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PubMed2003

Neuronal correlates of familiarity-driven decisions in artificial grammar learning.

It has been proposed on the basis of behavioural data that grammaticality judgments in implicit artificial grammar learning paradigms are largely driven by priming based on fragment familiarity. A prediction that follows from this account is that neural deactivation, a common correlate of repetition priming, should be observed for grammatical compared to ungrammatical stimuli. We conducted an event-related fMRI study to investigate neuronal correlates of such fragment-based priming. In a study phase, participants performed a short-term memory task on a series of strings of pseudofont characters. Scanning was performed in a subsequent test phase in which participants classified new strings as either grammatical or ungrammatical. Test strings differed systematically from training strings in terms of exemplar and fragment similarity. Behaviourally, participants classified strings as grammatical based on fragment familiarity. Differential activity was evident during string classification as reduced activity in left lateral occipital complex and bilateral lingual gyri for strings with high fragment familiarity compared to strings with low fragment familiarity. Thus, consistent with the hypothesis, neuronal facilitation in extrastriate occipital regions may constitute one basis of implicit grammaticality decisions based on fragment priming.

Adult↗

PubMed2003

Periodontal host modulation with antiproteinase, anti-inflammatory, and bone-sparing agents. A systematic review.

BACKGROUND: The use of modulating agents, including inhibition of matrix metalloproteinases (MMPs) with antiproteinases, blocking production of proinflammatory cytokines and prostaglandins with anti-inflammatory drugs, and inhibiting activation of osteoclasts with bone-sparing agents, has been postulated to be of therapeutic value as an adjunctive therapy to the management of chronic periodontitis. RATIONALE: The objective of this systematic review of the literature was to assess the adjunctive efficacy of antiproteinase, anti-inflammatory, and bone-sparing host-modulating agents in the treatment of gingivitis, aggressive periodontitis, and chronic periodontitis. FOCUSED QUESTIONS: 1. In patients with periodontal diseases, what is the effect of host-modulation agents, alone or combined with conventional therapy, compared to conventional therapy alone as assessed by clinical, radiographic, adverse, and patient-centered outcomes? 2. In patients with dental implants, what is the effect of host-modulation agents on implant success assessed by clinical, radiographic, adverse, and patient-centered outcomes? SEARCH PROTOCOL: MEDLINE, Embase, and the Cochrane Library databases were searched without language restrictions through April 1, 2002 for studies that used tetracycline (TET)-related matrix metalloproteinase (MMP) inhibitors, or non-steroidal anti-inflammatory drugs (NSAIDs) and bisphosphonate anti-osteolytic agents. The investigation also included hand searching of journals and contacting authors and industry experts. SELECTION CRITERIA INCLUSION CRITERIA: Only human studies (randomized controlled clinical trials, cohort studies, case-control studies, cross-sectional studies, and case series) were selected. Studies were on subjects with gingivitis, aggressive or chronic periodontitis, or dental implants. Interventions included TET-related MMP inhibitors, NSAIDs, or bisphosphonate anti-osteolytic agents. EXCLUSION CRITERIA: Studies that used MMP tissue inhibitors as diagnostic or prognostic indicators of periodontal disease or that evaluated short-term systemic antibodies or locally delivered levels of drugs with antiproteinase activity were excluded. DATA COLLECTION AND ANALYSIS: The primary outcomes for assessment were changes in bone or clinical attachment levels (CAL); secondary outcomes included clinical measures of plaque, gingival inflammation, probing depth (PD), and mobility. Summary data appropriate for meta-analysis were pooled using a weighted average and analyzed using a standardized difference; the results were checked with both fixed-effects and random-effects models. MAIN RESULTS: 1. A meta-analysis done on the studies reporting changes in CAL and PD following administration of sub-antimicrobial doses of doxycycline (SDD) in conjunction with scaling and root planing (SRP) in patients with periodontitis showed a statistically significant beneficial adjunctive effect. 2. There were insufficient data to provide meta-analyses on periodontal patients treated with other host-modulating agents; descriptive tables are included. 3. NSAIDS show promise in their ability to slow periodontal disease. 4. Preliminary data on bisphosphonate agents indicate there is a potential role for these agents in periodontitis management. 5. There are a very limited number of studies on host-modulating agents and dental implants and no analyses were possible. 6. Because the treatment methodologies and clinical variables differed considerably among the studies, it is difficult to summarize the information and identify a reliable total patient population. REVIEWERS' CONCLUSIONS: 1. Large multi-center trials are needed to evaluate the role of host-modulating agents in the treatment of periodontitis. 2. NSAIDS and bisphosphonate drugs may have a potential adjunctive role in periodontal therapy. 3. The adjunctive use of SDD with SRP is statistically more effective than SRP alone in reducing PD and in achieving CAL gain.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2005

