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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- George, Julie, et al.
(författare)
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Comprehensive genomic profiles of small cell lung cancer
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
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Tidskriftsartikel (refereegranskat)abstract
- We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
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| 3. |
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| 4. |
- Bakovic, Vid, et al.
(författare)
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Host plant-related genomic differentiation in the European cherry fruit fly, Rhagoletis cerasi
- 2019
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Ingår i: Molecular Ecology. - : WILEY. - 0962-1083 .- 1365-294X. ; 28:20, s. 4648-4666
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Tidskriftsartikel (refereegranskat)abstract
- Elucidating the mechanisms and conditions facilitating the formation of biodiversity are central topics in evolutionary biology. A growing number of studies imply that divergent ecological selection may often play a critical role in speciation by counteracting the homogenising effects of gene flow. Several examples involve phytophagous insects, where divergent selection pressures associated with host plant shifts may generate reproductive isolation, promoting speciation. Here, we use ddRADseq to assess the population structure and to test for host-related genomic differentiation in the European cherry fruit fly, Rhagoletis cerasi (L., 1758) (Diptera: Tephritidae). This tephritid is distributed throughout Europe and western Asia, and has adapted to two different genera of host plants, Prunus spp. (cherries) and Lonicera spp. (honeysuckle). Our data imply that geographic distance and geomorphic barriers serve as the primary factors shaping genetic population structure across the species range. Locally, however, flies genetically cluster according to host plant, with consistent allele frequency differences displayed by a subset of loci between Prunus and Lonicera flies across four sites surveyed in Germany and Norway. These 17 loci display significantly higher F-ST values between host plants than others. They also showed high levels of linkage disequilibrium within and between Prunus and Lonicera flies, supporting host-related selection and reduced gene flow. Our findings support the existence of sympatric host races in R. cerasi embedded within broader patterns of geographic variation in the fly, similar to the related apple maggot, Rhagoletis pomonella, in North America.
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| 5. |
- Bokhorst, Stef, et al.
(författare)
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Changing Arctic snow cover : A review of recent developments and assessment of future needs for observations, modelling, and impacts
- 2016
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 45:5, s. 516-537
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Forskningsöversikt (refereegranskat)abstract
- Snow is a critically important and rapidly changing feature of the Arctic. However, snow-cover and snowpack conditions change through time pose challenges for measuring and prediction of snow. Plausible scenarios of how Arctic snow cover will respond to changing Arctic climate are important for impact assessments and adaptation strategies. Although much progress has been made in understanding and predicting snow-cover changes and their multiple consequences, many uncertainties remain. In this paper, we review advances in snow monitoring and modelling, and the impact of snow changes on ecosystems and society in Arctic regions. Interdisciplinary activities are required to resolve the current limitations on measuring and modelling snow characteristics through the cold season and at different spatial scales to assure human well-being, economic stability, and improve the ability to predict manage and adapt to natural hazards in the Arctic region.
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| 6. |
- Schüler, Emil, et al.
(författare)
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Potential Biomarkers for Radiation-Induced Renal Toxicity following 177Lu-Octreotate Administration in Mice.
- 2015
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- C57BL/6N mice were i.v. injected with 0, 30, 60, 90, 120, or 150 MBq 177Lu-octreotate (0, 16, 29, 40, 48, and 54 Gy to the kidneys). At 4, 8, and 12 months after administration, radiation-induced effects were evaluated in relation to (a) global transcriptional variations in kidney tissues, (b) morphological changes in the kidneys, (c) changes in white and red blood cell count as well as blood levels of urea, and (d) changes in renal function using 99mTc-DTPA/99mTc-DMSA scintigraphy.
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| 7. |
- Schüler, Martin, et al.
(författare)
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Propper Planning and Preparation Prevents Piss Poor Performance (7P) -Training for the fictive scenario or learning to deal with reality?
- 2019
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Ingår i: VILÄR 5-6 december 2019, University West, Trollhättan. - Trollhättan : University West. - 9789188847430 - 9789188847447 ; , s. 17-17
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this study was to investigate critical incidents in a large medical exercise (mass casualty incident) including the Swedish Armed Forces (SwAF) and a regional hospital using activity theory. A total of 96 individuals played injured patients with a variety of injuries from simple cuts and bruises to severe head injuries. Patients were evacuated by different means of transportation i.e. minivan, ambulance, military as well as civilian ambulance helicopter.We participated in the final planning of the exercise in order to obtain access for the research team. Data was collected through observations, shadowing technique and 20 semi structured interviews. Professionals from the regional hospital and SwAF as well as evaluating personnel were interviewed. The interviewees were asked to describe significant events experienced during the exercise.Two researchers observed the triage and registration process in the ambulance intake and the emergency room of the hospital. One researcher observed the command and control (C2) function within the mass casualty management (MCM).Two students from the Swedish Defense University and three from University West collected data by playing injured patients according to the determined injure play card provided by SwAF. The students were instructed to observe what they themselves would classify as critical incidents based on their own subject i.e. education, economics and command and control studies. Five questions guided the observations: What happened? Who were involved? What consequences did the incident have? How were these consequences handled by the organization? Did the incident affect other areas?Data was analyzed, thematized and coded using the third generation of activity theory and its areas: tools, rules, community, division of labor, subject and object as a guide for identifying contradictions within the regional hospital and the emergency medical plan developed for handling large casualty events.Preliminary results indicated that participating personnel were not faced with conditions mimicking real life but learned to deal with a corrected version of reality i.e. preparations before the start of the exercise created shortcuts affecting the veracity of the exercise. This was manifested through contradictions within and between the activity systems and the conflicting motives carried by the objects.The results might impact the future designs of large exercises, influencing the conditions that the participants will face in exercises and thereby increasing preparedness for authentic situations.
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| 8. |
- Schüler, Martin, et al.
(författare)
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Safety Climate in Military Organizations : A Pilot Study of an Adjusted Multi-Domain Instrument
- 2019
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Ingår i: Proceedings of the Human Factors and Ergonomics Society Annual Meeting. - : sage journals. - 2169-5067 .- 1071-1813. ; 63:1, s. 1373-1377
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this pilot study is to adjust the NOSACQ-50 to the work environment of military organizations.NOSACQ-50 is a validated tool successfully used in several organizational domains to measure occupationalsafety climate (OSC). In general, few studies have been published investigating OSC in militaryorganizations. NOSACQ-50 consists of 50 items across 7 OSC dimensions, i.e. group members' sharedperceptions of: 1) management safety priority, commitment and competence; 2) management safetyempowerment; 3) management safety justice; 4) workers' safety commitment; 5) workers' safety priority andrisk non-acceptance; 6) safety communication, learning, and trust in co-workers' safety competence; 7)workers' trust in the efficacy of safety systems. To assess the relevance of the NOSACQ-50 items, a revisedversion of the instrument was sent to 11 military safety experts. In addition, 19 items pertaining to areas notcovered by NOSACQ-50 were validated by the same experts. After contents validation, data from 517participants from 4 garrisons were collected. The results showed that NOSACQ-50 had acceptable reliabilityscores (.70-.89.), and the factor structure was confirmed by confirmatory factor analysis (CFA). Principalcomponent analyses (PCA) of the supplementary 19 items showed that 12 items grouped into threedimensions (alpha .74-.91): Management enabling safety performance, personnel's knowledge of andcompetence in national laws regulating safety and Unit ethics. In conclusion, preliminary results showed theadjusted NOSACQ-50 instrument could be used to measure OSC in military organizations. However,additional studies must be performed to improve and develop military specific dimensions not covered byNOSACQ-50.
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