An Eight Component Decision-Making Model for Problem Gambling:A Systems Approach to Stimulate Integrative Research

Problem Gambling (PG) represents a serious problem for affected individuals, their families and society in general. Previous approaches to understanding PG have been confined to only a subset of the psychobiological factors influencing PG. We present a model that attempts to integrate potential causal factors across levels of organization, providing empirical evidence from the vast literature on PG and complimentary literatures in decision-making and addiction. The model posits that components are arranged systematically to bias decisions in favor of either immediately approaching or avoiding targets affording the opportunity for immediate reward. Dopamine, Testosterone and Endogenous Opioids favor immediate approach, while Serotonin and Cortisol favor inhibition. Glutamate is involved in associative learning between stimuli and promotes the approach response through its link to the DA reward system. GABA functions to monitor performance and curb impulsive decision-making. Finally, while very high levels of Norepinephrine can induce arousal to an extent that is detrimental to sound decision-making, the reactivity of the Norepinephrine system and its effects of Cortisol levels can shift the focus towards long-term consequences, thereby inhibiting impulsive decisions. Empirical evidence is provided showing the effects of each component on PG and decision-making across behavioural, neuropsychological, functional neuroimaging and genetic levels. Last, an effect size analysis of the growing pharmacotherapy literature is presented. It is hoped that this model will stimulate multi-level research to solidify our comprehension of biased decision-making in PG and suggest pharmacological and psychological approaches to treatment

Facilitated Anion Transport Induces Hyperpolarization of the Cell Membrane That Triggers Differentiation and Cell Death in Cancer Stem Cells

Facilitated anion transport potentially represents a powerful tool to modulate various cellular functions. However, research into the biological effects of small molecule anionophores is still at an early stage. Here we have used two potent anionophore molecules inspired in the structure of marine metabolites tambjamines to gain insight into the effect induced by these compounds at the cellular level. We show how active anionophores, capable of facilitating the transmembrane transport of chloride and bicarbonate in model phospholipid liposomes, induce acidification of the cytosol and hyperpolarization of plasma cell membranes. We demonstrate how this combined effect can be used against cancer stem cells (CSCs). Hyperpolarization of cell membrane induces cell differentiation and loss of stemness of CSCs leading to effective elimination of this cancer cell subpopulation.panishgovernment and the EU (FIS PI13/00089, FIS PI12/02838,FIS PI12/00956 and RD12/0036/0025), a grant from LaMaratóde TV3 Foundation (20132730), a grant from SEPAR(17/2014), Consejería de Educación de la Junta de Castilla yLeón (Project BU340U13), Ministerio de Economíaycompetitividad/Instituto de Salud Carlos III (SAF2014-55700-P), and ICREA Academia-201

Response Prediction in Chronic Hepatitis C by Assessment of IP-10 and IL28B-Related Single Nucleotide Polymorphisms

Background: High baseline levels of IP-10 predict a slower first phase decline in HCV RNA and a poor outcome following interferon/ribavirin therapy in patients with chronic hepatitis C. Several recent studies report that single nucleotide polymorphisms (SNPs) adjacent to IL28B predict spontaneous resolution of HCV infection and outcome of treatment among HCV genotype 1 infected patients. Methods and Findings: In the present study, we correlated the occurrence of variants at three such SNPs (rs12979860, rs12980275, and rs8099917) with pretreatment plasma IP-10 and HCV RNA throughout therapy within a phase III treatment trial (HCV-DITTO) involving 253 Caucasian patients. The favorable SNP variants (CC, AA, and TT, respectively) were associated with lower baseline IP-10 (P = 0.02, P = 0.01, P = 0.04) and were less common among HCV genotype 1 infected patients than genotype 2/3 (P<0.0001, P<0.0001, and P = 0.01). Patients carrying favorable SNP genotypes had higher baseline viral load than those carrying unfavorable variants (P = 0.0013, P = 0.029, P = 0.0004 respectively). Among HCV genotype 1 infected carriers of the favorable C, A, or T alleles, IP-10 below 150 pg/mL significantly predicted a more pronounced reduction of HCV RNA from day 0 to 4 (first phase decline), which translated into increased rates of RVR (62%, 53%, and 39%) and SVR (85%, 76%, and 75% respectively) among homozygous carriers with baseline IP-10 below 150 pg/mL. In multivariate analyses of genotype 1-infected patients, baseline IP-10 and C genotype at rs12979860 independently predicted the first phase viral decline and RVR, which in turn independently predicted SVR. Conclusions: Concomitant assessment of pretreatment IP-10 and IL28B-related SNPs augments the prediction of the first phase decline in HCV RNA, RVR, and final therapeutic outcome

