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1.	Lango Allen, Hana, et al. (författare) Hundreds of variants clustered in genomic loci and biological pathways affect human height. 2010 Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8 Tidskriftsartikel (refereegranskat)abstract Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
2.	Lundell, Anna-Carin, 1976, et al. (författare) Dihydrotestosterone levels at birth associate positively with higher proportions of circulating immature/naïve CD5+ B cells in boys. 2017 Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1 Tidskriftsartikel (refereegranskat)abstract Boys present with higher proportions of immature/naïve CD5+ B cells than girls up to 3 years of age. Boys also have higher fractions of regulatory T cells (Tregs) in early infancy, but the mechanisms for these sex-related differences are unknown. In the prospective FARMFLORA follow-up study of 23 boys and 25 girls, we investigated if these immunological differences remained at 8 years of age. We also examined if testosterone or dihydrotestosterone (DHT) levels at birth and at 8 years of age were associated with immune maturation. Immunological variables and androgen levels were examined and measured in blood samples obtained at birth, 3-5 days and at 8 years of age. Boys had higher proportions of CD5+ and immature/transitional CD24hiCD38hi B cells, whereas girls had higher fractions of B cells with a memory phenotype at 8 years of age. School-aged boys also presented with higher frequencies of Tregs, and a greater capacity to produce T-cell-associated cytokines. Among boys, higher cord blood DHT levels were associated with higher proportions of CD5+ B cells in early infancy and at 8 years of life. These results suggest that DHT actions in utero might be involved in the mechanism for delayed peripheral B-cell maturation in boys.
3.	Nilsson, Maria E., et al. (författare) Measurement of a comprehensive sex steroid profile in rodent serum by high-sensitive gas chromatography-tandem mass spectrometry. 2015 Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 156:7, s. 2492-502 Tidskriftsartikel (refereegranskat)abstract Accurate measurement of sex steroid concentrations in rodent serum is essential to evaluate mouse and rat models for sex steroid-related disorders. The aim of the present study was to develop a sensitive and specific gas chromatography-tandem mass spectrometry (GC-MS/MS) method to assess a comprehensive sex steroid profile in rodent serum. A major effort was invested in reaching an exceptionally high sensitivity for measuring serum estradiol concentrations. We established a GC-MS/MS assay with a lower limit of detection for estradiol, estrone, testosterone, dihydrotestosterone, progesterone, androstenedione and dehydroepiandrosterone of 0.3, 0.5, 4, 1.6, 8, 4 and 50 pg/ml, respectively, while the corresponding values for the lower limit of quantification were 0.5, 0.5, 8, 2.5, 74, 12 and 400 pg/ml, respectively. Calibration curves were linear, intra- and inter-assay CVs were low and accuracy was excellent for all analytes. The established assay was used to accurately measure a comprehensive sex steroid profile in female rats and mice according to estrus cycle phase. In addition, we characterized the impact of age, sex, gonadectomy, and estradiol treatment on serum concentrations of these sex hormones in mice. In conclusion, we have established a highly sensitive and specific GC-MS/MS method to assess a comprehensive sex steroid profile in rodent serum in a single run. This GC-MS/MS assay has, to the best of our knowledge, the best detectability reported for estradiol. Our method therefore represents an ideal tool to characterize sex steroid metabolism in a variety of sex steroid-related rodent models and in human samples with low estradiol levels.
4.	Wilhelmson, Anna S K, et al. (författare) Androgens regulate bone marrow B lymphopoiesis in male mice by targeting osteoblast-lineage cells. 2015 Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 156:4, s. 1228-36 Tidskriftsartikel (refereegranskat)abstract Testosterone has profound immune-modulatory actions, which may be important for the sexual dimorphism in immune-related disorders, such as autoimmune diseases. A well-known effect of androgens is inhibition of bone marrow B lymphopoiesis; however, a plausible target cell for this effect has not yet been presented. The aim of this study was to determine the target cell for androgen-mediated regulation of bone marrow B lymphopoiesis in males. We confirm higher number of bone marrow B cells in male mice with global inactivation of the androgen receptor (AR) and these global AR knockout (G-ARKO) mice had increased number of B cell precursors from the pro-B stage. Because osteoblast-lineage cells are known to support B lymphopoiesis at the pro-B stage, we investigated the effect on B lymphopoiesis in osteoblast-lineage cell-specific ARKO (O-ARKO) mice; O-ARKO mice had increased number of B cells in the bone marrow, and the number of B cell precursors was increased from the pro-B stage, demonstrating that O-ARKO mimics the bone marrow B lymphopoiesis pattern of G-ARKO mice. By contrast, O-ARKO mice displayed only minor changes in B cell numbers in the splenic compartment compared with G-ARKO. Further, O-ARKO mice had moderately reduced number of bone trabeculae in the vertebrae, whereas cortical bone was unaffected. In conclusion, androgens exert inhibitory effects on bone marrow B lymphopoiesis in males by targeting the AR in osteoblast-lineage cells. The identification of the likely target cell for androgen-mediated regulation of bone marrow B lymphopoiesis will contribute to elucidation of the mechanisms by which androgens modulate immune-related disorders.
5.	Beausang, Angela, et al. (författare) "Möjligheten att rädda några av dessa kvinnors liv har inte vägts in" 2014 Ingår i: Dagens Medicin. - : Dagens Medicin. Tidskriftsartikel (populärvet., debatt m.m.)abstract Namnet på Socialstyrelsens vägledning lyder: Hur upptäcka våldsutsatthet? Ja, det kan man verkligen fråga sig efter att ha läst detta föga vägledande dokument, skriver ett stort antal kritiska debattörer.
6.	Benrick, Anna, 1979, et al. (författare) A non-conservative polymorphism in the IL-6 signal transducer (IL6ST)/gp130 is associated with myocardial infarction in a hypertensive population. 2008 Ingår i: Regulatory peptides. - : Elsevier BV. - 0167-0115. ; 146:1-3, s. 189-96 Tidskriftsartikel (refereegranskat)abstract Inflammation is a key component in the development of atherosclerosis, and myocardial infarction (MI); therefore we investigated the association between an interleukin-6 signal transducer (IL6ST)/gp130 polymorphism, gp130 function and risk of MI. Structural modeling suggested that a non-conservative single nucleotide polymorphism in the gp130, Gly148Arg, can change the stability and functional properties of the molecule. In vitro studies were done with BAF/3 cells lacking endogenous gp130. Cells stably transfected with the gp130 148Arg variant proliferated less and showed slightly lower STAT-3 phosphorylation in response to gp130 stimulation as compared to cells transfected with gp130 148Gly. In a prospectively followed hypertensive cohort we identified 167 patients who suffered a MI during the study and compared them to matched controls (mean age 57 years, 73% males, n=482). Carriers of the 148Arg variant (f(Arg)=0.12) of the gp130 receptor had decreased odds ratio for MI in univariate analysis (0.56, 95% CI 0.34-0.91, p=0.02). In conclusion, a genetically determined structural variant of the IL-6 receptor subunit gp130 is, independently of other known risk factors, associated with decreased risk of MI. The variant is also associated with decreased IL-6 responsiveness and could lead to a configuration change in the gp130 receptor.
7.	Berglund, Torkel, et al. (författare) Slutrapport, fält- och laboratorietest av substanser för aktivering av det egna försvaret hos gran- och tallplantor 2012 Rapport (övrigt vetenskapligt/konstnärligt)
8.	Berndt, Sonja I., et al. (författare) Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture 2013 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69 Tidskriftsartikel (refereegranskat)abstract Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
9.	Bruce, Peter, 1986-, et al. (författare) Inconsistencies in How Environmental Risk Is Evaluated in Sweden for Dumping Dredged Sediment at Sea 2021 Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 8 Tidskriftsartikel (refereegranskat)abstract Millions of tons of dredged sediment are dumped at sea annually. International conventions limit dumping when there is a risk of adverse ecological effects, for example if the sediment is contaminated. However, the perception of risk differs substantially among stakeholders and in Sweden there is a lack of guidelines for how to address such risk. In the current study, we examined exemptions to the Swedish ban on dumping at sea, to explore the extent of dumping and how ecological aspects were considered in the evaluation of risks. We analyzed data from all cases granted exemption by county administrative boards and all court cases considering exemption to the ban from the beginning of 2015 to June 2020. We found that while dumping is the least common alternative management method for dredged sediment in total number of cases (98/792), dumping is the main method in terms of volume (30.8/38.2 million m3). When considering exemptions, the courts mainly evaluated the risk of exposure to contaminants and resuspended sediment for the environment adjacent to the dumpsite. The risks from contaminants were characterized based on various lines of reasoning, mainly relying on reference values not based on a scientific correlation to environmental risk. We argue that the evaluations were not in line with current regulations and international conventions as they insufficiently accounted for the ecotoxicological risk of the dumped sediment. These issues are potentially similar in other Baltic Sea countries, where there is a similar dependency on binary chemical limit values.
