| 1. |
- Alsaadi, Sarah, 1987-, et al.
(författare)
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Collective moral disengagement at school : A validation of a scale for Swedish children
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this study was to evaluate a recently developed classroom collective moral disengagement scale (CMD). The 18-item scale was evaluated on a sample of 1626 fourth grade students in Sweden. Through confirmatory factor analysis, the unidimensional structure of the scale was verified, and the internal consistency was good. The scale is related to individual moral disengagement and to bullying behavior both on an individual level, which supports the criteria validity of the scale and on class level, which supports the construct validity of the scale. Multigroup analyses demonstrated measurement invariance across gender. These results indicate that the scale can be used in studies on CMD, and girls’ and boys’ mean scores may be compared.
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| 2. |
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| 3. |
- Benatar, Michael, et al.
(författare)
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Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01) : a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
- 2024
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 23:7, s. 687-699
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Tidskriftsartikel (refereegranskat)abstract
- Background: Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder leading to muscle weakness and respiratory failure. Arimoclomol, a heat-shock protein-70 (HSP70) co-inducer, is neuroprotective in animal models of amyotrophic lateral sclerosis, with multiple mechanisms of action, including clearance of protein aggregates, a pathological hallmark of sporadic and familial amyotrophic lateral sclerosis. We aimed to evaluate the safety and efficacy of arimoclomol in patients with amyotrophic lateral sclerosis.Methods: ORARIALS-01 was a multinational, randomised, double-blind, placebo-controlled, parallel-group trial done at 29 centres in 12 countries in Europe and North America. Patients were eligible if they were aged 18 years or older and met El Escorial criteria for clinically possible, probable, probable laboratory-supported, definite, or familial amyotrophic lateral sclerosis; had an ALS Functional Rating Scale-Revised score of 35 or more; and had slow vital capacity at 70% or more of the value predicted on the basis of the participant's age, height, and sex. Patients were randomly assigned (2:1) in blocks of 6, stratified by use of a stable dose of riluzole or no riluzole use, to receive oral arimoclomol citrate 1200 mg/day (400 mg three times per day) or placebo. The Randomisation sequence was computer generated centrally. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was the Combined Assessment of Function and Survival (CAFS) rank score over 76 weeks of treatment. The primary outcome and safety were analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03491462, and is completed.Findings: Between July 31, 2018, and July 17, 2019, 287 patients were screened, 245 of whom were enrolled in the trial and randomly assigned. The modified intention-to-treat population comprised 239 patients (160 in the arimoclomol group and 79 in the placebo group): 151 (63%) were male and 88 (37%) were female; mean age was 57·6 years (SD 10·9). CAFS score over 76 weeks did not differ between groups (mean 0·51 [SD 0·29] in the arimoclomol group vs 0·49 [0·28] in the placebo group; p=0·62). Cliff's delta comparing the two groups was 0·039 (95% CI –0·116 to 0·194). Proportions of participants who died were similar between the treatment groups: 29 (18%) of 160 patients in the arimoclomol group and 18 (23%) of 79 patients in the placebo group. Most deaths were due to disease progression. The most common adverse events were gastrointestinal. Adverse events were more often deemed treatment-related in the arimoclomol group (104 [65%]) than in the placebo group (41 [52%]) and more often led to treatment discontinuation in the arimoclomol group (26 [16%]) than in the placebo group (four [5%]).Interpretation: Arimoclomol did not improve efficacy outcomes compared with placebo. Although available biomarker data are insufficient to preclude future strategies that target the HSP response, safety data suggest that a higher dose of arimoclomol would not have been tolerated.Funding: Orphazyme.
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| 4. |
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| 5. |
- Carneiro, Miguel, et al.
(författare)
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Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 345:6200, s. 1074-1079
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Tidskriftsartikel (refereegranskat)abstract
- The genetic changes underlying the initial steps of animal domestication are still poorly understood. We generated a high-quality reference genome for the rabbit and compared it to resequencing data from populations of wild and domestic rabbits. We identified more than 100 selective sweeps specific to domestic rabbits but only a relatively small number of fixed (or nearly fixed) single-nucleotide polymorphisms (SNPs) for derived alleles. SNPs with marked allele frequency differences between wild and domestic rabbits were enriched for conserved noncoding sites. Enrichment analyses suggest that genes affecting brain and neuronal development have often been targeted during domestication. We propose that because of a truly complex genetic background, tame behavior in rabbits and other domestic animals evolved by shifts in allele frequencies at many loci, rather than by critical changes at only a few domestication loci.
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| 6. |
- de Hoogh, Kees, et al.
(författare)
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Development of West-European PM2.5 and NO2 land use regression models incorporating satellite-derived and chemical transport modelling data
- 2016
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 151, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Satellite-derived (SAT) and chemical transport model (CTM) estimates of PM2.5 and NO2 are increasingly used in combination with Land Use Regression (LUR) models. We aimed to compare the contribution of SAT and CTM data to the performance of LUR PM2.5 and NO2 models for Europe. Four sets of models, all including local traffic and land use variables, were compared (LUR without SAT or CTM, with SAT only, with CTM only, and with both SAT and CTM). LUR models were developed using two monitoring data sets: PM2.5 and NO2 ground level measurements from the European Study of Cohorts for Air Pollution Effects (ESCAPE) and from the European AIRBASE network. LUR PM2.5 models including SAT and SAT+CTM explained ~60% of spatial variation in measured PM2.5 concentrations, substantially more than the LUR model without SAT and CTM (adjR(2): 0.33-0.38). For NO2 CTM improved prediction modestly (adjR(2): 0.58) compared to models without SAT and CTM (adjR(2): 0.47-0.51). Both monitoring networks are capable of producing models explaining the spatial variance over a large study area. SAT and CTM estimates of PM2.5 and NO2 significantly improved the performance of high spatial resolution LUR models at the European scale for use in large epidemiological studies.
