Publications by authors named "Sam Clark"

Here we confirm, using genome-scale RNA fragments in assembly competition assays, that multiple sub-sites (Packaging Signals, PSs) across the 5' two-thirds of the gRNA of Satellite Tobacco Necrosis Virus-1 make sequence-specific contacts to the viral CPs helping to nucleate formation of its T = 1 virus-like particle (VLP). These contacts explain why natural virions only package their positive-sense genomes. Asymmetric cryo-EM reconstructions of these VLPs suggest that interactions occur between amino acid residues in the N-terminal ends of the CP subunits and the gRNA PS loop sequences.

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Background: The effects of environmental disturbances on livestock are often observed indirectly through the variability patterns of repeated performance records over time. Sheep are frequently exposed to diverse extensive environments but currently lack appropriate measures of resilience (or sensitivity) towards environmental disturbance. In this study, random regression models were used to analyse repeated records of the fibre diameter of wool taken along the wool staple (bundle of wool fibres) to investigate how the genetic and environmental variance of fibre diameter changes with different growing environments.

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Article Synopsis
  • * There is a global disparity in awareness and access to effective treatment for HLH, with inconsistent terminology and classification criteria complicating diagnosis.
  • * The HiHASC group created comprehensive guidelines aimed at helping healthcare teams recognize and manage HLH in adults, emphasizing early diagnosis and identifying the cause using accessible tests while also acknowledging the need for specialized evaluations.
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Background: There can be variation between animals in how stable their genetic merit is across different environments due to genotype-by-environment (G×E) interactions. This variation could be used in breeding programs to select robust genotypes that combine high overall performance with stable genetic ranking across environments. There have been few attempts to validate breeding values for robustness in livestock, although this is a necessary step towards their implementation in selection decisions.

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Background: Commercial poultry production systems follow a pyramidal structure with a nucleus of purebred animals under controlled conditions at the top and crossbred animals under commercial production conditions at the bottom. Genetic correlations between the same phenotypes on nucleus and production animals can therefore be influenced by differences both in purebred-crossbred genotypes and in genotype-by-environment interactions across the two environments, known as macro-genetic environmental sensitivity (GES). Within each environment, genotype-by-environment interactions can also occur due to so-called micro-GES.

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While much attention and emphasis have been given to the role and value of advisory groups in social science research, less has been published on the experiences of those involved in such collaborative efforts. This article reflects on the experiences of academics, collaborators and self-advocacy experts who formed an advisory group for a research project focused on people with learning disabilities' experiences of renting their own homes. Our paper describes the collaboration, how it changed because of Covid and because of changing relationships, and what worked well and what was challenging.

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The reaction norm analysis of stability can be enhanced by partitioning the contribution of different types of G × E to the variation in slope. The slope of regression in a reaction norm model, where the performance of a genotype is regressed over an environmental covariable, is often used as a measure of stability of genotype performance. This method could be developed further by partitioning variation in the slope of regression into the two sources of genotype-by-environment interaction (G × E) which cause it: scale-type G × E (heterogeneity of variance) and rank-type G × E (heterogeneity of correlation).

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Understanding the effects of repeated testing on behaviour is essential for behavioural tests that are re-applied to the same individuals for research and welfare assessment purposes. Assessing the repeatability of behaviour can also help us understand the influence of persistent traits transient states on animal responses during testing. This study examined the repeatability of behavioural responses in an attention bias test developed for sheep as a measure of affective state.

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Many single-stranded, positive-sense RNA viruses regulate assembly of their infectious virions by forming multiple, cognate coat protein (CP)-genome contacts at sites termed Packaging Signals (PSs). We have determined the secondary structures of the bacteriophage MS2 ssRNA genome (gRNA) frozen in defined states using constraints from X-ray synchrotron footprinting (XRF). Comparison of the footprints from phage and transcript confirms the presence of multiple PSs in contact with CP dimers in the former.

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Background: Selection of livestock based on their robustness or sensitivity to environmental variation could help improve the efficiency of production systems, particularly in the light of climate change. Genetic variation in robustness arises from genotype-by-environment (G × E) interactions, with genotypes performing differently when animals are raised in contrasted environments. Understanding the nature of this genetic variation is essential to implement strategies to improve robustness.

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The roles of RNA sequence/structure motifs, Packaging Signals (PSs), for regulating assembly of an HBV genome transcript have been investigated in an efficient in vitro assay containing only core protein (Cp) and RNA. Variants of three conserved PSs, within the genome of a strain not used previously, preventing correct presentation of a Cp-recognition loop motif are differentially deleterious for assembly of nucleocapsid-like particles (NCPs). Cryo-electron microscopy reconstruction of the T = 4 NCPs formed with the wild-type gRNA transcript, reveal that the interior of the Cp shell is in contact with lower resolution density, potentially encompassing the arginine-rich protein domains and gRNA.

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Information on body weight and average daily gain (ADG) of growing animals is key not only to monitoring performance, but also for use in genetic evaluations in the pursuit of achieving sustainable genetic gain. Accurate calculation of ADG, however, requires serial measures of body weight over at least 70 days. This can be resource intensive and thus alternative approaches to predicting individual animal ADG warrant investigation.

