| 1. |
- den Ruijter, H. M., et al.
(författare)
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Common carotid intima-media thickness does not add to Framingham risk score in individuals with diabetes mellitus: the USE-IMT initiative
- 2013
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 56:7, s. 1494-1502
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to investigate whether measurement of the mean common carotid intima-media thickness (CIMT) improves cardiovascular risk prediction in individuals with diabetes. We performed a subanalysis among 4,220 individuals with diabetes in a large ongoing individual participant data meta-analysis involving 56,194 subjects from 17 population-based cohorts worldwide. We first refitted the risk factors of the Framingham heart risk score on the individuals without previous cardiovascular disease (baseline model) and then expanded this model with the mean common CIMT (CIMT model). The absolute 10 year risk for developing a myocardial infarction or stroke was estimated from both models. In individuals with diabetes we compared discrimination and calibration of the two models. Reclassification of individuals with diabetes was based on allocation to another cardiovascular risk category when mean common CIMT was added. During a median follow-up of 8.7 years, 684 first-time cardiovascular events occurred among the population with diabetes. The C statistic was 0.67 for the Framingham model and 0.68 for the CIMT model. The absolute 10 year risk for developing a myocardial infarction or stroke was 16% in both models. There was no net reclassification improvement with the addition of mean common CIMT (1.7%; 95% CI -1.8, 3.8). There were no differences in the results between men and women. There is no improvement in risk prediction in individuals with diabetes when measurement of the mean common CIMT is added to the Framingham risk score. Therefore, this measurement is not recommended for improving individual cardiovascular risk stratification in individuals with diabetes.
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| 2. |
- Wormser, David, et al.
(författare)
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Adult height and the risk of cause-specific death and vascular morbidity in 1 million people : individual participant meta-analysis
- 2012
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 41:5, s. 1419-1433
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.MethodsWe calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.ResultsFor people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.ConclusionAdult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
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| 3. |
- Barner, C., et al.
(författare)
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Effects on insulin sensitivity and body composition of combination therapy with GH and IGF1 in GH deficient adults with type 2 diabetes
- 2012
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 167:5, s. 697-703
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this trial was to evaluate the effect on insulin sensitivity and body composition of combination therapy with GH and IGF1 in adults with GH deficiency (GHD) and diabetes. Design, patients and methods: A 6-month randomised placebo-controlled pilot study. Fourteen adults with GHD and type 2 diabetes were included. All received rhGH (0.15 mg/day for 1 month and 0.3 mg/day for 5 months) and were randomised to rhIGF1 (15 μg/kg per day for 1 month and 30 μg/kg per day for 5 months) or placebo. Insulin sensitivity was evaluated with euglycaemic hyperinsulinaemic clamp and body composition by computed tomography of abdominal and thigh fat, as well as bioimpedance. Results: Twelve patients completed the study. They were overweight and obese; at baseline, insulin sensitivity (M-value) was low. IGF1 and IGF1 SDS increased in both groups, with the highest increase in the GH and IGF1 group. Positive changes in M-value by +1.4 mg/kg per min, in subcutaneous abdominal fat by -60.5 ml and in fat-free mass by +4.4% were seen in the GH and IGF1 group. Corresponding values in the GH and placebo-treated group were -1.5 mg/kg per min, +23 ml and -0.04% respectively (P=0.02, P=0.04 and P=0.03 for delta values between groups). No safety issues occurred. Conclusions: Combined GH and IGF1 treatment resulted in positive, but rather small effects, and might be a treatment option in a few selected patients.
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| 4. |
- Gianni, Stefano, et al.
(författare)
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Sequence-specific Long Range networks in PSD-95/Discs Large/ZO-1 (PDZ) Domains Tune Their Binding Selectivity
- 2011
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 286:31, s. 27167-27175
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Tidskriftsartikel (refereegranskat)abstract
- Protein-protein interactions mediated by modular protein domains are critical for cell scaffolding, differentiation, signaling, and ultimately, evolution. Given the vast number of ligands competing for binding to a limited number of domain families, it is often puzzling how specificity can be achieved. Selectivity may be modulated by intradomain allostery, whereby a remote residue is energetically connected to the functional binding site via side chain or backbone interactions. Whereas several energetic pathways, which could mediate intradomain allostery, have been predicted in modular protein domains, there is a paucity of experimental data to validate their existence and roles. Here, we have identified such functional energetic networks in one of the most common protein-protein interaction modules, the PDZ domain. We used double mutant cycles involving site-directed mutagenesis of both the PDZ domain and the peptide ligand, in conjunction with kinetics to capture the fine energetic details of the networks involved in peptide recognition. We performed the analysis on two homologous PDZ-ligand complexes and found that the energetically coupled residues differ for these two complexes. This result demonstrates that amino acid sequence rather than topology dictates the allosteric pathways. Furthermore, our data support a mechanism whereby the whole domain and not only the binding pocket is optimized for a specific ligand. Such cross-talk between binding sites and remote residues may be used to fine tune target selectivity.
