Search

An increasing demand in the marine industry to reduce emissions led to investigations into more efficient power conversion using fuels with sustainable production pathways. Solid Oxide Fuel Cells (SOFCs) are under consideration for long-range shipping, because of its high efficiency, low pollutant emissions, and fuel flexibility. SOFC systems also have great potential to cater for the heat demand in ships, but the heat integration is not often considered when assessing its feasibility. This study evaluates the electrical and heat efficiency of a 100 kW SOFC system for marine applications fuelled with methane, methanol, diesel, ammonia, or hydrogen. In addition, cathode off-gas recirculation (COGR) is investigated to tackle low oxygen utilisation and thus improve heat regeneration. The software Cycle Tempo is used to simulate the power plant, which uses a 1D model for the SOFCs. At nominal conditions, the highest net electrical efficiency (LHV) was found for methane (58.1%), followed by diesel (57.6%), and ammonia (55.1%). The highest heat efficiency was found for ammonia (27.4%), followed by hydrogen (25.6%). COGR resulted in similar electrical efficiencies, but increased the heat efficiency by 11.9% to 105.0% for the different fuels. The model was verified with a sensitivity analysis and validated by comparison with similar studies. It is concluded that COGR is a promising method to increase the heat efficiency of marine SOFC systems.

Gender dysphoria (GD) and Autism Spectrum Disorder (ASD) co-occur relatively often, but there is no evidence-based treatment for this specific group. Therefore, we examined the effects of a group intervention for adolescents with ASD and GD in a pilot study with a pre-post-test design. The adolescents completed questionnaires on quality of life, self-esteem, gender dysphoric feelings, and social responsiveness. Results show that participating in this peer support group seems to increase aspects of quality of life, i.e., increased parent-reported psychological well-being and decreased psychological complaints. Even though more research is needed, these results indicate that peer support is an invaluable part of treatment for adolescents with ASD and GD.

Gender dysphoria (GD) and Autism Spectrum Disorder (ASD) co-occur relatively often, but there is no evidence-based treatment for this specific group. Therefore, we examined the effects of a group intervention for adolescents with ASD and GD in a pilot study with a pre-post-test design. The adolescents completed questionnaires on quality of life, self-esteem, gender dysphoric feelings, and social responsiveness. Results show that participating in this peer support group seems to increase aspects of quality of life, i.e., increased parent-reported psychological well-being and decreased psychological complaints. Even though more research is needed, these results indicate that peer support is an invaluable part of treatment for adolescents with ASD and GD.

Lumacaftor/ivacaftor (LUM/IVA) improves outcomes in cystic fibrosis (CF) patients homozygous for Phe508del with ppFEV140%. There is limited safety or efficacy data in patients with ppFEV140%. We determined whether LUM/IVA in patients with ppFEV140 would reduce the rate of pulmonary exacerbations.This was a case control study performed on patients12 years, homozygous for Phe508del CFTR mutation and with ppFEV140%. Control subjects were matched for age, sex and ppFEV1, and had mutations ineligible for LUM/IVA. We assessed the rate of pulmonary exacerbations requiring intravenous antibiotics, the mean rate of change in ppFEV1 over 12 months and all adverse events.Data was collected from 7 Australian CF centres on 105 patients; 72 on LUM/IVA and 33 controls. LUM/IVA demonstrated a large reduction in exacerbations with an incident rate ratio of 0.455 (95%CI; 0.306 - 0.676), p 0.001 after adjusting for the number of exacerbations in the previous 12 months. LUM/IVA prolonged the time to first exacerbation and reduced the rate of decline in ppFEV1 over 12 months. Adverse events were common; chest tightness or dyspnoea was experienced by 55% and resulted in cessation of treatment in 32%.Treatment with LUM/IVA resulted in a substantially lower rate of pulmonary exacerbations, prolonged time to first exacerbation and slowed the rate of decline of ppFEV1 in participants with severe lung disease. Adverse reactions to LUM/IVA however were unacceptably frequent, and resulted in a very high discontinuation rate.

Ship designers hardly ever receive feedback from the actual operation of their designs apart from sea acceptance trials. Similarly, crews operating the vessels do not receive a clear picture of the energy performance and environmental footprint of different options. This paper proposes a methodology based on operational data from continuous monitoring, and applies it to an ocean patrol vessel of the Royal Netherlands Navy in order to identify the impact of diverse operational conditions on energy performance over the whole operating range, but also to examine the decision to equip the vessel with hybrid propulsion. Specifically, it introduces mean energy effectiveness indicator and mean total energy efficiency over discretised vessel speed, as the main tool in quantifying the energy gains and losses to assist in making better-advised design and operational decisions. Moreover, it demonstrates a dataset enrichment procedure, using manufacturers' information, in case not all needed sensors are available. Results suggest that electrical propulsion was 15–25% less efficient than the best mechanical propulsion mode, and on the overall energy performance of the vessel, increasing speed by 1 knot caused a 7% and 14% increase over the minimum (Formula presented.) /mile emissions between 8 and 14, and above 14 knots respectively.

Cystic fibrosis (CF) is a genetic disorder causing dysfunctional ion transport resulting in accumulation of viscous mucus that fosters chronic bacterial biofilm-associated infection in the airways. Achromobacter xylosoxidans and Stenotrophomonas maltophilia are increasingly prevalent CF pathogens and while Burkholderia cencocepacia is slowly decreasing, all are complicated by multidrug resistance that is enhanced by biofilm formation. This study investigates potential synergy between the antibiotics ciprofloxacin (0.5–128 µg/mL), colistin (0.5–128 µg/mL) and tobramycin (0.5–128 µg/mL) when combined with the neutral pH form of N-Acetylcysteine (NACneutral) (0.5–16.3 mg/mL) against 11 cystic fibrosis strains of Burkholderia, Stenotrophomonas and Achromobacter sp. in planktonic and biofilm cultures. We screened for potential synergism using checkerboard assays from which fraction inhibitory concentration indices (FICI) were calculated. Synergistic (FICI ≤ 0.5) and additive (0.5 &gt, FICI ≥ 1) combinations were tested on irreversibly attached bacteria and 48 h mature biofilms via time-course and colony forming units (CFU/mL) assays. This study suggests that planktonic FICI analysis does not necessarily translate to reduction in bacterial loads in a biofilm model. Future directions include refining synergy testing and determining further mechanisms of action of NAC to understand how it may interact with antibiotics to better predict synergy.

