Adaptive Prediction Error Coding in the Human Midbrain and Striatum Facilitates Behavioral Adaptation and Learning Efficiency.

Effective error-driven learning benefits from scaling of prediction errors to reward variability. Such behavioral adaptation may be facilitated by neurons coding prediction errors relative to the standard deviation (SD) of reward distributions. To investigate this hypothesis, we required participants to predict the magnitude of upcoming reward drawn from distributions with different SDs. After each prediction, participants received a reward, yielding trial-by-trial prediction errors. In line with the notion of adaptive coding, BOLD response slopes in the Substantia Nigra/Ventral Tegmental Area (SN/VTA) and ventral striatum were steeper for prediction errors occurring in distributions with smaller SDs. SN/VTA adaptation was not instantaneous but developed across trials. Adaptive prediction error coding was paralleled by behavioral adaptation, as reflected by SD-dependent changes in learning rate. Crucially, increased SN/VTA and ventral striatal adaptation was related to improved task performance. These results suggest that adaptive coding facilitates behavioral adaptation and supports efficient learning.This study was supported by the Wellcome Trust (W.S., P.C.F.), Bernard Wolfe Health Neuroscience Fund (P.C.F.) and the Niels Stensen Foundation (K.M.J.D.). We thank William Stauffer, Armin Lak and Joost Haarsma for useful discussions.This is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.neuron.2016.04.01

Sterilization of lung matrices by supercritical carbon dioxide

Lung engineering is a potential alternative to transplantation for patients with end-stage pulmonary failure. Two challenges critical to the successful development of an engineered lung developed from a decellularized scaffold include (i) the suppression of resident infectious bioburden in the lung matrix, and (ii) the ability to sterilize decellularized tissues while preserving the essential biological and mechanical features intact. To date, the majority of lungs are sterilized using high concentrations of peracetic acid (PAA) resulting in extracellular matrix (ECM) depletion. These mechanically altered tissues have little to no storage potential. In this study, we report a sterilizing technique using supercritical carbon dioxide (ScCO(2)) that can achieve a sterility assurance level 10(−6) in decellularized lung matrix. The effects of ScCO(2) treatment on the histological, mechanical, and biochemical properties of the sterile decellularized lung were evaluated and compared with those of freshly decellularized lung matrix and with PAA-treated acellular lung. Exposure of the decellularized tissue to ScCO(2) did not significantly alter tissue architecture, ECM content or organization (glycosaminoglycans, elastin, collagen, and laminin), observations of cell engraftment, or mechanical integrity of the tissue. Furthermore, these attributes of lung matrix did not change after 6 months in sterile buffer following sterilization with ScCO(2), indicating that ScCO(2) produces a matrix that is stable during storage. The current study's results indicate that ScCO(2) can be used to sterilize acellular lung tissue while simultaneously preserving key biological components required for the function of the scaffold for regenerative medicine purposes

Living with multimorbidity? The lived experience of multiple chronic conditions in later life

Multimorbidity is defined biomedically as the co-existence of two or more long-term conditions in an individual. Globally, the number of people living with multiple conditions is increasing, posing stark challenges both to the clinical management of patients and the organisation of health systems. Qualitative literature has begun to address how concurrency affects the self-management of chronic conditions, and the concept of illness prioritisation predominates. In this article, we adopt a phenomenological lens to show how older people with multiple conditions experience illness. This UK study was qualitative and longitudinal in design. Sampling was purposive and drew upon an existing cohort study. In total, 15 older people living with multiple conditions took part in 27 in-depth interviews. The practical stages of analysis were guided by Constructivist Grounded Theory. We argue that the concept of multimorbidity as biomedically imagined has limited relevance to lived experience, while concurrency may also be erroneous. In response, we outline a lived experience of multiple chronic conditions in later life, which highlights differences between clinical and lay assumptions and makes the latter visible

Evolution of the X-ray Emission of Radio-Quiet Quasars

We report new Chandra observations of seven optically faint, z \sim 4 radio-quiet quasars. We have combined these new observations with previous Chandra observations of radio-quiet quasars to create a sample of 174 sources. These sources have 0.1 < z < 4.7, and 10^{44} ergs s^{-1} < nu L_{nu} (2500 \AA) < 10^{48} ergs s^{-1}. The X-ray detection fraction is 90%. We find that the X-ray loudness of radio-quiet quasars decreases with UV luminosity and increases with redshift. The model that is best supported by the data has a linear dependence of optical-to-X-ray ratio, alpha_{ox}, on cosmic time, and a quadratic dependence of alpha_{ox} on log L_{UV}, where alpha_{ox} becomes X-ray quiet more rapidly at higher log L_{UV}. We find no significant evidence for a relationship between the X-ray photon index, Gamma_X, and the UV luminosity, and we find marginally significant evidence that the X-ray continuum flattens with increasing z (2 sigma). The Gamma_X-z anti-correlation may be the result of X-ray spectral curvature, redshifting of a Compton reflection component into the observed Chandra band, and/or redshifting of a soft excess out of the observed Chandra band. Using the results for Gamma_X, we show that the alpha_{ox}-z relationship is unlikely to be a spurious result caused by redshifting of the observable X-ray spectral region. A correlation between alpha_{ox} and z implies evolution of the accretion process. We present a qualitative comparison of these new results with models for accretion disk emission.Comment: Accepted by ApJ, 48 pages, 10 figures, 5 table

