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1.
  • van Bragt, JJMH, et al. (author)
  • Characteristics and treatment regimens across ERS SHARP severe asthma registries
  • 2020
  • In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
  • Journal article (peer-reviewed)abstract
    • Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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  • Wallen, K. E., et al. (author)
  • Integrating team science into interdisciplinary graduate education : an exploration of the SESYNC Graduate Pursuit
  • 2019
  • In: Journal of Environmental Studies and Sciences. - : Springer Science and Business Media LLC. - 2190-6483 .- 2190-6491. ; 9:2, s. 218-233
  • Journal article (peer-reviewed)abstract
    • Complex socio-environmental challenges require interdisciplinary, team-based research capacity. Graduate students are fundamental to building such capacity, yet formal opportunities for graduate students to develop these capacities and skills are uncommon. This paper presents an assessment of the Graduate Pursuit (GP) program, a formal interdisciplinary team science graduate research and training program administered by the National Socio-Environmental Synthesis Center (SESYNC). Quantitative and qualitative assessment of the program’s first cohort revealed that participants became significantly more comfortable with interdisciplinary research and team science approaches, increased their capacity to work across disciplines, and were enabled to produce tangible research outcomes. Qualitative analysis of four themes—(1) discipline, specialization, and shared purpose, (2) interpersonal skills and personality, (3) communication and teamwork, and (4) perceived costs and benefits—encompass participants’ positive and negative experiences and support findings from past assessments. The findings also identify challenges and benefits related to individual personality traits and team personality orientation, the importance of perceiving a sense of autonomy and independence, and the benefit of graduate training programs independent of the university and graduate program environment.
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  • Chadwick, D., et al. (author)
  • Digital inclusion and participation of people with intellectual disabilities during COVID-19 : A rapid review and international bricolage
  • 2022
  • In: Journal of Policy and Practice in Intellectual Disabilities. - : Wiley. - 1741-1122 .- 1741-1130. ; 19:3, s. 242-256
  • Journal article (peer-reviewed)abstract
    • The COVID-19 pandemic has meant a rapid transfer of everyday activities to the online world. Information and communication technologies (ICTs) have become more embedded than ever in people's lives. This investigation addresses how this change has affected the lives of people with intellectual disabilities (ID). A two-step design was used. A rapid review was conducted on empirical studies published between January 2019 and June 2021. Search terms related to ID, ICT use and COVID-19. A qualitative international bricolage was also conducted corresponding to author nationalities. Data gathered from the review and bricolage were analysed separately using thematic analysis and relationally synthesised. Digital solutions to provide access to COVID-19 information and guidance seemed inadequate but were seldom empirically studied. Digital poverty, literacy and exclusion remain significant issues for people with ID internationally. People and their carers experienced reduced and removed service provision, loneliness and impoverished daily lives during the pandemic; amelioration of which was facilitated by digital solutions. One solution often used was videoconferencing. Prior experience of digital participation, adequate finances, connection, support and digital literacy mentoring for both people with ID and those providing services and support facilitated digital inclusion. Digital exclusion during COVID-19 was exacerbated by sociopolitical, structural, individual and support-related barriers. Although awareness of digital exclusion appears to have been raised, the extent to which this has led to action and change remains unclear. Despite digital exclusion and digital participation benefitting continuation of life, social and emotional well-being and autonomy, COVID-19 has not provided the impetus to eradicate digital poverty for people with ID. Governmental support, digital education, creativity and problem solving are required to enable people with ID the human right to be included in the digital world at this essential time and into the future.
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  • Charchar, Fadi J., et al. (author)
  • Lifestyle management of hypertension : International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension
  • 2024
  • In: Journal of Hypertension. - : Wolters Kluwer. - 0263-6352 .- 1473-5598. ; 42:1, s. 23-49
  • Journal article (peer-reviewed)abstract
    • Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools.
