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- Askling, J, et al.
(author)
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Haematopoietic malignancies in rheumatoid arthritis : lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists
- 2005
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 64:10, s. 1414-1420
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Journal article (peer-reviewed)abstract
- BACKGROUND:Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, and maybe also of leukaemia and multiple myeloma. The effect of tumour necrosis factor (TNF) antagonists on lymphoma risk and characteristics is unclear.OBJECTIVE:To assess expected rates and relative risks of haematopoietic malignancies, especially those associated with TNF antagonists, in large population based cohorts of patients with RA.METHODS:A population based cohort study was performed of patients with RA (one prevalent cohort (n = 53,067), one incident cohort (n = 3703), and one TNF antagonist treated cohort 1999 through 2003 (n = 4160)), who were linked with the Swedish Cancer Register. Additionally, the lymphoma specimens for the 12 lymphomas occurring in patients with RA exposed to TNF antagonists in Sweden 1999 through 2004 were reviewed.RESULTS:Study of almost 500 observed haematopoietic malignancies showed that prevalent and incident patients with RA were at increased risk of lymphoma (SIR = 1.9 and 2.0, respectively) and leukaemia (SIR = 2.1 and 2.2, respectively) but not of myeloma. Patients with RA treated with TNF antagonists had a tripled lymphoma risk (SIR = 2.9) compared with the general population. After adjustment for sex, age, and disease duration, the lymphoma risk after exposure to TNF antagonists was no higher than in the other RA cohorts. Lymphomas associated with TNF antagonists had characteristics similar to those of other RA lymphomas.CONCLUSION:Overall, patients with RA are at equally increased risks for lymphomas and leukaemias. Patients with RA treated with TNF antagonists did not have higher lymphoma risks than other patients with RA. Prolonged observation is needed to determine the long term effects of TNF antagonists on lymphoma risk.
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- Askling, J, et al.
(author)
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Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists
- 2005
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 64:10, s. 1421-1426
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Journal article (peer-reviewed)abstract
- BACKGROUND:Existing studies of solid cancers in rheumatoid arthritis (RA) reflect cancer morbidity up until the early 1990s in prevalent cohorts admitted to hospital during the 1980s.OBJECTIVE:To depict the cancer pattern of contemporary patients with RA, from updated risk data from prevalent and incident RA populations. To understand the risk of solid cancer after tumour necrosis factor (TNF) treatment by obtaining cancer data from cohorts treated in routine care rather than trials.METHODS:A population based study of three RA cohorts (one prevalent, admitted to hospital 1990-2003 (n = 53,067), one incident, diagnosed 1995-2003 (n = 3703), and one treated with TNF antagonists 1999-2003 (n = 4160)), which were linked with Swedish nationwide cancer and census registers and followed up for cancer occurrence through 2003.RESULTS:With 3379 observed cancers, the prevalent RA cohort was at marginally increased overall risk of solid cancer, with 20-50% increased risks for smoke related cancers and +70% increased risk for non-melanoma skin cancer, but decreased risk for breast (-20%) and colorectal cancer (-25%). With 138 cancers, the incident RA cohort displayed a similar cancer pattern apart from non-decreased risks for colorectal cancer. TNF antagonist treated patients displayed solid cancer (n = 67) risks largely similar to those of other patients with RA.CONCLUSION:The cancer pattern in patients treated with TNF antagonists mirrors those of other contemporary as well as historic RA cohorts. The consistent increase in smoking associated cancers in patients with RA emphasises the potential for smoking cessation as a cancer preventive measure in RA.
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- Yager, P. L., et al.
