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Objectives: To develop an operational definition of contextual factors (CF) [1].Methods: Based on previously conducted interviews, we presented three CF types in a Delphi survey; Effect Modifying-, Outcome Influencing -and Measurement Affecting CFs. Subsequently, a virtual Special Interest Group (SIG) session was held for in depth discussion of Effect Modifying CFs.Results: Of 161 Delphi participants, 129 (80%) completed both rounds. After two rounds, we reached consen-sus (>70% agreeing) for all but two statements. The 45 SIG participants were broadly supportive.Conclusion: Through consensus we developed an operational definition of CFs, which was well received by OMERACT members. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

CuCrZr alloy is candidate heat sink material for the ITER blanket, first wall, and divertor. During ITER operation it will be exposed to a combination of elevated temperatures, heat flux, and intense fast neutron radiation. This environment will challenge the performance of components and joints based on CuCrZr. To address this issue, mechanical tests were performed with irradiated and reference specimens of CuCrZr and its joints with 316 L(N)-IG (ITER Grade) stainless steel made by hot isostatic pressing. The reactor exposure up to ∼0.7 dpa was performed in the BR2 reactor at SCK•CEN, in water at a temperature of 257 °C A special design was used to allow irradiation of specimens axially pre-stressed at different strain levels. The post-irradiation examination included: (i) tensile test, (ii) measurements of plastic deformation of samples axially loaded during irradiation (in situ creep test); (iii) thermal creep tests on irradiated samples. The fracture surfaces were examined in a hot cell using a Scanning Electron Microscope (SEM). The results were compared with data obtained from mechanical tests and SEM/EDX fracture surface analysis on non-irradiated reference samples. The level of a possible creep under irradiation is below the experimental uncertainty.

Background: Long-term follow-up from the randomized trial of interferon beta-1b (IFNB-1b) permitted the assessment of different definitions of no evidence of disease activity (NEDA) for predicting long-term outcome in multiple sclerosis (MS). Objective: To examine the predictive validity of different NEDA definitions. Methods: Predictive validity for negative disability outcomes (NDOs) at 16 years and survival at 21 years post-randomization were assessed. NEDA in the first 2 years was defined as follows: clinical NEDA: no relapses or Expanded Disability Status Scale (EDSS) progression from baseline to Year 2; NEDA-3a: no relapses, no confirmed ⩾1-point EDSS progression, and no new T2-active lesions; NEDA-3b: no relapses, no EDSS progression, and no increase in T2 burden of disease (T2-BOD); and NEDA-4: no relapses, no EDSS progression, and no increase in T2-BOD or atrophy. NDOs were defined as death, need for wheelchair, EDSS ⩾6, or progressive MS. Results: A total of 245 and 371 patients were evaluated at 16 and 21 years, respectively. Clinical NEDA predicted NDOs ( p = 0.0029), as did baseline EDSS ( p Conclusion: Clinical NEDA predicted long-term disability outcome. By contrast, definitions of NEDA that included on-therapy changes in magnetic resonance imaging variables did not increase the predictive validity.

Objective.Despite advances integrating patient-centered outcomes into rheumatologic studies, concerns remain regarding their representativeness across diverse patient groups and how this affects equity. The Outcome Measures in Rheumatology (OMERACT) Equity Working Group aims to determine whether and how to address equity issues within the core outcome sets of domains and instruments.Methods.We surveyed current and previous OMERACT meeting attendees and members of the Campbell and Cochrane Equity Group regarding whether to address equity issues within the OMERACT Filter 2.0 Core Outcome Sets and how to assess the appropriateness of domains, instruments, and measurement properties among diverse patients. At OMERACT 2016, results of the survey and a narrative review of differential psychosocial effects of rheumatoid arthritis (i.e., on men) were presented to stimulate discussion and develop a research agenda.Results.We proposed 6 moments for which an equity lens could be added to the development, selection, or testing of patient-reported outcome measures (PROM): (1) recruitment, (2) domain selection, (3) feasibility in diverse settings, (4) instrument validity, (5) thresholds of meaning, and (6) consideration of statistical power of subgroup analyses for outcome reporting.Conclusion.There is a need to (1) conduct a systematic review to assess how equity and population characteristics have been considered in PROM development and whether these differences influence the ranking of importance of outcome domains or a patient’s response to questionnaire items, and (2) conduct the same survey described above with patients representing groups experiencing health inequities.

