Studies on dorsal fin rot in farmed Atlantic salmon (Salmo salar L.) parr

Aspects of dorsal fin rot in farmed Atlantic salmon parr were investigated and the associated pathology described. Substantial evidence was obtained which suggested that the condition was caused and maintained by repeated bites from other parr. The gross histological and scanning electron microscopic appearance of the lesions were consistent with bite wounds and the typical pathology was reproduced by repeated simulated bites. During behavioural experiments the parr were observed to both bite and damage each others dorsal fins. The typical nodular lesions were more prevalent and took longer to heal at lower temperatures. Dorsal fin rot was found to occur in the absence of damage to the other fins and was more severe in smaller fish. The bacteria associated with the natural lesions and following controlled damage were studied, but not found to play a significant role in the aetiology. They were capable of neither initiating nor maintaining the lesions. The main site of bacterial colonisation appeared to be on exposed fin rays. It was demonstrated that the natural lesions started to resolve as soon as the fish were placed in isolation. A limited study failed to demonstrate a definite relationship between dorsal fin rot and increased susceptibility to Aeromonas salmonicida infection. The implications of all these findings for control of the condition are discussed

Multifunctional

The New Product Development (NPD) process in manufacturing industry, together with the application of multi functional teams in the process, has been well studied in the extant literature. Tools, and techniques used to assist project teams in NPD have also been investigated in detail. However, many of the claims of the effectiveness of 'tools’ such as Rapid Prototyping (RP) and techniques such as Failure Mode and Effects Analysis (FMEA) are anecdotal in nature, lacking empirical evidence, or promoted by authors with a commercial interest in the subject. Therefore, as part of the objectives of this research to provide more empirical data, case studies were conducted over a period of 12 years in companies such as Flymo, Kenwood, and Domnick Hunter. Key Performance Indicators (KPIs) were selected for the case studies to provide a rich source of quantitative and qualitative data from which some of the root causes of NPD problems were identified. A common NPD problem identified was project delays, following late changes to the specification and the product engineering. It was clear however, that not all of the changes had a negative impact on a project, indeed some teamwork studies encourage changes to improve the product value and quality. A 'penalty weighting' model to quantify the 'impact' of changes with respect to any benefits was developed to identify the most cost effective period for teamwork studies and provide an efficiency profile for each project. A strategic business approach for Rapid Prototyping activities was also presented together with a 'sub-group' methodology to encourage innovation and reduce 'front end' delays. Appropriate project management control documentation was developed for the NPD teams to support the control of various KPIs including product deliverables, product costs, capital spends and launch timing

Shame: In Defence of an Essential Moral Emotion

I argue that shame is an essential moral emotion, and that the capacity to feel shame is vital to allow us to pick out certain types of moral value. I do this by sketching out a general role for moral emotions, distinguishing shame from other moral emotions, notably guilt, and then arguing that shame has a distinctive role to play as a moral emotion that cannot be played by guilt. By marking out a key role for the emotions in moral life, I am able to address two key concerns about moral judgement. First, I am able to explain how we overcome frame problems, allowing us to notice and appropriately conceptualise moral concerns, against a backdrop of everyday life. Second, I can give an account of the apparent intrinsically-motivating nature of moral judgements. Shame, in central cases, is based on self-assessments of inadequacy; we judge ourselves to be less than we should be. This is contrasted with guilt, which centres on judgements of transgression against moral norms. It is also contrasted with embarrassment and humiliation, neither of which are primarily moral emotions. Shame has a distinctive role to play as a moral emotion. It is capable of picking out cases of moral value that guilt cannot; in particular, supererogatory value and cases of wrongdoing by collectives, in the absence of individual culpability. Pace the claims of numerous psychologists and philosophers, shame is not necessarily a dangerous emotion; rather, only certain types of shame have the potential to do damage to those experiencing them. Situationist arguments threaten the role of shame as a moral emotion, by suggesting that there are no robust character traits; these claims are mistaken. Therefore, I am able to sustain the conclusion that shame has a vital role to play in moral life

Combining SCADA and vibration data into a single anomaly detection model to predict wind turbine component failure

