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- Forsberg, A., et al.
(author)
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Once-only colonoscopy or two rounds of faecal immunochemical testing 2 years apart for colorectal cancer screening (SCREESCO): preliminary report of a randomised controlled trial
- 2022
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In: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:6, s. 513-521
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Journal article (peer-reviewed)abstract
- Background Screening for colorectal cancer is done with lower gastrointestinal endoscopy or stool-based tests. There is little evidence from randomised trials to show primary colonoscopy reduces mortality in colorectal cancer We aimed to investigate the effect of screening with once-only colonoscopy or two rounds of faecal immunochemical test screening on colorectal cancer mortality and incidence. Methods We did a randomised controlled trial in Sweden (SCREESCO). Residents in 18 of 21 regions who were age 60 years in the year of randomisation were identified from a population register maintained by the Swedish Tax Agency. A statistician with no further involvement in the trial used a randomised block method to assign individuals to once-only colonoscopy, two rounds of faecal immunochemical testing (OC-Sensor; 2 years apart), or a control group (no intervention; standard diagnostic pathways), in a ratio of 1:6 for colonoscopy versus control and 1:2 for faecal immunochemical testing versus control. Masking was not possible due to the nature of the trial. The primary endpoints of the trial are colorectal cancer mortality and colorectal cancer incidence. Here, we report preliminary participation rates, baseline findings, and adverse events from March, 2014, to December, 2020, in the two intervention groups after completion of recruitment and screening, up to the completion of the second faecal immunochemical testing round. Analyses were done in the intention-to-screen population, defined as all individuals who were randomly assigned to the respective study group. This study is registered with Clinical Trials.gov, NCT02078804. Findings Between March 1, 2014, and Dec 31, 2020, 278 280 people were induded in the study; 31 140 were assigned to the colonoscopy group, 60 300 to the faecal immunochemical test group, and 186 840 to the control group. 10 679 (35.1%) of 30 400 people who received an invitation for colonoscopy participated. 33 383 (55.5%) of 60 137 people who received a postal faecal immunochemical test participated. In the intention-to-screen analysis, colorectal cancer was detected in 49 (0.16%) of 31140 people in the colonoscopy group versus 121 (0. 20%) of 60 300 in the faecal immunochemical test group (relative risk [RR] 0.78, 95% CI 0.56-1.09). Advanced adenomas were detected in 637 (2.05%) people in the colonoscopy group and 968 (1.61%) in the faecal immunochemical test group (RR 1.27, 95% CI 1.15-1.41). Colonoscopy detected more right-sided advanced adenomas than faecal immunochemical testing. There were two perforations and 15 major bleeds in 16 555 colonoscopies. No intervention-related deaths occurred. Interpretation The diagnostic yield and the low number of adverse events indicate that the design from this trial, both for once-only colonoscopy and faecal immunochemical test screening, could be transferred to a population-based screening service if a benefit in disease-specific mortality is subsequently shown. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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- Strömberg, Ulf, 1964, et al.
