Tendon involvement and its association with pain and hand function in patients with osteoarthritis of the hand.

OBJECTIVE: To characterise the frequency and influence of tenosynovitis and tendon damage on pain and hand function using clinical examination and ultrasound (US) in hand osteoarthritis (HOA). METHODS: We included 86 patients with HOA and 23 age- and sex-matched control subjects. Extensor and flexor tendons of both hands were assessed by clinical examination and US for tenosynovitis, tendon damage. Conventional radiographs were acquired. Hand function was evaluated by the function subtest of the M-SACRAH questionnaire and the Moberg pick-up test. K-means cluster analyses was calculated to assess clusters based on radiographic features and sonographic tendon scores. RESULTS: Ultrasound identified the involvement of ≥ 1 tendon in 60/86 (69.8%) HOA patients compared with 2/23 (8.7%) subjects (p< 0.01) in the control group. In the HOA group, US detected tendon damage more often in flexor tendons compared with extensor tendons (2.1% 0.9%, p= 0.03), while tenosynovitis was observed more often in extensor tendons compared with flexor tendons (8% vs 0.6%, p< 0001). The sensitivity and specificity of clinical examination to detect tendon involvement was 81.4% and 34.6%, respectively on the patient level and 14.5% and 83.8% on the tendon level. The cluster analyses revealed one cluster with more radiographic features of HOA and more tendon damage while more tenosynovitis was found in cluster 2. M-SACRAH function did not correlate with tendon involvement on US. CONCLUSION: This study revealed a high frequency of tendon involvement in HOA. Tendon involvement on US did not impact hand function or self-reported pain.

Monitoring what matters to people with diabetes: Do we underestimate the importance of behaviour, attitude, and well-being?

OBJECTIVE: Despite improvements in diabetes monitoring and treatment many patients do not achieve treatment goals. Person-centred approaches have been proposed. However, their practical implementation lags. One barrier is uncertainty about which person-reported outcomes (PROs) should be considered to add the most value. We sought to identify PROs that may be prioritised. METHODS: We used data from a multi-stakeholder Delphi study aimed at developing a person-centred diabetes outcome set and analysed which PROs patients considered important for regular monitoring but healthcare providers less so. Linear regression analyses tested whether belonging to either stakeholder group would predict the importance attributed to an outcome. RESULTS: We found disagreement between patients and healthcare providers on eleven PROs. Stakeholder group predicted perceived importance for ten: self-management behaviours (including performance, perceived importance, motivation, and capacity), sleep quality, diabetes symptoms, screening visit attendance, health status, lifestyle behaviours, and side effects. CONCLUSION: Our findings suggest that, according to patients' preferences, self-management behaviours, health status and sleep are currently not adequately considered in diabetes management, compromising person-centred care. PRACTICAL IMPLICATIONS: This study suggests that prioritising these PROs can facilitate the implementation of more person-centred diabetes monitoring which may support better-informed treatment decisions to achieve treatment goals.

Temporal Recall Strategies in Rheumatoid Arthritis Patients' Emotionally Intense Life Events.

BACKGROUND: Rheumatoid arthritis (RA) patients often encounter psychological challenges due to chronic pain, fatigue, side effects of medications, and disability. This study examines the relationship between autobiographical narratives and recollection patterns in RA patients. We investigated how different recall strategies for positive life events affect the emotional processing of negative episodes. We hypothesized that vividly recalling positive life events provides psychological resources that support a more intense emotional elaboration of stressful memories, allowing individuals to delve deeper into negative life experiences. Additionally, we explored the impact of these perspectives on self-reported well-being and physical health, proposing that re-living positive events improves overall well-being. METHODS: We collected and analyzed high-point and low-point life-story episodes from 60 RA patients (85% female; age mean 61 ± 11 years; range 37-79) using episodic narrative interviews and the Narrative Categorical Content Analysis algorithm (NarrCat). Participants were categorized into 2 clusters based on their temporal perspective during high-point episodes: 25 used a Retrospective viewpoint, while 35 employed a Re-experiencing strategy. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS), and functioning was measured using the Health Assessment Questionnaire (HAQ). RESULTS: The Re-experiencing group, which was more likely to articulate their high-point episode in vivid and real-time narrative, used more psychological perspectives (U(58) = 223, p < 0.01) and showed heightened emotional frequency (U(58) = 280, p < 0.05; positive: U(58) = 328, p < 0.05; negative: U(58) = 278, p < 0.05) in low-point episodes. No significant difference emerged between the two groups regarding psychological state (anxiety, depressive symptoms) and physical impairment. CONCLUSIONS: Vividly recalling positive events may facilitate a deeper exploration of negative memories. The Re-experiencing group showed increased positive emotions during low points, suggesting better emotion regulation. However, no significant association was found between recalling strategies, psychological state, and physical impairment. This indicates that further research is needed to determine whether re-experiencing positive life events is adaptive or maladaptive.