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| 5. |
- Kaptoge, S., et al.
(författare)
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C-Reactive Protein, Fibrinogen, and Cardiovascular Disease Prediction
- 2012
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 367:14, s. 1310-1320
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Tidskriftsartikel (refereegranskat)abstract
- Background There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. Methods We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. Results The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P < 0.001), and yielded a net reclassification improvement of 1.52% and 0.83%, respectively, for the predicted 10-year risk categories of "low" (< 10%), " intermediate" (10% to < 20%), and "high" (>= 20%) (P < 0.02 for both comparisons). We estimated that among 100,000 adults 40 years of age or older, 15,025 persons would initially be classified as being at intermediate risk for a cardiovascular event if conventional risk factors alone were used to calculate risk. Assuming that statin therapy would be initiated in accordance with Adult Treatment Panel III guidelines (i.e., for persons with a predicted risk of >= 20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. Conclusions In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.)
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| 6. |
- Kaufmann, Thomas, et al.
(författare)
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Recent developments of the meshless radial point interpolation method for time-domain electromagnetics
- 2012
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Ingår i: International Journal of Numerical Modelling: Electronic Networks, Devices and Fields. - : Wiley. - 0894-3370 .- 1099-1204. ; 25:5-6, s. 468-489
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Forskningsöversikt (refereegranskat)abstract
- Meshless methods are a promising new field in computational electromagnetics. Instead of relying on an explicit mesh topology, a numerical solution is computed on an unstructured set of collocation nodes. This allows to model fine geometrical details with high accuracy and facilitates the adaptation of node distributions for optimization or refinement purposes. The radial point interpolation method (RPIM) is a meshless method based on radial basis functions. In this paper, the current state of the RPIM in electromagnetics is reviewed. The localized RPIM scheme is summarized, and the interpolation accuracy is discussed in dependence of important parameters. A time-domain implementation is presented, and important time iteration aspects are reviewed. New formulations for perfectly matched layers and waveguide ports are introduced. An unconditionally stable RPIM scheme is summarized, and its advantages for hybridization with the classical RPIM scheme are discussed in a practical example. The capabilities of an adaptive time-domain refinement strategy based on the experiences on a frequency-domain solver are discussed.
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| 7. |
- Kerstis, Birgitta, et al.
(författare)
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Depressive symptoms postpartum among parents are associated with marital separation : A Swedish cohort study
- 2014
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 42:7, s. 660-668
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To study whether there is an association between dyadic consensus, depressive symptoms, and parental stress during early parenthood and marital separation 6–8 years after childbirth, among couples in Sweden.Methods: At baseline, 393 couples were included. The couples answered three questionnaires, including: Dyadic consensus at 1 week post-partum, depressive symptoms at 3 months post-partum and parental stress at 18 months post-partum. The parents’ addresses were followed up after 6–8 years, to study the marital separation rate.Results: We found, 6–8 years after childbirth, that 20% of study couples were separated. Separation was associated with less dyadic consensus (mothers p < 0.001; fathers p < 0.001), depressive symptoms (mothers p = 0.022; fathers p = 0.041) and parental stress (mothers p = 0.002; fathers p = 0.040). The hazard ratio (HR) for marital separation was related to dyadic consensus for fathers (HR 0.51; 95% CI 0.28–0.92), depressive symptoms for mothers (HR 1.69; 95% CI 1.01–2.84) and fathers (HR 1.92; 95% CI 1.12–3.28), and the mother’s parental stress (HR 2.16; 95% CI 1.14–4.07).Conclusions: Understanding how dyadic consensus, depressive symptoms and parental stress are associated with marital separation is important for health professionals. It could be useful in developing interventions to provide parents with adequate support during pregnancy and early parenthood. This knowledge is also important for the public. Parents should get support in pregnancy and while bringing up children, which may help prevent marital separation and optimize conditions for the children.
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| 8. |
- Lomnytska, M. I., et al.
