| 1. |
- 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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| 5. |
- Saccardi, R, et al.
(författare)
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Benchmarking of survival outcomes following Haematopoietic Stem Cell Transplantation (HSCT): an update of the ongoing project of the European Society for Blood and Marrow Transplantation (EBMT) and Joint Accreditation Committee of ISCT and EBMT (JACIE)
- 2023
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Ingår i: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 58:6, s. 659-666
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Tidskriftsartikel (refereegranskat)abstract
- From 2016 EBMT and JACIE developed an international risk-adapted benchmarking program of haematopoietic stem cell transplant (HSCT) outcome to provide individual EBMT Centers with a means of quality-assuring the HSCT process and meeting FACT-JACIE accreditation requirements relating to 1-year survival outcomes. Informed by previous experience from Europe, North America and Australasia, the Clinical Outcomes Group (COG) established criteria for patient and Center selection, and a set of key clinical variables within a dedicated statistical model adapted to the capabilities of the EBMT Registry. The first phase of the project was launched in 2019 to test the acceptability of the benchmarking model through assessment of Centers’ performance for 1-year data completeness and survival outcomes of autologous and allogeneic HSCT covering 2013–2016. A second phase was delivered in July 2021 covering 2015–2019 and including survival outcomes. Reports of individual Center performance were shared directly with local principal investigators and their responses were assimilated. The experience thus far has supported the feasibility, acceptability and reliability of the system as well as identifying its limitations. We provide a summary of experience and learning so far in this ‘work in progress’, as well as highlighting future challenges of delivering a modern, robust, data-complete, risk-adapted benchmarking program across new EBMT Registry systems.
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| 6. |
- Lindholm, Caroline, et al.
(författare)
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The Quest for Welfare-Friendly Feeding of Broiler Breeders: Effects of Daily vs. 5:2 Feed Restriction Schedules
- 2018
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Ingår i: Poultry Science. - : OXFORD UNIV PRESS. - 0032-5791 .- 1525-3171. ; 97:2, s. 368-377
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Tidskriftsartikel (refereegranskat)abstract
- Restricted feeding of broiler breeders is required for improved long-term health and welfare. Because feeding frustration and hunger are major welfare concerns during rearing, many suggestions have been made to decrease the negative feelings of hunger while maintaining suitable growth rates and reproductive health. Non-daily ("skip-a-day") feeding schedules are commonly used around the world to increase portion sizes at meal times while restricting intake but these practices are prohibited in many countries due to welfare concerns on fasting days. We compared birds raised on a non-daily feeding schedule (2 non-consecutive fasting days per week, 5:2), previously suggested as a welfare-friendlier non-daily alternative, to birds raised on daily feed restriction. We found signs of increased physiological stress levels in 5:2 birds, including elevated heterophil to lymphocyte ratios (1.00 for 5:2 vs. 0.75 for daily fed at 12 weeks of age), increased adiposity (0.21% lean body weight [LBW] for 5:2 vs. 0.13% LBW for daily fed), and reduced muscle growth (pectoral muscle 5.94% LBW for 5: 2 vs. 6.52% LBW for daily fed). At the same time, 5:2 birds showed signs of lower anxiety before feeding times (activity was reduced from 10.30 in daily fed to 4.85) which may be a result of the lower feed competition associated with larger portion sizes. Although we found no difference in latency to first head movement in tonic immobility between the treatments (136.5 s on average for both groups), 5:2 birds generally showed more interest in a novel object in the home pen which indicated increased risk taking and reduced fear while fasting. The 5:2 birds in this study showed no signs of learning the feeding schedule, and this unpredictability may also increase stress. Taken together, the effects of 5:2 vs. daily feed restriction on the welfare of broiler breeder pullets remain inconclusive and differ between feeding and fasting days. In addition to reducing stress by minimizing the number of fasting days, we suggest that a shift to more predictable schedules may help improve the welfare of broiler breeder pullets.
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| 7. |
- Blackwell, Simon E., et al.
(författare)
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Optimism and mental imagery : A possible cognitive marker to promote well-being?
- 2013
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Ingår i: Psychiatry Research. - : ELSEVIER IRELAND LTD. - 0165-1781 .- 1872-7123. ; 206:1, s. 56-61
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Tidskriftsartikel (refereegranskat)abstract
- Optimism is associated with a range of benefits not only for general well-being, but also for mental and physical health. The development of psychological interventions to boost optimism derived from cognitive science would have the potential to provide significant public health benefits, yet cognitive markers of optimism are little understood. The current study aimed to take a first step in this direction by identifying a cognitive marker for optimism that could provide a modifiable target for innovative interventions. In particular we predicted that the ability to generate vivid positive mental imagery of the future would be associated with dispositional optimism. A community sample of 237 participants completed a survey comprising measures of mental imagery and optimism, and socio-demographic information. Vividness of positive future imagery was significantly associated with optimism, even when adjusting for socio-demographic factors and everyday imagery use. The ability to generate vivid mental imagery of positive future events may provide a modifiable cognitive marker of optimism. Boosting positive future imagery could provide a cognitive target for treatment innovations to promote optimism, with implications for mental health and even physical well-being. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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| 8. |
- Lindholm, Caroline, et al.
