Amplification and next generation sequencing of near full-length human enteroviruses for identification and characterisation from clinical samples

© 2018, The Author(s). More than 100 different enterovirus (EV) genotypes infect humans and contribute to substantial morbidity. However, current methods for characterisation of full-length genomes are based on Sanger sequencing of short genomic regions, which are labour-intensive and do not enable comprehensive characterisation of viral populations. Here, we describe a simple and sensitive protocol for the amplification and sequencing of near full-length genomes of human EV species using next generation sequencing. EV genomes were amplified from 89% of samples tested, with Ct values ranging between 15.7 and 39.3. These samples included 7 EV-A genotypes (CVA2, 5–7, 10, 16 and EV71), 19 EV-B genotypes (CVA9, CVB1-6, ECHO3, 4, 6, 7, 9, 11, 16, 18, 25, 29, 30, and EV69), 3 EV-C genotypes (CVA19 and PV2, 3) and 1 EV-D genotype (EV70). We characterised 70 EVs from 58 clinical stool samples and eight reference strains, with a minimum of 100X depth. We found evidence of co-infection in four clinical specimens, each containing two distinct EV genotypes (CVB3/ECHO7, CVB3/ECHO18 and ECHO9/30). Characterisation of the complete genome provided conclusive genotyping of EVs, which can be applied to investigate the intra-host virus evolution of EVs, and allows further identification and investigation of EV outbreaks

The sedimentology of river confluences

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Channel confluences are key nodes within large river networks, and yet surprisingly little is known about their spatial and temporal evolution. Moreover, because confluences are associated with vertical scour that typically extends to several times the mean channel depth, the deposits associated with such scours should have a high preservation potential within the rock record. Paradoxically, such scours are rarely observed, and their preservation and sedimentological interpretation are poorly understood. The present study details results from a physically‐based morphodynamic model that is applied to simulate the evolution and alluvial architecture of large river junctions. Boundary conditions within the model were defined to approximate the junction of the Ganges and Jamuna rivers, Bangladesh, with the model output being supplemented by geophysical datasets collected at this junction. The numerical simulations reveal several distinct styles of sedimentary fill that are related to the morphodynamic behaviour of bars, confluence scour downstream of braid bars, bend scour and major junction scour. Comparison with existing, largely qualitative, conceptual models reveals that none of these can be applied simply, although elements of each are evident in the deposits generated by the numerical simulation and observed in the geophysical data. The characteristics of the simulated scour deposits are found to vary according to the degree of reworking caused by channel migration, a factor not considered adequately in current conceptual models of confluence sedimentology. The alluvial architecture of major junction scours is thus characterized by the prevalence of erosion surfaces in conjunction with the thickest depositional sets. Confluence scour downstream of braid bar and bend scour sites may preserve some large individual sets, but these locations are typically characterized by lower average set thickness compared to major junction scour and by a lack of large‐scale erosional surfaces. Areas of deposition not related to any of the specific scour types highlighted above record the thinnest depositional sets. This variety in the alluvial architecture of scours may go some way towards explaining the paradox of ancient junction scours, that while abundant large scours are likely in the rock record, they have been reported rarely. The present results outline the likely range of confluence sedimentology and will serve as a new tool for recognizing and interpreting these deposits in the ancient fluvial record.This work was funded by a UK Natural Environment Research Council award to Sambrook Smith (NE/I023228/1), Bull (NE/I023864/1) and Nicholas (NE/I023120/1)

The planform mobility of river channel confluences: Insights from analysis of remotely sensed imagery

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.River channel confluences are widely acknowledged as important geomorphological nodes that control the downstream routing of water and sediment, and which are locations for the preservation of thick fluvial deposits overlying a basal scour. Despite their importance, there has been little study of the stratigraphic characteristics of river junctions, or the role of confluence morphodynamics in influencing stratigraphic character and preservation potential. As a result, although it is known that confluences can migrate through time, models of confluence geomorphology and sedimentology are usually presented from the perspective that the confluence remains at a fixed location. This is problematic for a number of reasons, not least of which is the continuing debate over whether it is possible to discriminate between scour that has been generated by autocyclic processes (such as confluence scour) and that driven by allocyclic controls (such as sea-level change). This paper investigates the spatial mobility of river confluences by using the 40-year record of Landsat Imagery to elucidate the styles, rates of change and areal extent over which large river confluence scours may migrate. On the basis of these observations, a new classification of the types of confluence scour is proposed and applied to the Amazon and Ganges-Brahmaputra-Meghna (GBM) basins. This analysis demonstrates that the drivers of confluence mobility are broadly the same as those that drive channel change more generally. Thus in the GBM basin, a high sediment supply, large variability in monsoonal driven discharge and easily erodible bank materials result in a catchment where over 80% of large confluences are mobile over this 40-year window; conversely this figure is < 40% for the Amazon basin. These results highlight that: i) the potential areal extent of confluence scours is much greater than previously assumed, with the location of some confluences on the Jamuna (Brahmaputra) River migrating over a distance of 20 times the tributary channel width; ii) extensive migration in the confluence location is more common than currently assumed, and iii) confluence mobility is often tied to the lithological and hydrological characteristics of the drainage basins that determine sediment yield.This work was funded by NERC grant NE/I023228/1 to Sambrook Smith, Bull, Nicholas and Best