(författare)
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Impact of genomic stability on protein expression in endometrioid endometrial cancer
- 2012
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 106:7, s. 1297-1305
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genomic stability is one of the crucial prognostic factors for patients with endometrioid endometrial cancer (EEC). The impact of genomic stability on the tumour tissue proteome of EEC is not yet well established.METHODS: Tissue lysates of EEC, squamous cervical cancer (SCC), normal endometrium and squamous cervical epithelium were subjected to two-dimensional (2D) gel electrophoresis and identification of proteins by MALDI TOF MS. Expression of selected proteins was analysed in independent samples by immunohistochemistry.RESULTS: Diploid and aneuploid genomically unstable EEC displayed similar patterns of protein expression. This was in contrast to diploid stable EEC, which displayed a protein expression profile similar to normal endometrium. Approximately 10% of the differentially expressed proteins in EEC were specific for this type of cancer with differential expression of other proteins observed in other types of malignancy (e.g., SCC). Selected proteins differentially expressed in 2D gels of EEC were further analysed in an EEC precursor lesion, that is, atypical hyperplasia of endometrium, and showed increased expression of CLIC1, EIF4A1 and PRDX6 and decreased expression of ENO1, ANXA4, EMD and Ku70.CONCLUSION: Protein expression in diploid and aneuploid genomically unstable EEC is different from the expression profile of proteins in diploid genomically stable EEC. We showed that changes in expression of proteins typical for EEC could already be detected in precursor lesions, that is, atypical hyperplasia of endometrium, highlighting their clinical potential for improving early diagnostics of EEC.
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| 9. |
- Mueller, T., et al.
(författare)
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Characterization and intercomparison of aerosol absorption photometers : result of two intercomparison workshops
- 2011
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 4:2, s. 245-268
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Tidskriftsartikel (refereegranskat)abstract
- Absorption photometers for real time application have been available since the 1980s, but the use of filter-based instruments to derive information on aerosol properties (absorption coefficient and black carbon, BC) is still a matter of debate. Several workshops have been conducted to investigate the performance of individual instruments over the intervening years. Two workshops with large sets of aerosol absorption photometers were conducted in 2005 and 2007. The data from these instruments were corrected using existing methods before further analysis. The inter-comparison shows a large variation between the responses to absorbing aerosol particles for different types of instruments. The unit to unit variability between instruments can be up to 30% for Particle Soot Absorption Photometers (PSAPs) and Aethalometers. Multi Angle Absorption Photometers (MAAPs) showed a variability of less than 5%. Reasons for the high variability were identified to be variations in sample flow and spot size. It was observed that different flow rates influence system performance with respect to response to absorption and instrumental noise. Measurements with non absorbing particles showed that the current corrections of a cross sensitivity to particle scattering are not sufficient. Remaining cross sensitivities were found to be a function of the total particle load on the filter. The large variation between the response to absorbing aerosol particles for different types of instruments indicates that current correction functions for absorption photometers are not adequate.
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| 10. |
- Schlebusch, Carina M., et al.
(författare)
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Possible positive selection for an arsenic-protective haplotype in humans
- 2013
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 121:1, s. 53-58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Arsenic in drinking water causes severe health effects. Indigenous people in the South American Andes have likely lived with arsenic-contaminated drinking water for thousands of years. Inhabitants of San Antonio de los Cobres (SAC) in the Argentinean highlands generally carry an AS3MT (the major arsenic-metabolizing gene) haplotype associated with reduced health risks due to rapid arsenic excretion and lower urinary fraction of the monomethylated metabolite.Objectives: We hypothesized an adaptation to high-arsenic living conditions via a possible positive selection for protective AS3MT variants and compared AS3MT haplotype frequencies among different indigenous groups. Methods: Indigenous groups we evaluated were a) inhabitants of SAC and villages near Salta in northern Argentina (n = 346), b) three Native American populations from the Human Genome Diversity Project (HGDP; n = 25), and c) five Peruvian populations (n = 97). The last two groups have presumably lower historical exposure to arsenic.Results: We found a significantly higher frequency of the protective AS3MT haplotype in the SAC population (68.7%) compared with the HGDP (14.3%, p < 0.001, Fisher exact test) and Peruvian (50.5%, p < 0.001) populations. Genome-wide microsatellite (n = 671) analysis showed no detectable level of population structure between SAC and Peruvian populations (measure of population differentiation FST = 0.006) and low levels of structure between SAC and HGDP populations (FST < 0.055 for all pairs of populations compared). Conclusions: Because population stratification seems unlikely to explain the differences in AS3MT haplotype frequencies, our data raise the possibility that, during a few thousand years, natural selection for tolerance to the environmental stressor arsenic may have increased the frequency of protective variants of AS3MT. Further studies are needed to investigate this hypothesis.
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| 11. |
- van der Harst, Pim, et al.
(författare)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 12. |
- Burman, Pia, et al.
(författare)
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Deaths Among Adult Patients With Hypopituitarism: Hypocortisolism During Acute Stress, and De Novo Malignant Brain Tumors Contribute to an Increased Mortality
- 2013
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:4, s. 1466-1475
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Tidskriftsartikel (refereegranskat)abstract
- Context: Patients with hypopituitarism have an increased standardized mortality rate. The basis for Objective: To investigate in detail the cause of death in a large cohort of patients with hypopituitarism Design and Methods: All-cause and cause-specific mortality in 1286 Swedish patients with Main Outcome Measures: Standardized mortality ratios (SMR) were calculated, with stratification for Results: An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence Conclusion: Two important causes of excess mortality were identified: first, adrenal crisis in response
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| 13. |
- Carlsson, A. C., et al.