Spirometry is usually performed under the supervision of a trained respiratory scientist to ensure acceptability and repeatability of results. To evaluate the quality of spirometry performance by adult cystic fibrosis (CF) patients with and without observation by a trained respiratory scientist, an observational, single centre study was conducted between February to December 2020. 74 adults were recruited and instructed to perform spirometry without supervision within 24 h of their remote CF clinic consultation. Spirometry was repeated at their consultation, supervised by a respiratory scientist using video conferencing. The majority of patients achieved grade A (excellent) or B (very good) spirometry quality with (95%) and without supervision (93%) independent of lung function severity. Similarly, forced expiratory volume in 1 second demonstrated no significant differences with paired spirometry performed within a 24 hour period. For a large proportion of adult CF patients, unsupervised portable spirometry produces acceptable and repeatable results.

Een belangrijk deel van onze interesse in de wereld om ons heen is gericht op dieren. Niet alleen voor de voedselproductie of het transport, maar ook vanwege onze empathie voor hen en onze fascinatie voor wat ze voor ons in veel andere rollen(kunnen) betekenen. Paarden, honden, katten en andere gezelschapsdieren maar ook veel landbouwhuisdieren worden als metgezel behandeld en met genegenheid verzorgd. Deze belangstelling voor de band tussen mens en dier is sinds eind vorige eeuw enorm toegenomen door onder andere de berichtgeving in de populaire pers over de positieve impact van dieren op het leven van mensen. Hierdoor is de nieuwsgierigheid van professionals en de samenleving gewekt om deze unieke relatie tussen mens en dier tot meerwaarde te brengen. Met de toenemende inzet van dieren in ons leven, rijst vanzelfsprekend de vraag of die mens-dier interactie wederzijds positief uitpakt. In 2019 is de zienswijze Dierbare Hulpverleners: welzijn voor mens en dier? van De Raad voor Dierenaangelegenheden (RDA) (Raad voor Dierenaangelegenheden, 2019) verschenen waarbij de vraag gesteld werd of, en op welke wijze, dieren bij interventies op verantwoorde wijze kunnen worden ingezet. Zowel in de dagelijkse omgang met, als de inzet van dieren, maar zeker ook in de wetenschappelijke literatuur, is veel vaker aandacht voor hoe dieren de kwaliteit van leven van de mens kunnen bevorderen in vergelijking met hoe de mens de kwaliteit van leven van dieren zouden kunnen verbeteren. Alhoewel deze thematiek het meest herkenbaar is bij sectoren waar dieren ingezet worden bij dierondersteunde interventies (zoals therapie) of hulp (blindengeleidehonden), moet het effect van de mens-dier interactie op het dier veel breder gezien worden. Ook bij de inzet van dieren in opsporing, beveiliging, sport, recreatie en vermaak is er sprake van een intensieve interactie tussen mens en dier. In sommige gevallen is de mens in het partnerschap met het dier zelfs geheel of gedeeltelijk afhankelijk van het dier. De mens-dier interactie is ook (indirect) zichtbaar in het management, en dan met name in de houderij en fokkerij van dieren. Daar waar mensen beslissen over huisvesting, voeding en fokdoelen van dieren, kan de kwaliteit van leven van dieren in gevaar komen wanneer onvoldoende rekening wordt gehouden met de behoeften en aanpassingsmogelijkheden van het dier. Gek genoeg is onderzoek naar het effect van de mens-dier interactie pas aan het einde van de vorige eeuw als een onderzoeksgebied opgekomen. Sindsdien is het onderzoek explosief gegroeid met multidisciplinaire onderzoeksgroepen over de hele wereld. Ook in Nederland wordt voornamelijk op universiteiten onderzoek gedaan naar de interactie tussen dieren, mensen en maatschappij. De thematiek wordt vanuit verschillende disciplines benaderd, waaronder ook vanuit het diergedrag en dierenwelzijn. Op het hbo wordt onderzoek gedaan naar diergedrag, dierenwelzijn en diermanagement; het effect van de mens-dier interactie op het dier heeft daar echter nog een ondergeschikte rol. Het lectoraat Human-Animal Interactions draagt bij aan het verder ontrafelen van wat zich af speelt in de mens-dier interactie en vooral ook wat het voor het dier betekent. De focus ligt bij twee diersoorten: paarden en honden. In de publicatie wordt verder ingegaan op hoede mens-dier interactie tot stand komt, hoe dierenwelzijn een rol speelt in de mens-dier interactie en in welke sectoren mensen met paarden en honden samenwerken.

BackgroundRheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the recent emergence of these events and the lack of guidance for rheumatologists addressing them, a European League Against Rheumatism task force was convened to harmonise expert opinion regarding their identification and management.MethodsFirst, the group formulated research questions for a systematic literature review. Then, based on literature and using a consensus procedure, 4 overarching principles and 10 points to consider were developed.ResultsThe overarching principles defined the role of rheumatologists in the management of irAEs, highlighting the shared decision-making process between patients, oncologists and rheumatologists. The points to consider inform rheumatologists on the wide spectrum of musculoskeletal irAEs, not fulfilling usual classification criteria of rheumatic diseases, and their differential diagnoses. Early referral and facilitated access to rheumatologist are recommended, to document the target organ inflammation. Regarding therapeutic, three treatment escalations were defined: (1) local/systemic glucocorticoids if symptoms are not controlled by symptomatic treatment, then tapered to the lowest efficient dose, (2) conventional synthetic disease-modifying antirheumatic drugs, in case of inadequate response to glucocorticoids or for steroid sparing and (3) biological disease-modifying antirheumatic drugs, for severe or refractory irAEs. A warning has been made on severe myositis, a life-threatening situation, requiring high dose of glucocorticoids and close monitoring. For patients with pre-existing rheumatic disease, baseline immunosuppressive regimen should be kept at the lowest efficient dose before starting immunotherapies.ConclusionThese statements provide guidance on diagnosis and management of rheumatic irAEs and aim to support future international collaborations.