10.	Coviello, Andrea D, et al. (författare) A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation. 2012 Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 8:7 Tidskriftsartikel (refereegranskat)abstract Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p=1.8×10(-106)), PRMT6 (rs17496332, 1p13.3, p=1.4×10(-11)), GCKR (rs780093, 2p23.3, p=2.2×10(-16)), ZBTB10 (rs440837, 8q21.13, p=3.4×10(-09)), JMJD1C (rs7910927, 10q21.3, p=6.1×10(-35)), SLCO1B1 (rs4149056, 12p12.1, p=1.9×10(-08)), NR2F2 (rs8023580, 15q26.2, p=8.3×10(-12)), ZNF652 (rs2411984, 17q21.32, p=3.5×10(-14)), TDGF3 (rs1573036, Xq22.3, p=4.1×10(-14)), LHCGR (rs10454142, 2p16.3, p=1.3×10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p=2.7×10(-08)), and UGT2B15 (rs293428, 4q13.2, p=5.5×10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p=2.5×10(-08), women p=0.66, heterogeneity p=0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ∼15.6% and ∼8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
11.	Ek, Weronica E, et al. (författare) Exploring the genetics of irritable bowel syndrome: a GWA study in the general population and replication in multinational case-control cohorts. 2015 Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 64, s. 1774-1782 Tidskriftsartikel (refereegranskat)abstract IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies.
12.	Eriksson, Anna-Lena, 1971, et al. (författare) Genetic Determinants of Circulating Estrogen Levels and Evidence of a Causal Effect of Estradiol on Bone Density in Men. 2018 Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 103:3, s. 991-1004 Tidskriftsartikel (refereegranskat)abstract Serum estradiol (E2) and estrone (E1) levels exhibit substantial heritability.To investigate the genetic regulation of serum E2 and E1 in men.Genome-wide association study in 11,097 men of European origin from nine epidemiological cohorts.Genetic determinants of serum E2 and E1 levels.Variants in/near CYP19A1 demonstrated the strongest evidence for association with E2, resolving to three independent signals. Two additional independent signals were found on the X chromosome; FAMily with sequence similarity 9, member B (FAM9B), rs5934505 (P = 3.4 × 10-8) and Xq27.3, rs5951794 (P = 3.1 × 10-10). E1 signals were found in CYP19A1 (rs2899472, P = 5.5 × 10-23), in Tripartite motif containing 4 (TRIM4; rs17277546, P = 5.8 × 10-14), and CYP11B1/B2 (rs10093796, P = 1.2 × 10-8). E2 signals in CYP19A1 and FAM9B were associated with bone mineral density (BMD). Mendelian randomization analysis suggested a causal effect of serum E2 on BMD in men. A 1 pg/mL genetically increased E2 was associated with a 0.048 standard deviation increase in lumbar spine BMD (P = 2.8 × 10-12). In men and women combined, CYP19A1 alleles associated with higher E2 levels were associated with lower degrees of insulin resistance.Our findings confirm that CYP19A1 is an important genetic regulator of E2 and E1 levels and strengthen the causal importance of E2 for bone health in men. We also report two independent loci on the X-chromosome for E2, and one locus each in TRIM4 and CYP11B1/B2, for E1.
13.	Eriksson, Anna-Lena, 1971, et al. (författare) The Bone Sparing Effects of 2-Methoxyestradiol Are Mediated via Estrogen Receptor-α in Male Mice. 2016 Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 157:11, s. 4200-4205 Tidskriftsartikel (refereegranskat)abstract 2-Methoxyestradiol (2ME2), a metabolite of 17β-estradiol (E2), exerts bone sparing effects in animal models. We hypothesized that the underlying mechanism is back conversion of 2ME2 to E2, which subsequently acts via estrogen receptor (ER)α. We measured serum E2 levels in orchidectomized wild-type (WT) mice treated with 2ME2 66.6 μg/d or placebo. In placebo-treated animals, E2 was below the detection limit. In 2ME2-treated mice, the serum E2 level was 4.97 ± 0.68 pg/mL. This corresponds to the level found in diesterus in cycling female mice. Next, we investigated bone parameters in orchidectomized WT and ERα knockout mice treated with 2ME2 or placebo for 35 days. 2ME2 (6.66 μg/d) preserved trabecular and cortical bone in WT mice. Trabecular volumetric-bone mineral density was 64 ± 20%, and trabecular bone volume/total volume was 60 ± 20% higher in the metaphyseal region of the femur in the 2ME2 group, compared with placebo (P < .01). Both trabecular number and trabecular thickness were increased (P < .01). Cortical bone mineral content in the diaphyseal region of the femur was 31 ± 3% higher in the 2ME2 group, compared with placebo (P < .001). This was due to larger cortical area (P < .001). Three-point bending showed an increased bone strength in WT 2ME2-treated animals compared with placebo (maximum load [Fmax] +19±5% in the 2ME2 group, P < .05). Importantly, no bone parameter was affected by 2ME2 treatment in ERα knockout mice. In conclusion, 2ME2 treatment of orchidectomized mice results in increased serum E2. ERα mediates the bone sparing effects of 2ME2. The likely mediator of this effect is E2 resulting from back conversion of 2ME2.
14.	Eriksson, Anna-Lena, 1971, et al. (författare) The COMT val158met polymorphism is associated with prevalent fractures in Swedish men. 2008 Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 42:1, s. 107-12 Tidskriftsartikel (refereegranskat)abstract INTRODUCTION: Sex steroids are important for growth and maintenance of the skeleton. Catechol-O-methyltransferase (COMT) is an estrogen degrading enzyme. The COMT val158met polymorphism results in a 60-75% difference in enzyme activity between the val (high activity=H) and met (low activity=L) variants. We have previously reported that this polymorphism is associated with bone mineral density (BMD) in young men. The aim of this study was to investigate associations between COMT val158met, BMD and fractures in elderly men. METHODS: Population-based study of Swedish men 75.4, SD 3.2, years of age. Fractures were reported using standardized questionnaires. Fracture and genotype data were available from 2,822 individuals. RESULTS: Total number of individuals with self-reported fracture was 989 (35.0%). Prevalence of >or=1 fracture was 37.2% in COMT(LL), 35.7% in COMT(HL) and 30.4% in COMT(HH) (p<0.05). Early fractures (50 years of age). The OR for fracture of the non-weight bearing skeleton in COMT(HH) compared with COMT(LL+HL) was 0.74 (95% CI 0.59-0.92). No associations between COMT val158met and BMD were found in this cohort of elderly men. CONCLUSIONS: The COMT val158met polymorphism is associated with life time fracture prevalence in elderly Swedish men. This association is mainly driven by early fractures (
15.	Heid, Iris M, et al. (författare) Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution 2010 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960 Tidskriftsartikel (refereegranskat)abstract Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
16.	Kindenberg, Björn, 1972-, et al. (författare) Budskap bortom raderna : Design-baserad forskning om undervisning för tolkande läsning 2019 Konferensbidrag (refereegranskat)abstract Tolkande och reflekterande läsning av skönlitteratur är en viktig del av ämnena svenska och svenska som andraspråk, inte minst i fostran av demokratiska medborgare (Svedner, 2012). Detta gör litteraturundervisningen till ett viktigt studieobjekt. Även om det genomförts många klassrumsstudier om litteraturundervisning (t.ex. Hultin, 2006; Bergman, 2007; Langer, 2011), har ganska få involverat lärare i forskningsprocessen. Vår studie utgår ifrån en design-baserad ansats (Cobb et al., 2003), där nio lärare från grundskolans tre stadier tillsammans med forskare planerat och genomfört undervisning i syfte att utveckla elevers tolkande och reflekterade läsning av skönlitterära texters budskap. Texters budskap är ett vanligt, men också omstritt (t.ex. Lundström et al., 2011) begrepp. I studien används begreppet budskap pragmatiskt, som en konkret utgångspunkt för undervisning där begreppet sedan breddas och fördjupas genom en iterativ serie av undervisningsinterventioner. I studien har följande forskningsfrågor formulerats: Vad innebär det att urskilja budskap i skönlitterära texter? Vad hindrar och möjliggör för elever att urskilja budskap i skönlitterära texter? Hur kan elevers förmåga att urskilja texters budskap fördjupas genom undervisning? Langers (2011) läsarpositioner används som ett teoretiskt och metodologiskt ramverk som väglett analys och undervisningsdesign. Det empiriska materialet består av elevtexter, inspelade elevsamtal, inspelade undervisningsavsnitt, lärares undervisningsmaterial och inspelade samtal mellan lärare och forskare. Resultatet visar bland annat att specifika undervisningsaktiviteter, exempelvis att försätta elever i situationer av aktivt budskapsskapande fördjupar elevers tolkning av text. Vidare visar resultaten att lärarens stöttning både kan underlätta och hindra elevers tolkning av text.
