| 1. |
- Bodin, Theo, et al.
(författare)
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Road traffic noise, air pollution and myocardial infarction: a prospective cohort study.
- 2016
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 89:5, s. 793-802
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Tidskriftsartikel (refereegranskat)abstract
- Both road traffic noise and air pollution have been linked to cardiovascular disease. However, there are few prospective epidemiological studies available where both road traffic noise and air pollution have been analyzed simultaneously. The aim of this study was to investigate the relation between road traffic noise, air pollution and incident myocardial infarction in both current (1-year average) and medium-term (3-year average) perspective.
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| 2. |
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| 3. |
- Ertzgaard, Per, 1958-, et al.
(författare)
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Oculomotor screening and neuro-visual rehabilitation following pediatric brain tumor resection
- 2023
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Ingår i: Journal of Pediatric Rehabilitation Medicine. - : Ios press. - 1874-5393 .- 1875-8894. ; , s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Visual difficulties are common after brain tumors, despite a lack of visual complaints at diagnosis. These include difficulties with eye movements, visual coordination, vergence, accommodation, and photophobia, in addition to more obvious problems such as visual field defects.This case report presents the results of a thorough neuro-visual evaluation in a boy with sequelae after a brain tumor including intermittent double vision that was not explained by routine visual examination. Subjective complaints included poor reading perseverance, intermittent blurred and double vision, headache around the eyes when performing near activities, less efficient eye movement behavior in reading tasks, and increased sensitivity to visual motion. The patient participated in a multidisciplinary visual rehabilitation program that included reading glasses with prism compensation and tinted glasses, as well as training with the aim of improving eye teaming, near vision functions, and perseverance in eye movements.The patient responded quickly to the vision therapy program, with positive changes after just four weeks. Repeated neuro-visual evaluations over eight months showed remarkable improvements that were stable over time. This encouraging case report supports the notion that neuro-visual evaluation and rehabilitation should be included in the follow-up of patients after brain tumors.
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| 4. |
- Hansson, Monika, et al.
(författare)
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Validation of a multiplex chip-based assay for the detection of autoantibodies against citrullinated peptides
- 2012
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Ingår i: ARTHRITIS RESEARCH & THERAPY. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 14:5, s. R201-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Autoantibodies directed against citrullinated proteins/peptides (ACPAs) are highly specific and predictive for the development of rheumatoid arthritis (RA). Different subgroups of RA patients, which have different prognoses and may require different treatments, are characterized by different autoantibody profiles. The objective of this study was to develop a microarray for the detection of multiple RA-associated autoantibodies, initially focusing on responses against citrullinated epitopes on candidate autoantigens in RA. Methods: The microarray is based on Phadia's ImmunoCAP ISAC system, with which reactivity to more than 100 antigens can be analyzed simultaneously, by using minute serum volumes (<10 mu l). Twelve citrullinated peptides, and the corresponding native arginine-containing control peptides, were immobilized in an arrayed fashion onto a chemically modified glass slide, allowing a three-dimensional layer with high binding capacity. The assay was optimized concerning serum dilution and glass surface, whereas each individual antigen was optimized concerning coupling chemistry, antigen concentration, and selection of spotting buffer. The performance of each peptide in the ImmunoCAP ISAC system was compared with the performance in enzyme-linked immunosorbent assays (ELISAs). Serum from 927 RA patients and 461 healthy controls from a matched case-control study were applied onto reaction sites on glass slides, followed by fluorescent-labeled anti-human immunoglobulin G (IgG) antibody. Fluorescence intensities were detected with a laser scanner, and the results analyzed by using image-analysis software. Results: Strong correlations between the ImmunoCAP ISAC system and ELISA results were found for individual citrullinated peptides (Spearman rho typically between 0.75 and 0.90). Reactivity of RA sera with the peptides was seen mainly in the anticyclic citrullinated peptide 2 (CCP2)-positive subset, but some additional reactivity with single citrullinated peptides was seen in the anti-CCP2-negative subset. Adjusting for reactivity against arginine-containing control peptides did not uniformly change the diagnostic performance for antibodies against the individual citrullinated peptides. Conclusions: The multiplexed array, for detection of autoantibodies against multiple citrullinated epitopes on candidate RA autoantigens, will be of benefit in studies of RA pathogenesis, diagnosis, and potentially as a guide to individualized treatment.
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| 5. |
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| 6. |
- Jonsson, B. G., et al.
(författare)
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Skogspolitiken hotar biologiska mångfalden
- 2008
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Ingår i: Dagens Nyheter. ; 14 april
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Ledande svenska forskare varnar för att det nationella naturarvet äventyras: Vi skäms över våra beslutsfattares likgiltighet för miljön. Den svenska skogen har förvandlats till en jättelik odlingsyta. Där förr otaliga arter levde samman i harmoni dominerar numera helt gran, tall och inplanterade främmande trädslag. Denna skogsodling utgör ett hot mot den biologiska mångfalden vilket strider mot riksdagens miljökvalitetsmål. Den svenska skogspolitiken vilar officiellt på att produktion av skogsråvara och miljö är likvärdiga mål. Men i praktiken har produktionen satts i första rummet. Bortåt 2 000 skogslevande arters överlevnad hotas på grund av den förda politiken. Vi är djupt oroade och skäms över att det rika Sverige inte arbetar effektivt för att nå nationella och internationella miljömål. Det skriver 14 ledande forskare i bland annat växtekologi, ekologisk zoologi och botanik.
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| 7. |
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| 8. |
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| 9. |
- Petersson, Jöran, et al.
(författare)
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Teaching dimensional analysis in secondary school mathematics
- 2021
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Ingår i: Abstract book nofa8. - : Western Norway University of Applied Sciences.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- AbstractIn its elementary form, the idea of dimensional analysis is to look at the unit of a magnitude, for example speed, and conclude that speed measured in m/s is a quotient having meters in the numerator and seconds in the denominator. However, despite dimensional analysis being a not un-common theme for research in mathematics education at tertiary level teaching, it seems in practice absent below that level. This is surprising since dimensional analysis is useful in mathematical problem solving involving proportionality. Even more so since, from halves and doubles in preschool to scalar multiplication in upper secondary school, proportionality permeates school mathematics and is well-researched (Lamon, 2007). Hence, the authors initiated a research project on how to teach dimensional analysis in school years 6-12. The novelty of this area made us choose didactical engineering (Artigue, 2015) as a theoretical framework suitable for developing the teaching of dimensional analysis. Accordingly, in a cycle of a priori and a posteriori analyses, the authors are developing an empirically based teaching model for dimensional analysis including the topic of constructing exercises for students. We present results from this on-going development project. ReferencesArtigue, M. (2015). Perspectives on Design Research: The Case of Didactical Engineering. In A. Bikner-Ahsbahs, C. Knipping, N. Presmeg. (Eds.). Approaches to Qualitative Research in Mathematics Education. Dordrecht: Springer.Lamon, S. J. (2007). Rational numbers and proportional reasoning: Towards a theoretical framework. In F.K. Lester (red) Second handbook of research on mathematics teaching and learning, vol 2 (pp. 629–668). Charlotte, NC: NCTM.
