Analysis of array spacing on tidal stream turbine farm performance using Large-Eddy Simulation

This is the final version. Available on open access from Elsevier via the DOI in this recordData availability Information on the data underpinning the results presented here, including how to access them, can be found in the Cardiff University data catalogue at 10.17035/d.2019.0083917166Design of efficient tidal arrays relies on the adopted spacing between turbines and their mutual interplay. Turbines affected by wake shadowing operate in harsher flow conditions, such as higher turbulence levels or lower incident velocity, which leads to reduced performance and larger extreme and fatigue loading. To extend the knowledge about turbine-to-turbine interplay in tidal arrays, high-fidelity numerical simulations using a Large-Eddy Simulation-Actuator Line Method (LES-ALM) are carried out to quantify the impact of row spacing. The developed Digital Offshore FArm Simulator (DOFAS) validates well with experimental data in terms of flow statistics and hydrodynamic coefficients, which demonstrate its adequacy to resolve the complex fluid-turbines interaction. In the cases with spacing of four and eight diameters between the rows, the lack of wake recovery has a detrimental effect on back-row turbines whose efficiency dramatically drops compared to those in the front-row. The LES-ALM captured the low-frequency wake meandering phenomenon responsible for uneven periodic loading on back-row turbines. The devices placed in the front-row suffer the largest thrust loads, blade-root bending moments and support structure moments, whilst the outermost back-row turbines experience the largest tower yaw moments due to their simultaneous exposure to low-momentum turbulent wakes and high-velocity free-stream flow. Finally, damage equivalent loads estimated by the LES-ALM are maximum for the front-row turbines except the tower yaw moment which is maximum on the outermost back-row turbines.Engineering and Physical Sciences Research Council (EPSRC)Ministerio de Ciencia, Innovación y Universidades of the Spanish Governmen

EffectS of non-nutritive sWeetened beverages on appetITe during aCtive weigHt loss (SWITCH): Protocol for a randomized, controlled trial assessing the effects of non-nutritive sweetened beverages compared to water during a 12-week weight loss period and a follow up weight maintenance period

Background Acute and medium-term intervention studies suggest that non-nutritive sweeteners (NNS) are beneficial for weight loss, however there is limited human data on the long-term effects of consuming NNS on weight loss, maintenance, and appetite. Further research is therefore required to elucidate the prolonged impact of NNS consumption on these outcome measures. Methods/design A randomized parallel groups design will be used to assess whether regular NNS beverage intake is equivalent to a water control in promoting weight loss over 12-weeks (weekly weight loss sessions; Phase I), then supporting weight maintenance over 40-weeks (monthly sessions; Phase II) and subsequently independent weight maintenance over 52-weeks (Phase III) in 432 participants. A subset of these participants (n = 116) will complete laboratory-based appetite probe days (15 sessions; 3 sessions each at baseline, at the start of phase I and the end of each phase). A separate subset (n = 50) will complete body composition scans (DXA) at baseline and at the end of each phase. All participants will regularly be weighed and will complete questionnaires and cognitive tasks to assess changes in body weight and appetitive behaviours. Measures of physical activity and biochemical markers will also be taken. Discussion The trial will assess the efficacy of NNS beverages compared to water during a behavioural weight loss and maintenance programme. We aim to understand whether the impact of NNS on weight, dietary adherence and well-being are beneficial or transient and effects on prolonged successful weight loss and weight maintenance through sustained changes in appetite and eating behaviour. Trial registration: Clinical Trials: NCT02591134; registered: 23.10.201

