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| 5. |
- Abe, O, et al.
(author)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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In: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Journal article (peer-reviewed)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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- 2019
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Journal article (peer-reviewed)
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- 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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- Wilking, N., et al.
(author)
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Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
- 2007
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:4, s. 694-700
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Journal article (peer-reviewed)abstract
- Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below theage of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. © 2007 Oxford University Press.
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| 19. |
- 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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| 20. |
- 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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| 21. |
- Falconer, D., et al.
(author)
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New Air-interface Technologies and Deployment Concepts
- 2006
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In: Technologies for the Wireless Future: Wireless World Research Forum (WWRF). - Chichester, UK : John Wiley & Sons. - 0470029056 - 9780470029053 ; , s. 131-226
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Book chapter (other academic/artistic)
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| 26. |
- 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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| 27. |
- Pihl, E., et al.
(author)
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Ten new insights in climate science 2020- A horizon scan
- 2020
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In: Global Sustainability. - : Cambridge University Press. - 2059-4798.
-
Journal article (peer-reviewed)abstract
- Non-technical summary We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in tropical ecosystems is weakening. Adverse impacts on human society include increasing water shortages and impacts on mental health. Options for solutions emerge from rethinking economic models, rights-based litigation, strengthened governance systems and a new social contract. The disruption caused by COVID-19 could be seized as an opportunity for positive change, directing economic stimulus towards sustainable investments. Technical summary A synthesis is made of ten fields within climate science where there have been significant advances since mid-2019, through an expert elicitation process with broad disciplinary scope. Findings include: (1) a better understanding of equilibrium climate sensitivity; (2) abrupt thaw as an accelerator of carbon release from permafrost; (3) changes to global and regional land carbon sinks; (4) impacts of climate change on water crises, including equity perspectives; (5) adverse effects on mental health from climate change; (6) immediate effects on climate of the COVID-19 pandemic and requirements for recovery packages to deliver on the Paris Agreement; (7) suggested long-term changes to governance and a social contract to address climate change, learning from the current pandemic, (8) updated positive cost-benefit ratio and new perspectives on the potential for green growth in the short- A nd long-term perspective; (9) urban electrification as a strategy to move towards low-carbon energy systems and (10) rights-based litigation as an increasingly important method to address climate change, with recent clarifications on the legal standing and representation of future generations. Social media summary Stronger permafrost thaw, COVID-19 effects and growing mental health impacts among highlights of latest climate science.
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| 28. |
- Al-Khatib, A, et al.
(author)
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Transition to non-collective states at high spin in Xe-124
- 2008
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In: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 36:1, s. 21-29
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Journal article (peer-reviewed)abstract
- Excited states in Xe-124 were populated in the reaction Se-82(Ca-48, 6n) Xe-124 and gamma-ray coincidence relationships were measured with the Gammasphere spectrometer. Two new bands are observed and several of the previously known bands are extended in the high-as well as in the low-spin region. Two irregular high-spin structures are also added. The irregularities are a fingerprint of a transition from collective to non-collective behaviour. Configuration assignments to the new structures are proposed on the basis of systematics and by comparing experimental properties with calculations within the framework of the cranking model.
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| 29. |
- Amnell, T, et al.
(author)
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Now, Next, and Future
- 2001
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In: Modelling and Verification of Parallel Processes (MOVEP'2k), Nantes, France June 19 to 23, 2000. LNCS Tutorial 2067.. ; , s. 100-125
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Conference paper (peer-reviewed)
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| 30. |
- 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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| 31. |
- Bengtsson-Palme, Johan, 1985, et al.
(author)
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Towards monitoring of antimicrobial resistance in the environment: For what reasons, how to implement it, and what are the data needs?
- 2023
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In: Environment International. - 0160-4120 .- 1873-6750. ; 178
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Journal article (peer-reviewed)abstract
- Antimicrobial resistance (AMR) is a global threat to human and animal health and well-being. To understand AMR dynamics, it is important to monitor resistant bacteria and resistance genes in all relevant settings. How-ever, while monitoring of AMR has been implemented in clinical and veterinary settings, comprehensive monitoring of AMR in the environment is almost completely lacking. Yet, the environmental dimension of AMR is critical for understanding the dissemination routes and selection of resistant microorganisms, as well as the human health risks related to environmental AMR. Here, we outline important knowledge gaps that impede implementation of environmental AMR monitoring. These include lack of knowledge of the 'normal' background levels of environmental AMR, definition of high-risk environments for transmission, and a poor understanding of the concentrations of antibiotics and other chemical agents that promote resistance selection. Furthermore, there is a lack of methods to detect resistance genes that are not already circulating among pathogens. We conclude that these knowledge gaps need to be addressed before routine monitoring for AMR in the environment can be implemented on a large scale. Yet, AMR monitoring data bridging different sectors is needed in order to fill these knowledge gaps, which means that some level of national, regional and global AMR surveillance in the envi-ronment must happen even without all scientific questions answered. With the possibilities opened up by rapidly advancing technologies, it is time to fill these knowledge gaps. Doing so will allow for specific actions against environmental AMR development and spread to pathogens and thereby safeguard the health and wellbeing of humans and animals.