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| 10. |
- Zirath, Hanna, et al.
(författare)
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MYC inhibition induces metabolic changes leading to accumulation of lipid droplets in tumor cells
- 2013
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 110:25, s. 10258-10263
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Tidskriftsartikel (refereegranskat)abstract
- The MYC genes are the most frequently activated oncogenes in human tumors and are hence attractive therapeutic targets. MYCN amplification leads to poor clinical outcome in childhood neuroblastoma, yet strategies to modulate the function of MYCN do not exist. Here we show that 10058-F4, a characterized c-MYC/Max inhibitor, also targets the MYCN/Max interaction, leading to cell cycle arrest, apoptosis, and neuronal differentiation in MYCN-amplified neuroblastoma cells and to increased survival of MYCN transgenic mice. We also report the discovery that inhibition of MYC is accompanied by accumulation of intracellular lipid droplets in tumor cells as a direct consequence of mitochondrial dysfunction. This study expands on the current knowledge of how MYC proteins control the metabolic reprogramming of cancer cells, especially highlighting lipid metabolism and the respiratory chain as important pathways involved in neuroblastoma pathogenesis. Together our data support direct MYC inhibition as a promising strategy for the treatment of MYC-driven tumors.
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| 11. |
- Aaltonen, H. Laura, et al.
(författare)
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Airspace dimension assessment with nanoparticles as a proposed biomarker for emphysema
- 2021
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 76:10, s. 1040-1043
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Tidskriftsartikel (refereegranskat)abstract
- Airspace dimension assessment with nanoparticles (AiDA) is a novel method to measure distal airspace radius non-invasively. In this study, AiDA radii were measured in 618 individuals from the population-based Swedish CArdiopulmonary BioImaging Study, SCAPIS. Subjects with emphysema detected by computed tomography were compared to non-emphysematous subjects. The 47 individuals with mainly mild-to-moderate visually detected emphysema had significantly larger AiDA radii, compared with non-emphysematous subjects (326±48 μm vs 291±36 μm); OR for emphysema per 10 μm: 1.22 (1.13-1.30, p<0.0001). Emphysema according to CT densitometry was similarly associated with larger radii compared with non-emphysematous CT examinations (316±41 μm vs 291 μm±26 μm); OR per 10 μm: 1.16 (1.08-1.24, p<0.0001). The results are in line with comparable studies. The results show that AiDA is a potential biomarker for emphysema in individuals in the general population.
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| 12. |
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| 13. |
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| 14. |
- Adler, Jan-Olof, et al.
(författare)
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The upgraded photon tagging facility at the MAX IV Laboratory
- 2013
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 715, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- A description is given of the upgraded photon tagging facility at the MAX IV Laboratory. Two magnetic spectrometers are used to momentum analyze post-bremsstrahlung electrons. The tagged photon range extends from 10 to 180 MeV with an energy resolution of about 300 keV. The system has been operated at rates up to 4 x 10(6) photons s(-1) MeV (-1). Different diagnostic tools are described as well as the experimental program.
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| 15. |
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| 16. |
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| 17. |
- Ahgren, Per, et al.
(författare)
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A study of doubletalk detection performance in the presence of acoustic echo path changes
- 2006
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Ingår i: IEEE transactions on consumer electronics. - Uppsala Univ, Dept Syst & Control, Informat Control, SE-75105 Uppsala, Sweden. Karlstad Univ, Dept Elect Engn, SE-65188 Karlstad, Sweden.. - 0098-3063 .- 1558-4127. ; 52:2, s. 515-522
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Tidskriftsartikel (refereegranskat)abstract
- An efficient and well-performing double-talk detection (DTD) algorithm is a vital part of a practically working acoustic echo canceller. However, recent algorithms are typically evaluated using a static time-invariant room acoustic impulse response, omitting a proper treatment of the case when the acoustic path is changing. In this work, we introduce a common framework to objectively evaluate how path changes affect the DTD performance. Via extensive numerical simulations, we conclude that the main factor in acoustic path changes affecting the DTD performance for some of the more common DTD algorithms is variations in the damping of the acoustic path.
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| 18. |
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| 19. |
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| 20. |
- Alexanderson, Helena, et al.
(författare)
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An Arctic perspective on dating Mid-Late Pleistocene environmental history
- 2014
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 92, s. 9-31
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Forskningsöversikt (refereegranskat)abstract
- To better understand Pleistocene climatic changes in the Arctic, integrated palaeoenvironmental andpalaeoclimatic signals from a variety of marine and terrestrial geological records as well as geochronologicage control are required, not least for correlation to extra-Arctic records. In this paper we discuss,from an Arctic perspective, methods and correlation tools that are commonly used to date ArcticPleistocene marine and terrestrial events. We review the state of the art of Arctic geochronology, withfocus on factors that affect the possibility and quality of dating, and support this overview by examples ofapplication of modern dating methods to Arctic terrestrial and marine sequences.Event stratigraphy and numerical ages are important tools used in the Arctic to correlate fragmentedterrestrial records and to establish regional stratigraphic schemes. Age control is commonly provided byradiocarbon, luminescence or cosmogenic exposure ages. Arctic Ocean deep-sea sediment successionscan be correlated over large distances based on geochemical and physical property proxies for sedimentcomposition, patterns in palaeomagnetic records and, increasingly, biostratigraphic data. Many of theseproxies reveal cyclical patterns that provide a basis for astronomical tuning.Recent advances in dating technology, calibration and age modelling allow for measuring smallerquantities of material and to more precisely date previously undatable material (i.e. foraminifera for 14C,and single-grain luminescence). However, for much of the Pleistocene there are still limits to the resolutionof most dating methods. Consequently improving the accuracy and precision (analytical andgeological uncertainty) of dating methods through technological advances and better understanding ofprocesses are important tasks for the future. Another challenge is to better integrate marine andterrestrial records, which could be aided by targeting continental shelf and lake records, exploringproxies that occur in both settings, and by creating joint research networks that promote collaborationbetween marine and terrestrial geologists and modellers.
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| 21. |
- Alhamdow, Ayman, et al.
(författare)
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Chimney sweeps in Sweden : a questionnaire-based assessment of long-term changes in work conditions, and current eye and airway symptoms
- 2017
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 90:2, s. 207-216
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To explore chimney sweeping work tasks, chimney sweeps’ use of protective equipment, and type of fuel used by clients, over time. Further, to assess work-relatedness of current eye and airway symptoms. Methods: In a cross-sectional study in 2011, male Swedish chimney sweeps (n = 483; age 21–69 years) answered a questionnaire about their occupational history and eye and airway symptoms. Results: Between 1960 and 2010, black-soot-sweeping in private homes was the major task, although it decreased during the time period, for chimney sweeps. Between 1975 and 2010, the use of petroleum oil decreased, whereas the use of pellets and wood increased. Also, the use of gloves and masks increased significantly. Black-soot-sweeping in industry was associated with work-related eye symptoms (prevalence odds ratio POR = 3.76, 95% CI: 1.72–8.24, for every 10% increment of working time, adjusted for age and tobacco smoking). Chimney sweeps also had slightly higher prevalence of cough with increasing black-soot-sweeping (POR = 1.06, 95% CI: 0.99–1.13 for every 10% increment, further adjusted for the use of mask), and the association was more pronounced, although nonsignificant, for black-soot-sweeping in industry (adjusted POR = 1.26, 95% CI: 0.98–1.61). Conclusions: Chimney sweeping tasks and use of protective equipment as well as type of fuel used by the clients changed significantly over the last 35 years, which may have changed chimney sweeps’ exposure to soot. Still, chimney sweeps in Sweden have black-soot-sweeping-related eye and airway symptoms.
