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| 2. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 3. |
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| 4. |
- Li, X., et al.
(författare)
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Cost-effectiveness of adding oseltamivir to primary care for influenza-like-illness: economic evaluation alongside the randomised controlled ALIC(4)E trial in 15 European countries
- 2023
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Ingår i: European Journal of Health Economics. - : Springer Science and Business Media LLC. - 1618-7598 .- 1618-7601. ; 24:6, s. 909-922
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Tidskriftsartikel (refereegranskat)abstract
- Background Oseltamivir is usually not often prescribed (or reimbursed) for non-high-risk patients consulting for influenza-like-illness (ILI) in primary care in Europe. We aimed to evaluate the cost-effectiveness of adding oseltamivir to usual primary care in adults/adolescents (13 years +) and children with ILI during seasonal influenza epidemics, using data collected in an open-label, multi-season, randomised controlled trial of oseltamivir in 15 European countries. Methods Direct and indirect cost estimates were based on patient reported resource use and official country-specific unit costs. Health-Related Quality of Life was assessed by EQ-5D questionnaires. Costs and quality adjusted life-years (QALY) were bootstrapped (N = 10,000) to estimate incremental cost-effectiveness ratios (ICER), from both the healthcare payers' and the societal perspectives, with uncertainty expressed through probabilistic sensitivity analysis and expected value for perfect information (EVPI) analysis. Additionally, scenario (self-reported spending), comorbidities subgroup and country-specific analyses were performed. Results The healthcare payers' expected ICERs of oseltamivir were euro22,459 per QALY gained in adults/adolescents and euro13,001 in children. From the societal perspective, oseltamivir was cost-saving in adults/adolescents, but the ICER is euro8,344 in children. Large uncertainties were observed in subgroups with comorbidities, especially for children. The expected ICERs and extent of decision uncertainty varied between countries (EVPI ranged euro1-euro35 per patient). Conclusion Adding oseltamivir to primary usual care in Europe is likely to be cost-effective for treating adults/adolescents and children with ILI from the healthcare payers' perspective (if willingness-to-pay per QALY gained > euro22,459) and cost-saving in adults/adolescents from a societal perspective.
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| 5. |
- Deans, Andrew R, et al.
(författare)
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Finding Our Way through Phenotypes.
- 2015
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.
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| 6. |
- Kirschbaum, Miko U.F., et al.
(författare)
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Is tree planting an effective strategy for climate change mitigation?
- 2024
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Ingår i: Science of the Total Environment. - : Elsevier B.V.. - 0048-9697 .- 1879-1026. ; 909
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Tidskriftsartikel (refereegranskat)abstract
- The world's forests store large amounts of carbon (C), and growing forests can reduce atmospheric CO2 by storing C in their biomass. This has provided the impetus for world-wide tree planting initiatives to offset fossil-fuel emissions. However, forests interact with their environment in complex and multifaceted ways that must be considered for a balanced assessment of the value of planting trees. First, one needs to consider the potential reversibility of C sequestration in trees through either harvesting or tree death from natural factors. If carbon storage is only temporary, future temperatures will actually be higher than without tree plantings, but cumulative warming will be reduced, contributing both positively and negatively to future climate-change impacts. Alternatively, forests could be used for bioenergy or wood products to replace fossil-fuel use which would obviate the need to consider the possible reversibility of any benefits. Forests also affect the Earth's energy balance through either absorbing or reflecting incoming solar radiation. As forests generally absorb more incoming radiation than bare ground or grasslands, this constitutes an important warming effect that substantially reduces the benefit of C storage, especially in snow-covered regions. Forests also affect other local ecosystem services, such as conserving biodiversity, modifying water and nutrient cycles, and preventing erosion that could be either beneficial or harmful depending on specific circumstances. Considering all these factors, tree plantings may be beneficial or detrimental for mitigating climate-change impacts, but the range of possibilities makes generalisations difficult. Their net benefit depends on many factors that differ between specific circumstances. One can, therefore, neither uncritically endorse tree planting everywhere, nor condemn it as counter-productive. Our aim is to provide key information to enable appropriate assessments to be made under specific circumstances. We conclude our discussion by providing a step-by-step guide for assessing the merit of tree plantings under specific circumstances.
