Dynamics of a molecular glass former: Energy landscapes for diffusion in ortho-terphenyl.

Relaxation times and transport processes of many glass-forming supercooled liquids exhibit a super-Arrhenius temperature dependence. We examine this phenomenon by computer simulation of the Lewis-Wahnström model for ortho-terphenyl. We propose a microscopic definition for a single-molecule cage-breaking transition and show that, when correlation behaviour is taken into account, these rearrangements are sufficient to reproduce the correct translational diffusion constants over an intermediate temperature range in the supercooled regime. We show that super-Arrhenius behaviour can be attributed to increasing negative correlation in particle movement at lower temperatures and relate this to the cage-breaking description. Finally, we sample the potential energy landscape of the model and show that it displays hierarchical ordering. Substructures in the landscape, which may correspond to metabasins, have boundaries defined by cage-breaking transitions. The cage-breaking formulation provides a direct link between the potential energy landscape and macroscopic diffusion behaviour.This work was supported by the University of Cambridge through a CHSS studentship to S.P.N., and by the European Research Council.This is the author accepted manuscript. The final version is available at http://dx.doi.org/10.1063/1.4954324

Best practice guidance for the use of strategies improved retention in randomised trials developed from two consensus workshops

OBJECTIVE: To develop best practice guidance for the use of retention strategies in randomised clinical trials (RCTs). DESIGN: Consensus development workshops. SETTING: Two UK Clinical Trials Units. PARTICIPANTS: 66 statisticians, clinicians, RCT coordinators, research scientists, research assistants, and data managers associated with RCTs. METHODS: The consensus development workshops were based on the consensus development conference method used to develop best practice for treatment of medical conditions. Workshops commenced with a presentation of the evidence for: incentives, communication, questionnaire format, behavioural, case management and methodological retention strategies identified by a Cochrane review and associated qualitative study. Three simultaneous group discussions followed, focused on: a) how convinced the workshop participants were by the evidence for retention strategies, b) barriers to the use of effective retention strategies, c) types of RCT follow-up that retention strategies could be used for, and d) strategies for future research. Summaries of each group discussion were fed back to the workshop. Coded content for both workshops were compared for agreement and disagreement. Agreed consensus on best practice guidance for retention was identified. RESULTS: Workshop participants agreed best practice guidance for the use of small financial incentives to improve response to postal questionnaires in RCTs. Use of 2nd class post was thought to be adequate for postal communication with RCT participants. The most relevant validated questionnaire was considered best practice for collecting RCT data. Barriers identified for the use of effective retention strategies were: the small improvements seen in questionnaire response for the addition of monetary incentives, and perceptions among trialists that some communication strategies are outdated. Furthermore, there was resistance to change existing retention practices thought to be effective. Face to face and electronic follow-up technologies were identified as retention strategies for further research. CONCLUSIONS: We developed best practice guidance for the use of retention strategies in RCTs and identified potential barriers to the use of effective strategies. The extent of agreement on best practice is limited by the variability in the currently available evidence. This guidance will need updating as new retention strategies are developed and evaluated

Gut microbiota of Type 1 diabetes patients with good glycaemic control and high physical fitness is similar to people without diabetes: an observational study

Type 1 diabetes is the product of a complex interplay between genetic susceptibility and exposure to environmental factors. Existing bacterial profiling studies focus on people who are most at risk at the time of diagnosis; there are limited data on the gut microbiota of people with long-standing Type 1 diabetes. This study compared the gut microbiota of patients with Type 1 diabetes and good glycaemic control and high levels of physical-fitness with that of matched controls without diabetes.Ten males with Type 1 diabetes and ten matched controls without diabetes were recruited; groups were matched for gender, age, BMI, peak oxygen uptake (VO2max ), and exercise habits. Stool samples were analysed using next-generation sequencing of the 16S rRNA gene to obtain bacterial profiles from each individual. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was implemented to predict the functional content of the bacterial operational taxonomic units.Faecalibacterium sp., Roseburia sp. and Bacteroides sp. were typically the most abundant members of the community in both patients with Type 1 diabetes and controls, and were present in every sample in the cohort. Each bacterial profile was relatively individual and no significant difference was reported between the bacterial profiles or the Shannon diversity indices of Type 1 diabetes compared with controls. The functional profiles were more conserved and the Type 1 diabetes group were comparable with the control group.We show that both gut microbiota and resulting functional bacterial profiles from patients with long-standing Type 1 diabetes in good glycaemic control and high physical fitness levels are comparable with those of matched people without diabetes. This article is protected by copyright. All rights reserved

Euler-Heisenberg lagrangians and asymptotic analysis in 1+1 QED, part 1: Two-loop

We continue an effort to obtain information on the QED perturbation series at high loop orders, and particularly on the issue of large cancellations inside gauge invariant classes of graphs, using the example of the l - loop N - photon amplitudes in the limit of large photons numbers and low photon energies. As was previously shown, high-order information on these amplitudes can be obtained from a nonperturbative formula, due to Affleck et al., for the imaginary part of the QED effective lagrangian in a constant field. The procedure uses Borel analysis and leads, under some plausible assumptions, to a number of nontrivial predictions already at the three-loop level. Their direct verification would require a calculation of this `Euler-Heisenberg lagrangian' at three-loops, which seems presently out of reach. Motivated by previous work by Dunne and Krasnansky on Euler-Heisenberg lagrangians in various dimensions, in the present work we initiate a new line of attack on this problem by deriving and proving the analogous predictions in the simpler setting of 1+1 dimensional QED. In the first part of this series, we obtain a generalization of the formula of Affleck et al. to this case, and show that, for both Scalar and Spinor QED, it correctly predicts the leading asymptotic behaviour of the weak field expansion coefficients of the two loop Euler-Heisenberg lagrangians.Comment: 28 pages, 1 figures, final published version (minor modifications, refs. added

