| 1. |
- Saxena, Richa, et al.
(författare)
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Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5829, s. 1331-1336
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Tidskriftsartikel (refereegranskat)abstract
- New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D - in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1 - and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.
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| 2. |
- Svensson, Per-Arne, 1969, et al.
(författare)
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Characterization of Brown Adipose Tissue in the Human Perirenal Depot
- 2014
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 22:8, s. 1830-1837
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo characterize brown adipose tissue (BAT) in the human perirenal adipose tissue depot. MethodPerirenal adipose tissue biopsies were obtained from 55 healthy kidney donors. Expression analysis was performed using microarray, real-time PCR, immunoblotting and immunohistochemistry. Additional studies using human stem cells were performed. ResultsUCP1 gene expression analysis revealed a large intra-individual variation in the perirenal adipose tissue biopsies. Both multi- and unilocular UCP1-positive adipocytes were detected in several of the adipose tissue samples analyzed by immunohistochemical staining. Microarray analysis identified 54 genes that were overexpressed in UCP1-positive perirenal adipose tissue. Real-time PCR analysis of BAT candidate genes revealed a set of genes that were highly correlated to UCP1 and a set of three transcription factor genes (PRDM16, PGC1, and RXR) that were highly correlated to each other. RXR displayed nuclear immunoreactivity in brown adipocytes and an increased gene expression during brown adipogenesis in human stem cells. ConclusionOur data provides the first molecular characterization of BAT in the perirenal adipose tissue depot. Furthermore, it highlights the transcription factor RXR as a new player in BAT development.
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| 3. |
- Taube, Magdalena, et al.
(författare)
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Evaluation of reference genes for gene expression studies in human brown adipose tissue.
- 2015
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Ingår i: Adipocyte. - : Informa UK Limited. - 2162-3945 .- 2162-397X. ; 4:4, s. 280-5
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Tidskriftsartikel (refereegranskat)abstract
- Human brown adipose tissue (BAT) has during the last 5 year been subjected to an increasing research interest, due to its putative function as a target for future obesity treatments. The most commonly used method for molecular studies of human BAT is the quantitative polymerase chain reaction (qPCR). This method requires normalization to a reference gene (genes with uniform expression under different experimental conditions, e.g. similar expression levels between human BAT and WAT), but so far no evaluation of reference genes for human BAT has been performed. Two different microarray datasets with samples containing human BAT were used to search for genes with low variability in expression levels. Seven genes (FAM96B, GNB1, GNB2, HUWE1, PSMB2, RING1 and TPT1) identified by microarray analysis, and 8 commonly used reference genes (18S, B2M, GAPDH, LRP10, PPIA, RPLP0, UBC, and YWHAZ) were selected and further analyzed by quantitative PCR in both BAT containing perirenal adipose tissue and subcutaneous adipose tissue. Results were analyzed using 2 different algorithms (Normfinder and geNorm). Most of the commonly used reference genes displayed acceptably low variability (geNorm M-values <0.5) in the samples analyzed, but the novel reference genes identified by microarray displayed an even lower variability (M-values <0.25). Our data suggests that PSMB2, GNB2 and GNB1 are suitable novel reference genes for qPCR analysis of human BAT and we recommend that they are included in future gene expression studies of human BAT.
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| 4. |
- Abbott, Allan, et al.