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| 36. |
- 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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| 38. |
- Grinin, V. P., et al.
(author)
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Modelling UX Ori star eclipses based on spectral observations with the Nordic Optical Telescope - I. RR Tau
- 2023
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 524:3, s. 4047-4061
-
Journal article (peer-reviewed)abstract
- Based on observations obtained with the Nordic Optical Telescope (NOT) we investigate the spectral variability of the Herbig Ae star RR Tau. This star belongs to the UX Ori family, characterized by very deep fadings caused by the screening of the star with opaque fragments (clouds) of the protoplanetary discs. At the moments of such minima one observes strong spectral variability due to the fact that the dust cloud occults, for an observer, not only the star but also a part of the region where the emission spectrum originates. We calculated a series of obscuration models to interpret the observed variability of the H a line parameters. We consider two main obscuration scenarios: (1) the dust screen rises vertically above the circumstellar disc, and (2) the screen intersects the line-of-sight moving azimuthally with the disc. In both cases, the model of the emission region consists of a compact magnetosphere and a magnetocentrifugal disc wind. Comparison with observations shows that the first scenario explains well the variability of the radiation flux, the equivalent width, as well as the asymmetry of the H a line during eclipses, while the second scenario explains them only partly. This permits us to suggest that in the case of RR Tau, the main causes of the eclipses are either a structured disc wind, or the charged dust lifted along the field lines of the poloidal component of the magnetic field of the circumstellar disc.
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| 42. |
- 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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| 43. |
- 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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| 44. |
- Kindmark, Andreas, et al.
(author)
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Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis
- 2008
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In: The Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 8:3, s. 186-195
-
Journal article (peer-reviewed)abstract
- One of the major goals of pharmacogenetics is to elucidate mechanisms and identify patients at increased risk of adverse events (AEs). To date, however, there have been only a few successful examples of this type of approach. In this paper, we describe a retrospective case–control pharmacogenetic study of an AE of unknown mechanism, characterized by elevated levels of serum alanine aminotransferase (ALAT) during long-term treatment with the oral direct thrombin inhibitor ximelagatran. The study was based on 74 cases and 130 treated controls and included both a genome-wide tag single nucleotide polymorphism and large-scale candidate gene analysis. A strong genetic association between elevated ALAT and the MHC alleles DRB1*07 and DQA1*02 was discovered and replicated, suggesting a possible immune pathogenesis. Consistent with this hypothesis, immunological studies suggest that ximelagatran may have the ability to act as a contact sensitizer, and hence be able to stimulate an adaptive immune response.
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| 45. |
- 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
-
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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| 46. |
- Leonardson, L., et al.
(author)
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Nitrogen Retention in Artificially Flooded Meadows
- 1994
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In: Ambio: a Journal of Human Environment. - 0044-7447. ; 23:6, s. 332-341
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Journal article (peer-reviewed)abstract
- Investigations of nitrogen retention in artificially flooded wetlands were performed in southern Sweden during 1991-1993. The purpose of the study was to investigate whether artificial flooding of meadows would be a possible means of reducing the nitrogen content in streams and rivers. Two case studies are presented, one from a sandy/organic soil, one from a peaty soil. Overall nitrogen retention was estimated by mass balance. Denitrification activity and plant biomass incorporation of nitrogen were used to complement and verify the mass-balance data. The study shows that artificial flooding of meadows did not contribute significantly to nitrogen retention in the introduced river water under the irrigation regimes utilized. The technique stimulated mineralization of the soil nitrogen pool to an extent which corresponded to the reduction of nitrate caused by denitrification. In the sandy/organic soil, denitrification was enhanced by the artificial flooding, while in the peat area the activity was lower than in a nonflooded reference area. Plant uptake of nitrogen was stimulated by flooding.
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| 47. |
- Lindström, U., et al.