ChemDB: a public database of small molecules and related chemoinformatics resources.

MOTIVATION: The development of chemoinformatics has been hampered by the lack of large, publicly available, comprehensive repositories of molecules, in particular of small molecules. Small molecules play a fundamental role in organic chemistry and biology. They can be used as combinatorial building blocks for chemical synthesis, as molecular probes in chemical genomics and systems biology, and for the screening and discovery of new drugs and other useful compounds. RESULTS: We describe ChemDB, a public database of small molecules available on the Web. ChemDB is built using the digital catalogs of over a hundred vendors and other public sources and is annotated with information derived from these sources as well as from computational methods, such as predicted solubility and three-dimensional structure. It supports multiple molecular formats and is periodically updated, automatically whenever possible. The current version of the database contains approximately 4.1 million commercially available compounds and 8.2 million counting isomers. The database includes a user-friendly graphical interface, chemical reactions capabilities, as well as unique search capabilities. AVAILABILITY: Database and datasets are available on http://cdb.ics.uci.edu.

Access to Information↗

PubMed2000

Intravascular ultrasound-guided interventions in coronary artery disease: a systematic literature review, with decision-analytic modelling, of outcomes and cost-effectiveness.

BACKGROUND: Intravascular ultrasound (IVUS) is the generic name for any ultrasound technology used in vivo within the blood vessels. More specifically, intracoronary ultrasound enables imaging of the coronary arteries from within the lumen. This review concentrates on the role of intracoronary ultrasound as an adjunct to interventional cardiology. OBJECTIVES: (1) To identify the literature on IVUS for guiding coronary interventions, and to synthesise evidence about outcomes compared with outcomes when IVUS guidance has not been used. (2) To use this evidence, together with other information about costs and outcomes, to model the cost effectiveness of IVUS guidance. (3) To synthesise the evidence on the reproducibility of measurements of cross-sectional area made using IVUS. METHODS DATA SOURCES: (1) Electronic searches of MEDLINE, EMBASE, Science Citation Index, Index to Scientific and Technical Proceedings, Engineering Compendex, Engineering Page One, Cochrane Library, Inside (British Library), 1990-98. (2) Contacting experts and centres of expertise, 1990-99. (3) Internet search, 1990-99. METHODS STUDY SELECTION: Studies of IVUS-guided coronary interventions performed on humans were included in the review. Non-English language studies were also included when they covered IVUS-guided stenting or angioplasty. Control evidence regarding outcomes without IVUS guidance was sought only from randomised controlled trials (RCTs). Studies investigating the reproducibility of measurements of cross-sectional area were included only if the results were expressed in terms of the mean and standard deviation of paired differences. METHODS DATA EXTRACTION: Checklists that covered study details, patient characteristics and results were completed independently by three reviewers. Consensus was reached on any disagreements. Local data were gathered on the costs of IVUS-guided stenting. METHODS DATA SYNTHESIS: Overall event rates were calculated by pooling patient results from the included studies. A decision-analytic model was used to combine information from the literature with cost estimates, in order to predict cost-effectiveness in terms of cost per restenosis event avoided by the use of IVUS guidance. The analysis was performed from the perspective of the healthcare provider. Sensitivity analysis was undertaken. A simple extrapolation was made to long-term outcome so that cost-utility (using quality-adjusted life years (QALYs)) could be estimated. The minimum detectable change in cross-sectional area was estimated from the reproducibility results. RESULTS: Only one study on IVUS-guided angioplasty satisfied the inclusion criteria, and there were no studies on IVUS-guided atherectomy or other IVUS-guided interventions that satisfied the inclusion criteria. Of the 15 articles on IVUS-guided stenting that satisfied the inclusion criteria, seven presented data on outcomes at 6 months post-intervention. The angiographic restenosis rate was 16 +/- 1%. This compared with 24 +/- 2% derived from five articles on stenting without IVUS guidance. Data for follow-up periods longer than 6 months were presented in only two studies. Data from a total of five studies were included in the decision-analytic model. The cost per restenosis event avoided was 1545 pound sterling. After extrapolation to long-term outcome, the calculated cost per QALY was 6438 pound sterling. The baseline QALY gain was only 0.03 years. Sensitivity analysis resulted in large differences between the best- and worst-case scenarios, for example, from a saving of 5000 pound sterling to a cost of 24,000 pound sterling restenosis event avoided. The smallest changes in cross-sectional area that could be measured were 1.6 mm2 by a single observer and 1.9 mm2 by different observers. CONCLUSIONS: Implications for healthcare: The evidence available is too weak for there to be any reliable implications for clinical practice. (ABSTRACT TRUNCATED)