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| 7. |
- de Oliveira, Kelin Gonçalves, et al.
(författare)
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Decoding of the surfaceome and endocytome in primary glioblastoma cells identifies potential target antigens in the hypoxic tumor niche
- 2024
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Ingår i: Acta Neuropathologica Communications. - : BioMed Central (BMC). - 2051-5960. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Immunotherapies with antibody-drug-conjugates (ADC) and CAR-T cells, targeted at tumor surface antigens (surfaceome), currently revolutionize clinical oncology. However, target identification warrants a better understanding of the surfaceome and how it is modulated by the tumor microenvironment. Here, we decode the surfaceome and endocytome and its remodeling by hypoxic stress in glioblastoma (GBM), the most common and aggressive brain tumor in adults. We employed a comprehensive approach for global and dynamic profiling of the surfaceome and endocytosed (endocytome) proteins and their regulation by hypoxia in patient-derived GBM cultures. We found a heterogeneous surface-endocytome profile and a divergent response to hypoxia across GBM cultures. We provide a quantitative ranking of more than 600 surface resident and endocytosed proteins, and their regulation by hypoxia, serving as a resource to the cancer research community. As proof-of-concept, the established target antigen CD44 was identified as a commonly and abundantly expressed surface protein with high endocytic activity. Among hypoxia induced proteins, we reveal CXADR, CD47, CD81, BSG, and FXYD6 as potential targets of the stressed GBM niche. We could validate these findings by immunofluorescence analyses in patient tumors and by increased expression in the hypoxic core of GBM spheroids. Selected candidates were finally confronted by treatment studies, showing their high capacity for internalization and ADC delivery. Importantly, we highlight the limited correlation between transcriptomics and proteomics, emphasizing the critical role of membrane protein enrichment strategies and quantitative mass spectrometry. Our findings provide a comprehensive understanding of the surface-endocytome and its remodeling by hypoxia in GBM as a resource for exploration of targets for immunotherapeutic approaches in GBM.
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| 8. |
- Forsberg, Sarah, et al.
(författare)
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Finger Food Meals as a Means of Improving Mealtimes for People with Motoric Eating Difficulties : A Pilot Study
- 2024
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Ingår i: Journal of Nutrition in Gerontology and Geriatrics. - : Routledge. - 2155-1197 .- 2155-1200. ; 43:2, s. 95-115
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Tidskriftsartikel (refereegranskat)abstract
- Motoric eating difficulties affecting the ability to eat according to established norms may result in loss of autonomy, reduced food intake and decreased social interaction. Finger food meals may affect the ability to eat independently and were therefore compared to regular meals for older adults >65 years with major motoric eating difficulties. In this pilot study the screening instrument MEOF-II, including additional questions about use of cutlery and fingers, was used to collect data regarding autonomy, food intake and social interaction through observations. Five women and one man participated in the study. Results showed that finger food meals facilitated autonomous eating since the participants were able to eat independently without relying on help from others. Less energy was spent on eating, which allowed for social interaction. However, finger food meals entail unfamiliar norms and culinary rules which may hinder eating; this is an important factor to consider in the implementation of such meals. Further studies on finger foods for older adults may consider larger and diverse cohorts, including healthy older adults, those with motoric difficulties and those with early stages of cognitive decline. Also, a wider variety of finger foods for specific cultural preferences and situations may be considered.
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| 9. |
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| 10. |
- Forsberg, Sarah, et al.
(författare)
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Perceptions and Attitudes about Eating with the Fingers-An Explorative Study among Older Adults with Motoric Eating Difficulties, Relatives and Professional Caregivers
- 2022
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Ingår i: Journal of Nutrition in Gerontology and Geriatrics. - : Routledge. - 2155-1197 .- 2155-1200. ; 41:1, s. 65-91
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Tidskriftsartikel (refereegranskat)abstract
- Difficulties of managing cutlery, manipulating food on the plate and transporting food to the mouth may negatively influence the ability for self-provision and nutritional status among older adults with motoric eating difficulties. The purpose was to explore perceptions and attitudes about eating with the fingers among older adults with motoric eating difficulties, and relatives and professional caregivers of older adults with motoric eating difficulties. Qualitative data was collected through individual interviews with older adults >65 years ( N = 14) with motoric eating difficulties and focus groups with relatives ( N = 15) and professional caregivers ( N = 15). Data was analyzed using deductive and inductive content analysis. Although the older adults had normative ideas about proper eating and culinary rules, they regularly consumed several foods with their fingers without previously reflecting upon this. Using bread to grip or wrap foods and inserting skewers into foods may increase the acceptability of eating with the fingers. However, the importance of the disease causing the eating difficulties, how it was perceived, and its severity were crucial in understanding how eating with the fingers was perceived. Finger foods may be suitable for older adults with major eating difficulties because they have developed a self-acceptance in relation to their condition over time.
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