17.	Locke, Adam E, et al. (författare) Genetic studies of body mass index yield new insights for obesity biology. 2015 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401 Tidskriftsartikel (refereegranskat)abstract Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
18.	Lundell, Anna-Carin, 1976, et al. (författare) Umbilical Cord Blood Androgen Levels in Girls and Boys Assessed by Gas Chromatography-Tandem Mass Spectrometry. 2017 Ingår i: The Journal of steroid biochemistry and molecular biology. - : Elsevier BV. - 1879-1220 .- 0960-0760. ; 171, s. 195-200 Tidskriftsartikel (refereegranskat)abstract Androgen exposure of the fetus during gestation plays an important role in human physiology and pathophysiology, but assessment of androgens, in particular dihydrotestosterone (DHT), in human umbilical cord blood is technically challenging. The aim of this study was to assess umbilical cord androgen levels, including DHT, at birth by a highly sensitive assay, and study their association with sex of the infant, sex-hormone-binding globulin (SHBG) levels, and gestational age at delivery. Swedish infants (27 girls, 26 boys) were recruited at maternity care clinics in Southern Sweden. Umbilical cord blood levels of dehydroepiandrosterone (DHEA), androstenedione, testosterone and DHT at delivery were assessed by a gas chromatography-tandem mass spectrometry assay. Cord blood levels of DHT were 2.4-fold higher in boys (median 27.8pg/mL) than in girls (11.5pg/mL), while the sex difference was less pronounced for testosterone (1.3-fold higher in boys) and non-significant for DHEA and androstenedione. Gestational age at delivery associated inversely with DHT levels in boys and with DHEA levels in girls. There was a strong inverse correlation between SHBG and DHEA in both sexes, while there were no associations between SHBG and testosterone or DHT levels. In conclusion, using state of the art technology, we report that there is a pronounced sexual dimorphism in human umbilical cord blood DHT levels. The possibility to assess a complete androgen profile in human cord blood opens up for future increased understanding of the biological impact of the fetal androgen milieu.
19.	Mellström, Dan, et al. (författare) Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men : MrOS Sweden 2006 Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 21:4, s. 529-535 Tidskriftsartikel (refereegranskat)abstract The role of androgens for bone health in elderly men is unclear. We show that free testosterone within the normal range is a predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly Swedish men. INTRODUCTION: Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Previous studies have clearly shown that serum levels of estradiol are associated with BMD, whereas more conflicting data have been presented regarding the predictive value of testosterone (T) for bone health in elderly men. The aim of this study was to investigate if serum levels of T are associated with BMD and/or prevalent fractures in a large cohort of elderly men. MATERIALS AND METHODS: In the Swedish part of the MrOS study (n = 2908; average age, 75.4 years), bone parameters were measured using DXA, and prevalent fractures were recorded using standardized questionnaires and by vertebral X-ray analyses. Serum levels of total T, total estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by radioimmunoassay, and free T (FT) and free E2 (FE2) were derived from the mass action equations. Height, weight, age, physical activity, smoking habits, and calcium intake were included together with FT and FE2 in regression models for BMD. RESULTS: FT was an independent positive predictor of BMD in total body, total hip, femur trochanter, and arm but not in the lumbar spine. The highest independent predictive value of FT was found in the arm and the hip (with a relatively high content of cortical bone). FE2 was an independent predictor of BMD at all bone sites studied, and the highest predictive value was seen for lumbar spine (with relatively high content of trabecular bone) BMD. FT but not FE2 was a positive predictor of total body bone area and BMC. FT levels below the median were independent predictors of prevalent osteoporosis-related fractures (OR, 1.56; 95% CI, 1.14-2.14; p < 0.01) and X-ray-verified vertebral fractures (OR, 2.00; 95% CI, 1.34-2.86; p < 0.001). The predictive value of FT for prevalent fractures was not affected by adjustment for BMD. CONCLUSIONS: These findings show that variation of FT within the normal range is an independent but modest predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly men. Our data indicate that not only estrogens but also androgens are of importance for bone health in elderly men. Longitudinal studies investigating the predictive value of T for fracture risk in elderly men are required.
20.	Mellström, Dan, 1945, et al. (författare) Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden. 2006 Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 0884-0431. ; 21:4, s. 529-35 Tidskriftsartikel (refereegranskat)abstract The role of androgens for bone health in elderly men is unclear. We show that free testosterone within the normal range is a predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly Swedish men. INTRODUCTION: Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Previous studies have clearly shown that serum levels of estradiol are associated with BMD, whereas more conflicting data have been presented regarding the predictive value of testosterone (T) for bone health in elderly men. The aim of this study was to investigate if serum levels of T are associated with BMD and/or prevalent fractures in a large cohort of elderly men. MATERIALS AND METHODS: In the Swedish part of the MrOS study (n = 2908; average age, 75.4 years), bone parameters were measured using DXA, and prevalent fractures were recorded using standardized questionnaires and by vertebral X-ray analyses. Serum levels of total T, total estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by radioimmunoassay, and free T (FT) and free E2 (FE2) were derived from the mass action equations. Height, weight, age, physical activity, smoking habits, and calcium intake were included together with FT and FE2 in regression models for BMD. RESULTS: FT was an independent positive predictor of BMD in total body, total hip, femur trochanter, and arm but not in the lumbar spine. The highest independent predictive value of FT was found in the arm and the hip (with a relatively high content of cortical bone). FE2 was an independent predictor of BMD at all bone sites studied, and the highest predictive value was seen for lumbar spine (with relatively high content of trabecular bone) BMD. FT but not FE2 was a positive predictor of total body bone area and BMC. FT levels below the median were independent predictors of prevalent osteoporosis-related fractures (OR, 1.56; 95% CI, 1.14-2.14; p < 0.01) and X-ray-verified vertebral fractures (OR, 2.00; 95% CI, 1.34-2.86; p < 0.001). The predictive value of FT for prevalent fractures was not affected by adjustment for BMD. CONCLUSIONS: These findings show that variation of FT within the normal range is an independent but modest predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly men. Our data indicate that not only estrogens but also androgens are of importance for bone health in elderly men. Longitudinal studies investigating the predictive value of T for fracture risk in elderly men are required.
