| 1. |
- Gregson, J., et al.
(author)
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Cardiovascular Risk Factors Associated With Venous Thromboembolism
- 2019
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In: JAMA Cardiology. - : American Medical Association (AMA). - 0965-2590 .- 2380-6583 .- 2380-6591. ; 4:2, s. 163-173
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Journal article (peer-reviewed)abstract
- IMPORTANCE It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). OBJECTIVE To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. DESIGN, SETTING, AND PARTICIPANTS This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CND], 25131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). RESULTS Of the 731728 participants from the ERFC. 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. CONCLUSIONS AND RELEVANCE Older age, smoking, and adiposity were consistently associated with higher VTE risk.
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| 2. |
- Kaptoge, S., et al.
(author)
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World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions
- 2019
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In: Lancet Global Health. - : Elsevier BV. - 2214-109X. ; 7:10
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Journal article (peer-reviewed)abstract
- Background To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0.685 (95% CI 0 . 629-0 741) to 0.833 (0 . 783-0- 882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
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| 3. |
- Hudson, Lawrence N, et al.
(author)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Journal article (peer-reviewed)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Berglund, U. W., et al.
(author)
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Validation and development of MTH1 inhibitors for treatment of cancer
- 2016
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:12, s. 2275-2283
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Journal article (peer-reviewed)abstract
- Background: Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment. Material and methods: Human cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models. Results: Here, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo. Conclusion: We demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.
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| 8. |
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| 9. |
- Felton, Adam, et al.
(author)
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Replacing monocultures with mixed-species : Ecosystem service implications of two production forest alternatives in Sweden
- 2016
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In: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 45:Suppl. 2, s. 124-139
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Journal article (peer-reviewed)abstract
- Whereas there is evidence that mixed-species approaches to production forestry in general can provide positive outcomes relative to monocultures, it is less clear to what extent multiple benefits can be derived from specific mixed-species alternatives. To provide such insights requires evaluations of an encompassing suite of ecosystem services, biodiversity, and forest management considerations provided by specific mixtures and monocultures within a region. Here, we conduct such an assessment in Sweden by contrasting even-aged Norway spruce (Picea abies)-dominated stands, with mixed-species stands of spruce and birch (Betula pendula or B. pubescens), or spruce and Scots pine (Pinus sylvestris). By synthesizing the available evidence, we identify positive outcomes from mixtures including increased biodiversity, water quality, esthetic and recreational values, as well as reduced stand vulnerability to pest and pathogen damage. However, some uncertainties and risks were projected to increase, highlighting the importance of conducting comprehensive interdisciplinary evaluations when assessing the pros and cons of mixtures.
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| 10. |
- Felton, Adam, et al.
(author)
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Replacing monocultures with mixed-species stands : Ecosystem service implications of two production forest alternatives in Sweden
- 2016
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In: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 45, s. 124-139
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Journal article (peer-reviewed)abstract
- Whereas there is evidence that mixed-species approaches to production forestry in general can provide positive outcomes relative to monocultures, it is less clear to what extent multiple benefits can be derived from specific mixed-species alternatives. To provide such insights requires evaluations of an encompassing suite of ecosystem services, biodiversity, and forest management considerations provided by specific mixtures and monocultures within a region. Here, we conduct such an assessment in Sweden by contrasting even-aged Norway spruce (Picea abies)-dominated stands, with mixed-species stands of spruce and birch (Betula pendula or B. pubescens), or spruce and Scots pine (Pinus sylvestris). By synthesizing the available evidence, we identify positive outcomes from mixtures including increased biodiversity, water quality, esthetic and recreational values, as well as reduced stand vulnerability to pest and pathogen damage. However, some uncertainties and risks were projected to increase, highlighting the importance of conducting comprehensive interdisciplinary evaluations when assessing the pros and cons of mixtures.
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| 11. |
- Jung, Christian, et al.
(author)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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In: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Journal article (peer-reviewed)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 12. |
- Merritt, Melissa A., et al.