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Background: We sought to define the prevalence and nature of patient-reported drug allergies, determine their impact on prescribing, and explore drug allergy knowledge and attitudes amongst anaesthetists.

Methods: We performed a prospective cross-sectional study in 213 UK hospitals in 2018. Elective surgical patients were interviewed, with a detailed allergy history taken in those self-reporting drug allergy.

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Viruses are ubiquitous pathogens of global impact. Prompted by the hypothesis that their earliest progenitors recruited host proteins for virion formation, we have used stringent laboratory evolution to convert a bacterial enzyme that lacks affinity for nucleic acids into an artificial nucleocapsid that efficiently packages and protects multiple copies of its own encoding messenger RNA. Revealing remarkable convergence on the molecular hallmarks of natural viruses, the accompanying changes reorganized the protein building blocks into an interlaced 240-subunit icosahedral capsid that is impermeable to nucleases, and emergence of a robust RNA stem-loop packaging cassette ensured high encapsidation yields and specificity.

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Our understanding of the activity of cationic antimicrobial peptides (AMPs) has focused on well-characterized natural sequences, or limited sets of synthetic peptides designed de novo. We have undertaken a comprehensive investigation of the underlying primary structural features that give rise to the development of activity in AMPs. We consider a complete set of all possible peptides, up to 7 residues long, composed of positively charged arginine (R) and / or hydrophobic tryptophan (W), two features most commonly associated with activity.

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Contemporary society has grown seemingly detached from the realities of growing old and subsequently, dying. A consequence, perhaps, of death becoming increasingly overmedicalised, nearly one in two UK nationals die institutional deaths. In this article we, two architectural scholars engaged in teaching, research and practice and a nurse and healthcare scholar with a focus on end-of-life care and peoples' experiences, wish to draw attention to a controversy resulting from a paucity in current literature on the terms of reference of the dying 'patient' as we navigate the future implications of the COVID-19 pandemic.

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The world is currently facing an unprecedented healthcare crisis caused by a pandemic novel beta coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The pathogen is spread by human-to-human transmission via droplets exposure and contact transfer, causing mild symptoms in the majority of cases, but critical illness, bilateral viral pneumonia, and acute respiratory distress syndrome (ARDS) in a minority. Currently, controlling infection to prevent the spread of SARS-CoV-2 is the primary public healthcare intervention used.

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mutations (DNM) create new genetic variance and are an important driver for long-term selection response. We hypothesized that genomic selection exploits mutational variance less than traditional selection methods such as mass selection or selection on pedigree-based breeding values, because DNM in selection candidates are not captured when the selection candidates' own phenotype is not used in genomic selection, DNM are not on SNP chips and DNM are not in linkage disequilibrium with the SNP on the chip. We tested this hypothesis with Monte Carlo simulation.

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Reference populations for genomic selection usually involve selected individuals, which may result in biased prediction of estimated genomic breeding values (GEBV). In a simulation study, bias and accuracy of GEBV were explored for various genetic models with individuals selectively genotyped in a typical nucleus breeding program. We compared the performance of three existing methods, that is, Best Linear Unbiased Prediction of breeding values using pedigree-based relationships (PBLUP), genomic relationships for genotyped animals only (GBLUP) and a Single-Step approach (SSGBLUP) using both.

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Carbon capture and storage is a transition technology from a past and present fuelled by coal, oil and gas and a planned future dominated by renewable energy sources. The technology involves the capture of carbon dioxide emissions from fossil fuel power stations and other point sources, compression of the CO into a fluid, transporting it and injecting it deep beneath the Earth's surface into depleted petroleum reservoirs and other porous formations. Once injected, the CO must be monitored to ensure that it is emplaced and assimilated as planned and that none leaks back to surface.

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Genomic prediction is emerging in a wide range of fields including animal and plant breeding, risk prediction in human precision medicine and forensic. It is desirable to establish a theoretical framework for genomic prediction accuracy when the reference data consists of information sources with varying degrees of relationship to the target individuals. A reference set can contain both close and distant relatives as well as 'unrelated' individuals from the wider population in the genomic prediction.

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Drug diversion has become a $100 billion a year problem for the healthcare industry. By far the leading source of such diversion is the obtaining of prescription drugs by bogus patients from ER staff, the author claims. Solving the problem will not be easy, he says, because drug seekers are experts in avoiding detection or in persuading health providers to supply them with the pharmaceuticals they want.

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An emergency code response team is seen as the answer by the author when intervention issues arise in connection with violence or potential violence by patients or others in the hospital. In the article he explains what is involved in recruiting and training such a team, the roles of its members in a crisis situation, and the preparation and follow-up necessary to perform its duties successfully.

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The Youth Access to Alcohol (YATA) project was implemented in 2002 by the Alcohol Advisory Council of New Zealand (ALAC) in thirty communities in New Zealand, with the aim of reducing the harm experienced by young people as a result of alcohol misuse in New Zealand through reducing the supply of alcohol by adults to young people. The communities include a mix of rural and urban from both Islands in New Zealand. The project uses a community action approach, which has included setting up collaborative partnerships of key agencies, the delivery of key strategies, and multimedia awareness raising campaigns.

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