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PubMed2002

Magnetoencephalography in presurgical epilepsy evaluation.

The introduction of whole-head magnetoencephalography (MEG) systems facilitating simultaneous recording from the entire brain surface has led to a major breakthrough of MEG in presurgical epilepsy evaluation. Localizations of the interictal spike zone with MEG showed excellent agreement with invasive electrical recordings, were useful to clarify the spatial relationship of the irritative spike zone to structural lesions, and could attribute epileptic activity to lobar subcompartments both in temporal lobe and extratemporal epilepsy. MEG was especially useful for the study of patients with non-lesional neocortical epilepsy and of patients with large lesions, where it provided unique information on the epileptogenic zone. It could reliably localize sensorimotor cortex prior to surgical procedures adjacent to central fissure. MEG language mapping yielded concordant results with the Wada test and cortical stimulation studies. MEG localizations of epileptic activity and essential brain regions were successfully integrated into frameless stereotaxy systems providing accurate functional information intraoperatively. Because MEG and EEG yield both complementary and confirmatory information, combined MEG-EEG recordings in conjunction with advanced source modeling techniques will further improve the noninvasive evaluation of epilepsy patients and constantly reduce the need for invasive procedures.

Brain↗

PubMed2005

STEPP--Search Tool for Exploration of Petri net Paths: a new tool for Petri net-based path analysis in biochemical networks.

To understand biochemical processes caused by, e. g., mutations or deletions in the genome, the knowledge of possible alternative paths between two arbitrary chemical compounds is of increasing interest for biotechnology, pharmacology, medicine, and drug design. With the steadily increasing amount of data from high-throughput experiments new biochemical networks can be constructed and existing ones can be extended, which results in many large metabolic, signal transduction, and gene regulatory networks. The search for alternative paths within these complex and large networks can provide a huge amount of solutions, which can not be handled manually. Moreover, not all of the alternative paths are generally of interest. Therefore, we have developed and implemented a method, which allows us to define constraints to reduce the set of all structurally possible paths to the truly interesting path set. The paper describes the search algorithm and the constraints definition language. We give examples for path searches using this dedicated special language for a Petri net model of the sucrose-to-starch breakdown in the potato tuber.

Algorithms↗

PubMed2002

The writing approaches of secondary students.

BACKGROUND: Research with college students has supported a model of writing approaches that defines the relationship between a writer and writing task along a deep and surface process continuum (Biggs, 1988). Based on that model, Lavelle (1993) developed the Inventory of Processes in College Composition which reflects students' motives and strategies as related to writing outcomes. It is also important to define the approaches of secondary students to better understand writing processes at that level, and development in written composition. AIMS: This study was designed to define the writing approaches of secondary students by factor analysing students' responses to items regarding writing beliefs and writing strategies, and to compare the secondary approaches to those of college students. A related goal was to explore the relationships of the secondary writing approaches to perceived self-regulatory efficacy for writing (Zimmerman & Bandura, 1994), writing preferences, and writing outcomes. SAMPLES: The initial, factor analytic phase involved 398 junior level high school students (11th grade) enrolled in a mandatory language arts class at each of three large Midwestern high schools (USA). Then, 49 junior level students enrolled in two language arts classes participated as subjects in the second phase. METHOD: Classroom teachers administered the Inventory of Processes in College Composition (Lavelle, 1993), which contained 72 true-or-false items regarding writing beliefs and strategies, during regular class periods. Data were factor analysed and the structure compared to that of college students. In the second phase, the new inventory, Inventory of Processes in Secondary Composition, was administered in conjunction with the Perceived Self-Regulatory Efficacy for Writing Inventory (Zimmerman & Bandura, 1994), and a writing preferences survey. A writing sample and grade in Language Arts classes were obtained and served as outcome variables. RESULTS: The factor structure of secondary writing reflected three process dimensions. The first factor, Elaborative-Expressive, describes a writing strategy based on personal investment and audience concern. The second factor, Planful-Procedural, denotes sticking to a plan, following the rules, and 'preparing' for writing. Achieving-Competitive, the third factor, reflects a 'teacher pleasing' strategy or doing only what needs to be done to get a good grade. Two factors from the college model, Elaborative and Procedural, were replicated, and two were not, Reflective-Revision and Low Self-Efficacy. Regression analyses supported that the processes in writing under a timed condition are different from those used when writing over time, and that students' perceptions of writing self-regulatory efficacy were predictive of writing success under both conditions.

