| 1. |
- Abdo, A. A., et al.
(författare)
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THE FIRST FERMI MULTIFREQUENCY CAMPAIGN ON BL LACERTAE : CHARACTERIZING THE LOW-ACTIVITY STATE OF THE EPONYMOUS BLAZAR
- 2011
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 730:2, s. 101-
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Tidskriftsartikel (refereegranskat)abstract
- We report on observations of BL Lacertae during the first 18 months of Fermi LAT science operations and present results from a 48 day multifrequency coordinated campaign from 2008 August 19 to 2008 October 7. The radio to gamma-ray behavior of BL Lac is unveiled during a low-activity state thanks to the coordinated observations of radio-band (Metsahovi and VLBA), near-IR/optical (Tuorla, Steward, OAGH, and MDM), and X-ray (RXTE and Swift) observatories. No variability was resolved in gamma rays during the campaign, and the brightness level was 15 times lower than the level of the 1997 EGRET outburst. Moderate and uncorrelated variability has been detected in UV and X-rays. The X-ray spectrum is found to be concave, indicating the transition region between the low- and high-energy components of the spectral energy distribution (SED). VLBA observation detected a synchrotron spectrum self-absorption turnover in the innermost part of the radio jet appearing to be elongated and inhomogeneous, and constrained the average magnetic field there to be less than 3 G. Over the following months, BL Lac appeared variable in gamma rays, showing flares (in 2009 April and 2010 January). There is no evidence for the correlation of gamma rays with the optical flux monitored from the ground in 18 months. The SED may be described by a single-zone or a two-zone synchrotron self-Compton (SSC) model, but a hybrid SSC plus external radiation Compton model seems to be preferred based on the observed variability and the fact that it provides a fit closest to equipartition.
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| 2. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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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.
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| 3. |
- Fall, Tove, et al.
(författare)
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The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis
- 2013
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 10:6, s. e1001474-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001). Conclusions: We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.
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| 4. |
- Uusitupa, M., et al.
(författare)
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Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome : a randomized study (SYSDIET)
- 2013
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 274:1, s. 52-66
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Tidskriftsartikel (refereegranskat)abstract
- Background Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. Methods We conducted a randomized dietary study lasting for 18-24weeks in individuals with features of metabolic syndrome (mean age 55years, BMI 31.6kgm-2, 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. Results Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmolL-1 95% CI -0.35; -0.01, P=0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P=0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P=0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37ngL-1, P= 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P=0.049) and magnesium (mg, -0.23, -0.41; -0.05, P=0.012) were associated with IL-1 Ra. Conclusions Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.
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| 5. |
- Pyykkö, O. T., et al.
(författare)
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APOE4 predicts amyloid-β in cortical brain biopsy but not idiopathic normal pressure hydrocephalus
- 2012
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 83:11, s. 1119-1124
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the association of apolipoprotein E (APOE) genotype, especially the APOE4 allele, to (1) idiopathic normal pressure hydrocephalus (iNPH) and (2) amyloid-β (Aβ) plaques in cortical brain biopsies of presumed NPH patients with and without a final clinical diagnosis of Alzheimer's disease (AD). Methods: 202 patients with presumed NPH were evaluated by intraventricular pressure monitoring and frontal cortical biopsy immunostained against Aβ (134 semiquantified by Aβ plaques/mm 2). The 202 patients and 687 cognitively healthy individuals were genotyped for APOE. The final clinical diagnoses in a median follow-up of 3.9 years were: 113 iNPH (94 shunt responsive, 16 shunt non-responsive, three not shunted); 36 AD (12 mixed iNPH + AD); 53 others. Results: The APOE genotypes distributed similarly in the 94 shunt responsive and 16 non-responsive iNPH patients and healthy controls. In multivariate analysis, the APOE4 allele correlated independently with Aβ plaques in the cortical biopsies (OR 8.7, 95% CI 3.6 to 20, p<0.001). The APOE4 allele in presumed NPH predicted later AD as follows: sensitivity 61%; specificity 77%; positive predictive value 37%; negative predictive value 90%. Conclusion: In presumed NPH patients, APOE4 associates independently with the presence of Aβ plaques in the frontal cortical biopsy. APOE4 is not a risk factor for iNPH and does not predict the response to shunt. Our data further support the view that the iNPH syndrome is a distinct dementing disease.
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| 8. |
- Tukiainen, T., et al.