(author)
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Colorectal cancer screening with fecal immunochemical testing or primary colonoscopy: An analysis of health equity based on a randomised trial
- 2022
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In: eClinicalMedicine. - : Elsevier BV. - 2589-5370. ; 47
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Journal article (peer-reviewed)abstract
- Background: We have addressed health equity attained by fecal immunochemical testing (FIT) and primary colonoscopy (PCOL), respectively, in the randomised controlled screening trial SCREESCO conducted in Sweden. Methods: We analysed data on the individuals recruited between March 2014, and March 2020, within the study registered with ClinicalTrials.gov, NCT02078804. Swedish population registry data on educational level, household income, country of birth, and marital status were linked to each 60-year-old man and woman who had been randomised to two rounds of FIT 2 years apart (n = 60,123) or once-only PCOL (n = 30,390). Furthermore, we geo-coded each study individual to his/her residential area and assessed neighbourhood-level data on deprivation, proportion of non-Western immigrants, population density, and average distance to healthcare center for colonoscopy. We estimated adjusted associations of each covariate with the colonoscopy attendance proportion out of all invited to respective arms; ie, the preferred outcome for addressing health equity. In the FIT arm, the test uptake and the colonoscopy uptake among the test positives were considered as the secondary outcomes. Findings: We found a marked socioeconomic gradient in the colonoscopy attendance proportion in the PCOL arm (adjusted odds ratio [95% credibility interval] between the groups categorised in the highest vs. lowest national quartile for household income: 2·20 [2·01–2·42]) in parallel with the gradient in the test uptake of the FIT × 2 screening (2·08 [1·96–2·20]). The corresponding gradient in the colonoscopy attendance proportion out of all invited to FIT was less pronounced (1·29 [1·16–1·42]), due to higher proportions of FIT positives in socioeconomically disadvantaged groups. Interpretation: The unintended risk of exacerbating inequalities in health by organised colorectal cancer screening may be higher with a PCOL strategy than a FIT strategy, despite parallel socioeconomic gradients in uptake. Funding: This work was supported by the Swedish Cancer Society under Grant 20 0719. CB and US provided economic support from the Swedish Research Council for Health, Working life, and Welfare under Grant 2020–00962.
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- Vergoossen, Dana L. E., et al.
(author)
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Enrichment of serum IgG4 in MuSK myasthenia gravis patients
- 2022
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In: Journal of Neuroimmunology. - : Elsevier. - 0165-5728 .- 1872-8421. ; 373
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Journal article (peer-reviewed)abstract
- Muscle-specific kinase (MuSK) myasthenia gravis (MG) is a neuromuscular autoimmune disease belonging to a growing group of IgG4 autoimmune diseases (IgG4-AIDs), in which the majority of pathogenic autoantibodies are of the IgG4 subclass. The more prevalent form of MG with acetylcholine receptor (AChR) antibodies is caused by IgG1-3 autoantibodies. A dominant role for IgG4 in autoimmune disease is intriguing due to its antiinflammatory characteristics. It is unclear why MuSK autoantibodies are predominantly IgG4. We hypothesized that MuSK MG patients have a general predisposition to generate IgG4 responses, therefore resulting in high levels of circulating IgG4. To investigate this, we quantified serum Ig isotypes and IgG subclasses using nephelometric and turbidimetric assays in MuSK MG and AChR MG patients not under influence of immunosuppressive treatment. Absolute serum IgG1 was increased in both MuSK and AChR MG patients compared to healthy donors. In addition, only MuSK MG patients on average had significantly increased and enriched serum IgG4. Although more MuSK MG patients had elevated serum IgG4, for most the IgG4 serum levels fell within the normal range. Correlation analyses suggest MuSK-specific antibodies do not solely explain the variation in IgG4 levels. In conclusion, although serum IgG4 levels are slightly increased, the levels do not support ubiquitous IgG4 responses in MuSK MG patients as the underlying cause of dominant IgG4 MuSK antibodies.
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- Schillings, Audrey, et al.
(author)
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Earth’s O+ Outflow and Escape during Various Solar Wind Conditions
- 2020
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Conference paper (peer-reviewed)abstract
- Ion outflow at Earth is studied since several decades and is important for the global atmospheric evolution. Over the years, spacecraft and technology improved leading to new studies and breakthrough in the field. With different mechanisms to gain energy and velocity such as field-aligned acceleration, centrifugal acceleration and transversal heating, a large amount of ions becomes gravitationally untrapped above the ionosphere. While some of these ions may enter the plasma sheet and partially be redirected towards Earth, majority of these ions reaches the high-latitude boundary region, such as the plasma mantle and are lost into the solar wind. We examined this phenomenon using Cluster European Spacecraft that covers these high-latitude regions. Here, we studied the influence of solar wind conditions on O+ outflow and escape during 7 years of observations (2001 to 2007). We found that O+ outflow is exponentially correlated with enhanced geomagnetic activity (Kp index) as well as with solar wind dynamic pressure and IMF. Under undisturbed magnetospheric conditions, the O+ outflow is typically 1012.5 m-2s-1 while it reaches 1014 m-2s-1 during major geomagnetic storms. Additionally, tracing (forward in time) about 25000 O+ ions initially observed in the plasma mantle showed that 98% of these ions escape directly through the magnetopause whereas only a few escape through the distant tail. In summary, the more disturbed the magnetosphere is, the more ion outflow and escape is observed.
