Contextual novelty changes reward representations in the striatum

Reward representation in ventral striatum is boosted by perceptual novelty, although the mechanism of this effect remains elusive. Animal studies indicate a functional loop (Lisman and Grace, 2005) that includes hippocampus, ventral striatum, and midbrain as being important in regulating salience attribution within the context of novel stimuli. According to this model, reward responses in ventral striatum or midbrain should be enhanced in the context of novelty even if reward and novelty constitute unrelated, independent events. Using fMRI, we show that trials with reward-predictive cues and subsequent outcomes elicit higher responses in the striatum if preceded by an unrelated novel picture, indicating that reward representation is enhanced in the context of novelty. Notably, this effect was observed solely when reward occurrence, and hence reward-related salience, was low. These findings support a view that contextual novelty enhances neural responses underlying reward representation in the striatum and concur with the effects of novelty processing as predicted by the model of Lisman and Grace (2005)

PaaS-IaaS Inter-Layer Adaptation in an Energy-Aware Cloud Environment

Cloud computing providers resort to a variety of techniques to improve energy consumption at each level of the cloud computing stack. Most of these techniques consider resource-level energy optimization at IaaS layer. This paper argues energy gains can be obtained by creating a cooperation between the PaaS layer (in charge of hosting the application/service) and the IaaS layer (in charge of handling the computing resources). It presents a novel method based on steering information and decision taking to trigger the PaaS and IaaS layers to adapt their energy mode in service operation, therefore enabling the Cloud stack to actively adapt to changing situations. Experimental results demonstrate such adaptation achieves dynamic energy management in each of the PaaS and IaaS cloud layers

Changing Patient and Public Beliefs About Antimicrobials and Antimicrobial Resistance (AMR) Using a Brief Digital Intervention.

BBackground: A key driver of antimicrobial resistance (AMR) is patient demand for unnecessary antibiotics, which is driven by patients’ beliefs about antibiotics and AMR. Few interventions have targeted beliefs to reduce inappropriate demand. Objective: To examine whether a brief, online algorithm-based intervention can change beliefs that may lead to inappropriate antibiotic demand (i.e. perceptions of antibiotic necessity and lack of concern about antibiotic harm). Design: Pre- and post-intervention study. Participants: Participants were 18 years or older, and residing in the United Kingdom, who self-selected to participate via Amazon mTurk, an online survey plaform, and via research networks. Intervention: Participants were presented with a hypothetical situation of cold and flu symptoms, then exposed to the intervention. The online intervention comprised: 1) a profiling tool identifying individual beliefs (antibiotic necessity, concerns, and knowledge) driving inappropriate antibiotic demand; 2) messages designed to change beliefs and knowledge (i.e. reduce antibiotic necessity, and increase antibiotic concerns and knowledge), and 3) an algorithm linking specific messages to specific beliefs and knowledge. Main measures: The profiling tool was repeated immediately after the intervention and compared with baseline scores to assess change in beliefs. A paired samples t-test was used to determine intervention effect. Key Results: A total of 100 respondents completed the study. A significant change in beliefs relating to inappropriate demand was observed after the intervention, with a reduction in beliefs about antibiotic necessity (t = 7.254; p < 0.0001), an increase in antibiotic concerns (t = −7.214; p < 0.0001), and increases in antibiotic and AMR knowledge (t = −4.651; p < 0.0001). Conclusion: This study is the first to demonstrate that patient beliefs about antibiotics and AMR associated with inappropriate demand can be changed by a brief, tailored online intervention. This has implications for the design of future interventions to reduce unnecessary antimicrobial use

Energy Efficiency Support through Intra-Layer Cloud Stack Adaptation

Energy consumption is a key concern in cloud computing. The paper reports on a cloud architecture to support energy efficiency at service construction, deployment, and operation. This is achieved through SaaS, PaaS and IaaS intra-layer self-adaptation in isolation. The self-adaptation mechanisms are discussed, as well as their implementation and evaluation. The experimental results show that the overall architecture is capable of adapting to meet the energy goals of applications on a per layer basis

A Risk Assessment Framework for Cloud Computing

Cloud service providers offer access to their resources through formal service level agreements (SLA), and need well-balanced infrastructures so that they can maximise the quality of service (QoS) they offer and minimise the number of SLA violations. This paper focuses on a specific aspect of risk assessment as applied in cloud computing: methods within a framework that can be used by cloud service providers and service consumers to assess risk during service deployment and operation. It describes the various stages in the service lifecycle whereas risk assessment takes place, and the corresponding risk models that have been designed and implemented. The impact of risk on architectural components, with special emphasis on holistic management support at service operation, is also described. The risk assessor is shown to be effective through the experimental evaluation of the implementation, and is already integrated in a cloud computing toolkit