(author)
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Comparison of anterior uveitis occurrence during treatment with secukinumab, adalimumab, infliximab and etanercept in spondyloarthritis
- 2020
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In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 79, s. 9-10
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Journal article (other academic/artistic)abstract
- Randomized controlled trials indicate that compared to tumor necrosis factor inhibitors (TNFi), secukinumab (SEC) has similar efficacy regarding axial inflammation in spondyloarthritis (SpA), better efficacy regarding cutaneous psoriasis, but is inferior in inflammatory bowel disease (IBD). However, the efficacy of SEC compared to TNFi in anterior uveitis (AU) has not been extensively studied.Objectives:To compare the occurrence of AU in patients with SpA treated with SEC, adalimumab (ADA), infliximab (IFX) or etanercept (ETN), in clinical practice.Methods:Patients with ankylosing spondylitis or undifferentiated SpA starting either SEC, ADA, IFX or ETN, in 2015 through 2017, were identified in the Swedish Rheumatology Quality register, and were linked to the national patient register for identification of AU. AU-flares were defined as the number of visits with an AU diagnosis, separated by a ≥60 days penalty interval, within ophthalmology outpatient care, during the respective bDMARD treatment.Follow-up started at the bDMARD initiation, and ended at the first of Dec 31st2017, death, emigration or discontinuation date of the bDMARD.To assess and accommodate treatment channeling, crude incidence rates for AU-flares were determined (A) for all bDMARD treatment starts, (B) excluding patients with an AU diagnosis during the year prior to the bDMARD start, and (C) in addition, excluding all first line bDMARD treatment starts.Hazard ratios (HR) for time until a first on-treatment AU diagnosis were estimated using Cox regression (ADA=reference), adjusted for sex, age, and any history of AU, and estimating robust confidence intervals to account for the individuals contributing multiple lines of treatment.Results:In total, 2,684 patients (52% women) contributed 3,255 treatment initiations. SEC was less frequently used as first line bDMARD and there was channeling of patients with previous AU, towards treatment with ADA, and away from ETN (Table 1). Further, AU occurred almost exclusively in patients with a pre-treatment history of AU (data not shown).Table 1.AnalysisTreat-ment starts, NPrevious AU1Age at treat-ment start, mean (sd)N Previous bDMARD, medianHR (95% CI) for first AU-diagnosisAU flares, NFollow-up2, yearsA. All treatment starts, N=3255SEC33321%48 (13)22.0 (1.2-3.3)52241ADA87234%44 (12)1Ref175973IFX71421%43 (14)00.9 (0.6-1.4)68677ETN133617%44 (14)00.9 (0.7-1.3)1021290B. Excluding patients with prior AU within 1 year before treatment start, N=2907SEC30413%47 (13)23.1 (1.4-7.3)10212ADA71119%44 (13)1Ref18792IFX63311%43 (14)01.0 (0.4-2.3)8599ETN125912%44 (14)01.8 (1.0-3.4)431204C. Excluding patients with prior AU within 1 year before treatment start and first line bDMARD, N=1288SEC28414%48 (13)22.5 (1.0-6.2)10198ADA37418%45 (13)1Ref11384IFX18512%45 (14)21.3 (0.4-4.0)4166ETN44517%47 (14)11.9 (0.9-4.0)234391) Anterior uveitis between 2001 and treatment start; 2) Total follow-up time for analyses of incidence rate.The incidence rates of AU-flares were higher for SEC and ETN compared to ADA and IFX, in the analyses (B, C) accommodating for channeling, figure 1.Compared to ADA, the adjusted HRs of a first on-treatment AU-diagnosis were also higher for SEC and ETA, Table 1.Conclusion:In clinical practice, SEC and ETN are associated with a higher incidence of AU than ADA and INF, suggesting a poorer protective effect of SEC and ETN against AU. These preliminary results should be interpreted in light of pronounced treatment channeling, which was only partly accommodated for.Disclosure of Interests:Ulf Lindström: None declared, Karin Bengtsson: None declared, Tor Olofsson: None declared, Daniela Di Giuseppe: None declared, Bente Glintborg Grant/research support from: Grants from Pfizer, Biogen and Abbvie, Helena Forsblad-d’Elia Grant/research support from: Unrestricted grant from Novartis., Consultant of: Advisory Board Fees from Sandoz, Novartis, and Abbvie, Lennart T.H. Jacobsson Consultant of: AbbVie, Eli Lilly, Janssen, Novartis and Pfizer, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma
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| 48. |
- Maroju, P. K., et al.
(author)
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Analysis of two-color photoelectron spectroscopy for attosecond metrology at seeded free-electron lasers
- 2021
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In: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 23:4
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Journal article (peer-reviewed)abstract
- The generation of attosecond pulse trains at free-electron lasers opens new opportunities in ultrafast science, as it gives access, for the first time, to reproducible, programmable, extreme ultraviolet (XUV) waveforms with high intensity. In this work, we present a detailed analysis of the theoretical model underlying the temporal characterization of the attosecond pulse trains recently generated at the free-electron laser FERMI. In particular, the validity of the approximations used for the correlated analysis of the photoelectron spectra generated in the two-color photoionization experiments are thoroughly discussed. The ranges of validity of the assumptions, in connection with the main experimental parameters, are derived.
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| 49. |
- Middelboe, T, et al.
(author)
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The Nordic Study on schizophrenic patients living in the community. Subjective needs and perceived help.