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- Schillings, Audrey, et al.
(author)
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The fate of O+ ions observed in the plasma mantle : particle tracing modelling and Cluster observations
- 2020
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Conference paper (peer-reviewed)abstract
- The atmospheric evolution on geological timescales is partly given by the atmospheric escape. This escape includes ion escape and particularly O+ ions. How much O+ ions escape from the Earth is the main focus of this study. Using the Tsyganenko and Weimer models to represent the magnetic and electric fields respectively, we traced 26200 O+ ions trajectories forward in time and studied their final positions in the Earth’s environment. Starting in the plasma mantle, the initial positions, thermal and parallel bulk velocities of O+ ions are taken from the European Cluster observations between 2001 and 2007. Most (98%) of the ions observed in the plasma mantle escape the Earth’s magnetosphere, with 20% of them directly through the dayside magnetopause. An interesting feature of the 80% escaping ions left is that very few reach the distant tail, they rather escape through the nightside magnetopause. Finally, no significant correlation was found between magnetospheric disturbed conditions and the final positions of the traced O+ ions.
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- Seikkula-Leino, Jaana, et al.
(author)
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Responding to Global Challenges through Education : Entrepreneurial, Sustainable, and Pro-Environmental Education in Nordic Teacher Education Curricula
- 2021
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In: Sustainability. - : MDPI. - 2071-1050. ; 13:22
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Journal article (peer-reviewed)abstract
- The United Nations’ Sustainable Development Goals (SDGs), and the European Union’s strategies both set goals for solving environmental challenges faced by societies and communities. As part of solving these challenges, both the UN and the EU stress the development of entrepreneurial and innovative education. Teacher education plays a crucial role in these efforts, since teachers and teacher educators have a significant impact on educating citizens far into the future. In this research, we studied how Nordic (Finnish, Swedish, and Icelandic) primary teacher education curricula involve entrepreneurial, sustainable, and pro-environmental education. For this study, the authors analyzed the B.Ed. curricula of three academic teacher education institutions in Spring 2021. We used qualitative content analysis as our research method. According to the results, all three curricula incorporated both entrepreneurship education and sustainable development to some extent, although often not very explicitly. Given the urgency of problems such as global climate change, the educational goals and contents in these curricula related to entrepreneurial education and sustainable development are very limited. The idea of integrating environmental/sustainable and entrepreneurship education could be promoted in the future more explicitly, with these interdisciplinary educational themes emphasised more strongly in the curricula and education policies.
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| 20. |
- Yazdani, S, et al.
(author)
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T cell responses at diagnosis of amyotrophic lateral sclerosis predict disease progression
- 2022
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 6733-
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Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, involving neuroinflammation and T cell infiltration in the central nervous system. However, the contribution of T cell responses to the pathology of the disease is not fully understood. Here we show, by flow cytometric analysis of blood and cerebrospinal fluid (CSF) samples of a cohort of 89 newly diagnosed ALS patients in Stockholm, Sweden, that T cell phenotypes at the time of diagnosis are good predictors of disease outcome. High frequency of CD4+FOXP3− effector T cells in blood and CSF is associated with poor survival, whereas high frequency of activated regulatory T (Treg) cells and high ratio between activated and resting Treg cells in blood are associated with better survival. Besides survival, phenotypic profiling of T cells could also predict disease progression rate. Single cell transcriptomics analysis of CSF samples shows clonally expanded CD4+ and CD8+ T cells in CSF, with characteristic gene expression patterns. In summary, T cell responses associate with and likely contribute to disease progression in ALS, supporting modulation of adaptive immunity as a viable therapeutic option.
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