(författare)
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Novel and established anthropometric measures and the prediction of incident cardiovascular disease : a cohort study
- 2013
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 37:12, s. 1579-1585
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to compare novel and established anthropometrical measures in their ability to predict cardiovascular disease (CVD), and to determine whether they improve risk prediction beyond classical risk factors in a cohort study of 60-year-old men and women. We also stratified the results according to gender to identify possible differences between men and women. Furthermore, we aimed to replicate our findings in a large independent cohort (The Malmo Diet and Cancer study-cardiovascular cohort).METHODS: This was a population-based study of 1751 men and 1990 women, aged 60 years and without CVD at baseline, with 375 incident cases of CVD during 11 years of follow-up. Weight, height, waist circumference (WC), hip circumference and sagittal abdominal diameter (SAD) were measured at baseline. Body mass index (BMI), waist-hip ratio (WHR), waist-hip-height ratio (WHHR), WC-to-height ratio (WCHR) and SAD-to-height ratio (SADHR) were calculated.RESULTS: All anthropometric measures predicted CVD in unadjusted Cox regression models per s.d. increment (hazard ratios, 95% confidence interval), while significant associations after adjustments for established risk CVD factors were noted for WHHR 1.20 (1.08-1.33), WHR 1.14 (1.02-1.28), SAD 1.13 (1.02-1.25) and SADHR 1.17 (1.06-1.28). WHHR had higher increases in C-statistics, and model improvements (likelihood ratio tests (P<0.001)). In the replication study (MDC-CC, n = 5180), WHHR was the only measure that improved Cox regression models in men (P = 0.01).CONCLUSION: WHHR, a new measure reflecting body fat distribution, showed the highest risk estimates after adjustments for established CVD risk factors. These findings were verified in men but not women in an independent cohort.
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| 14. |
- Den Ruijter, Hester M., et al.
(författare)
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Common Carotid Intima-Media Thickness Measurements in Cardiovascular Risk Prediction A Meta-analysis
- 2012
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Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598. ; 308:8, s. 796-803
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Tidskriftsartikel (refereegranskat)abstract
- Context The evidence that measurement of the common carotid intima-media thickness (CIMT) improves the risk scores in prediction of the absolute risk of cardiovascular events is inconsistent. Objective To determine whether common CIMT has added value in 10-year risk prediction of first-time myocardial infarctions or strokes, above that of the Framingham Risk Score. Data Sources Relevant studies were identified through literature searches of databases (PubMed from 1950 to June 2012 and EMBASE from 1980 to June 2012) and expert opinion. Study Selection Studies were included if participants were drawn from the general population, common CIMT was measured at baseline, and individuals were followed up for first-time myocardial infarction or stroke. Data Extraction Individual data were combined into 1 data set and an individual participant data meta-analysis was performed on individuals without existing cardiovascular disease. Results We included 14 population-based cohorts contributing data for 45 828 individuals. During a median follow-up of 11 years, 4007 first-time myocardial infarctions or strokes occurred. We first refitted the risk factors of the Framingham Risk Score and then extended the model with common CIMT measurements to estimate the absolute 10-year risks to develop a first-time myocardial infarction or stroke in both models. The C statistic of both models was similar (0.757; 95% CI, 0.749-0.764; and 0.759; 95% CI, 0.752-0.766). The net reclassification improvement with the addition of common CIMT was small (0.8%; 95% CI, 0.1%-1.6%). In those at intermediate risk, the net reclassification improvement was 3.6% in all individuals (95% CI, 2.7%-4.6%) and no differences between men and women. Conclusion The addition of common CIMT measurements to the Framingham Risk Score was associated with small improvement in 10-year risk prediction of first-time myocardial infarction or stroke, but this improvement is unlikely to be of clinical importance. JAMA. 2012;308(8):796-803 www.jama.com
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| 15. |
- Engström, David, 1976, et al.
(författare)
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Unconventional structure-assisted optical manipulation of high-index nanowires in liquid crystals
- 2012
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Ingår i: Optics Express. - 1094-4087. ; 20:7, s. 7741-7748
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Tidskriftsartikel (refereegranskat)abstract
- Stable optical trapping and manipulation of high-index particles in low-index host media is often impossible due to the dominance of scattering forces over gradient forces. Here we explore optical manipulation in liquid crystalline structured hosts and show that robust optical manipulation of high-index particles, such as GaN nanowires, is enabled by laser-induced distortions in long-range molecular alignment, via coupling of translational and rotational motions due to helicoidal molecular arrangement, or due to elastic repulsive interactions with confining substrates. Anisotropy of the viscoelastic liquid crystal medium and particle shape give rise to a number of robust unconventional trapping capabilities, which we use to characterize defect structures and study rheological properties of various thermotropic liquid crystals.