Adolescent↗

PubMed2006

Age-related connectivity changes in fMRI data from children listening to stories.

The way humans comprehend narrative speech plays an important part in human development and experience. A group of 313 children with ages 5-18 were subjected to a large-scale functional magnetic resonance imaging (fMRI) study in order to investigate the neural correlates of auditory narrative comprehension. The results were analyzed to investigate the age-related brain activity changes involved in the narrative language comprehension circuitry. We found age-related differences in brain activity which may either reflect changes in local neuroplasticity (of the regions involved) in the developing brain or a more global transformation of brain activity related to neuroplasticity. To investigate this issue, Structural Equation Modeling (SEM) was applied to the results obtained from a group independent component analysis (Schmithorst, V.J., Holland, S.K., et al., 2005. Cognitive modules utilized for narrative comprehension in children: a functional magnetic resonance imaging study. NeuroImage) and the age-related differences were examined in terms of changes in path coefficients between brain regions. The group Independent Component Analysis (ICA) had identified five bilateral task-related components comprising the primary auditory cortex, the mid-superior temporal gyrus, the most posterior aspect of the superior temporal gyrus, the hippocampus, the angular gyrus and the medial aspect of the parietal lobule (precuneus/posterior cingulate). Furthermore, a left-lateralized network (sixth component) was also identified comprising the inferior frontal gyrus (including Broca's area), the inferior parietal lobule, and the medial temporal gyrus. The components (brain regions) for the SEM were identified based on the ICA maps and the results are discussed in light of recent neuroimaging studies corroborating the functional segregation of Broca's and Wernicke's areas and the important role played by the right hemisphere in narrative comprehension. The classical Wernicke-Geschwind (WG) model for speech processing is expanded to a two-route model involving a direct route between Broca's and Wernicke's area and an indirect route involving the parietal lobe.

Adolescent↗

PubMed2003

Common language or Tower of Babel? On the evolutionary dynamics of signals and their meanings.

We investigate how the evolution of communication strategies affects signal credibility when there is common interest as well as a conflict between communicating individuals. Taking alarm calls as an example, we show that if the temptation to cheat is low, a single signal is used in the population. If the temptation increases cheaters will erode the credibility of a signal, and an honest mutant using a different signal ('a private code') will be very successful until this, in turn, is cracked by cheaters. In such a system, signal use fluctuates in time and space and hence the meaning of a given signal is not constant. When the temptation to cheat is too large, no honest communication can maintain itself in a Tower of Babel of many signals. We discuss our analysis in the light of the Green Beard mechanism for the evolution of altruism.

Altruism↗

PubMed1997

Relateralizing hypnosis: or, have we been barking up the wrong hemisphere?

Research and theory over the past couple decades have suggested that the right cerebral hemisphere might be the focus of brain activity during hypnosis. Recent evidence from electrodermal responding, visual event-related potentials, and Stroop interference, however, can make a case for a role of the left hemisphere in some hypnotic phenomena. Although hemispheric activation on hypnotic challenge may depend in large part on the kind of task the challenge might involve, several general aspects of hypnosis might be more appropriately seen as left-rather than right-hemisphere brain functions. Among these are concentrated attentional focus and the role of language in the establishment of hypnotic reality. A left-hemisphere theory of hypnosis is discussed in light of recent findings and theories about a left-hemisphere basis for synthetic or generational capabilities (Corballis, 1991) and a neuro-evolutionary model of a left-hemisphere dopaminergic activation system for the implementation of predetermined motor programs (Tucker & Williamson, 1984).

Attention↗

PubMed2005

MAPPER: a search engine for the computational identification of putative transcription factor binding sites in multiple genomes.