21.	Monstein, Hans-Jurg, 1946-, et al. (författare) Vasopressin receptor mRNA expression in the human gastrointestinal tract 2008 Ingår i: European Surgical Research. - : S. Karger AG. - 0014-312X .- 1421-9921. ; 40:1, s. 34-40 Tidskriftsartikel (refereegranskat)abstract Background/Aim: Vasopressin and oxytocin are closely related peptides, and both exert effects on the gastrointestinal function. In the present study, we wanted to map the expression of vasopressin receptor mRNAs (V1a, V1b/V3, and V2) in nontumorous tissue biopsy specimens of human gastrointestinal tract and surrounding tissues. Methods: Total and polyA+ RNAs were isolated from human tissue biopsy specimens using an automated nucleic acid extractor and, subsequently, converted into single-stranded cDNA. Seminested PCR amplifications were carried out, using gene-specific V1a, V1b/V3, and V2 receptor primers. The PCR amplicons were partially sequenced to confirm their identity. Results: The present study demonstrated the expression of vasopressin receptor mRNAs in human gastrointestinal tract, pancreas, kidney, lung, brain, and ovary. The expression pattern varied between different parts of the gastrointestinal tract. In the colon ascendens, V1a receptor mRNA expression could not be detected in 3 out of 4 analyzed tissue biopsy specimens. On the other hand, all the vasopressin receptor mRNAs were expressed in all colon transversum biopsy samples. Conclusions: V1a, V1b/V3, and V2 receptor mRNAs are widely expressed throughout human gastrointestinal tract and surrounding tissues. The data obtained provide information for further mapping and determination of the physiological role of the vasopressin receptor mRNA expression in normal and tumorous tissues.
22.	Ohlsson, Anna B., et al. (författare) UV-B Exposure of Indoor-Grown Picea abies Seedlings Causes an Epigenetic Effect and Selective Emission of Terpenes 2013 Ingår i: Zeitschrift für Naturforschung C - A Journal of Biosciences. - Tübingen : Verlag der Zeitschrift für Naturforschung. - 0939-5075 .- 1865-7125. ; 68:3-4, s. 139-147 Tidskriftsartikel (refereegranskat)abstract Terpenoids are involved in various defensive functions in plants, especially conifers. Epigenetic mechanisms, for example DNA methylation, can influence plant defence systems. The purpose of the present study was to investigate the influence of UV-B exposure on the release of terpenoids from spruce seedlings and on needle DNA methylation. Ten-week-old seedlings grown indoors were exposed to UV-B radiation during 4 h, and the volatile compounds emitted from the seedlings were analysed. Analysis of the volatiles 1, 3, and 22 d after this UV-B exposure showed that bornyl acetate, borneol, myrcene, and limonene contents increased during the first 3 days, while at day 22 the level of emission had returned to the control level. UV-B exposure decreased the level of DNA methylation in needles of young seedlings, reflected in methylation changes in CCGG sequences. Exposure of young seedlings to UV-B radiation might be a way to potentiate the general defensive capacity, improving their ability to survive in outdoor conditions. UV-B-induced defence is discussed in the light of epigenetic mechanisms.
23.	Ohlsson, Claes, 1965, et al. (författare) Genetic determinants of serum testosterone concentrations in men. 2011 Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 7:10 Tidskriftsartikel (refereegranskat)abstract Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n=871) and two de novo replication cohorts (n=4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p=1.2×10(-41) and rs6258, p=2.3×10(-22)). Subjects with ≥ 3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p=5.6×10(-16)). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.
24.	Ohlsson, Lars, et al. (författare) Increased level of circulating cell-free mitochondrial DNA due to a single bout of strenuous physical exercise 2020 Ingår i: European Journal of Applied Physiology. - : Springer. - 1439-6319 .- 1439-6327. ; 120, s. 897-905 Tidskriftsartikel (refereegranskat)abstract Purpose Physical exercise is reported to affect the immune response in various ways. Thus, the levels of pro-inflammatory cytokines as well as the abundance of circulating leukocytes are changed. In this study, the occurence of circulating cell-free mitochondrial DNA (cfmtDNA) and nuclear DNA (nDNA) was investigated in connection with a single bout of strenuous physical exercise. Methods Healthy volunteers performed a controlled ergo-spirometry cycle test and venous blood samples were taken at different time-points to analyze the concentration of blood components before, during and after the test. The number of circulating leukocytes was measured, as well as secretion of the soluble urokinase activator receptor (suPAR). Results Cf-mtDNA significantly increased during exercise, compared to baseline values and after 30 and 90 min of rest. Circulating leukocytes increased during exercise, but returned to baseline levels afterwards. Surface expression of the urokinase plasminogen activating receptor (uPAR) on neutrophils decreased significantly during exercise. The concentration of suPAR tended to increase during exercise but only significantly after 90 min of rest. Conclusion Increased concentration of cf-mtDNA indicates that cell damage takes place during high intensity training. Hypoxia and tissue damage are likely causes of cf-mtDNA from muscle cells. The levels of cf-mtDNA remain high during the initial rest, due to the decreasing numbers of leukocytes normally clearing the plasma from cf-mtDNA. The increased levels of suPAR further emphasize that strenuous physical exercise causes a reaction similar to inflammation. Further studies are needed to detect the source of increased cf-mtDNA and the corresponding increase of suPAR liberation.
25.	Poborilova, Zuzana, et al. (författare) DNA hypomethylation concomitant with the overproduction of ROS induced by naphthoquinone juglone on tobacco BY-2 suspension cells 2015 Ingår i: Environmental and Experimental Botany. - : Elsevier BV. - 0098-8472 .- 1873-7307. ; 113, s. 28-39 Tidskriftsartikel (refereegranskat)abstract Juglone, 5-hydroxy-1,4-naphthoquinone, is a naturally occurring plant secondary metabolite with allelopathic and cytotoxic properties. The cytotoxic effect of juglone and changes at the level of DNA methylation were investigated on a plant cell model, tobacco BY-2 cell suspension culture. We found that juglone in a concentration-dependent manner inhibits cell growth and causes creation of reactive oxygen species (ROS) that were visible mainly in nucleus, nucleolus, cytoplasm, and plasma membrane. Analysis of the changes in DNA methylation level using Luminometric Methylation Assay showed that juglone at the concentrations of 60 and 80 mu m causes hypomethylation of DNA. Decrease in DNA methylation was confirmed by the more sensitive technique, confocal immunofluorescence microscopy, already at 30 mu m, and was accompanied by significant overproduction of hydrogen peroxide, hydroxyl radicals, and superoxide anion radicals. The highest percentage of the signs of programed cell death, especially apoptic-like bodies that indicate DNA fragmentation was observed at 30 mu m of juglone. On the basis of results we suggest that overproduction of ROS is the main mechanism that causes hypomethylation of DNA, which may contribute to the initiation of the programmed cell death.
26.	Poborilova, Zuzana, et al. (författare) DNA methylation changes caused by lawsone 2014 Ingår i: International Journal of Agricultural and Biosystems Engineering. - 2319-3913. ; 8:7, s. 654-657 Tidskriftsartikel (refereegranskat)
27.	Schrage, Benedikt, et al. (författare) Lower socioeconomic status predicts higher mortality and morbidity in patients with heart failure 2021 Ingår i: Heart. - : BMJ PUBLISHING GROUP. - 1355-6037 .- 1468-201X. ; 107:3, s. 229-236 Tidskriftsartikel (refereegranskat)abstract Objective It is not fully understood whether and how socioeconomic status (SES) has a prognostic impact in patients with heart failure (HF). We assessed SES and its association with patient characteristics and outcomes in a contemporary and well-characterised HF cohort. Methods Socioeconomic risk factors (SERF) were defined in the Swedish HF Registry based on income (low vs high according to the annual median value), education level (no degree/compulsory school vs university/secondary school) and living arrangement (living alone vs cohabitating). Results Of 44 631 patients, 21% had no, 33% one, 30% two and 16% three SERF. Patient characteristics strongly and independently associated with lower SES were female sex and no specialist referral. Additional independent associations were older age, more severe HF, heavier comorbidity burden, use of diuretics and less use of HF devices. Lower SES was associated with higher risk of HF hospitalisation/mortality, and overall cardiovascular and non-cardiovascular events. These associations persisted after extensive adjustment for patient characteristics, treatments and care. The magnitude of the association increased linearly with the increasing number of coexistent SERF: HR (95% CI) 1.09 (1.05 to 1.13) for one, 1.16 (1.12 to 1.20) for two and 1.22 (1.18 to 1.28) for three SERF (p<0.01). Conclusions In a contemporary and well-characterised HF cohort and after comprehensive adjustment for confounders, lower SES was linked with multiple factors such as less use of HF devices and age, but most strongly with female sex and lack of specialist referral; and associated with greater risk of morbidity/mortality.
