| 1. |
- Wain, Louise V, et al.
(författare)
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Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:3, s. 416-425
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.
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| 2. |
- Andersson, Stefan, et al.
(författare)
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Metod- och kvalitetsbeskrivning för geografiskt fördelade emissioner till luft under 2017
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sverige rapporterar årligen nationella utsläpp till luft till UNFCCC (FN:s klimatkonvention) och CLRTAP (UNECE:s konvention om gränsöverskridande luftföroreningar), så kallade submissioner. Förutom emissioner på nationell nivå finns även behov av data med högre geografisk upplösning. För regional uppföljning av miljömålen behövs emissioner på kommun- och länsnivå.Detta dokument utgör en metod- och kvalitetsbeskrivning av geografiskt fördelade emissioner för åren 1990, 2000, 2005 samt 2010-2015. Emissionerna presenteras i 45 olika sektorer uppdelade på åtta huvudsektorer. Huvudsektorerna är El och uppvärmning, Industri (energi och processer), Transporter, Produktanvändning, Avfall och avlopp, Internationell luftfart och sjöfart, Jordbruk samt Arbetsmaskiner. Uppdelningen är förändrad jämfört med föregående år vad gäller industrins utsläpp samt utsläppen från energiförförsörjning, se avsnittet Förändringar i nationella totalemissioner samt sektorsindelning, jämfört med föregående år. De ämnen som ingår är växthusgaser, metaller, partiklar och övriga ämnen, totalt 29 ämnen.Arbetet med geografisk fördelning av Sveriges utsläpp till luft är sedan 2007 ett årligt projekt. Projektet har ett långsiktigt perspektiv med målsättningen att stegvis förbättra kvaliteten på geografiskt upplösta emissionsdata.
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| 3. |
- Andersson, Stefan, et al.
(författare)
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Metod- och kvalitetsbeskrivning för geografiskt fördelade emissioner till luft (submission 2018)
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sverige rapporterar årligen nationella utsläpp till luft till UNFCCC (FN:s klimatkonvention) och CLRTAP (UNECE:s konvention om gränsöverskridande luftföroreningar), så kallade submissioner. Förutom emissioner på nationell nivå finns även behov av data med högre geografisk upplösning. För regional uppföljning av miljömålen behövs emissioner på kommun- och länsnivå. Detta dokument utgör en metod- och kvalitetsbeskrivning av geografiskt fördelade emissioner för åren 1990, 2000, 2005 samt 2010-2016, rapporterade i submission 2018.Emissionerna presenteras i 55 olika sektorer uppdelade på nio huvudsektorer. Huvudsektorerna är El och fjärrvärme, Egen uppvärmning av bostäder och lokaler, Industri (energi och processer), Transporter, Arbetsmaskiner, Produktanvändning (inkl. lösningsmedel), Jordbruk, Avfall (inkl. avlopp) samt Utrikes transporter. Uppdelningen är förändrad jämfört med föregående år. För huvudsektorn Utrikes transporter fördelas eller redovisas inga växthusgaser geografiskt.Den geografiska fördelningen utförs huvudsakligen enligt konceptet ”topdown”. Detta innebär att emissioner bryts ner från en nationell totalemission för att uppnå en högre rumslig upplösning på lokal nivå. Nedbrytningen till högre rumslig upplösning kräver en geografisk begränsning av emissionerna och statistik på regional nivå.Metoden för geografisk fördelning tillåter för vissa utsläppskällor en hög rumslig upplösning (t.ex. för vägtrafik och industriprocesser). För flera sektorer är emellertid resultaten otillförlitliga om de ska studeras med högre upplösning än kommunnivå (i vissa fall även länsnivå). Resultaten från den geografiska fördelningen lagras i årsvisa emissionsdatabaser i SMHIs tekniska system för luftvårdsarbete; Airviro. Ur Airviro exporteras emissionerna till Excel-tabeller på läns- och kommunnivå. Emissionerna presenteras även på karta, samt i diagram. Publicering av resultaten sker via www.rus.lst.se. En presentation riktad mot allmänheten ges även på http://utslappisiffror.naturvardsverket.se/.Arbetet med geografisk fördelning av Sveriges utsläpp till luft är sedan 2007 ett årligt projekt. Projektet har ett långsiktigt perspektiv med målsättningen att stegvis förbättra kvaliteten på geografiskt upplösta emissionsdata. Resultaten för alla sektorer presenteras med samma geografiska upplösning även om kvaliteten varierar. På grund av detta krävs det att användare av dessa emissionsdata går igenom kvalitetsbeskrivningen och bedömer om osäkerheterna är acceptabla för den aktuella tillämpningen. Genom retroaktiva omräkningar säkerställs att metodförändringar inte orsakar trendbrott. I vissa fall har dock tillgängliga grunddata (t.ex. statistik) förändrats, vilket kan leda till icke-reella trendbrott.
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| 4. |
- CARLSSON, STEFAN, 1987, et al.
(författare)
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Orgasm-Associated Urinary Incontinence and Sexual Life after Radical Prostatectomy.