BackgroundRheumatoid arthritis (RA) is the most common autoimmune disease, and requires long-term treatment to suppress inflammation. Currently, methotrexate is initiated as first-line treatment when arthritis becomes clinically apparent with joint swelling. However, disease processes begin long before and become clinically recognizable when patients develop symptoms. We hypothesized that the ‘at risk phase’ of symptoms and subclinical joint-inflammation is a therapeutic window to permanently modify the disease course.ObjectivesWe studied if intervention in the pre-arthritis phase of arthralgia and subclinical joint inflammation prevents the development of clinical arthritis or reduces the burden of disease.MethodsIn this randomised, double-blind, 2-year proof-of-concept trial, adults with arthralgia clinically suspected of progressing to RA and MRI-detected subclinical joint-inflammation, recruited from all rheumatology outpatient-clinics in the southwest-Netherlands, were randomly assigned (1:1) to a single intramuscular glucocorticoid injection (120 mg) and a one-year course of oral methotrexate (up to 25 mg/week), or placebo injection and placebo tablets. Subsequently, participants were followed for another year without study medication. The primary endpoint was the development of clinically detectable arthritis (fulfilling the 2010 RA-criteria or involving ≥2 joints) that persisted for at least 2 weeks. Patient reported physical functioning, along with symptoms and workability, were key secondary endpoints and measured 4-monthly. Additionally, the course of MRI-detected inflammation was studied (the sum of tenosynovitis, synovitis, osteitis, scored with the RA-MRI Scoring (RAMRIS) method). All participants entered the intention-to-treat analysis. We performed two prespecified subgroup analyses. Firstly, analyses were restricted in participants with high risk of clinical arthritis development (PPV ≥70%). Secondly, analyses were stratified for ACPA-status. The trial is registered with the Netherlands Trials Registry (NTR4853 trial NL4599).ResultsFrom April 16th, 2015 to September 11th, 2019, we randomly assigned 236 participants to treatment (n=119) or placebo (n=117). After 24 months, arthritis free survival was similar in both groups (80% versus 82%, HR 0.81 (95%CI 0.45, 1.48)). Physical functioning improved more in the treatment-group during the first months and remained better (mean between-group difference over two-years HAQ -0·1(-0·2,-0·03;p=0·004). Similarly, pain (-9 on scale 0-100: (95%CI -12,-4; pConclusionMethotrexate, the cornerstone treatment of RA, initiated at the pre-arthritis stage of joint symptoms and subclinical inflammation, did not prevent the development of clinical arthritis, but modified the disease course as measured by sustained improvement in MRI-detected inflammation, related symptoms and impairments. These findings of sustained disease modification may open up a new treatment landscape in a pre-arthritis phase of RA, where limitations can be just as severe as at the onset of clinical arthritis.Figure 1.AcknowledgementsWe thank Prof. dr. R. ten Cate, prof. dr. S. le Cessie and dr. A.M.J. Langers for their role in the Data Safety and Monitoring Board. We thank all participants, and all rheumatologist of the following hospitals: Albert Schweitzer Hospital, Alrijne Hospital, Erasmus Medical Center, Haven-policlinic Rotterdam, IJselland Hospital, Ikazia Hospital, Franciscus Gasthuis & Vlietland Hospital, Groene Hart Hospital, Haaglanden Medical Center (all locations), Haga Hospital, Langeland Hospital, Meander Medical Center, Maasstad, Hospital, Reinier de Graaf Gasthuis, Reumazorg Zuid-West Nederland and Spaarne Gasthuis. We acknowledge the team of treating rheumatologists and research nurses of the LUMC, in particular Dr F.J. van der Giesen. Our gratitude also goes to the PhD students who scored MRIs for trial screening, in particular dr. H.W. van Steenbergen, dr. W. Nieuwenhuis, dr. R.M. ten Brink, dr. D.M. Boeters, dr. L. Mangnus, X.M.E. Matthijssen and F. Wouters. We thank dr. M. Reijnierse, prof. dr. S.C. Cannegieter and prof. dr. D. van der Heijde for their advice, and dr. J. Schoones for his help with the systematic literature search. We acknowledge the funder of the study: NWO ZonMW grant (program ‘translationeel onderzoek’, project number 95104004).Disclosure of InterestsNone declared.

Background & aims: The level of adherence to the updated guidelines of The European Societies for Clinical Nutrition and Metabolism (ESPEN) and for Blood and Marrow Transplantation (EBMT) on nutrition in intensively treated adult acute myeloid leukemia (AML) patients in clinical practice is unknown. The aim of this nationwide survey was to investigate ESPEN/EBMT nutritional guideline adherence during intensive AML treatment, variation in nutrition support practices among hospitals and whether these practices changed after guideline publication.Methods: All 22 Dutch hospitals providing (aftercare following) high-dose chemotherapy and/or hematopoietic stem cell transplantation for adult AML patients were surveyed on nutrition support practices during these intensive AML treatments. We used an online questionnaire in 2015 and semi structured telephone interviews in 2018-2019. Both surveys were completed by registered dieticians and addressed the use of enteral (EN) and parenteral (PN) nutrition. The ESPEN/EBMT nutritional guideline adherence was investigated through the telephone interviews.Results: High-level ESPEN/EBMT guideline adherence and/or uniformity among hospitals regarding nutrition support practices during intensive AML treatment were observed for nutritional screening,-aims, safe food handling and exercise training. Adherence to ESPEN/EBMT recommendations that were not implemented into national guidelines, including nutritional assessment and use of medical nutrition, was poor. All hospitals assessed nutritional intake,-impact symptoms and body weight, but muscle mass, physical performance and degree of systemic inflammation were rarely and variably monitored. Although the number of hospitals using EN as first-choice nutritional intervention increased from 3 hospitals in 2015 to 8 in 2019, PN remained the preferred method of nutrition support. Furthermore, the timing of medical nutrition varied.Conclusions: Although the use of EN increased after publication of the updated ESPEN/EBMT nutritional guidelines, adherence to these standards was limited and there was heterogeneity in nutrition support practices during intensive AML treatment among hospitals. Incorporating international nutritional standards into national guidelines by nutrition expert groups immediately upon publication may improve adherence. (c) 2020 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Bronchiectasis is reported to be more frequent in females. There have been no large studies examining the impact of biological sex on disease characteristics, aetiology, severity, quality of life or management. Patients were prospectively enrolled from 2015 -2018 in 3 linked bronchiectasis registries in Australia, Europe and India. Disease information was collected, including quality of life (QoL-B). Analyses were conducted cross-sectionally using baseline data. 13859 patients were included from 29 countries. 57.6% were female. The highest proportion of females were in Australia (70.9%) and lowest in India (43.1%). Male sex was associated with bronchiectasis caused by COPD and TB; while female sex was associated with post-infectious bronchiectasis, asthma, connective tissue disease and NTM. Men had more severe disease as measured by the bronchiectasis severity index, but females more likely to be infected with Pseudomonas aeruginosa. Women had greater disease impact across multiple QoL-B domains including social, emotional and treatment burden domains. Cough and sputum purulence were more severe in women while men most frequently complained of wheeze and breathlessness. Men were significantly less likely to receive evidence based interventions including testing for immunodeficiency and ABPA, long term antibiotic treatment for frequent exacerbators, pulmonary rehabilitation and airway clearance techniques. Conclusion: There are striking sex differences in aetiology, severity, quality of life and treatment in patients with bronchiectasis