BACKGROUND: Cis-regulatory modules are combinations of regulatory elements occurring in close proximity to each other that control the spatial and temporal expression of genes. The ability to identify them in a genome-wide manner depends on the availability of accurate models and of search methods able to detect putative regulatory elements with enhanced sensitivity and specificity. RESULTS: We describe the implementation of a search method for putative transcription factor binding sites (TFBSs) based on hidden Markov models built from alignments of known sites. We built 1,079 models of TFBSs using experimentally determined sequence alignments of sites provided by the TRANSFAC and JASPAR databases and used them to scan sequences of the human, mouse, fly, worm and yeast genomes. In several cases tested the method identified correctly experimentally characterized sites, with better specificity and sensitivity than other similar computational methods. Moreover, a large-scale comparison using synthetic data showed that in the majority of cases our method performed significantly better than a nucleotide weight matrix-based method. CONCLUSION: The search engine, available at http://mapper.chip.org, allows the identification, visualization and selection of putative TFBSs occurring in the promoter or other regions of a gene from the human, mouse, fly, worm and yeast genomes. In addition it allows the user to upload a sequence to query and to build a model by supplying a multiple sequence alignment of binding sites for a transcription factor of interest. Due to its extensive database of models, powerful search engine and flexible interface, MAPPER represents an effective resource for the large-scale computational analysis of transcriptional regulation.

Algorithms↗

PubMed2005

Evolutionary sequence analysis of complete eukaryote genomes.

BACKGROUND: Gene duplication and gene loss during the evolution of eukaryotes have hindered attempts to estimate phylogenies and divergence times of species. Although current methods that identify clusters of orthologous genes in complete genomes have helped to investigate gene function and gene content, they have not been optimized for evolutionary sequence analyses requiring strict orthology and complete gene matrices. Here we adopt a relatively simple and fast genome comparison approach designed to assemble orthologs for evolutionary analysis. Our approach identifies single-copy genes representing only species divergences (panorthologs) in order to minimize potential errors caused by gene duplication. We apply this approach to complete sets of proteins from published eukaryote genomes specifically for phylogeny and time estimation. RESULTS: Despite the conservative criterion used, 753 panorthologs (proteins) were identified for evolutionary analysis with four genomes, resulting in a single alignment of 287,000 amino acids. With this data set, we estimate that the divergence between deuterostomes and arthropods took place in the Precambrian, approximately 400 million years before the first appearance of animals in the fossil record. Additional analyses were performed with seven, 12, and 15 eukaryote genomes resulting in similar divergence time estimates and phylogenies. CONCLUSION: Our results with available eukaryote genomes agree with previous results using conventional methods of sequence data assembly from genomes. They show that large sequence data sets can be generated relatively quickly and efficiently for evolutionary analyses of complete genomes.

Animals↗

PubMed1985

An approach to the collection and manipulation of time-based data using the IBM PC and BASICA.

With the advent of increasingly integrated, powerful and inexpensive digital electronics, relatively powerful computers have become available to the general public. Along with this technological boom there has been a concomitant increase in the availability of over-the-counter software packages which can be used by research scientists for program development. In the past, the development of computer programs for the collection of large amounts of time-based data was expensive and time consuming; however, the introduction of the current generation of 16-bit microcomputers and associated hardware and software packages has enabled investigators with only a rudimentary knowledge of computers and interfacing to begin to design programs. The schemes and algorithms, developed using BASICA on an IBM-Personal Computer, which are described in this article can serve other investigators as models for the assembly of their own programs for the collection, manipulation and plotting of time-based data. The incorporation of inexpensive computer graphics hardware and software, which provided a simple solution to the problem of analysis and presentation of large amounts of data, will also be discussed.

Algorithms↗

PubMed1993

Vasoactive mediators and splanchnic perfusion.