- 2011
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Ingår i: The journal of sexual medicine. - : Oxford University Press (OUP). - 1743-6109 .- 1743-6095.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. Involuntary release of urine during sexual climax, orgasm-associated urinary incontinence, occurs frequently after radical prostatectomy. We know little about its prevalence and its effect on sexual satisfaction. Aim. To determine the prevalence of orgasm-associated incontinence after radical prostatectomy and its effect on sexual satisfaction. Methods. Consecutive series, follow-up at one point in calendar time of men having undergone radical prostatectomy (open surgery or robot-assisted laparoscopic surgery) at Karolinska University Hospital, Stockholm, Sweden, 2002-2006. Of the 1,411 eligible men, 1,288 (91%) men completed a study-specific questionnaire. Main Outcome Measure. Prevalence rate of orgasm-associated incontinence. Results. Of the 1,288 men providing information, 691 were sexually active. Altogether, 268 men reported orgasm-associated urinary incontinence, of whom 230 (86%) were otherwise continent. When comparing them with the 422 not reporting the symptom but being sexually active, we found a prevalence ratio (with 95% confidence interval) of 1.5 (1.2-1.8) for not being able to satisfy the partner, 2.1 (1.1-3.5) for avoiding sexual activity because of fear of failing, 1.5 (1.1-2.1) for low orgasmic satisfaction, and 1.4 (1.2-1.7) for having sexual intercourse infrequently. Prevalence ratios increase in prostate-cancer survivors with a higher frequency of orgasm-associated urinary incontinence. Conclusion. We found orgasm-associated urinary incontinence to occur among a fifth of prostate cancer survivors having undergone radical prostatectomy, most of whom are continent when not engaged in sexual activity. The symptom was associated with several aspects of sexual life. Nilsson AE, Carlsson S, Johansson E, Jonsson MN, Adding C, Nyberg T, Steineck G, and Wiklund NP. Orgasm-associated urinary incontinence and sexual life after radical prostatectomy. J Sex Med **;**:**-**.
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| 5. |
- Evangelou, Evangelos, et al.
(författare)
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Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
- 2011
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:2, s. 349-355
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p = 9.2 x 10(-9)), thereby confirming its role as a susceptibility locus for OA. Conclusion The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
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| 6. |
- Maudsdotter, Lisa, 1984-, et al.
(författare)
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Lactobacilli reduce cell cytotoxicity caused by Streptococcus pyogenes by producing lactic acid that degrades the toxic component lipoteichoic acid
- 2011
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 55:4, s. 1622-1628
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Tidskriftsartikel (refereegranskat)abstract
- Lactobacilli are known to prevent colonization by many pathogens; nevertheless, the mechanisms of their protective effect are largely unknown. In this work, we investigated the role of lactobacilli during infection of epithelial cells with group A streptococci (GAS). GAS cause a variety of illnesses ranging from noninvasive disease to more severe invasive infections, such as necrotizing fasciitis and toxic shock-like syndrome. Invasion of deeper tissues is facilitated by GAS-induced apoptosis and cell death. We found that lactobacilli inhibit GAS-induced host cell cytotoxicity and shedding of the complement regulator CD46. Further, survival assays demonstrated that lactic acid secreted by lactobacilli is highly bactericidal toward GAS. In addition, lactic acid treatment of GAS, but not heat killing, prior to infection abolishes the cytotoxic effects against human cells. Since lipoteichoic acid (LTA) of GAS is heat resistant and cytotoxic, we explored the effects of lactic acid on LTA. By applying such an approach, we demonstrate that lactic acid reduces epithelial cell damage caused by GAS by degrading both secreted and cell-bound LTA. Taken together, our experiments reveal a mechanism by which lactobacilli prevent pathogen-induced host cell damage.
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| 7. |
- Sahiström, Fredrik, et al.
(författare)
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Textural evolution of the Lovisa Zn-Pb-(Ag) deposit, Bergslagen, Sweden : insights from microscopy and 3D X-ray tomography
- 2019
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Ingår i: LIFE WITH ORE DEPOSITS ON EARTH, PROCEEDINGS OF THE 15TH SGA BIENNIAL MEETING, 2019, VOLS 1-4. - : SOC GEOLOGY APPLIED MINERAL DEPOSITS-SGA. - 9780852619629 ; , s. 443-446
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Konferensbidrag (refereegranskat)abstract
- The presently mined Lovisa deposit constitutes a c. 1.9 Ga, stratiform Zn-Pb-(Ag) sulphide mineralisation hosted by rhyolite-dominated meta volcanic rocks in the Bergslagen ore province, south central Sweden. The mineralised rock sequence at Lovisa has been subjected to polyphase ductile deformation, amphibolite facies regional metamorphism, and late-stage brittle deformation. The combined effects of these processes have produced a diversity of post-genetic ore textures within the sulphide horizons, including metablastic growth, piercements, ductile and brittle sulphide deformation, and durchbewegung and 'ball ore' textures. Here we report on the character and textural evolution of the Lovisa deposit in conjunction with regional metamorphism and deformation, utilising new data from ore- and electron microscopy combined with 3D tomography by means of novel XRT-XRF drill core scanning technique.
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| 8. |
- Scott, Robert A, et al.
(författare)
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No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels
- 2012
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Ingår i: Diabetes. - Alexandria, VA : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:5, s. 1291-1296
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Tidskriftsartikel (refereegranskat)abstract
- Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.
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| 9. |
- Styrkarsdottir, Unnur, et al.
(författare)
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GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 – 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10 −42 , β = −0.090) and confers risk of hip fracture (P = 1.0 × 10 −8 , OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.
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| 10. |
- Aidas, Kestutis, et al.
(författare)
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The Dalton quantum chemistry program system
- 2014
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Ingår i: WIREs Computational Molecular Science. - : Wiley. - 1759-0876 .- 1759-0884. ; 4:3, s. 269-284
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Tidskriftsartikel (refereegranskat)abstract
- Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, MOller-Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from for a number of UNIX platforms.
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