Nucleon isovector structure functions in (2+1)-flavor QCD with domain wall fermions

We report on numerical lattice QCD calculations of some of the low moments of the nucleon structure functions. The calculations are carried out with gauge configurations generated by the RBC and UKQCD collaborations with (2+1)-flavors of dynamical domain wall fermions and the Iwasaki gauge action ($\beta = 2.13$). The inverse lattice spacing is $a^{-1} = 1.73$ GeV, and two spatial volumes of ((2.7{\rm fm})^3) and ((1.8 {\rm fm})^3) are used. The up and down quark masses are varied so the pion mass lies between 0.33 and 0.67 GeV while the strange mass is about 12 % heavier than the physical one. The structure function moments we present include fully non-perturbatively renormalized iso-vector quark momentum fraction, (_{u-d}), helicity fraction, (< x >_{\Delta u - \Delta d}), and transversity, (_{\delta u - \delta d}), as well as an unrenormalized twist-3 coefficient, (d_1). The ratio of the momentum to helicity fractions, (_{u-d}/_{\Delta u - \Delta d}), does not show dependence on the light quark mass and agrees well with the value obtained from experiment. Their respective absolute values, fully renormalized, show interesting trends toward their respective experimental values at the lightest quark mass. A prediction for the transversity, (0.7 _{\delta u -\delta d} < 1.1), in the (\bar{\rm MS}) scheme at 2 GeV is obtained. The twist-3 coefficient, (d_1), though yet to be renormalized, supports the perturbative Wandzura-Wilczek relation.Comment: 14 pages, 22 figures

Engineering Collaborations in Medical Modeling and Simulation

Fifty years ago computer science was just beginning to see common acceptance as a growing discipline and very few universities had a computer science department although other departments were utilizing computers and software to enhance their methodologies. We believe modeling and simulation (M&S) is on a similar path. Many other disciplines utilize M&S to enhance their methodologies but we also believe that M&S fundamentals can be essential in making better decisions by utilizing the appropriate model for the problem at hand, expanding the solution space through simulation, and understanding it through visualization and proper analyses. After our students learn these fundamentals, we offer the opportunity to apply them to varied application areas. One such application area is medical M&S, which is a broad area involving anatomical modeling, planning and training simulations, image-guided procedures and more. In this paper, we share several research projects involving M&S and the collaborations that make them possible

Correlation of formative assessments as the means of predicting summative performance in paramedic students

Background: Paramedic programs use formative assessments to determine cognitive competency. Understanding the number of failed formative units as a probability of passing the summative exam will allow programs to set additional benchmarks. The purpose of this study was to determine whether failure in formative exams determines success on a summative exam. Methods: Formative and summative scores from 2011 – 2016 for paramedic students with accounts in Fisdap™, an Internet-based administrative database, were retrospectively reviewed for the following criteria: provided consent for research, completed all six formative (unit) examinations, and completed a summative (comprehensive) examination. Analyses were performed with Pearson correlations and linear regression. Results: A total of 1,406 student records were included based on inclusion criteria. Correlation with each formative and the summative examination were all significant, p \u3c 0.001: Cardiology 0.597; Airway 0.571; Medical 0.571; Trauma 0.566; Ob/Pediatrics 0.549; Operations 0.495. The cardiology exam was shown to have a moderate correlation on summative performance, whereas the operations exam had the weakest correlation. The number of formative examination failures was a significant predictor of the probability of passing the summative examination, t(1405) = –31.02, p \u3c 0.001. Zero failed unit examinations yielded a 100% probability of passing. Three failed formative exams yielded a 60.4% probability. Four failed attempts yielded a 44.8% probability. Failure of all six formative exams yielded a 13.4% probability of passing the Paramedic Readiness Exam Version 3. Conclusion: Not all formative examinations hold the same predictive power on the probability of passing a summative examination. Each had their own correlation value. Students who did not fail formative examinations have a 100% likelihood of passing the summative examination

Creativity and the computer nerd: an exploration of attitudes

This study arises from our concern that many of our best art and design students are failing to make the most of the opportunities provided by IT because of their fear or dislike of computers. This not only deprives them of useful skills, but, even more importantly, deprives many IT based developments of their input. In this paper we investigate the relationship between attitudes to creativity and to computers among students. We quickly discard an approach based on theories of personality types as philosophically and educationally problematic. An approach based on the self-concept of artists and designers, in relation to their own creativity and to their feelings about computers, offers more hope of progress. This means that we do not try to define the attributes of "creative people". Rather, we ask what creativity means to students of art and design and relate these responses to their attitudes to computers. Self-concept depends on how the subjects see themselves within society and culture, and is liable to change as culture changes. One major instrument of cultural change at the present time is the growth of IT itself. We then describe a first attempt at using a psychological method - Kelly's Repertory Grids - to investigate the self-concept of artists and designers. It is hoped to continue with this approach in further studies over the next few years