Algorithms↗

PubMed2007

Object identification and lexical/semantic access in children: a functional magnetic resonance imaging study of word-picture matching.

Theoretical models for lexical access to visual objects have been based mainly on adult data. To investigate the developmental aspects of object recognition and lexical access in children, a large-scale functional MRI (fMRI) study was performed in 283 normal children ages 5-18 using a word-picture matching paradigm in which children would match an aurally presented noun to one of two pictures (line drawings). Using group Independent Component Analysis (ICA), six task-related components were detected, including (a) the posterior superior temporal gyrus bilaterally; (b) the fusiform, inferior temporal, and middle occipital gyri bilaterally; (c) the dorsal aspect of the inferior frontal gyrus bilaterally, the left precuneus, the left superior/middle temporal gyrus, and the anterior cingulate; (d) the right medial fusiform gyrus; (e) a left-lateralized component including the inferior/middle frontal, middle temporal, medial frontal, and angular gyri, as well as the thalamus and the posterior cingulate; and (f) the ventral/anterior aspect of the inferior frontal gyrus bilaterally. Increased activation associated with age was seen in the components (b) and (d) (ventral visual pathway) for object recognition, and (c) and (f) likely associated with semantic maintenance and response selection. Increased activation associated with task performance was seen in components (b) and (d) (ventral visual pathway) while decreased activation associated with task performance was seen in component (f) (ventral/anterior inferior frontal gyrus). The results corroborate the continued development of the ventral visual pathway throughout the developmental period.

Acoustic Stimulation↗

PubMed2004

Regulatory motif finding by logic regression.