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| 16. |
- Engström, K., et al.
(författare)
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Can social capital explain mental health inequalities between immigrant groups?
- 2014
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Ingår i: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 24, s. 57-58
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundNearly 15% of Sweden’s population are immigrants and research has shown them to be one of the most susceptible groups to mental ill-health. The variance in mental health status can to a large extent be explained by different post-migrant factors. Social capital has been suggested to partly explain health inequalities between social groups and may be specifically important with regard to health inequalities between immigrant groups, due to its affinity with the concept of integration. This study aims to explore to what extent social capital can help to explain mental health inequalities between Swedish born and different immigrant groups.MethodsThe project is based on data from the Stockholm Public Health Cohort (SPHC). The SPHC combines information from repeated self-administered questionnaires, 2002 an onwards, with information from national and regional registers on a randomized sample of the adult population in Stockholm County. We employed a cross-sectional design using baseline data from 51,715 individuals from the SPHC. Mental health was measured using the 12-item General Health Questionnaire. Social capital was measured using indicators of bonding, bridging, and linking social capital. Immigrant status was decided depending on reason for immigration (refugee/labor). Mediation was tested using step-wise logistic regression.ResultsThe results show that refugees had greater risk of mental ill-health than labor immigrants. Among men both refugees and labor immigrants had greater risk of mental ill-health than Swedish born, which was true only for refugees among women. No significant differences in mental ill-health between Swedish born, labor immigrants and refugees remained after adjusting for social capital indicators.ConclusionsImmigrants in Sweden have greater risk of mental ill-health than Swedish born, both among men and women. Social capital seemed to explain most of the differences in mental ill-health between Swedish born and different immigrant groups. Increased knowledge of how social capital might mediate the effect of immigration status on mental health may be of significance for a variety of policy measures taken in the public-health arena and a step towards identifying elements of improvement of the integration process.
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| 17. |
- Engström, Olof, 1943, et al.
(författare)
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Gate stacks
- 2013
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Ingår i: Nanoscale CMOS: Innovative Materials, Modeling and Characterization. - : Wiley. ; , s. 23 - 67
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 18. |
- Evangelou, Evangelos, et al.
(författare)
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A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip
- 2014
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 73:12, s. 2130-2136
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. Methods We performed a two-stage meta-analysis on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. Results We accumulated 11 277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9x10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p= 5.6x10(-8)) and follow-up studies (p=7.3x10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9x10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2x10(-6), OR=1.27 in male specific analysis). Conclusions Novel genetic loci for hip OA were found in this meta-analysis of GWAS.
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| 19. |
- Fava, Cristiano, et al.
(författare)
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Serine/threonine kinase 39 is a candidate gene for primary hypertension especially in women: results from two cohort studies in Swedes.
- 2011
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Ingår i: Journal of Hypertension. - 1473-5598. ; 29, s. 484-491
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: As recently pinpointed by a genome-wide association study the serine/threonine kinase 39 (STK39) is a candidate gene for hypertension. This kinase is strongly implicated in sodium reabsorption by the kidney through its modulating effect on furosemide-sensitive and thiazide-sensitive channels. The aim of our study was to test the effects of the STK39 rs35929607A>G polymorphism on blood pressure (BP) levels and the prevalence and incidence of hypertension in middle-aged Swedes participating in two urban-based surveys in Malmö (Sweden). METHODS: The rs35929607A>G polymorphism was genotyped in 5634 participants included in the cardiovascular cohort of the 'Malmö Diet and Cancer-cardiovascular arm' (MDC-CVA) study and successively in 17 894 participants of the 'Malmö Preventive Project' (MPP) both at baseline and at reinvestigation after a mean of 23 years. The effect of the same single nucleotide polymorphism on salt sensitivity was tested in 39 participants of the Salt Reduction to Avoid Hypertension study. RESULTS: Both before and after adjustment for covariates, the functional rs35929607A>G polymorphism was associated with higher SBP and DBP values in the MDC-CVA, but not in the MPP. In both surveys, the polymorphism was associated with hypertension prevalence; after adjustment using the autosomal-dominant model, the odds ratio for hypertension ranged between 1.077 (MPP at baseline) and 1.151 (MDC-CVA) with P-value less than 0.05. After stratification for sex, the results remained statistically significant in women, but not in men. Carriers of the G-allele displayed an increase in salt sensitivity. CONCLUSION: Our results from two large cohort studies support previous evidence about the association of the STK39 rs35929607A>G variant with hypertension, especially in women. If further confirmed in successive studies, owing to its pivotal role in sodium reabsorption at the renal tubule level, STK39 might prove to be a suitable target for antihypertensive therapy. The greater effect of the STK39 rs35929607A>G polymorphism in women with respect to men deserves further investigation.