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  • Kurilshikov, Alexander, et al. (author)
  • Large-scale association analyses identify host factors influencing human gut microbiome composition
  • 2021
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53:2, s. 156-165
  • Journal article (peer-reviewed)abstract
    • To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
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  • Seifert, Tina, 1985, et al. (author)
  • A scaffold replacement approach towards new sirtuin 2 inhibitors
  • 2020
  • In: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896. ; 28:2
  • Journal article (peer-reviewed)abstract
    • Sirtuins (SIRT1-SIRT7) are an evolutionary conserved family of NAD(+)-dependent protein deacylases regulating the acylation state of epsilon-N-lysine residues of proteins thereby controlling key biological processes. Numerous studies have found association of the aberrant enzymatic activity of SIRTs with various diseases like diabetes, cancer and neurodegenerative disorders. Previously, we have shown that substituted 2-alkyl-chroman-4-one/chromone derivatives can serve as selective inhibitors of SIRT2 possessing an antiproliferative effect in two human cancer cell lines. In this study, we have explored the bioisosteric replacement of the chroman-4-one/chromone core structure with different less lipophilic bicyclic scaffolds to overcome problems associated to poor physiochemical properties due to a highly lipophilic substitution pattern required for achieve a good inhibitory effect. Various new derivatives based on the quinolin-4(1H)-one scaffold, bicyclic secondary sulfonamides or saccharins were synthesized and evaluated for their SIRT inhibitory effect. Among the evaluated scaffolds, the benzothiadiazine-1,1-dioxide-based compounds showed the highest SIRT2 inhibitory activity. Molecular modeling studies gave insight into the binding mode of the new scaffold-replacement analogues.
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  • Ahlström, G., et al. (author)
  • Health care utilisation among older people with Down syndrome compared to specific medical guidelines for health surveillance : a Swedish national register study
  • 2020
  • In: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 20:1
  • Journal article (peer-reviewed)abstract
    • Background: Specific medical guidelines for health surveillance exist for people with Down syndrome (DS) since 25 years but knowledge of adherence to the guidelines is lacking. The guidelines were developed to avoid unnecessary suffering from preventable conditions. The aims of the study were to investigate 1) planned health care visits in relation to the co-morbidities described in specific medical guidelines as a measure of adherence, 2) unplanned health care visits as a measure of potentially unmet health care needs and 3) gender differences in health care utilisation among older people with DS. Methods: This register-based study includes people with DS (n = 472) from a Swedish national cohort of people with intellectual disability (n = 7936), aged 55 years or more, and with at least one support according to the disability law, in 2012. Data on inpatient and outpatient specialist health care utilisation were collected from the National Patient Register for 2002–2012. Results: A total of 3854 inpatient and outpatient specialist health care visits were recorded during the 11 years, of which 54.6% (n = 2103) were planned, 44.0% (n = 1695) unplanned and 1.4% (n = 56) lacked information. More than half of the visits, 67.0% (n = 2582) were outpatient health care thus inpatient 33% (n = 1272). Most planned visits (29.4%, n = 618) were to an ophthalmology clinic, and most unplanned visits to an internal medicine clinic (36.6%, n = 621). The most common cause for planned visits was cataract, found at least once for 32.8% in this cohort, followed by arthrosis (8.9%), epilepsy (8.9%) and dementia (6.6%). Pneumonia, pain, fractures and epilepsy each accounted for at least one unplanned visit for approximately one-fourth of the population (27.1, 26.9, 26.3 and 19.7% respectively). Men and women had similar numbers of unplanned visits. However, women were more likely to have visits for epilepsy or fractures, and men more likely for pneumonia. Conclusions: Increased awareness of existing specific medical guidelines for people with DS is vital for preventive measures. The relatively few planned health care visits according to the medical guidelines together with a high number of unplanned visits caused by conditions which potentially can be prevented suggest a need of improved adherence to medical guidelines.