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| 22. |
- Andersson, Gerhard, et al.
(författare)
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Can the patient decide which modules to endorse? : an open trial of tailored internet treatment of anxiety disorders
- 2011
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Ingår i: Cognitive Behaviour Therapy. - : Routledge, Taylor and Francis Group. - 1650-6073 .- 1651-2316. ; 1:40, s. 57-64
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Tidskriftsartikel (refereegranskat)abstract
- Internet-delivered cognitive behaviour therapy commonly consists of disorder-specific modules that are based on face-to-face manuals. A recent development in the field is to tailor the treatment according to patient profile, which has the potential to cover comorbid conditions in association with anxiety and mood disorders. However, it could be that the patients themselves are able to decide what modules to use. The authors tested this in an open pilot trial with 27 patients with mixed anxiety disorders. Modules were introduced with a brief description, and patients could choose which modules to use. The exception was the two first modules and the last, which involved psychoeducation and relapse prevention. The treatment period lasted for 10 weeks. Results showed large within-group effect sizes, with an average Cohen’s d of 0.88. In a structured clinical interview, a majority (54%) had significantly improved 10 weeks after commencing treatment. Only one person dropped out. On the basis of results of this preliminary study, the authors suggest that the role of choice and tailoring should be further explored in controlled trials and that patient choice could be incorporated into Internet-delivered treatment packages.
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| 23. |
- Andersson, Jenny, et al.
(författare)
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Patient´s description of onset stroke symptoms : Oral Presentations. ESOC 2023 Abstract Book
- 2023
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Ingår i: European Stroke Journal. - : Sage Publications. - 2396-9873 .- 2396-9881. ; 8:2, s. 427-427
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Stroke symptoms vary and could be hard to recognize. In addition, stroke severity has decreased according to the National Institutes of Health Stroke Scale (NISSH), with less pronounced symptoms expression. Knowledge on the patient’s description of stroke symptoms is therefore needed. The aim was to describe patient’s symptoms at stroke onset.Methods: A qualitative content analysis was used. Data were collected through individual interviews with 27 patients (16 men and 11 women, median age 70.4 years). All patients were hospitalized with a first-time stroke. The interviews were conducted within 4 weeks of symptoms onset and before hospital discharge.Results: All patients had symptoms that affected their daily life. Some patients described having multiple symptoms at the same time, others had symptoms that began insidiously and worsened over time. Symptoms such as overwhelming fatigue or nausea were described as Premonition of becoming ill, feeling unwell or that something was wrong. Motoric bodily changes were multifaceted as slurred speech or dizziness, balance difficulties and losing control of the body or motor dysfunction. But also, that the surroundings were distorted, and solid objects moved around. Symptoms of Dazed and affected senses included confusion and visual impairment or headache.Conclusions: Stroke is a complex disease with several different symptoms’ expressions and could be difficult to recognize, especially when symptoms are less typical or perceived as not serious. Increased awareness of stroke symptoms among caregivers and among members of the community is important and needed.
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| 24. |
- Andersson, Jenny, et al.
(författare)
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Symptoms at stroke onset as described by patients: a qualitative study
- 2024
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Ingår i: BMC Neurology. - : Springer Nature. - 1471-2377. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Stroke is a common and severe disease that requires prompt care. Symptom expressions as one-sidedweakness and speech difficulties are common and included in public stroke campaigns. For some patients stroke canpresent with subtle and less common symptoms, difficult to interpret. The symptom severity assessed by the NationalInstitutes of Health Stroke Scale has decreased, and symptoms at onset may have changed. Therefore, we aimed toinvestigate how patients describe their symptoms at the onset of a first-time stroke.Methods:The study used a qualitative descriptive design and conventional content analysis. Data were collectedthrough recorded interviews with 27 patients aged 18 years and older hospitalised with a first-time stroke betweenOctober 2018 and April 2020. Data were analysed on a manifest level.Results: Symptoms at stroke onset were presented in two themes: Altered Reality and Discomfort and Changed BodyFunctions and described in five categories. Various types of symptoms were found. All symptoms were perceivedas sudden, persistent, and never experienced before and this appear as a “red thread” in the result. Regardless ofsymptom expressions, no specific symptom was described as more severe than another.Conclusions: Stroke symptoms were described with a variety of expressions. Many described complex symptomsnot typical of stroke, which can make it difficult to recognise the symptoms as a stroke and delay medical care. Publicstroke campaigns should emphasize the importance of seeking medical care at the slightest suspicion of stroke andcould be designed to help achieve this.
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| 25. |
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| 26. |
- Auffret, Alistair G., et al.
(författare)
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More warm-adapted species in soil seed banks than in herb layer plant communities across Europe
- 2023
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Ingår i: Journal of Ecology. - : John Wiley & Sons. - 0022-0477 .- 1365-2745. ; 111:5, s. 1009-1020
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Tidskriftsartikel (refereegranskat)abstract
- Responses to climate change have often been found to lag behind the rate of warming that has occurred. In addition to dispersal limitation potentially restricting spread at leading range margins, the persistence of species in new and unsuitable conditions is thought to be responsible for apparent time-lags. Soil seed banks can allow plant communities to temporarily buffer unsuitable environmental conditions, but their potential to slow responses to long-term climate change is largely unknown. As local forest cover can also buffer the effects of a warming climate, it is important to understand how seed banks might interact with land cover to mediate community responses to climate change. We first related species-level seed bank persistence and distribution-derived climatic niches for 840 plant species. We then used a database of plant community data from grasslands, forests and intermediate successional habitats from across Europe to investigate relationships between seed banks and their corresponding herb layers in 2763 plots in the context of climate and land cover. We found that species from warmer climates and with broader distributions are more likely to have a higher seed bank persistence, resulting in seed banks that are composed of species with warmer and broader climatic distributions than their corresponding herb layers. This was consistent across our climatic extent, with larger differences (seed banks from even warmer climates relative to vegetation) found in grasslands. Synthesis. Seed banks have been shown to buffer plant communities through periods of environmental variability, and in a period of climate change might be expected to contain species reflecting past, cooler conditions. Here, we show that persistent seed banks often contain species with relatively warm climatic niches and those with wide climatic ranges. Although these patterns may not be primarily driven by species’ climatic adaptations, the prominence of such species in seed banks might still facilitate climate-driven community shifts. Additionally, seed banks may be related to ongoing trends regarding the spread of widespread generalist species into natural habitats, while cool-associated species may be at risk from both short- and long-term climatic variability and change.