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| 20. |
- Fava, Cristiano, et al.
(författare)
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Vanin-1 T26I polymorphism, hypertension and cardiovascular events in two large urban-based prospective studies in Swedes.
- 2011
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Ingår i: Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 1590-3729 .- 0939-4753.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Vanin-1 (gene name VNN1) is an enzyme with pantetheinase activity generating the amino-thiol cysteamine which is implicated in the regulation of red-ox status through its effect on glutathione. We tested the hypothesis that the rs2294757 VNN1 T26I polymorphism could affect blood pressure (BP) levels, hypertension prevalence, and risk of incident cardiovascular events. METHODS AND RESULTS: The VNN1 T26I polymorphism was genotyped in 5664 participants of the cardiovascular cohort of the "Malmö Diet and Cancer" (MDC-CVA) study and successively in 17874 participants of the "Malmö Preventive project"(MPP). The incidence of cardiovascular events was monitored for an average of nearly 12 years of follow-up in the MDC-CVA and for 25 years in the MPP. Both before and after adjustment for sex, age and BMI in the MDC-CVA the polymorphism had a mild lowering effect on diastolic BP and hypertension, especially in females. However in MPP no effect on BP phenotypes was detectable. Before and after adjustment for major cardiovascular risk factors, the hazard ratio for incident ischemic stroke and coronary events in the MDC-CVA was not significantly different in carriers of different genotypes. CONCLUSIONS: Our data do not support a major role for the VNN1 T26I variant in determining BP level and incident ischemic events.
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| 21. |
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| 22. |
- Haq, S Raza, et al.
(författare)
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Side-Chain Interactions Form Late and Cooperatively in the Binding Reaction between Disordered Peptides and PDZ Domains
- 2012
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society. - 0002-7863 .- 1520-5126. ; 134:1, s. 599-605
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Tidskriftsartikel (refereegranskat)abstract
- Intrinsically disordered proteins are very common and mediate numerous protein-protein and protein-DNA interactions. While it is clear that these interactions are instrumental for the life of the mammalian cell, there is a paucity of data regarding their molecular binding mechanisms. Here we have used short peptides as a model system for intrinsically disordered proteins. Linear free energy relationships based on rate and equilibrium constants for the binding of these peptides to ordered target proteins, PDZ domains, demonstrate that native side-chain interactions form mainly after the rate-limiting barrier for binding and in a cooperative fashion. This finding suggests that these disordered peptides first form a weak encounter complex with non-native interactions. The data do not support the recent notion that the affinities of intrinsically disordered proteins toward their targets are generally governed by their association rate constants. Instead, we observed the opposite for peptide-PDZ interactions, namely, that changes in K-d correlate with changes in k(off).
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| 23. |
- Jansson, Jan-Håkan, et al.
(författare)
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Snus (Swedish smokeless tobacco) use and risk of stroke: pooled analyses of incidence and survival
- 2014
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 276:1, s. 87-95
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Tidskriftsartikel (refereegranskat)abstract
- Background. Snus is a moist smokeless tobacco product with high nicotine content. Its use has a short-term effect on the cardiovascular system, but the relationship between snus use and stroke is unclear. Objective. The aim of this study was to assess the associations between use of snus and incidence of and survival after stroke, both overall and according to subtypes. Methods. Pooled analyses of eight Swedish prospective cohort studies were conducted, including 130 485 men who never smoked. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of incidence and death after diagnosis using Cox proportional hazard regression models and case fatality and survival using logistic regression and Kaplan-Meier methods, respectively. Results. No associations were observed between the use of snus and the risk of overall stroke (HR 1.04, 95% CI 0.92-1.17) or of any of the stroke subtypes. The odds ratio (OR) of 28-day case fatality was 1.42 (95% CI 0.99-2.04) amongst users of snus who had experienced a stroke, and the HR of death during the follow-up period was 1.32 (95% CI 1.08-1.61). Conclusion. Use of snus was not associated with the risk of stroke. Hence, nicotine is unlikely to contribute importantly to the pathophysiology of stroke. However, case fatality was increased in snus users, compared with nonusers, but further studies are needed to determine any possible causal mechanisms.
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| 24. |
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| 25. |
- Lindberg, C A, et al.
(författare)
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Total desmosines in plasma and urine correlate with lung function.
- 2011
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936.
