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Abstract Background Alongside affective episodes, cognitive dysfunction is a core symptom of bipolar disorder. The intracellular parasite T. gondii has been positively associated with both, the diagnosis of bipolar disorder and poorer cognitive performance, across diagnostic boundaries. This study aims to investigate the association between T. gondii seropositivity, serointensity, and cognitive function in an euthymic sample of bipolar disorder. Methods A total of 76 participants with bipolar disorder in remission were tested for T. gondii-specific IgG and IgM antibodies and for cognitive performance using neuropsychological test battery. Cognitive parameters were categorized into three cognitive domains (attention and processing speed, verbal memory, and executive function). Statistical analysis of associations between continuous indicators of cognitive function as dependent variables in relationship to T. gondii, included multivariate analyses of co-variance for seropositivity, and partial correlations with IgG serointensity in IgG seropositives. All analyses were controlled for age and premorbid IQ. Results In seropositives (n = 27), verbal memory showed significant inverse partial correlations with IgG antibody levels (short delay free recall (r=–0.539, p = 0.005), long delay free recall (r=–0.423, p = 0.035), and immediate recall sum trial 1–5 (r=–0.399, p = 0.048)). Cognitive function did not differ between IgG seropositive and seronegative individuals in any of the cognitive domains (F (3,70) = 0.327, p = 0.806, n = 76). IgM positives (n = 7) were too few to be analyzed. Conclusions This investigation is the first to show an association between T. gondii IgG serointensity and memory function in a well-diagnosed bipolar disorder sample. It adds to the existing literature on associations between latent T. gondii infection and cognition in bipolar disorder, while further research is needed to confirm and expand our findings, eliminate potential sources of bias, and establish cause-effect relationships.

Assessing the performance of the ITER design for the tungsten (W) divertor Plasma Facing Units (PFUs) in a tokamak environment is a high priority issue to ensure efficient plasma operation. This paper reviews the most recent results derived from experiments and post-mortem analysis of the ITER-grade PFUs exposed in the WEST tokamak and the associated modelling, with a focus on understanding heat loading and damage evolution. Several shaping options, sharp or chamfered leading edge (LE), unshaped or shaped blocks with a toroidal bevel as foreseen in ITER, were investigated, under steady state heat fluxes of up to 120 MW⋅m−2 and 6 MW⋅m−2 on the sharp LE and top surface of the block, respectively. A very high spatial resolution (VHR) infrared (IR) camera (0.1 mm/pixel) was used to derive the temporal and surface distribution of the temperature and heat load on the castellated tungsten blocks for different geometric alignment and plasma conditions. Photonic modelling was required to reproduce the IR measurements in particular in the toroidal and poloidal gaps of the mono-block (MB) stacks where high apparent temperatures are observed. Specular reflection is found to be the dominant emitter in these parts of the blocks. W-cracking was observed on the leading edge of the blocks already within the first phase of plasma operation, during which the divertor was equipped with unshaped PFUs, including some intentionally misaligned blocks. Numerical analysis taking into account softening processes and mechanical stresses, revealed brittle failure due to transients as the dominant failure mechanisms. Ductile failure was observed in one particular block used for the melting experiment, therefore under extremely high steady state heat load conditions. W-melting achieved on actively cooled PFU exhibits specific features: shallow melting and slow melt displacement. Plasma exposure of pre-damaged PFUs at various damage levels (crack network and melted droplets) was carried out under high heat load conditions with several hours of cumulated plasma duration. IR data and preliminary surface analyses show no evidence of significant degradation damage progression under these conditions.

Abstract This paper is a contribution to the exploration of the parametric Kalman filter (PKF), which is an approximation of the Kalman filter, where the error covariances are approximated by a covariance model. Here we focus on the covariance model parameterized from the variance and the anisotropy of the local correlations, and whose parameters dynamics provides a proxy for the full error‐covariance dynamics. For this covariance model, we aim to provide the boundary condition to specify in the prediction of PKF for bounded domains, focusing on Dirichlet and Neumann conditions when they are prescribed for the physical dynamics. An ensemble validation is proposed for the transport equation and for the heterogeneous diffusion equation over a bounded 1D domain. This ensemble validation requires to specify the auto‐correlation time‐scale needed to populate boundary perturbation that leads to prescribed uncertainty characteristics. The numerical simulations show that the PKF is able to reproduce the uncertainty diagnosed from the ensemble of forecast appropriately perturbed on the boundaries, which show the ability of the PKF to handle boundaries in the prediction of the uncertainties. It results that Dirichlet condition on the physical dynamics implies Dirichlet condition on the variance and on the anisotropy.

Tungsten peaking is predicted in the core of a WEST plasma with total-f gyrokinetic simulations, including both collisional and turbulent transport. This prediction is validated with a synthetic diagnostic of the bolometry. Although nitrogen impurities are shown to reduce the neoclassical peaking of tungsten on-axis, the overall tungsten peaking increases when nitrogen impurities are present, as they reduce the turbulence screening off-axis. This finding is important for the plasma current ramp-up phase of ITER, where light impurities seeding will be desirable to achieve low temperatures at the plasma-facing components and reduce tungsten sputtering. It provides further argument for applying early ECRH heating to maintain margins on the core power balance. The neoclassical peaking factor is cross-verified between XGC and FACIT. The heat flux at separatrix and the heat load width are modeled by XGC and compared to WEST data.

The mission of WEST (tungsten-W Environment in Steady-state Tokamak) is to explore long pulse operation in a full tungsten (W) environment for preparing next-step fusion devices (ITER and DEMO) with a focus on testing the ITER actively cooled W divertor in tokamak conditions. Following the successful completion of phase 1 (2016-2021), phase 2 started in December 2022 with the lower divertor made entirely of actively cooled ITER-grade tungsten mono-blocks. A boronization prior the first plasma attempt allowed for a smooth startup with the new divertor. Despite the reduced operating window due to tungsten, rapid progress has been made in long pulse operation, resulting in discharges with a pulse length of 100 s and an injected energy of around 300 MJ per discharge. Plasma startup studies were carried out with equatorial boron nitride limiters to compare them with tungsten limiters, while Ion Cyclotron Resonance Heating assisted startup was attempted. High fluence operation in attached regime, which was the main thrust of the first campaigns, already showed the progressive build up of deposits and appearance of dust, impacting the plasma operation as the plasma fluence increased. In total, the cumulated injected energy during the first campaigns reached 43 GJ and the cumulated plasma time exceeded 5 h. Demonstration of controlled X-Point Radiator regime is also reported, opening a promising route for investigating plasma exhaust and plasma-wall interaction issues in more detached regime. This paper summarises the lessons learned from the manufacturing and the first operation of the ITER-grade divertor, describing the progress achieved in optimising operation in a full W environment with a focus on long pulse operation and plasma wall interaction.