Objective In early RA, some patients exhibit rapid radiographic progression (RRP) after one year, associated with poor functional prognosis. Matrices predicting this risk have been proposed, lacking precision or inadequately calibrated. We developed a matrix to predict RRP with high precision and adequate calibration. Methods Post-hoc analysis by pooling individual data from cohorts (ESPOIR and Leuven cohorts) and clinical trials (ASPIRE, BeSt and SWEFOT trials). Adult DMARD-naïve patients with active early RA for which the first therapeutic strategy after inclusion was to prescribe methotrexate or leflunomide were included. A logistic regression model to predict RRP was built. The best model was selected by 10-fold stratified cross-validation by maximizing the Area Under the Curve. Calibration and discriminatory power of the model were checked. The probabilities of RRP for each combination of levels of baseline characteristics were estimated. Results 1306 patients were pooled. 20.6% exhibited RRP. Four predictors were retained: rheumatoid factor positivity, presence of at least one RA erosion on X-rays, CRP > 30mg/l, number of swollen joints. The matrix estimates RRP probability for 36 combinations of level of baseline characteristics with a greatly enhanced precision compared with previously published matrices (95% CI: from ± 0.02 minimum to ± 0.08 maximum) and model calibration is excellent (P = 0.79). Conclusion A matrix proposing RRP probability with high precision and excellent calibration in early RA was built. Although the matrix has moderate sensitivity and specificity, it is easily usable and may help physicians and patients to make treatment decisions in daily clinical practice.

Once neglected in research and underappreciated in practice, there is renewed interest in bronchiectasis unrelated to cystic fibrosis. Bronchiectasis is a chronic lung disease characterised by chronic cough, sputum production and recurrent pulmonary exacerbations. It is diagnosed radiologically on high resolution computed tomography chest scan by bronchial dilatation (wider than the accompanying artery). The causes of bronchiectasis are diverse and include previous respiratory tract infections, chronic obstructive pulmonary disease, asthma, immunodeficiency and connective tissue diseases. A large proportion of cases are idiopathic, reflecting our incomplete understanding of disease pathogenesis. Progress in the evidence base is reflected in the 2017 European management guidelines and the 2015 update to the Australian guidelines. Effective airway clearance remains the cornerstone of bronchiectasis management. This should be personalised and reviewed regularly by a respiratory physiotherapist. There is now robust evidence for the long term use of oral macrolide antibiotics in selected patients to reduce exacerbation frequency. The routine use of long term inhaled corticosteroids and/or long-acting bronchodilators should be avoided, unless concomitant chronic obstructive pulmonary disease or asthma exists. The evidence for nebulised agents including hypertonic saline, mannitol and antibiotics is evolving; however, access is challenging outside tertiary clinics, and nebulising equipment is required. Smokers should be supported to quit. All patients should receive influenza and pneumococcal vaccination. Patients with impaired exercise capacity should attend pulmonary rehabilitation. There is an important minority of patients for whom aetiology-specific treatment exists. The prevalence of bronchiectasis is increasing worldwide; however, the burden of disease within Australia is not well defined. To this end, the Australian Bronchiectasis Registry began recruitment in 2016 and is interoperable with the European and United States bronchiectasis registries to enable collaborative research. The recent addition of a bronchiectasis diagnosis-related group to the Australian Refined Diagnostic Related Group classification system will allow definition of the disease burden within the Australian hospital system.

Multifunction ships, naval vessels in particular, need to reduce fuel consumption while maintaining manoeuvrability. Hybrid propulsion that runs a main diesel engine and electric drive in parallel can achieve this. However, a parallel control strategy needs to be developed. In this paper, we use a simulation model of a hybrid propulsion system to investigate two parallel control strategies for diesel mechanical and electrical propulsion on multifunction ships. For the case study frigate, parallel control can increase the ship top speed with 3 kts when using two 4 MW electric drives and two 10 MW main diesel engines, compared with the same baseline hybrid propulsion without parallel control. The diesel engine speed control with electric drive torque control strategy increases ship acceleration rate with 17% and reduces average engine thermal loading with 150 K. Moreover, the electric drive speed control with diesel engine torque control strategy can improve acceleration rate by 40%, while eliminating thermal loading fluctuation due to heavy seas, and also reducing engine average thermal loading with 150 K. Future combination of the proposed electric drive speed control strategy with an adaptive pitch control and optimal power split strategy can potentially further increase hybrid propulsion plant performance.

