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To achieve the full potential of tidal stream energy, developers are incentivised to use larger blades on tidal turbines. This requires validation of blade structural designs through full-scale blade fatigue tests to de-risk the engineering process. However, the loading scenarios encountered in testing facilities and those in reality could be significantly different, which induces errors in blade loads and fatigue damage. Here we characterise the unsteady tidal blade load variation through model-scale experiment. It was found that the standard deviations of thrust load range between 200% and 637% of condition without waves. This results in an increase of predicted fatigue damage between 6% and 18%. It was observed that the centre of effort shifts towards the blade root when encountering wave crests of opposing waves, which has not been reported in the literature to date. To reduce errors in fatigue test while the centre of effort is fixed, matching blade shear forces should be sacrificed to match target bending moment at the root. Matching blade shear forces leads to a reduction of predicted fatigue damage ranges from 17% to 25%, which can induce errors in fatigue testing. We anticipate our findings would facilitate the development of fatigue testing of tidal turbine blades.

Introduction Mutations in pre-mRNA processing factor 31 (PRPF31), a core protein of the spliceosomal tri-snRNP complex, cause autosomal-dominant retinitis pigmentosa (adRP). It has remained an enigma why mutations in ubiquitously expressed tri-snRNP proteins result in retina-specific disorders, and so far, the underlying mechanism of splicing factors-related RP is poorly understood. Methods We used the induced pluripotent stem cell (iPSC) technology to generate retinal organoids and RPE models from four patients with severe and very severe PRPF31-adRP, unaffected individuals and a CRISPR/Cas9 isogenic control. Results To fully assess the impacts of PRPF31 mutations, quantitative proteomics analyses of retinal organoids and RPE cells were carried out showing RNA splicing, autophagy and lysosome, unfolded protein response (UPR) and visual cycle-related pathways to be significantly affected. Strikingly, the patient-derived RPE and retinal cells were characterised by the presence of large amounts of cytoplasmic aggregates containing the mutant PRPF31 and misfolded, ubiquitin-conjugated proteins including key visual cycle and other RP-linked tri-snRNP proteins, which accumulated progressively with time. The mutant PRPF31 variant was not incorporated into splicing complexes, but reduction of PRPF31 wild-type levels led to tri-snRNP assembly defects in Cajal bodies of PRPF31 patient retinal cells, altered morphology of nuclear speckles and reduced formation of active spliceosomes giving rise to global splicing dysregulation. Moreover, the impaired waste disposal mechanisms further exacerbated aggregate formation, and targeting these by activating the autophagy pathway using Rapamycin reduced cytoplasmic aggregates, leading to improved cell survival. Conclusions Our data demonstrate that it is the progressive aggregate accumulation that overburdens the waste disposal machinery rather than direct PRPF31-initiated mis-splicing, and thus relieving the RPE cells from insoluble cytoplasmic aggregates presents a novel therapeutic strategy that can be combined with gene therapy studies to fully restore RPE and retinal cell function in PRPF31-adRP patients.

ObjectivesDuring a prospective study of S. aureus carriage in Royal Marines (RM) recruits, six S. argenteus strains were identified in four recruits undertaking military training together. As S. argenteus sepsis leads to mortality similar to S. aureus, we determined the potential for person-to-person transmission, to evaluate future outbreak risk.MethodsWe used whole-genome sequencing to characterise S. argenteus and investigate phylogenetic relationships between isolates. Participant colonisation with S. aureus and skin and soft tissue infection acquisition were recorded.ResultsAll six S. argenteus strains were spa-type t5078, ST2250. Strains were detected in 4/40 recruits in the same troop (training cohort) in weeks 1, 6 or 15 of training. No mec, tsst or LukPV genes were detected. We identified differences of 10-35 core SNPs between S. argenteus from different recruits. In two recruits, two S. argenteus strains were isolated; these could be distinguished by 3 and 15 core SNPs in each case. S. argenteus was not identified in any one of the other 21 participating troops (1,012 recruits).ConclusionsThe identification of S. argenteus within a single troop from the total recruit population supports a common source for transmission, supported by SNP analysis. The high number of SNPs between some isolates may indicate a common source of diverse isolates or a high level of S. argenteus mutation in carriage. S. argenteus ST2250 is a newly recognised lineage; a better understanding of the frequency of genetic changes during transmission and transition from asymptomatic carriage to disease is required.

The pancreas is particularly sensitive to acute cellular stress, but this has been difficult to evaluate using light microscopy. Pancreatic ischaemia associated with deceased organ donation negatively impacts whole-organ and isolated-islet transplantation outcomes. Post-mortem changes have also hampered accurate interpretation of ante-mortem pancreatic pathology. A rigorous histological scoring system accurately quantifying ischaemia is required to experimentally evaluate innovations in organ preservation and to increase rigour in clinical/research evaluation of underlying pancreatic pathology. We developed and validated an unbiased electron microscopy (EM) score of acute pancreatic exocrine cellular stress in deceased organ donor cohorts (development [n = 28] and validation [n = 16]). Standardised assessment led to clearly described numerical scores (0–3) for nuclear, mitochondrial and endoplasmic reticulum (ER) morphology and intracellular vacuolisation; with a maximum (worst) aggregate total score of 12. In the Validation cohort, a trend towards higher scores was observed for tail versus head regions (nucleus score following donation after brainstem death [DBD]: head 0.67 ± 0.19; tail 0.86 ± 0.11; p = 0.027) and donation after circulatory death (DCD) versus DBD (mitochondrial score: DCD (head + tail) 2.59 ± 0.16; DBD (head + tail) 2.38 ± 0.21; p = 0.004). Significant mitochondrial changes were seen ubiquitously even with short cold ischaemia, whereas nuclear and vacuolisation changes remained mild even after prolonged ischaemia. ER score correlated with cold ischaemia time (CIT) following DBD (pancreatic tail region: r = 0.796; p = 0.018). No relationships between CIT and EM scores were observed following DCD. In conclusion, we have developed and validated a novel EM score providing standardised quantitative assessment of subcellular ultrastructural morphology in pancreatic acinar cells. This provides a robust novel tool for gold standard measurement of acute cellular stress in studies evaluating surrogate measures of peri-transplant ischaemia, organ preservation technologies and in samples obtained for detailed pathological examination of underlying pancreatic pathology. © 2020 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.

