRUNCATED AT 250 WORDS)

Data Collection↗

Communicative ability in an audiological perspective. Theory and application to post-secondary school students.

The underlying assumption in the present study is that the individual's speech and hearing communicative ability is composed of three components, each corresponding to different functional systems of the brain: afferent functions (A) represent the auditory activity and sound perception largely corresponding to activity in the ascending auditory pathways. The central functions (C) include cortical auditory and language abilities controlled in parts of the left temporal lobe and subcortical centres. The efferent functions (E) consist of speech motor processes and articulation. A test battery of 20 tests measuring several aspects of afferent, central and efferent functions was applied to 11 hearing-impaired post-secondary school students and several control groups. All data were normalized with the normal materials as references. Individual communicative profiles were obtained from these primary data, which consisted of audiometric tests (tone and speech audiometry, impedance tests, brainstem response audiometry and phase audiometry), sound environmental tests with hearing aids (directional speech-in-noise, word localization, sound environment identification test), and language tests (reading tests, prosody, auditory memory and recall, phonology and articulation). Since the central functions cannot truly and directly be determined in hearing-imparied subjects, they were assessed under optimal listening conditions. Furthermore, central functions were estimated according to three different models: distributive, parallel model (model 1), multiplicative, serial model (model 2) and compensatory model (model 3). On the basis of these models, a three-component description of the communicative ability consisting of A,C and E functions was obtained. It was found that C and E functions were largely independent of the adult afferent functions, but C functions were negatively correctly to hearing in childhood. A preliminary comparison between the tests and a comparison between the models was performed by predicting benefit of hearing aid. Model 3 gave the best prediction. Beyond the three-component A,C, and E characterization of the students, a total communicative ability score could be calculated giving values from 37% to 79% of the normal mean. On the basis of the conceptual and statistical analyses, the test battery could be reduced to include tone 0-12 years, tone adults, word localization test (afferent); word chain, lecture test (central), articulatory test (efferent) and audiovisual test. The simple algorithm of adding the normalized loss of afferent (peripheral) function to the normalized results of the acoustic central tests seems to be promising for isolation for the central auditory capacity even in cases with peripheral impairment. It is concluded that a wider perspective is desirable in the diagnostic evaluation of the hearing-impaired individual in order to understand his communicative abilities and form a cornerstone in the planning of rehabilitation in conjunction with social and psychological factors.

Adolescent↗

So what do you propose we use instead? A reply to Block.

Unfortunately, Block's brilliant critique is terribly biased, much like a legal brief that presents only one side of the issues at suit. It does not distinguish between the Big Five model of phenotypic personality attributes from alternative models of the causal underpinnings of personality differences. Ironically, it attempts to explain away the extensive evidence for the Big Five model as largely the result of data prestructuring, with no acknowledgement of the unique contribution of the lexical approach to minimizing such problems. Even more seriously, it omits a good deal of crucial evidence favorable to the Big Five model, including studies of Block's own Q-set and independent investigations of personality-related terms in other languages. Sadly, Block's closing suggestions provide little in the way of specific proposals for alternatives that he would have us use instead.

Factor Analysis, Statistical↗

The hematologic system as a marker of organ dysfunction in sepsis.

Sepsis with acute organ dysfunction (severe sepsis) results from a systemic proinflammatory and procoagulant response to infection. Organ dysfunction in the patient with sepsis is associated with increased mortality. Although most organs have discrete anatomical boundaries and carry out unified functions, the hematologic system is poorly circumscribed and serves several unrelated functions. This review addresses the hematologic changes associated with sepsis and provides a framework for prompt diagnosis and rational drug therapy. Data sources used include published research and review articles in the English language related to hematologic alterations in animal models of sepsis and in critically ill patients. Hematologic changes are present in virtually every patient with severe sepsis. Leukocytosis, anemia, thrombocytopenia, and activation of the coagulation cascade are the most common abnormalities. Despite theoretical advantages of using granulocyte colony-stimulating factor to enhance leukocyte function and/or circulating numbers, large clinical trials with these growth factors are lacking. Recent studies support a reduction in the red blood cell transfusion threshold and the use of erythropoietin treatment to reduce transfusion requirements. Treatment of thrombocytopenia depends on the cause and clinical context but may include platelet transfusions and discontinuation of heparin or other inciting drugs. The use of activated protein C may provide a survival benefit in subsets of patients with severe sepsis. The hematologic system should not be overlooked when assessing a patient with severe sepsis. A thorough clinical evaluation and panel of laboratory tests that relate to this organ system should be as much a part of the work-up as taking the patient's blood pressure, monitoring renal function, or measuring liver enzymes.

Blood Transfusion↗

Disparities in health care by race, ethnicity, and language among the insured: findings from a national sample.