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  • Berendse, F, et al. (author)
  • Raised atmospheric CO2 levels and increased N deposition cause shifts in plant species composition and production in Sphagnum bogs
  • 2001
  • In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 7:5, s. 591-598
  • Journal article (peer-reviewed)abstract
    • Part of the missing sink in the global CO2 budget has been attributed to the positive effects of CO2 fertilization and N deposition on carbon sequestration in Northern Hemisphere terrestrial ecosystems. The genus Sphagnum is one of the most important groups of plant species sequestrating carbon in temperate and northern bog ecosystems, because of the low decomposability of the dead material it produces. The effects of raised CO2 and increased atmospheric N deposition on growth of Sphagnum and other plants were studied in bogs at four sites across Western Europe. Contrary to expectations, elevated CO2 did not significantly affect Sphagnum biomass growth. Increased N deposition reduced Sphagnum mass growth, because it increased the cover of vascular plants and the tall moss Polytrichum strictum. Such changes in plant species composition may decrease carbon sequestration in Sphagnum-dominated bog ecosystems.
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  • Brannon, A Rose, et al. (author)
  • Molecular Stratification of Clear Cell Renal Cell Carcinoma by Consensus Clustering Reveals Distinct Subtypes and Survival Patterns.
  • 2010
  • In: Genes & cancer. - : Sage. - 1947-6027 .- 1947-6019. ; 1:2, s. 152-163
  • Journal article (peer-reviewed)abstract
    • Clear cell renal cell carcinoma (ccRCC) is the predominant RCC subtype, but even within this classification, the natural history is heterogeneous and difficult to predict. A sophisticated understanding of the molecular features most discriminatory for the underlying tumor heterogeneity should be predicated on identifiable and biologically meaningful patterns of gene expression. Gene expression microarray data were analyzed using software that implements iterative unsupervised consensus clustering algorithms to identify the optimal molecular subclasses, without clinical or other classifying information. ConsensusCluster analysis identified two distinct subtypes of ccRCC within the training set, designated clear cell type A (ccA) and B (ccB). Based on the core tumors, or most well-defined arrays, in each subtype, logical analysis of data (LAD) defined a small, highly predictive gene set that could then be used to classify additional tumors individually. The subclasses were corroborated in a validation data set of 177 tumors and analyzed for clinical outcome. Based on individual tumor assignment, tumors designated ccA have markedly improved disease-specific survival compared to ccB (median survival of 8.6 vs 2.0 years, P = 0.002). Analyzed by both univariate and multivariate analysis, the classification schema was independently associated with survival. Using patterns of gene expression based on a defined gene set, ccRCC was classified into two robust subclasses based on inherent molecular features that ultimately correspond to marked differences in clinical outcome. This classification schema thus provides a molecular stratification applicable to individual tumors that has implications to influence treatment decisions, define biological mechanisms involved in ccRCC tumor progression, and direct future drug discovery.
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  • Cockerill, Christopher Alan, 1994-, et al. (author)
  • Genomic Consequences of Fragmentation in the Endangered Fennoscandian Arctic Fox (Vulpes lagopus)
  • 2022
  • In: Genes. - : MDPI AG. - 2073-4425. ; 13:11
  • Journal article (peer-reviewed)abstract
    • Accelerating climate change is causing severe habitat fragmentation in the Arctic, threatening the persistence of many cold-adapted species. The Scandinavian arctic fox (Vulpes lagopus) is highly fragmented, with a once continuous, circumpolar distribution, it struggled to recover from a demographic bottleneck in the late 19th century. The future persistence of the entire Scandinavian population is highly dependent on the northernmost Fennoscandian subpopulations (Scandinavia and the Kola Peninsula), to provide a link to the viable Siberian population. By analyzing 43 arctic fox genomes, we quantified genomic variation and inbreeding in these populations. Signatures of genome erosion increased from Siberia to northern Sweden indicating a stepping-stone model of connectivity. In northern Fennoscandia, runs of homozygosity (ROH) were on average ~1.47-fold longer than ROH found in Siberia, stretching almost entire scaffolds. Moreover, consistent with recent inbreeding, northern Fennoscandia harbored more homozygous deleterious mutations, whereas Siberia had more in heterozygous state. This study underlines the value of documenting genome erosion following population fragmentation to identify areas requiring conservation priority. With the increasing fragmentation and isolation of Arctic habitats due to global warming, understanding the genomic and demographic consequences is vital for maintaining evolutionary potential and preventing local extinctions.