Experimental data was obtained in order to investigate the effect of waves on the loads and performance of tidal turbines. An instrumented 1:15 scale tidal turbine was installed in the FloWave Ocean Energy Research Facility, and a wide range of regular wave conditions were generated; systematically varying both wave frequency and height. Waves were generated both following and opposing a fixed mean current velocity of 0.81 m/s. Data are made available of the measured turbine loads and environmental conditions obtained for five repeats of 24 wave conditions via https://doi.org/10.7488/ds/2472. A description of the data collection process, data processing, file structure and naming conventions are provided in this article. The analysis and presentation of the described dataset can be found in Ref. [1].

Wave tank tests aiming to reproduce realistic or site specific conditions will commonly involve using directionally spread, short-crested sea states. The measurement of these directional characteristics is required for the purposes of calibrating and validating the modelled sea state. Commonly used methods of directional spectrum reconstruction, based on directional spreading functions, have an inherent level of uncertainty associated with them. In this paper we aim to reduce the uncertainty in directional spectrum validation by introducing the SPAIR (Single-summation PTPD Approach with In-line Reflections) method, in combination with a directional wave gauge array. A variety of wave conditions were generated in the FloWave Ocean Energy Research Facility, Edinburgh, UK, to obtain a range of sea state and reflection scenarios. The presented approach is found to provide improved estimates of directional spectra over standard methods, reducing the mean apparent directional deviation down to below 6% over the range of sea states. Additionally, the method isolates incident and reflected spectra in both the frequency and time domain, and can separate these wave systems over 360°. The accuracy of the method is shown to be only slightly sensitive to the level of in-line reflection present, but at present cannot deal with oblique reflections. The SPAIR method, as presented or with slight modification, will allow complex directional sea states to be validated more effectively, enabling multidirectional wave basins to simulate realistic wave scenarios with increased confidence.

Site-specific wave data can be used to improve the realism of tank test conditions and resulting outputs. If this data is recorded in the presence of a current, then the combined conditions must be re-created to ensure wave power, wavelength and steepness are correctly represented in a tank. In this paper we explore the impacts of currents on the wave field and demonstrate a simple, effective methodology for re-creating combined wave-current scenarios. Regular waves, a parametric unidirectional spectrum, and a complex site-specific directional sea state were re-created with current velocities representing 0.25, 0.5, and 1.0 m/s full scale. Waves were generated at a number of angles relative to the current, providing observations of both collinear and non-collinear wave-current interactions. Wave amplitudes transformed by the current were measured and corrected linearly, ensuring desired frequency and wavenumber spectra in the presence of current were obtained. This empirical method proved effective after a single iteration. Frequency spectra were within 3% of desired and wave heights normally within 1%. The generation-measurement-correction procedure presented enables effective re-creation of complex wave-current scenarios. This capability will increase the realism of tank testing, and help de-risk devices prior to deployment at sea.

Background Stress fractures (SF) are one of the more severe overuse injuries in military training and therefore knowledge of potential risk factors is needed to assist in developing mitigating strategies. Purpose To develop a prediction model for risk of SF in Royal Marines (RM) recruits during an arduous military training program. Study Design Cohort study Methods 1,082 recruits (age range: 16-33 years) enrolled between September 2009 and July 2010, were prospectively followed through the 32-week RM training program. SF diagnosis was confirmed from a positive X-Ray or Magnetic Resonance Imaging (MRI) scan. Potential risk factors assessed at week-1 included recruit characteristics, anthropometric assessment, dietary supplement use, lifestyle habits, fitness assessment, blood samples, 25(OH)D, bone strength as measured by heel Broadband Ultrasound Attention (BUA), history of physical activity, and previous and current food intake. A logistic least absolute shrinkage selection operator (LASSO) regression with 10-fold cross-validation method was used to select potential predictors among 47 candidate variables. Model performance was assessed using measures of discrimination (c-index) and calibration. Bootstrapping was used for internal validation of the developed model and to quantify optimism. Results A total of 86 (8%) volunteer recruits presented with at least one SF during training. Twelve variables were identified as the most important risk factors of SF. Variables strongly associated with SF were age, body weight, pre-training weight bearing (WB) exercise, pre-training cycling and childhood intake of milk and milk products. The c-index for the prediction model was 0.73 (optimism-corrected c-index 0.68), which represents the model performance in future volunteers. Although 25(OH)D and VO2max had only a borderline statistical significant association with SF, the inclusion of these factors improved the performance of the model. Conclusion These findings will assist in identifying recruits at greater risk of SF during training, and support interventions to mitigate this injury risk. However, external validation of the model is still required.