Some aspects of signal analysis of WP 2 CROCUS and AKR-2 experiments in comparison to WP 4 NPP Goesgen measurements

In real world applications, robotic solutions remain impractical due to the challenges that arise in unknown and unstructured environments. To perform complex manipulation tasks in complex and cluttered situations, robots need to be able to identify the interaction possibilities with the scene, i.e. the affordances of the objects encountered. In unstructured environments with noisy perception, insufficient scene understanding and limited prior knowledge, this is a challenging task. In this work, we present an approach for grasping unknown objects in cluttered scenes with a humanoid robot in the context of a nuclear decommissioning task. Our approach combines the convenience and reliability of autonomous robot control with the precision and adaptability of teleoperation in a semi-autonomous selection of grasp affordances. Additionally, this allows exploiting the expert knowledge of an experienced human worker. To evaluate our approach, we conducted 75 real world experiments with more than 660 grasp executions on the humanoid robot ARMAR-6. The results demonstrate that high-level decisions made by the human operator, supported by autonomous robot control, contribute significantly to successful task execution.

Concrete exposure to high temperatures induces thermo-hygral phenomena, causing water phase changes, buildup of pore pressure and vulnerability to spalling. In order to predict these phenomena under various conditions, a three-phase transport model is proposed. The model is validated on X-ray CT data up to \SI{320}{\celsius}, showing good agreement of the temperature profiles and moisture changes. A dehydration description, traditionally derived from thermogravimetric analysis, was replaced by a formulation based on data from neutron radiography. In addition, treating porosity and dehydration evolution as independent processes, previous aproaches do not fulfill the solid mass balance. As a consequence, a new formulation is proposed that introduces the porosity as an independent variable, ensuring the latter condition.

Objective To validate standard self-report questionnaires for depression screening in patients with rheumatoid arthritis (RA) and compare these measures to one another and to the Montgomery-Asberg Depression Rating Scale (MADRS), a standardized structured interview. Methods In 9 clinical centers across Germany, depressive symptomatology was assessed in 262 adult RA patients at baseline (T0) and at 12 ± 2 weeks followup (T1) using the World Health Organization 5-Item Well-Being Index (WHO-5), the Patient Health Questionnaire (PHQ-9), and the Beck Depression Inventory II (BDI-II). The construct validity of these depression questionnaires (using convergent and discriminant validity) was evaluated using Spearman's correlations at both time points. The test–retest reliability of the questionnaires was evaluated in RA patients who had not undergone a psychotherapeutic intervention or received antidepressants between T0 and T1. The sensitivity and the specificity of the questionnaires were calculated using the results of the MADRS, a structured interview, as the gold standard. Results According to Spearman's correlation coefficients, all questionnaires met convergent validity criteria (ρ > |0.50|), with the BDI-II performing best, while correlations with age and disease activity for all questionnaires met the criteria for discriminant validity (ρ 80%) when using the MADRS as the gold standard. Conclusion The BDI-II best met the predefined criteria, and the PHQ-9 met most of the validity criteria, with lower sensitivity and specificity.

The Horizon2020 European project CORTEX aims at developing an innovative core monitoring technique that allows detecting anomalies in nuclear reactors, such as excessive vibrations of core internals, flow blockage, or coolant inlet perturbations. The technique will be mainly based on using the fluctuations in neutron flux recorded by in-core and ex-core instrumentation, from which the anomalies will be differentiated depending on their type, location and characteristics. The project will result in a deepened understanding of the physical processes involved, allowing utilities to detect operational problems at a very early stage. In this framework, neutron noise computational methods and models are developed. In parallel, mechanical noise experimental campaigns are carried out in two zero-power reactors: AKR-2 and CROCUS. The aim is to produce high quality neutron noise-specific experimental data for the validation of the models. In CROCUS, the COLIBRI experimental program was developed to investigate experimentally the radiation noise induced by fuel rods vibrations. In this way, the 2018 first CORTEX campaign in CROCUS consisted in experiments with a perturbation induced by a fuel rods oscillator. Eighteen fuel rods located at the periphery of the core fuel lattice were oscillated between ±0.5 mm and ±2.0 mm around their central position at a frequency ranging from 0.1 Hz to 2 Hz. Signals from 11 neutron detectors which were set at positions in-core and ex-core in the water reflector, were recorded. The present article documents the results in noise level of the experimental campaign. Neutron noise levels are compared for several oscillation frequencies and amplitudes, and at the various detector locations concluding to the observation of a spatial dependency of the noise in amplitude.