(författare)
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Growth heterogeneity in broiler breeder pullets is settled before the onset of feed restriction but is not predicted by size at hatch
- 2017
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Ingår i: Journal of Animal Science. - Champaign, IL, United States : American Society of Animal Science. - 0021-8812 .- 1525-3163. ; 95:1, s. 182-193
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Tidskriftsartikel (refereegranskat)abstract
- Uniform growth is a desirable trait in all large-scale animal production systems because it simplifies animal management and increases profitability. In parental broiler flocks, so-called broiler breeders, low growth uniformity is largely attributed to the feed competition that arises from quantitatively restricted feeding. As feed restriction is crucial to maintaining healthy and fertile breeders, several practices for reducing feed competition and the associated growth heterogeneity have been suggested and range from nutrient dilution by increasing fiber content in feed to intermittent fasting with increased portion size (“skip a day”), but no practice appears to be entirely effective. The fact that a large part of the heterogeneity remains even when feed competition is minimized suggests that some growth variation is caused by other factors. We investigated whether this variation arises during embryonic development (as measured by size at hatch) or during posthatch development by following the growth and body composition of birds of varying hatch sizes. Our results support the posthatch alternative, with animals that later grow to be small or large (here defined as >1 SD lighter or heavier than mean BW of the flock) being significantly different in size as early as 1 d after gaining access to feed (P < 0.05). We then investigated 2 possible causes for different postnatal growth: that high growth performance is linked 1) to interindividual variations in metabolism (as measured by cloacal temperature and verified by respirometry) or 2) to higher levels of social motivation (as measured in a social reinstatement T-maze), which should reduce the stress of being reared in large-scale commercial flocks. Neither of these follow-up hypotheses could account for the observed heterogeneity in growth. We suggest that the basis of growth heterogeneity in broiler breeder pullets may already be determined at the time of hatch in the form of qualitatively different maternal investments or immediately thereafter as an indirect result of differences in incubation conditions, hatching time, and resulting fasting time. Although this potential difference in maternal investment is not seen in body mass, tarsometatarsal length, or full body length of day-old chicks arriving at the farm, it may influence the development of differential feed and water intake during the first day of feeding, which in turn has direct effects on growth heterogeneity.
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| 9. |
- Spronk, Inge, et al.
(författare)
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Improved and standardized method for assessing years lived with disability after burns and its application to estimate the non-fatal burden of disease of burn injuries in Australia, New Zealand and the Netherlands
- 2020
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Ingår i: BMC Public Health. - : BMC. - 1471-2458. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- Background: Burden of disease estimates are an important resource in public health. Currently, robust estimates are not available for the burn population. Our objectives are to adapt a refined methodology (INTEGRIS method) to burns and to apply this new INTEGRIS-burns method to estimate, and compare, the burden of disease of burn injuries in Australia, New Zealand and the Netherlands.Methods: Existing European and Western-Australian health-related quality of life (HRQL) datasets were combined to derive disability weights for three homogenous burn injury groups based on percentage total body surface area (%TBSA) burned. Subsequently, incidence data from Australia, New Zealand, and the Netherlands from 2010 to 2017 were used to compute annual non-fatal burden of disease estimates for each of these three countries. Non-fatal burden of disease was measured by years lived with disability (YLD).Results: The combined dataset included 7159 HRQL (EQ-5D-3 L) outcomes from 3401 patients. Disability weights ranged from 0.046 (subgroup < 5% TBSA burned > 24 months post-burn) to 0.497 (subgroup > 20% TBSA burned 0-1 months post-burn). In 2017 the non-fatal burden of disease of burns for the three countries (YLDs/100,000 inhabitants) was 281 for Australia, 279 for New Zealand and 133 for the Netherlands.Conclusions: This project established a method for more precise estimates of the YLDs of burns, as it is the only method adapted to the nature of burn injuries and their recovery. Compared to previous used methods, the INTEGRIS-burns method includes improved disability weights based on severity categorization of burn patients; a better substantiated proportion of patients with lifelong disability based; and, the application of burn specific recovery timeframes. Information derived from the adapted method can be used as input for health decision making at both the national and international level. Future studies should investigate whether the application is valid in low- and middle- income countries.
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| 10. |
- van der Wal, M. B. A., et al.
(författare)
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Differential item functioning in the Observer Scale of the POSAS for different scar types
- 2014
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Ingår i: Quality of Life Research. - : Springer Science and Business Media LLC. - 0962-9343 .- 1573-2649. ; 23:7, s. 2037-2045
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Tidskriftsartikel (refereegranskat)abstract
- To investigate whether the Observer Scale of the Patient and Observer Scar Assessment Scale (POSAS) can serve as a generic measure for scar quality across different scar types. A collection of POSAS scores derived from several clinical trials on burn (n = 404), linear (n = 384), and keloidal scars (n = 282) was analyzed using the partial credit model of the Rasch analysis package RUMM2030. Differential item functioning (DIF) was observed for the Observer Scale of the POSAS between the three scar types for the items pliability, thickness, and surface area, which could be solved by item splitting. The items pigmentation and thickness showed disordered thresholds, considerable misfit, and unpredictability. Users of the Observer Scale of the POSAS must be aware that the raw scores obtained from burn, linear, and keloidal scars cannot be compared without the scar-specific DIF adjustment of the items pliability, thickness, and surface area.
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