4,671 research outputs found

    Antisocial Learning: Using Learning Window Width to Model Callous-Unemotional Traits?

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    Psychopathic traits and the childhood analogue, callous-unemotional traits, have been severely neglected by the research field in terms of mechanistic, falsifiable accounts. This is surprising given that some of the core symptoms of the disorder point towards problems with basic components of associative learning. In this manuscript we describe a new mechanistic account that is concordant with current cognitive theories of psychopathic traits and is also able to replicate previous empirical data. The mechanism we describe is one of individual differences in an index we have called, “learning window width”. Here we show how variation in this index would result in different outcome expectations which, in turn, would lead to differences in behaviour. The proposed mechanism is intuitive and simple with easily calculated behavioural implications. Our hope is that this model will stimulate discussion and the use of mechanistic and computational accounts to improve our understanding in this area of research

    A BAYESIAN ANALYSIS OF THE AGES OF FOUR OPEN CLUSTERS

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    In this paper we apply a Bayesian technique to determine the best fit of stellar evolution models to find the main sequence turn off age and other cluster parameters of four intermediate-age open clusters: NGC 2360, NGC 2477, NGC 2660, and NGC 3960. Our algorithm utilizes a Markov chain Monte Carlo technique to fit these various parameters, objectively finding the best fit isochrone for each cluster. The result is a high precision isochrone fit. We compare these results with the those of traditional “by eye” isochrone fitting methods. By applying this Bayesian technique to NGC 2360, NGC 2477, NGC 2660, and NGC 3960 we determine the ages of these clusters to be 1.35 ± 0.05, 1.02 ± 0.02, 1.64 ± 0.04, and 0.860 ± 0.04 Gyr, respectively. The results of this paper continue our effort to determine cluster ages to higher precision than that offered by these traditional methods of isochrone fitting

    A Computational Comparison of Optimization Methods for the Golomb Ruler Problem

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    The Golomb ruler problem is defined as follows: Given a positive integer n, locate n marks on a ruler such that the distance between any two distinct pair of marks are different from each other and the total length of the ruler is minimized. The Golomb ruler problem has applications in information theory, astronomy and communications, and it can be seen as a challenge for combinatorial optimization algorithms. Although constructing high quality rulers is well-studied, proving optimality is a far more challenging task. In this paper, we provide a computational comparison of different optimization paradigms, each using a different model (linear integer, constraint programming and quadratic integer) to certify that a given Golomb ruler is optimal. We propose several enhancements to improve the computational performance of each method by exploring bound tightening, valid inequalities, cutting planes and branching strategies. We conclude that a certain quadratic integer programming model solved through a Benders decomposition and strengthened by two types of valid inequalities performs the best in terms of solution time for small-sized Golomb ruler problem instances. On the other hand, a constraint programming model improved by range reduction and a particular branching strategy could have more potential to solve larger size instances due to its promising parallelization features

    Effects of study design and allocation on participant behaviour-ESDA: study protocol for a randomized controlled trial

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    Background: What study participants think about the nature of a study has been hypothesised to affect subsequent behaviour and to potentially bias study findings. In this trial we examine the impact of awareness of study design and allocation on participant drinking behaviour. Methods/Design: A three-arm parallel group randomised controlled trial design will be used. All recruitment, screening, randomisation, and follow-up will be conducted on-line among university students. Participants who indicate a hazardous level of alcohol consumption will be randomly assigned to one of three groups. Group A will be informed their drinking will be assessed at baseline and again in one month (as in a cohort study design). Group B will be told the study is an intervention trial and they are in the control group. Group C will be told the study is an intervention trial and they are in the intervention group. All will receive exactly the same brief educational material to read. After one month, alcohol intake for the past 4 weeks will be assessed. Discussion: The experimental manipulations address subtle and previously unexplored ways in which participant behaviour may be unwittingly influenced by standard practice in trials. Given the necessity of relying on self-reported outcome, it will not be possible to distinguish true behaviour change from reporting artefact. This does not matter in the present study, as any effects of awareness of study design or allocation involve bias that is not well understood. There has been little research on awareness effects, and our outcomes will provide an indication of the possible value of further studies of this type and inform hypothesis generation

    Excitotoxic lesions of the perirhinal cortex leave intact rats’ gustatory sensory preconditioning

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    We report findings from two sensory preconditioning experiments in which rats consumed two flavoured solutions, each with two gustatory components (AX and BY), composed of sweet, bitter, salt, and acid elements. After this pre-exposure, rats were conditioned to X by pairing with lithium chloride. Standard sensory preconditioning was observed: Consumption of flavour A was less than that of B. We found that sensory preconditioning was maintained when X was added to A and B. Both experiments included one group of rats with lesions of the perirhinal cortex, which did not influence sensory preconditioning. We discuss our findings in the light of other sensory preconditioning procedures that involve the perirhinal cortex and conclude that differences in experimental variables invoke different mechanisms of sensory preconditioning, which vary in their requirement of the perirhinal cortex. </jats:p

    Can people guess what happened to others from their reactions?

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    Are we able to infer what happened to a person from a brief sample of his/her behaviour? It has been proposed that mentalising skills can be used to retrodict as well as predict behaviour, that is, to determine what mental states of a target have already occurred. The current study aimed to develop a paradigm to explore these processes, which takes into account the intricacies of real-life situations in which reasoning about mental states, as embodied in behaviour, may be utilised. A novel task was devised which involved observing subtle and naturalistic reactions of others in order to determine the event that had previously taken place. Thirty-five participants viewed videos of real individuals reacting to the researcher behaving in one of four possible ways, and were asked to judge which of the four ‘scenarios’ they thought the individual was responding to. Their eye movements were recorded to establish the visual strategies used. Participants were able to deduce successfully from a small sample of behaviour which scenario had previously occurred. Surprisingly, looking at the eye region was associated with poorer identification of the scenarios, and eye movement strategy varied depending on the event experienced by the person in the video. This suggests people flexibly deploy their attention using a retrodictive mindreading process to infer events

    Comparative analyses of CTCF and BORIS occupancies uncover two distinct classes of CTCF binding genomic regions.