BACKGROUND: Neuroanatomical pattern classification using support vector machines (SVMs) has shown promising results in classifying Multiple Sclerosis (MS) patients based on individual structural magnetic resonance images (MRI). OBJECTIVES: To determine whether pattern classification using SVMs facilitates predicting conversion to clinically definite multiple sclerosis (CDMS) from clinically isolated syndrome (CIS). METHODS: We used baseline MRI data from 364 patients with CIS, randomised to interferon beta-1b or placebo. Non-linear SVMs and 10-fold cross-validation were applied to predict converters/non-converters (175/189) at two years follow-up based on clinical and demographic data, lesion-specific quantitative geometric features and grey-matter-to-whole-brain volume ratios. We applied linear SVM analysis and leave-one-out cross-validation to subgroups of converters (n=25) and non-converters (n=44) based on cortical grey matter segmentations. RESULTS: Highest prediction accuracies of 70.4% (p=8e-5) were reached with a combination of lesion-specific geometric (image-based) and demographic/clinical features. Cortical grey matter was informative for the placebo group (acc.: 64.6%, p=0.002) but not for the interferon group. Classification based on demographic/clinical covariates only resulted in an accuracy of 56% (p=0.05). Overall, lesion geometry was more informative in the interferon group, EDSS and sex were more important for the placebo cohort. CONCLUSIONS: Alongside standard demographic and clinical measures, both lesion geometry and grey matter based information can aid prediction of conversion to CDMS.

Objective.Despite the importance of shared decision making for delivering patient-centered care in rheumatology, there is no consensus on how to measure its process and outcomes. The aim of this Outcome Measures in Rheumatology (OMERACT) working group is to determine the core set of domains for measuring shared decision making in intervention studies in adults with osteoarthritis (OA), from the perspectives of patients, health professionals, and researchers.Methods.We followed the OMERACT Filter 2.0 method to develop a draft core domain set by (1) forming an OMERACT working group; (2) conducting a review of domains of shared decision making; and (3) obtaining opinions of all those involved using a modified nominal group process held at a session activity at the OMERACT 12 meeting.Results.In all, 26 people from Europe, North America, and Australia, including 5 patient research partners, participated in the session activity. Participants identified the following domains for measuring shared decision making to be included as part of the draft core set: (1) identifying the decision, (2) exchanging information, (3) clarifying views, (4) deliberating, (5) making the decision, (6) putting the decision into practice, and (7) assessing the effect of the decision. Contextual factors were also suggested.Conclusion.We proposed a draft core set of shared decision-making domains for OA intervention research studies. Next steps include a workshop at OMERACT 13 to reach consensus on these proposed domains in the wider OMERACT group, as well as to detail subdomains and assess instruments to develop a core outcome measurement set.

Objective.We aimed to evaluate how minimal (clinically) important differences (MCID/MID) were calculated in rheumatology in the past 2 decades and demonstrate how the calculation is compromised by the lack of interval scaling.Methods.We conducted a systematic literature review on articles reporting MCID calculation in osteoarthritis (OA) and rheumatoid arthritis (RA) from January 1, 1989, to May 9, 2014. We evaluated the methods of MCID calculation and recorded the ranges of MCID for common patient-reported outcome measures (PROM). Taking data from the Health Assessment Questionnaire (HAQ), we showed the effects of performing mathematical calculations on ordinal data.Results.A total of 330 abstracts were reviewed and 123 articles chosen for full text review. Thirty-six (19 OA, 16 RA and 1 OA-RA) articles were included in the final evaluation. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was the most frequently reported PROM with relevant calculations in OA, and the HAQ in RA. Sixteen articles used anchor-based methods alone for calculation of MCID, and 1 article used distribution-based methods alone. Nineteen articles used both anchor and distribution-based methods. Only 1 article calculated MCID using an interval scale. Wide ranges in MCID for the WOMAC in OA and HAQ in RA were noted. Ordinal-based derivations of MCID are shown to understate true change at the margins, and overstate change in the mid-range of a scale.Conclusion.The anchor-based method is commonly used in the calculation of MCID. However, the lack of interval scaling is shown to compromise validity of MCID calculation.