Synthesis of guidance available for assessing methodological quality and grading of evidence from qualitative research to inform clinical recommendations: a systematic literature review.

OBJECTIVE: To understand (1) what guidance exists to assess the methodological quality of qualitative research; (2) what methods exist to grade levels of evidence from qualitative research to inform recommendations within European Alliance of Associations for Rheumatology (EULAR). METHODS: A systematic literature review was performed in multiple databases including PubMed/Medline, EMBASE, Web of Science, COCHRANE and PsycINFO, from inception to 23 October 2020. Eligible studies included primary articles and guideline documents available in English, describing the: (1) development; (2) application of validated tools (eg, checklists); (3) guidance on assessing methodological quality of qualitative research and (4) guidance on grading levels of qualitative evidence. A narrative synthesis was conducted to identify key similarities between included studies. RESULTS: Of 9073 records retrieved, 51 went through to full-manuscript review, with 15 selected for inclusion. Six articles described methodological tools to assess the quality of qualitative research. The tools evaluated research design, recruitment, ethical rigour, data collection and analysis. Seven articles described one approach, focusing on four key components to determine how much confidence to place in findings from systematic reviews of qualitative research. Two articles focused on grading levels of clinical recommendations based on qualitative evidence; one described a qualitative evidence hierarchy, and another a research pyramid. CONCLUSION: There is a lack of consensus on the use of tools, checklists and approaches suitable for appraising the methodological quality of qualitative research and the grading of qualitative evidence to inform clinical practice. This work is expected to facilitate the inclusion of qualitative evidence in the process of developing recommendations at EULAR level.

Pregnancy outcomes in patients with systemic lupus erythematosus compared to a high-risk tertiary cohort and to standard population from the Austrian birth registry.

INTRODUCTION: Women with systemic lupus erythematosus (SLE) have a higher risk for fetal and maternal complications. We aimed to investigate maternal and fetal complications in pregnant women with SLE compared to a high-risk pregnancy cohort (HR) from a tertiary university center and a standard-risk general population (SR) from the Austrian Birth Registry. MATERIAL AND METHODS: In this retrospective data analysis, we compared the incidence of fetal/neonatal and maternal complications of pregnancies and deliveries of women with SLE to age, body mass index and delivery date-matched high-risk pregnancies from the same department, a progressive tertiary obstetric center and to a group of women, who represent pregnancies with standard obstetric risk from the Austrian Birth Registry. RESULTS: One hundred women with SLE were compared to 300 women with high-risk pregnancies and 207 039 women with standard-risk pregnancies. The incidence of composite maternal complications (preeclampsia, Hemolysis, Elevated Liver enzymes and Low Platelets [HELLP] syndrome, pregnancy-related hypertension, gestational diabetes mellitus, maternal death, thromboembolic events) was significantly higher in the SLE as compared to the SR group (28% vs. 6.28% SLE vs. SR, p = 0.001). There was no difference between the SLE and the HR groups (28% vs. 29.6% SLE vs. HR group, p = 0.80). The incidence of composite fetal complications (preterm birth before 37 weeks of gestation, stillbirths, birthweight less than 2500 g, fetal growth restriction, large for gestational age, admission to neonatal intensive care unit, 5-min Apgar <7) was also higher in the SLE than in the SR group (55% vs. 25.54% SLE vs. SR p < 0.001) while the higher incidence of adverse fetal outcome was detected in the HR than in the SLE group (55% vs. 75% SLE vs. HR group, p = 0.0005). CONCLUSIONS: Although composite fetal risk is higher in the SLE group than in the general population, it is still significantly lower as compared to high-risk pregnant women at a tertiary obstetric center. Prepregnancy counseling of women with SLE should put fetal and maternal risk in perspective, not only in relation to healthy, low risk cohorts, but also compared to mixed HR populations.