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the relationship between the matrix degradation biomarkers, desmosine and isodesmosine (desmosines), and lung function.Plasma and creatinine-corrected urinary total desmosines (P- and U-desmosines), lung function and carbon monoxide diffusion capacity (DL,CO) were measured in a cohort of subjects from the Swedish Twin Registry.Concentrations of U- and P-desmosines were measured in 349 and 318 subjects, respectively; approximately one-third of subjects had chronic obstructive pulmonary disease (COPD). Age, female gender, body mass index (BMI) and smoking were significantly associated with U-desmosines in a multiple linear regression analysis. In the overall population, after adjustments for age, gender, height, BMI and smoking, concentrations of U-desmosines were significantly correlated with all lung function measures, and P-desmosines with forced expiratory volume in 1 s and DL,CO (P<0.05). With the exception of residual volume versus P-desmosines, relationships between concentrations of desmosines and lung function measures were markedly stronger in subjects with COPD compared with those without COPD.These cross-sectional data showing associations between desmosines and several lung function variables suggest that desmosines, particularly U-desmosines, could be a useful biomarker of COPD status.
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| 26. |
- Mitrovic, I. Z., et al.
(författare)
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On the nature of the interfacial layer in ultra-thin TiN/LaluO3 gate stacks
- 2012
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 112:4, s. 044102-
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Tidskriftsartikel (refereegranskat)abstract
- We present a detailed investigation on the nature of the interfacial layer (IL) in ultra-thin TiN/LaLuO3 (LLO) gate stacks, which is of importance to facilitate CMOS scaling. The molecular beam deposited LaLuO3 films are found to be amorphous by high-resolution transmission electron microscopy. A similar to 9 angstrom thick LaLuO3/interlayer transition observed by medium energy ion scattering correlates with the presence of a dual silicate/SiO2-like interfacial layer derived from the analysis of photoelectron line positions and electron energy loss spectra. A theoretical model is used for the dielectric transition in a bi-layer LaLuO3/IL structure, linking physical and electrical characterization data. The obtained leakage current of 10(-3) A/cm(2) at 1.5 V and equivalent oxide thickness of 0.75 nm for TiN/LaLuO3 gate stacks are adequate for scaling in the 14-12 nm node.
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| 27. |
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| 28. |
- Nilsson, Hampus, et al.
(författare)
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Transition probabilities of astrophysical interest in the niobium ions Nb+ and Nb2
- 2010
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 511
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Tidskriftsartikel (refereegranskat)abstract
- Aims. We attempt to derive accurate transition probabilities for astrophysically interesting spectral lines of Nb II and Nb III and determine the niobium abundance in the Sun and metal-poor stars rich in neutron-capture elements. Methods. We used the time-resolved laser-induced fluorescence technique to measure radiative lifetimes in Nb II. Branching fractions were measured from spectra recorded using Fourier transform spectroscopy. The radiative lifetimes and the branching fractions were combined yielding transition probabilities. In addition, we calculated lifetimes and transition probablities in Nb II and Nb III using a relativistic Hartree-Fock method that includes core polarization. Abundances of the sun and five metal-poor stars were derived using synthetic spectra calculated with the MOOG code, including hyperfine broadening of the lines. Results. We present laboratory measurements of 17 radiative lifetimes in Nb II. By combining these lifetimes with branching fractions for lines depopulating the levels, we derive the transition probabilities of 107 Nb II lines from 4d(3)5p configuration in the wavelength region 2240-4700 angstrom. For the first time, we present theoretical transition probabilities of 76 Nb III transitions with wavelengths in the range 1430-3140 angstrom. The derived solar photospheric niobium abundance log epsilon(circle dot) = 1.44 +/- 0.06 is in agreement with the meteoritic value. The stellar Nb/Eu abundance ratio determined for five metal-poor stars confirms that the r-process is a dominant production method for the n-capture elements in these stars.
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| 29. |
- Pallavicini, Nicola, et al.
(författare)
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Cadmium isotope ratio measurements in environmental matrices by MC-ICP-MS
- 2014
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Ingår i: Journal of Analytical Atomic Spectrometry. - : Royal Society of Chemistry (RSC). - 0267-9477 .- 1364-5544. ; 29:9, s. 1570-1584
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Tidskriftsartikel (refereegranskat)abstract
- Various stages of an analytical method for high-precision cadmium (Cd) isotope ratio measurements by MC-ICP-MS (sample preparation, matrix separation, instrumental analysis and data evaluation) were critically evaluated and optimized for the processing of carbon-rich environmental samples. Overall reproducibility of the method was assessed by replicate preparation and Cd isotope ratio measurements in various environmental matrices (soil, sediment, Fe-Mn nodules, sludge, kidney, liver, leaves) and was found to be better than 0.1‰ (2σ for δ114Cd/110Cd) for the majority of samples. Cd isotope ratio data for several commercially-available reference materials are presented and compared with previously published results where available. The method was used in a pilot study focusing on the assessment of factors affecting Cd isotope composition in tree leaves. A summary of results obtained for a large number (n > 80) of birch (Betula pubescenes) leaves collected from different locations in Sweden and through the entire growing season is presented and potential reasons for observed variability in Cd isotope composition are discussed. Seasonal dynamics of element concentrations and isotope compositions in leaves were also compared for Os, Pb, Zn and Cd.