Geminivirus replication protein decreases PCNA sumoylation at two acceptor sites

Geminiviruses are plant viruses with circular, single-stranded DNA (ssDNA) genomes that infect a broad range of plants causing substantial crop diseases worldwide. They replicate in nuclei of infected cells by using host DNA replication machinery and an essential protein encoded in their genome designated Rep (replication-associated protein). This multifunctional protein induces the accumulation of the host factors involved in replication and it is capable of interacting with a lot of plant proteins including PCNA (Proliferating Cell Nuclear Antigen), a processivity factor that coordinates a wide range of processes involved in maintenance, duplication and transmission of the genome, and the sumoylation enzyme that conjugates SUMO to target proteins (SUMO-conjugating enzyme- SCE). PCNA modification by SUMO, and also ubiquitin, has long been known to be of key importance for determining how DNA damage is processed by the replisome and for maintenance of overall genome integrity. In yeast, PCNA sumoylation has been associated to DNA repair involving homologous recombination (HR). Previously, we reported that Rep ectopic expression does not result in broad changes in the sumoylation pattern of plant cells, but it modifies the sumoylation state of selected host proteins. In this work, we show, using a reconstituted sumoylation system in Escherichia coli, that tomato PCNA is sumoylated at two residues, K254 and K164, and that co-expression of the Rep protein suppresses PCNA sumoylation at these lysines. Finally, we confirm that PCNA is sumoylated and that Rep also interferes with PCNA sumoylation in planta.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

The influence of a full-time, immersive simulation-based clinical placement on physiotherapy student confidence during the transition to clinical practice

Background: Novice students may have limited learning opportunities during their early exposure to complex clinical environments, due to the priorities of patient care. Immersive, high-fidelity simulation provides an opportunity for physiotherapy students to be exposed to relatively complex scenarios in a safe learning environment before transitioning to the clinical setting. The present study evaluated the influence of immersive simulation on student confidence and competence. Methods: Sixty penultimate year physiotherapy students completed an 18-day full-time immersive simulation placement. The placement involved students spending 6 days working in each of three core practice areas (cardiopulmonary, musculoskeletal, neurological) in which they interacted with simulated patients portrayed by professional role-play actors. The patient scenarios were developed by groups of expert practitioners and incorporated full documentary and imaging information. Students completed a questionnaire to evaluate their confidence in the clinical environment at the start and completion of each 6-day rotation. Their clinical competence was evaluated at the end of each 6-day rotation using the Assessment of Physiotherapy Practice (APP) tool. In a secondary analysis, the clinical competence of this cohort was evaluated in comparison to a matched cohort of students from the same year group that had not completed an immersive simulation placement. Results: Student confidence improved significantly in each 6-day rotation (p < 0.001); however, it reduced again at the commencement of the next rotation, and there was no cumulative improvement in confidence over the 18-day placement (p = 0.22). Students who had completed the immersive simulation placement achieved higher APP (p < 0.001) scores in an evaluation of their competence to practice during their subsequent clinical placement. Conclusion: Immersive simulation provides a beneficial learning environment to enable physiotherapy students to transition from university-based education to working in the clinical environment

Comparative effectiveness and safety of rituximab versus subsequent anti-tumor necrosis factor therapy in patients with rheumatoid arthritis with prior exposure to anti-tumor necrosis factor therapies in the United States Corrona registry

INTRODUCTION: Patients with active rheumatoid arthritis (RA) despite anti-tumor necrosis factor(anti-TNF)agent treatment can switch to either a subsequent anti-TNF agent or a biologic with an alternative mechanism of action, such as rituximab; however, there are limited data available to help physicians decide between these 2 strategies. The objective of this analysis was to examine the effectiveness and safety of rituximab versus a subsequent anti-TNF agent in anti-TNF-experienced patients with RA using clinical practice data from the Corrona registry. METHODS: Rituximab-naive patients from the Corrona registry with prior exposure to \u3e /=1 anti-TNF agent who initiated rituximab or anti-TNF agents (2/28/2006-10/31/2012) were included. Two cohorts were analyzed: the trimmed population (excluding patients who fell outside the propensity score distribution overlap) and the stratified-matched population (stratified by 1 vs \u3e /=2 anti-TNF agents, then matched based on propensity score). The primary effectiveness outcome was achievement of low disease activity (LDA)/remission (Clinical Disease Activity Index \u3c /=10) at 1 year. Secondary outcomes included achievement of modified American College of Rheumatology (mACR) 20/50/70 responses and meaningful improvement ( \u3e /=0.25) in modified Health Assessment Questionnaire (mHAQ) score at 1 year. New cardiovascular, infectious and cancer events were reported. RESULTS: Estimates for LDA/remission, mACR response and mHAQ improvement were consistently better for rituximab than for anti-TNF agent users in adjusted analyses. The odds ratio for likelihood of LDA/remission in rituximab versus anti-TNF patients was 1.35 (95 % CI, 0.95-1.91) in the trimmed population and 1.54 (95 % CI, 1.01-2.35) in the stratified-matched population. Rituximab patients were significantly more likely than anti-TNF patients to achieve mACR20/50 and mHAQ improvement in the trimmed population and mACR20 and mHAQ in the stratified-matched population. The rate of new adverse events per 100 patient-years was similar between groups. CONCLUSIONS: In anti-TNF-experienced patients with RA, rituximab was associated with an increased likelihood of achieving LDA/remission, mACR response and physical function improvement, with a comparable safety profile, versus subsequent anti-TNF agent users. TRIAL REGISTRATION: ClinicalTrials.gov NCT01402661. Registered 25 July 2011