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| 7. |
- Li, X., et al.
(författare)
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Direct and Indirect Costs of Influenza-Like Illness Treated with and Without Oseltamivir in 15 European Countries: A Descriptive Analysis Alongside the Randomised Controlled ALIC(4)E Trial
- 2021
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Ingår i: Clinical Drug Investigation. - : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 41:8, s. 685-699
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective Influenza-like illness (ILI) leads to a substantial disease burden every winter in Europe; however, oseltamivir is not frequently prescribed to ILI patients in the primary-care setting. An open-label, multi-country, multi-season, randomised controlled trial investigated the effectiveness of oseltamivir for treating ILI in 15 European countries. We aimed to evaluate whether patients presenting with ILI in primary care and being managed with the addition of oseltamivir to usual care had lower average direct and indirect costs compared to patients with usual care alone. Methods Resource use data were extracted from participants' daily diaries. Itemised country-specific unit costs were collected through official tariffs, pharmacies or literature. Costs were converted to 2018 values. The null hypothesis was tested based on one-sided credible intervals (CrIs) obtained by bootstrapping. Base-case analysis estimated direct cost and productivity losses using itemised costed resource use and the human capital approach. Scenario analyses with self-reported spending rather than itemised costing were also performed. Results Patients receiving oseltamivir (N = 1306) reported fewer healthcare visits, medication uses, hospital attendances and paid-work hours lost than the other patients (N = 1298). Excluding the oseltamivir cost, the average direct costs were lower in patients treated with oseltamivir from all perspectives, but these differences were not statistically significant (perspective of patient: euro17 [0-95% Crl: 16-19] vs. euro24 [5-100% Crl: 18-29]; healthcare provider: euro37 [28-67] vs. euro44 [25-55]; healthcare payers: euro54 [45-85] vs. euro68 [45-81]; and society: euro423 [399-478] vs. euro451 [390-478]). Scenario and age-group analyses confirmed these findings, but with some between-country differences. Conclusion The average direct and indirect costs were consistently lower in patients treated with oseltamivir than in patients without from four perspectives (excluding the oseltamivir cost). However, these differences were not statistically significant.
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| 8. |
- Coulson, S. J., et al.
(författare)
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Introduction of invertebrates into the High Arctic via imported soils: the case of Barentsburg in the Svalbard
- 2013
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Ingår i: Biological Invasions. - : Springer Science and Business Media LLC. - 1387-3547 .- 1573-1464. ; 15:1, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- Forty six species of invertebrate were collected from the manure enriched imported soils below the abandoned cow sheds in the Russian mining town of Barentsburg, Svalbard. Of these, 11 (24 %) were new records for Svalbard, including Collembola, gamasid mites, Enchytraeidae and the first identified Lumbricidae. Many of the new records are species not frequently observed in the Arctic. It is hypothesized that these species arrived with the chernozem soils imported to Barentsburg for the greenhouses from central or southern European Russia, or with livestock. The observations presented here are the first records of human invertebrate introductions establishing in Svalbard outside of dwellings. It is not believed that the majority of new species records described present an immediate threat to the ecology of Svalbard but they may, especially Deuteraphorura variabilis, establish in the nutrient enriched floral communities beneath bird cliffs characteristic of Svalbard.
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| 9. |
- Coulson, S. J., et al.