(författare)
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Mild cognitive impairment associates with concurrent decreases in serum cholesterol and cholesterol-related lipoprotein subclasses
- 2012
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Ingår i: The Journal of Nutrition, Health & Aging. - : Springer Science and Business Media LLC. - 1279-7707 .- 1760-4788. ; 16:7, s. 631-635
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Accumulating evidence suggests that serum lipids are associated with cognitive decline and dementias. However, majority of the existing information concerns only serum total cholesterol (TC) and data at the level of lipoprotein fractions and subclasses is limited. The aim of this study was to explore the levels and trends of main cholesterol and triglyceride measures and eight lipoprotein subclasses during normal aging and the development of mild cognitive impairment by following a group of elderly for six years. Design: Longitudinal. Setting: City of Kuopio, Finland. Participants: 45 elderly individuals of which 20 developed mild cognitive impairment (MCI) during the follow-up. Measurement: On each visit participants underwent an extensive neuropsychological and clinical assessment. Lipoprotein levels were measured via 1H NMR from native serum samples. Results: Serum cholesterol and many primarily cholesterol-associated lipoprotein measures clearly decreased in MCI while the trends were increasing for those elderly people who maintained normal cognition. Conclusion: These findings suggest that a decreasing trend in serum cholesterol measures in elderly individuals may suffice as an indication for more detailed inspection for potential signs of cognitive decline.
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| 9. |
- Knuuttila, M., et al.
(författare)
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Castration Induces Up-Regulation of Intratumoral Androgen Biosynthesis and Androgen Receptor Expression in an Orthotopic VCaP Human Prostate Cancer Xenograft Model
- 2014
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440. ; 184:8, s. 2163-2173
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Tidskriftsartikel (refereegranskat)abstract
- Androgens are key factors involved in the development and progression of prostate cancer (PCa), and PCa growth can be suppressed by androgen deprivation therapy. In a considerable proportion of men receiving androgen deprivation therapy, however, PCa progresses to castration-resistant PCa (CRPC), making the development of efficient therapies challenging. We used an orthotopic VCaP human PCa xenograft model to study cellular and molecular changes in tumors after androgen deprivation therapy (castration). Tumor growth was monitored through weekly serum prostate-specific antigen measurements, and mice with recurrent tumors after castration were randomized to treatment groups. Serum prostate-specific antigen concentrations showed significant correlation with tumor volume. Castration-resistant tumors retained concentrations of intratumoral androgen (androstenedione, testosterone, and 5 alpha-dihydrotestosterone) at Levels similar to tumors growing in intact hosts. Accordingly, castration induced up-regulation of enzymes involved in androgen synthesis (CYP17A1, AKR1C3, and HSD17B6), as well as expression of full-length androgen receptor (AR) and AR splice variants (AR-V1 and AR-V7). Furthermore, AR target gene expression was maintained in castration-resistant xenografts. The AR antagonists enzalutamide (MDV3100) and ARN-509 suppressed PSA production of castration-resistant tumors, confirming the androgen dependency of these tumors. Taken together, the findings demonstrate that our VCaP xenograft model exhibits the key characteristics of clinical CRPC and thus provides a valuable tool for identifying druggable targets and for testing therapeutic strategies targeting AR signaling in CRPC.
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| 10. |
- Magnusdottir, O. K., et al.
(författare)
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Plasma alkylresorcinols C17:0/C21:0 ratio, a biomarker of relative whole-grain rye intake, is associated to insulin sensitivity : a randomized study
- 2014
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 68:4, s. 453-458
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVES: Few studies have used biomarkers of whole-grain intake to study its relation to glucose metabolism. We aimed to investigate the association between plasma alkylresorcinols (AR), a biomarker of whole-grain rye and wheat intake, and glucose metabolism in individuals with metabolic syndrome (MetS). SUBJECTS/METHODS: Participants were 30-65 years of age, with body mass index 27-40 kg/m(2) and had MetS without diabetes. Individuals were recruited through six centers in the Nordic countries and randomized to a healthy Nordic diet (ND, n=96), rich in whole-grain rye and wheat, or a control diet (n=70), for 18-24 weeks. In addition, associations between total plasma AR concentration and C17:0/C21:0 homolog ratio as an indication of the relative whole-grain rye intake, and glucose metabolism measures from oral glucose tolerance tests were investigated in pooled (ND + control) regression analyses at 18/24 weeks. RESULTS: ND did not improve glucose metabolism compared with control diet, but the AR C17:0/C21:0 ratio was inversely associated with fasting insulin concentrations (P=0.002) and positively associated with the insulin sensitivity indices Matsuda ISI (P=0.026) and disposition index (P=0.022) in pooled analyses at 18/24 weeks, even after adjustment for confounders. The AR C17:0/C21:0 ratio was not significantly associated with insulin secretion indices. Total plasma AR concentration was not related to fasting plasma glucose or fasting insulin at 18/24 weeks. CONCLUSIONS: The AR C17:0/C21:0 ratio, an indicator of relative whole-grain rye intake, is associated with increased insulin sensitivity in a population with MetS.
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