Partitioning of on-demand electron pairs

We demonstrate the high fidelity splitting of electron pairs emitted on demand from a dynamic quantum dot by an electronic beam splitter. The fidelity of pair splitting is inferred from the coincidence of arrival in two detector paths probed by a measurement of the partitioning noise. The emission characteristic of the on-demand electron source is tunable from electrons being partitioned equally and independently to electron pairs being split with a fidelity of 90%. For low beam splitter transmittance we further find evidence of pair bunching violating statistical expectations for independent fermions

Comparative Network Analysis of Preterm vs. Full-Term Infant-Mother Interactions

Several studies have reported that interactions of mothers with preterm infants show differential characteristics compared to that of mothers with full-term infants. Interaction of preterm dyads is often reported as less harmonious. However, observations and explanations concerning the underlying mechanisms are inconsistent. In this work 30 preterm and 42 full-term mother-infant dyads were observed at one year of age. Free play interactions were videotaped and coded using a micro-analytic coding system. The video records were coded at one second resolution and studied by a novel approach using network analysis tools. The advantage of our approach is that it reveals the patterns of behavioral transitions in the interactions. We found that the most frequent behavioral transitions are the same in the two groups. However, we have identified several high and lower frequency transitions which occur significantly more often in the preterm or full-term group. Our analysis also suggests that the variability of behavioral transitions is significantly higher in the preterm group. This higher variability is mostly resulted from the diversity of transitions involving non-harmonious behaviors. We have identified a maladaptive pattern in the maternal behavior in the preterm group, involving intrusiveness and disengagement. Application of the approach reported in this paper to longitudinal data could elucidate whether these maladaptive maternal behavioral changes place the infant at risk for later emotional, cognitive and behavioral disturbance

The development of accounting in UK universities:an oral history

This article reports on the development of the accounting discipline in universities in England and Scotland from the 1960s. Drawing on the oral history narratives of six distinguished accounting scholars who played a significant role in the discipline, this article documents (1) the initial influences on the teaching of accounting in English universities, (2) the different influences on the teaching of accounting in Scottish universities and (3) the influence of US universities and their scholars on the development of academic accounting in the United Kingdom. With a focus on the second wave of accounting professoriate who followed the London School of Economics (LSE) ‘Triumvirate’ of William Baxter, Harold Edey and David Solomons, this article provides first-hand insights into the shape and spread of university accounting education at a crucial stage of its development. This, in turn, develops an understanding of the contemporary academic accounting discipline in the United Kingdom.PostprintPeer reviewe

Exploring pig trade patterns to inform the design of risk-based disease surveillance and control strategies

An understanding of the patterns of animal contact networks provides essential information for the design of risk-based animal disease surveillance and control strategies. This study characterises pig movements throughout England and Wales between 2009 and 2013 with a view to characterising spatial and temporal patterns, network topology and trade communities. Data were extracted from the Animal and Plant Health Agency (APHA)’s RADAR (Rapid Analysis and Detection of Animal-related Risks) database, and analysed using descriptive and network approaches. A total of 61,937,855 pigs were moved through 872,493 movements of batches in England and Wales during the 5-year study period. Results show that the network exhibited scale-free and small-world topologies, indicating the potential for diseases to quickly spread within the pig industry. The findings also provide suggestions for how risk-based surveillance strategies could be optimised in the country by taking account of highly connected holdings, geographical regions and time periods with the greatest number of movements and pigs moved, as these are likely to be at higher risk for disease introduction. This study is also the first attempt to identify trade communities in the country, information which could be used to facilitate the pig trade and maintain disease-free status across the country in the event of an outbreak

A simulation study on the effects of neuronal ensemble properties on decoding algorithms for intracortical brain-machine interfaces

Background: Intracortical brain-machine interfaces (BMIs) harness movement information by sensing neuronal activities using chronic microelectrode implants to restore lost functions to patients with paralysis. However, neuronal signals often vary over time, even within a day, forcing one to rebuild a BMI every time they operate it. The term "rebuild" means overall procedures for operating a BMI, such as decoder selection, decoder training, and decoder testing. It gives rise to a practical issue of what decoder should be built for a given neuronal ensemble. This study aims to address it by exploring how decoders' performance varies with the neuronal properties. To extensively explore a range of neuronal properties, we conduct a simulation study. Methods: Focusing on movement direction, we examine several basic neuronal properties, including the signal-to-noise ratio of neurons, the proportion of well-tuned neurons, the uniformity of their preferred directions (PDs), and the non-stationarity of PDs. We investigate the performance of three popular BMI decoders: Kalman filter, optimal linear estimator, and population vector algorithm. Results: Our simulation results showed that decoding performance of all the decoders was affected more by the proportion of well-tuned neurons that their uniformity. Conclusions: Our study suggests a simulated scenario of how to choose a decoder for intracortical BMIs in various neuronal conditions

The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation

Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1. Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV c2-herpesvirus is most closely related to EBV BILF1 (15% amino acid sequence identity) but did not affect levels of surface MHC class I. An engineered mutant of BILF1 that was unable to activate G protein signaling pathways retained the ability to downregulate MHC class I, indicating that the immune-modulating and GPCR-signaling properties are two distinct functions of BILF1. These findings extend our understanding of the normal biology of an important human pathogen. The discovery of a third EBV lytic cycle gene that cooperates to interfere with MHC class I antigen processing underscores the importance of the need for EBV to be able to evade CD8+ T cell responses during the lytic replication cycle, at a time when such a large number of potential viral targets are expressed