(author)
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Investigation of Dietary Factors and Endometrial Cancer Risk Using a Nutrient-wide Association Study Approach in the EPIC and Nurses' Health Study (NHS) and NHSII
- 2015
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In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 24:2, s. 466-471
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Journal article (peer-reviewed)abstract
- Data on the role of dietary factors in endometrial cancer development are limited and inconsistent. We applied a "nutrient-wide association study" approach to systematically evaluate dietary risk associations for endometrial cancer while controlling for multiple hypothesis tests using the false discovery rate (FDR) and validating the results in an independent cohort. We evaluated endometrial cancer risk associations for dietary intake of 84 foods and nutrients based on dietary questionnaires in three prospective studies, the European Prospective Investigation into Cancer and Nutrition (EPIC; N = 1,303 cases) followed by validation of nine foods/nutrients (FDR <= 0.10) in the Nurses' Health Studies (NHS/NHSII; N = 1,531 cases). Cox regression models were used to estimate HRs and 95% confidence intervals (CI). In multivariate adjusted comparisons of the extreme categories of intake at baseline, coffee was inversely associated with endometrial cancer risk (EPIC, median intake 750 g/day vs. 8.6; HR, 0.81; 95% CI, 0.68-0.97, P-trend = 0.09; NHS/NHSII, median intake 1067 g/day vs. none; HR, 0.82; 95% CI, 0.70-0.96, P-trend = 0.04). Eight other dietary factors that were associated with endometrial cancer risk in the EPIC study (total fat, monounsaturated fat, carbohydrates, phosphorus, butter, yogurt, cheese, and potatoes) were not confirmed in the NHS/NHSII. Our findings suggest that coffee intake may be inversely associated with endometrial cancer risk. Further data are needed to confirm these findings and to examine the mechanisms linking coffee intake to endometrial cancer risk to develop improved prevention strategies. (C)2015 AACR.
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| 13. |
- Mårald, Erland, 1970-, et al.
(author)
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Forest governance and management across time : developing a new forest social contract
- 2017
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Book (peer-reviewed)abstract
- The influence of the past, and of the future on current-time tradeoffs in the forest arena are particularly relevant given the long-term successions in forest landscapes and the hundred years' rotations in forestry. Historically established path dependencies and conflicts determine our present situation and delimit what is possible to achieve. Similarly, future trends and desires have a large influence on decision making. Nevertheless, decisions about forest governance and management are always made in the present – in the present-time appraisal of the developed situation, future alternatives and in negotiation between different perspectives, interests, and actors.This book explores historic and future outlooks as well as current tradeoffs and methods in forest governance and management. It emphasizes the generality and complexity with empirical data from Sweden and internationally. It first investigates, from a historical perspective, how previous forest policies and discourses have influenced current forest governance and management. Second, it considers methods to explore alternative forest futures and how the results from such investigations may influence the present. Third, it examines current methods of balancing tradeoffs in decision-making among ecosystem services. Based on the findings the authors develop an integrated approach – Reflexive Forestry – to support exchange of knowledge and understandings to enable capacity building and the establishment of common ground. Such societal agreements, or what the authors elaborate as forest social contracts, are sets of relational commitment between involved actors that may generate mutual action and a common directionality to meet contemporary challenges.
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| 14. |
- Nilsson, Annika E, et al.
(author)
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Food security in the Arctic : Preliminary reflections from a resilience perspective
- 2013
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In: Arctic Resilience: Interim Report 2013. - Stockholm : Arctic Council. - 9789186125431 - 9789186125424 ; , s. 113-117
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Book chapter (other academic/artistic)abstract
- Chapter 10 discusses food security, which is emerging as a major cross-cutting issue in a changingArctic. The preliminary reflections presented in the chapter highlight that food security bringstogether concerns over a range of interacting environmental, social, economic, political andcultural changes. These include: food and water-borne diseases; increasing incidence of lifestylediseases; high costs of healthy foods; contamination; changing ecosystems that impede access tofood; high fuel costs; and loss of traditional knowledge. The chapter concludes that food security isintimately interlinked with social relations and cultural well-being.
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| 15. |
- Pattaro, Cristian, et al.
(author)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 16. |
- Pennells, Lisa, et al.
(author)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Journal article (peer-reviewed)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 17. |
- Bergquist, Annika, et al.
(author)
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Impact on follow-up strategies in patients with primary sclerosing cholangitis
- 2023
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In: Liver international (Print). - Chichester, United Kingdom : Wiley-Blackwell Publishing Inc.. - 1478-3223 .- 1478-3231. ; 43:1, s. 127-138
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival.METHODS: We collected retrospective data from 2,975 PSC patients from 27 centers. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from January 1, 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality.RESULTS: A broad variety of different follow-up strategies were reported. All except one center used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centers used scheduled ERCP in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, were 0.61 (0.47-0.80) for scheduled imaging with and without ERCP; 0.64 (0.48-0.86) for US/MRI and 0.53 (0.37-0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44-0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed.CONCLUSIONS: Follow-up strategies vary considerably across centers. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumor detection and increased endoscopic treatment of asymptomatic benign biliary strictures.
