White matter microstructure underlying default mode network connectivity in the human brain

Resting state functional magnetic resonance imaging (fMRI) reveals a distinct network of correlated brain function representing a default mode state of the human brain The underlying structural basis of this functional connectivity pattern is still widely unexplored We combined fractional anisotropy measures of fiber tract integrity derived from diffusion tensor imaging (DTI) and resting state fMRI data obtained at 3 Tesla from 20 healthy elderly subjects (56 to 83 years of age) to determine white matter microstructure e 7 underlying default mode connectivity We hypothesized that the functional connectivity between the posterior cingulate and hippocampus from resting state fMRI data Would be associated with the white matter microstructure in the cingulate bundle and fiber tracts connecting posterior cingulate gyrus With lateral temporal lobes, medial temporal lobes, and precuneus This was demonstrated at the p<0001 level using a voxel-based multivariate analysis of covariance (MANCOVA) approach In addition, we used a data-driven technique of joint independent component analysis (ICA) that uncovers spatial pattern that are linked across modalities. It revealed a pattern of white matter tracts including cingulate bundle and associated fiber tracts resembling the findings from the hypothesis-driven analysis and was linked to the pattern of default mode network (DMN) connectivity in the resting state fMRI data Out findings support the notion that the functional connectivity between the posterior cingulate and hippocampus and the functional connectivity across the entire DMN is based oil distinct pattern of anatomical connectivity within the cerebral white matter (C) 2009 Elsevier Inc All rights reserved

Scale-free network of a dengue epidemic

In this work we show that the dengue epidemic in the city of Singapore organized itself into a scale-free network of transmission as the 2000-2005 outbreaks progressed. This scale-free network of cluster comprised geographical breeding places for the aedes mosquitoes, acting as super-spreaders nodes in a network of transmission. The geographical organization of the network was analysed by the corresponding distribution of weekly number of new cases. Therefore, our hypothesis is that the distribution of dengue cases reflects the geographical organization of a transmission network, which evolved towards a power law as the epidemic intensity progressed until 2005. (c) 2007 Elsevier Inc. All rights reserved.

A decision support system to facilitate management of patients with acute gastrointestinal bleeding

Objective: To develop a model to predict the bleeding source and identify the cohort amongst patients with acute gastrointestinal bleeding (GIB) who require urgent intervention, including endoscopy. Patients with acute GIB, an unpredictable event, are most commonly evaluated and managed by non-gastroenterologists. Rapid and consistently reliable risk stratification of patients with acute GIB for urgent endoscopy may potentially improve outcomes amongst such patients by targeting scarce health-care resources to those who need it the most. Design and methods: Using ICD-9 codes for acute GIB, 189 patients with acute GIB and all. available data variables required to develop and test models were identified from a hospital medical records database. Data on 122 patients was utilized for development of the model and on 67 patients utilized to perform comparative analysis of the models. Clinical data such as presenting signs and symptoms, demographic data, presence of co-morbidities, laboratory data and corresponding endoscopic diagnosis and outcomes were collected. Clinical data and endoscopic diagnosis collected for each patient was utilized to retrospectively ascertain optimal management for each patient. Clinical presentations and corresponding treatment was utilized as training examples. Eight mathematical models including artificial neural network (ANN), support vector machine (SVM), k-nearest neighbor, linear discriminant analysis (LDA), shrunken centroid (SC), random forest (RF), logistic regression, and boosting were trained and tested. The performance of these models was compared using standard statistical analysis and ROC curves. Results: Overall the random forest model best predicted the source, need for resuscitation, and disposition with accuracies of approximately 80% or higher (accuracy for endoscopy was greater than 75%). The area under ROC curve for RF was greater than 0.85, indicating excellent performance by the random forest model Conclusion: While most mathematical models are effective as a decision support system for evaluation and management of patients with acute GIB, in our testing, the RF model consistently demonstrated the best performance. Amongst patients presenting with acute GIB, mathematical models may facilitate the identification of the source of GIB, need for intervention and allow optimization of care and healthcare resource allocation; these however require further validation. (c) 2007 Elsevier B.V. All rights reserved.

Evidence for a network transcriptional control of promiscuous gene expression in medullary thymic epithelial cells

The expression of peripheral tissue antigens (PTAs) in the thymus by medullary thymic epithelial cells (mTECs) is essential for the central self-tolerance in the generation of the T cell repertoire. Due to heterogeneity of autoantigen representation, this phenomenon has been termed promiscuous gene expression (PGE), in which the autoimmune regulator (Aire) gene plays a key role as a transcription factor in part of these genes. Here we used a microarray strategy to access PGE in cultured murine CD80(+) 3.10 mTEC line. Hierarchical clustering of the data allowed observation that PTA genes were differentially expressed being possible to found their respective induced or repressed mRNAs. To further investigate the control of PGE, we tested the hypothesis that genes involved in this phenomenon might also be modulated by transcriptional network. We then reconstructed such network based on the microarray expression data, featuring the guanylate cyclase 2d (Gucy2d) gene as a main node. In such condition, we established 167 positive and negative interactions with downstream PTA genes. Silencing Aire by RNA interference, Gucy2d while down regulated established a larger number (355) of interactions with PTA genes. T- and G-boxes corresponding to AIRE protein binding sites located upstream to ATG codon of Gucy2d supports this effect. These findings provide evidence that Aire plays a role in association with Gucy2d, which is connected to Several PTA genes and establishes a cascade-like transcriptional control of promiscuous gene expression in mTEC cells. (C) 2009 Elsevier Ltd. All rights reserved.