MOTIVATION: Multiple transcription factors coordinately control transcriptional regulation of genes in eukaryotes. Although many computational methods consider the identification of individual transcription factor binding sites (TFBSs), very few focus on the interactions between these sites. We consider finding TFBSs and their context specific interactions using microarray gene expression data. We devise a hybrid approach called LogicMotif composed of a TFBS identification method combined with the new regression methodology logic regression. LogicMotif has two steps: First, potential binding sites are identified from transcription control regions of genes of interest. Various available methods can be used in this step when the genes of interest can be divided into groups such as up-and downregulated. For this step, we also develop a simple univariate regression and extension method MFURE to extract candidate TFBSs from a large number of genes in the availability of microarray gene expression data. MFURE provides an alternative method for this step when partitioning of the genes into disjoint groups is not preferred. This first step aims to identify individual sites within gene groups of interest or sites that are correlated with the gene expression outcome. In the second step, logic regression is used to build a predictive model of outcome of interest (either gene expression or up- and down-regulation) using these potential sites. This 2-fold approach creates a rich diverse set of potential binding sites in the first step and builds regression or classification models in the second step using logic regression that is particularly good at identifying complex interactions. RESULTS: LogicMotif is applied to two publicly available datasets. A genome-wide gene expression data set of Saccharomyces cerevisiae is used for validation. The regression models obtained are interpretable and the biological implications are in agreement with the known resuts. This analysis suggests that LogicMotif provides biologically more reasonable regression models than previous analysis of this dataset with standard linear regression methods. Another dataset of S.cerevisiae illustrates the use of LogicMotif in classification questions by building a model that discriminates between up- and down-regulated genes in iron copper deficiency. LogicMotif identifies an inductive and two repressor motifs in this dataset. The inductive motif matches the binding site of the transcription factor Aft1p that has a key role in regulation of the uptake process. One of the novel repressor sites is highly present in transcription control regions of FeS genes. This site could represent a TFBS for an unknown transcription factor involved in repression of genes encoding FeS proteins in iron deficiency. We establish the robustness of the method to the type of outcome variable used by considering both continuous and binary outcome variables for this dataset. Our results indicate that logic regression used in combination with cluster/group operating binding site identification methods or with our proposed method MFURE is a powerful and flexible alternative to linear regression based motif finding methods. AVAILABILITY: Source code for logic regression is freely available as a package of the R programming language by Ruczinski et al. (2003) and can be downloaded at http://bear.fhcrc.org/~ingor/logic/download/download.html an R package for MFURE is available at http://www.stat.berkeley.edu/~sunduz/software.html

Algorithms↗

PubMedDate not supplied

The risk of invasive cervical cancer among Hispanics: evidence for targeted preventive interventions.

BACKGROUND: Mass screening for cervical cancer has considerably reduced invasive cancer rates; however, Hispanic Americans have not fully benefited. This study examined the relationship of demographic, socioeconomic, and acculturation factors to diagnostic stage prior to preventive interventions in a large Hispanic community (San Diego, CA, 1988-1991). METHODS: Age-adjusted incidence rates (IR) were estimated for three subareas: Hispanic community targeted with interventions, comparison Hispanic community, and remainder of county. Incident cases of cervical cancer in the California Cancer Registry were used to calculate incidence rate ratios (IRR) of in situ to invasive stage cancer and estimate differences in early detection between Hispanics and white non-Hispanics. Multiple logistic regression was used to examine the relationship of cancer stage to census-linked income, education, poverty status, foreign birth, and language spoken. RESULTS: The in situ cervical cancer IR is significantly lower for Hispanics than for white non-Hispanics in all three regions (P < 0.05). The overall IRR is 3.65 (95% CI 3.19, 4.18) for white non-Hispanics compared with 1.09 (95% CI 0.86, 1.38) for Hispanics. Hispanics in census tracts in the highest versus remaining quartiles for percentage of language-isolated households are at greater risk for invasive stage (OR = 2.10, 95% CI 1.27, 3. 40). White non-Hispanic women residing in census tracts in the highest versus lowest quartile of adults with less than 12 years education are at greater risk for invasive stage (OR = 2.10, 95% CI 1.31, 3.38). CONCLUSIONS: Results show efforts aimed at cervical cancer early detection for Hispanic women are needed and well targeted. White non-Hispanic women in low-education communities are also at risk. Population-based methods in this study can focus efforts in communities needing preventive interventions.

Acculturation↗

PubMed2006

Deriving pathway maps from automated text analysis using a grammar-based approach.

We demonstrate how automated text analysis can be used to support the large-scale analysis of metabolic and regulatory pathways by deriving pathway maps from textual descriptions found in the scientific literature. The main assumption is that correct syntactic analysis combined with domain-specific heuristics provides a good basis for relation extraction. Our method uses an algorithm that searches through the syntactic trees produced by a parser based on a Referent Grammar formalism, identifies relations mentioned in the sentence, and classifies them with respect to their semantic class and epistemic status (facts, counterfactuals, hypotheses). The semantic categories used in the classification are based on the relation set used in KEGG (Kyoto Encyclopedia of Genes and Genomes), so that pathway maps using KEGG notation can be automatically generated. We present the current version of the relation extraction algorithm and an evaluation based on a corpus of abstracts obtained from PubMed. The results indicate that the method is able to combine a reasonable coverage with high accuracy. We found that 61% of all sentences were parsed, and 97% of the parse trees were judged to be correct. The extraction algorithm was tested on a sample of 300 parse trees and was found to produce correct extractions in 90.5% of the cases.

