Learning and innovative elements of strategy adoption rules expand cooperative network topologies

Cooperation plays a key role in the evolution of complex systems. However, the level of cooperation extensively varies with the topology of agent networks in the widely used models of repeated games. Here we show that cooperation remains rather stable by applying the reinforcement learning strategy adoption rule, Q-learning on a variety of random, regular, small-word, scale-free and modular network models in repeated, multi-agent Prisoners Dilemma and Hawk-Dove games. Furthermore, we found that using the above model systems other long-term learning strategy adoption rules also promote cooperation, while introducing a low level of noise (as a model of innovation) to the strategy adoption rules makes the level of cooperation less dependent on the actual network topology. Our results demonstrate that long-term learning and random elements in the strategy adoption rules, when acting together, extend the range of network topologies enabling the development of cooperation at a wider range of costs and temptations. These results suggest that a balanced duo of learning and innovation may help to preserve cooperation during the re-organization of real-world networks, and may play a prominent role in the evolution of self-organizing, complex systems.Comment: 14 pages, 3 Figures + a Supplementary Material with 25 pages, 3 Tables, 12 Figures and 116 reference

Study protocol: evaluation of a parenting and stress management programme: a randomised controlled trial of Triple P discussion groups and stress control

<br>Background: Children displaying psychosocial problems are at an increased risk of negative developmental outcomes. Parenting practices are closely linked with child development and behaviour, and parenting programmes have been recommended in the treatment of child psychosocial problems. However, parental mental health also needs to be addressed when delivering parenting programmes as it is linked with parenting practices, child outcomes, and treatment outcomes of parenting programmes. This paper describes the protocol of a study examining the effects of a combined intervention of a parenting programme and a cognitive behavioural intervention for mental health problems.</br> <br>Methods: The effects of a combined intervention of Triple P Discussion Groups and Stress Control will be examined using a randomised controlled trial design. Parents with a child aged 3?8?years will be recruited to take part in the study. After obtaining informed consent and pre-intervention measures, participants will be randomly assigned to either an intervention or a waitlist condition. The two primary outcomes for this study are change in dysfunctional/ineffective parenting practices and change in symptoms of depression, anxiety, and stress. Secondary outcomes are child behaviour problems, parenting experiences, parental self-efficacy, family relationships, and positive parental mental health. Demographic information, participant satisfaction with the intervention, and treatment fidelity data will also be collected. Data will be collected at pre-intervention, mid-intervention, post-intervention, and 3-month follow-up.</br> <br>Discussion: The aim of this paper is to describe the study protocol of a randomised controlled trial evaluating the effects of a combined intervention of Triple P Discussion Groups and Stress Control in comparison to a waitlist condition. This study is important because it will provide evidence about the effects of this combined intervention for parents with 3?8?year old children. The results of the study could be used to inform policy about parenting support and support for parents with mental health problems. Trial registration ClinicalTrial.gov: NCT01777724, UTN: U1111-1137-1053.</br&gt

Fitness Ranking of Individual Mutants Drives Patterns of Epistatic Interactions in HIV-1

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule

N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor's ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system

Digit Ratio Predicts Sense of Direction in Women

The relative length of the second-to-fourth digits (2D:4D) has been linked with prenatal androgen in humans. The 2D:4D is sexually dimorphic, with lower values in males than females, and appears to correlate with diverse measures of behavior. However, the relationship between digit ratio and cognition, and spatial cognition in particular, has produced mixed results. In the present study, we hypothesized that spatial tasks separating cue conditions that either favored female or male strategies would examine this structure-function correlation with greater precision. Previous work suggests that males are better in the use of directional cues than females. In the present study, participants learned a target location in a virtual landscape environment, in conditions that contained either all directional (i.e., distant or compass bearing) cues, or all positional (i.e., local, small objects) cues. After a short delay, participants navigated back to the target location from a novel starting location. Males had higher accuracy in initial search direction than females in environments with all directional cues. Lower digit ratio was correlated with higher accuracy of initial search direction in females in environments with all directional cues. Mental rotation scores did not correlate with digit ratio in either males or females. These results demonstrate for the first time that a sex difference in the use of directional cues, i.e., the sense of direction, is associated with more male-like digit ratio.National Science Foundation (U.S.) (NSF ECCS-1028319)National Science Foundation (U.S.) (NSF Graduate Student Fellowship)Mary Elisabeth Rennie Endowment for Epilepsy Researc