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  • Dorrepaal, E, et al. (author)
  • Are growth forms consistent predictors of leaf litter quality and decomposability across peatlands along a latitudinal gradient?
  • 2005
  • In: Journal of Ecology. - : Wiley. - 1365-2745 .- 0022-0477. ; 93:4, s. 817-828
  • Journal article (peer-reviewed)abstract
    • Plant growth forms are widely used to predict the effects of environmental changes, such as climate warming and increased nitrogen deposition, on plant communities, and the consequences of species shifts for carbon and nutrient cycling. We investigated whether the relationship between growth forms and patterns in litter quality and decomposition are independent of environmental conditions and whether growth forms are as good as litter chemistry at predicting decomposability. We used a natural, latitudinal gradient in NW Europe as a spatial analogue for future increases in temperature and nitrogen availability. Our screening of 70 species typical of Sphagnum-dominated peatlands showed that leaf litters of Sphagnum mosses, evergreen and deciduous shrubs, graminoids and forbs differed significantly in litter chemistry and that the ranking of the growth forms was independent of the region for all litter chemistry variables. Differences among growth forms were usually larger than differences related to the environmental gradient. After 8 and 20 months incubation in outdoor, Sphagnum-based decomposition beds, growth forms generally differed in decomposability, but these patterns varied with latitude. Sphagnum litters decomposed slower than other litters in all regions, again explaining its high representation in organic deposits of peatlands. Forb litters generally decomposed fastest, while the differences among the other growth forms were small, particularly at higher latitudes. Multiple regression analyses showed that growth forms were better at predicting leaf litter decomposition than chemical variables in warm-temperate peatlands with a high N-load, but less so in the subarctic, low-N region. Our results indicate that environmental changes may be less important in determining ecosystem leaf litter chemistry directly than are their indirect effects through changes in the relative abundance of growth forms. However, climatic and nutritional constraints in high-latitude peatlands promote convergence towards nutrient-efficient plant traits, resulting in similar decomposition rates of vascular growth forms despite differences in litter chemistry. The usefulness of the growth-form concept in predicting plant community controls on ecosystem functioning is therefore somewhat limited.
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  • Elmhagen, Bodil, et al. (author)
  • Åtgärdsprogram för fjällräv, 2017–2021 : (Vulpes lagopus)
  • 2017
  • Reports (other academic/artistic)abstract
    • Fjällräven är klassificerad som starkt hotad i Sverige och akut hotad i Norge. På 1800-talet var det en vanligt förekommande art, men till följd av intensivt jakttryck reducerades populationen kraftigt i slutet av 1800-talet. Fjällräven fridlystes 1928 i Sverige och 1930 i Norge. Trots skydd har populationen inte återhämtat sig. Detta beror på ett flertal samverkande faktorer, framförallt låg populationsstorlek, ökad konkurrens från rödrävar som expanderar in i fjällvärlden, samt uteblivna eller mer oregelbundna lämmeltoppar som leder till födobrist. Dessutom har inavel och inavelsdepression med ökad dödlighet och minskad reproduktion dokumenterats i vissa delbestånd. Sjukdomar och parasiter utgör ett ytterligare hot mot de små delpopulationernas fortlevnad. Störningar från mänskliga aktiviteter kan utgöra ytterligare bidragande faktorer.År 2015 fanns omkring 240 reproducerande vuxna fjällrävar i Sverige och Norge, vilket utgör ett mått på beståndets minimala storlek. Inom EU är fjällräven en prioriterad art enligt habitatdirektivet, i Sverige är fjällräven fridlyst enligt artskyddsförordningen, och i Norge är fjällräven skyddad med ”fjällrävförskriften” enligt naturmangfoldloven.