Service users as peer research interviewers: why bother?

Drawing on two studies completed within the social housing sector, this chapter asks if there are advantages to peer interviewing, whereby those currently or recently receiving services interview their peers as part of a research project. Contribution is made to the broader methodological debate of how service users should be involved in research about their lives. Along with contributions from a peer interviewer, we examine the benefits to peer interviewers themselves, and whether there are any positive differences for the people being interviewed. This chapter argues that there are clear methodological advantages to peer interviewing as it can lend vital insights from rapport with those often regarded as ‘hardest to reach’. The chapter also discusses peer interviewing in terms of strategic risk and limitations, as well as practical and ethical considerations. Ways of developing peer research in general are also suggested

Olfactory variation in mouse husbandry and its implications for refinement and standardisation: UK survey of non-animal scents

With their highly sensitive olfactory system, the behaviour and physiology of mice are not only influenced by the scents of conspecifics and other species, but also by many other chemicals in the environment. The constraints of laboratory housing limit a mouse’s capacity to avoid aversive odours that could be present in the environment. Potentially odorous items routinely used for husbandry procedures, such as sanitizing products and gloves, could be perceived by mice as aversive or attractive, and affect their behaviour, physiology and experimental results. A survey was sent to research institutions in the UK to enquire about husbandry practices that could impact on the olfactory environment of the mouse. Responses were obtained from 80 individuals working in 51 institutions. Husbandry practices varied considerably. Seventy percent of respondents reported always wearing gloves for handling mice, with nitrile being the most common glove material (94%) followed by latex (23%) and vinyl (14%). Over six different products were listed for cleaning surfaces, floors, anaesthesia and euthanasia chambers and behavioural apparatus. In all cases Trigene™ (now called Anistel™) was the most common cleaning product used (43, 41, 40 and 49%, respectively). Depending on the attribute considered, between 7 and 19% of respondents thought that cleaning products definitely, or were likely to, have strong effects on standardization, mouse health, physiology or behaviour. Understanding whether and how these odours affect mouse welfare will help to refine mouse husbandry and experimental procedures through practical recommendations, to improve the quality of life of laboratory animals and the experimental data obtained

A robust design methodology suitable for application to one-off products

Robust design is an activity of fundamental importance when designing large, complex, one-off engineering products. Work is described which is concerned with the application of the theory of design of experiments and stochastic optimization methods to explore and optimize at the concept design stage. The discussion begins with a description of state-of-the-art stochastic techniques and their application to robust design. The content then focuses on a generic methodology which is capable of manipulating design algorithms that can be used to describe a design concept. An example is presented, demonstrating the use of the system for the robust design of a catamaran with respect to seakeeping

Integrated engineering environments for large complex products

An introduction is given to the Engineering Design Centre at the University of Newcastle upon Tyne, along with a brief explanation of the main focus towards large made-to-order products. Three key areas of research at the Centre, which have evolved as a result of collaboration with industrial partners from various sectors of industry, are identified as (1) decision support and optimisation, (2) design for lifecycle, and (3) design integration and co-ordination. A summary of the unique features of large made-to-order products is then presented, which includes the need for integration and co-ordination technologies. Thus, an overview of the existing integration and co-ordination technologies is presented followed by a brief explanation of research in these areas at the Engineering Design Centre. A more detailed description is then presented regarding the co-ordination aspect of research being conducted at the Engineering Design Centre, in collaboration with the CAD Centre at the University of Strathclyde. Concurrent Engineering is acknowledged as a strategy for improving the design process, however design coordination is viewed as a principal requirement for its successful implementation. That is, design co-ordination is proposed as being the key to a mechanism that is able to maximise and realise any potential opportunity of concurrency. Thus, an agentoriented approach to co-ordination is presented, which incorporates various types of agents responsible for managing their respective activities. The co-ordinated approach, which is implemented within the Design Co-ordination System, includes features such as resource management and monitoring, dynamic scheduling, activity direction, task enactment, and information management. An application of the Design Co-ordination System, in conjunction with a robust concept exploration tool, shows that the computational design analysis involved in evaluating many design concepts can be performed more efficiently through a co-ordinated approach

Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection.

