| 1. |
- Andersson, Natalie, et al.
(författare)
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Extensive clonal branching shapes the evolutionary history of high-risk pediatric cancers
- 2020
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Ingår i: Cancer Research. - 1538-7445. ; 80:7, s. 1512-1523
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Tidskriftsartikel (refereegranskat)abstract
- Darwinian evolution of tumor cells remains underexplored in childhood cancer. We here reconstruct the evolutionary histories of 56 pediatric primary tumors, including 24 neuroblastomas, 24 Wilms tumors and 8 rhabdomyosarcomas. Whole genome copy number and whole exome mutational profiling of multiple regions per tumor was performed followed by clonal deconvolution to reconstruct a phylogenetic tree for each tumor. Overall, 88% of the tumors exhibited genetic variation among primary tumor regions. This variability typically emerged through collateral phylogenetic branching, leading to spatial variability in the distribution of more than 50% (96/173) of detected diagnostically informative genetic aberrations. Single cell sequencing of 547 individual cancer cells from eight solid pediatric tumors confirmed branching evolution to be a fundamental underlying principle of genetic variation in all cases. Strikingly, cell-to-cell genetic diversity was almost twice as high in aggressive compared to clinically favorable tumors (median Simpson index of diversity 0.45 vs. 0.88; p=0.029). Similarly, a comparison of multiregional sampling data from a total of 274 tumor regions showed that new phylogenetic branches emerge at a higher frequency per sample and carry a higher mutational load in high-risk than in low-risk tumors. Timelines based on spatial genetic variation showed that the mutations most influencing relapse risk occur at initiation of clonal expansion in neuroblastoma and rhabdomyosarcoma, while in Wilms tumor they are late events. Thus, from an evolutionary standpoint, some high-risk childhood cancers are born bad, while others grow worse over time.
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| 2. |
- Bernardo, Ricardo, et al.
(författare)
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Retrofitting Domestic Hot Water Heaters for Solar Water Heating Systems in Single-Family Houses in a Cold Climate: A Theoretical Analysis
- 2012
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Ingår i: Energies. - : MDPI AG. - 1996-1073. ; 5:10, s. 4110-4131
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Tidskriftsartikel (refereegranskat)abstract
- One of the biggest obstacles to economic profitability of solar water heating systems is the investment cost. Retrofitting existing domestic hot water heaters when a new solar hot water system is installed can reduce both the installation and material costs. In this study, retrofitting existing water heaters for solar water heating systems in Swedish single-family houses was theoretically investigated using the TRNSYS software. Four simulation models using forced circulation flow with different system configurations and control strategies were simulated and analysed in the study. A comparison with a standard solar thermal system was also presented based on the annual solar fraction. The simulation results indicate that the retrofitting configuration achieving the highest annual performance consists of a system where the existing tank is used as storage for the solar heat and a smaller tank with a heater is added in series to make sure that the required outlet temperature can be met. An external heat exchanger is used between the collector circuit and the existing tank. For this retrofitted system an annual solar fraction of 50.5% was achieved. A conventional solar thermal system using a standard solar tank achieves a comparable performance for the same total storage volume, collector area and reference conditions.
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| 3. |
- Ekerstad, Niklas, et al.
(författare)
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Hospitalized frail elderly patients - atrial fibrillation, anticoagulation and 12 months outcomes
- 2018
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Ingår i: Clinical Interventions in Aging. - : DOVE MEDICAL PRESS LTD. - 1176-9092 .- 1178-1998. ; 13, s. 749-756
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Multiple chronic conditions and recurring acute illness are frequent among elderly people. One such condition is atrial fibrillation (AF), which increases the risk of stroke up to fivefold. The aim of this study was to investigate the prevalence of AF among hospitalized frail elderly patients, their use of anticoagulation and their 12-month outcomes. Patients and methods: This was a clinical observational study of acutely hospitalized frail patients over the age of 75 years. The CHA2DS2-VASc Score was used to evaluate ischemic stroke risk in patients with AF. Clinically relevant outcomes were the composite of ischemic stroke and/or bleeding within 12 months, which was considered as primary in the analysis, ischemic stroke/transient ischemic attack (TIA), mortality, bleeding and hospital care consumption. Students (test, Fishers exact test, Mann Whitney U test and a Cox proportional hazards model were used for the analyses. Results: The prevalence of AF was 47%, and 63% of them were prescribed an anticoagulant. AF patients without anticoagulation were older, more often females, more often in residential care, and they had worse Mini Nutritional Assessment and activities of daily living scores. Of the patients without anticoagulation, 56% had a documented contraindication. In univariate analysis, there were significantly more events among AF patients without anticoagulation regarding the composite outcome of ischemic stroke and/or bleeding (hazard ratio [1112] 3.65, 95% CI = 1.70-7.86; p amp;lt; 0.001). When adjusting for potential confounders in Cox regression analysis, the difference remained significant (HR 4.54, 95% CI = 1.83-11.25; p = 0.001). Conclusion: The prevalence of AF in a hospitalized frail elderly population was 47%. Of these, 63% were prescribed anticoagulation therapy. Almost half of the patients without stroke pro-phylaxis had no documented contraindication. At 1 year, there were significantly more events in terms of ischemic stroke and/or bleeding among AF patients without anticoagulation therapy than among those with.
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| 4. |
- Freitag-Pohl, Stefanie, et al.
(författare)
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Crystal structures of the Bacillus subtilis prophage lytic cassette proteins XepA and YomS.
