Risk, Unexpected Uncertainty, and Estimation Uncertainty: Bayesian Learning in Unstable Settings

Recently, evidence has emerged that humans approach learning using Bayesian updating rather than (model-free) reinforcement algorithms in a six-arm restless bandit problem. Here, we investigate what this implies for human appreciation of uncertainty. In our task, a Bayesian learner distinguishes three equally salient levels of uncertainty. First, the Bayesian perceives irreducible uncertainty or risk: even knowing the payoff probabilities of a given arm, the outcome remains uncertain. Second, there is (parameter) estimation uncertainty or ambiguity: payoff probabilities are unknown and need to be estimated. Third, the outcome probabilities of the arms change: the sudden jumps are referred to as unexpected uncertainty. We document how the three levels of uncertainty evolved during the course of our experiment and how it affected the learning rate. We then zoom in on estimation uncertainty, which has been suggested to be a driving force in exploration, in spite of evidence of widespread aversion to ambiguity. Our data corroborate the latter. We discuss neural evidence that foreshadowed the ability of humans to distinguish between the three levels of uncertainty. Finally, we investigate the boundaries of human capacity to implement Bayesian learning. We repeat the experiment with different instructions, reflecting varying levels of structural uncertainty. Under this fourth notion of uncertainty, choices were no better explained by Bayesian updating than by (model-free) reinforcement learning. Exit questionnaires revealed that participants remained unaware of the presence of unexpected uncertainty and failed to acquire the right model with which to implement Bayesian updating

Memory for medication side effects in younger and older adults: the role of subjective and objective importance

Older adults often experience memory impairments, but can sometimes use selective processing and schematic support to remember important information. The current experiments investigate to what degree younger and healthy older adults remember medication side effects that were subjectively or objectively important to remember. Participants studied a list of common side effects, and rated how negative these effects were if they were to experience them, and were then given a free recall test. In Experiment 1, the severity of the side effects ranged from mild (e.g., itching) to severe (e.g., stroke), and in Experiment 2, certain side effects were indicated as critical to remember (i.e., “contact your doctor if you experience this”). There were no age differences in terms of free recall of the side effects, and older adults remembered more severe side effects relative to mild effects. However, older adults were less likely to recognize critical side effects on a later recognition test, relative to younger adults. The findings suggest that older adults can selectively remember medication side effects, but have difficulty identifying familiar but potentially critical side effects, and this has implications for monitoring medication use in older age

“It would really support the wider harm reduction agenda across the board”: A qualitative study of the potential impacts of drug checking service delivery in Scotland

Drug checking services (DCS) enable individuals to voluntarily submit a small amount of a substance for analysis, providing information about the content of the substance along with tailored harm reduction support and advice. There is some evidence suggesting that DCS may lead to behaviour and system change, with impacts for people who use drugs, staff and services, and public health structures. The evidence base is still relatively nascent, however, and several evidence gaps persist. This paper reports on qualitative interviews with forty-three participants across three Scottish cities where the implementation of community-based DCS is being planned. Participants were drawn from three groups: professional participants; people with experience of drug use; and affected family members. Findings focus on perceived harm reduction impacts of DCS delivery in Scotland, with participants highlighting the potential for drug checking to impact a number of key groups including: individual service users; harm reduction services and staff; drug market monitoring structures and networks; and wider groups of people who use and sell drugs, in shaping their interactions with the drug market. Whilst continued evaluation of individual health behaviour outcomes is crucial to building the evidence base for DCS, the findings highlight the importance of extending evaluation beyond these outcomes. This would include evaluation of processes such as: information sharing across a range of parties; engagement with harm reduction and treatment services; knowledge building; and increased drug literacy. These broader dynamics may be particularly important for evaluations of community-based DCS serving individuals at higher-risk, given the complex relationship between information provision and health behaviour change which may be mediated by mental and physical health, stigma, criminalisation and the risk environment. This paper is of international relevance and adds to existing literature on the potential impact of DCS on individuals, organisations, and public health structures

MSDmotif: exploring protein sites and motifs

<p>Abstract</p> <p>Background</p> <p>Protein structures have conserved features – motifs, which have a sufficient influence on the protein function. These motifs can be found in sequence as well as in 3D space. Understanding of these fragments is essential for 3D structure prediction, modelling and drug-design. The Protein Data Bank (PDB) is the source of this information however present search tools have limited 3D options to integrate protein sequence with its 3D structure.</p> <p>Results</p> <p>We describe here a web application for querying the PDB for ligands, binding sites, small 3D structural and sequence motifs and the underlying database. Novel algorithms for chemical fragments, 3D motifs, ϕ/ψ sequences, super-secondary structure motifs and for small 3D structural motif associations searches are incorporated. The interface provides functionality for visualization, search criteria creation, sequence and 3D multiple alignment options. MSDmotif is an integrated system where a results page is also a search form. A set of motif statistics is available for analysis. This set includes molecule and motif binding statistics, distribution of motif sequences, occurrence of an amino-acid within a motif, correlation of amino-acids side-chain charges within a motif and Ramachandran plots for each residue. The binding statistics are presented in association with properties that include a ligand fragment library. Access is also provided through the distributed Annotation System (DAS) protocol. An additional entry point facilitates XML requests with XML responses.</p> <p>Conclusion</p> <p>MSDmotif is unique by combining chemical, sequence and 3D data in a single search engine with a range of search and visualisation options. It provides multiple views of data found in the PDB archive for exploring protein structures.</p

