Dissociation of Response and Feedback Negativity in Schizophrenia: Electrophysiological and Computational Evidence for a Deficit in the Representation of Value

Contrasting theories of schizophrenia propose that the disorder is characterized by a deficit in phasic changes in dopamine activity in response to ongoing events or, alternatively, by a weakness in the representation of the value of responses. Schizophrenia patients have reliably reduced brain activity following incorrect responses but other research suggests that they may have intact feedback-related potentials, indicating that the impairment may be specifically response-related. We used event-related brain potentials and computational modeling to examine this issue by comparing the neural response to outcomes with the neural response to behaviors that predict outcomes in patients with schizophrenia and psychiatrically healthy comparison subjects. We recorded feedback-related activity in a passive gambling task and a time estimation task and error-related activity in a flanker task. Patients’ brain activity following an erroneous response was reduced compared to comparison subjects but feedback-related activity did not differ between groups. To test hypotheses about the possible causes of this pattern of results, we used computational modeling of the electrophysiological data to simulate the effects of an overall reduction in patients’ sensitivity to feedback, selective insensitivity to positive or negative feedback, reduced learning rate, and a decreased representation of the value of the response given the stimulus on each trial. The results of the computational modeling suggest that schizophrenia patients exhibit weakened representation of response values, possibly due to failure of the basal ganglia to strongly associate stimuli with appropriate response alternatives

Correlation of pain relief with physical function in hand osteoarthritis: randomized controlled trial post hoc analysis

Abstract Introduction Nonsteroidal anti-inflammatory drugs are recommended for the relief of pain associated with hand osteoarthritis (OA) but do not alter the underlying structural changes that contribute to impaired physical function. The current analysis examined the relationship of pain relief with measures of function and global rating of disease in patients with hand OA. Methods This was a combined analysis of 2 prospective, randomized, double-blind, 8-week, multicenter, parallel-group studies comparing diclofenac sodium 1% gel with placebo gel (vehicle) in patients with radiographically confirmed mild to moderate hand OA. Patients (n = 783) aged ≥ 40 years applied diclofenac sodium 1% gel (2 g) or vehicle to each hand 4 times daily for 8 weeks. Outcome measures included pain intensity assessed on a 100-mm Visual Analog Scale (VAS); the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) subscales for pain, stiffness, and physical function (100-mm VAS); and a global rating of disease (100-mm VAS). Change in VAS pain intensity from baseline to week 8 was categorized (<0%, 0%-<15%, 15%-<30%, 30%-<50%, 50%-<70%, and ≥ 70%) without regard to treatment and compared in each category with the mean change from baseline in each AUSCAN subindex and the global rating of disease. Pearson correlations between changes in outcome measures from baseline to week 8 were calculated. Results Changes in VAS pain intensity were accompanied by similar changes in AUSCAN scores and global rating of disease. Pearson correlations confirmed significant associations (P < 0.001) between change in VAS pain intensity and changes in AUSCAN pain (correlation coefficient [r] = 0.81), AUSCAN function (r = 0.75), AUSCAN stiffness (r = 0.66), and global rating of disease (r = 0.76). Conclusions Pain relief correlated with improvements in physical function, stiffness, and global rating of disease in patients with hand OA, irrespective of treatment. This suggests that pain or anticipation of pain inhibits physical function and influences patient perception of disease severity in hand OA. These results also suggest that any intervention to relieve the pain of hand OA may improve function and patient perception of disease severity, despite the absence of a disease-modifying mechanism of action. Trial registration Clinicaltrials.gov NCT00171652, NCT00171665

PocketMatch: A new algorithm to compare binding sites in protein structures

Background: Recognizing similarities and deriving relationships among protein molecules is a fundamental
requirement in present-day biology. Similarities can be present at various levels which can be detected through comparison of protein sequences or their structural folds. In some cases similarities obscure at these levels could be present merely in the substructures at their binding sites. Inferring functional similarities between protein molecules by comparing their binding sites is still largely exploratory and not as yet a routine protocol. One of
the main reasons for this is the limitation in the choice of appropriate analytical tools that can compare binding sites with high sensitivity. To benefit from the enormous amount of structural data that is being rapidly accumulated, it is essential to have high throughput tools that enable large scale binding site comparison.