To restrict infection by Legionella pneumophila, mouse macrophages require Naip5, a member of the nucleotide-binding oligomerization domain leucine-rich repeat family of pattern recognition receptors, which detect cytoplasmic microbial products. We report that mouse macrophages restricted L. pneumophila replication and initiated a proinflammatory program of cell death when flagellin contaminated their cytosol. Nuclear condensation, membrane permeability, and interleukin-1beta secretion were triggered by type IV secretion-competent bacteria that encode flagellin. The macrophage response to L. pneumophila was independent of Toll-like receptor signaling but correlated with Naip5 function and required caspase 1 activity. The L. pneumophila type IV secretion system provided only pore-forming activity because listeriolysin O of Listeria monocytogenes could substitute for its contribution. Flagellin monomers appeared to trigger the macrophage response from perforated phagosomes: once heated to disassemble filaments, flagellin triggered cell death but native flagellar preparations did not. Flagellin made L. pneumophila vulnerable to innate immune mechanisms because Naip5+ macrophages restricted the growth of virulent microbes, but flagellin mutants replicated freely. Likewise, after intratracheal inoculation of Naip5+ mice, the yield of L. pneumophila in the lungs declined, whereas the burden of flagellin mutants increased. Accordingly, macrophages respond to cytosolic flagellin by a mechanism that requires Naip5 and caspase 1 to restrict bacterial replication and release proinflammatory cytokines that control L. pneumophila infection

The use of liver histopathology, lipid peroxidation and acetylcholinesterase assays as biomarkers of contaminant-induced stress in the Cape stumpnose, Rhabdosargus holubi (Teleostei: Sparidae), from selected South African estuaries

Three biomarkers of contaminant-induced stress (liver histopathology, the lipid peroxidation (LPx) assay and the acetylcholinesterase (AChE) assay) were adapted for application to the estuarine-dependent marine fish Rhabdosargus holubi (Steindachner, 1881). Specimens of R. holubi were collected using a seine net from 3 temporarily open/closed estuaries in the Eastern Cape, South Africa, each impacted by different anthropogenic activities. The East Kleinemonde estuary has a housing settlement on the banks in the lower reaches and some agriculture in its catchment. The Old Woman’s estuary has a golf course adjacent to its lower and middle reaches and is crossed by a national road in its upper reaches. The Mtana estuary is virtually pristine, with limited cattle grazing occurring along the banks of the estuary and some subsistence agriculture in the catchment. According to the biomarker results from this study, R. holubi from the East Kleinemonde were in good health, as reflected by low LPx and high AChE levels. The liver histopathology did, however, suggest possible previous exposure to stress (increased melanomacrophage centres, increased perivascular connective tissue and severe vacuolation). Overall, liver histopathology results did not differ significantly between estuaries. Fish from the Old Womans recorded significantly inhibited AChE and increased LPx, while fish from the Mtana exhibited significantly increased LPx only, suggesting possible exposure to anticholinesterase contaminants in the former estuary and some form of oxidative stress in the latter. Although water samples were collected from each of the 3 estuaries and analysed for polychlorinated biphenyls, organochlorines, organophosphorous pesticides and pyrethroids, none of these chemicals were detected. Aspesticide residues in water are highly variable, both temporally and spatially, future studies should focus on measuring tissue burdens of organisms in order to identify the contaminant stressor. This study has shown that while chemical analyses of water provide a ‘snap-shot’ of water quality at the time of sampling, biomonitoring can integrate past exposures to stress and is thus useful for identifying potential situations of concern that require further detailed investigation.Keywords: biomonitoring, pollution, estuaries, AChE, LPx, histopatholog

Mitochondrial ROS cause motor deficits induced by synaptic inactivity:implications for synapse pruning

Developmental synapse pruning refines burgeoning connectomes. The basic mechanisms of mitochondrial reactive oxygen species (ROS) production suggest they select inactive synapses for pruning: whether they do so is unknown. To begin to unravel whether mitochondrial ROS regulate pruning, we made the local consequences of neuromuscular junction (NMJ) pruning detectable as motor deficits by using disparate exogenous and endogenous models to induce synaptic inactivity en masse in developing Xenopus laevis tadpoles. We resolved whether: (1) synaptic inactivity increases mitochondrial ROS; and (2) antioxidants rescue synaptic inactivity induced motor deficits. Regardless of whether it was achieved with muscle (α-bugarotoxin), nerve (α-latrotoxin) targeted neurotoxins or an endogenous pruning cue (SPARC), synaptic inactivity increased mitochondrial ROS in vivo. The manganese porphyrins MnTE-2-PyP5+ and/or MnTnBuOE-2-PyP5+ blocked mitochondrial ROS to significantly reduce neurotoxin and endogenous pruning cue induced motor deficits. Selectively inducing mitochondrial ROS—using mitochondria-targeted Paraquat (MitoPQ)—recapitulated synaptic inactivity induced motor deficits; which were significantly reduced by blocking mitochondrial ROS with MnTnBuOE-2-PyP5+. We unveil mitochondrial ROS as synaptic activity sentinels that regulate the phenotypical consequences of forced synaptic inactivity at the NMJ. Our novel results are relevant to pruning because synaptic inactivity is one of its defining features