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1.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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2.
  • Wang, Li-San, et al. (författare)
  • Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
  • 2015
  • Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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  • Werren, John H, et al. (författare)
  • Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.
  • 2010
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 327:5963, s. 343-8
  • Tidskriftsartikel (refereegranskat)abstract
    • We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.
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  • Hibar, Derrek P., et al. (författare)
  • Novel genetic loci associated with hippocampal volume
  • 2017
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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  • Escott-Price, Valentina, et al. (författare)
  • Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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6.
  • Falster, Daniel, et al. (författare)
  • AusTraits, a curated plant trait database for the Australian flora
  • 2021
  • Ingår i: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
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7.
  • Siepielski, Adam M., et al. (författare)
  • Precipitation drives global variation in natural selection
  • 2017
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 355:6328, s. 959-962
  • Tidskriftsartikel (refereegranskat)abstract
    • Climate change has the potential to affect the ecology and evolution of every species on Earth. Although the ecological consequences of climate change are increasingly well documented, the effects of climate on the key evolutionary process driving adaptation-natural selection-are largely unknown. We report that aspects of precipitation and potential evapotranspiration, along with the North Atlantic Oscillation, predicted variation in selection across plant and animal populations throughout many terrestrial biomes, whereas temperature explained little variation. By showing that selection was influenced by climate variation, our results indicate that climate change may cause widespread alterations in selection regimes, potentially shifting evolutionary trajectories at a global scale.
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8.
  • Siepielski, Adam M, et al. (författare)
  • Response to Comment on "Precipitation drives global variation in natural selection"
  • 2018
  • Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 359:6374
  • Tidskriftsartikel (refereegranskat)abstract
    • The comment by Myers-Smith and Myers focuses on three main points: (i) the lack of a mechanistic explanation for climate-selection relationships, (ii) the appropriateness of the climate data used in our analysis, and (iii) our focus on estimating climate-selection relationships across (rather than within) taxonomic groups. We address these critiques in our response.
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  • Birgegard, A, et al. (författare)
  • Diagnostic issues of binge eating in eating disorders
  • 2013
  • Ingår i: European eating disorders review : the journal of the Eating Disorders Association. - : Wiley. - 1099-0968. ; 21:3, s. 175-183
  • Tidskriftsartikel (refereegranskat)
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  • Björk, Tabita, et al. (författare)
  • Reasons for non-participation in follow-up research on eating disorders
  • 2006
  • Ingår i: Eating and Weight Disorders. - 1124-4909 .- 1590-1262. ; 11:3, s. 147-153
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Lack of participation in follow-ups is thought to be a serious bias in outcome research on eating disorders; however, little systematic knowledge exists about the problem. The present study aimed to delineate non-participation in long-term follow-up research, and explore the reasons for non-participation.METHOD: Eating disorder patients (N=840) entering a naturalistic, longitudinal multi-centre study were divided into participators (N=508) and non-participators (N=332) in 36-month follow-ups. Non-participators were further classified as either active (i.e. refused participation or failed to attend scheduled appointments) or passive non-participators (i.e. could not be traced).RESULTS: Active non-participators exhibited significantly lower levels of general and eating disorder psychopathology at intake compared to participators, while passive non-participators reported higher levels of hostility.DISCUSSION: Systematic exploration of non-participation in longitudinal research can help to mitigate the problem of indistinct results due to missing data. Barriers to successful longitudinal research and how to overcome non-participation at endpoint are discussed.
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  • Dominoni, Davide M., et al. (författare)
  • Why conservation biology can benefit from sensory ecology
  • 2020
  • Ingår i: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 4:4, s. 502-511
  • Tidskriftsartikel (refereegranskat)abstract
    • Anthropogenic sensory pollutants, such as noise, light and chemicals, are affecting biodiversity. This Perspective uses an understanding of animal sensory ecology to explore how these impacts can be mitigated. Global expansion of human activities is associated with the introduction of novel stimuli, such as anthropogenic noise, artificial lights and chemical agents. Progress in documenting the ecological effects of sensory pollutants is weakened by sparse knowledge of the mechanisms underlying these effects. This severely limits our capacity to devise mitigation measures. Here, we integrate knowledge of animal sensory ecology, physiology and life history to articulate three perceptual mechanisms-masking, distracting and misleading-that clearly explain how and why anthropogenic sensory pollutants impact organisms. We then link these three mechanisms to ecological consequences and discuss their implications for conservation. We argue that this framework can reveal the presence of 'sensory danger zones', hotspots of conservation concern where sensory pollutants overlap in space and time with an organism's activity, and foster development of strategic interventions to mitigate the impact of sensory pollutants. Future research that applies this framework will provide critical insight to preserve the natural sensory world.
