Large-scale multielectrode recording and stimulation of neural activity

Large circuits of neurons are employed by the brain to encode and process information. How this encoding and processing is carried out is one of the central questions in neuroscience. Since individual neurons communicate with each other through electrical signals (action potentials), the recording of neural activity with arrays of extracellular electrodes is uniquely suited for the investigation of this question. Such recordings provide the combination of the best spatial (individual neurons) and temporal (individual action-potentials) resolutions compared to other large-scale imaging methods. Electrical stimulation of neural activity in turn has two very important applications: it enhances our understanding of neural circuits by allowing active interactions with them, and it is a basis for a large variety of neural prosthetic devices. Until recently, the state-of-the-art in neural activity recording systems consisted of several dozen electrodes with inter-electrode spacing ranging from tens to hundreds of microns. Using silicon microstrip detector expertise acquired in the field of high-energy physics, we created a unique neural activity readout and stimulation framework that consists of high-density electrode arrays, multi-channel custom-designed integrated circuits, a data acquisition system, and data-processing software. Using this framework we developed a number of neural readout and stimulation systems: (1) a 512-electrode system for recording the simultaneous activity of as many as hundreds of neurons, (2) a 61-electrode system for electrical stimulation and readout of neural activity in retinas and brain-tissue slices, and (3) a system with telemetry capabilities for recording neural activity in the intact brain of awake, naturally behaving animals. We will report on these systems, their various applications to the field of neurobiology, and novel scientific results obtained with some of them. We will also outline future directions

Predictive validity of the UK clinical aptitude test in the final years of medical school:a prospective cohort study

Peer reviewedPublisher PD

Position Reconstruction in Drift Chambers operated with Xe, CO2 (15%)

We present measurements of position and angular resolution of drift chambers operated with a Xe,CO$_2$(15%) mixture. The results are compared to Monte Carlo simulations and important systematic effects, in particular the dispersive nature of the absorption of transition radiation and non-linearities, are discussed. The measurements were carried out with prototype drift chambers of the ALICE Transition Radiation Detector, but our findings can be generalized to other drift chambers with similar geometry, where the electron drift is perpendicular to the wire planes.Comment: 30 pages, 18 figure

Fixed-Parameter Tractable Distances to Sparse Graph Classes

We show that for various classes $\mathcal{C}$ of sparse graphs, and several measures of distance to such classes (such as edit distance and elimination distance), the problem of determining the distance of a given graph $\small{G}$ to $\mathcal{C}$ is fixed-parameter tractable. The results are based on two general techniques. The first of these, building on recent work of Grohe et al. establishes that any class of graphs that is slicewise nowhere dense and slicewise first-order definable is FPT. The second shows that determining the elimination distance of a graph $\small{G}$ to a minor-closed class $\mathcal{C}$ is FPT. We demonstrate that several prior results (of Golovach, Moser and Thilikos and Mathieson) on the fixed-parameter tractability of distance measures are special cases of our first method

Sintering of calcium phosphates with a femtosecond pulsed laser for hard tissue engineering

The authors acknowledge support from the sponsors of this work; the EPSRC LUMIN (EP/K020234/1) and EU-Marie-Curie-IAPP LUSTRE (324538) projects.Direct laser sintering on hard tissues is likely to open new pathways for personalised medicine. To minimise irradiation damage of the surrounding soft tissues, lasers operating at wavelengths that are ‘safe’ for the tissues and biomaterials with improved optical properties are required. In this work laser sintering is demonstrated with the use of an ultrafast, femtosecond (100 fs) pulsed laser operating at a wavelength of 1045 nm and two existing calcium phosphate minerals (brushite and hydroxyapatite) which have been improved after doping with iron (10 mol%). Femtosecond laser irradiation caused transformation of the Fe3+-doped brushite and Fe3+-doped HAp samples into β-calcium pyrophosphate and calcium-iron-phosphate, respectively, with simultaneous evidence for microstructural sintering and densification. After estimating the temperature profile at the surface of the samples we suggest that soft tissues over 500 μm from the irradiated zone would be safe from thermal damage. This novel laser processing provides a means to control the phase constitution and the morphology of the finished surfaces. The porous structure of β-pyrophosphate might be suitable for applications in bone regeneration by supporting osteogenic cell activity while, the densified Fe3+-rich calcium-iron-phosphate may be promising for applications like dental enamel restoration.PostprintPeer reviewe

Space charge in drift chambers operated with the Xe,CO2(15%) mixture

Using prototype modules of the ALICE Transition Radiation Detector we investigate space charge effects and the dependence of the pion rejection performance on the incident angle of the ionizing particle. The average pulse height distributions in the drift chambers operated with the Xe,CO2(15%) mixture provide quantitative information on the gas gain reduction due to space charge accumulating during the drift of the primary ionization. Our results demonstrate that the pion rejection performance of a TRD is better for tracks which are not at normal incidence to the anode wires. We present detailed simulations of detector signals, which reproduce the measurements and lend strong support to our interpretation of the measurements in terms of space charge effects.Comment: 18 pages, 10 figures, accepted for publication in Nucl.Instrum.Meth. A. Data files available at http://www-alice.gsi.de/tr

Adherence to a Mediterranean diet and Alzheimer's disease risk in an Australian population