Building collaboration in multi-agent systems using reinforcement learning

© Springer Nature Switzerland AG 2018. This paper presents a proof-of concept study for demonstrating the viability of building collaboration among multiple agents through standard Q learning algorithm embedded in particle swarm optimisation. Collaboration is formulated to be achieved among the agents via competition, where the agents are expected to balance their action in such a way that none of them drifts away of the team and none intervene any fellow neighbours territory, either. Particles are devised with Q learning for self training to learn how to act as members of a swarm and how to produce collaborative/collective behaviours. The produced experimental results are supportive to the proposed idea suggesting that a substantive collaboration can be build via proposed learning algorithm

ADVANCE-TBI study protocol: traumatic brain injury outcomes in UK military personnel serving in Afghanistan between 2003 and 2014 - a longitudinal cohort study

INTRODUCTION: Outcomes of traumatic brain injury (TBI) are highly variable, with cognitive and psychiatric problems often present in survivors, including an increased dementia risk in the long term. Military personnel are at an increased occupational risk of TBI, with high rates of complex polytrauma including TBI characterising the UK campaign in Afghanistan. The ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE)-TBI substudy will describe the patterns, associations and long-term outcomes of TBI in the established ADVANCE cohort. METHODS AND ANALYSIS: The ADVANCE cohort comprises 579 military personnel exposed to major battlefield trauma requiring medical evacuation, and 566 matched military personnel without major trauma. TBI exposure has been captured at baseline using a standardised interview and registry data, and will be refined at first follow-up visit with the Ohio State Method TBI interview (a National Institute of Neurological Disorders and Stroke TBI common data element). Participants will undergo blood sampling, MRI and detailed neuropsychological assessment longitudinally as part of their follow-up visits every 3-5 years over a 20-year period. Biomarkers of injury, neuroinflammation and degeneration will be quantified in blood, and polygenic risk scores calculated for neurodegeneration. Age-matched healthy volunteers will be recruited as controls for MRI analyses. We will describe TBI exposure across the cohort, and consider any relationship with advanced biomarkers of injury and clinical outcomes including cognitive performance, neuropsychiatric symptom burden and function. The influence of genotype will be assessed. This research will explore the relationship between military head injury exposure and long-term outcomes, providing insights into underlying disease mechanisms and informing prevention interventions. ETHICS AND DISSEMINATION: The ADVANCE-TBI substudy has received a favourable opinion from the Ministry of Defence Research Ethics Committee (ref: 2126/MODREC/22). Findings will be disseminated via publications in peer-reviewed journals and presentations at conferences

Prevalence, prenatal screening and neonatal features in children with Down syndrome: a registry-based national study

BACKGROUND: Down syndrome (DS) is one of the most common chromosomal abnormalities among newborns. In recent years advances in perinatal and neonatal care have improved chance of survival for the children with DS. The objective of this Registry-Based study was to get more accurate data of DS prevalence with evaluation of antenatal screening, neonatal and maternal features among total births in Croatia from 2009 to 2012. ----- METHODS: We used retrospectively collected data for DS newborns from the medical birth database and perinatal mortality database for the period of 2009-2012. Differences between DS and the referent population for each year in quantitative measures were assessed with the independent t-test. Other differences in nominal and categorical values were analyzed with the chi-square test. ----- RESULTS: The total prevalence for DS in the period of 2009-2012 was 7.01 per 10,000 births, while the live-birth prevalence was 6.49 per 10,000 births. The significant differences (p < 0.05) between the DS and reference populations for each year were noticed for birth weight and length, gestational age, mother age, Apgar score of ≥6 after 5 min and breastfeeding. Among newborns with DS, there were 64 (53.33 %) males and 56 (46.67 %) females versus 88,587 (51.76 %) males and 82,553 (48.23 %) females in the reference population. In the DS group compared to the reference population the mean birth weight was 2845 grams versus 3467 grams in males and 2834 grams versus 3329 grams in females, respectively, with a mean birth length of 47 cm versus 50 cm for both genders. The mean gestational age of the DS births was 37 weeks and the mean age of the mothers was 32.6 years, versus 39 weeks and 29.1 years, respectively, in the reference population. Only 68.3 % of children with DS were breastfed from birth, compared with 94.72 % of children in the reference population. ----- CONCLUSIONS: The significant differences for neonatal and maternal features between DS and the referent population were found similar to other studies. The total prevalence of DS in Croatia in the period of 2009-2012 was lower than the previously estimated prevalence based on EUROCAT data. The establishment of a new national registry of congenital malformations covering 99 % of all births in Croatia is necessary to improve the health and prosperity of children, adolescents and adults with DS in Croatia