28.	Speliotes, Elizabeth K., et al. (författare) Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index 2010 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948 Tidskriftsartikel (refereegranskat)abstract Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
29.	Stenvall, Anna, et al. (författare) Relationships between uptake of [68Ga]Ga-DOTA-TATE and absorbed dose in [177Lu]Lu-DOTA-TATE therapy 2022 Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 12:1 Tidskriftsartikel (refereegranskat)abstract Background: Somatostatin receptor 68Ga PET imaging is standard for evaluation of a patient’s suitability for 177Lu peptide receptor radionuclide therapy of neuroendocrine tumours (NETs). The 68Ga PET serves to ensure sufficient somatostatin receptor expression, commonly evaluated qualitatively. The aim of this study is to investigate the quantitative relationships between uptake in 68Ga PET and absorbed doses in 177Lu therapy. Method: Eighteen patients underwent [68Ga]Ga-DOTA-TATE PET imaging within 20 weeks prior to their first cycle of [177Lu]Lu-DOTA-TATE. Absorbed doses for therapy were estimated for tumours, kidney, spleen, and normal liver parenchyma using a hybrid SPECT/CT–planar method. Gallium-68 activity concentrations were retrieved from PET images and also used to calculate SUVs and normalized SUVs, using blood and tissue for normalization. The 68Ga activity concentrations per injected activity, SUVs, and normalized SUVs were compared with 177Lu activity concentrations 1 d post-injection and 177Lu absorbed doses. For tumours, for which there was a variable number per patient, both inter- and intra-patient correlations were analysed. Furthermore, the prediction of 177Lu tumour absorbed doses based on a combination of tumour-specific 68Ga activity concentrations and group-based estimates of the effective half-lives for grade 1 and 2 NETs was explored. Results: For normal organs, only spleen showed a significant correlation between the 68Ga activity concentration and 177Lu absorbed dose (r = 0.6). For tumours, significant, but moderate, correlations were obtained, with respect to both inter-patient (r = 0.7) and intra-patient (r = 0.45) analyses. The correlations to absorbed doses did not improve when using 68Ga SUVs or normalized SUVs. The relationship between activity uptakes for 68Ga PET and 177Lu SPECT was stronger, with correlation coefficients r = 0.8 for both inter- and intra-patient analyses. The 177Lu absorbed dose to tumour could be predicted from the 68Ga activity concentrations with a 95% coverage interval of − 65% to 248%. Conclusions: On a group level, a high uptake of [68Ga]Ga-DOTA-TATE is associated with high absorbed doses at 177Lu-DOTA-TATE therapy, but the relationship has a limited potential with respect to individual absorbed dose planning. Using SUV or SUV normalized to reference tissues do not improve correlations compared with using activity concentration per injected activity.
30.	Strandberg, Louise, 1981, et al. (författare) IL6 and IL1B polymorphisms are associated with fat mass in older men: the MrOS Study Sweden. 2008 Ingår i: Obesity (Silver Spring, Md.). - : Wiley. - 1930-7381 .- 1930-739X. ; 16:3, s. 710-3 Tidskriftsartikel (refereegranskat)abstract There is growing evidence that immune functions are linked to the regulation of body fat. Our studies of knockout mice indicate that both endogenous interleukin (IL)-6 and IL-1 can suppress mature-onset obesity. We now investigated whether four common polymorphisms of the IL6 and IL1 systems are associated with the fat mass measured with dual-energy X-ray absorptiometry (DXA) in elderly men (n = 3,014). The study subjects were from the Swedish part of the MrOS multicenter population study and 69-81 years of age. The IL6 -174 G>C (Minor allele frequency (MAF) = 48%) gene promoter polymorphism was associated with the primary outcome total fat mass (P = 0.006) and regional fat masses, but not with lean body mass. The IL1B -31T>C (MAF = 34%) polymorphism was also associated with total fat (P = 0.007) and regional fat masses, but not lean body mass. The IL-1 receptor antagonist (IL-1ra) gene (IL1RN) +2018 T>C (MAF = 27%) polymorphism (in linkage disequilibrium (LD) with a well-studied variable number tandem repeat of 86 base pair (bp)) and IL1B +3953 C>T (MAF = 26%) polymorphism were not associated with total fat mass. In conclusion, the IL-1 and IL-6 systems, shown to suppress mature-onset obesity in experimental animals, contain gene polymorphisms that are associated with fat, but not lean, mass in elderly men.
31.	Wernstedt, Ingrid, 1978, et al. (författare) A common polymorphism in the interleukin-6 gene promoter is associated with overweight 2004 Ingår i: Int J Obes Relat Metab Disord. ; 28:10, s. 1272-9 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Human body fat mass is to a large extent genetically determined, but little is known about the susceptibility genes for common obesity. Interleukin-6 (IL-6) suppresses body fat mass in rodents, and IL-6 treatment increases energy expenditure in both rodents and humans. The -174 G/C single-nucleotide polymorphism (SNP) in the IL-6 gene promoter is common in many populations, and -174 C-containing promoters have been found to be weaker enhancers of transcription. Moreover, a SNP at position -572 in the IL-6 promoter has recently been reported to affect transcription. The objective was to investigate the association between the IL-6 gene promoter SNPs and obesity. DESIGN: Trans-sectional association study of IL-6 gene promoter SNPs and indices of obesity. SUBJECTS: Two study populations, the larger one consisting of hypertensive individuals (mean age 57 y, 73% males, n=485) and the other consisting of 20 y younger nonobese healthy females (n=74). MEASUREMENTS: Genotyping for the -174 IL-6 G/C and the -572 G/C SNPs, body mass index (BMI), serum leptin levels, serum IL-6 levels, C-reactive protein, fasting blood glucose and various blood lipids. RESULTS: The common -174 C allele (f(C)=0.46), but not any -572 allele, was associated with higher BMI and higher serum leptin levels in both study populations. In the larger population, there were significant odds ratios for the association of CC (2.13) and GC (1.76) genotypes with overweight (BMI>25 kg/m(2)). Moreover, as the C allele was common, it accounted for a significant population-attributable risk of overweight (12%; CI 2-21%), although its average effect was modest in this sample. CONCLUSION: Genetically determined individual differences in production of IL-6 may be relevant for the regulation of body fat mass.
32.	Wu, Jianyao, et al. (författare) Enzalutamide Reduces the Bone Mass in the Axial but not the Appendicular Skeleton in Male Mice. 2016 Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 157:2, s. 969-977 Tidskriftsartikel (refereegranskat)abstract Testosterone is a crucial regulator of the skeleton but the role of the androgen receptor (AR) for the maintenance of the adult male skeleton is unclear. In the present study, the role of the AR for bone metabolism and skeletal growth after sexual maturation was evaluated by means of the drug enzalutamide, which is a new AR antagonist used in the treatment of prostate cancer patients. Nine-week-old male mice were treated with 10, 30, or 100 mg/kg/day of enzalutamide for 21 days or were surgically castrated, and compared with vehicle-treated gonadal intact mice. Although orchidectomy (orx) reduced the cortical bone thickness and trabecular bone volume fraction in the appendicular skeleton, these parameters were unaffected by enzalutamide. In contrast, both enzalutamide and orx reduced the bone mass in the axial skeleton as demonstrated by reduced lumbar spine areal bone mineral density (p<0.001) and trabecular bone volume fraction in L5 vertebrae (p<0.001) compared with vehicle-treated gonadal intact mice. A compression test of the L5 vertebrae revealed that the mechanical strength in the axial skeleton was significantly reduced by enzalutamide (maximal load at failure, -15.3±3.5%; p<0.01). The effects of enzalutamide in the axial skeleton were associated with a high bone turnover. In conclusion, enzalutamide reduces the bone mass in the axial but not the appendicular skeleton in male mice after sexual maturation. We propose that the effect of testosterone on the axial skeleton in male mice is mainly mediated via the AR.