Results: Here we present a new algorithm PocketMatch for comparison of binding sites in a frame invariant
manner. Each binding site is represented by 90 lists of sorted distances capturing shape and chemical nature of the site. The sorted arrays are then aligned using an incremental alignment method and scored to obtain PMScores for pairs of sites. A comprehensive sensitivity analysis and an extensive validation of the algorithm have been carried out. Perturbation studies where the geometry of a given site was retained but the residue types were changed randomly, indicated that chance similarities were virtually non-existent. Our analysis also demonstrates that shape information alone is insufficient to discriminate between diverse binding sites, unless
combined with chemical nature of amino acids.

Conclusions: A new algorithm has been developed to compare binding sites in accurate, efficient and
high-throughput manner. Though the representation used is conceptually simplistic, we demonstrate that along
with the new alignment strategy used, it is sufficient to enable binding comparison with high sensitivity. Novel methodology has also been presented for validating the algorithm for accuracy and sensitivity with respect to geometry and chemical nature of the site. The method is also fast and takes about 1/250th second for one comparison on a single processor. A parallel version on BlueGene has also been implemented

An exploratory trial implementing a community-based child oral health promotion intervention for Australian families from refugee and migrant backgrounds: a protocol paper for Teeth Tales

Introduction: Inequalities are evident in early childhood caries rates with the socially disadvantaged experiencing greater burden of disease. This study builds on formative qualitative research, conducted in the Moreland/Hume local government areas of Melbourne, Victoria 2006–2009, in response to community concerns for oral health of children from refugee and migrant backgrounds. Development of the community-based intervention described here extends the partnership approach to cogeneration of contemporary evidence with continued and meaningful involvement of investigators, community, cultural and government partners. This trial aims to establish a model for child oral health promotion for culturally diverse communities in Australia.<p></p> Methods and analysis: This is an exploratory trial implementing a community-based child oral health promotion intervention for Australian families from refugee and migrant backgrounds. Families from an Iraqi, Lebanese or Pakistani background with children aged 1–4 years, residing in metropolitan Melbourne, were invited to participate in the trial by peer educators from their respective communities using snowball and purposive sampling techniques. Target sample size was 600. Moreland, a culturally diverse, inner-urban metropolitan area of Melbourne, was chosen as the intervention site. The intervention comprised peer educator led community oral health education sessions and reorienting of dental health and family services through cultural Competency Organisational Review (CORe).<p></p> Ethics and dissemination: Ethics approval for this trial was granted by the University of Melbourne Human Research Ethics Committee and the Department of Education and Early Childhood Development Research Committee. Study progress and output will be disseminated via periodic newsletters, peer-reviewed research papers, reports, community seminars and at National and International conferences.<p></p&gt

To Act and Learn: A Bakhtinian Exploration of Action Learning

This paper considers the work of the Russian social philosopher and cultural theorist, Mikhail Mikhailovich Bakhtin as a source of understanding for those involved in action learning. Drawing upon data gathered over two years during the evaluation of 20 action learning sets in the north of England, we will seek to work with the ideas of Bakhtin to consider their value for those involved in action learning. We consider key Bakhtin features such as Making Meaning, Participative Thinking, Theoreticism and Presence, Others and Outsideness, Voices and Carnival to highlight how Bakhtin's can enhance our understanding of the nature of action and learning

Glucose enhancement of human memory: A comprehensive research review of the glucose memory facilitation effect