BACKGROUND: Racial and ethnic disparities in health care have been well documented, but poorly explained. OBJECTIVE: To examine the effect of access barriers, including English fluency, on racial and ethnic disparities in health care. RESEARCH DESIGN: Cross-sectional analysis of the Community Tracking Survey (1996-1997). SUBJECTS: Adults 18 to 64 years with private or Medicaid health insurance. MEASURES: Independent variables included race, ethnicity, and English fluency. Dependent variables included having had a physician or mental health visit, influenza vaccination, or mammogram during the past year. RESULTS: The health care use pattern for English-speaking Hispanic patients was not significantly different than for non-Hispanic white patients in the crude or multivariate models. In contrast, Spanish-speaking Hispanic patients were significantly less likely than non-Hispanic white patients to have had a physician visit (RR, 0.77; 95% CI, 0.72-0.83), mental health visit (RR, 0.50; 95% CI, 0.32-0.76), or influenza vaccination (RR, 0.30; 95% CI, 0.15-0.52). After adjustment for predisposing, need, and enabling factors, Spanish-speaking Hispanic patients showed significantly lower use than non-Hispanic white patients across all four measures. Black patients had a significantly lower crude relative risk of having received an influenza vaccination (RR, 0.73; 95% CI, 0.58-0.87). Adjustment for additional factors had little impact on this effect, but resulted in black patients being significantly less likely than non-Hispanic white patients to have had a visit with a mental health professional (RR, 0.46; 95% CI, 0.37-0.55). CONCLUSIONS: Among insured nonelderly adults, there are appreciable disparities in health-care use by race and Hispanic ethnicity. Ethnic disparities in care are largely explained by differences in English fluency, but racial disparities in care are not explained by commonly used access factors.

Adult↗

Toward rigorous comprehension of biological complexity: modeling, execution, and visualization of thymic T-cell maturation.

One of the problems biologists face is a data set too large to comprehend in full. Experimenters generate data at an ever-growing pace, each from their own niche of interest. Current theories are each able, at best, to capture and model only a small part of the data. We aim to develop a general approach to modeling that will help broaden biological understanding. T-cell maturation in the thymus is a telling example of the accumulation of experimental data into a large disconnected data set. The thymus is responsible for the maturation of stem cells into mature T cells, and its complexity divides research into different fields, for example, cell migration, cell differentiation, histology, electron microscopy, biochemistry, molecular biology, and more. Each field forms its own viewpoint and its own set of data. In this study we present the results of a comprehensive integration of large parts of this data set. The integration is performed in a two-tiered visual manner. First, we use the visual language of Statecharts, which makes specification precise, legible, and executable on computers. We then set up a moving graphical interface that dynamically animates the cells, their receptors, the different gradients, and the interactions that constitute thymic maturation. This interface also provides a means for interacting with the simulation.

Cell Communication↗

The impact of developmental visuospatial learning difficulties on British Sign Language.

There has been substantial research interest in recent years in the relationship between the development of language and cognition, especially where dissociations can be seen between them. Williams syndrome, a rare congenital disorder characterized by a fractionation of higher cortical functions, with relatively preserved language but marked difficulties with visuospatial constructive cognition, has been extensively studied. The case of Heather, who is remarkably similar to the characteristic phenotype of Williams syndrome in physical appearance and cognitive abilities, but who is also congenitally deaf and a user of British Sign Language, provides the first opportunity to explore the consequences of specific visuospatial learning difficulties on the linguistic system when the language used is visuospatial. Heather shows a pattern of impaired drawing ability and visual form discrimination, but preserved ability to discriminate faces. She has a large vocabulary in British Sign Language, and overall presents a picture of relative competence in British Sign Language grammar. However, she shows specific deficits in those areas of British Sign Language which directly rely on spatial representations for linguistic purposes. A number of theories as to the nature of her impairments and those found in Williams syndrome are discussed, using models of the relationship between language and visuospatial cognition based on data from this unique case.

Adult↗

Language processing modulated by literacy: a network analysis of verbal repetition in literate and illiterate subjects.