Within the 9th European Framework programme, since 2021 EUROfusion is operating five tokamaks under the auspices of a single Task Force called ‘Tokamak Exploitation’. The goal is to benefit from the complementary capabilities of each machine in a coordinated way and help in developing a scientific output scalable to future largre machines. The programme of this Task Force ensures that ASDEX Upgrade, MAST-U, TCV, WEST and JET (since 2022) work together to achieve the objectives of Missions 1 and 2 of the EUROfusion Roadmap: i) demonstrate plasma scenarios that increase the success margin of ITER and satisfy the requirements of DEMO and, ii) demonstrate an integrated approach that can handle the large power leaving ITER and DEMO plasmas. The Tokamak Exploitation task force has therefore organized experiments on these two missions with the goal to strengthen the physics and operational basis for the ITER baseline scenario and for exploiting the recent plasma exhaust enhancements in all four devices (PEX: Plasma EXhaust) for exploring the solution for handling heat and particle exhaust in ITER and develop the conceptual solutions for DEMO. The ITER Baseline scenario has been developed in a similar way in ASDEX Upgrade, TCV and JET. Key risks for ITER such as disruptions and run-aways have been also investigated in TCV, ASDEX Upgrade and JET. Experiments have explored successfully different divertor configurations (standard, super-X, snowflakes) in MAST-U and TCV and studied tungsten melting in WEST and ASDEX Upgrade. The input from the smaller devices to JET has also been proven successful to set-up novel control schemes on disruption avoidance and detachment.

Superconducting (SC) tokamak JT-60SA plays an essential role in fusion research and development by supporting and complementing the ITER project, providing directions to the DEMO design activity and fostering next generation scientists and engineers. Since the short circuit incident at the terminal joints of equilibrium field coil #1 during the integrated commissioning (IC) in March 2021, both EU and JA implementing agencies (IAs) have examined how to ensure safe operation of JT-60SA by mitigating the risk of possible discharge occurrence inside the cryostat. Based on the experience of the global Paschen tests, the IAs have established a strategy of risk mitigation measures, which is a combination of (i) reinforcement of insulation, (ii) avoiding unnecessary voltage application to the coil systems and (iii) immediate de-energization of the coils when deteriorated vacuum conditions are detected. Thanks to the considerable efforts of the Integrated Project Team members, the IC restarted in May 2023. After confirmation of the SC state of the coil systems (TF, EF and CS), the coil energization test and the plasma operation phase 1 (OP-1) started. The first plasma was successfully achieved on 23 October 2023 with a limited value of voltage and current applied to the coils. The plasma configuration control was also confirmed with low plasma current and low auxiliary heating power conditions. Based on the IO–F4E–QST collaboration, activities of JT-60SA have been shared with the IO and provided an important lesson for ITER assembly and commissioning, and will provide an outstanding contribution to fusion research at large. After OP-1, maintenance & enhancement phase 1 (M/E-1) starts from January 2024, in which in-vessel components are installed, and heating and diagnostic systems are extensively upgraded to allow a high power heating experiment planned in OP-2. In order to make the best use of JT-60SA, a newly organized JT-60SA experiment team will refine the research plan for the future high heating power operation phase.

The coronavirus disease (COVID-19) pandemic and the social distancing resulting thereof are having a great impact on psychological well-being. Studies investigating resilience found that it impacts mental health during crises. This study aimed to evaluate the influence of pre-crisis temperament on resilience in individuals with bipolar disorder during the COVID-19 pandemic. An online survey was conducted in Austria between April and June 2020, including 36 individuals with bipolar disorder and 39 healthy controls. Resilience was assessed with the 13-item resilience scale, and temperament was measured with the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire (TEMPS-A). The bipolar disorder group showed lower resilience than the control group, and scored higher on the TEMPS-A for depressive, cyclothymic, and anxious temperaments. Resilience could be predicted by anxious temperament in individuals with bipolar disorder, and correlated negatively with depressive symptoms in both groups. The results suggest that anxious temperament influences the resilience of individuals with bipolar disorder, likely more than temporary hardships, such as the first months of the COVID-19 crisis. It is therefore important to improve the resilience of individuals with bipolar disorder not only by short-term interventions, but by strengthening resilience and reducing anxious temperament in the long term.

Introduction Patients with bipolar disorder have a hig risk of becoming overweight and obese, associated with an increased risk of somatic diseases and premature mortality. The Austrian BIPFAT/BIPLONG study aims at investigating lipid metabolism, psychosocial functioning, and cognitive parameters in bipolar disorder (BD). Objectives The aim was to investigate to what extent overweight, obesity and metabolic syndrome (MetS) are associated with clinical symptoms (e.g. suicidality, depressive symptoms) and cognitive factors (attention, memory, executive function) in BD. Methods In addition to anamnestic interview and psychological tests, all participants were tested with a neuropsychological test battery including the Trail Making Test A/B, the Stroop Color and Word Interference Test, the d2 Test of Attention Revised, Digit Span, Digit-Symbol-Test, and the California Verbal Learning Test. Additionally, body mass index (BMI) and variables defining MetS including waist circumference, serum triglycerides, high-density lipoprotein, blood pressure, and fasting glucose levels have been collected in DSM-5 diagnosed patients with BD and healthy controls. Results In our Austrian bipolar cohort (n=290), the median BMI was 27.9 (SD=5.9), 30.5 % of the patients were overweight (BMI = 25.5-29.9) and 24.6% of the patients were obese (BMI ≥ 30.0). In the control group (n=183), the median BMI was 24.5 (SD=4.8), 15.2% were overweight and 8.0% were obese. A sub-analysis in 215 patients showed that compared to overweight patients, normal weight patients showed more suicidal ideation in psychiatric history (χ2(2)=7.97, p=.019). In addition, there was a significant association between suicidal ideation and glucose (r=.15, p=.043) and cholesterol (r=−.17, p=.028). In another sub-analysis with 148 euthymic bipolar patients, we found a high prevalence of MetS in patients with BD (30.4% versus 15.4% in healthy controls) associated with impaired executive function compared to patients without MetS or healthy controls with and without MetS (p=.020). Clinical variables (illness duration, suicidality, number of affective episodes, medication, age of onset, and history of psychosis) did not relate to MetS in BD (p > .05). A longitudinal analysis in 52 patients (35 without MetS and 17 with MetS) did not find an association of MetS on the one-year trajectory of cognitive decline in BD. In contrast, high baseline BMI predicted a decrease in the patient’s performance in working memory in the 12-months observation period. Conclusions The BIPFAT/BIPLONG study demonstrated a high prevalence of overweight, obesity and MetS in bipolar patients with adverse effects on cognitive function. Clinical variables such as suicidality were not related to the presence of obesity or MetS. Clinical impact and further (unpublished) results will be presented. Disclosure of Interest None Declared

Vitamin D status may impact acute affective symptomatology and the severity of symptoms in patients with bipolar disorder (BD). Therefore, this cross-sectional study analyzed 25(OH)D, 24,25(OH)2D, and the vitamin D metabolite ratio (VMR) in BD and correlated the results with clinical affective symptomatology and functionality. The inactive precursor 25(OH)D, and its principal catabolite 24,25(OH)2D, were measured simultaneously with a validated liquid chromatography–tandem mass spectrometry method in 170 BD outpatients and 138 healthy controls. VMR was calculated as follows: VMR = 100×(24,25(OH)2D/25(OH)D). The psychometric assessment comprised: Beck Depression Inventory-II, Hamilton Depression Rating Scale, Young Mania Rating Scale, Global Assessment of Functioning, and number of suicide attempts. We did not find a significant difference between patients and controls in the concentrations of 25(OH)D and 24,25(OH)2D. Additionally, the VMR was comparable in both groups. The calculations for the clinical parameters showed a negative correlation between the Young Mania Rating Scale and 24,25(OH)2D (r = −0.154, p = 0.040), as well as the Young Mania Rating Scale and the VMR (r = −0.238, p = 0.015). Based on the small effect size and the predominantly euthymic sample, further exploration in individuals with manic symptoms would be needed to confirm this association. In addition, long-term clinical markers and an assessment in different phases of the disease may provide additional insights.

Recent evidence on the association between vitamin D and cognition in mentally healthy individuals is inconsistent. Furthermore, the link between vitamin D and cognitive ability in individuals with bipolar disorder has not been studied yet. Thus, we aimed to investigate the association between 25-hydroxyvitamin D (25(OH)D), 24,25 dihydroxyvitamin D (24,25(OH)2D, the vitamin D metabolite ratio (VMR) and cognition in a cohort of euthymic patients with bipolar disorder. Vitamin D metabolites were measured simultaneously by liquid-chromatography tandem mass-spectrometry in serum samples from 86 outpatients with bipolar disorder and 93 healthy controls. Neither the inactive precursor 25(OH)D, nor the primary vitamin D catabolite 24,25(OH)2D, or the vitamin D metabolite ratio were significantly associated with the domains “attention”, “memory”, or “executive function” in individuals with bipolar disorder and healthy controls. Further, no vitamin D deficiency effect or interaction group × vitamin D deficiency was found in the cognitive domain scores. In summary, the present study does not support vitamin D metabolism as a modulating factor of cognitive function in euthymic BD patients. Considering the current study’s cross-sectional design, future research should expand these results in a longitudinal setting and include additional aspects of mental health, such as manic or depressive symptoms, long-term illness course and psychopharmacological treatment.

Abstract Background The coronavirus disease (COVID-19) pandemic, a global health crisis, has resulted in widespread socioeconomic restrictions including lockdown, social distancing, and self-isolation. To date, little is known about the psychological impact of the COVID-19 pandemic and lockdown on patients with bipolar disorder as a particularly vulnerable group. Methods An online survey was conducted in Austria at two points of measurement (T1 April 2020 during the first lockdown vs. T2 May 2020 at post-lockdown). The sample comprises 20 patients with bipolar disorder (mean age = 49.4 ± 15.6 years) and 20 healthy controls (mean age = 32.7 ± 9.6 years). A 2 × 2 factorial design to compare two time points (T1 vs. T2) and two groups (patients vs. healthy controls) was used. Main outcome measures included the Brief Symptom Inventory-18 (BSI-18) and a (non-validated and non-standardized) assessment to determine COVID-19 fears and emotional distress due to social distancing. Multiple linear regression analyses were used to assess the longitudinal association of COVID-19 fears/emotional distress due to social distancing during lockdown (T1) and psychological symptoms after lockdown (T2). Results At T1, results demonstrated higher scores in BSI-18 subscales depression, anxiety and global severity index as well as emotional distress due to social distancing in bipolar patients compared to controls. There was a significant time x group interaction in the BSI-18 subscale somatization showing a decreasing trend in patients with BD compared to controls. No time effects in BSI-18 subscales or COVID-19 fears/emotional distress due to social distancing were observed. Regression analyses showed that COVID-19 fears during lockdown predicted somatization, only in patients. Conclusions There was a connection between the lockdown measures and somatization symptoms observed in patients. When the first steps of easing the social restrictions in May 2020 took place, somatization decreased only in the bipolar compared to the control group. Higher COVID-19 fears during lockdown predicted later symptoms at post-lockdown. Long-term impacts of the COVID-19 pandemic need further investigations to improve current therapeutic approaches and prevent fears and distress during lockdown in individuals with bipolar disorder in times of crisis.

Introduction Immune mediated inflammatory processes are involved in the aetiopathogenesis of bipolar disorder (BD) and weight associated comorbidities. Tryptophan breakdown via indoleamine 2,3-dioxygenase-1 (IDO-1) along the kynurenine axis concomitant with a pro-inflammatory state was found more active in BD but also associated with overweight/obesity. Objectives Aims of our study were to investigate 1.) the tryptophan metabolism in BD compared to mentally healthy controls, 2.) differences in weight classes, 3.) in a longitudinal setting, dependent on the incidence of BD episodes and euthymia. Methods At the Medical University Graz anthropometric and clinical data as well as peripheral tryptophan and kynurenine were assessed in serum samples of 226 individuals with BD and 142 controls. For 75 individuals with BD a longitudinal assessment with three samples was performed. Serum concentrations of tryptophan and kynurenine were determined by reverse-phase high-performance liquid chromatography. The kynurenine/tryptophan was used as a proxy for IDO-1 activity. Results showed a higher kynurenine/tryptophan ratio in BD compared to controls and in overweight compared to normal weight persons. Levels remained stable over time. In the longitudinal course, no differences were found between individuals who were constantly euthymic or not as well who had an illness episode or none. Conclusions Findings indicate that IDO-1 activity might constitute more a trait and not a state marker of BD. Accelerated tryptophan breakdown along the kynurenine axis may be further facilitated by overweight. This may increase the risk of accumulation of neurotoxic metabolites which impacts BD symptomatology, cognition, and somatic comorbidities. Disclosure No significant relationships.

The connection between cognitive function and the “Big Five” personality traits (openness, conscientiousness, extraversion, agreeableness, and neuroticism) in the general population is well known; however, studies researching bipolar disorder (BD) are scarce. Therefore, this study aimed to investigate the Big Five as predictors of executive function, verbal memory, attention, and processing speed in euthymic individuals with BD (cross-sectional: n = 129, including time point t1; longitudinal: n = 35, including t1 and t2). Participants completed the NEO Five-Factor Inventory, the Color and Word Interference Test, the Trail Making Test, the d2 Test of Attention Revised, and the California Verbal Learning Test. The results showed a significant negative correlation between executive function and neuroticism at t1. Changes in cognitive function between t1 and t2 did not correlate with and could not be predicted by the Big Five at t1. Additionally, worse executive function at t2 was predicted by higher neuroticism and lower conscientiousness at t1, and high neuroticism was a predictor of worse verbal memory at t2. The Big Five might not strongly impact cognitive function over short periods; however, they are significant predictors of cognitive function. Future studies should include a higher number of participants and more time in between points of measurement.

Quantitative risk assessment is required by some regulations in specific situations, such as major risk evaluations. The bowtie method, which combines fault and event trees and includes safety barriers, is a valid quantitative method for analyzing industrial risks and a tool for decision-making and safety management. At present, accounting for uncertainties associated with reliability data is not necessarily mandatory in quantitative risk assessment. The quantitative method, as currently implemented, introduces uncertainties that are not addressed in the bowtie. Input data uncertainties linked to choosing values among different sources lead to variability in the results. The possibility method, presented in this article corrects this bias by considering all scenarios, without excluding those with a very low probability. For an industrial company, this specificity can allow to ensure the completeness and the robustness of its risk analysis. This study highlights the impact of uncertainties on the quantification of a bowtie. Besides obtaining a probability, it enables decision-makers to have access to the uncertainty related to the result. This information is essential to judge the trustworthiness of the analysis and to manage risks based on uncertainties. This study allows the development of an advanced bowtie method, by considering the uncertainties associated with the input data.

The ongoing pandemic of coronavirus disease (COVID-19) is a global health crisis that has posed enormous pressure on workers in the health sector (WHS), having a massive impact on their mental health. In this study, we aimed to evaluate the sleep quality of WHS during the pandemic and compare frontline WHS to those who are not directly engaged in the care of COVID-19 patients. This cross-sectional, self-reported online survey assessed the sleep quality of WHS in Austria using the Pittsburgh Sleep Quality Index (PSQI). The same questionnaire was sent out two times. Due to the unequal sample and anonymity of the study participants, we analyzed the data of each time point separate from each other. The first study was conducted in April/May 2020, during the first lockdown in Austria (Study1), and the second study was conducted in July/August 2020, when the social restrictions were loosened (Study2). T-test was used to compare the mean values of PSQI scores between frontline vs. non-frontline WHS, while two two-way ANCOVAs were used to analyze differences in the PSQI mean scores (controlled for age) for male vs. female between frontline vs. non-frontline WHS. During the first lockdown in Austria (Study1) we identified a shorter sleep duration of frontline WHS compared to the non-frontline group, however the difference in global PSQI score between these groups was statistically not significant. In the period after loosened restrictions (Study2) the sleep quality, sleep latency, sleep duration, sleep efficiency and global PSQI score was worse in frontline WHS compared to the non-frontline WHS. Furthermore, female WHS scored higher in the PSQI indicating a worse sleep than male WHS. In addition, nurses and nursing assistants had a higher prevalence of poor sleep quality than other occupational groups. Our results indicate that the COVID-19 pandemic negatively impacts the sleep of WHS, affecting particularly frontline WHS. Preventive interventions aiming to promote good sleep quality in WHS during a healthcare crisis like this pandemic are essential to enhance resilience and mitigate the vulnerability of this specific population.

Combined high-fusion performance and long-pulse operation is one of the key integration challenges for fusion energy development in magnetic devices. Addressing these challenges requires an integrated vision of physics and engineering aspects with the purpose of simultaneously increasing time duration and fusion performance. Significant progress has been made in tokamaks and stellarators, including very recent achievement in duration and/or performance. This progress is reviewed by analyzing the experimental data (109 plasma pulses with a total of 3200 data points, i.e. on average 29 data per pulse) provided by ten tokamaks (in alphabetical order: Axially Symmetric Divertor Experiment Upgrade, DIII-D, Experimental Advanced Superconducting Tokamak, Joint European Torus, JT-60 Upgrade, Korea Superconducting Tokamak Advanced Research, tokamak à configuration variable, Tokamak Fusion Test Reactor, Tore Supra, W Environment in Steady-State Tokamak) and two stellarators (Large Helical Device and Wendelstein 7-X) expanding the pioneering work of Kikuchi (Kikuchi M. and Azumi M. 2015 Frontiers in Fusion Research II: Introduction to Modern Tokamak Physics (Springer)). Data have been gathered up to January 2022 and coordination has been provided by the recently created International Energy Agency-International Atomic Energy Agency international C oordination on I nternational C hallenges on L ong duration OP eration group. By exploiting the multi-machine international database, recent progress in terms of injected energies (e.g. 1730 MJ in L-mode, 425 MJ in H-mode), durations (1056 s in L-mode, 101 s in H-mode), injected powers, and sustained performance will be reviewed. Progress has been made to sustain long-pulse operation in tokamaks and stellarators with superconducting coils, actively cooled components, and/or with metallic walls. The graph of the fusion triple products as a function of duration shows a dramatic reduction of, at least two orders of magnitude when increasing the plasma duration from less than 1 s to 100 s. Indeed, long-pulse operation is usually reached in dominant electron-heating modes at reduced density (current drive optimization) but with low ion temperatures ranging from 1 to 3 keV for discharges above 100 s. Difficulties in extending the duration may arise from coupling high heating powers over long durations and the evolving plasma-wall interaction towards an unstable operational domain. Possible causes limiting the duration and critical issues to be addressed prior to ITER operation and DEMO design are reported and analyzed.

WEST database analysis shows a correlation of the recycled neutral source around the separatrix with core performances. This observation questions the causality chain between particle source and turbulent transport up to the core in L-mode, high recycling plasmas, an unavoidable phase of all scenarios. The best core performances correlate with the lowest values of the density at the separatrix, ${n_{{\text{sep}}}}$ , similarly to ASDEX Upgrade (AUG) tokamak and Joint European Torus (JET) tokamak in H-mode (Verdoolaege et al 2021 Nucl. Fusion 61 076006). Reflectometry in the midplane provides ${n_{{\text{sep}}}}$ , while the temperature at the separatrix, ${T_{{\text{sep}}}}$ is inferred by the ‘two-point model’ using Langmuir probe data on divertor targets. Lower separatrix resistivity does not correlate with better core performances, unlike H-mode observations (Eich et al 2020 Nucl. Fusion 60 056016). As expected in the presence of an efficient neutral source due to recycling fluxes, ${n_{{\text{sep}}}}$ correlates with the D recycled particle flux at the divertor measured by visible spectroscopy. Coherently, at a given controlled central line integrated density $\bar n$ , lower ${n_{{\text{sep}}}}$ correlates with a larger density gradient around the separatrix as well as a larger global density peaking, $\bar n/\langle n\rangle $ , measured by interferometry. The latter correlates as well with lower collisionality in the core, similarly to JET and AUG H-modes (Angioni et al 2007 Nucl. Fusion 47 1326). The correlations reported allow phrasing the subsequent causality question: what is the interplay chain between low neutral recycling at the divertor plates, low density at the separatrix, high density peaking at the separatrix, high global density peaking, higher central temperature and better core energy confinement quality? Understanding the causality chain is essential to prepare ITER operation and design DEMO scenarios where the ratio of the divertor leg to the ionization length will be larger and where the pumped flux with respect to the plasma volume will be lower than presently operating tokamaks.

The ECRH system formerly used in Tore Supra is being upgraded to start on WEST in 2023, at a power level of 1MW and frequency of 105 GHz. Its ultimate 3MW/1000s capability is expected to enlarge the WEST operational domain by increasing margins with respect to H-mode access, and by providing additional flexibility in terms of achievable scenarios using impurity and/or MHD control. This flexibility is made possible using an antenna based on three steerable mirrors for controlled power injection. In order to determine an appropriate range of EC wave injection angles for WEST scenarios, the fast and reliable ray-tracing code REMA has been interfaced with the WEST IMAS database. This allows the EC power damping rate to be quickly assessed, as well as deposition profiles to be predicted in realistic plasma conditions. Based on a typical WEST discharge at central magnetic field B0~3.6 T, central line-averaged electron density nl~4 × 1019 m−3 and central electron temperature Te0~3keV, ray-tracing calculations have been performed. Comprehensive poloidal and toroidal angle scans, as well as variations of Bt, nl and Te0 with respect to the reference parameters have allowed an adequate range of injection angles to be determined for efficient use of ECRH and/or ECCD in typical WEST scenarios, and compared with the mechanical limits set by the antenna mechanical characteristics. In order to further characterize the effect of this new power source in WEST scenarios, EC wave deposition and current profiles from ray-tracing calculations have been included in integrated simulation codes. It has been shown that this additional power source could allow central electron heating to be achieved, potentially alleviating the issue of radiative collapse caused by impurities observed in some situations.

Background: During the peak of the COVID-19 pandemic, healthcare workers worked under stressful conditions, challenging their individual resilience. Therefore, we explored the bidirectional influence of resilience and the factors of COVID-19 work-related fears and anhedonia in Austrian healthcare workers. Methods: Healthcare workers in Austria completed an online survey at two points in time. The first measurement started in winter 2020/2021 (t1), and a second measurement began approximately 1.5 years later (t2). One hundred and eight six individuals completed both surveys and were investigated in a longitudinal design. We applied the Resilience Scale, the Snaith-Hamilton Pleasure Scale, and a self-created questionnaire assessing COVID-19 work-related fears. We used a repeated measures analysis of variance and applied Pearson-Correlations as well as univariate and multivariate analyses of covariance. Results: Resilience was significantly correlated with COVID-19 work-related fears and anhedonia at both points in time in all participants. We found no significant differences for frontline vs. non-frontline workers at t1 and t2. Resilience decreased significantly over time. Limitations: Most subjects were examined cross-sectionally. Frontline workers were underrepresented in our sample. Conclusion: Our findings highlight the importance of resilience in healthcare providers. Steps must be taken to maintain and promote resilience in healthcare workers. We suggest that the improvement of resilience, dealing with fears and uncertainty, and the ability to experience joy might have a beneficial influence on the respective other categories as well.

Turbulence in hot magnetized plasmas is shown to generate permeable localized transport barriers that globally organize into the so-called "ExB staircase" [G. Dif-Pradalier et al., Phys. Rev. E, 82, 025401(R) (2010)]. Its domain of existence and dependence with key plasma parameters is discussed theoretically. Based on these predictions, staircases are observed experimentally in the Tore Supra tokamak by means of high-resolution fast-sweeping X-mode reflectometry. This observation strongly emphasizes the critical role of mesoscale self-organization in plasma turbulence and may have far-reaching consequences for turbulent transport models and their validation.

Abstract Introduction The coronavirus disease (COVID‐19) pandemic and consequent restrictions including social distancing had a great impact on everyday life. To date, little is known about how the restrictions affected sleep, which is commonly disturbed in bipolar disorder (BD). The aim of this study was to elucidate sleep patterns during the pandemic in Austrian BD individuals. Methods An online survey assessed sleep with the Pittsburgh Sleep Quality Index (PSQI) and COVID‐19‐associated attitudes, fears, and emotional distress of 20 BD individuals and 19 controls (HC) during the pandemic. The survey was conducted in April 2020, when very strict regulations were declared, and repeated in May, when they were loosened. Results Individuals with BD reported overall poor sleep according to PSQI sum at both time points. Subjective sleep quality, sleep latency, daytime sleepiness, and PSQI sum were worse in individuals with BD than in HC. Individuals with BD informed themselves more frequently about pandemic‐related topics. Higher information frequency and more COVID‐19 fears (about the virus, own infection, contracting others) correlated with worse PSQI values. Regression models found in BD group that higher information frequency as well as higher COVID‐19 fears in April predicted worse sleep characteristics in May, in particular subjective sleep quality, sleep duration, sleep efficiency, and daytime sleepiness. Conclusion As sufficient sleep duration and quality are essential for well‐being and particularly important for vulnerable BD individuals, it is important that information about the pandemic is gathered to a reasonable extent and mental health professionals include COVID‐19‐related fears when currently treating BD.

Background: Metabolic syndrome (MetS) is more prevalent in individuals with bipolar disorder and has a negative impact on cognition, in particular on executive function, which is already impaired in individuals with bipolar disorder compared to healthy controls.Methods: In a cross-sectional study, we compared 148 euthymic patients with bipolar disorder and 117 healthy controls in cognitive function depending on the diagnosis of MetS. A neuropsychological test battery was used including the Trail Making Test A/B, Stroop Color and Word Interference Test, the d2 Test of Attention Revised, and the California Verbal Learning Test. In addition, MetS variables as well as the defining variables waist circumference, serum triglyceride levels, high-density lipoprotein cholesterol levels, blood pressure, fasting glucose levels, and body mass index were compared between patients and controls. In addition, illness-related variables were associated with MetS in individuals with bipolar disorder.Results: The prevalence of MetS in patients with bipolar disorder was higher than in controls (30.4 vs. 15.4%). Patients with bipolar disorder with MetS had impaired executive function compared to patients without MetS or healthy controls with and without MetS (p = 0.020). No MetS effects or interaction MetS × Group was found in attention/processing speed (p = 0.883) and verbal learning/memory (p = 0.373). Clinical variables (illness duration, suicidality, number of affective episodes, medication, age of onset, and history of psychosis) did not relate to MetS in bipolar disorder (p > 0.05).Conclusion: Bipolar disorder comorbid with MetS bears additional risk for impaired executive function. Executive function includes action planning, inhibition, and impulse control and could play a critical role in keeping long-term goals in mind associated with gaining and maintaining a healthy weight.

For haul truck drivers it is becoming increasingly difficult to find appropriate parking at the end of a shift. Proper, legal, and safe overnight parking spots are crucial for truck drivers in order for them to be able to comply with Hours of Service regulation, reduce fatigue, and improve road safety. The lack of parking spaces affects the backbone of the economy because 70% of all United States domestic freight shipments (in terms of value) are transported by trucks. Many research projects provide real-time truck parking occupancy information at a given stop. However, truck drivers ultimately need to know whether parking spots will be available at a downstream stop at their expected arrival time. We propose a machine-learning-based model that is capable of accurately predicting occupancy 30, 60, 90, and 120 min ahead. The model is based on the fusion of Extreme Gradient Boosting (XGBoost) and Long Short-Term Memory (LSTM) with the help of a feed-forward neural network. Our results show that prediction of truck parking occupancy can be achieved with small errors. Root mean square error metrics are 2.1, 2.9, 3.5, and 4.1 trucks for the four different horizons, respectively. The unique feature of our proposed model is that it requires only historic occupancy data. Thus, any truck occupancy detection system could also provide forecasts by implementing our model.

Abstract Background Older adults with cancer experience negative long‐term functional effects of both cancer and treatments. Exercise may minimize their age‐related and cancer‐related functional decline. Methods We conducted a multicentre open‐label 12 month randomized clinical trial with two parallel arms including participants aged ≥70 years with lymphoma or carcinoma requiring curative treatment. The study started at the beginning of any phase of cancer treatment (surgery, chemotherapy, or radiotherapy). The usual care group (UCG) received the current national recommendations in physical activity (a guideline without specific counselling). The intervention group (IG) received 1 year phoned physical activity advice individually adapted to physical assessment (twice a month during the first 6 months and then monthly). The primary outcome was the proportion of subjects with a 1 year decreased short physical performance battery (SPPB) score of 1 point or more. Physical, cognitive, and clinical secondary outcomes were also investigated. Results We allocated 301 participants (age 76.7 ± 5.0, female 60.6%) to each group. At baseline, the median SPPB was 10/12 in both groups. Breast was the most frequent tumour site (35.7%). After 1 year, 14.0% of participants in the UCG and 18.7% in the IG had a decrease in SPPB score of 1 point or more (P = 0.772). At 2 years, there was no difference in SPPB, gait speed, International Physical Activity Questionnaire score, and verbal fluency. Subgroup analyses after 2 years showed a decline in SPPB for 29.8% of UCG and 5.0% of IG breast cancer participants (P = 0.006), in 21.7% of UCG and 6.2% of IG female participants (P = 0.019), and in 24.5% of UCG and 11.1% of IG normal nutritional status participants (P = 0.009). Falls, hospitalization, institutionalization, and death rates were similar in both groups. Conclusions Personalized phoned physical activity advice had not reduced functional decline at 1 year but provided preliminary evidence that may prevent physical performance decline at 2 years in older adults with breast cancer.

The gut–brain axis plays a role in major depressive disorder (MDD). Gut-bacterial metabolites are suspected to reduce low-grade inflammation and influence brain function. Nevertheless, randomized, placebo-controlled probiotic intervention studies investigating metabolomic changes in patients with MDD are scarce. The PROVIT study (registered at clinicaltrials.com NCT03300440) aims to close this scientific gap. PROVIT was conducted as a randomized, single-center, double-blind, placebo-controlled multispecies probiotic intervention study in individuals with MDD (n = 57). In addition to clinical assessments, metabolomics analyses (1H Nuclear Magnetic Resonance Spectroscopy) of stool and serum, and microbiome analyses (16S rRNA sequencing) were performed. After 4 weeks of probiotic add-on therapy, no significant changes in serum samples were observed, whereas the probiotic groups’ (n = 28) stool metabolome shifted towards significantly higher concentrations of butyrate, alanine, valine, isoleucine, sarcosine, methylamine, and lysine. Gallic acid was significantly decreased in the probiotic group. In contrast, and as expected, no significant changes resulted in the stool metabolome of the placebo group. Strong correlations between bacterial species and significantly altered stool metabolites were obtained. In summary, the treatment with multispecies probiotics affects the stool metabolomic profile in patients with MDD, which sets the foundation for further elucidation of the mechanistic impact of probiotics on depression.

Background: Sleep disturbances are common early warning signs of an episode of bipolar disorder, and early recognition can favorably impact the illness course. Symptom monitoring via a smartphone app is an inexpensive and feasible method to detect an early indication of changes such as sleep. The study aims were (1) to assess the acceptance of apps and (2) to validate sleeping times measured by the smartphone app UP!.Methods:UP! was used by 22 individuals with bipolar disorder and 23 controls. Participants recorded their time of falling asleep and waking-up using UP! for 3 weeks. Results were compared to a validated accelerometer and the Pittsburgh Sleep Quality Index. Additionally, participants were interviewed regarding early warning signs and their feedback for apps as monitoring tools in bipolar disorder (NCT03275714).Results: With UP!, our study did not find strong reservations concerning data protection or continual smartphone usage. Correlation analysis demonstrates UP! to be a valid tool for measuring falling asleep and waking-up times.Discussion: Individuals with bipolar disorder assessed the measurement of sleep disturbances as an early warning sign with a smartphone as positive. The detection of early signs could change an individual's behavior and strengthen self-management. The study showed that UP! can be used to measure changes in sleep durations accurately. Further investigation of smartphone apps' impact to measure other early signs could significantly contribute to clinical treatment and research in the future through objective, continuous, and individual data collection.

Bipolar disorder (BD) is associated with impairments in cognitive functions, in which metabolic factors, e.g., overweight, seem to play a significant role. The aim of this study was to investigate the association between nutritional factors and cognitive performance in euthymic individuals with BD. A study cohort of 56 euthymic individuals with BD was compared to a sample of 53 mentally healthy controls. To assess cognitive function, the following tests were applied: California Verbal Learning Test, Trail Making Test A/B, d2 Test of Attention-Revised, and Stroop’s Color-Word Interference Test. Furthermore, a 4-day food record was processed to evaluate dietary intake of macronutrients, specific micronutrients, and food diversity. Body mass index and waist to height ratio were calculated to assess overweight and central obesity. Results showed no nutritional differences between individuals with BD and controls. Individuals with BD performed worse in the d2 test than controls. Hierarchical regression analyses yielded no association between cognitive and nutritional parameters. However, waist to height ratio was negatively correlated with almost all cognitive tests. Central obesity seems to affect cognitive functioning in BD, while the lack of finding differences in nutritional data might be due to problems when collecting data and the small sample size. Consequently, further studies focusing on objectively measuring food intake with adequate sample size are needed.

Immune-mediated inflammatory processes and oxidative stress are involved in the aetiopathogenesis of bipolar disorder (BD) and weight-associated comorbidities. Tryptophan breakdown via indoleamine 2,3-dioxygenase-1 (IDO-1) along the kynurenine axis concomitant with a pro-inflammatory state was found to be more active in BD, and associated with overweight/obesity. This study aimed to investigate tryptophan metabolism in BD compared to controls (C), stratified by weight classes, in a longitudinal setting, dependent on the incidence of BD episodes. Peripheral tryptophan, kynurenine, and neopterin were assessed in the serum of 226 BD individuals and 142 C. Three samples in a longitudinal assessment were used for 75 BD individuals. Results showed a higher kynurenine/tryptophan in both BD compared to C and overweight compared to normal weight persons. Levels remained stable over time. In the longitudinal course, no differences were found between individuals who were constantly euthymic or not, or who had an illness episode or had none. Findings indicate that tryptophan, kynurenine, and IDO-1 activity may play a role in pathophysiology in BD but are not necessarily associated with clinical manifestations. Accelerated tryptophan breakdown along the kynurenine axis may be facilitated by being overweight. This may increase the risk of accumulation of neurotoxic metabolites, impacting BD symptomatology, cognition, and somatic comorbidities.

Combined high-fusion performance and long-pulse operation is one of the key integration challenges for fusion energy development in magnetic devices. Addressing these challenges requires an integrated vision of physics and engineering aspects with the purpose of simultaneously increasing time duration and fusion performance. Significant progress has been made in tokamaks and stellarators, including very recent achievement in duration and/or performance. This progress is reviewed by analyzing the experimental data (109 plasma pulses with a total of 3200 data points, i.e. on average 29 data per pulse) provided by ten tokamaks (in alphabetical order: Axially Symmetric Divertor Experiment Upgrade, DIII-D, Experimental Advanced Superconducting Tokamak, Joint European Torus, JT-60 Upgrade, Korea Superconducting Tokamak Advanced Research, tokamak à configuration variable, Tokamak Fusion Test Reactor, Tore Supra, W Environment in Steady-State Tokamak) and two stellarators (Large Helical Device and Wendelstein 7-X) expanding the pioneering work of Kikuchi (Kikuchi M. and Azumi M. 2015 Frontiers in Fusion Research II: Introduction to Modern Tokamak Physics (Springer)). Data have been gathered up to January 2022 and coordination has been provided by the recently created International Energy Agency-International Atomic Energy Agency international C oordination on I nternational C hallenges on L ong duration OP eration group. By exploiting the multi-machine international database, recent progress in terms of injected energies (e.g. 1730 MJ in L-mode, 425 MJ in H-mode), durations (1056 s in L-mode, 101 s in H-mode), injected powers, and sustained performance will be reviewed. Progress has been made to sustain long-pulse operation in tokamaks and stellarators with superconducting coils, actively cooled components, and/or with metallic walls. The graph of the fusion triple products as a function of duration shows a dramatic reduction of, at least two orders of magnitude when increasing the plasma duration from less than 1 s to 100 s. Indeed, long-pulse operation is usually reached in dominant electron-heating modes at reduced density (current drive optimization) but with low ion temperatures ranging from 1 to 3 keV for discharges above 100 s. Difficulties in extending the duration may arise from coupling high heating powers over long durations and the evolving plasma-wall interaction towards an unstable operational domain. Possible causes limiting the duration and critical issues to be addressed prior to ITER operation and DEMO design are reported and analyzed. [ABSTRACT FROM AUTHOR]

Probabilistic bowtie risk analysis is a quantitative risk analysis method widely used by industry and recommended by regulatory bodies for studying major hazard scenarios. Its standard use consists in estimating the mean frequency of occurrence of the top event and subsequent consequences by propagating the mean frequency of occurrence of basic events through fault and event trees. Such a practice does not take full advantage of the probabilistic nature of bowtie risk analysis. In this paper, we use an industrial case study to introduce a new and simple graphical representation of probabilistic Bowtie (BT) results that provides a readily interpretable interface with the regulatory risk matrix used by decision-makers. Instead of collapsing the probability distribution of occurrence of an undesirable event into a single value, which may be misleading, it expresses the risk of occurrence as a likelihood of belonging to each level of the risk matrix. This representation is very informative in terms of risk assessment. Slightly more complex than a single value in a risk matrix, this representation more informative in terms of risk assessment and some benefits can be expected for decision-making. It could typically lead to optimization of the asset integrity management policy (periodic inspection and maintenance) or an improved definition of the testing strategy for the safety barriers.

Currently, there is a strong demand for quantitative risk analysis. There is a challenge in describing the process dynamic behaviour in case of failures. We suggest a methodology that combines dynamic simulation (with ASPEN PLUS DYNAMICSTM 9.0 tool), lessons learnt from accidents to identify the most likely deviations and risk matrices. In fact, there is a real interest in knowing the system behaviour during malfunctions for safety analyses. For this purpose, dynamic simulation is an efficient tool to predict the time evolution of process parameters during deviations from normal operating conditions. Moreover, the knowledge of the process dynamic behaviour and the profiles of the operating parameters during a degraded mode permits adequate safety barrier recommendations. The case study concerns a continuous process of propylene glycol (C3H8O2) production. The synthesis reaction involves three consecutive competitive reactions leading to the formation of by-products: di and tri glycols (C6H14O3 and C9H20O4 respectively). The process is composed of a CSTR reactor and two distillation columns in series. The objective is to study the propagation of deviations along the process. This work provides a new perspective on risk quantification through the analysis of deviation propagation along a process involving cascade distillation columns.

The dynamic simulation of a chemical process is carried out to quantify the potential consequences that may arise in response to a deviation propagation. For this purpose, a case study is based on the industrial alkylation of benzene by propene to cumene with the production of a by-product (diisopropylbenzene). It consists of a packed bed reactor and a train of three distillation columns (C-1 to C-3). The presence of a recycle stream from the second distillation column to the reactor feed should be noted. This study examines various scenarios that describe the dynamic response of the alkylation process to a temperature reduction of the reboiler steam in one of the distillation columns. Then, the behaviour of the reactor and the separation unit is analysed to determine the consequences. The computational results show that the effects associated with a temperature reduction of 20 'C of the steam in C-1 can propagate through all the units of the chemical process. This result is due to an increased concentration of light hydrocarbons in downstream equipment. Therefore, a permanent overpressure and a vent release are observed at the top of C-2. On the contrary, C-3 only has a temporary pressure increase that is not high enough to open the safety valve of this column. The objective of this study is to examine the influence of the characteristics of the process safety valve installed at the top of C-2 on the deviation propagation consequences. The results show how these effects are determined not only by the operating conditions of the equipment but also by the vent relief specifications. This study demonstrates in particular that dynamic simulations can be recognized as an important tool for safer industrial operations due to their capability of studying the process deviation propagation.

Bipolar disorder (BPD) is a mood disorder, which is characterized by alternating affective states, namely (hypo)mania, depression, and euthymia. Evidence is growing that BPD has indeed a biologic substrate characterized by chronic inflammation, oxidative stress, and disturbed energy metabolism. Apart from this, there is obviously a hereditary component of this disease with multi-genetic factors. Most probably a susceptibility threshold favors the outbreak of clinical disease after a cascade of stress events that remain to be elucidated in more detail. Evidence is also growing that weak points in brain energy metabolism contribute to outbreak and severity of BPD. Conventional psychopharmacologic therapy must be reassessed under the aspects of weight cycling and development of central obesity as a deterioration factor for a worse clinical course leading to early cardiovascular events in BPD subgroups.

Obesity and weight gain in bipolar disorder (BD) have multifactorial underlying causes such as medication side effects, atypical depressive symptomatology, genetic variants, and disturbances in the neuro-endocrinal system. Therefore, we aim to explore the associations between food craving (FC), clinical parameters, psychotropic medication, and appetite-related hormones. In this cross-sectional investigation, 139 individuals with BD and 93 healthy controls (HC) completed the food craving inventory (FCI). In addition, blood samples (including leptin and acylated ghrelin) were analyzed and sociodemographic and anthropometric data were collected. Individuals with BD reported higher frequencies of total FC as well as craving for fat and fast food than HC. Additionally, we found a significant negative correlation between FC and ghrelin levels in BD. Smokers with BD reported significantly more craving for high fat foods than non-smokers. Age was significantly associated with FC independent of group. Individuals with BD taking olanzapine and quetiapine reported higher frequencies of craving for sweet food, while patients currently taking lithium reported less total FC compared to those without lithium therapy. Likewise, patients currently taking valproate reported less total FC and less craving for sweets than those not taking valproate. FC appears to be of clinical relevance in individuals with BD. Contrary to previous data, this does not seem to be a female phenomenon only and might encompass more than the specific craving for carbohydrates. Although due to the cross sectional design, causality cannot be determined, the association between depressive symptomatology and fast food craving warrants further research.