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| 27. |
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| 28. |
- Austeng, Dordi, et al.
(författare)
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Incidence of and risk factors for neonatal morbidity after active perinatal care : extremely preterm infants study in Sweden (EXPRESS)
- 2010
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 99:7, s. 978-992
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004-2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage >= 3. Eighty-five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty-seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.
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| 29. |
- Balakrishnan Kumar, Ramakrishnan, et al.
(författare)
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Structural and Functional Analysis of Calcium Ion Mediated Binding of 5-Lipoxygenase to Nanodiscs
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- An important step in the production of inflammatory mediators of the leukotriene family is the Ca2+ mediated recruitment of 5 Lipoxygenase (5LO) to nuclear membranes. To study this reaction in vitro, the natural membrane mimicking environment of nanodiscs was used. Nanodiscs with 10.5 nm inner diameter were made with the lipid POPC and membrane scaffolding protein MSP1E3D1. Monomeric and dimeric 5LO were investigated. Monomeric 5LO mixed with Ca2+ and nanodiscs are shown to form stable complexes that 1) produce the expected leukotriene products from arachidonic acid and 2) can be, for the first time, visualised by native gel electrophoresis and negative stain transmission electron micros-copy and 3) show a highest ratio of two 5LO per nanodisc. We interpret this as one 5LO on each side of the disc. The dimer of 5LO is visualised by negative stain transmission electron microscopy and is shown to not bind to nanodiscs. This study shows the advantages of nanodiscs to obtain basic structural information as well as functional information of a complex between a monotopic membrane protein and the membrane.
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| 30. |
- Bauer, Susanne
(författare)
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Cell type-specific translatome analysis of mouse models of three genetic neurodegenerative diseases
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The burden neurodegenerative diseases place on patients, their loved ones, and the healthcare system is significant, and despite extensive research efforts, there is currently no cure. Since degenerative changes in the brain can begin years before symptoms appear, early intervention is critical. Additionally, neurodegenerative diseases target certain brain regions and neuron types early on. A more comprehensive understanding of the affected cells during the presymptomatic phase is therefore crucial for an effective and targeted intervention. Herein, we isolated, sequenced, and analyzed translatome samples from six neuronal cell types in knock-in mouse models of three monogenic neurodegenerative diseases at a presymptomatic stage: genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Huntington’s disease (HD). To obtain the translatome samples, we used RiboTag to immunoprecipitate HA-tagged ribosomes with their translating mRNAs from targeted cell types. We analyzed six cell types across two brain regions: cerebral and cerebellar glutamatergic and GABAergic neurons, and cerebral parvalbumin (PV) and somatostatin (SST)-expressing neurons. In the first paper, we focused our analysis on the prion diseases, gCJD (E200K) and FFI (D178N). Here observed a similar response of SST+ neurons, a cell type not previously reported as affected, in both disease models. This was characterized by upregulation of ribosomeassociated genes, and downregulation of cytoskeleton and synapse-associated genes in FFI. Weighted gene co-expression network analysis of SST+ neurons pointed towards the downregulation of mTOR inhibition as a potential mechanism underlying the observed gene expression changes. In the second paper, we analyzed a 129S4-HdhQ200 knock-in mouse model of HD. Histological and behavioral assessment revealed pathological changes in the striatum and cerebellum at 9 months and a later, mild behavioral phenotype. Translatome analysis indicated a surprisingly strong response in reportedly resistant glutamatergic neurons of the cerebellum, marked by upregulation of cell cycle regulators Ccnd1 and chromobox protein genes. In the third paper, we aimed to compare disease-specific responses of PV+ neurons across the three disease models. This analysis revealed a milder response in HD compared to prion disease at comparable disease stages. Functional analysis further indicated PV+ neurons may respond differently in the investigated diseases, showing upregulation of immune response-associated pathways in gCJD, neurodegenerative-disease pathways in FFI, and autophagy in HD. Lastly, the generation of mouse models such as were used in papers I-III requires stable and predictable transgene expression without interfering with the expression of endogenous genes. In the fourth paper, we conducted a pilot study to compare three potential loci, Rpl6, Rpl7, and Eef1a1, as potential safe harbors for transgene integration. Preliminary results indicated that the Rpl6 locus may be best suited for our purposes. Furthermore, this work generated a novel dataset consisting of translatome profiles of six cell types in three neurodegenerative disease models. This provides gene expression data at a previously unavailable level of cellular resolution, especially in prion disease. We believe that this data will serve as a valuable resource for future research and help expand our understanding of the early molecular mechanisms in neurodegenerative disease beyond the scope of this thesis.
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| 31. |
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| 32. |
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| 33. |
- Bergfeldt, Nora, et al.
(författare)
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Identification of microbial pathogens in Neolithic Scandinavian humans
- 2024
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Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- With the Neolithic transition, human lifestyle shifted from hunting and gathering to farming. This change altered subsistence patterns, cultural expression, and population structures as shown by the archaeological/zooarchaeological record, as well as by stable isotope and ancient DNA data. Here, we used metagenomic data to analyse if the transitions also impacted the microbiome composition in 25 Mesolithic and Neolithic hunter-gatherers and 13 Neolithic farmers from several Scandinavian Stone Age cultural contexts. Salmonella enterica, a bacterium that may have been the cause of death for the infected individuals, was found in two Neolithic samples from Battle Axe culture contexts. Several species of the bacterial genus Yersinia were found in Neolithic individuals from Funnel Beaker culture contexts as well as from later Neolithic context. Transmission of e.g. Y. enterocolitica may have been facilitated by the denser populations in agricultural contexts.
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| 34. |
- Bergfeldt, Nora, et al.
(författare)
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Identification of microbial pathogens in Neolithic Scandinavian humans
- 2024
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Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- With the Neolithic transition, human lifestyle shifted from hunting and gathering to farming. This change altered subsistence patterns, cultural expression, and population structures as shown by the archaeological/zooarchaeological record, as well as by stable isotope and ancient DNA data. Here, we used metagenomic data to analyse if the transitions also impacted the microbiome composition in 25 Mesolithic and Neolithic hunter-gatherers and 13 Neolithic farmers from several Scandinavian Stone Age cultural contexts. Salmonella enterica, a bacterium that may have been the cause of death for the infected individuals, was found in two Neolithic samples from Battle Axe culture contexts. Several species of the bacterial genus Yersinia were found in Neolithic individuals from Funnel Beaker culture contexts as well as from later Neolithic context. Transmission of e.g. Y. enterocolitica may have been facilitated by the denser populations in agricultural contexts.
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| 35. |
- Bergqvist, Filip, et al.