Abstracting and Indexing↗

PubMed2000

Multicentre research and the WISECARE experience. Workflow Information Systems for European Nursing Care.

The benefits of collaborative research are becoming recognized increasingly within the profession of nursing due to the associated increased likelihood of funding, variety of practice settings and increased access to resources that collaboration brings. While such benefits have made collaborative research one of the most desirable strategies for achieving the goals of research, the potential problems of language and communication, culturally sensitive instruments, access to subjects, availability of technology and lack of research resources have complicated collaborative international research initiatives. Review of the literature, although encouraging such initiatives, does little to provide information regarding the processes involved in multinational collaboration or the associated advantages and disadvantages to guide those embarking on such large scale, multinational, cross-cultural studies. The diverse meanings of collaboration within research initiatives further hamper this understanding. Positive definitions focus on aspects such as sharing expertise, making a valuable contribution to the research and ultimately shared ownership of the accomplishments of the research. One such research project led by nurses was the WISECARE project. WISECARE (Workflow Information Systems for European Nursing Care) was funded by the European Commission and aimed to improve cancer nursing practice and ultimately patient outcomes through the integration and utilization of state of the art information technology. Such a project was developed as a result of nursing's apparent invisibility within health care delivery and the problems experienced by nurses in articulating their worth within an increasingly cost-conscious health care system. Oncology care was selected as the domain for the project not only because this speciality of nursing already has an established network of nurses throughout Europe in the European Oncology Nursing Society (EONS) but also because the practice of cancer nursing encompasses all aspects of nursing care. This paper will address the advantages and disadvantages associated with collaboration, using the WISECARE project as an example.

Communication Barriers↗

PubMed2005

Providing visualisation support for the analysis of anatomy ontology data.

BACKGROUND: Improvements in technology have been accompanied by the generation of large amounts of complex data. This same technology must be harnessed effectively if the knowledge stored within the data is to be retrieved. Storing data in ontologies aids its management; ontologies serve as controlled vocabularies that promote data exchange and re-use, improving analysis. The Edinburgh Mouse Atlas Project stores the developmental stages of the mouse embryo in anatomy ontologies. This project is looking at the use of visual data overviews for intuitive analysis of the ontology data. RESULTS: A prototype has been developed that visualises the ontologies using directed acyclic graphs in two dimensions, with the ability to study detail in regions of interest in isolation or within the context of the overview. This is followed by the development of a technique that layers individual anatomy ontologies in three-dimensional space, so that relationships across multiple data sets may be mapped using physical links drawn along the third axis. CONCLUSION: Usability evaluations of the applications confirmed advantages in visual analysis of complex data. This project will look next at data input from multiple sources, and continue to develop the techniques presented to provide intuitive identification of relationships that span multiple ontologies.

Anatomy↗

PubMedDate not supplied

NIPALSTREE: a new hierarchical clustering approach for large compound libraries and its application to virtual screening.

A hierarchical clustering algorithm--NIPALSTREE--was developed that is able to analyze large data sets in high-dimensional space. The result can be displayed as a dendrogram. At each tree level the algorithm projects a data set via principle component analysis onto one dimension. The data set is sorted according to this one dimension and split at the median position. To avoid distortion of clusters at the median position, the algorithm identifies a potentially more suited split point left or right of the median. The procedure is recursively applied on the resulting subsets until the maximal distance between cluster members exceeds a user-defined threshold. The approach was validated in a retrospective screening study for angiotensin converting enzyme (ACE) inhibitors. The resulting clusters were assessed for their purity and enrichment in actives belonging to this ligand class. Enrichment was observed in individual branches of the dendrogram. In further retrospective virtual screening studies employing the MDL Drug Data Report (MDDR), COBRA, and the SPECS catalog, NIPALSTREE was compared with the hierarchical k-means clustering approach. Results show that both algorithms can be used in the context of virtual screening. Intersecting the result lists obtained with both algorithms improved enrichment factors while losing only few chemotypes.