Inhibitory network interactions shape the auditory processing of natural communication signals in the songbird auditory forebrain

The role of GABA in the central processing of complex auditory signals is not fully understood. We have studied the involvement of GABA(A)-mediated inhibition in the processing of birdsong, a learned vocal communication signal requiring intact hearing for its development and maintenance. We focused on caudomedial nidopallium (NCM), an area analogous to parts of the mammalian auditory cortex with selective responses to birdsong. We present evidence that GABA(A)-mediated inhibition plays a pronounced role in NCM`s auditory processing of birdsong. Using immunocytochemistry, we show that approximately half of NCM`s neurons are GABAergic. Whole cell patch-clamp recordings in a slice preparation demonstrate that, at rest, spontaneously active GABAergic synapses inhibit excitatory inputs onto NCM neurons via GABA(A) receptors. Multi-electrode electrophysiological recordings in awake birds show that local blockade of GABA(A)-mediated inhibition in NCM markedly affects the temporal pattern of song-evoked responses in NCM without modifications in frequency tuning. Surprisingly, this blockade increases the phasic and largely suppresses the tonic response component, reflecting dynamic relationships of inhibitory networks that could include disinhibition. Thus processing of learned natural communication sounds in songbirds, and possibly other vocal learners, may depend on complex interactions of inhibitory networks.

Modulation of Mediotemporal and Ventrostriatal Function in Humans by Delta 9-Tetrahydrocannabinol A Neural Basis for the Effects of Cannabis sativa on Learning and Psychosis

Context: Cannabis sativa use can impair verbal learning, provoke acute psychosis, and increase the risk of schizophrenia. It is unclear where C sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms. Objectives: To investigate the effects of 2 main psychoactive constituents of C sativa, Delta 9-tetrahydrocannabinol (Delta 9-THC) and cannabidiol, on regional brain function during verbal paired associate learning. Design: Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task. Each imaging session was preceded by the ingestion of Delta 9-THC (10 mg), cannabidiol (600 mg), or placebo in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject design. Setting: University research center. Participants: Fifteen healthy, native English-speaking, right-handed men of white race/ethnicity who had used C sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime. Main Outcome Measures: Regional brain activation ( blood oxygen level-dependent response), performance in a verbal learning task, and objective and subjective ratings of psychotic symptoms, anxiety, intoxication, and sedation. Results: Delta 9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety, intoxication, and sedation, whereas no significant effect was noted on these parameters following administration of cannabidiol. Performance in the verbal learning task was not significantly modulated by either drug. Administration of Delta 9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident. Delta 9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs, which was directly correlated with concurrently induced psychotic symptoms. In contrast, administration of cannabidiol had no such effect. Conclusion: The modulation of mediotemporal and ventrostriatal function by Delta 9-THC may underlie the effects of C sativa on verbal learning and psychotic symptoms, respectively.

Network structures of Bis-GMA/TEGDMA resins differ in DC, shrinkage-strain, hardness and optical properties as a function of reducing agent

Objectives. To evaluate the influence of different tertiary amines on degree of conversion (DC), shrinkage-strain, shrinkage-strain rate, Knoop microhardness, and color and transmittance stabilities of experimental resins containing BisGMA/TEGDMA (3: 1 wt), 0.25wt% camphorquinone, 1wt% amine (DMAEMA, CEMA, DMPT, DEPT or DABE). Different light-curing protocols were also evaluated. Methods. DC was evaluated with FTIR-ATR and shrinkage-strain with the bonded-disk method. Shrinkage-strain-rate data were obtained from numerical differentiation of shrinkage-strain data with respect to time. Color stability and transmittance were evaluated after different periods of artificial aging, according to ISO 7491: 2000. Results were evaluated with ANOVA, Tukey, and Dunnett`s T3 tests (alpha = 0.05). Results. Studied properties were influenced by amines. DC and shrinkage-strain were maximum at the sequence: CQ < DEPT < DMPT <= CEMA approximate to DABE < DMAEMA. Both DC and shrinkage were also influenced by the curing protocol, with positive correlations between DC and shrinkage-strain and DC and shrinkage-strain rate. Materials generally decreased in L* and increased in b*. The strong exception was the resin containing DMAEMA that did not show dark and yellow shifts. Color varied in the sequence: DMAEMA < DEPT < DMPT < CEMA < DABE. Transmittance varied in the sequence: DEPT approximate to DABE < DABE approximate to DMPT approximate to CEMA < DMPT approximate to CEMA approximate to DMAEMA, being more evident at the wavelength of 400 nm. No correlations between DC and optical properties were observed. Significance. The resin containing DMAEMA showed higher DC, shrinkage-strain, shrinkage-strain rate, and microhardness, in addition to better optical properties. (C) 2011 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Relational learning in children with deafness and cochlear implants

This four-experiment series sought to evaluate the potential of children with neurosensory deafness and cochlear implants to exhibit auditory-visual and visual-visual stimulus equivalence relations within a matching-to-sample format. Twelve children who became deaf prior to acquiring language (prelingual) and four who became deaf afterwards (postlingual) were studied. All children learned auditory-visual conditional discriminations and nearly all showed emergent equivalence relations. Naming tests, conducted with a subset of the: children, showed no consistent relationship to the equivalence-test outcomes.. This study makes several contributions: to the literature on stimulus equivalence. First; it demonstrates that both pre- and postlingually deaf children-can: acquire auditory-visual equivalence-relations after cochlear implantation, thus demonstrating symbolic functioning. Second, it directs attention to a population that may be especially interesting for researchers seeking to analyze the relationship. between speaker and listener repertoires. Third, it demonstrates the feasibility of conducting experimental studies of stimulus control processes within the limitations of a hospital, which these children must visit routinely for the maintenance of their cochlear implants.