Åtgärder för att rädda fjällräven genomfördes i Sverige och Finland under 1998–2002 genom EU-Life Nature projektet SEFALO. Projektet fortsatte i en andra fas, SEFALO+ (2003–2008) som även involverade Norge. Båda projekten inkluderade åtgärder som stödutfodring, rödrävsjakt och inventeringar. I Norge startade flera åtgärder 2004 på uppdrag av Miljødirektoratet (tidigare Direktoratet for naturforvaltning). Sedan dess har en kombination av åtgärder genomförts i olika delbestånd: avel och utsättning av valpar, stödutfodring, samt kontroll av rödrävsbestånden. Avelsprojekt för fjällräv startade 2005 och de första valparna sattes ut 2006. Inom EU-Interregprojektet Felles Fjellrev (2010–2013) genomfördes utvidgade åtgärder i Jämtlands län samt Nord- och Sør-Trøndelag, med riktade åtgärder i mindre fjällområden mellan de fyra större delbestånden av fjällräv.För att fjällrävsstammen ska återuppnå en gynnsam bevarandestatus bör bevarandeåtgärderna fortsätta inom ramen för det svensk-norska åtgärdsprogrammet. Den långsiktiga visionen är att skapa en stabil och livskraftig stam med gynnsam bevarandestatus utan behov av ytterligare åtgärder. Det är emellertid långt tills denna vision uppnås och i detta program definieras konkreta målsättningar på lång (2035) och kort (2021) sikt. I detta program föreslås fortsatt genomförande av centrala åtgärder i form av stödutfodring och rödrävskontroll. Dessutom ska orsakerna till rödrävens ökade förekomst på fjället hanteras genom åtgärder mot de faktorer som gynnar expansionen. Avel och utsättning från det norska avelsprojektet, alternativt translokering av rävar mellan delpopulationerna, föreslås som åtgärd för att förstärka små populationer, etablera fjällrävar i mellanområden samt minska graden av inavel. Populationernas hälsostatus bör övervakas och vid ett utbrott ska behandling sättas in. Riktade informationskampanjer ska utformas för att minska konflikt och störning med människan.De åtgärder som förutsätts finansieras av Naturvårdsverket och Miljødirektoratet för genomförande av åtgärdsprogram för hotade arter beräknas totalt uppgå till 15, 1 miljoner kronor respektive 47,6 miljoner kronor under programmets giltighetsperiod 2017–2021.
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  • Fagerlind, Helen, 1975, et al. (author)
  • Development of an In-depth European Accident Causation Database and the Driving Reliability and Error Analysis Method, DREAM 3.0
  • 2008
  • In: 3rd International Conference ESAR (Expert Symposium on Accident Research). - Hannover, Tyskland.
  • Conference paper (other academic/artistic)abstract
    • The SafetyNet project was formulated in part to address the need for safety oriented European road accident data. One of the main tasks included within the project was the development of a methodology for better understanding of accident causation together with the development of an associated database involving data obtained from on-scene or “nearly on-scene” accident investigations. Information from these investigations was complemented by data from follow-up interviews with crash participants to determine critical events and contributory factors to the accident occurrence. A method for classification of accident contributing factors, known as DREAM 3.0, was developed and tested in conjunction with the SafetyNet activities. Collection of data and case analysis for some 1 000 individual crashes have recently been completed and inserted into the database and therefore aggregation analyses of the data are now being undertaken. This paper describes the methodology development, an overview of the database and the initial aggregation analyses.
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  • Fortin, G. M., et al. (author)
  • Glutamate corelease promotes growth and survival of midbrain dopamine neurons
  • 2012
  • In: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 32:48, s. 17477-17491
  • Journal article (peer-reviewed)abstract
    • Recent studies have proposed that glutamate corelease by mesostriatal dopamine (DA) neurons regulates behavioral activation by psychostimulants.How and when glutamate release by DA neurons might play this role remains unclear. Considering evidence for early expression of the type 2 vesicular glutamate transporter in mesencephalic DA neurons, we hypothesized that this cophenotype is particularly important during development. Using a conditional gene knock-out approach to selectively disrupt the Vglut2 gene in mouse DA neurons, we obtained in vitro and in vivo evidence for reduced growth and survival of mesencephalic DA neurons, associated with a decrease in the density of DA innervation in the nucleus accumbens, reduced activity-dependent DA release, and impaired motor behavior. These findings provide strong evidence for a functional role of the glutamatergic cophenotype in the development of mesencephalic DA neurons, opening new perspectives into the pathophysiology of neurodegenerative disorders involving the mesostriatal DA system.