Algorithms↗

PubMed2002

Accelerating Monte Carlo simulations of radiation therapy dose distributions using wavelet threshold de-noising.

The Monte Carlo dose calculation method works by simulating individual energetic photons or electrons as they traverse a digital representation of the patient anatomy. However, Monte Carlo results fluctuate until a large number of particles are simulated. We propose wavelet threshold de-noising as a postprocessing step to accelerate convergence of Monte Carlo dose calculations. A sampled rough function (such as Monte Carlo noise) gives wavelet transform coefficients which are more nearly equal in amplitude than those of a sampled smooth function. Wavelet hard-threshold de-noising sets to zero those wavelet coefficients which fall below a threshold; the image is then reconstructed. We implemented the computationally efficient 9,7-biorthogonal filters in the C language. Transform results were averaged over transform origin selections to reduce artifacts. A method for selecting best threshold values is described. The algorithm requires about 336 floating point arithmetic operations per dose grid point. We applied wavelet threshold de-noising to two two-dimensional dose distributions: a dose distribution generated by 10 MeV electrons incident on a water phantom with a step-heterogeneity, and a slice from a lung heterogeneity phantom. Dose distributions were simulated using the Integrated Tiger Series Monte Carlo code. We studied threshold selection, resulting dose image smoothness, and resulting dose image accuracy as a function of the number of source particles. For both phantoms, with a suitable value of the threshold parameter, voxel-to-voxel noise was suppressed with little introduction of bias. The roughness of wavelet de-noised dose distributions (according to a Laplacian metric) was nearly independent of the number of source electrons, though the accuracy of the de-noised dose image improved with increasing numbers of source electrons. We conclude that wavelet shrinkage de-noising is a promising method for effectively accelerating Monte Carlo dose calculations by factors of 2 or more.

Algorithms↗

PubMedDate not supplied

The medical folder as an active tool in defining the clinical decision-making process.

Whenever the user of a consultation system needs to know a large amount of information items that are possibly inter-related, a system that is able to cooperate with the user can simplify the interaction and increase its speed. In fact, these systems can recognize the goals of the user, individuate the information related to his goals, and finally focus their attention on this information [1]. This paper describes research work on the design and creation of a medical folder management system capable of establishing cooperative dialogue with users who have access to the information contained therein. Particular attention has thus been paid to the problems of man-computer dialogue and user models. The research work has addressed the problem of integrating into the system knowledge about the medical domain and users (physicians are only used for the time being), which are both necessary to activate a cooperative dialogue. After analysing the literature on the problems of user models, this paper presents and formalizes a study performed at the IVth Surgical Clinic of the Rome University Umberto I General Hospital to identify and represent how, when, and with what goals the physician consults the medical folder, as well as the dialogue procedures he normally adopts. The paper also illustrates important characteristics of the CADMIO prototype, which has been developed since the study was made. CADMIO stores information about users for use in recognizing and interpreting their behaviour, providing help, and in acquiring and returning further information. Whilst always bearing in mind the physician's pre-established goals, it structures information to facilitate his consultation activity, offering him options for the retrieval of further information semantically linked to that already obtained.

Decision Making, Computer-Assisted↗

PubMed2006

Feature-guided clustering of multi-dimensional flow cytometry datasets.

