360 research outputs found

    Lamb Street, Coventry, West Midlands : post-excavation assessment report

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    Between December 2018 and March 2019, Salford Archaeology carried out an archaeological excavation on Lamb Street, within the historic core of Coventry city centre (centred on NGR SP 33270 79350). This uncovered significant remains deriving from the medieval and post-medieval periods, together with a considerable assemblage of artefacts. Some rare evidence for Roman activity in Coventry was also recovered from the excavation. Following completion of the fieldwork, an assessment was made of the project archive, with a view todefining the costs of completing an appropriate programme of post-excavation analysis and publication. This assessment examined the results of the excavationand assessed the potential for further analysis of each category of data with regard to the project’s research aims, in accordance with professional guidelines laid out by Historic England

    Molecular dynamics simulations of mechanical failure in polymorphic arrangements of amyloid fibrils containing structural defects

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    We examine how the different steric packing arrangements found in amyloid fibril polymorphs can modulate their mechanical properties using steered molecular dynamics simulations. Our calculations demonstrate that for fibrils containing structural defects, their ability to resist force in a particular direction can be dominated by both the number and molecular details of the defects that are present. The simulations thereby suggest a hierarchy of factors that govern the mechanical resilience of fibrils, and illustrate the general principles that must be considered when quantifying the mechanical properties of amyloid fibres containing defects

    Genomic Diversity among Actinomyces naeslundii strains and closely related species.

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    The aim of this study was to investigate and clarify the ambiguous taxonomy of Actinomyces naeslundii and its closely related species using state-of-the-art high-throughput sequencing techniques, and, furthermore, to determine whether sub-clusters identified within Actinomyces oris and Actinomyces naeslundii in a previous study by multi locus sequence typing (MLST) using concatenation of seven housekeeping genes should either be classified as subspecies or distinct species. The strains in this study were broadly classified under Actinomyces naeslundii group as A. naeslundii genospecies I and genospecies II. Based on MLST data analysis, these were further classified as A. oris and A. naeslundii. The whole genome sequencing of selected strains of A. oris (n = 17) and A. naeslundii (n = 19) was carried out using Illumina Genome Analyzer IIxe and Roche 454 allowing paired-end and single-reads sequencing, respectively. The sequences obtained were aligned using CLC Genomic workbench version 5.1 and annotated using RAST (Rapid Annotation using Subsystem Technology) release version 59 accessible online. Additionally, genomes of seven publicly available strains of Actinomyces (k20, MG1, c505, OT175, OT171, OT170, and A. johnsonii) were also included. Comparative genomic analysis (CGA) using Mauve, Progressive Mauve, gene-by-gene, Core, and Pan Genome, and finally Digital DNA-DNA homology (DDH) analysis was carried out. DDH values were obtained using in silico genome–genome comparison. Evolutionary analysis using ClonalFrame was also undertaken. The mutation and recombination events were compared using chi-square test among A. oris and A. naeslundii isolates (analysis methods are not included in the study). CGA results were consistent with previous traditional classification using MLST. It was found that strains of Actinomyces k20, MG1, c505, and OT175 clustered in A. oris group of isolates, while OT171, OT170, and A. johnsonii appeared as separate branches. Similar clustering to MLST was observed for other isolates. The mutation and recombination events were significantly higher in A. oris than A. naeslundii, highlighting the diversity of A. oris strains in the oral cavity. These findings suggest that A. oris forms six distinct groups, whereas A. naeslundii forms three. The correct designation of isolates will help in the identification of clinical Actinomyces isolates found in dental plaque. Easily accessible online genomic sequence data will also accelerate the investigation of the biochemical characterisation and pathogenesis of this important group of micro-organisms

    Prospective subgroup analyses of the randomized MCL-002 (SPRINT) study: lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma.

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    In the mantle cell lymphoma (MCL)-002 study, lenalidomide demonstrated significantly improved median progression-free survival (PFS) compared with investigator's choice (IC) in patients with relapsed/refractory MCL. Here we present the long-term follow-up data and results of preplanned subgroup exploratory analyses from MCL-002 to evaluate the potential impact of demographic factors, baseline clinical characteristics and prior therapies on PFS. In MCL-002, patients with relapsed/refractory MCL were randomized 2:1 to receive lenalidomide (25 mg/day orally on days 1-21; 28-day cycles) or single-agent IC therapy (rituximab, gemcitabine, fludarabine, chlorambucil or cytarabine). The intent-to-treat population comprised 254 patients (lenalidomide, n = 170; IC, n = 84). Subgroup analyses of PFS favoured lenalidomide over IC across most characteristics, including risk factors, such as high MCL International Prognostic Index score, age ≥65 years, high lactate dehydrogenase (LDH), stage III/IV disease, high tumour burden, and refractoriness to last prior therapy. By multivariate Cox regression analysis, factors associated with significantly longer PFS (other than lenalidomide treatment) included normal LDH levels (P < 0·001), nonbulky disease (P = 0·045), <3 prior antilymphoma treatments (P = 0·005), and ≥6 months since last prior treatment (P = 0·032). Overall, lenalidomide improved PFS versus single-agent IC therapy in patients with relapsed/refractory MCL, irrespective of many demographic factors, disease characteristics and prior treatment history