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

Teaching the science of learning

The science of learning has made a considerable contribution to our understanding of effective teaching and learning strategies. However, few instructors outside of the field are privy to this research. In this Tutorial Review, we focus on six specific cognitive strategies that have received robust support from decades of research: spaced practice, interleaving, retrieval practice, elaboration, concrete examples, and dual coding. We describe the basic research behind each strategy and relevant applied research, present examples of existing and suggested implementation, and make recommendations for further research that would broaden the reach of these strategies

Molecular changes in the expression of human colonic nutrient transporters during the transition from normality to malignancy

Healthy colonocytes derive 60–70% of their energy supply from short-chain fatty acids, particularly butyrate. Butyrate has profound effects on differentiation, proliferation and apoptosis of colonic epithelial cells by regulating expression of various genes associated with these processes. We have previously shown that butyrate is transported across the luminal membrane of the colonic epithelium via a monocarboxylate transporter, MCT1. In this paper, using immunohistochemistry and in situ hybridisation histochemistry, we have determined the profile of MCT1 protein and mRNA expression along the crypt to surface axis of healthy human colonic tissue. There is a gradient of MCT1 protein expression in the apical membrane of the cells along the crypt-surface axis rising to a peak in the surface epithelial cells. MCT1 mRNA is expressed along the crypt-surface axis and is most abundant in cells lining the crypt. Analysis of healthy colonic tissues and carcinomas using immunohistochemistry and Western blotting revealed a significant decline in the expression of MCT1 protein during transition from normality to malignancy. This was reflected in a corresponding reduction in MCT1 mRNA expression, as measured by Northern analysis. Carcinoma samples displaying reduced levels of MCT1 were found to express the high affinity glucose transporter, GLUT1, suggesting that there is a switch from butyrate to glucose as an energy source in colonic epithelia during transition to malignancy. The expression levels of MCT1 in association with GLUT1 could potentially be used as determinants of the malignant state of colonic tissue

Transparent Meta-Analysis of Prospective Memory and Aging

Prospective memory (ProM) refers to our ability to become aware of a previously formed plan at the right time and place. After two decades of research on prospective memory and aging, narrative reviews and summaries have arrived at widely different conclusions. One view is that prospective memory shows large age declines, larger than age declines on retrospective memory (RetM). Another view is that prospective memory is an exception to age declines and remains invariant across the adult lifespan. The present meta-analysis of over twenty years of research settles this controversy. It shows that prospective memory declines with aging and that the magnitude of age decline varies by prospective memory subdomain (vigilance, prospective memory proper, habitual prospective memory) as well as test setting (laboratory, natural). Moreover, this meta-analysis demonstrates that previous claims of no age declines in prospective memory are artifacts of methodological and conceptual issues afflicting prior research including widespread ceiling effects, low statistical power, age confounds, and failure to distinguish between various subdomains of prospective memory (e.g., vigilance and prospective memory proper)

Task-Selective Memory Effects for Successfully Implemented Encoding Strategies

Previous behavioral evidence suggests that instructed strategy use benefits associative memory formation in paired associate tasks. Two such effective encoding strategies–visual imagery and sentence generation–facilitate memory through the production of different types of mediators (e.g., mental images and sentences). Neuroimaging evidence suggests that regions of the brain support memory reflecting the mental operations engaged at the time of study. That work, however, has not taken into account self-reported encoding task success (i.e., whether participants successfully generated a mediator). It is unknown, therefore, whether task-selective memory effects specific to each strategy might be found when encoding strategies are successfully implemented. In this experiment, participants studied pairs of abstract nouns under either visual imagery or sentence generation encoding instructions. At the time of study, participants reported their success at generating a mediator. Outside of the scanner, participants further reported the quality of the generated mediator (e.g., images, sentences) for each word pair. We observed task-selective memory effects for visual imagery in the left middle occipital gyrus, the left precuneus, and the lingual gyrus. No such task-selective effects were observed for sentence generation. Intriguingly, activity at the time of study in the left precuneus was modulated by the self-reported quality (vividness) of the generated mental images with greater activity for trials given higher ratings of quality. These data suggest that regions of the brain support memory in accord with the encoding operations engaged at the time of study