The Mediterranean diet (MeDi), due to its correlation with a low morbidity and mortality for many chronic diseases, has been widely recognised as a healthy eating model. We aimed to investigate, in a cross-sectional study, the association between adherence to a MeDi and risk for Alzheimer's disease (AD) and mild cognitive impairment (MCI) in a large, elderly, Australian cohort. Subjects in the Australian Imaging, Biomarkers and Lifestyle Study of Ageing cohort (723 healthy controls (HC), 98 MCI and 149 AD participants) completed the Cancer Council of Victoria Food Frequency Questionnaire. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of AD and MCI status in multinominal logistic regression models that were adjusted for cohort age, sex, country of birth, education, apolipoprotein E genotype, total caloric intake, current smoking status, body mass index, history of diabetes, hypertension, angina, heart attack and stroke. There was a significant difference in adherence to the MeDi between HC and AD subjects (P < 0.001), and in adherence between HC and MCI subjects (P < 0.05). MeDi is associated with change in Mini-Mental State Examination score over an 18-month time period (P < 0.05) in HCs. We conclude that in this Australian cohort, AD and MCI participants had a lower adherence to the MeDi than HC participants.S Gardener, Y Gu, S R Rainey-Smith, J B Keogh, P M Clifton, S L Mathieson, K Taddei, A Mondal, V K Ward, N Scarmeas, M Barnes, K A Ellis, R Head, C L Masters, D Ames, S L Macaulay, C C Rowe, C Szoeke and R N Martins for the AIBL Research Grou

Scans for signatures of selection in Russian cattle breed genomes reveal new candidate genes for environmental adaptation and acclimation

Domestication and selective breeding has resulted in over 1000 extant cattle breeds. Many of these breeds do not excel in important traits but are adapted to local environments. These adaptations are a valuable source of genetic material for efforts to improve commercial breeds. As a step toward this goal we identified candidate regions to be under selection in genomes of nine Russian native cattle breeds adapted to survive in harsh climates. After comparing our data to other breeds of European and Asian origins we found known and novel candidate genes that could potentially be related to domestication, economically important traits and environmental adaptations in cattle. The Russian cattle breed genomes contained regions under putative selection with genes that may be related to adaptations to harsh environments (e.g., AQP5, RAD50, and RETREG1). We found genomic signatures of selective sweeps near key genes related to economically important traits, such as the milk production (e.g., DGAT1, ABCG2), growth (e.g., XKR4), and reproduction (e.g., CSF2). Our data point to candidate genes which should be included in future studies attempting to identify genes to improve the extant breeds and facilitate generation of commercial breeds that fit better into the environments of Russia and other countries with similar climates

Consumer behaviour in tourism: Concepts, influences and opportunities

Although consumer behaviour (CB) is one of the most researched areas in the field of tourism, few extensive reviews of the body of knowledge in this area exist. This review article examines what we argue are the key concepts, external influences and opportune research contexts in contemporary tourism CB research. Using a narrative review, we examine the CB literature published in three major tourism journals from 2000 to 2012. Of 519 articles identified and reviewed, 191 are included in this article. We examine the development of and scope for future research on nine key concepts, including decision-making, values, motivations, self-concept and personality, expectations, attitudes, perceptions, satisfaction, trust and loyalty. We then examine three important external influences on tourism behaviour, technology, Generation Y and the rise in concern over ethical consumption. Finally, we identify and discuss five research contexts that represent major areas for future scholarship: group and joint decision-making, under-researched segments, cross-cultural issues in emerging markets, emotions and consumer misbehaviour. Our examination of key research gaps is concluded by arguing that the hedonic and affective aspects of CB research in tourism must be brought to bear on the wider CB and marketing literature

Analysis of Rare, Exonic Variation amongst Subjects with Autism Spectrum Disorders and Population Controls

We report on results from whole-exome sequencing (WES) of 1,039 subjects diagnosed with autism spectrum disorders (ASD) and 870 controls selected from the NIMH repository to be of similar ancestry to cases. The WES data came from two centers using different methods to produce sequence and to call variants from it. Therefore, an initial goal was to ensure the distribution of rare variation was similar for data from different centers. This proved straightforward by filtering called variants by fraction of missing data, read depth, and balance of alternative to reference reads. Results were evaluated using seven samples sequenced at both centers and by results from the association study. Next we addressed how the data and/or results from the centers should be combined. Gene-based analyses of association was an obvious choice, but should statistics for association be combined across centers (meta-analysis) or should data be combined and then analyzed (mega-analysis)? Because of the nature of many gene-based tests, we showed by theory and simulations that mega-analysis has better power than meta-analysis. Finally, before analyzing the data for association, we explored the impact of population structure on rare variant analysis in these data. Like other recent studies, we found evidence that population structure can confound case-control studies by the clustering of rare variants in ancestry space; yet, unlike some recent studies, for these data we found that principal component-based analyses were sufficient to control for ancestry and produce test statistics with appropriate distributions. After using a variety of gene-based tests and both meta- and mega-analysis, we found no new risk genes for ASD in this sample. Our results suggest that standard gene-based tests will require much larger samples of cases and controls before being effective for gene discovery, even for a disorder like ASD. © 2013 Liu et al