33.	Zhai, Guangju, et al. (författare) Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms. 2011 Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 7:4 Tidskriftsartikel (refereegranskat)abstract Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands--yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15 × 10(-36)), SULT2A1 (rs2637125; p = 2.61 × 10(-19)), ARPC1A (rs740160; p = 1.56 × 10(-16)), TRIM4 (rs17277546; p = 4.50 × 10(-11)), BMF (rs7181230; p = 5.44 × 10(-11)), HHEX (rs2497306; p = 4.64 × 10(-9)), BCL2L11 (rs6738028; p = 1.72 × 10(-8)), and CYP2C9 (rs2185570; p = 2.29 × 10(-8)). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS.
34.	Abrahamsson, Anna, et al. (författare) Litteratursökning gällande olycksprediktionsmodeller och riskindex för plankorsningar mellan väg och järnväg 1991 Rapport (övrigt vetenskapligt/konstnärligt)
35.	Aglago, Elom K., et al. (författare) Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort 2020 Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 18:3, s. 6-666 Tidskriftsartikel (refereegranskat)abstract Background & Aims: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. Results: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80–0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82–0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83–1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78–0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18–1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). Conclusions: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.
36.	Alt Murphy, Margit, 1970, et al. (författare) Acceleration based Activity Levels during Subacute Inpatient Stroke Rehabilitation 2017 Ingår i: Procedia Technology. - : Elsevier BV. - 2212-0173. ; 27, s. 120-121 Tidskriftsartikel (refereegranskat)abstract People after stroke have difficulties to reach sufficient physical activity level during their rehabilitation and particularly outside the therapy time. We aim to quantify activity levels and investigate differences in motor activity in weekdays and weekends in a subacute stage after stroke. Data from multiple three-axis accelerometers was collected during two 48h sessions in 11 patients. The activity level and symmetry indices were sensitive to variations in weekend and weekdays. This information is valuable in rehabilitation planning and management and enables identification of those in risk of low physical activity and inactivity. (C) 2017 The Authors. Published by Elsevier
37.	Alt Murphy, Margit, 1970, et al. (författare) Acceleration based activity metrics during subacute inpatient stroke rehabilitation 2016 Ingår i: Procedia Technology, Biosensors 2016, 25-27 May, Göteborg, Sweden.. Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract People after stroke have difficulties to reach sufficient physical activity level during their rehabilitation and particularly outside the therapy time. We aim to quantify activity levels and investigate differences in motor activity in weekdays and weekends in a subacute stage after stroke. Data from multiple three-axis accelerometers was collected during two 48h sessions in 11 patients. The activity level and symmetry indices were sensitive to variations in weekend and weekdays. This information is valuable in rehabilitation planning and management and enables identification of those in risk of low physical activity and inactivity.
38.	Alt Murphy, Margit, 1970, et al. (författare) Comparison of Accelerometer-Based Arm, Leg and Trunk Activity at Weekdays and Weekends During Subacute Inpatient Rehabilitation After Stroke 2019 Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 51:6, s. 426-433 Tidskriftsartikel (refereegranskat)abstract Objective: To determine whether there are differences in arm, leg and trunk activity measured by acceleration between weekdays and weekends in people undergoing rehabilitation in the subacute stage after stroke. Patients: Twenty-eight individuals with stroke (mean age 55.4 years; severe to mild impairment) and 10 healthy controls. Methods: A set of 5 3-axial accelerometers were used on the trunk, wrists and ankles during 2 48-h sessions at weekdays and over a weekend. Day-time acceleration raw data were expressed as the signal magnitude area. Asymmetry between the affected and less-affected limb was calculated as a ratio. Results: Participants with stroke used their both arms and legs less at weekends than on weekdays (p<0.05, effect size 0.3 2-0.5 7). Asymmetry between the affected and less-affected arm was greater at weekends (p < 0.05, effect size 0.32). All activity measures, apart from the less-affected arm on weekdays, were lower in stroke compared with controls (p<0.05, effect size 0.4-0.8). No statistically significant differences were detected between weekday and weekend activity for the control group. One-third of participants perceived the trunk sensor as inconvenient to wear. Conclusion: Increased focus needs to be applied on activities carried out during weekends at rehabilitation wards.
39.	Alwerud, Anna, et al. (författare) Omvärld, närvärld, invärld : Kompetensplan för Lunds universitets bibliotek 2018-20 2018 Annan publikation (populärvet., debatt m.m.)
40.	Amzaleg, Y., et al. (författare) Estrogens and selective estrogen receptor modulators differentially antagonize Runx2 in ST2 mesenchymal progenitor cells 2018 Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 183, s. 10-17 Tidskriftsartikel (refereegranskat)abstract Estrogens attenuate bone turnover by inhibiting both osteoclasts and osteoblasts, in part through antagonizing Runx2. Apparently conflicting, stimulatory effects in osteoblast lineage cells, however, sway the balance between bone resorption and bone formation in favor of the latter. Consistent with this dualism, 17 beta-estradiol (E2) both stimulates and inhibits Runx2 in a locus-specific manner, and here we provide evidence for such locus specific regulation of Runx2 by E2 in vivo. We also demonstrate dual, negative and positive, regulation of Runx2-driven alkaline phosphatase (ALP) activity by increasing E2 concentrations in ST2 osteoblast progenitor cells. We further compared the effects of E2 to those of the Selective Estrogen Receptor Modulators (SERMs) raloxifene (ral) and lasofoxifene (las) and the phytoestrogen puerarin. We found that E2 at the physiological concentrations of 0.1-1 nM, as well as ral and las, but not puerarin, antagonize Runx2-driven ALP activity. At >= 10 nM, E2 and puerarin, but not ral or las, stimulate ALP relative to the activity measured at 0.1-1 nM. Contrasting the difference between E2 and SERMs in ST2 cells, they all shared a similar dose-response profile when inhibiting preosteoclast proliferation. That ral and las poorly mimic the locus-and concentration-dependent effects of E2 in mesenchymal progenitor cells may help explain their limited clinical efficacy.
41.	Ansved, Tor, et al. (författare) Enzyme-histochemical and morphological characteristics of fast- and slow-twitch skeletal muscle after brain infarction in the rat 1996 Ingår i: Journal of the Neurological Sciences. - 1878-5883. ; 144:1-2, s. 14-20 Tidskriftsartikel (refereegranskat)abstract The right middle cerebral artery was permanently occluded in 12-week-old male spontaneously hypertensive rats. After the surgery the rats were subjected to repeated behavioural tests during the observation period. Fourteen weeks after surgery the fast-twitch extensor digitorum longus (EDL) and the slow-twitch soleus muscle of both sides were removed and examined with regard to muscle fibre characteristics obtained by histochemical and morphometrical methods. Comparisons were made with age-matched controls. Limb placement and the ability to traverse a beam or a rotating pole were repeatedly tested 2-13 weeks after the operation. In spite of permanent sensorimotor deficits in limb placement and when traversing a rotating pole or beam, no increase in pathological changes was noted in either EDL or soleus. The number and proportion of fibre types remained unchanged in both muscles. There was no difference in muscle fibre size in either EDL or soleus. It is concluded that brain infarction in the rat, although causing marked impairment of contralateral motor function, does not have a major influence on the muscle-fibre morphology or fibre-type composition, irrespective of muscle type.
