| 1. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 2. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 5. |
- Zhou, XP, et al.
(författare)
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Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
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| 10. |
- Gonzalez-Beltran, AN, et al.
(författare)
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Community standards for open cell migration data
- 2020
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Ingår i: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Cell migration research has become a high-content field. However, the quantitative information encapsulated in these complex and high-dimensional datasets is not fully exploited owing to the diversity of experimental protocols and non-standardized output formats. In addition, typically the datasets are not open for reuse. Making the data open and Findable, Accessible, Interoperable, and Reusable (FAIR) will enable meta-analysis, data integration, and data mining. Standardized data formats and controlled vocabularies are essential for building a suitable infrastructure for that purpose but are not available in the cell migration domain. We here present standardization efforts by the Cell Migration Standardisation Organisation (CMSO), an open community-driven organization to facilitate the development of standards for cell migration data. This work will foster the development of improved algorithms and tools and enable secondary analysis of public datasets, ultimately unlocking new knowledge of the complex biological process of cell migration.
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| 11. |
- Hopfner, M., et al.
(författare)
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Validation of MIPAS ClONO2 measurements
- 2007
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 7, s. 257-281
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Tidskriftsartikel (refereegranskat)abstract
- Altitude profiles of ClONO2 retrieved with the IMK (Institut fur Meteorologie und Klimaforschung) science-oriented data processor from MIPAS/Envisat (Michelson Interferometer for Passive Atmospheric Sounding on Envisat) mid-infrared limb emission measurements between July 2002 and March 2004 have been validated by comparison with balloon-borne (Mark IV, FIRS2, MIPAS-B), airborne (MIPAS-STR), ground-based (Spitsbergen, Thule, Kiruna, Harestua, Jungfraujoch, Izana, Wollongong, Lauder), and spaceborne (ACE-FTS) observations. With few exceptions we found very good agreement between these instruments and MIPAS with no evidence for any bias in most cases and altitude regions. For balloon-borne measurements typical absolute mean differences are below 0.05 ppbv over the whole altitude range from 10 to 39 km. In case of ACE-FTS observations mean differences are below 0.03 ppbv for observations below 26 km. Above this altitude the comparison with ACE-FTS is affected by the photochemically induced diurnal variation of ClONO2. Correction for this by use of a chemical transport model led to an overcompensation of the photochemical effect by up to 0.1 ppbv at altitudes of 30-35 km in case of MIPAS-ACE-FTS comparisons while for the balloon-borne observations no such inconsistency has been detected. The comparison of MIPAS derived total column amounts with ground-based observations revealed no significant bias in the MIPAS data. Mean differences between MIPAS and FTIR column abundances are 0.11 +/- 0.12 x 10(14) cm(-2) (1.0 +/- 1.1%) and -0.09 +/- 0.19 x 10(14) cm(-2) (-0.8 +/- 1.7%), depending on the coincidence criterion applied. chi(2) tests have been performed to assess the combined precision estimates of MIPAS and the related instruments. When no exact coincidences were available as in case of MIPAS-FTIR or MIPAS-ACE-FTS comparisons it has been necessary to take into consideration a coincidence error term to account for chi(2) deviations. From the resulting chi(2) profiles there is no evidence for a systematic over/underestimation of the MIPAS random error analysis.
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| 14. |
- Weiner, M. W., et al.
(författare)
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Military risk factors for Alzheimer's disease
- 2013
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 9:4, s. 445-451
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are signature injuries of the wars in Iraq and Afghanistan and have been linked to an increased risk of Alzheimer's disease (AD) and other dementias. A meeting hosted by the Alzheimer's Association and the Veterans' Health Research Institute (NCIRE) in May 2012 brought together experts from the U.S. military and academic medical centers around the world to discuss current evidence and hypotheses regarding the pathophysiological mechanisms linking TBI, PTSD, and AD. Studies underway in civilian and military populations were highlighted, along with new research initiatives such as a study to extend the Alzheimer's Disease Neuroimaging Initiative (ADNI) to a population of veterans exposed to TBI and PTSD. Greater collaboration and data sharing among diverse research groups is needed to advance an understanding and appropriate interventions in this continuum of military injuries and neurodegenerative disease in the aging veteran. (C) 2013 The Alzheimer's Association. All rights reserved.
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| 19. |
- Djalali, A, et al.