Previous behavioral and functional neuroimaging data indicate that certain aspects of phonological processing may not be acquired spontaneously, but are modulated by learning an alphabetic written language, that is, learning to read and write. It appears that learning an alphabetic written language modifies the auditory-verbal (spoken) language processing competence in a nontrivial way. We have previously suggested, based on behavioral and functional neuroimaging data, that auditory-verbal and written language interact not only during certain language tasks, but that learning and developing alphabetic written language capacities significantly modulates the spoken language system. Specifically, the acquisition of alphabetic orthographic knowledge has a modulatory influence on sublexical phonological processing and the awareness of sublexical phonological structure. We have suggested that developing an orthographic representation system for an alphabetic written language, and integrating a phoneme-grapheme correspondence with an existing infrastructure for auditory-verbal language processing, will result in a modified language network. Specifically, we suggest that the parallel interactive processing characteristics of the underlying language-processing brain network differ in literate and illiterate subjects. Therefore, the pattern of interactions between the regions of a suitably defined large-scale functional-anatomical network for language processing will differ between literate and illiterate subjects during certain language tasks. In order to investigate this hypothesis further, we analyzed the observed covariance structure in a PET data set from a simple auditory-verbal repetition paradigm in literate and illiterate subjects, with a network approach based on structural equation modeling (SEM). Based on a simple network model for language processing, the results of the present network analysis indicate that the network interactions during word and pseudoword repetition in the illiterate group differ, while there were no significant differences in the literate group. The differences between the two tasks in the illiterate group may reflect differences in attentional modulation of the language network, executive aspects of verbal working memory and the articulatory organization of verbal output. There were no significant differences between the literate and illiterate group during word repetition. In contrast, the network interactions differed between the literate and illiterate group during pseudoword repetition. In addition to differences similar to those observed in the illiterate group between word and pseudoword repetition, there were differences related to the interactions of the phonological loop between the groups. In particular, these differences related to the interaction between Broca's area and the inferior parietal cortex as well as the posterior-midinsula bridge between Wernicke's and Broca's area. In conclusion, the results of this network analysis are consistent with our previously presented results and support the hypothesis that learning to read and write during childhood influences the functional architecture of the adult human brain. In particular, the basic auditory-verbal language network in the human brain is modified as a consequence of acquiring orthographic language skills.

Adult↗

Templeting and self-assembly.

Templeting and self-assembly represent the two extremes of the spectrum of determinate pattern-assembly processes. A templeted pattern can be defined as one that requires a prepattern or templet explicitly specifying the final topology of the pattern. Conversely, a self-assembling pattern can be defined as one for which the inherent constraints of the precursor elements alone are sufficient to specify the final pattern. Both concepts can be directly expressed in matrix notation, and a simple matrix measure, the templeting index, characterizes the relative amount of templeting or of self-assembly in any particular system. With this language, a fundamental principle of pattern-assembly becomes evident: in the determinate realm, some patterns can only be assembled using the same-sized templets--templets that are at least as large as the final pattern.

Mathematics↗

Knowing its gender without knowing its name: differential access to lexical information in a jargonaphasic patient.

According to recent models of word production, when we name a picture, we first retrieve the meaning of the object, and then we independently retrieve the written or sound form of the word corresponding to the picture. In languages like French, in which words have a gender, theoretical models disagree with respect to the moment at which this information is retrieved. The lemma model (Levelt et al., 1999) posits that we access this information before the sound or written form of the word is retrieved. In contrast, the"Independent network"(IN) model (Caramazza, 1997) model posits that we access gender after retrieval of either the sound or written form of the word. This paper reports a single-case study of an aphasic patient, BA, who showed deficits affecting spoken and written production in the presence of largely preserved comprehension abilities. Experimental testing indicated that she presented with a deficit functionally localized in the access to lexical representations. Results in picture naming and in gender identification also revealed that BA identified the gender above chance level, whether she produced a correct response, a phonemic error, or a neologism. In contrast, when she was unable to produce a spoken or written response, she could not identify the gender. This pattern of performance is consistent with the lemma model in which access to lexical syntax is required before access to phonological form can take place.

Acoustic Stimulation↗

The influence of age and gender on drug use in the United Kingdom--a review.

The aim of this study is to review UK epidemiological research in light of studies on the influence of age and gender on drug use in young people. Literature for this review came from English language publications using a structured search strategy. Within the UK, drug use is commoner in young males than other population groups. When integrated social development models are employed, drug use is seen to be determined by the complex interaction of factors such as age, parental monitoring, and peer group associations. Suggested research directions include combining structural equation modeling with large-scale, UK-based longitudinal social development model studies to develop prevention and intervention efforts that are sensitive to the role of individual, social, and cultural factors.

Adolescent↗

Nomenclature of the finer branches of the biliary tree: canals, ductules, and ductular reactions in human livers.

The work of liver stem cell biologists, largely carried out in rodent models, has now started to manifest in human investigations and applications. We can now recognize complex regenerative processes in tissue specimens that had only been suspected for decades, but we also struggle to describe what we see in human tissues in a way that takes into account the findings from the animal investigations, using a language derived from species not, in fact, so much like our own. This international group of liver pathologists and hepatologists, most of whom are actively engaged in both clinical work and scientific research, seeks to arrive at a consensus on nomenclature for normal human livers and human reactive lesions that can facilitate more rapid advancement of our field.

Biliary Tract↗