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| 2. |
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- 2019
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Journal article (peer-reviewed)
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| 5. |
- Wormser, David, et al.
(author)
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Adult height and the risk of cause-specific death and vascular morbidity in 1 million people : individual participant meta-analysis
- 2012
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In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 41:5, s. 1419-1433
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Journal article (peer-reviewed)abstract
- BackgroundThe extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.MethodsWe calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.ResultsFor people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.ConclusionAdult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
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| 7. |
- Angers-Loustau, A., et al.
(author)
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The challenges of designing a benchmark strategy for bioinformatics pipelines in the identification of antimicrobial resistance determinants using next generation sequencing technologies
- 2018
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In: F1000Research. - : F1000 Research Ltd. - 2046-1402. ; 7
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Journal article (peer-reviewed)abstract
- Next-Generation Sequencing (NGS) technologies are expected to play a crucial role in the surveillance of infectious diseases, with their unprecedented capabilities for the characterisation of genetic information underlying the virulence and antimicrobial resistance (AMR) properties of microorganisms. In the implementation of any novel technology for regulatory purposes, important considerations such as harmonisation, validation and quality assurance need to be addressed. NGS technologies pose unique challenges in these regards, in part due to their reliance on bioinformatics for the processing and proper interpretation of the data produced. Well-designed benchmark resources are thus needed to evaluate, validate and ensure continued quality control over the bioinformatics component of the process. This concept was explored as part of a workshop on "Next-generation sequencing technologies and antimicrobial resistance" held October 4-5 2017. Challenges involved in the development of such a benchmark resource, with a specific focus on identifying the molecular determinants of AMR, were identified. For each of the challenges, sets of unsolved questions that will need to be tackled for them to be properly addressed were compiled. These take into consideration the requirement for monitoring of AMR bacteria in humans, animals, food and the environment, which is aligned with the principles of a "One Health" approach.
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| 8. |
- Carvalho, E. de, et al.
(author)
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EU FP7 INFSO-ICT-317669 METIS, D3.1 Positioning of multi-node/multi-antenna technologies
- 2013
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Reports (other academic/artistic)abstract
- This document describes the research activity in multi-node/multi-antenna technologies within METIS and positions it with respect to the state-of-the-art in the academic literature and in the standardization bodies. Based on the state-of-the-art and as well as on the METIS objectives,we set the research objectives and we group the different activities (or technology components) into research clusters with similar research objectives. The technologycomponents and the research objectives have been set to achieve an ambidextrous purpose. On one side we aim at providing the METIS system with those technological components that are a natural but non-trivial evolution of 4G. On the other side, we aim at seeking for disruptivetechnologies that could radically change 5G with respect to 4G. Moreover, we mapped the different technology components to METIS’ other activities and to the overall goals of theproject.
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| 9. |
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| 10. |
- Palmer, Nicholette D, et al.
(author)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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In: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Journal article (peer-reviewed)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 11. |
- Bengtsson, Jan, et al.
(author)
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Grasslands-more important for ecosystem services than you might think
- 2019
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In: Ecosphere. - : Wiley. - 2150-8925 .- 2150-8925. ; 10:2
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Journal article (peer-reviewed)abstract
- Extensively managed grasslands are recognized globally for their high biodiversity and their social and cultural values. However, their capacity to deliver multiple ecosystem services (ES) as parts of agricultural systems is surprisingly understudied compared to other production systems. We undertook a comprehensive overview of ES provided by natural and semi-natural grasslands, using southern Africa (SA) and northwest Europe as case studies, respectively. We show that these grasslands can supply additional non-agricultural services, such as water supply and flow regulation, carbon storage, erosion control, climate mitigation, pollination, and cultural ES. While demand for ecosystems services seems to balance supply in natural grasslands of SA, the smaller areas of semi-natural grasslands in Europe appear to not meet the demand for many services. We identified three bundles of related ES from grasslands: water ES including fodder production, cultural ES connected to livestock production, and population-based regulating services (e.g., pollination and biological control), which also linked to biodiversity. Greenhouse gas emission mitigation seemed unrelated to the three bundles. The similarities among the bundles in SA and northwestern Europe suggest that there are generalities in ES relations among natural and semi-natural grassland areas. We assessed trade-offs and synergies among services in relation to management practices and found that although some trade-offs are inevitable, appropriate management may create synergies and avoid trade-offs among many services. We argue that ecosystem service and food security research and policy should give higher priority to how grasslands can be managed for fodder and meat production alongside other ES. By integrating grass-lands into agricultural production systems and land-use decisions locally and regionally, their potential to contribute to functional landscapes and to food security and sustainable livelihoods can be greatly enhanced.
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| 12. |
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| 13. |
- Fantini, R, et al.
(author)
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EU FP7 INFSO-ICT-317669 METIS, D3.2 First performance results for multi-node/multi-antenna transmission technologies
- 2014
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Reports (other academic/artistic)abstract
- This deliverable describes the current results of the multi-node/multi-antenna technologies investigated within METIS and analyses the interactions within and outside Work Package 3. Furthermore, it identifies the most promising technologies based on the current state of obtained results. This document provides a brief overview of the results in its first part. The second part, namely the Appendix, further details the results, describes the simulation alignment efforts conducted in the Work Package and the interaction of the Test Cases. The results described here show that the investigations conducted in Work Package 3 are maturing resulting in valuable innovative solutions for future 5G systems.
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| 14. |
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| 17. |
- Jönsen, Andreas, et al.
