Beliefs about the Minds of Others Influence How We Process Sensory Information

Attending where others gaze is one of the most fundamental mechanisms of social cognition. The present study is the first to examine the impact of the attribution of mind to others on gaze-guided attentional orienting and its ERP correlates. Using a paradigm in which attention was guided to a location by the gaze of a centrally presented face, we manipulated participants' beliefs about the gazer: gaze behavior was believed to result either from operations of a mind or from a machine. In Experiment 1, beliefs were manipulated by cue identity (human or robot), while in Experiment 2, cue identity (robot) remained identical across conditions and beliefs were manipulated solely via instruction, which was irrelevant to the task. ERP results and behavior showed that participants' attention was guided by gaze only when gaze was believed to be controlled by a human. Specifically, the P1 was more enhanced for validly, relative to invalidly, cued targets only when participants believed the gaze behavior was the result of a mind, rather than of a machine. This shows that sensory gain control can be influenced by higher-order (task-irrelevant) beliefs about the observed scene. We propose a new interdisciplinary model of social attention, which integrates ideas from cognitive and social neuroscience, as well as philosophy in order to provide a framework for understanding a crucial aspect of how humans' beliefs about the observed scene influence sensory processing

Behavioral activation for dementia caregivers: scheduling pleasant events and enhancing communications

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Considering the role of cognitive control in expert performance

© 2014, Springer Science+Business Media Dordrecht. Dreyfus and Dreyfus’ (1986) influential phenomenological analysis of skill acquisition proposes that expert performance is guided by non-cognitive responses which are fast, effortless and apparently intuitive in nature. Although this model has been criticised (e.g., by Breivik Journal of Philosophy of Sport, 34, 116–134 2007, Journal of the Philosophy of Sport, 40, 85–106 2013; Eriksen 2010; Montero Inquiry:An interdisciplinary Journal of Philosophy, 53, 105–122 2010; Montero and Evans 2011) for over-emphasising the role that intuition plays in facilitating skilled performance, it does recognise that on occasions (e.g., when performance goes awry for some reason) a form of ‘detached deliberative rationality’ may be used by experts to improve their performance. However, Dreyfus and Dreyfus (1986) see no role for calculative problem solving or deliberation (i.e., drawing on rules or mental representations) when performance is going well. In the current paper, we draw on empirical evidence, insights from athletes, and phenomenological description to argue that ‘continuous improvement’ (i.e., the phenomenon whereby certain skilled performers appear to be capable of increasing their proficiency even though they are already experts; Toner and Moran 2014) among experts is mediated by cognitive (or executive) control in three distinct sporting situations (i.e., in training, during pre-performance routines, and while engaged in on-line skill execution). We conclude by arguing that Sutton et al. Journal of the British Society for Phenomenology, 42, 78–103 (2011) ‘applying intelligence to the reflexes’ (AIR) approach may help to elucidate the process by which expert performers achieve continuous improvement through analytical/mindful behaviour during training and competition

Carrier-mediated magnetoelectricity in complex oxide heterostructures

While tremendous success has been achieved to date in creating both single phase and composite magnetoelectric materials, the quintessential electric-field control of magnetism remains elusive. In this work, we demonstrate a linear magnetoelectric effect which arises from a novel carrier-mediated mechanism, and is a universal feature of the interface between a dielectric and a spin-polarized metal. Using first-principles density functional calculations, we illustrate this effect at the SrRuO$_3$/SrTiO$_3$ interface and describe its origin. To formally quantify the magnetic response of such an interface to an applied electric field, we introduce and define the concept of spin capacitance. In addition to its magnetoelectric and spin capacitive behavior, the interface displays a spatial coexistence of magnetism and dielectric polarization suggesting a route to a new type of interfacial multiferroic

Neutrino-Nucleus Interactions

The study of neutrino oscillations has necessitated a new generation of neutrino experiments that are exploring neutrino-nuclear scattering processes. We focus in particular on charged-current quasi-elastic scattering, a particularly important channel that has been extensively investigated both in the bubble-chamber era and by current experiments. Recent results have led to theoretical reexamination of this process. We review the standard picture of quasi-elastic scattering as developed in electron scattering, review and discuss experimental results, and discuss additional nuclear effects such as exchange currents and short-range correlations that may play a significant role in neutrino-nucleus scattering