Australian data regarding the management of patients with bronchiectasis is scarce. We sought to compare the management of adults with bronchiectasis attending tertiary Australian centres with recent national and international guidelines. The Australian Bronchiectasis Registry is a centralised database of patients with radiologically confirmed bronchiectasis unrelated to cystic fibrosis recruited from 14 tertiary Australian hospitals. We excluded children (

A need exists to identify the sources of risks associated with the process automation systems within petrochemical companies or similar energy related industries. These companies use many different process automation technologies in its value chain. A crucial part of the process automation system is the information technology component featuring in the supervisory control layer. The ever-changing technology within the process automation layers and the rate at which it advances pose a risk to safe and predictable automation system performance. The age of the automation equipment also provides challenges to the operations and maintenance managers of the plant due to obsolescence and unavailability of spare parts. The main objective of this research was to determine the risk sources associated with the equipment that is part of the process automation systems. A secondary objective was to establish whether technology managers and technicians were aware of the risks and share the same viewpoint on the importance of the risks associated with automation systems. A conceptual model for risk sources of automation systems was formulated from models and frameworks in literature. This model comprised six categories of risk which forms the basis for identifying specific risks. This model was used to develop a questionnaire that was sent to 172 instrument technicians and technology managers in the company to obtain primary data. 75 completed and useful responses were received. These responses were analyzed statistically to determine the highest risk sources and to determine whether there was difference in opinion between technology managers and technicians. The most important risks that were revealed in this study are: 1) the lack of skilled technicians, 2) integration capability of third-party system software, 3) reliability of the process automation hardware, 4) excessive costs pertaining to performing maintenance and migrations on process automation systems, and 5) requirements of having third-party communication interfacing compatibility as well as real-time communication networks.

Background Rheumatic immune-related adverse events (irAEs) are increasingly recognized musculoskeletal manifestations in cancer patients receiving immune checkpoint targeted immunotherapy (1). Since they represent a spectrum of new clinical entities and a robust evidence base is lacking, a task force was convened to harmonize expert consensus regarding their identification and management due to the lack of dedicated clinical trials. Objectives To develop EULAR recommendations for the diagnosis and the management of rheumatic irAEs due to cancer immunotherapy, based on literature and expert opinion. Methods Recommendations were developed according to the 2014 EULAR Standard Operating Procedures. The task force consisted of 19 clinical experts from Europe and North America (14 rheumatologists, 2 internists and 3 oncologists), 1 clinical epidemiologist, 1 allied health professional and 2 patient representatives. During the first meeting, the group defined the focus of the task force, the target population, and formulated research questions. A systematic literature research was performed by one fellow (MK) with the help of a librarian. Based on available evidence and using a consensus procedure, recommendations were developed during a second meeting. The level of agreement was determined by an anonymous voting process. Results 4 overarching principles and 10 recommendations were developed. The overarching principles define the role of rheumatologists and highlight the shared decision-making process between patients, oncologists and rheumatologists. One recommendation addresses the referral process, two address the diagnosis, and five address the therapeutic strategy of cancer patients experiencing rheumatic, musculoskeletal, and systemic signs or symptoms while receiving immunotherapy. An additional recommendation was included to address pre-existing rheumatic conditions and the last focuses on the diagnostic approach before immunotherapy. Conclusion These recommendations provide the basis of a EULAR consensus on the diagnosis and the management of rheumatic irAEs. Reference [1] Calabrese LH, Calabrese C, Cappelli LC. Rheumatic immune-related adverse events from cancer immunotherapy. Nat Rev Rheumatol. 2018 Oct;14(10):569-579. Disclosure of Interests Marie Kostine: None declared, Axel Finckh Grant/research support from: Bristol-Myers Squibb, Pfizer Inc, Consultant for: AbbVie, A2Bio, Bristol-Myers Squibb, MSD, Roche, Pfizer Inc, and UCB, Clifton Bingham Grant/research support from: BMS, Consultant for: AbbVie, BMS, Eli Lilly, Genentech/Roche, Janssen, Pfizer, Sanofi/Regeneron, Karen Visser: None declared, Jan Leipe Grant/research support from: Novartis, Pfizer; Scientific Support: Novartis, Pfizer, Consultant for: AbbVie, AstraZeneca, Bristol-Myers Squibb, Celgene, Hospira, Janssen-Cilag, LEO Pharma, Lilly, Novartis, Roche, Sanofi, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Janssen-Cilag, Lilly, Novartis, MSD, Pfizer, Roche, Sanofi, UCB, Hendrik Schulze-Koops Grant/research support from: Novartis, Pfizer, Roche, Consultant for: Abbvie, Actelion, Amgen, AstraZeneca, Biogen International, BMS, Celgene, Chugai, GSK, Hospira, Janssen-Cilag, Leo Pharmaceuticals, Lilly, MSD, Medac, Merck, Novartis, Pfizer, Hexal Sandoz, Sanofi, Roche, UCB, Paid instructor for: Abbvie, Actelion, Amgen, AstraZeneca, Biogen International, BMS, Celgene, Chugai, GSK, Hospira, Janssen-Cilag, Leo Pharmaceuticals, Lilly, MSD, Medac, Merck, Novartis, Pfizer, Hexal Sandoz, Sanofi, Roche, UCB, Speakers bureau: Abbvie, Actelion, Amgen, AstraZeneca, Biogen International, BMS, Celgene, Chugai, GSK, Hospira, Janssen-Cilag, Leo Pharmaceuticals, Lilly, MSD, Medac, Merck, Novartis, Pfizer, Hexal Sandoz, Sanofi, Roche, UCB, Ernest Choy Grant/research support from: Amgen, Bio-Cancer, Chugai Pharma, Ferring Pharmaceuticals, Novimmune, Pfizer, Roche, and Union Chimique Belge, Consultant for: Abbvie, Amgen, AstraZeneca, Biogen, BMS, Boehringer Ingelheim, Celgene, Chelsea Therapeutics, Chugai Pharma, Daiichi Sankyo, Eli Lilly, Ferring Pharmacuetical, GlaxoSmithKline, Hospita, ISIS, Jazz Pharmaceuticals, Janssen, MedImmune, Merrimack Pharmaceutical, Merck Sharp & Dohme, Napp, Novimmune, Novartis, ObsEva, Pfizer, Regeneron, Roche, R-Pharm, SynAct Pharma, Sanofi-Genzyme, Tonix and Union Chimique Belge, Speakers bureau: Amgen, BMS, Boehringer Ingelheim, Chugai Pharma, Eli Lilly, Hospira, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis, and Union Chimique Belge, Karolina Benesova Grant/research support from: Scientific Projects (IIT) I’m involved in as an investigator have been supported, but not initiated or designed by Abbvie and Novartis, Consultant for: Advisory board member on early disease detection for Novartis, Timothy R. Radstake: None declared, Andrew Cope: None declared, Oliver Lambotte: None declared, Jacques-Eric Gottenberg Grant/research support from: Bristol-Myers Squibb, Grant/research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Lilly, Pfizer, Sanofi-Genzyme, UCB Pharma, Consultant for: Bristol-Myers Squibb, Eli Lilly, UCB, Sanofi-Genzyme, Pfizer, Yves Allenbach: None declared, Marianne Visser: None declared, Cindy Rusthoven: None declared, Lone Thomasen: None declared, Shahin Jamal Consultant for: Consultant for Abbvie, Amgen, BMS, Eli Lilly, Pfizer, Janssen, Merck, UCB, Aurelien Marabelle: None declared, James Larkin: None declared, John Haanen Consultant for: Amgen, Merck, MSD, Helsinn, Tesaro and Hexaland, Leonard Calabrese Consultant for: Bristol-Myers-Squibb, Genentech and Astra-Zeneca., Xavier Mariette Grant/research support from: Servier, Consultant for: AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Pfizer, UCB Pharma, Thierry Schaeverbeke: None declared