Reducing downtime through predictive or condition-based maintenance is a promising strategy to help reduce costs associated with wind farm operation and maintenance. To help effectively monitor wind turbine condition, operators now rely on multiply sources of data to make informed operational decisions which can minimise downtime, increasing availability and profitability of any given site. Two of such approaches are SCADA temperature and vibration monitoring, which are typically performed in isolation and compared over time for both fault diagnostics and reliability analysis. Presenting two separate case studies, this paper describes a methodology to bring multiple data sources together to diagnose faults by using a single-class support vector machine classifier to assess normal behaviour model error, with results showing that anomalies can be detected more consistently when compared to more standard approaches of analysing each data source in isolation

Identification of bioactive lipids associated with osteoarthritis pain and pathology through targeted lipidomic analyses

Osteoarthritis (OA) is the leading cause of disability in the older population and is characterised by the degradation of the affected joint and development of chronic pain. There are currently no approved treatments that halt or reverse the joint pathology, and current treatments for associated pain are unsuitable for long-term treatment. There is also the need to identify those at high risk of developing OA that would benefit from early intervention. The oxylipins are oxidised lipid metabolites of polyunsaturated fatty acids (PUFAs), which play a central role in the regulation of the inflammatory response. They have also been reported to be involved in pain signalling and so present as attractive potential biomarkers and therapeutic targets for OA. This thesis aimed to develop methods to quantify a panel of pro- and anti-inflammatory oxylipins in biological samples using liquid chromatography-mass spectrometry (LC-MS/MS); and apply this method to clinical and pre-clinical studies involving participants with OA and animal models of the disease. The LC-MS/MS method developed covered the omega-3 and omega-6 PUFAs and many of their metabolites including eicosanoids, docosanoids, and endocannabinoids. The method was optimised over a 25 minute run time which allowed good separation of isomeric compounds and was sensitive into the picomolar range. Application of the method to plasma and serum collected from healthy volunteers (n=10) found significantly high levels of many oxylipins in serum compared to plasma. In a longitudinal study of healthy young adults who had suffered acute knee injury and are at high risk of developing OA in the future (n=47), levels of omega-3 PUFAs and their metabolites were significantly higher immediately after injury compared to later time points and controls. The opposite was observed for pro-inflammatory eicosanoids, which were significantly lower immediately after injury compared to later time points. At two years after injury, levels of the DHETs (metabolites of soluble epoxide hydrolase (sEH)) were associated with worse knee symptom scores. Measuring the oxylipins in a community cohort of people with varying levels knee pain and OA (n=154) identified metabolites of LOX and CYP450 as being associated with radiographic OA. Levels of 8,9-EET, 14,15-DHET, 12-HpETE, and AEA were also associated with measures of self reported pain. Stratification of participants based pain and radiographic OA scores showed significantly higher levels of several EETs, 14- & 17-HDHA, and the HETEs. Baseline levels of 8,9-EET, 5-HETE, and 5,6-DHET were also associated with pain scores collected at 3 years follow-up. Using the destabilisation of the medial meniscus (DMM) model of OA, oxylipins were measured at 4, 8, and 12 weeks post model induction. Levels of prostaglandins, HETEs, EETs, and 12-HpETE were associated with synovitis and cartilage degradation scores at 4 and 8 weeks post-surgery; and levels of 17-HDHA were associated with less pain at 16-weeks post-injury. Targeting the sEH enzyme in the DMM model using an inhibitor called TPPU showed complete reversal of pain behaviour, decreased levels of DHETs, and increased EET:DHET ratios. Levels of 8,9-DHET were also associated with worse pain scores. During the COVID-19 pandemic the method was repurposed and serum from n=50 patients were measured for their oxylipin profile. Levels of both pro- and anti-inflammatory oxylipins were significantly higher in COVID-19 patients compared to controls. There were significant positive correlations between specialised pro-resolving mediators (SPMs), pro-inflammatory bioactive lipids, and anti-spike antibody binding. Levels of linoleic acid and 5,6-DHET were significantly lower in SARS-CoV-2 patients who died. These studies suggest a role of the oxylipins in OA pathology and associated pain phenotypes, and identify potential targets for therapeutic intervention for both joint pathology and pain. Through validation in replication cohorts, there is also the potential of using key oxylipins identified here, to predict future pain score. Future studies should look at the difference between serum/plasma and synovial fluid profiles of oxylipins in people with OA which may gave further mechanistic insight into their role in the pathogenesis of OA