(författare)
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Inhibition of mPGES-1 or COX-2 Results in Different Proteomic and Lipidomic Profiles in A549 Lung Cancer Cells
- 2019
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacological inhibition of microsomal prostaglandin E synthase (mPGES)-1 for selective reduction in prostaglandin E-2 (PGE(2)) biosynthesis is protective in experimental models of cancer and inflammation. Targeting mPGES-1 is envisioned as a safer alternative to traditional non-steroidal anti-inflammatory drugs (NSAIDs). Herein, we compared the effects of mPGES-1 inhibitor Compound III (CIII) with the cyclooxygenase (COX)-2 inhibitor NS-398 on protein and lipid profiles in interleukin (IL)-1 beta-induced A549 lung cancer cells using mass spectrometry. Inhibition of mPGES-1 decreased PGE(2) production and increased PGF(2 alpha) and thromboxane B-2 (TXB2) formation, while inhibition of COX-2 decreased the production of all three prostanoids. Our proteomics results revealed that CIII downregulated multiple canonical pathways including eIF2, eIF4/P70S6K, and mTOR signaling, compared to NS-398 that activated these pathways. Moreover, pathway analysis predicted that CIII increased cell death of cancer cells (Z = 3.8, p = 5.1E-41) while NS-398 decreased the same function (Z = -5.0, p = 6.5E-35). In our lipidomics analyses, we found alterations in nine phospholipids between the two inhibitors, with a stronger alteration in the lysophospholipid (LPC) profile with NS-398 compared to CIII. Inhibition of mPGES-1 increased the concentration of sphinganine and dihydroceramide (C16:0D hCer), while inhibition of COX-2 caused a general decrease in most ceramides, again suggesting different effects on cell death between the two inhibitors. We showed that CIII decreased proliferation and potentiated the cytotoxic effect of the cytostatic drugs cisplatin, etoposide, and vincristine when investigated in a live cell imaging system. Our results demonstrate differences in protein and lipid profiles after inhibition of mPGES-1 or COX-2 with important implications on the therapeutic potential of mPGES-1 inhibitors as adjuvant treatment in cancer. We encourage further investigations to illuminate the clinical benefit of mPGES-1 inhibitors in cancer.
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| 36. |
- Boström, Ola, 1963, et al.
(författare)
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Comparison of car seats in low speed rear-end impacts using the BioRID dummy and the new neck injury criterion (NIC).
- 2000
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Ingår i: Accident Analysis and Prevention. ; 32:2, s. 321-328
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Tidskriftsartikel (refereegranskat)abstract
- Long-term whiplash associated disorders (WAD) 1-3 sustained in low velocity rear-end impacts is the most common disability injury in Sweden. Therefore, to determine neck injury mechanisms and develop methods to measure neck-injury related parameters are of importance for current crash-safety research. A new neck injury criterion (NIC) has previously been proposed and evaluated by means of dummy, human and mathematical rear-impact simulations. So far, the criterion appears to be sensitive to the major car and collision related risk factors for injuries with long-term consequences. To further evaluate the applicability of NIC, four seats were tested according to a recently proposed sled-test procedure. 'Good' as well as 'bad' seats were chosen on the basis of a recently presented disability risk ranking list. The dummy used in the current tests was the Biofidelic Rear Impact Dummy (BioRID). The results of this study showed that NICmax values were generally related to the real-world risk of long-term WAD 1-3. Furthermore, these results suggested that NICmax calculated from sled tests using the BioRID dummy can be used for evaluating the neck injury risk of different car seats.
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| 37. |
- Bourdieu, Pierre, et al.
(författare)
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Leve idrottspedagogiken : En vänbok tillägnad Lars-Magnus Engström
- 2005
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Vem ägnar sig åt idrott? Vilken betydelse har fritiden i barns och ungdomars liv? Vad innebär hälsa i skolämnet idrott och hälsa?Leve idrottspedagogiken! tillägnas Lars-Magnus Engström. Texterna i boken speglar delar av det idrottspedagogiska forskningsområdet i Sverige, vars framväxt Lars-Magnus Engström varit den främste företrädaren för. Läsaren får här ta del av exempelvis idrottskulturen, fritidskulturen och skolans ämne idrott och hälsa. Genomgående handlar texterna om villkoren för barns och ungdomars deltagane och om de olika lärprocesser som sker i anslutning till idrottsutövning.Lars-Magnus Engström har gjort betydande insatser som forskare och lärare samt som professor vid Lärarhögskolan i Stockholm och vid Gymnastik- och idrottshögskolan. I snart fyrtion år har han arbetat med studier kring påverkans- och lärprocesser i idrott. Hans forskning har främst kretsat kring människors idrottsvanor och vilka som utvecklar en fysiskt aktiv livsstil. Idrotts- och motionsutövningar ger både ett så kallat egenvärde och investeringsvärde. Med dessa begrepp bland många andra har Lars-Magnus Engström bidragit till en fördjupad vetenskaplig förståelse av idrottskulturen.De flesta författarna har eller har haft Lars-Magnus Engström som handledare och tillhör forskningsgruppen för pedagogik, idrott och fritidskultur. Redaktörer för boken är Karin Redelius och Håkan Larsson.
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| 38. |
- Brattås, Per Ludvik, et al.
(författare)
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Impact of differential and time-dependent autophagy activation on therapeutic efficacy in a model of Huntington disease
- 2021
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8627 .- 1554-8635. ; 17:6, s. 1316-1329
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Tidskriftsartikel (refereegranskat)abstract
- Activation of macroautophagy/autophagy, a key mechanism involved in the degradation and removal of aggregated proteins, can successfully reverse Huntington disease phenotypes in various model systems. How neuronal autophagy impairments need to be considered in Huntington disease progression to achieve a therapeutic effect is currently not known. In this study, we used a mouse model of HTT (huntingtin) protein aggregation to investigate how different methods and timing of autophagy activation influence the efficacy of autophagy-activating treatment in vivo. We found that overexpression of human TFEB, a master regulator of autophagy, did not decrease mutant HTT aggregation. On the other hand, Becn1 overexpression, an autophagic regulator that plays a key role in autophagosome formation, partially cleared mutant HTT aggregates and restored neuronal pathology, but only when administered early in the disease progression. When Becn1 was administered at a later stage, when prominent mutant HTT accumulation and autophagy impairments have occurred, Becn1 overexpression did not rescue the mutant HTT-associated phenotypes. Together, these results demonstrate that the targets used to activate autophagy, as well as the timing of autophagy activation, are crucial for achieving efficient therapeutic effects.
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| 39. |
- Brattås, Per Ludvik, et al.
(författare)
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TRIM28 Controls a Gene Regulatory Network Based on Endogenous Retroviruses in Human Neural Progenitor Cells
- 2017
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 18:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Endogenous retroviruses (ERVs), which make up 8% of the human genome, have been proposed to participate in the control of gene regulatory networks. In this study, we find a region- and developmental stage-specific expression pattern of ERVs in the developing human brain, which is linked to a transcriptional network based on ERVs. We demonstrate that almost 10,000, primarily primate-specific, ERVs act as docking platforms for the co-repressor protein TRIM28 in human neural progenitor cells, which results in the establishment of local heterochromatin. Thereby, TRIM28 represses ERVs and consequently regulates the expression of neighboring genes. These results uncover a gene regulatory network based on ERVs that participates in control of gene expression of protein-coding transcripts important for brain development.
