A circuit mechanism for irrationalities in decision-making and NMDA receptor hypofunction: behaviour, computational modelling, and pharmacology

Decision-making biases can be systematic features of normal behaviour, or deficits underlying neuropsychiatric symptoms. We used behavioural psychophysics, spiking-circuit modelling and pharmacological manipulations to explore decision-making biases in health and disease. Monkeys performed an evidence integration task in which they showed a pro-variance bias (PVB): a preference to choose options with more variable evidence. The PVB was also present in a spiking circuit model, revealing a neural mechanism for this behaviour. Because NMDA receptor (NMDA-R) hypofunction is a leading hypothesis for neuropathology in schizophrenia, we simulated behavioural effects of NMDA-R hypofunction onto either excitatory or inhibitory neurons in the model. These were tested experimentally using the NMDA-R antagonist ketamine, yielding changes in decision-making consistent with lowered cortical excitation/inhibition balance from NMDA-R hypofunction onto excitatory neurons. These results provide a circuit-level mechanism that bridges across explanatory scales, from the synaptic to the behavioural, in neuropsychiatric disorders where decision-making biases are prominent. Significance People can make apparently irrational decisions because of underlying features in their decision circuitry. Deficits in the same neural circuits may also underlie debilitating cognitive symptoms of neuropsychiatric patients. Here, we reveal a neural circuit mechanism explaining an irrationality frequently observed in healthy humans making binary choices – the pro-variance bias. Our circuit model could be perturbed by introducing deficits in either excitatory or inhibitory neuron function. These two perturbations made specific, dissociable predictions for the types of irrational decisionmaking behaviour produced. We used the NMDA-R antagonist ketamine, an experimental model for schizophrenia, to test if these predictions were relevant to neuropsychiatric pathophysiology. The results were consistent with impaired excitatory neuron function, providing important new insights into the pathophysiology of schizophrenia

A circuit mechanism for decision-making biases and NMDA receptor hypofunction

Decision-making biases can be features of normal behaviour, or deficits underlying neuropsychiatric symptoms. We used behavioural psychophysics, spiking-circuit modelling and pharmacological manipulations to explore decision-making biases during evidence integration. Monkeys showed a pro-variance bias (PVB): a preference to choose options with more variable evidence. The PVB was also present in a spiking circuit model, revealing a potential neural mechanism for this behaviour. To model possible effects of NMDA receptor (NMDA-R) antagonism on this behaviour, we simulated the effects of NMDA-R hypofunction onto either excitatory or inhibitory neurons in the model. These were then tested experimentally using the NMDA-R antagonist ketamine, a pharmacological model of schizophrenia. Ketamine yielded an increase in subjects' PVB, consistent with lowered cortical excitation/inhibition balance from NMDA-R hypofunction predominantly onto excitatory neurons. These results provide a circuit-level mechanism that bridges across explanatory scales, from the synaptic to the behavioural, in neuropsychiatric disorders where decision-making biases are prominent

Elicitation of a pungent sensation does not implicate memory modulation in adolescents aged 14-16

Ref no. 701.12/KKK33Pungent sensation induced by allyl isothiocyanate which is a functional ingredient in a Japanese horseradish called wasabi involves the activation of transient receptor potential ankyrin 1 (TRPA1). It has been suggested that TRPA1 is associated with cognitive impairment in Alzheimer’s disease and neuroprotection on dentate gyrus granule cells. As our previous studies focus on daily-life strategies such as physical exercise and sleep for memory enhancement in adolescents, we further investigate whether elicitation of a pungent sensation would modulate memory recall. In the present study, children aged 14-16 spend 1 minute to orally taste wasabi to acquire a pungent sense, followed by an immediate 5-minute memory recall test displaying ten random combinations of three to four English alphabets plus one to two Arabic numbers in each attempt. Our results showed that the pungent sensation induced by wasabi showed no significant modulation on memory recall in the adolescents. This implicates that immediate elicitation of a pungent sensation in which TRPA1 may be involved does not help memory recall in adolescents.postprin

Effectiveness of a mobile smoking cessation service in reaching elderly smokers and predictors of quitting

<p>Abstract</p> <p>Background</p> <p>Different smoking cessation programmes have been developed in the last decade but utilization by the elderly is low. We evaluated a pilot mobile smoking cessation service for the Chinese elderly in Hong Kong and identified predictors of quitting.</p> <p>Methods</p> <p>The Mobile Smoking Cessation Programme (MSCP) targeted elderly smokers (aged 60 or above) and provided service in a place that was convenient to the elderly. Trained counsellors provided individual counselling and 4 week's free supply of nicotine replacement therapy (NRT). Follow up was arranged at 1 month by face-to-face and at 3 and 6 months by telephone plus urinary cotinine validation. A structured record sheet was used for data collection. The service was evaluated in terms of process, outcome and cost.</p> <p>Results</p> <p>102 governmental and non-governmental social service units and private residential homes for the elderly participated in the MSCP. We held 90 health talks with 3266 elderly (1140 smokers and 2126 non-smokers) attended. Of the 1140 smokers, 365 (32%) received intensive smoking cessation service. By intention-to-treat, the validated 7 day point prevalence quit rate was 20.3% (95% confidence interval: 16.2%–24.8%). Smoking less than 11 cigarettes per day and being adherent to NRT for 4 weeks or more were significant predictors of quitting. The average cost per contact was US$54 (smokers only); per smoker with counselling: US$168; per self-reported quitter: US$594; and per cotinine validated quitter: US$827.</p> <p>Conclusion</p> <p>This mobile smoking cessation programme was acceptable to elderly Chinese smokers, with quit rate comparable to other comprehensive programmes in the West. A mobile clinic is a promising model to reach the elderly and probably other hard to reach smokers.</p