(author)
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Direct and indirect costs for systemic lupus erythematosus in Sweden. A nationwide health economic study based on five defined cohorts
- 2016
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In: Seminars in Arthritis & Rheumatism. - : Elsevier BV. - 0049-0172 .- 1532-866X. ; 45:6, s. 684-690
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Research review (peer-reviewed)abstract
- Objectives: The main objectives of this study were to calculate total costs of illness and cost -driving disease features among patients with systemic lupus erythematosus (SLE) in Sweden. Methods: Five cohorts of well-defined SLE patients, located in different parts of the country were merged. Incident and prevalent cases from 2003 through 2010 were included. The American College of Rheumatology (ACR) classification criteria was used. From the local cohorts, data on demographics, disease activity (SLEDAI 2K), and organ damage (SDI) were collected. Costs for inpatient care, specialist outpatient care and drugs were retrieved from national registries at the National Board of Health and Welfare. Indirect costs were calculated based on sickness leave and disability pensions from the Swedish Social Insurance Agency. Results: In total, 1029 SLE patients, 88% females, were included, and approximately 75% were below 65 years at the end of follow-up, and thus in working age. The mean number of annual specialist physician visits varied from six to seven; mean annual inpatient days were 3.1-3.6, and mean annual sick leave was 123-148 days, all per patient. The total annual cost was 208,555 SEK ($33,369 = 22,941(sic)), of which direct cost was 63,672kr ($10,188 = 7004(sic)) and the indirect cost was 144,883 SEK ($23,181 = 15,937(sic)), all per patient. The costs for patients with short disease duration were higher. Higher disease activity as measured by a SLEDAI 2K score > 3 was associated with approximately 50% increase in both indirect and direct costs. Damage in the neuropsychiatric and musculoskeletal domains were also linked to higher direct and indirect costs, while organ damage in the renal and ocular systems increased direct costs. Conclusion: Based on this study and an estimate of slightly more than 6000 SLE patients in Sweden, the total annual cost for SLE in the country is estimated at $188 million (= 129.5 million (sic)). Both direct (30%) and indirect costs (70%) are substantial. Medication accounts for less than 10% of the total cost. The tax paid national systems for health care and social security in Sweden ensure equal access to health care, sick leave reimbursements, and disability pensions nationwide. Our extrapolated annual costs for SLE in Sweden are therefore the best supported estimations thus far, and they clearly underline the importance of improved management, especially to reduce the indirect costs. (C) 2016 Elsevier Inc. All rights reserved.
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| 18. |
- Karlsson, T., et al.
(author)
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50 forgotten Miras
- 2016
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In: Journal of the American Association of Variable Star Observers. - 0271-9053 .- 2380-3606. ; 44:2, s. 156-163
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Journal article (peer-reviewed)
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| 19. |
- Leonard, Dag, et al.
(author)
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Coronary Heart Disease in Systemic Lupus Erythematosus Is Associated With Interferon Regulatory Factor-8 Gene Variants
- 2013
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In: Circulation: Cardiovascular Genetics. - : BMJ. - 1942-325X .- 1942-3268. ; 72:Suppl. 3, s. 270-270
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Journal article (peer-reviewed)abstract
- Background- Patients with systemic lupus erythematosus have increased morbidity and mortality in coronary heart disease (CHD). We asked whether there was a genetic influence on CHD in systemic lupus erythematosus. Methods and Results- The association between single-nucleotide polymorphisms (SNPs) and CHD in 2 populations of patients with systemic lupus erythematosus was assessed. Patients were genotyped on a custom 12k Illumina Array. The allele frequencies were compared between patients with (n=66) and without (n=509) CHD. We found 61 SNPs with an association (P<0.01) to CHD, with the strongest association for 3 SNPs located in the interferon regulatory factor-8 (IRF8) gene. Comparison of the allele frequencies of these 61 SNPs in patients with (n=27) and without (n=212) CHD in the second study population revealed that 2 SNPs, rs925994 and rs10514610 in IRF8 (linkage disequilibrium, r(2)=0.84), were associated with CHD in both study populations. Meta-analysis of the SNP rs925994 gave an odds ratio of 3.6 (2.1-6.3), P value 1.9x10(-6). The identified IRF8 allele remained as a risk factor for CHD after adjustment for traditional CHD risk factors. The IRF8 risk allele was associated with the presence of carotid plaques (P<0.001) and increased intima-media thickness (P=0.01). By electrophoretic mobility shift assays, we show weaker binding of protein to the risk allele of the highly linked SNP rs11117415, and by flow cytometry, a reduced frequency of circulating B cells was detected in patients with the IRF8 risk allele. Conclusions- There is a considerable genetic component for CHD in systemic lupus erythematosus, with IRF8 as a strong susceptibility locus.
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| 20. |
- Rosell, Johan, et al.
(author)
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Time dependent effects of adjuvant tamoxifen therapy on cerebrovascular disease : results from a randomised trial
- 2011
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 104:6, s. 899-902
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Journal article (peer-reviewed)abstract
- BACKGROUND: Tamoxifen has been associated with an increased risk of stroke. There is, however, little information on the effect in the post-treatment period. Using data from the Swedish Breast Cancer Group adjuvant trial of 5 vs 2 years of tamoxifen treatment, we now report both short-term and long-term effects on morbidity as well as mortality because of cerebrovascular disease. METHODS: Data from the Swedish National Hospital Discharge Registry combined with information from the Swedish Cause of Death Registry was used to define events of disease. Hazard ratios (HRs) were estimated using Cox regression. RESULTS: Comparing patients randomised to 5 years of tamoxifen with patients randomised to 2 years of tamoxifen, the incidence of cerebrovascular diseases was increased (HR 1.70, 95% CI 1.05-2.75) during the active treatment phase and reduced after the active treatment period (HR 0.78, 95% CI 0.63-0.96), and the difference in HR between the two time-periods was significant (P 0.0033). The mortality from cerebrovascular diseases was increased during the treatment period (HR 3.18, 95% CI 1.03-9.87) and decreased during the post-treatment period (HR 0.60, 95% CI 0.40-0.90) with a significant difference in HR between the two periods of follow-up (P=0.0066). Similar results were seen for subgroups of cerebrovascular diseases, such as stroke and ischaemic stroke. CONCLUSION: In an adjuvant setting, tamoxifen was associated with an increased risk of cerebrovascular disease during treatment, but a decreased risk in the post-treatment period.
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| 21. |
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| 22. |
- Thurang, Anna, et al.
(author)
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Women's experiences of caring when in treatment for alcohol dependency
- 2010
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In: Scandinavian Journal of Caring Sciences. - 0283-9318 .- 1471-6712. ; 24:4, s. 700-706
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Journal article (peer-reviewed)abstract
- Despite the fact of increased levels of alcohol dependency in women and gender differences in how the disease affects men and women, the research on alcohol dependency continues to have a dominating perspective on men. The meaning of the phenomenon of caring in formal care for women with alcohol dependency is not well known. Thus, formal caregivers may find it problematic to know what is caring for women with alcohol dependency. The aim of the study was to illuminate the meaning of caring in formal care for women with alcohol dependency, as narrated by the women. The study was performed using a phenomenological-hermeneutic method. Data were collected in ten in-depth interviews with alcohol-dependent women. The themes presented are availability, being a patient and being a learner. The findings reveal that the women with alcohol dependency receiving a mandate from formal care, experience the relation between them and their caregiver as a mutual transformation. Within the mutual transformation, the participants experienced being respected as a responsible human being which renders possibilities for the women with alcohol dependency to continue in formal care even when the struggle against the disease became hard. Continual meetings with the caregiver allowed the women to gain structure in their daily life as well as allowing the women and their caregivers to develop mutual transformation, which both relieved the women's suffering and increased their experience of being involved in the care process.
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| 23. |
- Ainomäe, Ahti, et al.
(author)
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Distributed largest eigenvalue detection
- 2017
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In: 2017 IEEE International Conference on Acoustics, Speech, and Signal Processing, ICASSP 2017. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781509041176 ; , s. 3519-3523
-
Conference paper (peer-reviewed)abstract
- Cognitive radio (CR) systems need to detect the presence of a primary user (PU) signal by continuously sensing the spectrum area of interest. Radiowave propagation effects like fading and shadowing often complicate sensing of spectrum holes because the PU signal can be weak in a particular area. Cooperative spectrum sensing is seen as a prospective solution to enhance the detection of PU signals. In this paper we study distributed spectrum sensing, based on the largest eigenvalue of adaptively estimated correlation matrices (CMs) of received signals. The PU signal is assumed to be temporally correlated. In this paper an Combine and Adapt (CTA) least Mean Square (LMS) diffusion based mean vector estimation scheme is proposed. No fusion center (FC) for estimation or detection is used. We analyse the resulting detection performance and verify the theoretical findings through simulations.
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| 24. |
- Belmeguenai, Amor, et al.
(author)
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Intrinsic Plasticity Complements Long-Term Potentiation in Parallel Fiber Input Gain Control in Cerebellar Purkinje Cells
- 2010
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In: The Journal of Neuroscience. - 1529-2401. ; 30:41, s. 13630-13643
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Journal article (peer-reviewed)abstract
- Synaptic gain control and information storage in neural networks are mediated by alterations in synaptic transmission, such as in long-term potentiation (LTP). Here, we show using both in vitro and in vivo recordings from the rat cerebellum that tetanization protocols for the induction of LTP at parallel fiber (PF)-to-Purkinje cell synapses can also evoke increases in intrinsic excitability. This form of intrinsic plasticity shares with LTP a requirement for the activation of protein phosphatases 1, 2A, and 2B for induction. Purkinje cell intrinsic plasticity resembles CA1 hippocampal pyramidal cell intrinsic plasticity in that it requires activity of protein kinaseA (PKA) and case in kinase 2 (CK2) and is mediated by a downregulation of SK-type calcium-sensitive K conductances. In addition, Purkinje cell intrinsic plasticity similarly results in enhanced spine calcium signaling. However, there are fundamental differences: first, while in the hippocampus increases in excitability result in a higher probability for LTP induction, intrinsic plasticity in Purkinje cells lowers the probability for subsequent LTP induction. Second, intrinsic plasticity raises the spontaneous spike frequency of Purkinje cells. The latter effect does not impair tonic spike firing in the target neurons of inhibitory Purkinje cell projections in the deep cerebellar nuclei, but lowers the Purkinje cell signal-to-noise ratio, thus reducing the PF readout. These observations suggest that intrinsic plasticity accompanies LTP of active PF synapses, while it reduces at weaker, nonpotentiated synapses the probability for subsequent potentiation and lowers the impact on the Purkinje cell output.
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| 25. |
- Bengtsson, Caroline, et al.
(author)
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Incident chronic rhinosinusitis is associated with impaired sleep quality: Results of the RhiNE study
- 2019
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In: Journal of Clinical Sleep Medicine. - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 15:6, s. 899-905
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Journal article (peer-reviewed)abstract
- Study Objectives: Chronic rhinosinusitis (CRS) is a common inflammatory disease of the nasal cavity and paranasal sinuses. Associations between CRS and poor sleep quality have been reported. This 10-year follow-up study investigates possible associations between incident CRS and sleep quality. Methods: A questionnaire was sent to 16,500 individuals in Sweden, Norway, Denmark, Iceland and Estonia in 2000. It included questions on airway diseases, age, sex, body mass index, smoking habits, comorbidities, education and sleep quality. In 2010, a second questionnaire was sent to the same individuals, with a response rate of 53%. A subgroup of 5,145 individuals without nasal symptoms in 2000 was studied. Multiple logistic regression was performed to examine associations between CRS (defined according to the European position paper on rhinosinusitis and nasal polyps epidemiological criteria) at follow-up and sleep quality, with adjustment for potential confounders. Individuals with the respective sleep problem at baseline were excluded. Results: Over 10 years, 141 (2.7%) of the individuals without nasal symptoms in 2000 had developed CRS. CRS was associated with difficulties inducing sleep (adjusted odds ratio 2.81 [95% CI 1.67–4.70]), difficulties maintaining sleep (2.07 [1.35–3.18]), early morning awakening (3.03 [1.91–4.81]), insomnia (2.21 [1.46–3.35]), excessive daytime sleepiness (2.85 [1.79–4.55]), and snoring (3.31 [2.07–5.31]). Three insomnia symptoms at baseline increased the risk of CRS at follow-up by 5.00 (1.93–12.99). Conclusions: Incident CRS is associated with impaired sleep quality and excessive daytime sleepiness. Insomnia symptoms may be a risk factor for the development of CRS. © 2019 American Academy of Sleep Medicine. All rights reserved.
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| 26. |
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| 27. |
- Bengtsson, J., et al.
(author)
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Effect of probiotics (Lactobacillus plantarum 299 plus Bifidobacterium Cure21) in patients with poor ileal pouch function: a randomised controlled trial
- 2016
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 51:9, s. 1087-1092
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Journal article (peer-reviewed)abstract
- Objective: Poor pouch function after restorative proctocolectomy for ulcerative colitis is a considerable problem. Pouchitis and functional disorders are the most common reasons. Probiotics seem to have a beneficial effect in pouchitis but have not been assessed in functional pouch disorders. The aim was to analyse the effects of probiotics in patients with poor pouch function.Methods: Thirty-three patients were randomized to probiotics (Lactobacillus plantarum 299 and Bifidobacterium infantis Cure 21) or placebo in a double blinded, 1:1 fashion. The treatment effect was assessed by the pouch functional score (PFS; 0-15, 15 worst), pouchitis disease activity index (PDAI; 0-18, 18 worst), and levels of four faecal biomarkers of inflammation (calprotectin, lactoferrin, myeloperoxidase [MPO] and eosinophilic cationic protein [ECP]).Results: Thirty-two patients were included (probiotics=17, placebo=16). There was no difference in change in the PFS from before to after treatment between the groups (median difference: -1.00, 95% C.I. -3.00 to 0.00, p=0.119). Furthermore, probiotics had no effect on PDAI (median difference: 0.00, 95% C.I. 0.00-1.00, p=0.786), or on faecal biomarkers. Significant correlations were observed between PDAI and each of the faecal biomarkers at study start. There were no correlations between PFS or PDAI symptom subscore and the biomarkers. PDAI endoscopic and histologic subscores correlated significantly to each of the biomarkers.Conclusion: The hypothesis that probiotics improves pouch-related dysfunction was not confirmed. Faecal biomarkers could play a future role in the management of pouch patients.
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| 28. |
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| 29. |
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| 30. |
- Bengtsson, Karin, 1980, et al.
(author)
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Are ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis associated with an increased risk of cardiovascular events? A prospective nationwide population-based cohort study
- 2017
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In: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 19:1
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Journal article (peer-reviewed)abstract
- Background: To investigate the risk of first-time acute coronary syndrome (ACS), stroke and venous thromboembolism (VTE) in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA) and undifferentiated spondyloarthritis (uSpA), compared to each other and to the general population (GP). Methods: This is a prospective nationwide cohort study. Cohorts with AS (n = 6448), PsA (n = 16,063) and uSpA (n = 5190) patients and a GP (n = 266,435) cohort, were identified 2001-2009 in the Swedish National Patient and Population registers. The follow-up began 1 January 2006, or 6 months after the first registered spondyloarthritis (SpA) diagnosis thereafter, and ended at ACS/stroke/VTE event, death, emigration or 31 December 2012. Crude and age- and sex-standardized incidence rates (SIRs) and hazard ratios (HRs) were calculated for incident ACS, stroke or VTE, respectively. Results: Standardized to the GP cohort, SIRs for ACS were 4.3, 5.4 and 4.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort, respectively, compared to 3.2 in the GP cohort. SIRs for stroke were 5.4, 5.9 and 5.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort compared to 4.7 in the GP cohort. Corresponding SIRs for VTE were 3.6, 3.2 and 3.5 events per 1000 person-years at risk compared to 2.2 in the GP cohort. Age-and sex-adjusted HRs (95% CI) for ACS events were significantly increased in AS (1.54 (1.31-1.82)), PsA (1.76 (1.59-1.95)) and uSpA (1.36 (1.05-1.76)) compared to GP. Age-adjusted HRs for ACS was significantly decreased in female AS patients (0.59 (0.37-0.97)) compared to female PsA patients. Age-and sex-adjusted HRs for stroke events were significantly increased in AS (1.25 (1.06-1.48)) and PsA (1.34 (1.22-1.48)), and nonsignificantly increased in uSpA (1.16 (0.91-1.47)) compared to GP. For VTE the age-and sex-adjusted HRs for AS, PsA and uSpA were equally and significantly increased with about 50% compared to GP. Conclusions: Patients with AS, PsA and uSpA are at increased risk for ACS and stroke events, which emphasizes the importance of identification of and intervention against cardiovascular risk factors in SpA patients. Increased alertness for VTE is warranted in patients with SpA.
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| 31. |
- Bengtsson, Karin, et al.
(author)
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Cardiac conduction disturbances in patients with ankylosing spondylitis : results from a 5-year follow-up cohort study
- 2019
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In: RMD Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 5:2
-
Journal article (peer-reviewed)abstract
- Objectives: To describe electrocardiographic (ECG) development in patients with ankylosing spondylitis (AS) and identify associations between baseline characteristics and cardiac conduction disturbances (CCD) at 5-year follow-up.Methods: In a longitudinal cohort study, 172 patients (54% men, mean age (SD) of 50 (13) years at baseline) with AS underwent ECG, physical examination, questionnaires and laboratory testing at baseline and at 5-year follow-up. Descriptive statistics and univariate and age- and sex-adjusted logistic regression analyses were used. CCD included both atrioventricular and intraventricular blocks.Results: Twenty-three of the 172 patients (13.4%) had a CCD at follow-up. Eight patients had developed a new CCD and eight had normalised their ECG. In the age- and sex-adjusted analyses, CCD at baseline (OR 24.8, 95% CI 7.3 to 84.5), male sex (OR 6.4, 95% CI 2.0 to 20.8), history of anterior uveitis (OR 4.4, 95% CI 1.3 to 14.5), higher ASDAS-CRP (OR 2.3, 95% CI 1.3 to 4.0), greater waist circumference (OR 1.3, 95% CI 1.1 to 1.6, per 5 cm), and medication with antiplatelets (OR 7.0, 95% CI 1.5 to 31.8) and beta-blockers (OR 3.4, 95% CI 1.0 to 11.5) were associated with a CCD at follow-up. Higher age and longer symptom duration were highly correlated and were both associated with a CCD at follow-up.Conclusions: The presence of CCD in AS is in part dynamic and associated with both AS and non-AS characteristics. Our results suggest that patients especially prone to present with CCDs are older men with a previous CCD, longer symptom duration, higher AS disease activity, a history of anterior uveitis and medication reflecting cardiovascular disease.
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| 32. |
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| 33. |
- Bengtsson, Karin, 1980, et al.
(author)
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Comparisons between comorbid conditions and health care consumption in rheumatoid arthritis patients with or without biological disease-modifying antirheumatic drugs : a register-based study
- 2016
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In: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 17:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Symptoms and prognosis of patients with rheumatoid arthritis (RA) have improved with more intensive therapy, including the biological disease-modifying anti-rheumatic drugs (bDMARDs). Real life data concerning how comorbidities are distributed among patients treated or not treated with bDMARDs are scarce. Our objective was to investigate differences in comorbidity and health care consumption in RA patients, with and without bDMARDs.METHODS: This cross-sectional study was performed in the Southwestern part of Sweden. Patients, aged ≥ 18 years and diagnosed with RA in secondary health care during 2009-2010, were identified in the regional health care database. Aggregated data of comorbidity and health care consumption were retrieved between 2006 and 2010. RA patients treated with bDMARDs on 31st December 2010 were identified in the Swedish Rheumatology Quality Register (SRQ), which includes the biologics register Anti-Rheumatic Therapy in Sweden (ARTIS). Descriptive, comparative, univariate and multiple logistic regression analyses were used to identify factors associated with bDMARDs.RESULTS: Seven thousand seven hundred and twelve (7712) RA patients were identified (age 64.8 ± 14.9 years, women 74.3%), of whom 1137 (14.7%) were treated with bDMARDs. Overall, the most common comorbidities were infections (69.2%), hypertension (41.1%), chronic respiratory disease (15.3%), ischemic heart disease (14.0%) and malignancy (13.7%). Patients without bDMARDs were older and had more comorbidity. In the multiple logistic regression analysis, older age, cerebrovascular and chronic respiratory disease, heart failure, depression and malignancy were all associated with no present bDMARDs. Infections were associated with bDMARDs. Patients treated with bDMARDs consumed more secondary outpatient care but less visits in primary health care compared to patients without bDMARDs.CONCLUSIONS: Patients treated with bDMARDs versus no bDMARDs were younger and had significantly lower period prevalence for most common comorbidities, with the exception of infections. Differences in comorbidities between RA patients with or without bDMARDs should be taken into consideration when evaluating effectiveness and safety of bDMARDs in ordinary care.
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| 34. |
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| 35. |
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| 36. |
- Bengtsson, Karin, 1980, et al.
(author)
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Risk of cardiac rhythm disturbances and aortic regurgitation in different spondyloarthritis subtypes in comparison with general population : A register-based study from Sweden
- 2018
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:4, s. 541-548
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Journal article (peer-reviewed)abstract
- Objectives To describe the incidence of atrioventricular (AV) block II-III, atrial fibrillation (AF), pacemaker implantation (PM) and aortic regurgitation in patients with ankylosing spondylitis (AS), undifferentiated spondyloarthritis (uSpA) and psoriatic arthritis (PsA) compared with the general population (GP) and with each other. Methods A prospective nationwide study with cohorts of patients with AS (n=6448), PsA (n=16 063) and uSpA (n=5190) and a GP (n=2 66 435) cohort, identified in 2001-2009 in the Swedish National Patient and Population registers. Follow-up began on 1 January 2006 and ended at event, death, emigration or 31 December 2012. Age-standardised and sex-standardised incidence rates and hazard ratios (HRs) were calculated. Results The highest incidence rates were noted for AF (5.5-7.4 events per 1000 person-years), followed by PM (1.0-2.0 events per 1000 person-years). HRs for AV block, AF, PM and aortic regurgitation were significantly increased in AS (HRs 2.3, 1.3, 2.1 and 1.9), uSpA (HRs 2.9, 1.3, 1.9 and 2.0) and PsA (HRs 1.5, 1.5, 1.6 and 1.8) compared with the GP cohort. The highest HRs were seen for AV block in male uSpA (HR 4.2) and AS (HR 2.5) compared with GP. Compared with PsA, significantly increased HRs were noted for PM (HR 1.5) in AS and for AV block (HR 1.8) in uSpA. Conclusions Patients with SpA are at increased risk of aortic regurgitation, cardiac rhythm disturbances and, as a probable consequence, also PM. Particularly for AF, the most common arrhythmia, increased caution is warranted, whereas AV block should be looked for especially in men with AS or uSpA.
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| 37. |
- Bengtsson, Lars, et al.
(author)
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Comparing University-Ownership Technology Transfer Systems With University-Inventor Technology Transfer Systems In Scandinavian Universities – A Question Of Focusing On Licensing Or Spin-Off Business Models?
- 2014
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In: University-Industry-Interaction 4/2014. - 9789491901119 ; , s. 339-353
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Conference paper (peer-reviewed)abstract
- Universities have become important components of the national innovation systems in innovation driven economies. To strengthen the university related flow of mainly technological knowledge into commercialized products many European countries have followed the American example and changed from an inventor-ownership system to a university-owned system (Genua & Rossi, 2011). Today most European countries have adopted a university-ownership system but with varying characteristics (Genua & Rossi, 2011). One of the strongest effects of changing to a university-owned system is a strengthening of the university support structures especially the founding or expansion of a Technology-Transfer organization (TTO). Most research indicates an increased output of patent applications, university-owned patents and license deals from the European universities (Genua & Rossi, 2011; Siegel et al, 2007). Will the university owned system give privilege to patents and license deals instead of trying to capture a higher value from university ownership in a university spinout as Kenney & Patton’s (2009; 2011) research indicate? The Scandinavian countries have since a decade changed university laws, policies and allocated specific resources in order to stimulate commercialization of university research. While Denmark and Norway changed intellectual property laws in favor of university ownership and pushed for commercialization early in the 2000's, Sweden retained the professor’s privilege system or university inventor system. The paper reports on a survey of Scandinavian universities’ technology-transfer offices regarding their patenting, licensing and university-spin-off activities in the years from 2000 to 2012. Results show an increase in commercialization activities in Denmark and Norway confirming earlier results by Genua and Rossi (2011). The Danish development shows a clear increase of patenting and licensing activity but a stagnation of university spin-outs. The Norwegian development is less clear but also here a pattern of more licensing and stagnation of spinouts is visible. In contrast Swedish universities’ TTO-systems are organized for spinouts and produce mostly university spinouts. Patenting is done also in Sweden but primarily in conjunction with the spinout process. Moreover, pure licensing deals are rare in the Swedish system. The study provides some support for Kenney and Patton’s (2009; 2011) results that university owned systems favour the business model of patenting and licensing while university inventor systems favour the business model of spinoffs. This study does however note the effect of other factors than the university intellectual property regime as important in the development. These are government initiatives and resource allocations for university commercialization, the capabilities of the TTO and the universities’ choice of commercialization support structure.
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| 38. |
- Bengtsson-Palme, Johan, 1985, et al.
(author)
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Metaxa2 Database Builder: enabling taxonomic identification from metagenomic or metabarcoding data using any genetic marker
- 2018
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In: Bioinformatics (Oxford, England). - : Oxford University Press (OUP). - 1367-4811 .- 1367-4803. ; 34:23, s. 4027-4033
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Journal article (peer-reviewed)abstract
- Correct taxonomic identification of DNA sequences is central to studies of biodiversity using both shotgun metagenomic and metabarcoding approaches. However, no genetic marker gives sufficient performance across all the biological kingdoms, hampering studies of taxonomic diversity in many groups of organisms. This has led to the adoption of a range of genetic markers for DNA metabarcoding. While many taxonomic classification software tools can be re-trained on these genetic markers, they are often designed with assumptions that impair their utility on genes other than the SSU and LSU rRNA. Here, we present an update to Metaxa2 that enables the use of any genetic marker for taxonomic classification of metagenome and amplicon sequence data.We evaluated the Metaxa2 Database Builder on eleven commonly used barcoding regions and found that while there are wide differences in performance between different genetic markers, our software performs satisfactorily provided that the input taxonomy and sequence data are of high quality.Freely available on the web as part of the Metaxa2 package at http://microbiology.se/software/metaxa2/.Supplementary data are available at Bioinformatics online.
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| 39. |
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| 40. |
- Berthold, E., et al.
(author)
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Tumour necrosis factor-α/etanercept complexes in serum predict long-term efficacy of etanercept treatment in seronegative rheumatoid arthritis
- 2018
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In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 47:1, s. 22-26
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Journal article (peer-reviewed)abstract
- Objective: To study whether serum levels of tumour necrosis factor-α (TNF-α), free or bound to etanercept, in biological-naïve adults with rheumatoid arthritis (RA) could predict the long-term efficacy of etanercept, measured as drug survival. Method: We identified 145 biological-naïve patients with RA starting treatment with etanercept at the Department of Rheumatology, Skåne University Hospital (1999–2008), of whom 16 had seronegative and 129 seropositive RA. TNF-α in serum was quantified using enzyme-linked immunosorbent assay in samples from the onset of treatment and at 6 week follow-up. Drug survival time was used to evaluate the long-term efficacy of etanercept. Results: Levels of TNF-α were significantly increased at follow-up compared to at the start. At the 6 week follow-up, circulating TNF-α mainly comprised TNF-α in complex with etanercept. Longer drug survival time correlated with increased TNF-α at 6 week follow-up in the patients with seronegative RA, but not in the seropositive patients. Conclusion: We demonstrated that levels of circulating TNF-α increased in almost all individuals after initiation of treatment with etanercept and that this increase mainly comprised TNF-α in complex with etanercept. More importantly, this increase may predict drug survival in adults with seronegative, but not seropositive, RA and suggests that measuring TNF-α/etanercept complexes in serum may be relevant in patients with seronegative RA.
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| 41. |
- Bjermer, Leif, et al.
(author)
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Local and systemic effects of inhaled AZD9164 compared with tiotropium in patients with COPD
- 2013
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In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 107:1, s. 84-90
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Journal article (peer-reviewed)abstract
- There is still a need for new agents which improve upon the therapeutic index of tiotropium, the current standard of care for many patients with chronic obstructive pulmonary disease (COPD). We examined in patients with COPD the efficacy of single doses of AZD9164, an M3-selective muscarinic antagonist, to identify an appropriate dose-range for future studies. COPD patients (n = 28) inhaled AZD9164 (100, 400 and 1200 μg), tiotropium (18 μg) and placebo at 5 study centre visits (Clinicaltrials.gov identifier NCT00939211). The effects of these test drugs on average (Eav), peak (Emax) and trough (E22–26) forced expiratory volume in one second (FEV1) were assessed, as were systemically-mediated effects and the safety and exposure of single doses of AZD9164. AZD9164 100, 400 and 1200 μg caused increases in FEV1 to peak effects of 12, 17 and 12% above baseline respectively, following an initial transient and dose-related fall in FEV1 and associated increase in mild respiratory symptoms such as cough. Bronchodilation was maintained overnight, with minimal FEV1 decline. AZD9164 400 and 1200 μg produced larger effects than tiotropium on E22–26 (p < 0.05; both doses) while AZD9164 400 μg also had larger effects on Emax (p = 0.001) and Eav (p < 0.05). There were no serious adverse events and statistically significant systemic effects were observed only with AZD9164 1200 μg. AZD9164 may improve upon the therapeutic index of tiotropium, increasing the magnitude and duration of lung function improvements without increasing systemically-mediated adverse events. The initial bronchoconstrictor effect of AZD9164 requires further investigation.
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| 42. |
- Bosco, C, et al.
(author)
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Exploring the high-resolution mapping of gender-disaggregated development indicators
- 2017
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In: Journal of the Royal Society, Interface. - : The Royal Society. - 1742-5662 .- 1742-5689. ; 14:129
-
Journal article (peer-reviewed)abstract
- Improved understanding of geographical variation and inequity in health status, wealth and access to resources within countries is increasingly being recognized as central to meeting development goals. Development and health indicators assessed at national or subnational scale can often conceal important inequities, with the rural poor often least well represented. The ability to target limited resources is fundamental, especially in an international context where funding for health and development comes under pressure. This has recently prompted the exploration of the potential of spatial interpolation methods based on geolocated clusters from national household survey data for the high-resolution mapping of features such as population age structures, vaccination coverage and access to sanitation. It remains unclear, however, how predictable these different factors are across different settings, variables and between demographic groups. Here we test the accuracy of spatial interpolation methods in producing gender-disaggregated high-resolution maps of the rates of literacy, stunting and the use of modern contraceptive methods from a combination of geolocated demographic and health surveys cluster data and geospatial covariates. Bayesian geostatistical and machine learning modelling methods were tested across four low-income countries and varying gridded environmental and socio-economic covariate datasets to build 1×1 km spatial resolution maps with uncertainty estimates. Results show the potential of the approach in producing high-resolution maps of key gender-disaggregated socio-economic indicators, with explained variance through cross-validation being as high as 74–75% for female literacy in Nigeria and Kenya, and in the 50–70% range for many other variables. However, substantial variations by both country and variable were seen, with many variables showing poor mapping accuracies in the range of 2–30% explained variance using both geostatistical and machine learning approaches. The analyses offer a robust basis for the construction of timely maps with levels of detail that support geographically stratified decision-making and the monitoring of progress towards development goals. However, the great variability in results between countries and variables highlights the challenges in applying these interpolation methods universally across multiple countries, and the importance of validation and quantifying uncertainty if this is undertaken.
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| 43. |
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| 44. |
- Browning, Kathryn L., et al.
(author)
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Human Lipoproteins at Model Cell Membranes : Effect of Lipoprotein Class on Lipid Exchange
- 2017
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Journal article (peer-reviewed)abstract
- High and low density lipoproteins (HDL and LDL) are thought to play vital roles in the onset and development of atherosclerosis; the biggest killer in the western world. Key issues of initial lipoprotein (LP) interactions at cellular membranes need to be addressed including LP deposition and lipid exchange. Here we present a protocol for monitoring the in situ kinetics of lipoprotein deposition and lipid exchange/removal at model cellular membranes using the non-invasive, surface sensitive methods of neutron reflection and quartz crystal microbalance with dissipation. For neutron reflection, lipid exchange and lipid removal can be distinguished thanks to the combined use of hydrogenated and tail-deuterated lipids. Both HDL and LDL remove lipids from the bilayer and deposit hydrogenated material into the lipid bilayer, however, the extent of removal and exchange depends on LP type. These results support the notion of HDL acting as the 'good' cholesterol, removing lipid material from lipid-loaded cells, whereas LDL acts as the 'bad' cholesterol, depositing lipid material into the vascular wall.
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| 45. |
- Browning, T. K., et al.
(author)
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Human lipoproteins at model cell membranes : Role of the lipoprotein class on lipid dynamics
- 2017
-
In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
-
Journal article (peer-reviewed)abstract
- High and low density lipoproteins (HDL and LDL) are thought to play vital roles in the onset and development of atherosclerosis; the biggest killer in the western world. Key issues of initial lipoprotein (LP) interactions at cellular membranes need to be addressed including LP deposition and lipid exchange. Here we present a protocol for monitoring the in situ kinetics of lipoprotein deposition and lipid exchange/removal at model cellular membranes using the non-invasive, surface sensitive methods of neutron reflection and quartz crystal microbalance with dissipation. For neutron reflection, lipid exchange and lipid removal can be distinguished thanks to the combined use of hydrogenated and tail-deuterated lipids. Both HDL and LDL remove lipids from the bilayer and deposit hydrogenated material into the lipid bilayer, however, the extent of removal and exchange depends on LP type. These results support the notion of HDL acting as the ‘good’ cholesterol, removing lipid material from lipid-loaded cells, whereas LDL acts as the ‘bad’ cholesterol, depositing lipid material into the vascular wall.