Development of a Core Outcome Set for effectiveness trials aimed at optimising prescribing in older adults in care homes

Background: Prescribing medicines for older adults in care homes is known to be sub-optimal. Whilst trials testing interventions to optimise prescribing in this setting have been published, heterogeneity in outcome reporting has hindered comparison of interventions, thus limiting evidence synthesis. The aim of this study was to develop a core outcome set (COS), a list of outcomes which should be measured and reported, as a minimum, for all effectiveness trials involving optimising prescribing in care homes. The COS was developed as part of the Care Homes Independent Pharmacist Prescribing Study (CHIPPS). Methods: A long-list of outcomes was identified through a review of published literature and stakeholder input. Outcomes were reviewed and refined prior to entering a two-round online Delphi exercise and then distributed via a web link to the CHIPPS Management Team, a multidisciplinary team including pharmacists, doctors and Patient Public Involvement representatives (amongst others), who comprised the Delphi panel. The Delphi panellists (n = 19) rated the importance of outcomes on a 9-point Likert scale from 1 (not important) to 9 (critically important). Consensus for an outcome being included in the COS was defined as ≥70% participants scoring 7–9 and <15% scoring 1–3. Exclusion was defined as ≥70% scoring 1–3 and <15% 7–9. Individual and group scores were fed back to participants alongside the second questionnaire round, which included outcomes for which no consensus had been achieved. Results: A long-list of 63 potential outcomes was identified. Refinement of this long-list of outcomes resulted in 29 outcomes, which were included in the Delphi questionnaire (round 1). Following both rounds of the Delphi exercise, 13 outcomes (organised into seven overarching domains: medication appropriateness, adverse drug events, prescribing errors, falls, quality of life, all-cause mortality and admissions to hospital (and associated costs)) met the criteria for inclusion in the final COS. Conclusions: We have developed a COS for effectiveness trials aimed at optimising prescribing in older adults in care homes using robust methodology. Widespread adoption of this COS will facilitate evidence synthesis between trials. Future work should focus on evaluating appropriate tools for these key outcomes to further reduce heterogeneity in outcome measurement in this context

Structural basis for native agonist and synthetic inhibitor recognition by the Pseudomonas aeruginosa quorum sensing regulator PqsR (MvfR)

Bacterial populations co-ordinate gene expression collectively through quorum sensing (QS), a cell-to-cell communication mechanism employing diffusible signal molecules. The LysR-type transcriptional regulator (LTTR) protein PqsR (MvfR) is a key component of alkyl-quinolone (AQ)-dependent QS in Pseudomonas aeruginosa. PqsR is activated by 2-alkyl-4-quinolones including the Pseudomonas quinolone signal (PQS; 2-heptyl-3-hydroxy-4(1H)-quinolone), its precursor 2-heptyl-4- hydroxyquinoline (HHQ) and their C9 congeners, 2-nonyl-3-hydroxy-4(1H)-quinolone (C9-PQS) and 2-nonyl-4-hydroxyquinoline (NHQ). These drive the autoinduction of AQ biosynthesis and the up-regulation of key virulence determinants as a function of bacterial population density. Consequently, PqsR constitutes a potential target for novel antibacterial agents which attenuate infection through the blockade of virulence. Here we present the crystal structures of the PqsR co-inducer binding domain (CBD) and a complex with the native agonist NHQ. We show that the structure of the PqsR CBD has an unusually large ligand-binding pocket in which a native AQ agonist is stabilized entirely by hydrophobic interactions. Through a ligand-based design strategy we synthesized and evaluated a series of 50 AQ and novel quinazolinone (QZN) analogues and measured the impact on AQ biosynthesis, virulence gene expression and biofilm development. The simple exchange of two isosteres (OH for NH2) switches a QZN agonist to an antagonist with a concomitant impact on the induction of bacterial virulence factor production. We also determined the complex crystal structure of a QZN antagonist bound to PqsR revealing a similar orientation in the ligand binding pocket to the native agonist NHQ. This structure represents the first description of an LTTR-antagonist complex. Overall these studies present novel insights into LTTR ligand binding and ligand-based drug design and provide a chemical scaffold for further anti-P. aeruginosa virulence drug development by targeting the AQ receptor PqsR

Selenium isotope evidence for progressive oxidation of the Neoproterozoic biosphere