Prognostic Factors for Early Recurrence After Resection of Pancreatic Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: More than half of pancreatic ductal adenocarcinomas (PDACs) recur within 12 months after curative-intent resection. This systematic review and meta-analysis was conducted to identify all reported prognostic factors for early recurrence in resected PDACs. METHODS: After a systematic literature search, a meta-analysis was conducted using a random effects model. Separate analyses were performed for adjusted vs unadjusted effect estimates as well as reported odds ratios (ORs) and hazard ratios (HRs). Risk of bias was assessed using the Quality in Prognostic Studies tool, and evidence was rated according to Grading of Recommendations Assessment, Development and Evaluation recommendations. RESULTS: After 2903 abstracts were screened, 65 studies were included. Of these, 28 studies (43.1%) defined early recurrence as evidence of recurrence within 6 months, whereas 34 (52.3%) defined it as evidence of recurrence within 12 months after surgery. Other definitions were uncommon. Analysis of unadjusted ORs and HRs revealed 41 and 5 prognostic factors for early recurrence within 6 months, respectively. When exclusively considering adjusted data, we identified 25 and 10 prognostic factors based on OR and HR, respectively. Using a 12-month definition, we identified 38 (OR) and 15 (HR) prognostic factors from unadjusted data and 38 (OR) and 30 (HR) prognostic factors from adjusted data, respectively. On the basis of frequency counts of adjusted data, preoperative carbohydrate antigen 19-9, N status, nondelivery of adjuvant therapy, grading, and tumor size based on imaging were identified as key prognostic factors for early recurrence. CONCLUSIONS: Reported prognostic factors of early recurrence vary considerably. Identified key prognostic factors could aid in the development of a risk stratification framework for early recurrence. However, prospective validation is necessary.

2023 EULAR classification criteria for hand osteoarthritis.

OBJECTIVES: The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on self-reported data and radiographic features. METHODS: The classification criteria sets were developed in three phases. In phase 1, we identified criteria that discriminated hand OA from controls. In phase 2, we used a consensus-based decision analysis approach to derive a clinician-based evaluation of the relative importance of the criteria. In phase 3, we refined the scoring system, determined the cut-offs for disease classification and compared the sensitivity and specificity of the European Alliance of Associations for Rheumatology (EULAR) criteria with the 1990 American College of Rheumatology (ACR) criteria. RESULTS: In persons with hand symptoms and no other disease (including psoriasis) or acute injury that can explain the hand symptoms (mandatory criteria), hand OA can be classified based on age, duration of morning stiffness, number of joints with osteophytes and joint space narrowing, and concordance between symptoms and radiographic findings. Using a sum of scores based on each diagnostic element, overall hand OA can be classified if a person achieves 9 or more points on a 0-15 scale. The cut-off for interphalangeal OA and thumb base OA is 8 points. While the EULAR criteria demonstrated better sensitivity than the ACR criteria in the phase 1 data set, the performance of the two criteria sets was similar in two external cohorts. CONCLUSIONS: International experts developed the EULAR criteria to classify overall hand OA, interphalangeal OA and thumb base OA in clinical studies using a rigorous methodology.

The impact of the SARS-CoV2 pandemic on the prescription of thyroid medication in Austria - A nationwide population-based registry analysis.