GBA mutation promotes early mitochondrial dysfunction in 3D neurosphere models

Glucocerebrosidase (GBA) mutations are the most important genetic risk factor for the development of Parkinson disease (PD). GBA encodes the lysosomal enzyme glucocerebrosidase (GCase). Loss-of-GCase activity in cellular models has implicated lysosomal and mitochondrial dysfunction in PD disease pathogenesis, although the exact mechanisms remain unclear. We hypothesize that GBA mutations impair mitochondria quality control in a neurosphere model.We have characterized mitochondrial content, mitochondrial function and macroautophagy flux in 3D-neurosphere-model derived from neural crest stem cells containing heterozygous and homozygous N370SGBA mutations, under carbonyl cyanide-m-chlorophenyl-hydrazine (CCCP)- induced mitophagy.Our findings on mitochondrial markers and ATP levels indicate that mitochondrial accumulation occurs in mutant N370SGBA neurospheres under basal conditions, and clearance of depolarised mitochondria is impaired following CCCP-treatment. A significant increase in TFEB-mRNA levels, the master regulator of lysosomal and autophagy genes, may explain an unchanged macroautophagy flux in N370SGBA neurospheres. PGC1α-mRNA levels were also significantly increased following CCCP-treatment in heterozygote, but not homozygote neurospheres, and might contribute to the increased mitochondrial content seen in cells with this genotype, probably as a compensatory mechanism that is absent in homozygous lines.Mitochondrial impairment occurs early in the development of GCase-deficient neurons. Furthermore, impaired turnover of depolarised mitochondria is associated with early mitochondrial dysfunction.In summary, the presence of GBA mutation may be associated with higher levels of mitochondrial content in homozygous lines and lower clearance of damaged mitochondria in our neurosphere model

Learning in anticipation of reward and punishment: perspectives across the human lifespan

Learning to act to receive reward and to withhold to avoid punishment has been found to be easier than learning the opposite contingencies in young adults. To what extent this type of behavioral adaptation might develop during childhood and adolescence and differ during aging remains unclear. We therefore tested 247 healthy individuals across the human life span (7-80 years) with an orthogonalized valenced go/no-go learning task. Computational modeling revealed that peak performance in young adults was attributable to greater sensitivity to both reward and punishment. However, in children and adolescents, we observed an increased bias toward action but not reward sensitivity. By contrast, reduced learning in midlife and older adults was accompanied by decreased reward sensitivity and especially punishment sensitivity along with an age-related increase in the Pavlovian bias. These findings reveal distinct motivation-dependent learning capabilities across the human life span, which cannot be probed using conventional go/reward no-go/punishment style paradigms that have important implications in lifelong education

"I want to be a furious leopard with magical wings and super power": developing an ethico-interpretive framework for detecting Chinese students' funds of identity

The Avatar Project was a two-week English project in which Chinese high school students in an internationalised school in Shanghai China explored the topic of cultural and individual identity. The project synthesised prospective education with the Funds of Identity approach, both of which have particular relevance within an internationalised teaching context. During the project, students created three identity texts: a written reflection, a word cloud and an avatar which were later used as data for this article. This article presents findings from the project and critically evaluates the effectiveness of avatars and word clouds as strategies for detecting students’ funds of identity. A multimodal approach to data collection and analysis was adopted in order to ensure that the interpretation of students’ work remained situated within their lived experience. The project revealed the existence of social, practical, institutional and cultural funds of identity. However, it also detected more problematic forms of funds of identity related to political and philosophical beliefs which I label ideological and existential funds of identity. While avatars and word clouds were effective in drawing out students’ out-of-school identities, the written reflections were ultimately more useful in revealing students’ funds of identity and also ensuring that any interpretations remained within the participants’ horizon of intended meaning. The project also brought about significant transformation in the way I viewed my students

Matter, Literacy, and English Language Teaching in an Underprivileged School in Spain

This article analyzes the processes and findings of a collaborative action research (CAR) project that aimed to analyze the potential of materiality to radically transform the way English was taught and learned in an underprivileged public school in Spain. The CAR drew on new materialisms and new literacy studies to explore the relationship between matter and English language teaching from socioeconomic, sociocultural, and technological perspectives. The main pedagogical strategy consisted of widening the quantity and quality of the material resources in the English classroom, precisely to draw a material link between the English classroom and the students' homes, communities, and the informal literacies they enacted in them. Through two cycles of inquiry, the CAR team put into practice two multimodal and artifactual workshops with a group of nine children from underprivileged, minority backgrounds. A variety of qualitative strategies were used (including classroom recordings, student interviews, and photographs) to confirm that the insights from new materialisms and new literacy studies had generated opportunities for meaningful English learning within a culturally sustaining pedagogy

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects