Neural regions associated with gain-loss frequency and average reward in older and younger adults

Research on the biological basis of reinforcement-learning has focused on how brain regions track expected value based on average reward. However, recent work suggests that humans are more attuned to reward frequency. Furthermore, older adults are less likely to use expected values to guide choice than younger adults. This raises the question of whether brain regions assumed to be sensitive to average reward, like the medial and lateral PFC, also track reward frequency, and whether there are age-based differences. Older (60-81 years) and younger (18-30 years) adults performed the Soochow Gambling task, which separates reward frequency from average reward, while undergoing fMRI. Overall, participants preferred options that provided negative net payoffs, but frequent gains. Older adults improved less over time, were more reactive to recent negative outcomes, and showed greater frequency-related activation in several regions, including DLPFC. We also found broader recruitment of prefrontal and parietal regions associated with frequency value and reward prediction errors in older adults, which may indicate compensation. The results suggest greater reliance on average reward for younger adults than older adults

Spatial models with covariates improve estimates of peat depth in blanket peatlands.

Peatlands are spatially heterogeneous ecosystems that develop due to a complex set of autogenic physical and biogeochemical processes and allogenic factors such as the climate and topography. They are significant stocks of global soil carbon, and therefore predicting the depth of peatlands is an important part of establishing an accurate assessment of their magnitude. Yet there have been few attempts to account for both internal and external processes when predicting the depth of peatlands. Using blanket peatlands in Great Britain as a case study, we compare a linear and geostatistical (spatial) model and several sets of covariates applicable for peatlands around the world that have developed over hilly or undulating terrain. We hypothesized that the spatial model would act as a proxy for the autogenic processes in peatlands that can mediate the accumulation of peat on plateaus or shallow slopes. Our findings show that the spatial model performs better than the linear model in all cases-root mean square errors (RMSE) are lower, and 95% prediction intervals are narrower. In support of our hypothesis, the spatial model also better predicts the deeper areas of peat, and we show that its predictive performance in areas of deep peat is dependent on depth observations being spatially autocorrelated. Where they are not, the spatial model performs only slightly better than the linear model. As a result, we recommend that practitioners carrying out depth surveys fully account for the variation of topographic features in prediction locations, and that sampling approach adopted enables observations to be spatially autocorrelated

Antipsychotics and Torsadogenic Risk: Signals Emerging from the US FDA Adverse Event Reporting System Database

Background: Drug-induced torsades de pointes (TdP) and related clinical entities represent a current regulatory and clinical burden. Objective: As part of the FP7 ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly available US FDA Adverse Event Reporting System (FAERS) database to detect signals of torsadogenicity for antipsychotics (APs). Methods: Four groups of events in decreasing order of drug-attributable risk were identified: (1) TdP, (2) QT-interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence interval (CI) was calculated through a cumulative analysis from group 1 to 4. For groups 1+2, ROR was adjusted for age, gender, and concomitant drugs (e.g., antiarrhythmics) and stratified for AZCERT drugs, lists I and II (http://www.azcert.org, as of June 2011). A potential signal of torsadogenicity was defined if a drug met all the following criteria: (a) four or more cases in group 1+2; (b) significant ROR in group 1+2 that persists through the cumulative approach; (c) significant adjusted ROR for group 1+2 in the stratum without AZCERT drugs; (d) not included in AZCERT lists (as of June 2011). Results: Over the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group 1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria, the following potential signals of torsadogenicity were found: amisulpride (25 cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82-84.60), cyamemazine (11; 15.48, 6.87-34.91), and olanzapine (189; 7.74, 6.45-9.30). Conclusions: This pharmacovigilance analysis on the FAERS found 3 potential signals of torsadogenicity for drugs previously unknown for this risk

Game theory of mind

This paper introduces a model of ‘theory of mind’, namely, how we represent the intentions and goals of others to optimise our mutual interactions. We draw on ideas from optimum control and game theory to provide a ‘game theory of mind’. First, we consider the representations of goals in terms of value functions that are prescribed by utility or rewards. Critically, the joint value functions and ensuing behaviour are optimised recursively, under the assumption that I represent your value function, your representation of mine, your representation of my representation of yours, and so on ad infinitum. However, if we assume that the degree of recursion is bounded, then players need to estimate the opponent's degree of recursion (i.e., sophistication) to respond optimally. This induces a problem of inferring the opponent's sophistication, given behavioural exchanges. We show it is possible to deduce whether players make inferences about each other and quantify their sophistication on the basis of choices in sequential games. This rests on comparing generative models of choices with, and without, inference. Model comparison is demonstrated using simulated and real data from a ‘stag-hunt’. Finally, we note that exactly the same sophisticated behaviour can be achieved by optimising the utility function itself (through prosocial utility), producing unsophisticated but apparently altruistic agents. This may be relevant ethologically in hierarchal game theory and coevolution