The brain relies upon glucose as its primary fuel. In recent years, a rich literature has developed from both human and animal studies indicating that increases in circulating blood glucose can facilitate cognitive functioning. This phenomenon has been termed the ‘glucose memory facilitation effect’. The purpose of this review is to discuss a number of salient studies which have investigated the influence of glucose ingestion on neurocognitive performance in individuals with (a) compromised neurocognitive capacity, as well as (b) normally functioning individuals (with a focus on research conducted with human participants). The proposed neurocognitive mechanisms purported to underlie the modulatory effect of glucose on neurocognitive performance will also be considered. Many theories have focussed upon the hippocampus, given that this brain region is heavily implicated in learning and memory. Further, it will be suggested that glucose is a possible mechanism underlying the phenomenon that enhanced memory performance is typically observed for emotionally laden stimuli

Morphology and characteristics of radio pulsars

This review describes the observational properties of radio pulsars, fast rotating neutron stars, emitting radio waves. After the introduction we give a list of milestones in pulsar research. The following chapters concentrate on pulsar morphology: the characteristic pulsar parameters such as pulse shape, pulsar spectrum, polarization and time dependence. We give information on the evolution of pulsars with frequency since this has a direct connection with the emission heights, as postulated in the radius to frequency mapping (RFM) concept. We deal successively with the properties of normal (slow) pulsars and of millisecond (fast-recycled) pulsars. The final chapters give the distribution characteristics of the presently catalogued 1300 objects.Comment: 33 pages, PDF with 30 PostScript figures, see http://springerlink.metapress.com/link.asp?id=d6k3a6wunb138dpl Accepted by Astronomy & Astrophysivs Review

The Means/Side-Effect Distinction in Moral Cognition: A Meta-Analysis

Experimental research suggests that people draw a moral distinction between bad outcomes brought about as a means versus a side effect (or byproduct). Such findings have informed multiple psychological and philosophical debates about moral cognition, including its computational structure, its sensitivity to the famous Doctrine of Double Effect, its reliability, and its status as a universal and innate mental module akin to universal grammar. But some studies have failed to replicate the means/byproduct effect especially in the absence of other factors, such as personal contact. So we aimed to determine how robust the means/byproduct effect is by conducting a meta-analysis of both published and unpublished studies (k = 101; 24,058 participants). We found that while there is an overall small difference between moral judgments of means and byproducts (standardized mean difference = 0.87, 95% CI 0.67 – 1.06; standardized mean change = 0.57, 95% CI 0.44 – 0.69; log odds ratio = 1.59, 95% CI 1.15 – 2.02), the mean effect size is primarily moderated by whether the outcome is brought about by personal contact, which typically involves the use of personal force

Cost-effectiveness of Implementing Low-Tidal Volume Ventilation in Patients With Acute Lung Injury

Background: Despite widespread guidelines recommending the use of lung-protective ventilation (LPV) in patients with acute lung injury (ALI), many patients do not receive this lifesaving therapy. We sought to estimate the incremental clinical and economic outcomes associated with LPV and determined the maximum cost of a hypothetical intervention to improve adherence with LPV that remained cost-effective. Methods: Adopting a societal perspective, we developed a theoretical decision model to determine the cost-effectiveness of LPV compared to non-LPV care. Model inputs were derived from the literature and a large population-based cohort of patients with ALI. Cost-effectiveness was determined as the cost per life saved and the cost per quality-adjusted life-years (QALYs) gained. Results: Application of LPV resulted in an increase in QALYs gained by 15% (4.21 years for non-LPV vs 4.83 years for LPV), and an increase in lifetime costs of $7,233 per patient with ALI ($99,588 for non-LPV vs $106,821 for LPV). The incremental cost-effectiveness ratios for LPV were$22,566 per life saved at hospital discharge and $11,690 per QALY gained. The maximum, cost-effective, per patient investment in a hypothetical program to improve LPV adherence from 50 to 90$9,482. Results were robust to a wide range of economic and patient parameter assumptions. Conclusions: Even a costly intervention to improve adherence with low-tidal volume ventilation in patients with ALI reduces death and is cost-effective by current societal standards.NIH F32HL090220.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84154/1/Cooke - CEA LPV.pd