(författare)
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Art of Disaster Preparedness in European Union:a Survey on the Health Systems. PLOS Currents Disasters. Dec 17 ed 1
- 2014
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Ingår i: PLOS Currents. - : Public Library of Science (PLoS). - 2157-3999.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Naturally occurring and man-made disasters have been increasing in the world, including Europe, over the past several decades. Health systems are a key part of any community disaster management system. The success of preparedness and prevention depends on the success of activities such as disaster planning, organization and training. The aim of this study is to evaluate health system preparedness for disasters in the 27 European Union member countries. Method: A cross-sectional analysis study was completed between June-September 2012. The checklist used for this survey was a modified from the World Health Organization toolkit for assessing health-system capacity for crisis management. Three specialists from each of the 27 European Union countries were included in the survey. Responses to each survey question were scored and the range of preparedness level was defined as 0-100%, categorized in three levels as follows: Acceptable; Transitional; or Insufficient. Results: Response rate was 79.1%. The average level of disaster management preparedness in the health systems of 27 European Union member states was 68% (Acceptable). The highest level of preparedness was seen in the United Kingdom, Luxemburg, and Lithuania. Considering the elements of disaster management system, the highest level of preparedness score was at health information elements (86%), and the lowest level was for hospitals, and educational elements (54%). Conclusion: This survey study suggests that preparedness level of European Union countries in 2012 is at an acceptable level but could be improved. Elements such as hospitals and education and training suffer from insufficient levels of preparedness. The European Union health systems need a collective strategic plan, as well as enough resources, to establish a comprehensive and standardized disaster management strategy plan. A competency based training curriculum for managers and first responders is basic to accomplishing this goal.
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| 20. |
- Khorram-Manesh, Amir, 1958, et al.
(författare)
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Education in Disaster Management: What Do We Offer and What Do We Need? Proposing a New Global Program.
- 2016
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Ingår i: Disaster Medicine and Public Health Preparedness. - : Cambridge University Press (CUP). - 1935-7893 .- 1938-744X. ; 10:6, s. 854-873
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Although there is a significant willingness to respond to disasters, a review of post-event reports following incidents shows troubling repeated patterns with poorly integrated response activities and response managers inadequately trained for the requirements of disasters. This calls for a new overall approach in disaster management. METHODS: An in-depth review of the education and training opportunities available to responders and disaster managers has been undertaken, as well as an extensive review of the educational competencies and their parent domains identified by subject matter experts as necessary for competent performance. RESULTS: Seven domains of competency and competencies that should be mastered by disaster mangers were identified. This set of domains and individual competencies was utilized to define a new and evolving curriculum. In order to evaluate and assess the mastery of each competency, objectives were more widely defined as activities under specific topics, as the measurable elements of the curriculum, for each managerial level. CONCLUSIONS: This program enables interagency cooperation and collaboration and could be used to increase and improve decision-makers' understanding of disaster managers' capabilities; at the strategic/tactical level to promote the knowledge and capability of the disaster managers themselves; and as continuing education or further career development for disaster managers at the operational level. (Disaster Med Public Health Preparedness. 2016;page 1 of 20).
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| 21. |
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| 22. |
- Van der Meer, J. M. R., et al.
(författare)
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IL-15 superagonist N-803 improves IFNγ production and killing of leukemia and ovarian cancer cells by CD34+ progenitor-derived NK cells
- 2020
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Ingår i: Cancer Immunology and Immunotherapy. - : Springer Science and Business Media Deutschland GmbH. - 0340-7004 .- 1432-0851.
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic natural killer (NK) cell transfer is a potential immunotherapy to eliminate and control cancer. A promising source are CD34 + hematopoietic progenitor cells (HPCs), since large numbers of cytotoxic NK cells can be generated. Effective boosting of NK cell function can be achieved by interleukin (IL)-15. However, its in vivo half-life is short and potent trans-presentation by IL-15 receptor α (IL-15Rα) is absent. Therefore, ImmunityBio developed IL-15 superagonist N-803, which combines IL-15 with an activating mutation, an IL-15Rα sushi domain for trans-presentation, and IgG1-Fc for increased half-life. Here, we investigated whether and how N-803 improves HPC-NK cell functionality in leukemia and ovarian cancer (OC) models in vitro and in vivo in OC-bearing immunodeficient mice. We used flow cytometry-based assays, enzyme-linked immunosorbent assay, microscopy-based serial killing assays, and bioluminescence imaging, for in vitro and in vivo experiments. N-803 increased HPC-NK cell proliferation and interferon (IFN)γ production. On leukemia cells, co-culture with HPC-NK cells and N-803 increased ICAM-1 expression. Furthermore, N-803 improved HPC-NK cell-mediated (serial) leukemia killing. Treating OC spheroids with HPC-NK cells and N-803 increased IFNγ-induced CXCL10 secretion, and target killing after prolonged exposure. In immunodeficient mice bearing human OC, N-803 supported HPC-NK cell persistence in combination with total human immunoglobulins to prevent Fc-mediated HPC-NK cell depletion. Moreover, this combination treatment decreased tumor growth. In conclusion, N-803 is a promising IL-15-based compound that boosts HPC-NK cell expansion and functionality in vitro and in vivo. Adding N-803 to HPC-NK cell therapy could improve cancer immunotherapy.