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    BackgroundCTCF and BORIS (CTCFL), two paralogous mammalian proteins sharing nearly identical DNA binding domains, are thought to function in a mutually exclusive manner in DNA binding and transcriptional regulation.ResultsHere we show that these two proteins co-occupy a specific subset of regulatory elements consisting of clustered CTCF binding motifs (termed 2xCTSes). BORIS occupancy at 2xCTSes is largely invariant in BORIS-positive cancer cells, with the genomic pattern recapitulating the germline-specific BORIS binding to chromatin. In contrast to the single-motif CTCF target sites (1xCTSes), the 2xCTS elements are preferentially found at active promoters and enhancers, both in cancer and germ cells. 2xCTSes are also enriched in genomic regions that escape histone to protamine replacement in human and mouse sperm. Depletion of the BORIS gene leads to altered transcription of a large number of genes and the differentiation of K562 cells, while the ectopic expression of this CTCF paralog leads to specific changes in transcription in MCF7 cells.ConclusionsWe discover two functionally and structurally different classes of CTCF binding regions, 2xCTSes and 1xCTSes, revealed by their predisposition to bind BORIS. We propose that 2xCTSes play key roles in the transcriptional program of cancer and germ cells

    Complement-Mediated Virus Infectivity Neutralisation by HLA Antibodies Is Associated with Sterilising Immunity to SIV Challenge in the Macaque Model for HIV/AIDS.

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    Sterilising immunity is a desired outcome for vaccination against human immunodeficiency virus (HIV) and has been observed in the macaque model using inactivated simian immunodeficiency virus (SIV). This protection was attributed to antibodies specific for cell proteins including human leucocyte antigens (HLA) class I and II incorporated into virions during vaccine and challenge virus preparation. We show here, using HLA bead arrays, that vaccinated macaques protected from virus challenge had higher serum antibody reactivity compared with non-protected animals. Moreover, reactivity was shown to be directed against HLA framework determinants. Previous studies failed to correlate serum antibody mediated virus neutralisation with protection and were confounded by cytotoxic effects. Using a virus entry assay based on TZM-bl cells we now report that, in the presence of complement, serum antibody titres that neutralise virus infectivity were higher in protected animals. We propose that complement-augmented virus neutralisation is a key factor in inducing sterilising immunity and may be difficult to achieve with HIV/SIV Env-based vaccines. Understanding how to overcome the apparent block of inactivated SIV vaccines to elicit anti-envelope protein antibodies that effectively engage the complement system could enable novel anti-HIV antibody vaccines that induce potent, virolytic serological response to be developed

    Global metabolic changes induced by plant-derived pyrrolizidine alkaloids following a human poisoning outbreak and in a mouse model

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    Several hundred cases of Hirmi Valley Liver Disease (HVLD), an often fatal liver injury, occurred from 2001 to 2011 in a cluster of rural villages in Tigray, Ethiopia. HVLD is principally caused by contamination of the food supply with plant derived pyrrolizidine alkaloids (PAs), with high exposure to the pesticide DDT among villagers increasing their susceptibility. In an untargeted global approach we aimed to identify metabolic changes induced by PA exposure through 1H NMR spectroscopic based metabolic profiling. We analysed spectra acquired from urine collected from HVLD cases and controls and a murine model of PA exposure and PA/DDT co-exposure, using multivariate partial least squares discriminant analysis. In the human models we identified changes in urinary concentrations of tyrosine, pyruvate, bile acids, N-acetylglycoproteins, N-methylnicotinamide and formate, hippurate, p-cresol sulphate, p-hydroxybenzoate and 3-(3-hydroxyphenyl) propionic acid. Tyrosine and p-cresol sulphate were associated with both exposure and disease. Similar changes to tyrosine, one-carbon intermediates and microbial associated metabolites were observed in the mouse model, with tyrosine correlated with the extent of liver damage. These results provide mechanistic insight and implicate the gut microflora in the human response to challenge with toxins. Pathways identified here may be useful in translational research and as “exposome” signals

    Using coloured filters to reduce the symptoms of visual stress in children with reading delay

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    Background: Meares Irlen Syndrome (MIS), otherwise known as “visual stress”, is one condition that can cause difficulties with reading. Aim: This study aimed to compare the effect of two coloured-filter systems on the symptoms of visual stress in children with reading delay. Methods: The study design was a pre-test, post-test, randomized head-to-head comparison of two filter systems on the symptoms of visual stress in school children. A total of 68 UK mainstream schoolchildren with significant impairment in reading ability completed the study. Results: The filter systems appeared to have a large effect on the reported symptoms between pre and post three-month time points (d = 2.5, r = 0.78). Both filter types appeared to have large effects (Harris d = 1.79, r = 0.69 and DRT d = 3.22, r = 0.85). Importantly, 35% of participants’ reported that their symptoms had resolved completely; 72% of the 68 children appeared to gain improvements in three or more visual stress symptoms. Conclusion and significance: The reduction in symptoms, which appeared to be brought about by the use of coloured filters, eased the visual discomfort experienced by these children when reading. This type of intervention therefore has the potential to facilitate occupational engagement
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