Analysis of Serological Surveillance Data: Patterns of Blood Borne Infection and Heterogeneity in People who Inject Drugs

A large proportion of blood-borne viruses (BBV) are transmitted via injecting drug use. Understanding patterns of risk and monitoring trends over time in people who inject drugs (PWID) is therefore a crucial part of developing public health policy. Risks of infection with hepatitis C and B (HCV, HBV) and HIV in PWID are investigated using serial cross-sectional surveillance data, in particular via force of infection (FOI) models. Standard models are extended to include a wealth of covariate data. Individual variability is considered via bivariate shared frailty models and correlations between infections. Gamma, inverse Gaussian and time-varying frailty models are fitted to investigate how variability in risk evolves throughout injecting career. Finally, models are extended to the trivariate case and different forms of component frailty models are proposed. Recent initiates were found to be at high risk of infection, in particular in London and the North West. Subsequently the FOI is broadly constant, and similar across different regions. Frailty models indicate that there is substantial individual variability in risk, although this declines over the course of injecting career. Females have higher overall risks of HCV and HBV, but are less heterogeneous than males. Including covariate data on demographics and a number of risk factors only resulted in modest reductions in frailty variance. Correlations between HCV-HBV and HBV-HIV associations were stronger than for HCV-HIV; trivariate models including additional pairwise components for HCV-HBV and HBV-HIV provided an improvement in model fit compared to a shared frailty model. Many of the results in this thesis point towards greater variation in risk at initiation, potentially due to the varied circumstances in which individuals start injecting, followed by more comparable risks in those with established injecting behaviour. The relative importance of injecting and sexual risk may explain patterns of risk and correlation in the three infections

Inspection models for automotive parts remanufacture

Remanufacturing can be classed as the act of bringing end-of-use products back to “like new” conditions with warranty to match. The field has been steadily growing in recent years due to a cultural shift towards sustainable practices. ‘Inspection’ is the action of assessing parts in order to determine the needed actions to bring them back to standard, and is a critical factor. Previous work by Errington and Ridley in this area have shown the necessity of increased structure and tools to aid automotive remanufacturing inspection. This aim of this research was to investigate the inspection issues faced by automotive parts remanufacturers within the UK and develop tools to alleviate the lack of guidance on inspection activities. Case study methods were used at five different companies to identify the issues, this included over-reliance on inspector expertise, difficulties in knowledge share, and an aging workforce. A 4-part model was developed to combat these issues, and was later validated through both industry and academic review, and an expert panel to ensure robustness and rjgour. This research was unique in that it approached inspection by focusing on the practices and methods rather than a business or strategic perspective targeting cost effectiveness rather than operational efficacy. The beneficiaries of this research include academia and industry, with academia furthering the building of benchmarking for inspection, and a new method of investigating inspection within remanufacturing. Industry can use this research to further refine their inspection practices and in training with new staff.Remanufacturing can be classed as the act of bringing end-of-use products back to “like new” conditions with warranty to match. The field has been steadily growing in recent years due to a cultural shift towards sustainable practices. ‘Inspection’ is the action of assessing parts in order to determine the needed actions to bring them back to standard, and is a critical factor. Previous work by Errington and Ridley in this area have shown the necessity of increased structure and tools to aid automotive remanufacturing inspection. This aim of this research was to investigate the inspection issues faced by automotive parts remanufacturers within the UK and develop tools to alleviate the lack of guidance on inspection activities. Case study methods were used at five different companies to identify the issues, this included over-reliance on inspector expertise, difficulties in knowledge share, and an aging workforce. A 4-part model was developed to combat these issues, and was later validated through both industry and academic review, and an expert panel to ensure robustness and rjgour. This research was unique in that it approached inspection by focusing on the practices and methods rather than a business or strategic perspective targeting cost effectiveness rather than operational efficacy. The beneficiaries of this research include academia and industry, with academia furthering the building of benchmarking for inspection, and a new method of investigating inspection within remanufacturing. Industry can use this research to further refine their inspection practices and in training with new staff

Lactobacillus ruminis strains cluster according to their mammalian gut source

peer-reviewedBackground Lactobacillus ruminis is a motile Lactobacillus that is autochthonous to the human gut, and which may also be isolated from other mammals. Detailed characterization of L. ruminis has previously been restricted to strains of human and bovine origin. We therefore sought to expand our bio-bank of strains to identify and characterise isolates of porcine and equine origin by comparative genomics. Results We isolated five strains from the faeces of horses and two strains from pigs, and compared their motility, biochemistry and genetic relatedness to six human isolates and three bovine isolates including the type strain 27780T. Multilocus sequence typing analysis based on concatenated sequence data for six individual loci separated the 16 L. ruminis strains into three clades concordant with human, bovine or porcine, and equine sources. Sequencing the genomes of four additional strains of human, bovine, equine and porcine origin revealed a high level of genome synteny, independent of the source animal. Analysis of carbohydrate utilization, stress survival and technological robustness in a combined panel of sixteen L. ruminis isolates identified strains with optimal survival characteristics suitable for future investigation as candidate probiotics. Under laboratory conditions, six human isolates of L. ruminis tested were aflagellate and non-motile, whereas all 10 strains of bovine, equine and porcine origin were motile. Interestingly the equine and porcine strains were hyper-flagellated compared to bovine isolates, and this hyper-flagellate phenotype correlated with the ability to swarm on solid medium containing up to 1.8% agar. Analysis by RNA sequencing and qRT-PCR identified genes for the biosynthesis of flagella, genes for carbohydrate metabolism and genes of unknown function that were differentially expressed in swarming cells of an equine isolate of L. ruminis. Conclusions We suggest that Lactobacillus ruminis isolates have potential to be used in the functional food industry. We have also identified a MLST scheme able to distinguish between strains of L. ruminis of different origin. Genes for non-digestible oligosaccharide metabolism were identified with a putative role in swarming behaviour.This work was supported by a Principal Investigator Award (07/IN.1/B1780) from Science Foundation Ireland to P.W. O’Toole