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| 23. |
- Allan, Eric, et al.
(författare)
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Interannual variation in land-use intensity enhances grassland multidiversity
- 2014
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 111:1, s. 308-313
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Tidskriftsartikel (refereegranskat)abstract
- Although temporal heterogeneity is a well-accepted driver of biodiversity, effects of interannual variation in land-use intensity (LUI) have not been addressed yet. Additionally, responses to land use can differ greatly among different organisms; therefore, overall effects of land-use on total local biodiversity are hardly known. To test for effects of LUI (quantified as the combined intensity of fertilization, grazing, and mowing) and interannual variation in LUI (SD in LUI across time), we introduce a unique measure of whole-ecosystem biodiversity, multidiversity. This synthesizes individual diversity measures across up to 49 taxonomic groups of plants, animals, fungi, and bacteria from 150 grasslands. Multidiversity declined with increasing LUI among grasslands, particularly for rarer species and aboveground organisms, whereas common species and belowground groups were less sensitive. However, a high level of interannual variation in LUI increased overall multidiversity at low LUI and was even more beneficial for rarer species because it slowed the rate at which the multidiversity of rare species declined with increasing LUI. In more intensively managed grasslands, the diversity of rarer species was, on average, 18% of the maximum diversity across all grasslands when LUI was static over time but increased to 31% of the maximum when LUI changed maximally over time. In addition to decreasing overall LUI, we suggest varying LUI across years as a complementary strategy to promote biodiversity conservation.
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| 24. |
- Bolton, Douglas K., et al.
(författare)
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Continental-scale land surface phenology from harmonized Landsat 8 and Sentinel-2 imagery
- 2020
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Ingår i: Remote Sensing of Environment. - : Elsevier BV. - 0034-4257. ; 240
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Tidskriftsartikel (refereegranskat)abstract
- Dense time series of Landsat 8 and Sentinel-2 imagery are creating exciting new opportunities to monitor, map, and characterize temporal dynamics in land surface properties with unprecedented spatial detail and quality. By combining imagery from the Landsat 8 Operational Land Imager and the MultiSpectral Instrument on-board Sentinel-2A and -2B, the remote sensing community now has access to moderate (10–30 m) spatial resolution imagery with repeat periods of ~3 days in the mid-latitudes. At the same time, the large combined data volume from Landsat 8 and Sentinel-2 introduce substantial new challenges for users. Land surface phenology (LSP) algorithms, which estimate the timing of phenophase transitions and quantify the nature and magnitude of seasonality in remotely sensed land surface conditions, provide an intuitive way to reduce data volumes and redundancy, while also furnishing data sets that are useful for a wide range of applications including monitoring ecosystem response to climate variability and extreme events, ecosystem modelling, crop-type discrimination, and land cover, land use, and land cover change mapping, among others. To support the need for operational LSP data sets, here we describe a continental-scale land surface phenology algorithm and data product based on harmonized Landsat 8 and Sentinel-2 (HLS) imagery. The algorithm creates high quality times series of vegetation indices from HLS imagery, which are then used to estimate the timing of vegetation phenophase transitions at 30 m spatial resolution. We present results from assessment efforts evaluating LSP retrievals, and provide examples illustrating the character and quality of information related to land cover and terrestrial ecosystem properties provided by the continental LSP dataset that we have developed. The algorithm is highly successful in ecosystems with strong seasonal variation in leaf area (e.g., deciduous forests). Conversely, results in evergreen systems are less interpretable and conclusive.
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| 25. |
- Djalali, Ahmadreza, et al.
(författare)
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Identifying deficiencies in national and foreign medical team responses through expert opinion surveys: implications for education and training.
- 2014
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Ingår i: Prehospital and disaster medicine. - 1049-023X. ; 29:4, s. 364-8
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Tidskriftsartikel (refereegranskat)abstract
- Unacceptable practices in the delivery of international medical assistance are reported after every major international disaster; this raises concerns about the clinical competence and practice of some foreign medical teams (FMTs). The aim of this study is to explore and analyze the opinions of disaster management experts about potential deficiencies in the art and science of national and FMTs during disasters and the impact these opinions might have on competency-based education and training.
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