42.	Arvidsson, Inger, et al. (författare) Discrepancies in pain presentation caused by adverse psychosocial conditions as compared to pain due to high physical workload? 2012 Ingår i: Work: A Journal of Prevention, Assessment & Rehabilitation. - 1875-9270. ; 41, s. 2472-2475 Tidskriftsartikel (refereegranskat)abstract Disorders in the musculoskeletal system have been associated with a high physical workload as well as psychosocial and individual factors. It is however not obvious which of these factors that is most important to prevent. Musculoskeletal disorders in neck and upper extremity was assessed by interview and clinical examination in 79 teachers and 93 assisting nurses, all females. Psychosocial work environment was assessed by questionnaire. The physical workload was recorded by technical measurements of postures, movements and muscular load, in 9 teachers and 12 nurses. The physical workload was lower among the teachers, but they had a more demanding psychosocial work environment. Among the nurses, but not in the teachers, the neck-shoulder disorders were associated with a high body mass index (BMI). The teachers reported neck-shoulder complaints to a higher extent than the nurses, but had much lower prevalence of diagnoses in the clinical examination (12% vs. 25%; POR 0.3 CI 0.1 - 1.2; adjusted for age and BMI). The results suggest that adverse psychosocial conditions among the teachers give rise to a different kind of pain in the neck-shoulder region than from physical overload, troublesome but not as severe as the one afflicting the nurses.
43.	Austin, Thomas R, et al. (författare) Large-scale circulating proteome association study (CPAS) meta-analysis identifies circulating proteins and pathways predicting incident hip fractures. 2024 Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 1523-4681. ; 39:2, s. 139-149 Tidskriftsartikel (refereegranskat)abstract Hip fractures are associated with significant disability, high cost, and mortality. However, the exact biological mechanisms underlying susceptibility to hip fractures remain incompletely understood. In an exploratory search of the underlying biology as reflected through the circulating proteome, we performed a comprehensive Circulating Proteome Association Study (CPAS) meta-analysis for incident hip fractures. Analyses included 6430 subjects from two prospective cohort studies (Cardiovascular Health Study and Trøndelag Health Study) with circulating proteomics data (aptamer-based 5K SomaScan version 4.0 assay; 4979 aptamers). Associations between circulating protein levels and incident hip fractures were estimated for each cohort using age and sex-adjusted Cox regression models. Participants experienced 643 incident hip fractures. Compared with the individual studies, inverse-variance weighted meta-analyses yielded more statistically significant associations, identifying 23 aptamers associated with incident hip fractures (conservative Bonferroni correction 0.05/4979, P<1.0×10-5). The aptamers most strongly associated with hip fracture risk corresponded to two proteins of the growth hormone/insulin growth factor system (GHR and IGFBP2), as well as GDF15 and EGFR. High levels of several inflammation-related proteins (CD14, CXCL12, MMP12, ITIH3) were also associated with increased hip fracture risk. Ingenuity pathway analysis identified reduced LXR/RXR activation and increased acute phase response signaling to be overrepresented among those proteins associated with increased hip fracture risk. These analyses identified several circulating proteins and pathways consistently associated with incident hip fractures. These findings underscore the usefulness of the meta-analytic approach for comprehensive CPAS in a similar manner as has previously been observed for large-scale human genetic studies. Future studies should investigate the underlying biology of these potential novel drug targets.
44.	Benrick, Anna, 1979, et al. (författare) Resveratrol Is Not as Effective as Physical Exercise for Improving Reproductive and Metabolic Functions in Rats with Dihydrotestosterone-Induced Polycystic Ovary Syndrome 2013 Ingår i: Evidence-Based Complementary and Alternative Medicine. - : Hindawi Limited. - 1741-427X .- 1741-4288. Tidskriftsartikel (refereegranskat)abstract Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disorder associated with obesity and insulin resistance that often precedes the development of type-2 diabetes. Rats continuously exposed to dihydrotestosterone from prepuberty display typical reproductive and metabolic PCOS characteristics including anovulation, polycystic ovaries, insulin resistance, and obesity. Our aim was to investigate if resveratrol improves reproductive and metabolic functions in PCOS rats. The effect was compared to exercise. Control and PCOS rats were treated with vehicle or resveratrol (400mg·kg−1·day−1) for 5-6 weeks. Another group of PCOS rats received vehicle treatment and exercised for 5-6 weeks. Insulin sensitivity was determined by euglycemic-hyperinsulinemic clamp. The glucose infusion rate was lower in the PCOS-vehicle group compared to control-vehicle rats (). Exercise increased insulin sensitivity compared with PCOS-vehicle rats (), but resveratrol did not. Resveratrol treatment and exercise resulted in smaller adipocytes, upregulated estrogen-related receptor α gene expression in subcutaneous fat, and improved estrus cyclicity in the previously acyclic PCOS rats. Although resveratrol had positive effects on adiposity and cyclicity in a similar manner to exercise, resveratrol does not seem to be a good candidate for treating insulin resistance associated with PCOS because no improvement in insulin sensitivity was observed in PCOS rats on normal chow.
45.	Benyamine, Isak, 1963- (författare) Konstnärliga undervisningspraktiker : Genealogier, diskurser och makt 2019 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract This dissertation is about art teaching practices at upper secondary schools with a focus on theatre and at university arts programmes with a focus on film. More specifically, it addresses the factors that have contributed to current teaching practices in art education today and how students and teachers in interaction with each other shape, become part of and identify with the norms and values that emerge through these practices.The overarching question concerns how norms and values emerge as power/knowledge processes in the teaching process. The genealogical study presented examines how art education is constructed at a policy level. The study discusses how, in past eras, investigators, researchers and educators described what students needed to do during their education to develop into professional artists, how teaching practices were designed and justified, and how art was distinct from other activities and forms of knowledge in education. The interaction study presented examines the act of teaching. It discusses how, the participants shape each other and establish norms and values in relation to notions of what art “is” and can be.The conditions of possibilities in art teaching practices has been identified in three discourses. The discourse of conversation governs the format and organisation of the teaching practice. It is assumed that through conversation the students can develop their artistic ability. The discourse of freedom identifies how students submit to the vague, flexible and ever-changing notions of what art signifies. The discourse of production describes how the artistic work in the teaching practice takes precedence over an acquisition of established knowledge.The importance of the participants’ own experiences and feelings, therapeutic conversations, the liberation from conventional education discourses, confession practices and the establishment of a production discourse all emerge as important techniques in art teaching practices. Core values and norms are expressed through these techniques.The study shows that participants in art teaching practices develop the skills of self-evaluation, self-analysis and self-governance. The notion of an individualised, exploratory educational experience clashes with a process that directs the students to align themselves with the shared norms and values of the art world, of its content and expression. Students perceive their artistic output as unique while the art produced can be understood as expression of a normalisation process that strives to maintain the values and norms in art teaching practices. In summery the dissertation shows that the participants’ learning process is of an exploratory nature. Rather than acquiring and assimilating established knowledge, the participants learn by finding their own paths in a knowledge-formation process in which they discover the artistic potential of their own experiences and insights.
46.	Berglund, Torkel, et al. (författare) Nicotinamide; antioxidative and DNA hypomethylation effects in plant cells 2017 Ingår i: Plant physiology and biochemistry (Paris). - : Elsevier. - 0981-9428 .- 1873-2690. ; 118, s. 551-560 Tidskriftsartikel (refereegranskat)abstract The effects of nicotinamide (NIC) and its natural plant metabolites nicotinic acid (NIA) and trigonelline (TRIG) were studied with respect to defense in plant cell cultures. NIC and NIA could protect against oxidative stress damage caused by 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH), which generates free radicals. Damage was analyzed as DNA strand breaks in cell cultures of Pisum sativum (garden pea), Daucus carota (carrot), Populus tremula L. × P. tremuloides (hybrid aspen) and Catharanthus roseus (Madagascar periwinkle), monitored by single cell gel electrophoresis (comet assay), and assays of cell leakage in C. roseus. The activities of aconitase and fumarase enzymes, which have key roles in energy metabolism, were analyzed in P. sativum cultures after treatment with NIC or NIA. Aconitase activity was increased by NIA, and fumarase activity was increased by both compounds. These compounds were shown to promote glutathione metabolism in P. sativum cultures, and NIC was shown to have a global DNA hypomethylating effect. Neither TRIG nor poly(ADP-ribose) polymerase (PARP) inhibitor 3-aminobenzamide offered any protection against DNA damage or cell leakage, nor did they promote aconitase or fumarase activities, or glutathione metabolism. By this broad approach addressing multiple biochemical factors and different plant species, we demonstrate that NIC and NIA protect plant cells from oxidative stress, and that NIC clearly exerts an epigenetic effect; decreased DNA methylation. This indicates that these compounds have important roles in the regulation of metabolism in plant cells, especially in connection to stress.