Risk of Infection Associated With Subsequent Biologic Agent Use After Rituximab: Results From a National Rheumatoid Arthritis Patient Registry

OBJECTIVE: To assess whether the time between the last rituximab infusion and initiation of a different biologic agent influenced infection risk in patients with rheumatoid arthritis (RA). METHODS: Patients with RA who newly initiated rituximab within the Consortium of Rheumatology Researchers of North America registry were included if they switched to a nonrituximab biologic agent and had \u3e /=1 followup visit within 12 months of switching. Patients were categorized by duration of time between their last rituximab infusion and initiation of a subsequent biologic agent (\u3c /=5 months, 6-11 months, and \u3e /=12 months). The primary outcome was time to first infectious event. Adjusted Cox regression models estimated the association between time to starting a subsequent biologic agent and infection. RESULTS: A total of 44 overall infections (7 serious, 37 nonserious) were reported during the 12-month followup in the 215 patients included in this analysis (104 switched at \u3c /=5 months, 67 at 6-11 months, and 44 at \u3e /=12 months). Median (interquartile range) time to infection was 4 (2-5) months. Infection rates per patient-year in the \u3c /=5-month, 6-11-month, and \u3e /=12-month groups were 0.34 (95% confidence interval [95% CI] 0.22-0.52), 0.30 (95% CI 0.17-0.52), and 0.41 (95% CI 0.22-0.77), respectively. After adjustment, time to switch to a subsequent biologic agent was not associated with infection, which remained unchanged when number and rate of rituximab retreatments were included in the models. CONCLUSION: In this real-world cohort of patients with RA, infection rates ranged from 0.30 to 0.41 per patient-year, with no significant difference in the rate between patients who initiated a subsequent biologic agent earlier versus later after rituximab treatment

Effectiveness of Rituximab for the Treatment of Rheumatoid Arthritis in Patients with Prior Exposure to Anti-TNF: Results from the CORRONA Registry

OBJECTIVE: To characterize the real-world effectiveness of rituximab (RTX) in patients with rheumatoid arthritis. METHODS: Clinical effectiveness at 12 months was assessed in patients who were prescribed RTX based on the Clinical Disease Activity Index (CDAI). Change in CDAI was calculated (CDAI at 12 mos minus at initiation). Achievement of remission or low disease activity (LDA; CDAI \u3c /= 10) among those with moderate/high disease activity at the time of RTX initiation was compared based on prior anti-tumor necrosis factor agent (anti-TNF) use (1 vs \u3e /= 2) using logistic regression models. RESULTS: Patients (n = 265) were followed for 12 months with a mean change in CDAI of -8.1 (95% CI -9.8 - -6.4). Of the 218 patients with moderate/high disease activity at baseline, patients with 1 prior anti-TNF (baseline CDAI 25.0) demonstrated a mean change in CDAI of -10.1 (95% CI -13.2 - -7.0); patients with \u3e /= 2 prior anti-TNF (baseline CDAI 30.0) demonstrated a mean change of -10.5 (95% CI -12.9 - -8.0). The unadjusted OR for achieving LDA/remission in patients with moderate/high disease activity at baseline exposed to \u3e /= 2 versus 1 prior anti-TNF was 0.40 (95% CI 0.22-0.73), which was robust to 4 different adjusted models (OR range 0.38-0.44). CONCLUSION: A good clinical response was observed in all patients; however, patients previously treated with 1 anti-TNF, who had lower baseline CDAI and a greater opportunity for clinical improvement compared with patients previously treated with \u3e /= 2 anti-TNF, were more likely to achieve LDA/remission