(författare)
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The invertebrate fauna of anthropogenic soils in the High-Arctic settlement of Barentsburg, Svalbard
- 2013
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Ingår i: Polar Research. - : Norwegian Polar Institute. - 0800-0395 .- 1751-8369. ; 32
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Tidskriftsartikel (refereegranskat)abstract
- The terrestrial environment of the High Arctic consists of a mosaic of habitat types. In addition to the natural habitat diversity, various human-influenced types may occur. For the resident invertebrate fauna, these anthropogenic habitats may be either unusually favourable or detrimental. In the town of Barentsburg, Svalbard, soils were imported for the greenhouses from southern Russia. These soils were subsequently discarded outside the greenhouses and have become augmented with manure from the cowsheds. Both the greenhouse and the cowsheds are now derelict. This site represents an unusually nutrient-rich location with considerable development of organic soils, in stark contrast to the naturally forming organic soils in Svalbard, which are typically thin and nutrient poor. Few previous studies have examined the soil invertebrate communities of human-disturbed or -created habitats in the Arctic. In an often nutrient-poor terrestrial environment, it is unclear how the invertebrate fauna will react to such nutrient enhancement. In these soils, 46 species of invertebrates were determined. Eleven species have not been recorded from other habitats in Svalbard and are hence likely to have been introduced. The native species assemblage in the anthropogenic soils was not atypical for many natural sites in Svalbard. Despite the enriched organic soils and highly ameliorated winter temperature conditions, the soil invertebrate fauna biodiversity does not appear to be enhanced beyond the presence of certain probably introduced species.
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| 10. |
- Temu, Stella G., et al.
(författare)
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Molecular, morphological and chemical variation of the Usnea pectinata aggregate from Tanzania, São Tomé and Príncipe
- 2022
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Ingår i: The Lichenologist. - : Cambridge University Press. - 0024-2829 .- 1096-1135. ; 54:5, s. 291-298
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the molecular, chemical and morphological variation in the Usnea pectinata aggregate using 42 specimens, 22 from Tanzania and 20 from São Tomé and Príncipe. A total of 31 sequences (13 ITS, 13 nuLSU and 5 RPB1) were generated. The results are presented in two phylogenies: first a three-markers ‘backbone’ phylogeny for the U. pectinata aggregate, where six distinct, strongly supported subclades indicate considerable genetic variation in the dataset; and second, an ITS phylogeny with 47 terminals along with a mapping of morphological and chemistry data. Several well-supported monophyletic clades were recovered in both phylogenies and these may well represent separate species in the complex referred to here as the U. pectinata aggregate. Three morphotypes characterized by axis pigmentation and four by branch shape were noted. Six chemotypes were observed.
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| 11. |
- Tolba, R. H., et al.
(författare)
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Defining Standards in Experimental Microsurgical Training: Recommendations of the European Society for Surgical Research (ESSR) and the International Society for Experimental Microsurgery (ISEM)
- 2017
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Ingår i: European Surgical Research. - : S. Karger AG. - 0014-312X .- 1421-9921. ; 58:5-6, s. 246-262
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Tidskriftsartikel (refereegranskat)abstract
- Background: Expectations towards surgeons in modern surgical practice are extremely high with minimal complication rates and maximal patient safety as paramount objectives. Both of these aims are highly dependent on individual technical skills that require sustained, focused, and efficient training outside the clinical environment. At the same time, there is an increasing moral and ethical pressure to reduce the use of animals in research and training, which has fundamentally changed the practice of microsurgical training and research. Various animal models were introduced and widely used during the mid-20th century, the pioneering era of experimental microsurgery. Since then, high numbers of ex vivo training concepts and quality control measures have been proposed, all aiming to reduce the number of animals without compromising quality and outcome of training. Summary: Numerous microsurgical training courses are available worldwide, but there is no general agreement concerning the standardization of microsurgical training. The major aim of this literature review and recommendation is to give an overview of various aspects of microsurgical training. We introduce here the findings of a previous survey-based analysis of microsurgical courses within our network. Basic principles behind microsurgical training (3Rs, good laboratory practice, 3Cs), considerations around various microsurgical training models, as well as several skill assessment tools are discussed. Recommendations are formulated following intense discussions within the European Society for Surgical Research (ESSR) and the International Society for Experimental Microsurgery (ISEM), based on scientific literature as well as on several decades of experience in the field of experimental (micro) surgery and preclinical research, represented by the contributing authors. Key Messages: Although ex vivo models are crucial for the replacement and reduction of live animal use, living animals are still indispensable at every level of training which aims at more than just a basic introduction to microsurgical techniques. Modern, competency-based microsurgical training is multi-level, implementing different objective assessment tools as outcome measures. A clear consensus on fundamental principles of microsurgical training and more active international collaboration for the sake of standardization are urgently needed. (C) 2017 S. Karger AG, Basel
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