Objective.To describe the experience of a first-time participant (“newbie”) training program at the Outcome Measures in Rheumatology 12 meeting in 2014.Methods.We conducted newbie sessions at OMERACT 12, including a 2-hour introductory session on Day 1, followed by 1-h evening followup sessions on days 1–4 of OMERACT 12. Pre- and postmeeting surveys assessed participants’ level of comfort with the principles of the OMERACT Filters 1.0 (truth, discrimination, feasibility), and Filter 2.0 (the essential tools for OMERACT methodology), the different types of OMERACT sessions, and whether participants felt welcome.Results.In all, 25 new attendees participated in the introductory session and 10–16 attended followup sessions. Fewer participants reported being somewhat or extremely uncomfortable with the meeting, comparing Day 1 (preintroductory session) to days 1–4 (post): (1) with different OMERACT sessions: 56% (pre) versus 6%, 0%, 8%, and 6% (post days 1–4, respectively); and (2) with principles of the OMERACT filter, 64% (pre) versus 7%, 0%, 8%, and 0% (post), respectively. Most reported feeling welcome (100%) and that they were able to contribute substantively to breakout sessions (87%) on Day 1 evening; results were sustained on days 2–4.Conclusion.First-time participant training sessions increased the comfort level of the participants with the OMERACT meeting structure and filter, and increased the ability of the new attendees to feel they could contribute to the OMERACT process.

Background: Treatment of multiple sclerosis (MS) with interferon β can lead to the development of antibodies directed against interferon β that interfere with treatment efficacy. Several observational studies have proposed different HLA alleles and genetic variants associated with the development of antibodies against interferon β. Objective: To validate the proposed genetic markers and to identify new markers. Methods: Associations of genetic candidate markers with antibody presence and development were examined in a post hoc analysis in 941 patients treated with interferon β-1b in the Betaferon® Efficacy Yielding Outcomes of a New Dose (BEYOND) and BEtaseron®/BEtaferon® in Newly Emerging multiple sclerosis For Initial Treatment (BENEFIT) prospective phase III trials. All patients were treated with interferon β-1b for at least 6 months. In addition, a genome-wide association study was conducted to identify new genetic variants. Results: We confirmed an increased risk for carriers of HLA-DRB1*04:01 (odds ratio (OR) = 3.3, p = 6.9 × 10−4) and HLA-DRB1*07:01 (OR = 1.8, p = 3.5 × 10−3) for developing neutralizing antibodies (NAbs). Several additional, previously proposed HLA alleles and genetic variants showed nominally significant associations. In the exploratory analysis, variants in the HLA region were associated with NAb development at genome-wide significance (OR = 2.6, p = 2.30 × 10−15). Conclusion: The contribution of HLA alleles and HLA-associated single-nucleotide polymorphisms (SNPs) to the development and titer of antibodies against interferon β was confirmed in the combined analysis of two multi-national, multi-center studies.

Somatic angiotensin-converting enzyme (ACE) contains two active sites, the C- and N-domain, from which the C-domain is supposed to play a major role in blood pressure regulation and is therefore a promising pharmacological target to reduce blood pressure without side-effects. We report for the first time that tryptophan-containing dipeptides such as Ile-Trp or Val-Trp, which were recently found in food protein hydrolysates, are selective and competitive inhibitors for the C-domain with a selectivity factor of 40 and 70, respectively. Structure-activity studies showed that an N-terminal aliphatic amino acid and a tryptophan moiety in the P2' position are favourable structures for C-domain inhibition in dipeptides. In contrast, the lactotripeptides Ile-Pro-Pro and Val-Pro-Pro, which were widely used as ingredients for hypotensive food, showed a slight selectivity for the N-domain. Hence, tryptophan containing dipeptides are interesting ingredients for functional foods as a natural prevention for hypertension with reduced side effects due to its selective inhibition of the C-domain.

Objective.The importance of contextual factors (CF) for appropriate patient-specific care is widely acknowledged. However, evidence in clinical trials on how CF influence outcomes remains sparse. The 2014 Outcome Measures in Rheumatology (OMERACT) Handbook introduced the role of CF in outcome assessment and defined them as “potential confounders and/or effect modifiers of outcomes in randomized controlled trials.” Subsequently, the CF Methods Group (CFMG) was formed to develop guidance on how to address CF in clinical trials.Methods.First, the CFMG conducted an e-mail survey of OMERACT working groups (WG) to analyze how they had addressed CF in outcome measurement so far. The results facilitated an informed discussion at the OMERACT 2016 CFMG Special Interest Group (SIG) session, with the aim of gaining preliminary consensus regarding an operational definition of CF and to make a first selection of potentially relevant CF.Results.The survey revealed that the WG had mostly used the OMERACT Handbook and/or the International Classification of Functioning, Disability and Health (ICF) definition. However, significant heterogeneity was found in the methods used to identify, refine, and categorize CF candidates. The SIG participants agreed on using the ICF as a framework along with the OMERACT Handbook definition. A list with 28 variables was collected including person-related factors and physical and social environments. Recommendations from the SIG guided the CFMG to formulate 3 preliminary projects on how to identify and analyze CF.Conclusion.New methods are urgently needed to assist researchers to identify and characterize CF that significantly influence the interpretation of results in clinical trials. The CFMG defined first steps to develop further guidance.