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  • Fäh, Donat, et al. (författare)
  • Coupled seismogenic geohazards in Alpine regions
  • 2012
  • Ingår i: Bollettino di Geofisica Teorica ed Applicata. - 0006-6729. ; 53:4, s. 485-508
  • Tidskriftsartikel (refereegranskat)abstract
    • COupled seismogenic GEohazards in Alpine Regions (COGEAR) is an interdisciplinary natural hazard project investigating the hazard chain induced by earthquakes. It addresses tectonic processes and the related variability of seismicity in space and time, earthquake forecasting and short-term precursors, and strong ground motion as a result of source and complex path effects. We study non-linear wave propagation phenomena, liquefaction and triggering of landslides in soil and rock, as well as earthquake-induced snow avalanches. The Valais, and in particular parts of the Rhone, Visper, and Matter valleys have been selected as study areas. Tasks include detailed field investigations, development and application of numerical modeling techniques, assessment of the susceptibility to seismically induced effects, and installation of different monitoring systems to test and validate our models. These systems are for long-term operation and include a continuous GPS and seismic networks, a test installation for observing earthquake precursors, and a system to study site-effects and non-linear phenomena in two test areas (Visp, St. Niklaus / Randa). Risk-related aspects relevant for buildings and lifelines are also considered
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22.
  • Hansson, L M, et al. (författare)
  • How do eating disorder patients eat after treatment? Dietary habits and eating behaviour three years after entering treatment.
  • 2011
  • Ingår i: Eating and Weight Disorders. - 1124-4909 .- 1590-1262. ; 16:1, s. e1-8
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Improvements in psychological symptoms and weight have often been demonstrated following eating disorder (ED) treatment, but it is not clear to what extent eating behaviour itself is normalised. This cross-sectional study aimed to investigate dietary habits and eating behaviour in ED patients three years after entering treatment.METHOD: ED patients (N=70) were divided into those who had recovered (N=36), and those who still suffered from bulimic (N=18) or anorexic (N=16) psychopathology. Patients were compared to a female normal control group of similar age (N=61), and assessments were made on a dietary questionnaire, as well as the BDI, EDI-2, SASB and SCL-90.RESULTS: With some notable exceptions eating patterns in recovered patients resembled those of controls. Dieting was most evident in recovered and current bulimic patients, while restrictive eating and vegetarianism was found in recovered or current anorexic patients. A majority of the patients with ongoing EDs avoided fatty foods.DISCUSSION: Risk behaviours such as restrictive eating, dieting and food avoidance, may have an important impact on relapse rates, and it may therefore be imperative to continue to monitor eating behaviour in ED patients following treatment termination to ensure better long-term outcome.
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  • Lee, Bruce Y., et al. (författare)
  • Research gaps and opportunities in precision nutrition : an NIH workshop report
  • 2022
  • Ingår i: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 116:6, s. 1877-1900
  • Tidskriftsartikel (refereegranskat)abstract
    • Precision nutrition is an emerging concept that aims to develop nutrition recommendations tailored to different people's circumstances and biological characteristics. Responses to dietary change and the resulting health outcomes from consuming different diets may vary significantly between people based on interactions between their genetic backgrounds, physiology, microbiome, underlying health status, behaviors, social influences, and environmental exposures. On 11-12 January 2021, the National Institutes of Health convened a workshop entitled "Precision Nutrition: Research Gaps and Opportunities" to bring together experts to discuss the issues involved in better understanding and addressing precision nutrition. The workshop proceeded in 3 parts: part I covered many aspects of genetics and physiology that mediate the links between nutrient intake and health conditions such as cardiovascular disease, Alzheimer disease, and cancer; part II reviewed potential contributors to interindividual variability in dietary exposures and responses such as baseline nutritional status, circadian rhythm/sleep, environmental exposures, sensory properties of food, stress, inflammation, and the social determinants of health; part III presented the need for systems approaches, with new methods and technologies that can facilitate the study and implementation of precision nutrition, and workforce development needed to create a new generation of researchers. The workshop concluded that much research will be needed before more precise nutrition recommendations can be achieved. This includes better understanding and accounting for variables such as age, sex, ethnicity, medical history, genetics, and social and environmental factors. The advent of new methods and technologies and the availability of considerably more data bring tremendous opportunity. However, the field must proceed with appropriate levels of caution and make sure the factors listed above are all considered, and systems approaches and methods are incorporated. It will be important to develop and train an expanded workforce with the goal of reducing health disparities and improving precision nutritional advice for all Americans.
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25.