    Dynamics of direct inter-pack encounters in endangered African wild dogs

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    Aggressive encounters may have important life history consequences due to the potential for injury and death, disease transmission, dispersal opportunities or exclusion from key areas of the home range. Despite this, little is known of their detailed dynamics, mainly due to the difficulties of directly observing encounters in detail. Here, we describe detailed spatial dynamics of inter-pack encounters in African wild dogs (Lycaon pictus), using data from custom-built high-resolution GPS collars in 11 free-ranging packs. On average, each pack encountered another pack approximately every 7 weeks and met each neighbour twice each year. Surprisingly, intruders were more likely to win encounters (winning 78.6% of encounters by remaining closer to the site in the short term). However, intruders did tend to move farther than residents toward their own range core in the short-term (1 h) post-encounter, and if this were used to indicate losing an encounter, then the majority (73.3%) of encounters were won by residents. Surprisingly, relative pack size had little effect on encounter outcome, and injuries were rare (<15% of encounters). These results highlight the difficulty of remotely scoring encounters involving mobile participants away from static defendable food resources. Although inter-pack range overlap was reduced following an encounter, encounter outcome did not seem to drive this, as both packs shifted their ranges post-encounter. Our results indicate that inter-pack encounters may be lower risk than previously suggested and do not appear to influence long-term movement and ranging

    Developing assessments for child exposure to intimate partner violence in Switzerland – A study of medico-legal reports in clinical settings

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    Purpose: Evidence to inform assessment of needs of children exposed to intimate partner violence (IPV) in health settings is limited. A Swiss hospital-based medico-legal consultation for adult victims of violence also detects children’s exposure to IPV and refers cases to the Pediatrics Child Abuse and Neglect Team. Based on a conceptual ecological framework, this study examined the nature and circumstances of children’s exposure to IPV described in accounts collected by nurses in consultations with adult IPV victims. Methods: From 2011-2014, 438 parents (88% female) of 668 children aged 0 to 18 sought medico-legal care from the Violence Medical Unit in Lausanne Switzerland, following assaults by intimate partners (85% male). As part of the consultation, nurses completed a semi-structured questionnaire with victimized parents, recording their answers in the patient file. Victims’ statements about the abuse, their personal, family and social contexts, and their children’s exposure to IPV were analyzed. Descriptive statistics and qualitative thematic content analyses were conducted to identify, from the victimized parents’ accounts, elements useful to understand the nature and circumstances of children’s exposure and involvement during violent events. Results: Parent statements on specific violent events described children being present in 75% of the cases. Children were said to be exposed to, and responded to, severe physical violence, serious threats and insults, in the context of repeated assaults and coercive control. Families, especially mothers, were often coping with additional socio-economic vulnerabilities. Conclusions: Implications for further developing assessments of children living with IPV, especially in health settings were identified

    Predicting Landscape-Genetic Consequences of Habitat Loss, Fragmentation and Mobility for Multiple Species of Woodland Birds

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    Inference concerning the impact of habitat fragmentation on dispersal and gene flow is a key theme in landscape genetics. Recently, the ability of established approaches to identify reliably the differential effects of landscape structure (e.g. land-cover composition, remnant vegetation configuration and extent) on the mobility of organisms has been questioned. More explicit methods of predicting and testing for such effects must move beyond post hoc explanations for single landscapes and species. Here, we document a process for making a priori predictions, using existing spatial and ecological data and expert opinion, of the effects of landscape structure on genetic structure of multiple species across replicated landscape blocks. We compare the results of two common methods for estimating the influence of landscape structure on effective distance: least-cost path analysis and isolation-by-resistance. We present a series of alternative models of genetic connectivity in the study area, represented by different landscape resistance surfaces for calculating effective distance, and identify appropriate null models. The process is applied to ten species of sympatric woodland-dependant birds. For each species, we rank a priori the expectation of fit of genetic response to the models according to the expected response of birds to loss of structural connectivity and landscape-scale tree-cover. These rankings (our hypotheses) are presented for testing with empirical genetic data in a subsequent contribution. We propose that this replicated landscape, multi-species approach offers a robust method for identifying the likely effects of landscape fragmentation on dispersal

    Scalable Rules for Coherent Group Motion in a Gregarious Vertebrate

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    Individuals of gregarious species that initiate collective movement require mechanisms of cohesion in order to maintain advantages of group living. One fundamental question in the study of collective movement is what individual rules are employed when making movement decisions. Previous studies have revealed that group movements often depend on social interactions among individual members and specifically that collective decisions to move often follow a quorum-like response. However, these studies either did not quantify the response function at the individual scale (but rather tested hypotheses based on group-level behaviours), or they used a single group size and did not demonstrate which social stimuli influence the individual decision-making process. One challenge in the study of collective movement has been to discriminate between a common response to an external stimulus and the synchronization of behaviours resulting from social interactions. Here we discriminate between these two mechanisms by triggering the departure of one trained Merino sheep (Ovis aries) from groups containing one, three, five and seven naïve individuals. Each individual was thus exposed to various combinations of already-departed and non-departed individuals, depending on its rank of departure. To investigate which individual mechanisms are involved in maintaining group cohesion under conditions of leadership, we quantified the temporal dynamic of response at the individual scale. We found that individuals' decisions to move do not follow a quorum response but rather follow a rule based on a double mimetic effect: attraction to already-departed individuals and attraction to non-departed individuals. This rule is shown to be in agreement with an adaptive strategy that is inherently scalable as a function of group size
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