BACKGROUND: Flow cytometry produces large multi-dimensional datasets of the physical and molecular characteristics of individual cells. The objective of this study was to simplify the cytometry datasets by arranging or clustering "objects" (cells) into a smaller number of relatively homogeneous groups (clusters) on the basis of interobject similarities and dissimilarities. RESULTS: The algorithm was designed to be driven by histogram features; that is, the relevant single parameter histogram features were used to guide multidimensional k-means clustering without an a priori estimate of cluster number. To test this approach, we simulated cell-derived datasets using protein-coated microspheres (artificial "cells"). The microspheres were constructed to provide 119 populations in 40 samples. The feature-guided (FG) approach accurately identified 100% of the predetermined cluster combinations. In contrast, an approach based on the partition index (PI) cluster validity measure accurately identified 83.2% of the clusters. Direct comparisons of the two methods indicated that the FG method was significantly more accurate than PI in identifying both the number of clusters and the number of objects within the clusters (p<.0001). CONCLUSION: We conclude that parameter feature analysis can be used to effectively guide k-means clustering of flow cytometry datasets.

Algorithms↗

PubMed1997

Trading spaces: computation, representation, and the limits of uninformed learning.

Some regularities enjoy only an attenuated existence in a body of training data. These are regularities whose statistical visibility depends on some systematic recoding of the data. The space of possible recoding is, however, infinitely large--it is the space of applicable Turing machines. As a result, mappings that pivot on such attenuated regularities cannot, in general, be found by brute-force search. The class of problems that present such mappings we call the class of "type-2 problems." Type-1 problems, by contrast, present tractable problems of search insofar as the relevant regularities can be found by sampling the input data as originally coded. Type-2 problems, we suggest, present neither rare nor pathological cases. They are rife in biologically realistic settings and in domains ranging from simple animat (simulated animal or autonomous robot) behaviors to language acquisition. Not only are such problems rife--they are standardly solved! This presents a puzzle. How, given the statistical intractability of these type-2 cases, does nature turn the trick? One answer, which we do not pursue, is to suppose that evolution gifts us with exactly the right set of recording biases so as to reduce specific type-2 problems to (tractable) type-1 mappings. Such a heavy-duty nativism is no doubt sometimes plausible. But we believe there are other, more general mechanisms also at work. Such mechanisms provide general (not task-specific) strategies for managing problems of type-2 complexity. Several such mechanisms are investigated. At the heart of each is a fundamental poly--namely, the maximal exploitation of states of representation already achieved by prior, simpler (type-1) learning so as to reduce the amount of subsequent computational search. Such exploitation both characterizes and helps make unitary sense of a diverse range of mechanisms. These include simple incremental learning (Elman 1993), modular connectionism (Jacobs et al. 1991), and the developmental hypothesis of "representational redescription" (Karmiloff-Smith 1979; 1992). In addition, the most distinctive features of human cognition--language and culture--may themselves be viewed as adaptations enabling this representation/computation trade-off to be pursued on an even grander scale.

Humans↗

PubMed2006

Breastfeeding and verbal ability of 3-year-olds in a multicity sample.

OBJECTIVES: Our goal was to analyze the effect of maternal verbal ability and education on the association between breastfeeding and children's cognitive functioning. First, we hypothesized that maternal verbal abilities account for a large portion of the association between breastfeeding and child verbal abilities. Second, we hypothesized that after adjusting for maternal verbal abilities, a positive effect of breastfeeding will be most evident among highly educated mothers, because these mothers may have more opportunity to engage in cognitively stimulating parenting than do mothers with less education. PATIENTS AND METHODS: With data on 1645 American-born mothers participating in a longitudinal birth cohort study, we used linear regression to determine the influence of breastfeeding for at least 1 month on the Peabody Picture Vocabulary Test-Third Edition scores of 3-year-old children. Models were adjusted for an extensive set of demographic characteristics, including mother's Peabody Picture Vocabulary Test and the Home Observation for Measurement of the Environment score. Mothers were categorized into 1 of 3 educational-status groups: no high school diploma, high school diploma, and some post-secondary education. RESULTS: In unadjusted mean comparisons, breastfed children had Peabody Picture Vocabulary Test scores that were 6.6 points higher than children who were not breastfed. After adjusting for demographic characteristics and maternal verbal ability, the coefficient dropped to 1.72. Among mothers with education beyond high school, the children's Peabody Picture Vocabulary Test scores in adjusted models were 2.2 points higher for breastfed children. Among mothers with a high school diploma or less, there were no significant differences in the children's Peabody Picture Vocabulary Test scores by breastfeeding status. These results were consistent in white, black, and Hispanic children. CONCLUSIONS: Maternal Peabody Picture Vocabulary Test scores mediate much of the association between breastfeeding and child verbal abilities. The beneficial effects of breastfeeding on children's cognition may emerge only when breastfeeding is done in conjunction with other positive parenting behaviors. The advantageous effects of breastfeeding do not seem to be solely attributable to the superior nutrient content of breast milk.