Metrics and textural features of MRI diffusion to improve classification of pediatric posterior fossa tumors

BACKGROUND AND PURPOSE: Qualitative radiologic MR imaging review affords limited differentiation among types of pediatric posterior fossa brain tumors and cannot detect histologic or molecular subtypes, which could help to stratify treatment. This study aimed to improve current posterior fossa discrimination of histologic tumor type by using support vector machine classifiers on quantitative MR imaging features. MATERIALS AND METHODS: This retrospective study included preoperative MRI in 40 children with posterior fossa tumors (17 medulloblastomas, 16 pilocytic astrocytomas, and 7 ependymomas). Shape, histogram, and textural features were computed from contrast-enhanced T2WI and T1WI and diffusivity (ADC) maps. Combinations of features were used to train tumor-type-specific classifiers for medulloblastoma, pilocytic astrocytoma, and ependymoma types in separation and as a joint posterior fossa classifier. A tumor-subtype classifier was also produced for classic medulloblastoma. The performance of different classifiers was assessed and compared by using randomly selected subsets of training and test data. RESULTS: ADC histogram features (25th and 75th percentiles and skewness) yielded the best classification of tumor type (on average >95.8% of medulloblastomas, >96.9% of pilocytic astrocytomas, and >94.3% of ependymomas by using 8 training samples). The resulting joint posterior fossa classifier correctly assigned >91.4% of the posterior fossa tumors. For subtype classification, 89.4% of classic medulloblastomas were correctly classified on the basis of ADC texture features extracted from the Gray-Level Co-Occurence Matrix. CONCLUSIONS: Support vector machine–based classifiers using ADC histogram features yielded very good discrimination among pediatric posterior fossa tumor types, and ADC textural features show promise for further subtype discrimination. These findings suggest an added diagnostic value of quantitative feature analysis of diffusion MR imaging in pediatric neuro-oncology

Exploring Emotion Representation to Support Dialogue in Police Training on Child Interviewing

Police officers when dealing with interviewing children have to cope with a complex set of emotions from a vulnerable witness. Triggers for recognising those emotions and how to build rapport are often the basis of learning exercises. However, current training pulls together the full complexity of emotions during role-playing which can be over-whelming and reduce appropriate learning focus. Interestingly a serious game’s interface can provide valuable training not because it represents full complex, multimedia interactions but because it can restrict emotional complexity and increase focus during the interactions on key factors for emotional recognition. The focus of this paper is to report on a specific aspect that was explored during the development of a serious game that aims to address the current police-training needs of child interviewing techniques, where the recognition of emotions plays an important role in understanding how to build rapport with children. The review of literature reveals that emotion recognition, through facial expressions, can contribute significantly to the perceived quality of communication. For this study an ‘emotions map’ was created and tested by 41 participants to be used in the development of a targeted interface design to support the different levels of emotion recognition. The emotions identified were validated with a 70 % agreement across experts and non-experts highlighting the innate role of emotion recognition. A discussion is made around the role of emotions and game-based systems to support their identification for work-based training. As part of the graphical development of the Child Interview Stimulator (CIS) we examined different levels of emotional recognition that can be used to support the in-game graphical representation of a child’s response during a police interview

X inactivation in females with X-linked Charcot-Marie-Tooth disease.

X-linked Charcot-Marie-Tooth disease (CMT1X) is the second most common inherited neuropathy, caused by mutations in gap junction beta-1 (GJB1). Males have a uniformly moderately severe phenotype while females have a variable phenotype, suggested to be due to X inactivation. We aimed to assess X inactivation pattern in females with CMT1X and correlate this with phenotype using the CMT examination score to determine whether the X inactivation pattern accounted for the variable phenotype in females with CMT1X. We determined X inactivation pattern in 67 females with CMT1X and 24 controls using the androgen receptor assay. We were able to determine which X chromosome carried the GJB1 mutation in 30 females. There was no difference in X inactivation pattern between patients and controls. In addition, there was no correlation between X inactivation pattern in blood and phenotype. A possible explanation for these findings is that the X inactivation pattern in Schwann cells rather than in blood may explain the variable phenotype in females with CMT1X