Background /objective: There are no large, multi-centre studies of Australians with bronchiectasis. The Australian Bronchiectasis Registry (ABR) was established in 2015 to create a longitudinal research platform. We aimed to describe the baseline characteristics of adult ABR participants and assess the impact of disease severity and exacerbation phenotype on quality of life (QoL). Methods The ABR is a centralised database of patients with radiologically confirmed bronchiectasis unrelated to cystic fibrosis. We analysed the baseline data of adult patients (≥18 years). Results From March 2016–August 2018, 799 adults were enrolled from 14 Australian sites. Baseline data were available for 589 adults predominantly from six tertiary centres (420 female, median age 71 years (interquartile range 64–77), 14% with chronic Pseudomonas aeruginosa infection). Most patients had moderate or severe disease based on the Bronchiectasis Severity Index (BSI) (84%) and FACED (59%) composite scores. Using Global Lung function Initiative-2012 reference equations, the majority of patients (48%) had normal spirometry; only 34% had airflow obstruction (FEV1/FVC Conclusions The largest cohort of Australian adults with bronchiectasis has been described. Using contemporary criteria, most patients with bronchiectasis did not have airflow obstruction. The frequent exacerbation trait connotes poorer QoL and greater health-care utilisation.

Objectives: Cystic fibrosis-related diabetes (CFRD) impacts approximately 40 to 50% of adults with cystic fibrosis (CF). Effective diabetes education has been shown to improve long-term self-management and quality of life. This survey explores the educational needs of patients with or developing CFRD and sets out to identify the optimal mode of delivery for diabetes education. Methods: Adult pre- and post-transplant patients with CFRD and early glucose metabolism abnormalities from the Royal Prince Alfred Hospital CF Clinic were invited to partake in an online survey via email or text message in December 2020. The study protocol was approved by the Sydney Local Health District Ethics Committee (X20-0434). Results: 46 participants completed the survey with a response rate of 45% (female 54%;CFRD 78%;mean duration since CFRD diagnosis: 13 years;post-transplant 15%). Main sources of diabetes education for participants were the CF Clinic (65%);Google search (30%) and their general practitioner (13%). 72% of participants with CFRD felt they had enough information to manage their diabetes but favoured having a diabetes education resource package. The majority of participants preferred to receive CFRD information via an email package (61%), while others favoured perusing an educational website (37%) or phone app (24%), when requested (44%) or every 6 months (31%). The most common categories of diabetes-related information requested by participants with CFRD were updated diabetic technology (75%), CF diet and food diaries (58%), exercise (56%), management of hyper-(58%) or hypoglycemia (47%) and diabetes and alcohol consumption (42%). Conclusion: Patients with CFRD and early glucose metabolism abnormalities have ongoing educational needs and may require improved resources, preferably via virtual platforms, to supplement in-person care. Future research on the clinical impact of increasing virtual education will be necessary during this COVID-19 pandemic and beyond.

Progressing limits on pollutant emissions oblige ship owners to reduce the environmental impact of their operations. Fuel cells may provide a suitable solution, since they are fuel efficient while they emit few hazardous compounds. Various choices can be made with regard to the type of fuel cell system and logistic fuel, and it is unclear which have the best prospects for maritime application. An overview of fuel cell types and fuel processing equipment is presented, and maritime fuel cell application is reviewed with regard to efficiency, gravimetric and volumetric density, dynamic behaviour, environmental impact, safety and economics. It is shown that low temperature fuel cells using liquefied hydrogen provide a compact solution for ships with a refuelling interval up to a tens of hours, but may result in total system sizes up to five times larger than high temperature fuel cells and more energy dense fuels for vessels with longer mission requirements. The expanding infrastructure of liquefied natural gas and development state of natural gas-fuelled fuel cell systems can facilitate the introduction of gaseous fuels and fuel cells on ships. Fuel cell combined cycles, hybridisation with auxiliary electricity storage systems and redundancy improvements are identified as topics for further study.

In 2013, potato spindle tuber viroid (PSTVd) was identified in 17 lots of seven dahlia cultivars at a single company in the Netherlands. Analysis of the genotypes showed highest identities with a PSTVd genome from dahlias in Japan. The dahlia isolate could be transferred experimentally to tomato and potato. In tomato this resulted in mild chlorosis and stunting; in potato no symptoms appeared, nor in aerial parts, nor in tubers. The infections in dahlias were eradicated by destroying all infected lots at the infested company. No infections were found in lots of the same cultivars grown by other companies. Moreover, PSTVd was not detected in any of the lots of three other companies that had bought dahlia planting material of the infested company. In 2014, PSTVd was not found in a survey including all cultivars in which PSTVd had been identified in 2013. Therefore, it was concluded that PSTVd had been eradicated in dahlias in the Netherlands.

