Winnerless Competition in Neural Dynamics; Cluster Synchronisation of Coupled Oscillators

Systems of globally coupled phase oscillators can have robust attractors that are heteroclinic networks. Such a heteroclinic network is generated, where the phases cluster into three groups, within a specific regime of parameters when the phase oscillators are globally coupled using the function $g(\varphi) = -\sin(\varphi + \alpha) + r \sin(2\varphi + \beta)$. The resulting network switches between 30 partially synchronised states for a system of $N=5$ oscillators. Considering the states that are visited and the time spent at those states a spatio-temporal code can be generated for a given navigation around the network. We explore this phenomenon further by investigating the effect that noise has on the system, how this system can be used to generate a spatio-temporal code derived from specific inputs and how observation of a spatio-temporal code can be used to determine the inputs that were presented to the system to generate a given coding. We show that it is possible to find chaotic attractors for certain parameters and that it is possible to detail a genetic algorithm that can find the parameters required to generate a specific spatio-temporal code, even in the presence of noise. In closing we briefly explore the dynamics where $N>5$ and discuss this work in relation to winnerless competition.EPSR

Irus and his jovial crew : representations of beggars in Vincent Bourne and other eighteenth-century writers of Latin verse

Alastair Fowler has written, with reference to the time of Milton, of ‘Latin's special role in a bilingual culture’, and this was still true in the early eighteenth century. The education of the elite placed great emphasis on the art of writing Latin verse and modern, as well as ancient, writers of Latin continued to be widely read. Collections of Latin verse, by individual writers such as Vincent Bourne (c. 1694–1747) or by groups such as Westminster schoolboys or bachelors of Christ Church, Oxford, could run into multiple editions, and included poems on a wide range of contemporary topics, as well as reworkings of classical themes. This paper examines a number of eighteenth-century Latin poems dealing with beggars, several of which are here translated for the first time. Particular attention is paid to the way in which the Latin poems recycled well-worn tropes about beggary which were often at variance with the experience of real-life beggars, and to how the specificities of Latin verse might heighten negative representations of beggars in a genre which, as a manifestation of elite culture, appealed to the very class which was politically and legally responsible for controlling them

Spatiotemporal coding of inputs for a system of globally coupled phase oscillators

Copyright © 2008 The American Physical SocietyWe investigate the spatiotemporal coding of low amplitude inputs to a simple system of globally coupled phase oscillators with coupling function g(ϕ)=−sin(ϕ+α)+rsin(2ϕ+β) that has robust heteroclinic cycles (slow switching between cluster states). The inputs correspond to detuning of the oscillators. It was recently noted that globally coupled phase oscillators can encode their frequencies in the form of spatiotemporal codes of a sequence of cluster states [P. Ashwin, G. Orosz, J. Wordsworth, and S. Townley, SIAM J. Appl. Dyn. Syst. 6, 728 (2007)]. Concentrating on the case of N=5 oscillators we show in detail how the spatiotemporal coding can be used to resolve all of the information that relates the individual inputs to each other, providing that a long enough time series is considered. We investigate robustness to the addition of noise and find a remarkable stability, especially of the temporal coding, to the addition of noise even for noise of a comparable magnitude to the inputs

Differences in intracellular localisation of ANKH mutants that relate to mechanisms of calcium pyrophosphate deposition disease and craniometaphyseal dysplasia

ANKH mutations are associated with calcium pyrophosphate deposition disease and craniometaphyseal dysplasia. This study investigated the effects of these ANKH mutants on cellular localisation and associated biochemistry. We generated four ANKH overexpression-plasmids containing either calcium pyrophosphate deposition disease or craniometaphyseal dysplasia linked mutations: P5L, E490del and S375del, G389R. They were transfected into CH-8 articular chondrocytes and HEK293 cells. The ANKH mutants dynamic differential localisations were imaged and we investigated the interactions with the autophagy marker LC3. Extracellular inorganic pyrophosphate, mineralization, ENPP1 activity expression of ENPP1, TNAP and PIT-1 were measured. P5L delayed cell membrane localisation but once recruited into the membrane it increased extracellular inorganic pyrophosphate, mineralization, and ENPP1 activity. E490del remained mostly cytoplasmic, forming punctate co-localisations with LC3, increased mineralization, ENPP1 and ENPP1 activity with an initial but unsustained increase in TNAP and PIT-1. S375del trended to decrease extracellular inorganic pyrophosphate, increase mineralization. G389R delayed cell membrane localisation, trended to decrease extracellular inorganic pyrophosphate, increased mineralization and co-localised with LC3. Our results demonstrate a link between pathological localisation of ANKH mutants with different degrees in mineralization. Furthermore, mutant ANKH functions are related to synthesis of defective proteins, inorganic pyrophosphate transport, ENPP1 activity and expression of ENPP1, TNAP and PIT-1

'Hail England old England my country & home': Englishness and the Local in John Clare’s Writings

This article rethinks John Clare's connection to place, as well as the concepts of ‘place’ and ‘the local’ themselves. It argues that the localism of his work was enabled by potential alienation and displacement and was connected to a sense of wider national community. Clare's writings attempt to think of England in two related ways: as a political community brought together at times of threat, and as a community of taste brought together by a way of apprehending the natural world. His early patriotic verse is often strained and unconvincing, but poems such as ‘The Flitting’ present an idea of ‘native poesy’ that embodies the local and the national through careful description of the natural world. However, this idea was itself mediated through metropolitan attempts to reclaim the customs and literature of ‘merry England’. Thus Clare's localism and nationalism are shown to be ambivalent and uncanny

A national registry to assess the value of cardiovascular magnetic resonance imaging after primary percutaneous coronary intervention pathway activation:a feasibility cohort study

Background Cardiovascular magnetic resonance (CMR) is increasingly used in patients who activate the primary percutaneous coronary intervention (PPCI) pathway to assess heart function. It is uncertain whether having CMR influences patient management or the risk of major adverse cardiovascular events in these patients. Objective To determine whether or not it is feasible to set up a national registry, linking routinely collected data from hospital information systems (HISs), to investigate the role of CMR in patients who activate the PPCI pathway. Design A feasibility prospective cohort study. Setting Four 24/7 PPCI hospitals in England and Wales (two with and two without a dedicated CMR facility). Participants Patients who activated the PPCI pathway and underwent an emergency coronary angiogram. Interventions CMR either performed or not performed within 10 weeks of the index event. Main outcome measures A. Feasibility parameters – (1) patient consent implemented at all hospitals, (2) data extracted from more than one HIS and successfully linked for andgt; 90% of consented patients at all four hospitals, (3) HIS data successfully linked with Hospital Episode Statistics (HES) and Patient Episode Database Wales (PEDW) for andgt; 90% of consented patients at all four hospitals and (4) CMR requested and carried out for ≥ 10% of patients activating the PPCI pathway in CMR hospitals. B. Key drivers of cost-effectiveness for CMR (identified from simple cost-effectiveness models) in patients with (1) multivessel disease and (2) unobstructed coronary arteries. C. A change in clinical management arising from having CMR (defined using formal consensus and identified using HES follow-up data in the 12 months after the index event). Results A. (1) Consent was implemented (for all hospitals, consent rates were 59–74%) and 1670 participants were recruited. (2) Data submission was variable – clinical data available for ≥ 82% of patients across all hospitals, biochemistry and echocardiography (ECHO) data available for ≥ 98%, 34% and 87% of patients in three hospitals and medications data available for 97% of patients in one hospital. (3) HIS data were linked with hospital episode data for 99% of all consented patients. (4) At the two CMR hospitals, 14% and 20% of patients received CMR. B. In both (1) multivessel disease and (2) unobstructed coronary arteries, the difference in quality-adjusted life-years (QALYs) between CMR and no CMR [‘current’ comparator, stress ECHO and standard ECHO, respectively] was very small [0.0012, 95% confidence interval (CI) –0.0076 to 0.0093 and 0.0005, 95% CI –0.0050 to 0.0077, respectively]. The diagnostic accuracy of the ischaemia tests was the key driver of cost-effectiveness in sensitivity analyses for both patient subgroups. C. There was consensus that CMR leads to clinically important changes in management in five patient subgroups. Some changes in management were successfully identified in hospital episode data (e.g. new diagnoses/procedures, frequency of outpatient episodes related to cardiac events), others were not (e.g. changes in medications, new diagnostic tests). Conclusions A national registry is not currently feasible. Patients were consented successfully but conventional consent could not be implemented nationally. Linking HIS and hospital episode data was feasible but HIS data were not uniformly available. It is feasible to identify some, but not all, changes in management in the five patient subgroups using hospital episode data. The delay in obtaining hospital episode data influenced the relevance of some of our study objectives. Future work To test the feasibility of conducting the study using national data sets (e.g. HES, British Cardiovascular Intervention Society audit database, Diagnostic Imaging Dataset, Clinical Practice Research Datalink). Funding The National Institute for Health Research (NIHR) Health Services and Delivery Research programme. This study was designed and delivered in collaboration with the Clinical Trials and Evaluation Unit, a UK Clinical Research Collaboration-registered clinical trials unit that, as part of the Bristol Trials Centre, is in receipt of NIHR clinical trials unit support funding. </jats:sec