Adolescent↗

PubMed1998

Estimating total Barthel scores from just three items: the European Stroke Database 'minimum dataset' for assessing functional status at discharge from hospital.

BACKGROUND: The European Stroke Database (ESDB) Project aims to develop a 'common clinical language' for stroke care by agreeing on terminology, definitions and clinical assessments. Each area of stroke assessment has a 'minimum dataset', which can be collected routinely and more detailed information can be added for particular studies. Measurement of patients' functional status at discharge is essential for assessing the impact of hospital care, but even simple activities of daily living scales like the Barthel index may not be easy to use routinely on busy acute units. We thus aimed to further simplify the 20-point Barthel index by reducing it to a few key items. METHODS: We initially analysed data on 169 consecutive stroke patients discharged from one British hospital and found that a simple formula involving the combined subscores for urinary continence (Blad), bed-chair transfers C (Trans) and indoor mobility (Mob)-(Blad + Trans + Mob) x 2.39 + 0.14-predicted the total BI score to within 1 point in 79% and to within 2 points in 95% of cases. We then tested this three-item Barthel index (BI3) in four different stroke datasets (total n = 824). RESULTS: The predictions were accurate to +/-1 point in 72-81% and to +/-2 points in 88-97% of cases, and BI3 accounted for 95% of the variance in total Barthel score. It was more accurate in patients without obvious mental impairment. CONCLUSIONS: For studies involving large groups of stroke patients, it is sufficient to know about each patient's continence, transfers and indoor mobility at discharge, in order to estimate the total Barthel score. These measures have therefore been incorporated, together with a simple observational measure of cognitive status, into the database minimum dataset for short-term functional outcome and are now being validated in international studies.

Activities of Daily Living↗

PubMed2002

On the nature and evolution of the neural bases of human language.

The traditional theory equating the brain bases of language with Broca's and Wernicke's neocortical areas is wrong. Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, and comprehending the meaning of sentences. When we hear or read a word, neural structures involved in the perception or real-world associations of the word are activated as well as posterior cortical regions adjacent to Wernicke's area. Many areas of the neocortex and subcortical structures support the cortical-striatal-cortical circuits that confer complex syntactic ability, speech production, and a large vocabulary. However, many of these structures also form part of the neural circuits regulating other aspects of behavior. For example, the basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human linguistic ability and abstract reasoning. The cerebellum, traditionally associated with motor control, is active in motor learning. The basal ganglia are also key elements in reward-based learning. Data from studies of Broca's aphasia, Parkinson's disease, hypoxia, focal brain damage, and a genetically transmitted brain anomaly (the putative "language gene," family KE), and from comparative studies of the brains and behavior of other species, demonstrate that the basal ganglia sequence the discrete elements that constitute a complete motor act, syntactic process, or thought process. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. As Dobzansky put it, "Nothing in biology makes sense except in the light of evolution" (cited in Mayr, 1982). That applies with as much force to the human brain and the neural bases of language as it does to the human foot or jaw. The converse follows: the mark of evolution on the brains of human beings and other species provides insight into the evolution of the brain bases of human language. The neural substrate that regulated motor control in the common ancestor of apes and humans most likely was modified to enhance cognitive and linguistic ability. Speech communication played a central role in this process. However, the process that ultimately resulted in the human brain may have started when our earliest hominid ancestors began to walk.

Anatomy, Comparative↗