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| 40. |
- Bresell, Anders, et al.
(författare)
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Bioinformatic and enzymatic characterization of the MAPEG superfamily
- 2005
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 272:7, s. 1688-1703
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Tidskriftsartikel (refereegranskat)abstract
- The membrane associated proteins in eicosanoid and glutathione metabolism (MAPEG) superfamily includes structurally related membrane proteins with diverse functions of widespread origin. A total of 136 proteins belonging to the MAPEG superfamily were found in database and genome screenings. The members were found in prokaryotes and eukaryotes, but not in any archaeal organism. Multiple sequence alignments and calculations of evolutionary trees revealed a clear subdivision of the eukaryotic MAPEG members, corresponding to the six families of microsomal glutathione transferases (MGST) 1, 2 and 3, leukotriene C4 synthase (LTC4), 5-lipoxygenase activating protein (FLAP), and prostaglandin E synthase. Prokaryotes contain at least two distinct potential ancestral subfamilies, of which one is unique, whereas the other most closely resembles enzymes that belong to the MGST2/FLAP/LTC4 synthase families. The insect members are most similar to MGST1/prostaglandin E synthase. With the new data available, we observe that fish enzymes are present in all six families, showing an early origin for MAPEG family differentiation. Thus, the evolutionary origins and relationships of the MAPEG superfamily can be defined, including distinct sequence patterns characteristic for each of the subfamilies. We have further investigated and functionally characterized representative gene products from Escherichia coli, Synechocystis sp., Arabidopsis thaliana and Drosophila melanogaster, and the fish liver enzyme, purified from pike (Esox lucius). Protein overexpression and enzyme activity analysis demonstrated that all proteins catalyzed the conjugation of 1-chloro-2,4-dinitrobenzene with reduced glutathione. The E. coli protein displayed glutathione transferase activity of 0.11 µmol·min−1·mg−1 in the membrane fraction from bacteria overexpressing the protein. Partial purification of the Synechocystis sp. protein yielded an enzyme of the expected molecular mass and an N-terminal amino acid sequence that was at least 50% pure, with a specific activity towards 1-chloro-2,4-dinitrobenzene of 11 µmol·min−1·mg−1. Yeast microsomes expressing the Arabidopsis enzyme showed an activity of 0.02 µmol·min−1·mg−1, whereas the Drosophila enzyme expressed in E. coli was highly active at 3.6 µmol·min−1·mg−1. The purified pike enzyme is the most active MGST described so far with a specific activity of 285 µmol·min−1·mg−1. Drosophila and pike enzymes also displayed glutathione peroxidase activity towards cumene hydroperoxide (0.4 and 2.2 µmol·min−1·mg−1, respectively). Glutathione transferase activity can thus be regarded as a common denominator for a majority of MAPEG members throughout the kingdoms of life whereas glutathione peroxidase activity occurs in representatives from the MGST1, 2 and 3 and PGES subfamilies.
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| 41. |
- Breton, Gwenna, et al.
(författare)
-
Comparison of sequencing data processing pipelines and application to underrepresented African human populations
- 2021
-
Ingår i: BMC Bioinformatics. - : BioMed Central (BMC). - 1471-2105. ; 22:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Population genetic studies of humans make increasing use of high-throughput sequencing in order to capture diversity in an unbiased way. There is an abundance of sequencing technologies, bioinformatic tools and the available genomes are increasing in number. Studies have evaluated and compared some of these technologies and tools, such as the Genome Analysis Toolkit (GATK) and its "Best Practices" bioinformatic pipelines. However, studies often focus on a few genomes of Eurasian origin in order to detect technical issues. We instead surveyed the use of the GATK tools and established a pipeline for processing high coverage full genomes from a diverse set of populations, including Sub-Saharan African groups, in order to reveal challenges from human diversity and stratification. Results We surveyed 29 studies using high-throughput sequencing data, and compared their strategies for data pre-processing and variant calling. We found that processing of data is very variable across studies and that the GATK "Best Practices" are seldom followed strictly. We then compared three versions of a GATK pipeline, differing in the inclusion of an indel realignment step and with a modification of the base quality score recalibration step. We applied the pipelines on a diverse set of 28 individuals. We compared the pipelines in terms of count of called variants and overlap of the callsets. We found that the pipelines resulted in similar callsets, in particular after callset filtering. We also ran one of the pipelines on a larger dataset of 179 individuals. We noted that including more individuals at the joint genotyping step resulted in different counts of variants. At the individual level, we observed that the average genome coverage was correlated to the number of variants called. Conclusions We conclude that applying the GATK "Best Practices" pipeline, including their recommended reference datasets, to underrepresented populations does not lead to a decrease in the number of called variants compared to alternative pipelines. We recommend to aim for coverage of > 30X if identifying most variants is important, and to work with large sample sizes at the variant calling stage, also for underrepresented individuals and populations.
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| 42. |
- Breton, Gwenna, et al.
(författare)
-
Comparison of sequencing data processing pipelines and application to underrepresented human populations
-
Ingår i: BMC Bioinformatics. - 1471-2105.
-
Tidskriftsartikel (refereegranskat)abstract
- Population genetic studies of humans make increasing use of high-throughput sequencing in order to capture human diversity in an unbiased way. There is an abundance of sequencing technologies, bioinformatic tools and the available genomes are increasing in number. Studies have evaluated and compared some of these technologies and tools, such as the Genome Analysis Toolkit (GATK) and its “Best Practices” bioinformatic pipelines. However, studies often focus on few genomes of Eurasian origin in order to detect technical issues. We instead surveyed the use of the GATK tools and established a pipeline for processing high coverage full genomes from a diverse set of populations, including Sub-Saharan African groups, in order to reveal challenges from human diversity and stratification.We started by surveying 29 studies using high-throughput sequencing data, and compared their strategies for data pre-processing and variant calling. We found that processing of data is very variable across studies, that the GATK “Best Practices” are seldom followed strictly and that processing pipelines are often not reported in full details. We then compared three versions of the GATK pipeline, differing in the inclusion of an indel realignment step and with a modification of the base quality score recalibration step. We applied the pipelines on a diverse set of 28 individuals. We compared the pipelines in terms of count of called variants and overlap of the callsets. We found that the pipelines resulted in similar callsets, in particular after callset filtering. We also ran one of the pipeline on a larger dataset of 179 individuals. We noted that including more individuals at the joint genotyping step resulted in different counts of variants. At the individual level, we observed that the average genome coverage was correlated to the number of variants called.We conclude that applying the GATK “Best Practices” pipeline, including their recommended reference datasets, to underrepresented populations does not lead to a decrease in the number of called variants compared to alternative pipelines. We recommend to aim for a coverage of >30X, and to work with large sample sizes at the variant calling stage, also for underrepresented individuals and populations.
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| 43. |
- Breton, Gwenna, et al.