Background Gadoxetic acid (Primovist™)-enhanced magnetic resonance imaging (P-MRI) scans have higher accuracy and increased detection of small colorectal liver metastases (CRLM) compared to CT scans or conventional MRI scans. But, P-MRI scans are still inconsistently acquired in the diagnostic work up of patients with CRLM. The aim of this study was to determine the influence of P-MRI scans on treatment plan proposition and subsequently the clinical course of the patient. Methods Eighty-three consecutive patients with potentially resectable CRLM based on a conventional CT scan underwent P-MRI scanning prior to treatment. Treatment plans proposed by the multidisciplinary team were compared before and after P-MRI scanning and related to the final treatment and diagnosis, the accuracy for the CT scan and P-MRI scan was calculated. Results P-MRI scans led to a change of treatment in 15 patients (18%) and alteration of extensiveness of local therapy in another 17 patients (20%). All changes were justified leading to an accuracy of 93% for treatment proposition based on P-MRI scan, compared to an accuracy of 75% for the CT scan. Conclusions P-MRI scans provide additional information that can aid in proposing the most suitable treatment for patients with CRLM and might prevent short-term reintervention. Electronic supplementary material The online version of this article (10.1186/s12880-018-0289-x) contains supplementary material, which is available to authorized users.

MRI scan protocols 1.5 Tesla and 3 Tesla Ingenia. Both scanning protocols of 1.5â T and 3â T Ingenia are displayed in a table in the order of acquiring the sequences. (DOCX 20 kb)

OBJECTIVE The aim of this study was to assess whether baseline characteristics in patients with undifferentiated arthritis or early RA affect the possibility of achieving drug-free remission after 1 year (DFR1 year) of early remission induction therapy. METHODS We included 375 patients participating in the IMPROVED study who achieved remission (DAS < 1.6) after 4 months (early remission) and were by protocol able to achieve DFR1 year. Having started with MTX plus prednisone, patients tapered prednisone to zero; after 8 months, those still in remission tapered MTX to zero, while those not in remission restarted prednisone. Characteristics of patients achieving and not achieving DFR1 year were compared. Logistic regression was performed to identify predictors of DFR1 year. RESULTS After 1 year, 119 patients (32%) were in DFR. Presence of RF, fulfilling the 2010 criteria for RA, and a low tender joint count were associated with achieving DFR1 year, whereas presence of ACPA was not. None of the baseline characteristics was independently associated with DFR1 year. DFR1 year was sustained for 4 months in 65% of the patients. ACPA-positive patients less often had sustained DFR than ACPA-negative patients (58% vs 80%, P = 0.013). CONCLUSION After 1 year of remission-steered treatment, 32% of the patients who had achieved early remission after 4 months were able to taper medication and achieved DFR. Neither the presence of ACPA nor any other baseline characteristics were independently associated with achieving DFR1 year, but in ACPA-positive patients DFR was less often sustained.

Recommendations and guidelines for management and treatment of rheumatic diseases exist to help rheumatologists deliver optimal care for their patients in an evidence-based way. However, not all practical questions and medical difficulties encountered by rheumatologists in daily clinical practice can be addressed using these existing guidelines. Moreover, time in practice is limited and usually does not allow for extensive systematic literature research to find evidence regarding a specific medical question that needs answering in due time. Therefore, an essential skill for doctors and those in training, besides medical knowledge and examination skills, is to be able to search for, withdraw and appraise published evidence applicable to a confined topic. A so called CAT – critically appraised topic – is a compact systematic literature research following a strictly formulated PICO to answer a clinical question encountered in daily practice. Results can be presented in department meetings and stored in a database for education purposes and use in daily practice. This presentation will address the structure, the carrying out, as well as important pros and cons of the CAT. Examples will be given drawn from the experience of young rheumatologists in training in the Netherlands.\n\nDisclosure of Interest None declared

Background In early rheumatoid arthritis (RA), some patients exhibit rapid radiographic progression (RRP) after one year, associated with poor functional prognosis. Identifying at the time of diagnosis the characteristics predictive of RRP is of importance. Several matrices predicting this risk have been proposed over the last years. They were limited somewhat in terms of precision or were built using specific populations. Objectives To develop a matrix to predict RRP with better precision and generalizability by pooling databases from various studies. Methods The study is based on the pooling of individual data from cohorts (ESPOIR and Leuven) and clinical trials (BeSt, SWEFOT and ASPIRE). Included patients were adult DMARD-naive patients with recent suspected or confirmed diagnosis of active RA for which the first therapeutic strategy after inclusion was to prescribe MTX or leflunomide in monotherapy for at least 3 months. The main outcome was the presence after one year of RRP defined as an increase in modified Sharp score (vSHS) of at least 5 points between baseline and year one. Baseline characteristics were compared by the presence of RRP to search for predictors. A logistic regression model to predict RRP was built. The best model was selected by 10-fold stratified cross-validation by maximizing the Area Under the Curve (AUC). Calibration and discriminatory power of the model were assessed. Model parameters were extracted to estimate the probability of a RRP for each combination of level of baseline characteristics. Results The data of 1306 patients were pooled. After one year, 236 exhibited RRP (20.6%, CI 95% [18.2–22.9], mean probability of RRP of 0.21). Model of prediction of RRP included as baseline characteristics Rheumatoid Factor (RF) positivity (OR=2.1 CI 95% [1.5–3.0]; p 95% [1.7–3.2]; p 30mg/l (OR=2.1 CI 95% [1.5–3.0]; p 10 (OR=1.5 CI 95% [1.01–2.2]; p=0.048). Model calibration was good (Hosmer and Lemeshow test: p=0.79). AUC was 0.68. The matrix proposes estimated RRP probability for 36 combinations of level of baseline characteristics. Its range goes from patients with a 4.1 fold lower risk of RRP compared to average risk (probability of 0.05 CI 95% [0.03–0.08], patient with CRP 95% [0.39–0.55], patient with CRP >30, with RF, with erosive disease on X-ray, with >10 swollen joints). Conclusions A matrix proposing RRP probability at one year with better precision (i.e. narrower CI 95% than those previously published) in early RA for various combinations of levels of a few common baseline characteristics has been built using several databases. However, discriminating power is not ideal. Further investigations will be needed to fully explore the potential complexity of predicting RRP in early RA. Disclosure of Interest None declared