BACKGROUND: Case reports indicate a clinical connection between SARS-CoV-2 and thyroid dysfunctions. However, evidence from large population-based registry analyses is sparse, especially in Europe, where iodine deficiency is common. This study aimed to analyze the impact of the COVID-19 pandemic on healthcare provision for thyroid diseases in Austria. METHODS: We performed a retrospective, population-based registry analysis of the Austrian health insurance fund database, covering more than 9 million inhabitants. Data from all patients with prescriptions of thyroid-specific drugs and/or inpatient thyroid-related diagnoses from 2017 to 2019 (pre-pandemic years) were compared to 2020 and 2021 (pandemic years; characterized by high numbers of SARS-CoV2 infections and population-wide vaccination strategy). The incidence rates of thyroid medication prescriptions for hypothyroidism and hyperthyroidism were calculated for every year to evaluate the impact of the pandemic. RESULTS: The incidence rate for total thyroid medication prescription was 539.07/100,000 individuals (534.23-543.93 95%CI) in 2018 and declined during the pandemic (2020: 387.19/100,000 (383.12-391.29 95%CI); 2021: 336.90/100,000 (333.11-340.73 95%CI)). Similarly, the incidence rate for levothyroxine prescription was higher pre-pandemic (2018: 465.46/100,000 (460.97-469.98 95%CI) and declined during the pandemic (2020: 348.14/100,000 (344.28-352.03 95%CI); 2021: 300.30/100,000 (296.7-303.91 95%CI). The incidence rates of thiamazole prescriptions (2018: 10.24/100,000 (9.58-10.93 95%CI); 2020: 8.62/100,000 (8.03-9.26 95%CI); 2021: 11.17/100,000 (10.49-11.89 95%CI) were stable. CONCLUSIONS: These findings suggest no clinically significant impact of SARS-CoV2 and/or vaccination on thyroid function at a population level.

Lifestyle interventions in the management of systemic sclerosis: a systematic review of the literature.

Objectives: We aimed to investigate the efficacy of lifestyle interventions for the management of SSc. Methods: We searched the MEDLINE, Embase, Web of Science and CINAHL databases in June 2021. We included studies conducted on five or more patients with SSc published between 1 January 2000 and the search date evaluating lifestyle interventions, excluding systematic reviews without meta-analyses. Critical appraisal was conducted using critical appraisal tools from the Joanna Briggs Institute. Thirty-six studies were included for full-text evaluation. Results: A total of 17 studies evaluated the effect of physical exercise alone, whereas 14 studies evaluated educational interventions for mental health management, often with physical exercise as a central component. At an aggregated level, these studies support patient education and physical exercise for the improvement of physical function, in particular hand and mouth function. Studies on diet and nutrition were few (n = 5) and pertained to gastrointestinal as well as anthropometric outcomes; these studies were insufficient to support any conclusions. Conclusion: Physical exercise and patient education should be considered for improving physical function in patients with SSc. These interventions can be provided alongside pharmacotherapy, but there is no evidence supporting that they can be a substitute. Further research should aim at assessing the effects of reductions of harmful exposures, including tobacco smoking and alcohol, improving sleep and enhancing social relations, three hitherto underexplored facets of lifestyle in the context of SSc.

Effects of lung inflammation and injury on pulmonary tissue penetration of meropenem and vancomycin in a model of unilateral lung injury.

OBJECTIVE: The timing and dosing of antimicrobial therapy are key in the treatment of pneumonia in critically ill patients. It is uncertain whether the presence of lung inflammation and injury affects tissue penetration of intravenously administered antimicrobial drugs. The effects of lung inflammation and injury on tissue penetration of two antimicrobial drugs commonly used for pneumonia were determined in an established model of unilateral lung injury. METHODS: Unilateral lung injury was induced in the left lung of 13 healthy pigs through cyclic rinsing; the right healthy lung served as control. Infusions of meropenem and vancomycin were administered and concentrations of these drugs in lung tissue, blood, and epithelial lining fluid (ELF) were compared over a period of 6 h. RESULTS: Median vancomycin lung tissue concentrations and penetration ratio were higher in inflamed and injured lungs compared with uninflamed and uninjured lungs (AUC0-6h: P = 0.003 and AUCdialysate/AUCplasma ratio: P = 0.003), resulting in higher AUC0-24/MIC. Median meropenem lung tissue concentrations and penetration ratio in inflamed and injured lungs did not differ from that in uninflamed and uninjured lungs (AUC0-6: P = 0.094 and AUCdialysate/AUCplasma ratio: P = 0.173). The penetration ratio for both vancomycin and meropenem into ELF was similar in injured and uninjured lungs. CONCLUSION: Vancomycin penetration into lung tissue is enhanced by acute inflammation and injury, a phenomenon barely evident with meropenem. Therefore, inflammation in lung tissue influences the penetration into interstitial lung tissue, depending on the chosen antimicrobial drug. Measurement of ELF levels alone might not identify the impact of inflammation and injury.

Influence of malocclusion on OHRQoL in adolescents in initial orthodontic treatment phase.

OBJECTIVES: Besides correcting malocclusions, another main objective of orthodontic treatment is to improve patients' oral health-related quality of life (OHRQoL). This study aimed to assess changes in OHRQoL of children within the first six months of orthodontic therapy with fixed orthodontic appliances. METHODS: 85 patients aged 11 to 14 years requiring fixed orthodontic appliance therapy were included. The children completed the German version of the Child Perceptions Questionnaire (CPQ-G-11-14) before (T0), 1 month (T1) and 6 months (T2) after the start of orthodontic treatment. The type of malocclusion was categorized according to the Index of Orthodontic Treatment Need (IOTN). RESULTS: The initial type of malocclusion affected the children's OHRQoL, whereas gender and age did not. The IOTN dental health component (DHC) had a significant impact on the CPQ score (median CPQ of 15.00 for the group DHC 4 vs. 22.50 for DHC 5, p = 0.032). The onset of orthodontic treatment initially affected the CPQ domains "Oral symptoms" and "Functional limitations, with a change versus baseline of 2.00 (p = 0.001), but improved again after 6 months. Regression analysis demonstrated that children with an IOTN DHC 5 malocclusion experienced a greater impact on their ORHQoL, as indicated by a CPQ score 7.35 points higher than that of children with an IOTN DHC 4 malocclusion (p = 0.015). CONCLUSIONS: At the beginning of orthodontic treatment, the OHRQoL slightly worsens, probably due to the discomfort and appearance of the appliances. However, 6 months after the start of orthodontic treatment, OHRQoL improved again in patients with severe malocclusion (IOTN 4 and 5), and approached baseline values. CLINICAL RELEVANCE: The results help the clinician to better understand specific aspects of oral health that may be affected by different malocclusions, thereby improving the child's satisfaction and overall quality of life.

A national evaluation analysis and expert interview study of real-world data sources for research and healthcare decision-making.

Real-world data (RWD) can provide intel (real-world evidence, RWE) for research and development, as well as policy and regulatory decision-making along the full spectrum of health care. Despite calls from global regulators for international collaborations to integrate RWE into regulatory decision-making and to bridge knowledge gaps, some challenges remain. In this work, we performed an evaluation of Austrian RWD sources using a multilateral query approach, crosschecked against previously published RWD criteria and conducted direct interviews with representative RWD source samples. This article provides an overview of 73 out of 104 RWD sources in a national legislative setting where major attempts are made to enable secondary use of RWD (e.g. law on the organisation of research, "Forschungsorganisationsgesetz"). We were able to detect omnipresent challenges associated with data silos, variable standardisation efforts and governance issues. Our findings suggest a strong need for a national health data strategy and data governance framework, which should inform researchers, as well as policy- and decision-makers, to improve RWD-based research in the healthcare sector to ultimately support actual regulatory decision-making and provide strategic information for governmental health data policies.

Efficacy of lifestyle interventions in the management of systemic lupus erythematosus: a systematic review of the literature.

We performed a systematic review to explore existing evidence regarding the efficacy of lifestyle interventions for the management of systemic lupus erythematosus (SLE). The search was conducted on the 22nd of June 2021 for publications between 1st of January 2000 and the date of search. Additional articles within the aforementioned timeframe and until December 2023 were added by hand searching. Databases utilized were Medline, Embase, Web of Science, and Cinahl. Lifestyle interventions were defined as any intervention encompassing one or more of the following: physical exercise, diet and nutrition, mental health, harmful exposures, sleep, and social relations. The Joanna Briggs Institute critical appraisal tools were used for risk of bias assessment. The search yielded 11,274 unique records, we assessed the full text of 199 records, and finally included 102 studies. Overall, the quality of the evidence is limited, and there were multiple sources of heterogeneity. The two domains most extensively researched were mental health (40 records) and physical exercise (39 records). Psychological interventions had a positive effect on depressive symptoms, anxiety, and health-related quality of life (HRQoL), whereas physical exercise improved fatigue, depressive symptoms, aerobic capacity, and physical functioning. Studies on diet and nutrition (15 records) support that low fat intake and Mediterranean diet may be beneficial for reducing cardiovascular risk, but large interventional studies are lacking. Studies on harmful exposures (7 records) support photoprotection and use of sunscreen. While studies imply benefits regarding disease burden and drug efficacy in non-smokers and regarding HRQoL in normal-weight patients, more survey is needed on tobacco smoking and alcohol consumption, as well as weight control strategies. Studies on social relations (1 record) and sleep (no records) were sparse or non-existent. In conclusion, psychosocial interventions are viable for managing depressive symptoms, and exercise appears essential for reducing fatigue and improving aerobic capacity and physical function. Photoprotection should be recommended to all patients. Lifestyle interventions should be considered a complement, not a substitute, to pharmacotherapy.