- 2019
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Ingår i: Acta Crystallographica Section D: Structural Biology. - 2059-7983. ; 75, s. 1028-1039
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Tidskriftsartikel (refereegranskat)abstract
- As part of the Virus-X Consortium that aims to identify and characterize novel proteins and enzymes from bacteriophages and archaeal viruses, the genes of the putative lytic proteins XepA from Bacillus subtilis prophage PBSX and YomS from prophage SPβ were cloned and the proteins were subsequently produced and functionally characterized. In order to elucidate the role and the molecular mechanism of XepA and YomS, the crystal structures of these proteins were solved at resolutions of 1.9 and 1.3 Å, respectively. XepA consists of two antiparallel β-sandwich domains connected by a 30-amino-acid linker region. A pentamer of this protein adopts a unique dumbbell-shaped architecture consisting of two discs and a central tunnel. YomS (12.9 kDa per monomer), which is less than half the size of XepA (30.3 kDa), shows homology to the C-terminal part of XepA and exhibits a similar pentameric disc arrangement. Each β-sandwich entity resembles the fold of typical cytoplasmic membrane-binding C2 domains. Only XepA exhibits distinct cytotoxic activity in vivo, suggesting that the N-terminal pentameric domain is essential for this biological activity. The biological and structural data presented here suggest that XepA disrupts the proton motive force of the cytoplasmatic membrane, thus supporting cell lysis.
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| 5. |
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| 7. |
- Hoffman, Tove, et al.
(författare)
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Co-Occurrence of Francisella, Spotted Fever Group Rickettsia, and Midichloria in Avian-Associated Hyalomma rufipes
- 2022
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Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- The migratory behavior of wild birds contributes to the geographical spread of ticks and their microorganisms. In this study, we aimed to investigate the dispersal and co-occurrence of Francisella and spotted fever group Rickettsia (SFGR) in ticks infesting birds migrating northward in the African-Western Palaearctic region (AWPR). Birds were trapped with mist nests across the Mediterranean basin during the 2014 and 2015 spring migration. In total, 575 ticks were collected from 244 birds. We screened the ticks for the species Francisella tularensis, the genus Francisella, and SFGR by microfluidic real-time PCR. Confirmatory analyses and metagenomic sequencing were performed on tick samples that putatively tested positive for F. tularensis during initial screenings. Hyalomma rufipes was the most common tick species and had a high prevalence of Francisella, including co-occurrence of Francisella and SFGR. Metagenomic analysis of total DNA extracted from two H. rufipes confirmed the presence of Francisella, Rickettsia, and Midichloria. Average nucleotide identity and phylogenetic inference indicated the highest identity of the metagenome-assembled genomes to a Francisella-like endosymbiont (FLE), Rickettsia aeschlimannii, and Midichloria mitochondrii. The results of this study suggest that (i) FLE- and SFGR-containing ticks are dispersed by northbound migratory birds in the AWPR, (ii) H. rufipes likely is not involved in transmission of F. tularensis in the AWPR, and (iii) a dual endosymbiosis of FLEs and Midichloria may support some of the nutritional requirements of H. rufipes.
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| 8. |
- Hua, Hakan, et al.
(författare)
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Quality of life, effort and disturbance perceived in noise: A comparison between employees with aided hearing impairment and normal hearing
- 2013
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Ingår i: International Journal of Audiology. - : Informa Healthcare. - 1499-2027 .- 1708-8186. ; 52:9, s. 642-649
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aims were to compare health-related quality of life (HRQOL) and hearing handicap between two groups of employees with normal hearing and aided hearing impairment (HI). HRQOL was also compared to a normative population. The second aim was to compare perceived effort (PE) and disturbance after completing a task in office noise between the two study groups. Design: A Swedish version of the short form-36 (SF-36) and the hearing handicap inventory for adults (HHIA) was used to determine HRQOL and hearing handicap. The Borg-CR 10 scale was used to measure PE and disturbance. Study sample: Hearing impaired (n = 20) and normally hearing (n = 20) participants. The normative sample comprised of 597 matched respondents. Results: Hearing-impaired employees report relatively good HRQOL in relation to the normative population, but significantly lower physical functioning and higher PE than their normally-hearing peers in noise. Results from the HHIA showed mild self-perceived hearing handicap. Conclusions: The current results demonstrate that physical health status can be negatively affected even at a mild-moderate severity of HI, and that a higher PE is reported from this group when performing a task in noise, despite the regular use of hearing aids.
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| 9. |
- Jerrhag, Daniel, et al.
(författare)
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Epidemiology and time trends of distal forearm fractures in adults - a study of 11.2 million person-years in Sweden
- 2017
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: A distal forearm fracture is a very common injury causing both suffering and substantial health care costs. The incidence of this fracture type seemed to increase worldwide until the middle 1980’s, but thereafter most reports have shown stable or decreasing rates. As few large studies have been presented lately we aimed to describe recent epidemiology and time trends of distal forearm fractures in adults. We paid special attention to fractures in working ages as they present challenges in terms of treatment and costs for sick-leave, and have not previously been thoroughly investigated. Methods: By use of population data from Statistics Sweden and official in- and out-patient register data of men and women (≥17 years) in Sweden (Skåne region), we ascertained distal forearm fractures and estimated age- and sex-specific rates and time-trends from year 1999 to 2010 (11.2 million person-years (py)). Results: The total incidence rate was 278 per 100,000 py (31,233 fractures) with 23% higher annual numbers 2010 compared with 1999. An increase in the annual age standardized incidence was found in men, +0.7% per annum (95% confidence interval (CI) 0.1, 1.4), and women, +0.9% (95% CI 0.5, 1.3), driven mainly by an increasing incidence in working ages (17-64 years). Also, expected demographic changes including a 25% population increase may result in 38% more fractures until 2050, compared to 2017. Conclusions: The incidence of distal forearm fractures in adults in southern Sweden is increasing, mainly driven by an increase in working ages. In combination with expected demographic changes these findings may present substantial challenges for the future.
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