  • Levallius, J, et al. (författare)
  • Some stay the same: Personality change after treatment for eating disorder
  • 2017
  • Ingår i: EUROPEAN PSYCHIATRY. - : Cambridge University Press (CUP). - 0924-9338 .- 1778-3585. ; 41, s. S555-S555
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Strong evidence establishes a close relationship between personality traits and mental illness; where personality can be said to influences the likelihood, severity and longevity of a mental disorder. Personality is usually seen as fixed, yet there is a growing body of evidence for the changeability of personality, though this has rarely been studied in relation to mental disorders.ObjectiveTo study the longitudinal interplay between personality and eating disorders (EDs), particularly the associations between personality, recovery and treatment modality.AimsTo investigate changes in the five domains and thirty lower-level facets of personality in non-underweight EDs, and its associations to intervention and outcome.MethodsTwo hundred and nine adults with EDs enrolled either in a four-month multimodal psychodynamic group-therapy (DAY) or four-six month internet-based supported cognitive behavioural therapy (iCBT). ED diagnosis and personality (by the five-factor model) were assessed at baseline, termination and 6-month follow up. Structural equation modeling was used to analyze domain-level development, and reliable change (RCI) for facet-level development.ResultsRemission rate at end of treatment was 71% in DAY and 55% in iCBT. Over time, Neuroticism decreased significantly while Extraversion, Openness and Conscientiousness increased (P < 0.01). Treatment and outcome had little influence on domain-level change. At the facet-level, 28% of patients reliably changed in any given facet, and there were several differences in pattern based on treatment and outcome.ConclusionsThis study lends support for the possibility of personality change and its relevance for recovery from EDs.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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  • Ramirez, Florence D.C., et al. (författare)
  • Lateral and radial viscosity structure beneath Fennoscandia inferred from seismic and magnetotelluric observations
  • 2024
  • Ingår i: Physics of the Earth and Planetary Interiors. - : Elsevier B.V.. - 0031-9201 .- 1872-7395. ; 351
  • Tidskriftsartikel (refereegranskat)abstract
    • Fennoscandia is continuously uplifting in response to past deglaciation, termed glacial isostatic adjustment or GIA, and its mantle viscosity is well constrained from ice sheet and sea level data. Here, we compare those GIA-constrained viscosities for the Fennoscandian upper mantle with geophysically-constrained viscosities. We construct the upper mantle viscosity structure of Fennoscandia by inferring temperature and water content from seismic and magnetotelluric (MT) data. Using a 1-D MT model for Fennoscandian cratons together with a global seismic model, we infer an upper mantle viscosity (below 250 km) of ∼1021±2 Pa·s, which encompasses the GIA-constrained viscosities of 1020 − 1021 Pa·s. The GIA viscosities are better matched if the Fennoscandian upper mantle is a wet harzburgite or a dry pyrolite, where pyrolite is ∼10 times more viscous than harzburgite. Using the average temperatures and water contents for harzburgitic upper mantle, the GIA viscosities require 1–4 mm grain sizes indicating a diffusion creep regime. In northwestern Fennoscandia, where a high-resolution 2-D resistivity model is available, greater inferred mantle water content implies viscosities that are 10–100 times lower than those for the Fennoscandian Craton. Our work suggests that the combination of seismic and MT observations can improve upper mantle viscosity estimates, especially for regions with laterally-varying viscosity structures or where GIA constraints are not available. Although our method represents an important step forward, viscosity uncertainty can be further reduced by incorporating additional constraints on rock composition, grain size and mantle stress, as well as more accurate geophysical data, into the viscosity calculation.
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28.
  • Uddin, M. N., et al. (författare)
  • The Mechanistic Role of Thymoquinone in Parkinson's Disease: Focus on Neuroprotection in Pre-Clinical Studies
  • 2021
  • Ingår i: Current Molecular Pharmacology. - : Bentham Science Publishers Ltd.. - 1874-4672. ; 14:6, s. 1083-1092
  • Tidskriftsartikel (refereegranskat)abstract
    • Thymoquinone (TQ) is one of the leading phytochemicals, which is abundantly found in Nigella sativa L. seeds. TQ exhibited various biological effects such as antioxidant, anti-inflammatory, antimicrobial, and anti-tumoral in several pre-clinical studies. Parkinson's disease (PD) is a long-term neurodegenerative disease with movement difficulties, and the common feature of neurodegeneration in PD patients is caused by dopaminergic neural damage in the substantia nigra pars compacta. The neuroprotective activity of TQ has been studied in various neurological disorders. TQ-mediated neuroprotection against PD is yet to be reported in a single frame; therefore, this review is intended to narrate the potentiality of TQ in the therapy of PD. TQ has been shown to protect against neurotoxins via amelioration of neuroinflammation, oxidative stress, and apoptosis, thereby protecting neurodegeneration in PD models. TQ could be an emerging therapeutic intervention in PD management, but mechanistic studies remain to be investigated to clarify its neuroprotective role.
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