(författare)
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Analgesic prescriptions received by patients before commencing the BOA model of care for osteoarthritis: a Swedish national registry study with matched reference and clinical guideline benchmarking
- 2022
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 93, s. 51-58
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - Swedish clinical guidelines for osteoarthritis (OA) prioritize patient education, exercise, and-if necessary-weight reduction before considering adjunct pharmacological intervention. Contrariwise, we investigated the proportion and type of dispensed analgesic prescriptions in Sweden received by patients during 3 years before commencing non-pharmacological primary care interventions for OA (2008-2016) compared with the general population. Furthermore, we analyzed the proportion of analgesic prescriptions dispensed before (2008-2012) compared with after (2012-2016) guideline publication in terms of concordance with clinical guideline recommendations. Patients and methods - Patients with hip or knee OA (n = 72,069) from the Better Management of OA national quality register receiving non-pharmacological interventions in primary care between 2008 and 2016 were included (OA cohort). An age, sex, and residence matched reference cohort (n = 216,207) was formed from the Swedish Total Population Register. Based on a period 3 years prior to inclusion in the OA cohort, Swedish Prescribed Drug Register data was linked to both the OA and reference cohorts. Results - Compared with the reference cohort, a distinctly larger proportion of the OA cohort had dispensed prescriptions for most types of analgesics, increasing exponentially each year prior to commencing non-pharmacological intervention. Since guideline publication, the proportion of the OA cohort having no dispensed prescription analgesics prior to non-pharmacological primary care intervention concordantly increased by 5.0% (95% CI 4.2-5.9). Furthermore, dispensed prescriptions concordantly decreased for non-selective NSAIDs -8.6% (CI -9.6 to -7.6), weak opioids -6.8% (CI -7.7 to -5.9), glucosamine -9.5% (CI -9.8 to -8.8). and hyaluronic acid -1.6% (CI -1.8 to -1.5) but discordantly increased for strong opioids 2.8% (CI 2.1-3.4) and glucocorticoid intra-articular injection for hip OA 2.1% (CI 1.0-3.1). Interpretation - In Sweden, dispensed prescription of analgesics commonly occurred before initiating non-pharmacological primary care interventions for OA but reduced modestly after guideline publication, which prioritizes non-pharmacological before pharmacological interventions. Additional modest improvements occurred in the stepped-care prioritization of analgesic prescription types. However, future strategies are required to curb an increase of strong opioids prescription for OA and glucocorticoid intra-articular injection for hip OA.
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| 5. |
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| 7. |
- Bergström, Sara, et al.
(författare)
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Miljöbedömning och miljöbeskrivning i väg- och järnvägsprojekt : Vägledning
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna vägledning förmedlar Trafikverkets syn på hur de båda processerna miljöbedömning och miljöbeskrivning bör tillämpas i planläggning och projektering av väg- och järnvägsprojekt, med utgångspunkt från lagkrav, praxis och Trafikverkets erfarenheter. Den tar även upp innehållet i de båda dokumenten miljökonsekvensbeskrivning och miljöbeskrivning som kommer ut av de båda processerna. Vägledningen syftar till att bidra till integrering av miljöaspekter i planläggning och projektering av vägar och järnvägar samt till en god kvalitet på genomförande och redovisning. Den syftar även till att miljöbedömningar och miljöbeskrivningar ska genomföras på ett likartat sätt i hela Trafikverket och få en jämn kvalitet. Vägledningen riktar sig främst till Trafikverkets konsulter och egna miljöspecialister som gör miljöbedömningar och miljöbeskrivningar i Trafikverkets väg- och järnvägsprojekt. Vägledningen ersätter Trafikverkets Handbok om metodik för miljökonsekvensbeskrivning för vägar och järnvägar (Trafikverket 2011:090). Den ersätter också texter om MKB och miljöbeskrivning i Trafikverkets Rapport planläggning av vägar och järnvägar. Vägledningen innehåller bland annat:relevant lagstiftning och målbeskrivning om hur miljö integreras samt miljöbedömningens roll och moment i planläggningens olika skedensamråd, samrådsunderlag, utredning om betydande miljöpåverkan och miljökonsekvensbeskrivningens (MKB) innehåll Trafikverkets syn på hantering av miljöaspekter, behov av att koppla dessa till miljöintressen för vilka konsekvenser beskrivs
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| 8. |
- Brimdyr, Kajsa, et al.