(author)
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A carbon budget for the Amundsen Sea Polynya, Antarctica: Estimating net community production and export in a highly productive polar ecosystem
- 2016
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In: Elementa-Science of the Anthropocene. - : University of California Press. - 2325-1026. ; 4
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Journal article (peer-reviewed)abstract
- Polynyas, or recurring areas of seasonally open water surrounded by sea ice, are foci for energy and material transfer between the atmosphere and the polar ocean. They are also climate sensitive, with both sea ice extent and glacial melt influencing their productivity. The Amundsen Sea Polynya (ASP) is the greenest polynya in the Southern Ocean, with summertime chlorophyll a concentrations exceeding 20 mu g L-1. During the Amundsen Sea Polynya International Research Expedition (ASPIRE) in austral summer 2010-11, we aimed to determine the fate of this high algal productivity. We collected water column profiles for total dissolved inorganic carbon (DIC) and nutrients, particulate and dissolved organic matter, chlorophyll a, mesozoo-plankton, and microbial biomass to make a carbon budget for this ecosystem. We also measured primary and secondary production, community respiration rates, vertical particle flux and fecal pellet production and grazing. With observations arranged along a gradient of increasing integrated dissolved inorganic nitrogen drawdown (Delta DIN; 0.027-0.74 mol N m(-2)), changes in DIC in the upper water column (ranging from 0.2 to 4.7 mol C m(-2)) and gas exchange (0-1.7 mol C m(-2)) were combined to estimate early season net community production (sNCP; 0.2-5.9 mol C m(-2)) and then compared to organic matter inventories to estimate export. From a phytoplankton bloom dominated by Phaeocystis antarctica, a high fraction (up to similar to 60%) of sNCP was exported to sub-euphotic depths. Microbial respiration remineralized much of this export in the mid waters. Comparisons to short-term (2-3 days) drifting traps and a year-long moored sediment trap capturing the downward flux confirmed that a relatively high fraction (3-6%) of the export from similar to 100 m made it through the mid waters to depth. We discuss the climate-sensitive nature of these carbon fluxes, in light of the changing sea ice cover and melting ice sheets in the region.
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- Yager, P. L., et al.
(author)
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ASPIRE The Amundsen Sea Polynya International Research Expedition
- 2012
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In: Oceanography. - : The Oceanography Society. - 1042-8275. ; 25:3, s. 40-53
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Journal article (peer-reviewed)abstract
- In search of an explanation for some of the greenest waters ever seen in coastal Antarctica and their possible link to some of the fastest melting glaciers and declining summer sea ice, the Amundsen Sea Polynya International Research Expedition (ASPIRE) challenged the capabilities of the US Antarctic Program and RVIB Nathaniel B. Palmer during Austral summer 2010-2011. We were well rewarded by both an extraordinary research platform and a truly remarkable oceanic setting. Here we provide further insights into the key questions that motivated our sampling approach during ASPIRE and present some preliminary findings, while highlighting the value of the Palmer for accomplishing complex, multifaceted oceanographic research in such a challenging environment.
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- Askling, Johan, et al.
(author)
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Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas : relative risks and time trends in the Swedish Biologics Register
- 2009
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In: Annals of the Rheumatic Diseases. - London, UK : BMJ. - 0003-4967 .- 1468-2060. ; 68:5, s. 648-653
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Journal article (peer-reviewed)abstract
- BACKGROUND:Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis (RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern.METHODS:Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n = 67,743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 (n = 6604) were identified. A general population comparator (n = 471,024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals.RESULTS:Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26,981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients (336 lymphomas during 365,026 person-years) and 2.72 (95% CI 1.82 to 4.08) versus the general population comparator (1568 lymphomas during 3,355,849 person-years). RA patients starting anti-TNF therapy in 1998-2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent.CONCLUSION:Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.
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- Bertilsson, Stefan, et al.
(author)
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The under-ice microbiome of seasonally frozen lakes
- 2013
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In: Limnology and Oceanography. - : Wiley. - 0024-3590 .- 1939-5590. ; 58:6, s. 1998-2012
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Research review (peer-reviewed)abstract
- Compared to the well-studied open water of the ‘‘growing’’ season, under-ice conditions in lakes are characterized by low and rather constant temperature, slow water movements, limited light availability, and reduced exchange with the surrounding landscape. These conditions interact with ice-cover duration to shape microbial processes in temperate lakes and ultimately influence the phenology of community and ecosystem processes. We review the current knowledge on microorganisms in seasonally frozen lakes. Specifically, we highlight how under-ice conditions alter lake physics and the ways that this can affect the distribution and metabolism of auto- and heterotrophic microorganisms. We identify functional traits that we hypothesize are important for understanding under-ice dynamics and discuss how these traits influence species interactions. As ice coverage duration has already been seen to reduce as air temperatures have warmed, the dynamics of the under- ice microbiome are important for understanding and predicting the dynamics and functioning of seasonally frozen lakes in the near future.
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- Capo, Eric, et al.