Neoproterozoic (1,000–542 Myr ago) Earth experienced profound environmental change, including ‘snowball’ glaciations, oxygenation and the appearance of animals. However, an integrated understanding of these events remains elusive, partly because proxies that track subtle oceanic or atmospheric redox trends are lacking. Here we utilize selenium (Se) isotopes as a tracer of Earth redox conditions. We find temporal trends towards lower δ82/76Se values in shales before and after all Neoproterozoic glaciations, which we interpret as incomplete reduction of Se oxyanions. Trends suggest that deep-ocean Se oxyanion concentrations increased because of progressive atmospheric and deep-ocean oxidation. Immediately after the Marinoan glaciation, higher δ82/76Se values superpose the general decline. This may indicate less oxic conditions with lower availability of oxyanions or increased bioproductivity along continental margins that captured heavy seawater δ82/76Se into buried organics. Overall, increased ocean oxidation and atmospheric O2 extended over at least 100 million years, setting the stage for early animal evolution

Translational toxicology in setting occupational exposure limits for dusts and hazard classification – a critical evaluation of a recent approach to translate dust overload findings from rats to humans

Background We analyze the scientific basis and methodology used by the German MAK Commission in their recommendations for exposure limits and carcinogen classification of “granular biopersistent particles without known specific toxicity” (GBS). These recommendations are under review at the European Union level. We examine the scientific assumptions in an attempt to reproduce the results. MAK’s human equivalent concentrations (HECs) are based on a particle mass and on a volumetric model in which results from rat inhalation studies are translated to derive occupational exposure limits (OELs) and a carcinogen classification. Methods We followed the methods as proposed by the MAK Commission and Pauluhn 2011. We also examined key assumptions in the metrics, such as surface area of the human lung, deposition fractions of inhaled dusts, human clearance rates; and risk of lung cancer among workers, presumed to have some potential for lung overload, the physiological condition in rats associated with an increase in lung cancer risk. Results The MAK recommendations on exposure limits for GBS have numerous incorrect assumptions that adversely affect the final results. The procedures to derive the respirable occupational exposure limit (OEL) could not be reproduced, a finding raising considerable scientific uncertainty about the reliability of the recommendations. Moreover, the scientific basis of using the rat model is confounded by the fact that rats and humans show different cellular responses to inhaled particles as demonstrated by bronchoalveolar lavage (BAL) studies in both species. Conclusion Classifying all GBS as carcinogenic to humans based on rat inhalation studies in which lung overload leads to chronic inflammation and cancer is inappropriate. Studies of workers, who have been exposed to relevant levels of dust, have not indicated an increase in lung cancer risk. Using the methods proposed by the MAK, we were unable to reproduce the OEL for GBS recommended by the Commission, but identified substantial errors in the models. Considerable shortcomings in the use of lung surface area, clearance rates, deposition fractions; as well as using the mass and volumetric metrics as opposed to the particle surface area metric limit the scientific reliability of the proposed GBS OEL and carcinogen classification.International Carbon Black Associatio

The Inflammatory Kinase MAP4K4 Promotes Reactivation of Kaposi's Sarcoma Herpesvirus and Enhances the Invasiveness of Infected Endothelial Cells

Kaposi's sarcoma (KS) is a mesenchymal tumour, which is caused by Kaposi's sarcoma herpesvirus (KSHV) and develops under inflammatory conditions. KSHV-infected endothelial spindle cells, the neoplastic cells in KS, show increased invasiveness, attributed to the elevated expression of metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). The majority of these spindle cells harbour latent KSHV genomes, while a minority undergoes lytic reactivation with subsequent production of new virions and viral or cellular chemo- and cytokines, which may promote tumour invasion and dissemination. In order to better understand KSHV pathogenesis, we investigated cellular mechanisms underlying the lytic reactivation of KSHV. Using a combination of small molecule library screening and siRNA silencing we found a STE20 kinase family member, MAP4K4, to be involved in KSHV reactivation from latency and to contribute to the invasive phenotype of KSHV-infected endothelial cells by regulating COX-2, MMP-7, and MMP-13 expression. This kinase is also highly expressed in KS spindle cells in vivo. These findings suggest that MAP4K4, a known mediator of inflammation, is involved in KS aetiology by regulating KSHV lytic reactivation, expression of MMPs and COX-2, and, thereby modulating invasiveness of KSHV-infected endothelial cells. © 2013 Haas et al