Ultrasonic additive manufacturing - a hybrid production process for novel functional products

Ultrasonic Additive Manufacturing (UAM), or Ultrasonic Consolidation as it is also referred, is a hybrid form of manufacture, primarily for metal components. The unique nature of the process permits extremely novel functionality to be realised such as multi-material structures with embedded componentry. UAM has been subject to research and investigation at Loughborough University since 2001. This paper introduces UAM then details a number of key findings in a number of areas that have been of particular focus at Loughborough in recent years. These include; the influence of pre-process material texture on interlaminar bonding, secure fibre positioning through laser machined channels, and freeform electrical circuitry integration

A nanometre-scale fibre-to-matrix interface characterization of an ultrasonically consolidated metal matrix composite

Future ‘smart’ structures have the potential to revolutionize many engineering applications. One of the possible methods for creating smart structures is through the use of shape memory alloy (SMA) fibres embedded into metal matrices. Ultrasonic consolidation (UC) allows the embedding of SMAs into metal matrices while retaining the SMA's intrinsic recoverable deformation property. In this work, NiTi SMA fibres were successfully embedded into an Al 3003 (0) matrix via the UC layer manufacturing process. Initially the plastic flow of the Al matrix and the degree of fibre encapsulation were observed using optical microscopy. Then microstructural grain and sub-grain size variation of the Al 3003 (0) matrix at the fibre–matrix interface, and the nature of the fibre–matrix bonding mechanism, were studied via the use of focused ion beam (FIB) cross-sectioning, FIB imaging, scanning electron microscopy, and mechanical peel testing. The results show that the inclusion of the NiTi SMA fibres had a significant effect on the surrounding Al matrix microstructure during the UC process. Additionally, the fibre–matrix bonding mechanism appeared to be mechanical entrapment with the SMA surface showing signs of fatigue from the UC embedding process

Ultrasonic additive manufacturing research at Loughborough University

Ultrasonic Additive Manufacturing (UAM) has been subject to research and investigation at Loughborough University since 2001. In recent years, three particular areas of significant focus have been: • The influence of pre-process material texture on interlaminar bonding. • Secure fibre positioning through laser machined channels. • Freeform electrical circuitry integration. This paper details the key findings and a number of conclusions from these work areas. The results of this work have led to the further research and developmental applications for the UAM technology

Serine Phosphorylation of the Hepatitis C Virus NS5A Protein Controls the Establishment of Replication Complexes

The hepatitis C virus (HCV) nonstructural 5A (NS5A) protein is highly phosphorylated and involved in both virus genome replication and virion assembly. We and others have identified serine 225 in NS5A to be a phosphorylation site, but the function of this posttranslational modification in the virus life cycle remains obscure. Here we describe the phenotype of mutants with mutations at serine 225; this residue was mutated to either alanine (S225A; phosphoablatant) or aspartic acid (S225D; phosphomimetic) in the context of both the JFH-1 cell culture infectious virus and a corresponding subgenomic replicon. The S225A mutant exhibited a 10-fold reduction in genome replication, whereas the S225D mutant replicated like the wild type. By confocal microscopy, we show that, in the case of the S225A mutant, the replication phenotype correlated with an altered subcellular distribution of NS5A. This phenotype was shared by viruses with other mutations in the low-complexity sequence I (LCS I), namely, S229D, S232A, and S235D, but not by viruses with mutations that caused a comparable replication defect that mapped to domain II of NS5A (P315A, L321A). Together with other components of the genome replication complex (NS3, double-stranded RNA, and cellular lipids, including phosphatidylinositol 4-phosphate), the mutation in NS5A was restricted to a perinuclear region. This phenotype was not due to cell confluence or another environmental factor and could be partially transcomplemented by wild-type NS5A. We propose that serine phosphorylation within LCS I may regulate the assembly of an active genome replication complex

Using Twitter™ to drive research impact : a discussion of strategies, opportunities and challenges

Researchers have always recognised the importance of disseminating the findings of their work, however, recently the need to proactively plan and drive the impact of those findings on the wider society has become a necessity. Firstly, this is because funders require evidence of return from investment and secondly and crucially because national research assessments are becoming powerful determinants of future funding. In research studies associated with nursing, impact needs to be demonstrated by showing the effect on a range of stakeholders including service users, patients, carers, the nursing workforce and commissioners. Engaging these groups is a well-known challenge influenced by lack of access to academic journals, lack of time to read long complex research papers and lack of opportunities to interact directly with the researchers. This needs to be addressed urgently to enable nursing research to increase the impact that it has on health delivery and the work of clinical practitioners. Social media is potentially a novel way of enabling research teams to both communicate about research as studies progress and to disseminate findings and research funders are increasingly using it to publicise information about research programmes and studies they fund. A search of the healthcare literature reveals that advice and guidance on the use of social media for research studies is not well understood or exploited by the research community. This paper, therefore, explores how using social networking platforms, notably Twitter™ offers potential new ways for communicating research findings, accessing diverse and traditionally hard-to-reach audiences, knowledge exchange at an exponential rate, and enabling new means of capturing and demonstrating research impact. The paper discusses approaches to initiate the setup of social networking platforms in research projects and considers the practical challenges of using Twitter™ in nursing and healthcare research. The discussion is illuminated with examples from our current research. In summary, we suggest that the use of social media micro-blogging platforms is a contemporary, fast, easy and cost effective way to augment existing ways of disseminating research which helps drive impact