OBJECTIVE: To provide an overview of the splanchnic hemodynamic response to circulatory shock. DATA SOURCES: Previous studies performed in our own laboratory, as well as a computer-assisted search of the English language literature (MEDLINE, 1966 to 1991), followed by a selective review of pertinent articles. STUDY SELECTION: Studies were selected that demonstrated relevance to the splanchnic hemodynamic response to circulatory shock, either by investigating the pathophysiology or documenting the sequelae. Article selection included clinical studies as well as studies in appropriate animal models. DATA EXTRACTION: Pertinent data were abstracted from the cited articles. RESULTS OF DATA SYNTHESIS: The splanchnic hemodynamic response to circulatory shock is characterized by a selective vasoconstriction of the mesenteric vasculature mediated largely by the renin-angiotensin axis. This vasospasm, while providing a natural selective advantage to the organism in mild-to-moderate shock (preserving relative perfusion of the heart, kidneys, and brain), may, in more severe shock, cause consequent loss of the gut epithelial barrier, or even hemorrhagic gastritis, ischemic colitis, or ischemic hepatitis. From a physiologic standpoint, nonpulsatile cardiopulmonary bypass, a controlled form of circulatory shock, has been found experimentally to significantly increase circulating levels of angiotensin II, the hormone responsible for this selective splanchnic vasoconstriction. CONCLUSIONS: While angiotensin II has been viewed primarily as the mediator responsible for the increased total vascular resistance seen during (and after) cardiopulmonary bypass, it may also cause the disproportionate decrease in mesenteric perfusion, as measured in human subjects by intraluminal gastric tonometry and galactose clearance by the liver, as well as the consequent development of the multiple organ failure syndrome seen in 1% to 5% of patients after cardiac surgery.

Angiotensin II↗

PubMed2000

[Aphasia research and speech localization in the brain].

Aphasia research has become an acknowledged branch of modern cognitive neuropsychology research whose aim is to explore more fully the structures of knowledge and of cerebral processes which might both be affected in patients with aphasia. Up to the second half of this century, a model based on a specific cerebral localisation of language processes had emerged based on brain localisation research by Broca and Wernicke (among others). New modern neuroimaging techniques, however, such as computed tomography and magnetic resonance imaging (MRI), but also functional imaging modalities such as positron emission tomography or functional MRI, have modified these concepts. It emerges that in comprehension as well as in production of language, not only a few well defined centres are responsible for the activity, but there is a synchronised activity in large neuronal networks connecting various regions located both in the cortex and in the deep subcortical structures; today, this activity can be demonstrated best in a non-invasive and reproducible way with functional MRI.

Aphasia↗

PubMed1993

Specification of models in large expert systems based on causal probabilistic networks.

Problems involved in the specification of large expert systems are discussed. In the specification of causal probabilistic networks conditional probability tables for all nodes have to be provided. These conditional probability tables can often be described by models that specify the nature of interaction between nodes. Various types of models are described and a program that handles such models is presented. Large causal probabilistic networks often contain several copies of identical tables or structures. A header facility that provides common definitions of such repeated elements is proposed. This facility makes specifications much shorter and easier to construct and maintain.

Expert Systems↗

PubMed1982

SPBS: statistical programs for biological sciences. Minicomputer software for applying routine biostatistical methods.

The main routine statistical analyses can be carried out from start to finish on a minicomputer with basic language capability and greater than or equal to 32000 bytes of random access memory. However, no statistical software packs for minicomputers are ever complete enough for exhaustive analysis of most problems. Taking account of the requirements of statistical models, this paper gives an outline of how to set up a program. Examples are given from the package of statistical programs developed at this institute. The advantages and disadvantages of making these analyses on minicomputers are discussed, in comparison with the use of statistical programs requiring large computers.

Biometry↗

PubMed2002

Why is magical ideation related to leftward deviation on an implicit line bisection task?

Right hemispatial inattention is a neurocognitive deficit observed in thought-disordered schizophrenia patients, persons with schizotypal personality disorder and healthy participants with high scores on schizotypy scales. We administered a schizotypy inventory, the Magical Ideation (MI) scale, to forty healthy, right-handed men who had copied and later recalled the Rey-Osterrieth complex figure. Implicit line bisection performances were defined as the bisecting lines of the complex figure's large rectangle and were recorded for the copy and delay conditions. MI scores were significantly correlated with a leftward shift in bisections in the delay but not copy condition, indicating a significant relationship between the degree of right hemispatial inattention and number of magical beliefs in healthy participants. We describe a model in which these beliefs are conceptualized as a consequence of a hemispheric imbalance, specifically, of a "right hemisphere processing bias". This model accounts for (1) the leftward shifts in spatial attention and (2) the language deficits associated with psychosis and related symptom clusters which have hitherto been addressed in separate literatures. Clinically, the Rey-Osterrieth test may provide a means to assess implicit hemispatial inattention in psychotic patients.