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015

Neuropsychological Contributions to Symptomatology in Eating Disordered Patients

The present study examined the claim that neuropsychological deficits in set-shifting and emotional decision making are present in eating disordered patients, and to what extent these deficits relate to specific aspects of disordered eating. Sixteen eating disordered patients and 38 controls were given a battery of neuropsychological measures, as well as questionnaires measuring disordered eating. Compared to controls, patients demonstrated poorer performance on tasks of set-shifting, but not decision making, psychomotor speed, working memory, or IQ. Across groups, poor set-shifting was correlated with food-, shape-, and weight concerns, and restricting, whereas poor decision making was correlated to restricting. The study demonstrates that set-shifting deficits are present in eating disordered patients, and that specific relations exist between cognitive performance in different domains and disordered eating.MAS

Neural Substrates Related to Constructing Novel Events

This dissertation explored the cognitive processes and neural substrates underlying the simulation and construction of novel mental representations, by manipulating factors influencing construction ability. Across four experiments, subjects constructed novel events by relating multiple cue words to a single context word in order to make a coherent representation. Experiments 1 and 2 tested whether memory deficits related to age and amnesia due to medial temporal lobe lesions affect event construction performance. Both older adults and patients with amnesia showed deficits in event construction, with poorer performance at increasing mnemonic loads. Moreover, older adults’ construction ability was associated with memory performance, suggesting that associative encoding processes are crucial for simulation tasks. Experiments 3a and 3b examined whether semantic congruency between items and context influences event construction and subsequent memory. In Experiment 3a, younger adults constructed imagined events with from cue words that were typically or atypically related to the context word. Atypical events were less coherent, and were rated as poorer in quality and more difficult to construct. Experiment 3b also showed an advantage for typical trials on a cued recall test, suggesting the congruency of an imagined event with prior knowledge has a strong influence on its subsequent retrieval. Experiment 4 used fMRI to determine the neural correlates of imagining. Constructing imagined events activated the hippocampus, medial prefrontal regions, and default mode network regions in comparison to a baseline condition. Moreover, clusters of activation in the anterior hippocampus were positively correlated with construction task performance across all task conditions, whereas activity in the medial frontal poles varied with individual differences in the typicality of imagined events. Posterior hippocampus was associated with the novelty of imagined events, but did not correlate strongly with the anterior hippocampus or task performance. Taken together, these studies suggest that these regions are crucial when constructing a novel imagined event, regardless of the nature of the stimuli. In particular, the hippocampus may be necessary to bind items during the construction process, especially as representations become increasingly complex.Ph

Older adults with lower autobiographical memory abilities report less age-related decline in everyday cognitive function

Abstract Background Individuals differ in how they remember the past: some richly re-experience specific details of past episodes, whereas others recall only the gist of past events. Little research has examined how such trait mnemonics, or lifelong individual differences in memory capacities, relate to cognitive aging. We specifically examined trait episodic autobiographical memory (AM, the tendency to richly re-experience episodic details of past events) in relation to complaints of everyday cognitive functioning, which are known to increase with age. Although one might predict that individuals reporting higher trait-level episodic AM would be resistant to age-related decline in everyday function, we made the opposite prediction. That is, we predicted that those with lower trait-level episodic AM would be better equipped with compensatory strategies, practiced throughout the lifespan, to cope with age-related memory decline. Those with higher trait-level episodic AM would have enhanced sensitivity to age-related cognitive changes due to their tendency to rely on their perceived above-average memory function. Methods We tested these predictions in 959 older adults aged 50–93 using online subjective and objective measures of memory and cognitive function. Our key measures of interest were the Survey of Autobiographical Memory, a measure of autobiographical memory abilities; and the Cognitive Failures Questionnaire, a measure of everyday cognitive function. Results In keeping with our prediction, we found that complaints of day-to-day memory slips and errors (normally elevated with age) remained stable or even decreased with age among those reporting lower trait-level episodic AM, whereas those reporting higher trait-level episodic AM reported the expected age-related increase in such errors. This finding was specific to episodic AM and not observed for other autobiographical memory capacities (e.g., semantic, spatial). It was further unaccounted for by response bias or objectively assessed cognitive abilities. Conclusions Congenitally low trait-level episodic AM may paradoxically confer a functional advantage in aging. This could be due to well-developed non-episodic strategies not present in those with higher abilities, who are more sensitive to age-related memory decline attributable to medial temporal lobe changes. Our findings emphasize the importance of considering individual differences when studying cognitive aging trajectories