47.	Berglund, Torkel, et al. (författare) Protection of spruce seedlings against pine weevil attacks by treatment of seeds or seedlings with nicotinamide, nicotinic acid and jasmonic acid 2016 Ingår i: Forestry (London). - : Oxford University Press. - 0015-752X .- 1464-3626. ; 89:2, s. 127-135 Tidskriftsartikel (refereegranskat)abstract Sustainable methods are required to protect newly planted tree seedlings from insect herbivore attack. To this end, here Norway spruce (Picea abies (L.) Karst.) seeds were treated with 2.5 mM nicotinamide (NIC), 2.5 mM nicotinic acid (NIA), 3 mM jasmonic acid (JA) or 0.2 mM 5-azacytidine (5-Aza), and 6-month-old seedlings grown from these seeds were planted at a reforestation area in central Sweden. Attack by pine weevils (Hylobius abietis) was reduced by 50 per cent by NIC treatment, 62.5 per cent by JA treatment and 25 per cent by 5-Aza treatment, when compared with seedlings grown from untreated seeds. Watering 18-month-old spruce seedlings with 2 mM NIC or 2 mM NIA did reduce attack during the first season in the field by 40 and 53 per cent, respectively, compared with untreated plants. Girdling was also reduced by the different treatments. Analysis of conifer seedlings treated with 5-Aza points at a possible involvement of epigenetic mechanisms in this defensive capacity. This is supported by a reduced level of DNA methylation in the needles of young spruce seedlings grown in a greenhouse from NIC-treated seeds. Seed treatment for seedling defense potentiation is simple, inexpensive and also a new approach for forestry with many potential applications.
48.	Bernhardsson, Katarina, et al. (författare) Obduktion och mjuka texter : Shared Reading som metod på universitetet 2022 Ingår i: Shared Reading i Skandinavia : Forskning og praksis - Forskning og praksis. - 9788293298212 - 9788293298229 ; , s. 257-287 Bokkapitel (refereegranskat)abstract This chapter discusses how Shared Reading (SR) can be used as a method when teaching university students in professional education. Drawing on experiences from both the Medical School and the Creative Writing Program, the chapter shows how SR can be used to enhance professional development in two different settings. In Medical School, SR is used to create a space for exploration of relational and emotional aspects of the profession, which is here exemplified with the reading of poetry after the students’ first autopsy. In the Creative Writing Program, SR is used to slow down the reading, giving the students the opportunity to read the text as if it was still a work-in-progress, and a so-called ‘flexible’ text. The discussion shows the versatility of the method: how as, even as the method is the same, the differences come from the educational context, and what the students learn is to a large extent dependent on their future profession.
49.	Blomqvist, Evalena, et al. (författare) Optimerad rening av HCI och SO2 med minskade kalktillsatser vid torr rökgasrening 2007 Rapport (populärvet., debatt m.m.)abstract Fokus för detta projekt är att optimera rening av saltsyra (HCl) och svaveldioxid (SO2) i ett torrt reningssystem kopplat till en avfallsförbränningsprocess. För att uppnå effektiv rening av HCl och SO2 från rökgasen tillsätts ofta stora mängder absorbent. En minskad absorbentförbrukning ger dubbel ekonomisk vinning för anläggningsägaren då både förbruknings- och deponeringskostnader kan reduceras. Syftet med projektet är att studera effekten av temperatur och vattenhalt i rökgasen, dvs relativ fukthalt (RH) för absorption av HCl och SO2 med normal släckt kalk. Effektiviteten hos en absorbenter med högre porvolym och specifik yta (sprängd släckt kalk) undersöktes också. Resultat från 26 mätdygn, utförda på Borås Energi och Miljö (BEMABs) 20 MW avfallsförbränningsanläggning, visar en positiv korrelation mellan effektiviteten hos normal släckt kalk och RH. Variation i RH uppnåddes genom att sänka rökgastemperaturen i filtret och/eller genom att befukta det inkommande bränslet. Genom att enbart befukta bränslet, motsvarande en 20 % vattenhalt i rökgasen, ökade endast RH marginellt till 3,62 % jämfört med normalnivå på 3,28 %. Mängden tillsatt kalk reducerades under dessa förhållanden endast med 5 %. En 10 ºC temperatursänkning av rökgasen till 143 ºC vid filtret resulterade i en ökning av RH till 4,06%, vilket medförde en 13 % reduktion av kalkförbrukningen. En kombinationen av både lägre rökgas och befuktat bränsle genererade den kraftigaste ökning av RH, 4,84%, och således också den kraftigaste reduktion (26 %) av mängden tillsatt normal släckt kalk. Effektiviteten hos sprängd släckt kalk testades också vid normala driftsförhållanden under sju mätdygn. Dessa experiment visade på en halverad förbrukning jämfört med motsvarande förbrukning av normal släckt kalk. Vidare indikerade testen att den sprängda kalken besitter samma känslighet för variation i RH som normal släckt kalk inom det naturligt uppkomna temperaturvariationerna i processen (145-165 oC). Detta antyder att det finns utrymme för ytterligare effektiviseringspotentialer och därmed minskade tillsattsmängder även för den sprängda kalken. Det finns stora kostnadsreduktioner att vinna med minskad absorbentförbrukning. Genom att optimera BEMABs anläggning med avseende på RH kan en 20% reduktion av normal släckt kalk erhållas. En optimering som motsvara en minskning av kostnaderna med dryga 700 000 SEK. Om sprängd släckt kalk skulle användas i stället skulle kostnaderna reduceras med ytterligare ca 700 000 SEK. Ett FTIR-system för on-line mätning av HCl och SO2 i partikelhaltiga rökgaser utvärderades inom projektet. Mätmetoden anger relativa förändringar i halter med tiden och mäter inte absolut. Validering av systemet visade att 80% av HCl och 20% av SO2 återfinns i gasfasen. Det bör dock noteras att SO2 halterna var mycket låga. Nyckelord: Kalkeffektivitet, relativ fukthalt, HCl, SO2, absorption, avfallsförbränning, Rökgasrening
50.	Bonfiglio, F., et al. (författare) Female-Specific Association Between Variants on Chromosome 9 and Self-Reported Diagnosis of Irritable Bowel Syndrome 2018 Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 155:1, s. 168-179 Tidskriftsartikel (refereegranskat)abstract BACKGROUND & AIMS: Genetic factors are believed to affect risk for irritable bowel syndrome (IBS), but there have been no sufficiently powered and adequately sized studies. To identify DNA variants associated with IBS risk, we performed a genome-wide association study (GWAS) of the large UK Biobank population-based cohort, which includes genotype and health data from 500,000 participants. METHODS: We studied 7,287,191 high-quality single nucleotide polymorphisms in individuals who self-reported a doctor's diagnosis of IBS (cases; n = 9576) compared to the remainder of the cohort (controls; n = 336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n = 249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories to obtain biological insights from the observed associations. RESULTS: We identified a genome-wide significant association on chromosome 9q31.2 (single nucleotide polymorphism rs10512344; P = 3.57 x 10(-8)) in a region previously linked to age at menarche, and 13 additional loci of suggestive significance (P < 5.0 x 10(-6)). Sex-stratified analyses revealed that the variants at 9q31.2 affect risk of IBS in women only (P = 4.29 x 10(-10) in UK Biobank) and also associate with constipation-predominant IBS in women (P = .015 in the tertiary cohort) and harder stools in women (P = .0012 in the population-based sample). Functional annotation of the 9q31.2 locus identified 8 candidate genes, including the elongator complex protein 1 gene (ELP1 or IKB-KAP), which is mutated in patients with familial dysautonomia. CONCLUSIONS: In a sufficiently powered GWAS of IBS, we associated variants at the locus 9q31.2 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS.

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