Adult↗

PubMed2003

Spread of cattle led to the loss of matrilineal descent in Africa: a coevolutionary analysis.

Matrilineal descent is rare in human societies that keep large livestock. However, this negative correlation does not provide reliable evidence that livestock and descent rules are functionally related, because human cultures are not statistically independent owing to their historical relationships (Galton's problem). We tested the hypothesis that when matrilineal cultures acquire cattle they become patrilineal using a sample of 68 Bantu- and Bantoid-speaking populations from sub-Saharan Africa. We used a phylogenetic comparative method to control for Galton's problem, and a maximum-parsimony Bantu language tree as a model of population history. We tested for coevolution between cattle and descent. We also tested the direction of cultural evolution--were cattle acquired before matriliny was lost? The results support the hypothesis that acquiring cattle led formerly matrilineal Bantu-speaking cultures to change to patrilineal or mixed descent. We discuss possible reasons for matriliny's association with horticulture and its rarity in pastoralist societies. We outline the daughter-biased parental investment hypothesis for matriliny, which is supported by data on sex, wealth and reproductive success from two African societies, the matrilineal Chewa in Malawi and the patrilineal Gabbra in Kenya.

Africa South of the Sahara↗

PubMed1989

A BASIC program for the estimation of Michaelis-Menten parameters by the direct linear plot.

The use of manual graphical methods for the estimation of Michaelis-Menten kinetic parameters as recommended by Eisenthal and Cornish-Bowden (Biochem. J. 139 (1974) 715-720) was found to be impractical for large (n greater than 5) sample numbers. A BASIC program providing the rank ordered coordinates of intersections, which correspond to estimates of Km and Vmax in the direct linear plot method, is described.

Cytochrome P-450 Enzyme System↗

PubMed2001

Etiologic determination of childhood developmental delay.

To determine the etiologic yield in young children with developmental delay referred to sub-specialty clinics for evaluation. Over an 18-month period, all children less than 5 years of age referred to the ambulatory pediatric neurology or developmental pediatrics clinics of the Montreal Children's Hospital for initial evaluation of a suspected developmental delay were enrolled. Features evident on history or physical examination were determined at intake as were the laboratory tests (and their rationale) requested by the evaluating physicians. Six months post initial assessment, detailed chart review was undertaken to determine if an etiology was found and the basis for such a determination. Bivariate and multivariate logistic regression was used to test for associations between factors present at intake and successful ascertainment of an underlying etiology. Two hundred and twenty-four children met study criteria. Etiologic yield varied across childhood developmental delay subtypes, and was 44/80 for global developmental delay [GDD] (55%), 13/22 for motor delay [MD] (59.1%), 3/72 for developmental language disorders [DLD] (4.2%), and 1/50 for autistic spectrum disorders [ASD] (2%). For GDD, the presence of historical features or findings on physical examination was associated with greater likelihood for successful etiologic determination with the following items significant in multiple logistic regression analysis; microcephaly, antenatal toxin exposure, focal findings. For MD, physical findings or the co-existence of a cerebral palsy symptom complex predicted a successful search for etiology. For both groups, the severity of the delay did not predict etiologic yield. For both groups, a small number of etiologic categories accounted for the majority of diagnoses made. Etiologic yield in childhood developmental delay is largely dependent on the specific developmental delay subtype. Paradigms for systematic evaluation of this common child health problem can be suggested, however they await validation.

Autistic Disorder↗

PubMed2004

Impact of different software implementations on the performance of the Maxmin method for diverse subset selection.

Besides the choice of an automated software method for selecting 'maximally diverse' compounds from a large pool of molecules, it is the implementation of the algorithm that critically determines the usefulness of the approach. The speed of execution of two implementations of the Maxmin algorithm is compared for the selection of maximally diverse subsets of large compound collections. Different versions of the software are compared using various C compiler options and Java virtual machines. The analysis shows that the Maxmin algorithm can be implemented in both languages yielding sufficient speed of execution. For large compound libraries the Java version outperformes the C version. While the Java version selects the same compounds independent of the virtual machine used, the C version produces slightly different subsets depending on the compiler and on the optimization settings.

Algorithms↗