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| 46. |
- Dengler, Juergen, et al.
(author)
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GrassPlot - a database of multi-scale plant diversity in Palaearctic grasslands
- 2018
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In: Phytocoenologia. - : Schweizerbart. - 0340-269X. ; 48:3, s. 331-347
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Journal article (peer-reviewed)abstract
- GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). GrassPlot collects plot records (releves) from grasslands and other open habitats of the Palaearctic biogeographic realm. It focuses on precisely delimited plots of eight standard grain sizes (0.0001; 0.001;... 1,000 m(2)) and on nested-plot series with at least four different grain sizes. The usage of GrassPlot is regulated through Bylaws that intend to balance the interests of data contributors and data users. The current version (v. 1.00) contains data for approximately 170,000 plots of different sizes and 2,800 nested-plot series. The key components are richness data and metadata. However, most included datasets also encompass compositional data. About 14,000 plots have near-complete records of terricolous bryophytes and lichens in addition to vascular plants. At present, GrassPlot contains data from 36 countries throughout the Palaearctic, spread across elevational gradients and major grassland types. GrassPlot with its multi-scale and multi-taxon focus complements the larger international vegetationplot databases, such as the European Vegetation Archive (EVA) and the global database " sPlot". Its main aim is to facilitate studies on the scale-and taxon-dependency of biodiversity patterns and drivers along macroecological gradients. GrassPlot is a dynamic database and will expand through new data collection coordinated by the elected Governing Board. We invite researchers with suitable data to join GrassPlot. Researchers with project ideas addressable with GrassPlot data are welcome to submit proposals to the Governing Board.
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| 47. |
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| 48. |
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| 49. |
- Eriksson, J. K., et al.
(author)
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Is ankylosing spondylitis a risk factor for cardiovascular disease, and how do these risks compare with those in rheumatoid arthritis?
- 2017
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:2, s. 364-370
-
Journal article (peer-reviewed)abstract
- Aims To assess and compare the incidence of cardiovascular (CV) events, by CV phenotype, between patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA) and the general population. Methods Using linkages of national and populationbased registers, we identified one cohort of prevalent patients with AS (n=5358), one with RA (n=37 245) and one with matched general population subjects (n=25 006). These cohorts were identified in 2006 through 2011 and were followed in 31 December 2012, for first ever occurrence of acute coronary syndromes (ACS), deep venous thromboembolism, pulmonary embolism and stroke, respectively. For each outcome, we calculated incidence rates standardised to the age and sex distribution of the AS cohort, as well as relative risks using Cox proportional hazards models. Results Based on 69 ACS events during 20 251 person-years of follow-up of the patients with AS, and 966 events during 127 014 person-years in the RA cohort, the age/sex-adjusted relative risks for ACS compared with the general population was 1.3 (95% Cl 1.0 to 1.7) for AS and 1.7 (1.4 to 2.0) for RA. For thromboembolic events, the corresponding risks were 1.4 (1.1 to 1.9) in AS and 1.8 (1.5 to 2.1) in RA. Finally, for stroke, the relative risks were 1.5 (1.1 to 2.0) in AS and 1.5 (1.2 to 1.8) in RA, compared with the general population. Conclusions Prevalent patients with AS are at a 30%-50% increased risk of incident CV events. When compared with patients with RA, this level of increase was similar for stroke, but only half as high for ACS and thrombotic events.
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| 50. |
- Forsblad d'Elia, Helena, 1961, et al.
(author)
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Drug adherence, response and predictors thereof for tocilizumab in patients with rheumatoid arthritis: results from the Swedish biologics register
- 2015
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In: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 54:7, s. 1186-1193
-
Journal article (peer-reviewed)abstract
- Objective. To evaluate drug adherence, clinical response and predictors thereof for tocilizumab in patients with RA in routine care based on prospectively collected data from the Swedish biologics register, Anti-Rheumatic Therapies in Sweden. Methods. RA patients who had started with tocilizumab from September 2008 until March 2012 were identified. Cox regression and logistic regression models were used. Results. A total of 530 RA patients were included, of whom 80.6% were female, 64.7% were on concomitant DMARDs, of which 300 were on MTX and 12% were biologic naive. The overall 6 month, 1 and 2 year estimated drug continuations were 79%, 64% and 50%, respectively. In the multivariate analyses, a low initial level of CRP [hazard ratio (HR) 0.76/1S. D. (95% CI 0.63, 0.91)], high HAQ score [HR 1.23/1S.D. (95% CI 1.06, 1.44)] and prior exposure to different biologics [HR 1.43 (95% CI 1.12, 1.83)] were predictors for drug termination, whereas concomitant DMARD therapy was not. European League Against Rheumatism (EULAR) good, moderate, and no response were achieved by 184 (46.7%), 133 (33.8%) and 77 (19.5%) patients, respectively. Predictors for EULAR good response vs no response (at 2.5-8 months) were low HAQ [odds ratio (OR) 0.56/1S. D. (95% CI 0.40, 0.78)], high 28-joint DAS [OR 2.0/1S. D. (95% CI 1.44, 2.78)] and not being on prednisolone [OR 0.47 (95% CI 0.25, 0.88)] at baseline. Conclusion. In this RA cohort treated with tocilizumab, the estimated 1 year drug continuation was 64% and 80% of the patients achieved a EULAR response. Drug discontinuation was not predicted by no concomitant DMARD, but by low CRP, high HAQ and prior exposure to biologics.
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