The transcriptional repressor protein NsrR senses nitric oxide directly via a [2Fe-2S] cluster

The regulatory protein NsrR, a member of the Rrf2 family of transcription repressors, is specifically dedicated to sensing nitric oxide (NO) in a variety of pathogenic and non-pathogenic bacteria. It has been proposed that NO directly modulates NsrR activity by interacting with a predicted [Fe-S] cluster in the NsrR protein, but no experimental evidence has been published to support this hypothesis. Here we report the purification of NsrR from the obligate aerobe Streptomyces coelicolor. We demonstrate using UV-visible, near UV CD and EPR spectroscopy that the protein contains an NO-sensitive [2Fe-2S] cluster when purified from E. coli. Upon exposure of NsrR to NO, the cluster is nitrosylated, which results in the loss of DNA binding activity as detected by bandshift assays. Removal of the [2Fe-2S] cluster to generate apo-NsrR also resulted in loss of DNA binding activity. This is the first demonstration that NsrR contains an NO-sensitive [2Fe-2S] cluster that is required for DNA binding activity

‘Nothing about us without us’ : disabled people determining their human rights through the UNCRPD

The human rights and fundamental freedoms of disabled persons are set out in the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD). This paper firstly focuses on the importance of the involvement of disabled people at all levels of decision-making. The second part of the paper identifies those aspects of the UNCRPD that reflect the direct involvement of disabled people. Finally, it considers how human rights bodies can best build on this specific aspect of the UNCRPD in order to realize the potential of the Convention as a determining factor in affirming disabled people rights in an effective and meaningful manner.peer-reviewe

Jupiter's X‐Ray and UV Dark Polar Region

We present 14 simultaneous Chandra X-ray Observatory (CXO)-Hubble Space Telescope (HST) observations of Jupiter's Northern X-ray and ultraviolet (UV) aurorae from 2016 to 2019. Despite the variety of dynamic UV and X-ray auroral structures, one region is conspicuous by its persistent absence of emission: the dark polar region (DPR). Previous HST observations have shown that very little UV emission is produced by the DPR. We find that the DPR also produces very few X-ray photons. For all 14 observations, the low level of X-ray emission from the DPR is consistent (within 2-standard deviations) with scattered solar emission and/or photons spread by Chandra's Point Spread Function from known X-ray-bright regions. We therefore conclude that for these 14 observations the DPR produced no statistically significant detectable X-ray signature

The influence of blood on the efficacy of intraperitoneally applied phospholipids for prevention of adhesions

<p>Abstract</p> <p>Background</p> <p>The formation of adhesions following abdominal surgery is a well known problem. In previous studies we demonstrated the efficacy and safety of intraperitoneally applied phospholipids in order to prevent adhesion formation. This study evaluates the influence of blood on the efficacy of intraperitoneally applied phospholipids for prevention of adhesions.</p> <p>Methods</p> <p>In 40 Chinchilla rabbits adhesions were induced by median laparotomy, standardized abrasion of the visceral and parietal peritoneum in defined areas of the ventral abdominal wall and the caecum. The animals were randomly divided into four groups. They received either phospholipids 3.0% or normal saline (NaCl 0,9%) (5 ml/kg body weight). In 50% of the rabbits we simulated intraperitoneal bleeding by administration of blood (1,5 ml/kg body weight). The other half served as control group. Ten days following the operation the animals were sacrificed and adhesion formation was assessed by computer aided planimetry and histopathologic examination.</p> <p>Results</p> <p>The median adhesion surface area in the NaCl-group (n = 9) amounted to 68,72 mm², in the NaCl+Blood-group (n = 10) 147,68 mm². In the Phospholipid (PhL)-group (n = 9) the median adhesion surface area measured 9,35 mm², in the PhL+Blood-group (n = 9) 11,95 mm². The phospholipid groups had a significantly smaller adhesion surface area (p < 0.05).</p> <p>Conclusion</p> <p>Again these results confirm the efficacy of phospholipids in the prevention of adhesions in comparison to NaCl (p = 0,04). We also demonstrated the adhesion preventing effect of phospholipids in the presence of intraperitoneal blood.</p