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  • Hasselgren, Malin, et al. (author)
  • Genetic rescue in an inbred Arctic fox (Vulpes lagopus) population
  • 2018
  • In: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 285:1875
  • Journal article (peer-reviewed)abstract
    • Isolation of small populations can reduce fitness through inbreeding depression and impede population growth. Outcrossing with only a few unrelated individuals can increase demographic and genetic viability substantially, but few studies have documented such genetic rescue in natural mammal populations. We investigate the effects of immigration in a subpopulation of the endangered Scandinavian arctic fox (Vulpes lagopus), founded by six individuals and isolated for 9 years at an extremely small population size. Based on a long-term pedigree (105 litters, 543 individuals) combined with individual fitness traits, we found evidence for genetic rescue. Natural immigration and gene flow of three outbred males in 2010 resulted in a reduction in population average inbreeding coefficient (f), from 0.14 to 0.08 within 5 years. Genetic rescue was further supported by 1.9 times higher juvenile survival and 1.3 times higher breeding success in immigrant first-generation offspring compared with inbred offspring. Five years after immigration, the population had more than doubled in size and allelic richness increased by 41%. This is one of few studies that has documented genetic rescue in a natural mammal population suffering from inbreeding depression and contributes to a growing body of data demonstrating the vital connection between genetics and individual fitness.
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  • Hemphill, Elisa June Keeling, et al. (author)
  • Genetic consequences of conservation action: Restoring the arctic fox (Vulpes lagopus) population in Scandinavia
  • 2020
  • In: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 248
  • Journal article (peer-reviewed)abstract
    • The Arctic fox (Vulpes lagopus) population in Fennoscandia experienced a drastic bottleneck in the late 19th century as a result of high hunting pressure. In the 1990s, despite nearly 70 years of protection, the population showed no signs of recovery. In order to mitigate the population decline and facilitate re-establishment, conservation actions including supplementary feeding and red fox culling were implemented in 1998, followed by the reintroduction of foxes from a captive breeding programme, starting in 2006. A positive demographic impact of these actions is evident from a doubling of the population size over the past decade. We used genetic data collected in eight subpopulations between 2008 and 2015 to address whether the recent demographic recovery has been complemented by changes in genetic variation and connectivity between subpopulations. Our results show that genetic variation within subpopulations has increased considerably during the last decade, while genetic differentiation among subpopulations has decreased. A marked shift in metapopulation dynamics is evident during the study period, suggesting substantially increased migration across the metapopulation. This shift followed the recolonization of an extinct subpopulation through the release of foxes from the captive breeding programme and was synchronized in time with the implementation of supplementary feeding and red fox culling in stepping stone patches between core subpopulations in mid-Scandinavia. Indeed, the increase in genetic variation and connectivity in the Scandinavian arctic fox population suggests that metapopulation dynamics have been restored, which may indicate an increase in the long-term viability of the population.
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  • Jalalvand, E, et al. (author)
  • Ciliated neurons lining the central canal sense both fluid movement and pH through ASIC3
  • 2016
  • In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 10002-
  • Journal article (peer-reviewed)abstract
    • Cerebrospinal fluid-contacting (CSF-c) cells are found in all vertebrates but their function has remained elusive. We recently identified one type of laterally projecting CSF-c cell in lamprey spinal cord with neuronal properties that expresses GABA and somatostatin. We show here that these CSF-c neurons respond to both mechanical stimulation and to lowered pH. These effects are most likely mediated by ASIC3-channels, since APETx2, a specific antagonist of ASIC3, blocks them both. Furthermore, lowering of pH as well as application of somatostatin will reduce the locomotor burst rate. The somatostatin receptor antagonist counteracts the effects of both a decrease in pH and of somatostatin. Lateral bending movement imposed on the spinal cord, as would occur during natural swimming, activates CSF-c neurons. Taken together, we show that CSF-c neurons act both as mechanoreceptors and as chemoreceptors through ASIC3 channels, and their action may protect against pH-changes resulting from excessive neuronal activity.