(författare)
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Deciphering early human history using Approximate Bayesian Computation and 74 whole genomes from Central and Southern Africa
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Human evolutionary history in Africa before and after the out-of-Africa event remains largely unexplored, due to lack of genome sequence data, limited representation of populations and limitations of presently available inference methods. We generated high-coverage genomes from 49 Central African individuals, from five rainforest hunter-gatherer populations and four neighboring populations, and from 25 Khoe-San individuals, from five populations. We analyzed these genomes jointly with 104 comparative genomes from worldwide populations. We showed that rainforest hunter-gatherers and Khoe-San populations define two distinct major axes of genetic variation both at the worldwide and Sub-Saharan scales. This new data provides unprecedented resolution to unravel complex genetic differentiation among rainforest hunter-gatherer populations in particular. Using both deterministic and Approximate Bayesian Computation inferences, we found strong support for gene flow throughout the entire history of Central and Southern Africa, and an early divergence, some 250-370 kya ago, of Khoe-San ancestors from the lineage ancestral to all Central African populations. This event was followed, still in the presence of gene-flow, some 80-240 kya, by the divergence of lineages ancestral to rainforest hunter-gatherers and their neighbors. Finally, divergence between the different Khoe-San populations likely predated that of eastern and western rainforest hunter-gatherers which occurred 16-44 kya. Altogether, our results indicate that a tree-like history of Central Africa incorporating gene-flow among ancient lineages as well as among recent lineages can explain genomic variation observed among populations today.
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| 44. |
- Breton, Gwenna
(författare)
-
Human demographic history : Insights on the human past based on genomes from Southern through Central Africa
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Evidence from paleontology, archaeology and population genetics support that modern humans originated in Africa. While the out-of-Africa event and subsequent colonization of all continents are well documented, human history in Africa at that time and before is less studied. Some current-day hunter-gatherer populations trace most of their genetic lineages to populations who inhabited Sub-Saharan Africa until the arrival of farming. They are informative about human history before and after the arrival of farming.I studied high-coverage genomes from two such groups, the Khoe-San from Southern Africa and the rainforest hunter-gatherers from Central Africa. I generated a total of 74 genomes, significantly increasing the number of genomes from Sub-Saharan African hunter-gatherers. I compared several versions of a commonly used pipeline for high-coverage genomes and showed that using standard ascertained reference datasets has no significant impact on variant calling in populations from Sub-Saharan Africa. Using the full genome information, I described the genetic diversity in the Khoe-San and in the rainforest hunter-gatherers and showed that gene flow from agropastoralist groups increased the Khoe-San genetic diversity. I also detected a signal of population size decline in the Khoe-San around the time of the out-of-Africa event, and I evaluated the power of the method to detect bottlenecks by applying it to simulated data. I investigated the history of modern humans in Africa by estimating divergence times between populations and applying an Approximate Bayesian Computation analysis. We confirmed that the earliest divergence event was between the Khoe-San ancestral lineage and the rest of modern humans, ~250-350 kya. I also showed that the possibility of high gene flow should be incorporated in models of human evolution.I furthermore examined SNP array data for two BaTwa populations from Zambia and showed that 20-30% of their autosomal diversity is hunter-gatherer-like. The estimated times for the admixture between a presumably local hunter-gatherer population and incoming agropastoralist groups are consistent with archaeological records.In this thesis, I investigated questions related to human history in Sub-Saharan Africa, from the emergence of modern humans ~300 kya to recent events related to the expansion of farming.
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| 45. |
- Breton, Gwenna, et al.
(författare)
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Lactase Persistence Alleles Reveal Partial East African Ancestry of Southern African Khoe Pastoralists
- 2014
-
Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 24:8, s. 852-858
-
Tidskriftsartikel (refereegranskat)abstract
- The ability to digest milk into adulthood, lactase persistence (LP), as well as specific genetic variants associated with LP, is heterogeneously distributed in global populations [1-4]. These variants were most likely targets of selection when some populations converted from hunter-gatherer to pastoralist or farming lifestyles [5-7]. Specific LP polymorphisms are associated with particular geographic regions and populations [1-4, 8-10]; however, they have not been extensively studied in southern Africa. We investigate the LP-regulatory region in 267 individuals from 13 southern African populations (including descendants of hunter-gatherers, pastoralists, and agropastoralists), providing the first comprehensive study of the LP-regulatory region in a large group of southern Africans. The "East African" LP single-nucleotide polymorphism (SNP) (14010G>C) was found at high frequency (>20%) in a strict pastoralist Khoe population, the Nama of Namibia, suggesting a connection to East Africa, whereas the "European" LP SNP (13910C>T) was found in populations of mixed ancestry. Using genome-wide data from various African populations, we identify admixture (13%) in the Nama, from an Afro-Asiatic group dating to >1,300 years ago, with the remaining fraction of their genomes being from San hunter-gatherers. We also find evidence of selection around the LCT gene among Khoe-speaking groups, and the substantial frequency of the 14010C variant among the Nama is best explained by adaptation to digesting milk. These genome-local and genome-wide results support a model in which an East African group brought pastoralist practices to southern Africa and admixed with local hunter-gatherers to form the ancestors of Khoe people.
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| 46. |
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| 47. |
- Brink, Mikael, et al.
(författare)
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Multiplex Analyses of Antibodies Against Citrullinated Peptides in Individuals Prior to Development of Rheumatoid Arthritis
- 2013
-
Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 65:4, s. 899-910
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Tidskriftsartikel (refereegranskat)abstract
- Objective The presence of antibodies against cyclic citrullinated peptides has been demonstrated to precede the onset of symptoms of rheumatoid arthritis (RA) by several years. The aim of this study was to analyze antibodies against 10 citrullinated autoantigen-derived peptides for reactivity before the onset of RA symptoms. Methods A casecontrol study was conducted within the Medical Biobank of Northern Sweden. The study was performed in 409 individuals, 386 of whom donated 717 blood samples before the onset of symptoms of RA (pre-patients). The median period of time predating the onset of RA was 7.4 years. A total of 1,305 population-based control subjects were also studied. Antibodies to 10 citrullinated peptides, fibrinogen 573 (Fib573), Fib591, Fib3652, Fib72, Fib74, -enolase (citrullinated -enolase peptide 1 [CEP-1]), triple-helical type II collagen peptide C1 (citC1III), filaggrin, vimentin 217 (Vim217), and Vim6075, were analyzed using a microarray system. Results The fluorescence intensity of antibodies against Fib3652, Fib74, CEP-1, citC1III, and filaggrin was significantly increased in pre-patients compared with controls (P < 0.001). The levels of the earliest-detectable antibodies (Fib591 and Vim6075) fluctuated over time, with only a slight increase after the onset of disease. The frequency of antibodies against Fib3652, CEP-1, and filaggrin increased gradually, reaching the highest levels before symptom onset. The frequency of a cluster of antibodies, citC1III, Fib573, and Fib74, increased only slightly before the onset of symptoms but increased prominently after disease onset. The odds ratio for the development of RA in individuals expressing both CEP-1 and Fib3652 antibodies (using data from samples obtained <3.35 years predating symptom onset) was 40.4 (95% confidence interval 19.882.3) compared with having either antibody alone. Conclusion Development of an immune response toward citrullinated peptides is initially restricted but expands with time to induce a more specific response, with levels, particularly those of antibodies against CEP-1, Fib3652, and filaggrin, increasing during the predating time period closer to the onset of symptoms.