Life outcomes after paediatric kidney transplantation: a qualitative, biographical study in long-term survivors.

OBJECTIVE: The objective of this study was to analyse the narrative life stories of children with end-stage kidney disease (ESKD) and their families to determine how health professionals can effectively support these children to achieve better life outcomes. DESIGN: Qualitative narrative biographic study. SETTING: We invited every long-term survivor of paediatric kidney transplants and their families at the Medical University of Vienna between 2008 and 2013 to participate in this study. PARTICIPANTS: Nineteen patients (women: n=8, 42%) and 34 family members (women: n=22, 65%) were interviewed. The patients had a mean age of 7.6 (SD±5.6) years at the time of transplantation and 22.2 (SD±5.4) at the time of interview. MAIN OUTCOMES MEASURES: A qualitative narrative biographical analysis was combined with computational structured topic models using the Latent Dirichlet Allocation. RESULTS: The overarching finding was the desire for normality in daily life in long-term survivors and their families but with different perceptions of what normality looks like and predominance of this aspect evolving. Different strategies were used by patients (focused on their advancement) and caregivers (normality for all family members). Siblings played a major role in supporting survivors' social inclusion. CONCLUSIONS: The strong desire for normality confirms recent findings of the Standardised Outcomes in Nephrology Group initiative, which proposes survival and life participation as core outcomes in children with chronic kidney disease. Our study should be a starting point for an international effort to identify typologies and stratified interventions for children with ESKD and their families, particularly siblings.

Antimicrobial Drug Penetration Is Enhanced by Lung Tissue Inflammation and Injury.

Rationale: Pneumonia is a frequent and feared complication in intubated critically ill patients. Tissue concentrations of antimicrobial drugs need to be sufficiently high to treat the infection and also prevent development of bacterial resistance. It is uncertain whether pulmonary inflammation and injury affect antimicrobial drug penetration into lung tissue.Objectives: To determine and compare tissue and BAL fluid concentrations of ceftaroline fosamil and linezolid in a model of unilateral acute lung injury in pigs and to evaluate whether dose adjustment is necessary to reach sufficient antimicrobial concentrations in injured lung tissue.Methods: After induction of unilateral acute lung injury, ceftaroline fosamil and linezolid were administered intravenously. Drug concentrations were measured in lung tissue through microdialysis and in blood and BAL fluid samples during the following 8 hours. The primary endpoint was the tissue concentration area under the concentration curve in the first 8 hours (AUC0-8 h) of the two antimicrobial drugs.Measurements and Main Results: In 10 pigs, antimicrobial drug concentrations were higher in inflamed and injured lung tissue compared with those in uninflamed and uninjured lung tissue (median ceftaroline fosamil AUC0-8 h [and interquartile range] = 26.7 mg ⋅ h ⋅ L-1 [19.7-39.0] vs. 16.0 mg ⋅ h ⋅ L-1 [13.6-19.9], P = 0.02; median linezolid AUC0-8 h 76.0 mg ⋅ h ⋅ L-1 [68.1-96.0] vs. 54.6 mg ⋅ h ⋅ L-1 [42.7-60.9], P = 0.01), resulting in a longer time above the minimal inhibitory concentration and in higher peak concentrations and dialysate/plasma ratios. Penetration into BAL fluid was excellent for both antimicrobials, but without left-to-right differences (ceftaroline fosamil, P = 0.78; linezolid, P = 1.00).Conclusions: Tissue penetration of two commonly used antimicrobial drugs for pneumonia is enhanced by early lung tissue inflammation and injury, resulting in longer times above the minimal inhibitory concentration. Thus, lung tissue inflammation ameliorates antimicrobial drug penetration during the acute phase.