(author)
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Lake sedimentary dna research on past terrestrial and aquatic biodiversity: Overview and recommendations
- 2021
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In: Quaternary. - : MDPI. - 2571-550X. ; 4:1
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Research review (peer-reviewed)abstract
- The use of lake sedimentary DNA to track the long-term changes in both terrestrial and aquatic biota is a rapidly advancing field in paleoecological research. Although largely applied nowadays, knowledge gaps remain in this field and there is therefore still research to be conducted to ensure the reliability of the sedimentary DNA signal. Building on the most recent literature and seven original case studies, we synthesize the state-of-the-art analytical procedures for effective sampling, extraction, amplification, quantification and/or generation of DNA inventories from sedimentary ancient DNA (sedaDNA) via high-throughput sequencing technologies. We provide recommendations based on current knowledge and best practises.
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- Garcia, Sarahi L, et al.
(author)
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Contrasting patterns of genome-level diversity across distinct co-occurring bacterial populations
- 2018
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In: The ISME Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 12:3, s. 742-755
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Journal article (peer-reviewed)abstract
- To understand the forces driving differentiation and diversification in wild bacterial populations, we must be able to delineate and track ecologically relevant units through space and time. Mapping metagenomic sequences to reference genomes derived from the same environment can reveal genetic heterogeneity within populations, and in some cases, be used to identify boundaries between genetically similar, but ecologically distinct, populations. Here we examine population-level heterogeneity within abundant and ubiquitous freshwater bacterial groups such as the acI Actinobacteria and LD12 Alphaproteobacteria (the freshwater sister clade to the marine SAR11) using 33 single-cell genomes and a 5-year metagenomic time series. The single-cell genomes grouped into 15 monophyletic clusters (termed "tribes") that share at least 97.9% 16S rRNA identity. Distinct populations were identified within most tribes based on the patterns of metagenomic read recruitments to single-cell genomes representing these tribes. Genetically distinct populations within tribes of the acI Actinobacterial lineage living in the same lake had different seasonal abundance patterns, suggesting these populations were also ecologically distinct. In contrast, sympatric LD12 populations were less genetically differentiated. This suggests that within one lake, some freshwater lineages harbor genetically discrete (but still closely related) and ecologically distinct populations, while other lineages are composed of less differentiated populations with overlapping niches. Our results point at an interplay of evolutionary and ecological forces acting on these communities that can be observed in real time.
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- Svensson, Ulrika S H, et al.
(author)
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Artemisinin induces omeprazole metabolism in human beings
- 1998
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In: Clinical Pharmacology and Therapeutics. - 0009-9236 .- 1532-6535. ; 64, s. 160-
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Journal article (peer-reviewed)abstract
- Objective: This study investigated whether time-dependent artemisinin pharmacokinetics correlated to CYP3A4 or CYP2C19 activity in vivo. Methods: Artemisinin (two oral doses per day of 250 mg) was given to nine healthy Vietnamese subjects for 7 days (day 1 to day 7), Single 20 mg doses of omeprazole were given orally on day -7, day 1, and day 7, Single doses of artemisinin and omeprazole were given in combination on day 14 after a 6-day washout period. The pharmacokinetics of artemisinin, omeprazole, hydroxyomeprazole, and omeprazole sulfone were evaluated on days -7, 1, 7, and 14, On the same days urine was collected for the determination of 6 beta-hydroxycortisol and cortisol excretion. Results: Areas under plasma concentration-time curves (AUC) for artemisinin and omeprazole decreased on day 7 to 20% (95% confidence intervals, 13%, 28%) and 35% (25%, 46%), respectively, compared with values on day 1, AUC ratios for hydroxyomeprazole/omeprazole increased 2.2-fold (1,7, 2.7) on day 7 compared with values on day 1, Al values were normalized at day 14, There were no significant changes in the omeprazole sulfone/omeprazole ratio or in the 6 beta-hydroxycortisol/cortisol ratio between the study days. In one subject found to have poor CYP2C19 metabolization, the elimination of omeprazole increased after artemisinin exposure, with no change in the hydroxyomeprazole/omeprazole AUC ratio. Conclusion: Artemisinin did not alter CYP3A4 activity, whereas an increase in CYP2C19 activity was observed. The increased elimination of omeprazole in both poor and extensive CYP2C19 metabolizers suggests artemisinin induces both CYP2C19 and another enzyme.
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- Ahlner, J, et al.
(author)
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CYP2D6, serotonin and suicide
- 2010
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In: Pharmacogenomics. - 1744-8042. ; 11:7, s. 903-905
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Journal article (other academic/artistic)
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