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  • Karlsson, P., et al. (author)
  • Stakeholder consensus for decision making in eye-gaze control technology for children, adolescents and adults with cerebral palsy service provision: findings from a Delphi study
  • 2021
  • In: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 21:1
  • Journal article (peer-reviewed)abstract
    • BackgroundLimited research exists to guide clinical decisions about trialling, selecting, implementing and evaluating eye-gaze control technology. This paper reports on the outcomes of a Delphi study that was conducted to build international stakeholder consensus to inform decision making about trialling and implementing eye-gaze control technology with people with cerebral palsy.MethodsA three-round online Delphi survey was conducted. In Round 1, 126 stakeholders responded to questions identified through an international stakeholder Advisory Panel and systematic reviews. In Round 2, 63 respondents rated the importance of 200 statements generated by in Round 1. In Round 3, 41 respondents rated the importance of the 105 highest ranked statements retained from Round 2.ResultsStakeholders achieved consensus on 94 of the original 200 statements. These statements related to person factors, support networks, the environment, and technical aspects to consider during assessment, trial, implementation and follow-up. Findings reinforced the importance of an individualised approach and that information gathered from the user, their support network and professionals are central when measuring outcomes. Information required to support an application for funding was obtained.ConclusionThis Delphi study has identified issues which are unique to eye-gaze control technology and will enhance its implementation with people with cerebral palsy.
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50.
  • Linde, C., et al. (author)
  • Rationale and design of the PREFERS (Preserved and Reduced Ejection Fraction Epidemiological Regional Study) Stockholm heart failure study : an epidemiological regional study in Stockholm county of 2.1 million inhabitants
  • 2016
  • In: European Journal of Heart Failure. - : John Wiley & Sons. - 1388-9842 .- 1879-0844. ; 18:10, s. 1287-1297
  • Journal article (peer-reviewed)abstract
    • Aims: Heart failure (HF) with preserved (HFpEF) or reduced (HFrEF) ejection fraction is associated with poor prognosis and quality of life. While the incidence of HFrEF is declining and HF treatment is effective, HFpEF is increasing, with no established therapy. PREFERS Stockholm is an epidemiological study with the aim of improving clinical care and research in HF and to find new targets for drug treatment in HFpEF ( https://internwebben.ki.se/sites/default/files/20150605_4d_research_appendix_final.pdf). Methods: Patients with new-onset HF (n = 2000) will be characterized at baseline and after 1-year follow-up by standardized protocols for clinical evaluation, echocardiography, and ECG. In one subset undergoing elective coronary bypass surgery (n = 100) and classified according to LV function, myocardial biopsies will be collected during surgery, and cardiac magnetic resonance (CMR) imaging will be performed at baseline and after 1 year. Blood and tissue samples will be stored in a biobank. We will characterize and compare new-onset HFpEF and HFrEF patients regarding clinical findings and cardiac imaging, genomics, proteomics, and transcriptomics from blood and cardiac biopsies, and by established biomarkers of fibrosis, inflammation, haemodynamics, haemostasis, and thrombosis. The data will be explored by state-of-the-art bioinformatics methods to investigate gene expression patterns, sequence variation, DNA methylation, and post-translational modifications, and using systems biology approaches including pathway and network analysis. Conclusions: In this epidemiological HF study with biopsy studies in a subset of patients, we aim to identify new biomarkers of disease progression and to find pathophysiological mechanisms to support explorations of new treatment regimens for HFpEF. 
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