Cigarette smoke exposure facilitates allergic sensitization in mice

BACKGROUND: Active and passive smoking are considered as risk factors for asthma development. The mechanisms involved are currently unexplained. OBJECTIVE: The aim of this study was to determine if cigarette smoke exposure could facilitate primary allergic sensitization. METHODS: BALB/c mice were exposed to aerosolized ovalbumin (OVA) combined with air or tobacco smoke (4 exposures/day) daily for three weeks. Serology, lung cytopathology, cytokine profiles in bronchoalveolar lavage fluid (BALF) and on mediastinal lymph node cultures as well as lung function tests were performed after the last exposure. The natural history and the immune memory of allergic sensitization were studied with in vivo recall experiments. RESULTS: Exposure to OVA induced a small increase in OVA-specific serum IgE as compared with exposure to PBS (P < 0.05), while no inflammatory reaction was observed in the airways. Exposure to cigarette smoke did not induce IgE, but was characterized by a small but significant neutrophilic inflammatory reaction. Combining OVA with cigarette smoke not only induced a significant increase in OVA-specific IgE but also a distinct eosinophil and goblet cell enriched airway inflammation albeit that airway hyperresponsiveness was not evidenced. FACS analysis showed in these mice increases in dendritic cells (DC) and CD4(+ )T-lymphocytes along with a marked increase in IL-5 measured in the supernatant of lymph node cell cultures. Immune memory experiments evidenced the transient nature of these phenomena. CONCLUSION: In this study we show that mainstream cigarette smoke temporary disrupts the normal lung homeostatic tolerance to innocuous inhaled allergens, thereby inducing primary allergic sensitization. This is characterized not only by the development of persistent IgE, but also by the emergence of an eosinophil rich pulmonary inflammatory reaction

Randomised double-blind trial of megestrol acetate vs placebo in treatment-naive advanced hepatocellular carcinoma

10.1038/bjc.2011.333British Journal of Cancer1057945-952BJCA

Distribution and Extinction of Ungulates during the Holocene of the Southern Levant

BACKGROUND: The southern Levant (Israel, Palestinian Authority and Jordan) has been continuously and extensively populated by succeeding phases of human cultures for the past 15,000 years. The long human impact on the ancient landscape has had great ecological consequences, and has caused continuous and accelerating damage to the natural environment. The rich zooarchaeological data gathered at the area provide a unique opportunity to reconstruct spatial and temporal changes in wild species distribution, and correlate them with human demographic changes. METHODOLOGY: Zoo-archaeological data (382 animal bone assemblages from 190 archaeological sites) from various time periods, habitats and landscapes were compared. The bone assemblages were sorted into 12 major cultural periods. Distribution maps showing the presence of each ungulate species were established for each period. CONCLUSIONS: The first major ungulate extinction occurred during the local Iron Age (1,200-586 BCE), a period characterized by significant human population growth. During that time the last of the largest wild ungulates, the hartebeest (Alcelaphus buselaphus), aurochs (Bos primigenius) and the hippopotamus (Hippopotamus amphibius) became extinct, followed by a shrinking distribution of forest-dwelling cervids. A second major wave of extinction occurred only in the 19th and 20th centuries CE. Furthermore, a negative relationship was found between the average body mass of ungulate species that became extinct during the Holocene and their extinction date. It is thus very likely that the intensified human activity through habitat destruction and uncontrolled hunting were responsible for the two major waves of ungulate extinction in the southern Levant during the late Holocene

The Novel μ-Opioid Receptor Antagonist GSK1521498 Decreases Both Alcohol Seeking and Drinking: Evidence from a New Preclinical Model of Alcohol Seeking.

Distinct environmental and conditioned stimuli influencing ethanol-associated appetitive and consummatory behaviors may jointly contribute to alcohol addiction. To develop an effective translational animal model that illuminates this interaction, daily seeking responses, maintained by alcohol-associated conditioned stimuli (CSs), need to be dissociated from alcohol drinking behavior. For this, we established a procedure whereby alcohol seeking maintained by alcohol-associated CSs is followed by a period during which rats have the opportunity to drink alcohol. This cue-controlled alcohol-seeking procedure was used to compare the effects of naltrexone and GSK1521498, a novel selective μ-opioid receptor antagonist, on both voluntary alcohol-intake and alcohol-seeking behaviors. Rederived alcohol-preferring, alcohol-nonpreferring, and high-alcohol-drinking replicate 1 line of rats (Indiana University) first received 18 sessions of 24 h home cage access to 10% alcohol and water under a 2-bottle choice procedure. They were trained subsequently to respond instrumentally for access to 15% alcohol under a second-order schedule of reinforcement, in which a prolonged period of alcohol-seeking behavior was maintained by contingent presentations of an alcohol-associated CS acting as a conditioned reinforcer. This seeking period was terminated by 20 min of free alcohol drinking access that achieved significant blood alcohol concentrations. The influence of pretreatment with either naltrexone (0.1-1-3 mg/kg) or GSK1521498 (0.1-1-3 mg/kg) before instrumental sessions was measured on both seeking and drinking behaviors, as well as on drinking in the 2-bottle choice procedure. Naltrexone and GSK1521498 dose-dependently reduced both cue-controlled alcohol seeking and alcohol intake in the instrumental context as well as alcohol intake in the choice procedure. However, GSK1521498 showed significantly greater effectiveness than naltrexone, supporting its potential use for promoting abstinence and preventing relapse in alcohol addiction.The present study was funded by Medical Research Council Programme Grant (no. G1002231) and by GlaxoSmithKline (GSK), which has a commercial interest in GSK1521498. Charles R. Goodlett was funded by a grant from the IUPUI International Development Fund, which supported his sabbatical leave at the University of Cambridge. Maria Pilar Garcia-Pardo was funded by Val+id para investigadores en formación (Conselleria de educacion, Generalitat Valenciana), which also supported her stay at the University of Cambridge (January-April 2014) as a Visiting Student.This is the accepted manuscript. The final version is available from NPG at http://dx.doi.org/10.1038/npp.2015.15