Objective.The aim of this Outcome Measures in Rheumatology (OMERACT) Working Group was to determine the core set of outcome domains and subdomains for measuring the effectiveness of shared decision-making (SDM) interventions in rheumatology clinical trials.Methods.Following the OMERACT Filter 2.0, and based on a previous literature review of SDM outcome domains and a nominal group process at OMERACT 2014, (1) an online Delphi survey was conducted to gather feedback on the draft core set and refine its domains and subdomains, and (2) a workshop was held at the OMERACT 2016 meeting to gain consensus on the draft core set.Results.A total of 170 participants completed Round 1 of the Delphi survey, and 116 completed Round 2. Respondents came from 29 countries, with 49% being patients/caregivers. Results showed that 14 out of the 17 subdomains within the 7 domains exceeded the 70% criterion (endorsement ranged from 83% to 100% of respondents). At OMERACT 2016, only 8% of the 96 attendees were patients/caregivers. Despite initial votes of support in breakout groups, there was insufficient comfort about the conceptualization of these 7 domains and 17 subdomains for these to be endorsed at OMERACT 2016 (endorsement ranged from 17% to 68% of participants).Conclusion.Differences between the Delphi survey and consensus meeting may be explained by the manner in which the outcomes were presented, variations in participant characteristics, and the context of voting. Further efforts are needed to address the limited understanding of SDM and its outcomes among OMERACT participants.

Objective.To describe the experience of the first-time participant (newbie) training program at the Outcome Measures in Rheumatology (OMERACT) 2016 meeting.Methods.We conducted new participant sessions at OMERACT 2016, including a 2-h introductory session on Day 1 followed by 1-h evening followup sessions on days 1–4. Pre- and post-meeting surveys assessed participants’ levels of comfort with the principles of the OMERACT Filter 2.0 (the essential tools for OMERACT methodology) and the different types of OMERACT sessions, and whether participants felt welcome. In addition, on the final day, a nominal group technique was used to elicit problematic components of the meeting and to develop solutions to those problems.Results.Of the 43 new attendees, 38 participated in the introductory session and 14–18 attended the followup sessions. Comparing Day 1 (preintroductory session) to days 1–3 (post), a similar proportion understood different types of sessions extremely well [45% (pre) versus 47%, 44%, and 36% (post), respectively], and a higher proportion understood principles of the OMERACT filter extremely well [22% (pre) versus 55%, 44%, and 40% (post), respectively]. Most reported feeling welcome (86.7%) and felt they contributed to breakout sessions (93.3%) on the evening of Day 1; results were sustained on days 2–3. The most commonly reported “best” experience included the OMERACT culture and the most common reported experience needing improvement included facilitation issues during breakouts.Conclusion.The first-time participants came to OMERACT 2016 with a high baseline level of understanding. They rapidly attained a high comfort level with participation and provided concrete and innovative solutions to the most commonly reported experiences needing improvement.

The present article gives an overview of the first experimental campaigns carried out in the AKR-2 and CROCUS reactors within the framework of the Horizon 2020 European project CORTEX. CORTEX aims at developing innovative core monitoring techniques that allow detecting anomalies in nuclear reactors, e.g. excessive vibrations of core internals. The technique will be mainly based on using the fluctuations in neutron flux, i.e. noise analysis. The project will result in a deepened understanding of the physical processes involved. This will allow utilities to detect operational problems at a very early stage, and to take proper actions before such problems have any adverse effect on plant safety and reliability. The purpose of the experimental campaigns in the AKR-2 and CROCUS reactors is to produce noise-specific experimental data for the validation of the neutron noise computational models developed within this framework. The first campaigns at both facilities consisted in measurements at reference static states, and with the addition of mechanical perturbations. In the AKR-2 reactor, perturbations were induced by two devices: a rotating absorber and a vibrating absorber, both sets in experimental channels close to the core. In CROCUS, the project benefited from the COLIBRI experimental program: 18 periphery fuel rods were oscillated at a maximum of ±2 mm around their central position in the Hz range. The present article documents the experimental setups and measurements for each facility and perturbation type.