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| 18. |
- Cavalieri, Sandra, et al.
(author)
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The EU’s Arctic Footprint
- 2011
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In: Journal of Nordregio. ; :2
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Journal article (pop. science, debate, etc.)
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| 19. |
- Christensen, Miyase, et al.
(author)
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Arctic sea-ice and the communication of climate change
- 2017
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In: Popular Communication. - : Taylor & Francis. - 1540-5702 .- 1540-5710. ; 15:4, s. 249-268
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Journal article (peer-reviewed)abstract
- Media play a major role in framing key political issues such as climate change, and the melting of the Arctic snow and ice has become a bellwether of global climate change through the mediations of the region and its wildlife. While Arctic change has scientific significance for understanding global warming, it also plays a key role in the popular communication of global climate change and its impacts. This article addresses questions such as how the Arctic and its sea ice have become become powerful images of climate change, and what roles scientific activities, technologies, and networks play in relation to media and mediation. Drawing upon earlier research on the role of the media and framing in relation to climate change in general and upon Arctic climate change in particular, we explore how media framings are linked with various dynamics such as scientific practice and the institutional structure of the media system.
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| 20. |
- Christensen, Miyase, et al.
(author)
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Changing Arctic : Changing World
- 2013. - 1
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In: Media and the Politics of Arctic Climate Change. - New York : Palgrave Macmillan. - 9781137266224 ; , s. 157-171
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Book chapter (peer-reviewed)
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| 21. |
- Christensen, Miyase, et al.
(author)
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Eyes on the Ice
- 2013
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In: Le Monde diplomatique. - 1478-6591. ; :November, s. 10-11
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Journal article (pop. science, debate, etc.)abstract
- A new report confirms that we are responsible for global warming. The continued melting of the Arctic’s sea ice is now widely seen to be true. So too is the idea that this has major global consequences. Is the situation reversible?
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| 22. |
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| 23. |
- Christensen, Miyase, et al.
(author)
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Media, Communication, and the Environment in Precarious Times
- 2018
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In: Journal of Communication. - : Oxford University Press. - 0021-9916 .- 1460-2466. ; 68:2, s. 267-277
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Journal article (peer-reviewed)abstract
- The seminal 1983 "Ferments in the Field" collection made limited reference to environmental issues and concerns. Considering communication media and technological artifacts as both nature and culture and, more specifically, through defining media as both infrastructural environments and content, we discuss how challenges brought about by environmental change can inform contemporary media and communication research and environmental communication. The materiality of e-waste, which has resonance for cultural, political, economic, and geographic analyses, is used as an illuminating case in point. We link the implications ensuing from the e-waste issue with the roles mediation and communication of environmental narratives play, and how they can be informed by such "medianatures," as well as geopolitical considerations.
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| 24. |
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| 25. |
- Dumont, R. J., et al.
(author)
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Multi-megawatt, gigajoule plasma operation in Tore Supra
- 2014
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In: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 56:7
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Journal article (peer-reviewed)abstract
- Integrating several important technological elements required for long pulse operation in magnetic fusion devices, the Tore Supra tokamak routinely addresses the physics and technology issues related to this endeavor and, as a result, contributes essential information on critical issues for ITER. During the last experimental campaign, components of the radiofrequency system including an ITER relevant launcher (passive active multijunction (PAM)) and continuous wave/3.7 GHz klystrons, have been extensively qualified, and then used to develop steady state scenarios in which the lower hybrid (LH), ion cyclotron (IC) and electron cyclotron (EC) systems have been combined in fully stationary shots (duration similar to 150 s, injected power up to similar to 8MW, injected/extracted energy up to similar to 1 GJ). Injection of LH power in the 5.0-6.0MW range has extended the domain of accessible plasma parameters to higher densities and non-inductive currents. These discharges exhibit steady electron internal transport barriers (ITBs). We report here on various issues relevant to the steady state operation of future devices, ranging from operational aspects and limitations related to the achievement of long pulses in a fully actively cooled fusion device (e. g. overheating due to fast particle losses), to more fundamental plasma physics topics. The latter include a beneficial influence of IC resonance heating on the magnetohydrodynamic (MHD) stability in these discharges, which has been studied in detail. Another interesting observation is the appearance of oscillations of the central temperature with typical periods of the order of one to several seconds, caused by a nonlinear interplay between LH deposition, MHD activity and bootstrap current in the presence of an ITB.
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