- 2001
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In: European psychiatry. - 0924-9338 .- 1778-3585. ; 16:4, s. 207-14
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Journal article (peer-reviewed)abstract
- In a community sample of 418 persons diagnosed with schizophrenia, subjective needs and perceived help was measured by the Camberwell Assessment of Need (CAN). The mean number of reported needs was 6.2 and the mean number of unmet needs 2.6. The prevalence of needs varied substantially between the need areas from 3.6% ('telephone') to 84.0% ('psychotic symptoms'). The rate of satisfaction estimated as the percentage of persons satisfied with the help provided within an area varied between 20.0% ('telephone') and 80.6% ('food'). The need areas concerning social and interpersonal functioning demonstrated the highest proportion of unmet to total needs. In a majority of need areas the patients received more help from services than from relatives, but in the areas of social relations the informal network provided substantial help. In general the patients reported a need for help from services clearly exceeding the actual amount of help received. In a linear regression model symptom load (BPRS) and impaired functioning (GAF) were significant predictors of the need status, explaining 30% of the variance in total needs and 20% of the variance in unmet needs. It is concluded that the mental health system fails to detect and alleviate needs in several areas of major importance to schizophrenic patients. Enhanced collaboration between the care system and the informal network to systematically map the need profile of the patients seems necessary to minimise the gap between perceived needs and received help.
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| 50. |
- Ohlsson, Claes, 1965, et al.
(author)
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Growth hormone and bone.
- 1998
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In: Endocrine reviews. - 0163-769X. ; 19:1, s. 55-79
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Journal article (peer-reviewed)abstract
- It is well known that GH is important in the regulation of longitudinal bone growth. Its role in the regulation of bone metabolism in man has not been understood until recently. Several in vivo and in vitro studies have demonstrated that GH is important in the regulation of both bone formation and bone resorption. In Figure 9 a simplified model for the cellular effects of GH in the regulation of bone remodeling is presented (Fig. 9). GH increases bone formation in two ways: via a direct interaction with GHRs on osteoblasts and via an induction of endocrine and autocrine/paracrine IGF-I. It is difficult to say how much of the GH effect is mediated by IGFs and how much is IGF-independent. GH treatment also results in increased bone resorption. It is still unknown whether osteoclasts express functional GHRs, but recent in vitro studies indicate that GH regulates osteoclast formation in bone marrow cultures. Possible modulations of the GH/IGF axis by glucocorticoids and estrogens are also included in Fig. 9. GH deficiency results in a decreased bone mass in both man and experimental animals. Long-term treatment (> 18 months) of GHD patients with GH results in an increased bone mass. GH treatment also increases bone mass and the total mechanical strength of bones in rats with a normal GH secretion. Recent clinical studies demonstrate that GH treatment of patients with normal GH secretion increases biochemical markers for both bone formation and bone resorption. Because of the short duration of GH treatment in man with normal GH secretion, the effect on bone mass is still inconclusive. Interestingly, GH treatment to GHD adults initially results in increased bone resorption with an increased number of bone-remodeling units and more newly produced unmineralized bone, resulting in an apparent low or unchanged bone mass. However, GH treatment for more than 18 months gives increased bone formation and bone mineralization of newly produced bone and a concomitant increase in bone mass as determined with DEXA. Thus, the action of GH on bone metabolism in GHD adults is 2-fold: it stimulates both bone resorption and bone formation. We therefore propose "the biphasic model" of GH action in bone remodeling (Fig. 10). According to this model, GH initially increases bone resorption with a concomitant bone loss that is followed by a phase of increased bone formation. After the moment when bone formation is stimulated more than bone resorption (transition point), bone mass is increased. However, a net gain of bone mass caused by GH may take some time as the initial decrease in bone mass must first be replaced (Fig. 10). When all clinical studies of GH treatment of GHD adults are taken into account, it appears that the "transition point" occurs after approximately 6 months and that a net increase of bone mass will be seen after 12-18 months of GH treatment. It should be emphasized that the biphasic model of GH action in bone remodeling is based on findings in GHD adults. It remains to be clarified whether or not it is valid for subjects with normal GH secretion. A treatment intended to increase the effects of GH/IGF-I axis on bone metabolism might include: 1) GH, 2) IGF, 3) other hormones/factors increasing the local IGF-I production in bone, and 4) GH-releasing factors. Other hormones/growth factors increasing local IGF may be important but are not discussed in this article. IGF-I has been shown to increase bone mass in animal models and biochemical markers in humans. However, no effect on bone mass has yet been presented in humans. Because the financial cost for GH treatment is high it has been suggested that GH-releasing factors might be used to stimulate the GH/IGF-I axis. The advantage of GH-releasing factors over GH is that some of them can be administered orally and that they may induce a more physiological GH secretion. (ABSTRACT TRUNCATED)
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