Ships, in particular service vessels, need to reduce fuel consumption, emissions and cavitation noise while maintaining manoeuvrability and preventing engine overloading. Diesel mechanical propulsion with controllable pitch propellers can provide high fuel efficiency with good manoeuvrability. However, the conventional control strategy with fixed combinator curves limits control freedom in trading-off performance characteristics. In order to evaluate performance of current state-of-the-art and future alternative propulsion systems and their control, a validated propulsion system model is required. To this end, this paper proposes a propulsion model with a Mean Value First Principle (MVFP) diesel engine model that can be parameterised with publicly available manufacturer data and further calibrated with obligatory FAT measurements. The model uses a novel approach to predict turbocharger performance based on Zinner blowdown, the Buchi power and flow balance and the elliptic law for turbines, and does not require detailed information such as compressor and turbine maps. This model predicts system performance within 5% of actual measurements during Factory Acceptance Tests (FAT) of the diesel engines and Sea Acceptance Tests (SAT) of a case study navy ship. Moreover, this paper proposes measures of performance that objectively quantify the fuel consumption, acceleration rate, engine thermal loading and propeller cavitation during trial, design and off-design conditions in specified benchmark manoeuvres, within an hour simulation time. In our experiments, we find that, depending on the control strategy, up to 30% of fuel can be saved, thermal engine loading can be reduced by 90 K, and acceleration time by 50% for a case study Holland class patrol vessel.

After-treatment technologies are adopted in automobiles and ships to meet strict emission regulations, which increase exhaust back pressure. Furthermore, underwater exhaust systems are employed on board ships to save space, and reduce noise and pollution on working decks. However, water at exhaust outlet creates a flow resistance for the exhaust gases, which adds to the back pressure. High back pressure reduces the operating limits of an engine, increases fuel consumption, and can lead to exhaust smoke. While the effects of back pressure were recognized earlier, there is a lack of experimentally validated research on the performance limits of a turbocharged, marine diesel engine against high back pressure for the entire operating window. The focus of this research is to provide a comprehensive understanding of back pressure effects on marine diesel engine performance, and to identify limits of acceptable back pressure along with methods to tackle high back pressure. In this work, a pulse turbocharged, medium speed, diesel engine was tested at different loads and engine speeds; against different values of static back pressure. Additionally, mean value model simulations could be validated and were used to compare the performance of a pulse and constant pressure turbocharged engine against high back pressures of 1 meter water-column (mWC), and for two different values of valve overlap. Using the validated simulation model, the conceptual basis for the engine smoke limit as well as for thermal overloading is investigated. A methodology applying the conceptual basis to define boundaries of acceptable back pressures has been presented in this paper. A combination of pulse turbocharger systems and small valve overlap showed to significantly improve back pressure handling capabilities of engines.

Background Rheumatic immune-related adverse events (irAEs) are increasingly recognized musculoskeletal manifestations in cancer patients receiving immune checkpoint targeted immunotherapy. Since they represent a spectrum of new clinical entities and a robust evidence base is lacking, a task force was convened to harmonize expert consensus regarding their identification and management due to the lack of dedicated clinical trials. Our aim was to develop EULAR recommendations for the diagnosis and the management of rheumatic irAEs due to cancer immunotherapy, based on literature and expert opinion. Methods Recommendations were developed according to the 2014 EULAR Standard Operating Procedures. The task force consisted of 19 clinical experts from Europe and North America (14 rheumatologists, 2 internists and 3 oncologists), 1 clinical epidemiologist, 1 allied health professional and 2 patient representatives. During the first meeting, the group defined the focus of the task force, the target population, and formulated research questions. A systematic literature research was performed by one fellow (MK) with the help of a librarian. Based on available evidence and using a consensus procedure, recommendations were developed during a second meeting. The level of agreement was determined by an anonymous voting process. Results 4 overarching principles and 10 recommendations were developed. The overarching principles define the role of rheumatologists and highlight the shared decision-making process between patients, oncologists and rheumatologists. One recommendation addresses the referral process, two address the diagnosis, and five address the therapeutic strategy of cancer patients experiencing rheumatic, musculoskeletal, and systemic signs or symptoms while receiving immunotherapy. An additional recommendation was included to address pre-existing rheumatic conditions and the last focuses on the diagnostic approach before immunotherapy. Conclusions These recommendations provide the basis of a EULAR consensus on the diagnosis and the management of rheumatic irAEs, worthwhile for rheumatologists, internists and oncologists. Legal entity responsible for the study EULAR, European League Against Rheumatism. Funding EULAR, European League Against Rheumatism. Disclosure All authors have declared no conflicts of interest.

To assess depressive symptoms severity and dispositional optimism in patients with recent onset arthritis both before and after 4 months treatment. Two hundred twenty-two patients with recent onset RA and undifferentiated arthritis in the IMPROVED study filled out the Beck Depression Inventory (BDI-II) to assess depressive symptoms severity and the Life Orientation Test Revised (LOT-R) to measure optimism before and after 4 months of treatment. All patients were treated with methotrexate 25 mg/week and prednisone 60 mg/day (tapered to 7.5 mg/day in 7 weeks). Linear regression analysis was used to assess the association between the disease activity score (DAS) and its components (tender joint count, general well-being measured with a visual analogue scale (VAS), swollen joint count, and erythrocyte sedimentation rate) with the BDI-II an LOT-R scores. In general, depressive symptoms were mild. The DAS was an independent predictor of depressive symptoms scores both at baseline and after 4 months follow-up, in particular tender joint count and VAS global health. Disease activity was not associated with the level of optimism. Nevertheless, patients who achieved clinical remission improved significantly more in both depression score and optimism score than patients who did not. Patients with early arthritis report improvement in depressive symptoms and optimism with improvement in disease activity and achieving clinical remission. Depression scores are associated with pain and unwell being but not with swollen joint counts and inflammatory parameters.

Personalized medicine where each patient receives the right drug and the right intensity of drug treatment for as long as needed or safe is the goal of medicine. The identification of predictors of response is the first step toward this. In rheumatoid arthritis (RA), several prediction matrices were designed to predict the risk of rapid radiological progression (RRP) in the first year of treatment, on either disease modifying anti-rheumatic drug (DMARD) monotherapy or combination therapy with prednisone or a biological agent. Both clinical markers and biomarkers of response to either anti-TNF or different mode of action biological agents, and of successful discontinuation of these agents once the treatment goal has been achieved, have been identified in different studies. Most of these markers need validation in other cohorts. Research into combining clinical markers and biomarkers of response could lead to identification of risk profiles resulting in a new step toward personalized medicine in RA.