The ITGAV rs3738919 variant and susceptibility to rheumatoid arthritis in four Caucasian sample sets

INTRODUCTION: Angiogenesis is an important process in the development of destructive synovial pannus in rheumatoid arthritis (RA). The ITGAV +gene encodes a cell cycle-associated antigen, integrin alphanubeta 3, which plays a role in RA angiogenesis. Previously, two independent studies identified an association between the major allele of the ITGAV single-nucleotide polymorphism (SNP) rs3738919 and RA. We therefore tested this association in an independent study using New Zealand (NZ) and Oxford (UK) RA case control samples. METHODS: We compared genotype frequencies in 740 NZ Caucasian RA patients and 553 controls genotyped for rs3738919, using a polymerase chain reaction-restriction fragment length polymorphism assay. A TaqMan genotyping SNP assay was used to type 713 Caucasian RA patients and 515 control samples from Oxford for the rs3738919 variant. Association of rs3738919 with RA was tested in these two sample sets using the chi-square goodness-of-fit test. The Mantel-Haenszel test was used to perform a meta-analysis, combining the genetic results from four independent Caucasian case control cohorts, consisting of 3,527 cases and 4,126 controls. Haplotype analysis was also performed using SNPs rs3911238, rs10174098 and rs3738919 in the Wellcome Trust Case Control Consortium, NZ and Oxford case control samples. RESULTS: We found no evidence for association between ITGAV and RA in either the NZ or Oxford sample set (odds ratio [OR] = 0.88, P(allelic) = 0.11 and OR = 1.18, P(allelic) = 0.07, respectively). Inclusion of these data in a meta-analysis (random effects) of four independent cohorts (3,527 cases and 4,126 controls) weakens support for the hypothesis that rs3738919 plays a role in the development of RA (OR(combined) = 0.92, 95% confidence interval 0.80 to 1.07; P = 0.29). No consistent haplotype associations were evident. CONCLUSIONS: Association of ITGAV SNP rs7378919 with RA was not replicated in NZ or Oxford case control sample sets. Meta-analysis of these and previously published data lends limited support for a role for the ITGAV in RA in Caucasians of European ancestry

Association of Variants at 1q32 and STAT3 with Ankylosing Spondylitis Suggests Genetic Overlap with Crohn's Disease

Ankylosing spondylitis (AS) is a common inflammatory arthritic condition. Overt inflammatory bowel disease (IBD) occurs in about 10% of AS patients, and in addition 70% of AS cases may have subclinical terminal ileitis. Spondyloarthritis is also common in IBD patients. We therefore tested Crohn's disease susceptibility genes for association with AS, aiming to identify pleiotropic genetic associations with both diseases. Genotyping was carried out using Sequenom and Applied Biosystems TaqMan and OpenArray technologies on 53 markers selected from 30 Crohn's disease associated genomic regions. We tested genotypes in a population of unrelated individual cases (n = 2,773) and controls (n = 2,215) of white European ancestry for association with AS. Statistical analysis was carried out using a Cochran-Armitage test for trend in PLINK. Strong association was detected at chr1q32 near KIF21B (rs11584383, P = 1.6×10−10, odds ratio (OR) = 0.74, 95% CI:0.68–0.82). Association with disease was also detected for 2 variants within STAT3 (rs6503695, P = 4.6×10−4. OR = 0.86 (95% CI:0.79–0.93); rs744166, P = 2.6×10−5, OR = 0.84 (95% CI:0.77–0.91)). Association was confirmed for IL23R (rs11465804, P = 1.2×10−5, OR = 0.65 (95% CI:0.54–0.79)), and further associations were detected for IL12B (rs10045431, P = 5.2×10−5, OR = 0.83 (95% CI:0.76–0.91)), CDKAL1 (rs6908425, P = 1.1×10−4, OR = 0.82 (95% CI:0.74–0.91)), LRRK2/MUC19 (rs11175593, P = 9.9×10−5, OR = 1.92 (95% CI: 1.38–2.67)), and chr13q14 (rs3764147, P = 5.9×10−4, OR = 1.19 (95% CI: 1.08–1.31)). Excluding cases with clinical IBD did not significantly affect these findings. This study identifies chr1q32 and STAT3 as ankylosing spondylitis susceptibility loci. It also further confirms association for IL23R and detects suggestive association with another 4 loci. STAT3 is a key signaling molecule within the Th17 lymphocyte differentiation pathway and further enhances the case for a major role of this T-lymphocyte subset in ankylosing spondylitis. Finally these findings suggest common aetiopathogenic pathways for AS and Crohn's disease and further highlight the involvement of common risk variants across multiple diseases