Information Visualisation for Project Management: Case Study of Bath Formula Student Project

This paper contributes to a better understanding and design of dashboards for monitoring of engineering projects based on the projects’ digital footprint and user-centered design approach. The paper presents an explicit insight-based framework for the evaluation of dashboard visualisations and compares the performance of two groups of student engineering project managers against the framework: a group with the dashboard visualisations and a group without the dashboard. The results of our exploratory study demonstrate that student project managers who used the dashboard generated more useful information and exhibited more complex reasoning on the project progress, thus informing knowledge of the provision of information to engineers in support of their project understanding

Doctors and nurses benefit from interprofessional online education in dermatology

<p>Abstract</p> <p>Background</p> <p>Benefits of online learning in the health sector have been demonstrated in previous studies. We examined the potential benefits of a joint web-based curriculum on atopic eczema for health personnel.</p> <p>Methods</p> <p>Enrolled doctors and nurses had access to the curriculum for 8 weeks. After the course learners completed a questionnaire. Two dermatologists rated the quality of the submitted homework assignments. Based on data from the project's budget and the Norwegian Medical Association, we estimated the saved travel expenses.</p> <p>Results</p> <p>Eighty-eight learners (46 doctors) registered for the course. We received 55 questionnaires (response rate 63%). Twenty-seven learners (31%; 16 doctors, 11 nurses; χ²= 0.03; P = 0.87) used the discussion forum. We found no significant differences in the total questionnaire scores between doctors and nurses. The homework assignments were given an average score of 3.6 for doctors and 3.5 for nurses (P = 0.8) by rater 1. Rater 2 scored 3.9 and 3.6 for doctors and nurses respectively (P = 0.2). The break-even between travel/hotel expenses and course development costs occurred at 135 saved travel refund applications.</p> <p>Conclusions</p> <p>Doctors and nurses were equally satisfied with a joint web-based course on atopic eczema. The use of an online discussion forum was limited but similar between doctors and nurses. There were no significant differences in the quality of submitted homework assignments. The cost of developing the course was 716 841 NOK and the first 86 learners saved 455 198 NOK in travel expenses.</p

A note on the factorization conjecture

We give partial results on the factorization conjecture on codes proposed by Schutzenberger. We consider finite maximal codes C over the alphabet A = {a, b} with C \cap a^* = a^p, for a prime number p. Let P, S in Z , with S = S_0 + S_1, supp(S_0) \subset a^* and supp(S_1) \subset a^*b supp(S_0). We prove that if (P,S) is a factorization for C then (P,S) is positive, that is P,S have coefficients 0,1, and we characterize the structure of these codes. As a consequence, we prove that if C is a finite maximal code such that each word in C has at most 4 occurrences of b's and a^p is in C, then each factorization for C is a positive factorization. We also discuss the structure of these codes. The obtained results show once again relations between (positive) factorizations and factorizations of cyclic groups

Respiratory viral pathogens among Singapore military servicemen 2009 - 2012: Epidemiology and clinical characteristics

10.1186/1471-2334-14-204BMC Infectious Diseases141-BIDM

The Drosophila melanogaster PeptideAtlas facilitates the use of peptide data for improved fly proteomics and genome annotation

<p>Abstract</p> <p>Background</p> <p>Crucial foundations of any quantitative systems biology experiment are correct genome and proteome annotations. Protein databases compiled from high quality empirical protein identifications that are in turn based on correct gene models increase the correctness, sensitivity, and quantitative accuracy of systems biology genome-scale experiments.</p> <p>Results</p> <p>In this manuscript, we present the <it>Drosophila melanogaster </it>PeptideAtlas, a fly proteomics and genomics resource of unsurpassed depth. Based on peptide mass spectrometry data collected in our laboratory the portal <url>http://www.drosophila-peptideatlas.org</url> allows querying fly protein data observed with respect to gene model confirmation and splice site verification as well as for the identification of proteotypic peptides suited for targeted proteomics studies. Additionally, the database provides consensus mass spectra for observed peptides along with qualitative and quantitative information about the number of observations of a particular peptide and the sample(s) in which it was observed.</p> <p>Conclusion</p> <p>PeptideAtlas is an open access database for the <it>Drosophila </it>community that has several features and applications that support (1) reduction of the complexity inherently associated with performing targeted proteomic studies, (2) designing and accelerating shotgun proteomics experiments, (3) confirming or questioning gene models, and (4) adjusting gene models such that they are in line with observed <it>Drosophila </it>peptides. While the database consists of proteomic data it is not required that the user is a proteomics expert.</p