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| 48. |
- Broqvist, Mari, et al.
(författare)
-
National Model for Transparent Prioritisation in Swedish Health Care : Reviderad version
- 2011
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- "Det demokratiska samtalet och människors acceptans av nödvändiga prioriteringar förutsätter kunskaper om på vilka grunder prioriteringar görs, vilka möjligheter man som patient har att påverka dessa och vilka vägar man kan gå om man inte är nöjd med den gjorda prioriteringen. Hälso- och sjukvården har en skyldighet att utveckla metoder för att sådan information finns tillgänglig både för dem som är patienter idag och för dem som kan förväntas bli patienter i framtiden".Detta citat är hämtat ur den proposition som innehåller riktlinjerna för hur prioriteringar ska gå till inom hälso- och sjukvård. En ökad öppenhet kring de prioriteringar som alltid sker i sjukvården kräver instrument både för att kommunicera prioriteringar till medborgarna och för att kommunicera etiska överväganden och olika ställningstaganden mellan personer som ska göra prioriteringar. Behovet av ett systematiskt och enhetligt arbetssätt att göra prioriteringar på växte fram i slutet av 1990-talet i Landstinget i Östergötland. I samband med att Socialstyrelsen påbörjande arbetet med de första nationella riktlinjerna (för hjärtsjukvård) blev behovet av att ytterligare precisera och tydliggöra metoden för prioriteringar än mer tydligt. De allmänt beskrivna prioriteringsprinciperna i propositionen var inte tillräckliga för att vägleda mer praktiska arbeten och röster höjdes om en mer konkret beskrivning av arbete med att rangordna tillstånd och behov.Med tiden växte också ett behov fram i enskilda landsting och verksamheter att kunna använda erfarenheter från Socialstyrelsens sätt att ta fram prioriteringar i lokala prioriteringsarbeten.En arbetsgrupp med företrädare från Socialstyrelsen och Prioriteringscentrum, andra organisationer som arbetat med prioriteringar såsom Landstinget i Östergötland, Stockholms läns landsting, Västra Götaland, Södra sjukvårdsregionen, Svenska Läkaresällskapet, Svensk sjuksköterskeförening och Vårdförbundet tog 2006 fram det ursprungliga förslaget till en nationell modell för öppna vertikala prioriteringar. Förslaget förankrades hos myndigheter, yrkesförbund och personer med särskilda kunskaper inom området.
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| 49. |
- Broqvist, Mari, et al.
(författare)
-
Nationell modell för öppna prioriteringar inom hälso- och sjukvård : Reviderad version
- 2011
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- "Det demokratiska samtalet och människors acceptans av nödvändiga prioriteringar förutsätter kunskaper om på vilka grunder prioriteringar görs, vilka möjligheter man som patient har att påverka dessa och vilka vägar man kan gå om man inte är nöjd med den gjorda prioriteringen. Hälso- och sjukvården har en skyldighet att utveckla metoder för att sådan information finns tillgänglig både för dem som är patienter idag och för dem som kan förväntas bli patienter i framtiden".Detta citat är hämtat ur den proposition som innehåller riktlinjerna för hur prioriteringar ska gå till inom hälso- och sjukvård. En ökad öppenhet kring de prioriteringar som alltid sker i sjukvården kräver instrument både för att kommunicera prioriteringar till medborgarna och för att kommunicera etiska överväganden och olika ställningstaganden mellan personer som ska göra prioriteringar. Behovet av ett systematiskt och enhetligt arbetssätt att göra prioriteringar på växte fram i slutet av 1990-talet i Landstinget i Östergötland. I samband med att Socialstyrelsen påbörjande arbetet med de första nationella riktlinjerna (för hjärtsjukvård) blev behovet av att ytterligare precisera och tydliggöra metoden för prioriteringar än mer tydligt. De allmänt beskrivna prioriteringsprinciperna i propositionen var inte tillräckliga för att vägleda mer praktiska arbeten och röster höjdes om en mer konkret beskrivning av arbete med att rangordna tillstånd och behov.Med tiden växte också ett behov fram i enskilda landsting och verksamheter att kunna använda erfarenheter från Socialstyrelsens sätt att ta fram prioriteringar i lokala prioriteringsarbeten.En arbetsgrupp med företrädare från Socialstyrelsen och Prioriteringscentrum, andra organisationer som arbetat med prioriteringar såsom Landstinget i Östergötland, Stockholms läns landsting, Västra Götaland, Södra sjukvårdsregionen, Svenska Läkaresällskapet, Svensk sjuksköterskeförening och Vårdförbundet tog 2006 fram det ursprungliga förslaget till en nationell modell för öppna vertikala prioriteringar. Förslaget förankrades hos myndigheter, yrkesförbund och personer med särskilda kunskaper inom området.
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| 50. |
- Broström, Anders, 1963-, et al.
(författare)
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Effects of Long-term Nocturnal Oxygen Treatment in Patients With Severe Heart Failure
- 2005
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Ingår i: Journal of Cardiovascular Nursing. - Philadelphia : Lippincott Williams & Wilkins. - 0889-4655 .- 1550-5049. ; 20:6, s. 385-395
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Tidskriftsartikel (refereegranskat)abstract
- Sleep-disordered breathing (SDB) is common in patients with heart failure (HF) and leads to disturbed sleep. The objective of this study was to determine the persistent effects of long-term nocturnal oxygen treatment in patients with severe HF regarding (1) objective outcomes, such as steep. SDB, cardiac function, and functional capacity; (2) subjective outcomes, such as self-assessed sleep difficulties, daytime sleepiness, and health-related quality of life (HRQOL); and (3) the relationship between objective and subjective outcomes. In this open nonrandomized experimental study, 22 patients, median age 71 years, with severe HF were studied before and after 3 months of receiving nocturnal oxygen. The measures used were overnight polysomnography, echocardiography, 6-minute walk test, self-assessed sleep difficulties (Uppsala Sleep Inventory-HF), daytime sleepiness (Epworth Sleepiness Scale), and HRQOL (36-ltem Short Form Health Survey and Minnesota Living with Heart Failure Questionnaire). SDB, with a 90% dominance of central sleep apnea, occurred in 41 % of the patients with severe HF before intervention. After intervention, functional capacity improved for both the whole group of patients with HF (P < .01) and HF patients with SDB (P < .05). No improvements regarding cardiac function, objective sleep, subjective sleep, or SDB were seen, except for a decrease of ‚â•4% desaturations (P < 05). HRQOL did not differ significantly between HF patients with and without SDB before or after intervention with nocturnal oxygen. Long-term nocturnal oxygen treatment improved functional capacity in patients with severe HF, with or without SDB. No improvements were seen regarding sleep, daytime sleepiness, SDB, cardiac function, or HRQOL.
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