(författare)
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Skin-to-skin contact after birth : Developing a research and practice guideline
- 2023
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 112:8, s. 1633-1643
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Forskningsöversikt (refereegranskat)abstract
- AimSkin-to-skin contact immediately after birth is recognised as an evidence-based best practice and an acknowledged contributor to improved short- and long-term health outcomes including decreased infant mortality. However, the implementation and definition of skin-to-skin contact is inconsistent in both practice and research studies. This project utilised the World Health Organization guideline process to clarify best practice and improve the consistency of application. MethodsThe rigorous guideline development process combines a systematic review with acumen and judgement of experts with a wide range of credentials and experience. ResultsThe developed guideline received a strong recommendation from the Expert Panel. The result concluded that there was a high level of confidence in the evidence and that the practice is not resource intensive. Research gaps were identified and areas for continued work were delineated. ConclusionThe World Health Organization guideline development process reached the conclusion immediate, continuous, uninterrupted skin-to-skin contact should be the standard of care for all mothers and all babies (from 1000 g with experienced staff if assistance is needed), after all modes of birth. Delaying non-essential routine care in favour of uninterrupted skin-to-skin contact after birth has been shown to be safe and allows for the progression of newborns through their instinctive behaviours.
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| 9. |
- Ebrahimi, Babak, 1987, et al.
(författare)
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Estimation of Norwegian Asphalt Surfacing Lifetimes Using Survival Analysis Coupled with Road Spatial Data
- 2019
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Ingår i: Journal of Transportation Engineering Part B: Pavements. - 2573-5438. ; 145:3
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Tidskriftsartikel (refereegranskat)abstract
- Combinations of different factors and their relative importance have a mixed effect on the longevity of pavements, which are essential to be understood to enhance long-term maintenance planning. This study used spatial road data from Norway followed by integrating temporal-spatial and statistical analyses to show a potential approach to estimate the lifetimes of asphalt surfacing. For the statistical part, a stratified Cox proportional hazard model was used to understand the relationship between longevity of surface mixtures and different factors, while avoiding having predefined assumptions rooted in deterministic modeling. In addition, rutting was used as the response variable to determine distress-specific asphalt surfacing lifetimes and to handle censored data. Inclusion of rutting as the response variable showed that the median technical lifetime of asphalt surfacing is about 2 years shorter than that of the maintenance activity records. The results showed the significance of each covariate; however, aggregate nominal maximum size and heavy traffic volume were consistently the significant covariates across the studied traffic classes. In addition, the results were fitted to reference categories in each covariate to show a practical approach to interpret absolute values of lifetimes from a survival table.
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| 10. |
- Eising, Stefanie, et al.
(författare)
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Type 1 diabetes risk analysis on dried blood spot samples from population-based newborns: design and feasibility of an unselected case-control study
- 2007
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Ingår i: Paediatric and Perinatal Epidemiology. - : Wiley. - 0269-5022 .- 1365-3016. ; 21:6, s. 507-517
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Tidskriftsartikel (refereegranskat)abstract
- Development of type 1 diabetes mellitus (T1D) may be triggered pre- or perinatally by multiple factors. Identifying new predisposing T1D markers or combinations of markers in a large, well-characterised case-control collection may be important for future T1D prevention. The present work describes the design and feasibility of a large and unselected case-control study, which will define and evaluate prediction criteria for T1D at the time of birth. Danish registries (Biological Specimen Bank for Neonatal Screening, and the National Discharge Registry) made it possible to identify and collect dried blood spots (DBS) from newborns who later developed T1D (cases) born 1981-2002. DBS samples from 2086 cases and two matching control subjects per case were analysed for genetic and immune factors that are associated with T1D: (a) candidate genes (HLA, INS and CTLA4), (b) cytokines and inflammatory markers, (c) islet auto-antibodies (GAD65A, IA-2A). The objective of the study was to define reliable prediction tools for T1D using samples available at the time of birth. In a unique approach, the study linked a large unselected and population-based sample resource to well-ascertained clinical databases and advanced technology. It combined genetic, immunological and demographic data to develop prediction algorithms. It also provided a resource for future studies in which new genetic markers can be included as they are identified.
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