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| 30. |
- Petersson, K., et al.
(författare)
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SU‐E‐T‐809 : A Grading‐Study Based Tool to Assist in the Choice of Treatment Modality
- 2011
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Ingår i: Medical Physics. - : Wiley. - 0094-2405. ; 38:6, s. 3677-3677
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: It is common for radiation oncologists (ROs) today to have a mixed arsenal of radiotherapy treatment modalities at their disposal. To optimize a clinic's use of its different treatment modalities, while at the same time giving every patient an optimal treatment, is not a trivial task. The purpose of this study was to give ROs a tool to choose between available modalities. This would help to ensure that the most advanced modality is available for the patients that really benefits from this treatment, and allow for a more optimal use of the clinic's assets. This study included different modalities such as 3DCRT, step‐and‐shoot IMRT, and helical tomotherapy. Methods: Twenty‐three patients that had received treatment for tumours in different anatomical regions with the tomotherapy system were chosen. All tomotherapy plans were converted into seven‐beam step‐ and‐shoot IMRT plans using the treatment planning system SharePlan. When feasible, conventional 3DCRT plans were also created by our most experienced planner. A side‐by‐side demonstration of every patient's plans was performed. Ten experienced ROs were individually asked to compare and grade the plans. The results were statistically analysed by using Sign test. Results: The results show that for all regions combined, the TT plans were considered somewhat better than the IMRT plans and much better than the 3DCRT plans (p<0.05). Divided into the different anatomical regions, however, the perceived superiority of the TT plans, as compared to step‐and‐shoot IMRT, was only significant for the patients treated in the abdominal and pelvic region. Conclusions: Based on the ROs grading scores obtained in the present study, priority for treatment with the TT system should be given to patients with tumours in the abdominal and pelvic region. Other factors, such as the overall treatment time and the machine occupancy, may also be important for the final choice of treatment.
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| 31. |
- Rodushkin, Ilya, et al.
(författare)
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Elemental and isotopic characterization of cane and beet sugars
- 2011
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Ingår i: Journal of Food Composition and Analysis. - : Elsevier BV. - 0889-1575 .- 1096-0481. ; 24:1, s. 70-78
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Tidskriftsartikel (refereegranskat)abstract
- An interlaboratory program designed to assess the feasibility of using multi-element and isotopic measurements for determining the geographic origin of sugars permitted an intercomparison of the performance (in terms of limits of detection, reproducibility and bias) of various analytical techniques: inductively coupled plasma (ICP)-optical emission spectrometry (OES); different variations of ICP-mass spectrometry (MS): quadrupole (QMS), sector-field (SFMS) and multi-collector (MC-ICP-MS); thermal ionization MS (TIMS); and isotope ratio MS (IRMS). These various methods were applied to cane (raw and refined) and beet (refined) sugars from different origins. Concentrations of 63 elements and isotope ratios of Pb, Sr and C in sugar samples are reported. Determining the geographic origin of sugars appears feasible using elemental fingerprinting
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| 32. |
- Rodushkin, Ilya, et al.
(författare)
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Isotopic analyses by ICP-MS in clinical samples
- 2013
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 405:9, s. 2785-2797
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Tidskriftsartikel (refereegranskat)abstract
- This critical review focuses on inductively coupled plasma mass spectrometry (ICP-MS) based applications for isotope abundance ratio measurements in various clinical samples relevant to monitoring occupational or environmental exposure, human provenancing and reconstruction of migration pathways as well as metabolic research. It starts with a brief overview of recent advances in ICP-MS instrumentation, followed by selected examples that cover the fields of accurate analyte quantification using isotope dilution, tracer studies in nutrition and toxicology, and areas relying upon natural or man-made variations in isotope abundance ratios (Pb, Sr, actinides and stable heavy elements). Finally, some suggestions on future developments in the field are provided
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| 33. |
- Ståhlberg, Anders, 1975, et al.
(författare)
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Normal and Functional TP53 in Genetically Stable Myxoid/Round Cell Liposarcoma
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Myxoid/round-cell liposarcoma (MLS/RCLS) is characterized by either the fusion gene FUS-DDIT3 or the less commonly occurring EWSR1-DDIT3 and most cases carry few or no additional cytogenetic changes. There are conflicting reports concerning the status and role of TP53 in MLS/RCLS. Here we analysed four MLS/RCLS derived cell lines for TP53 mutations, expression and function. Three SV40 transformed cell lines expressed normal TP53 proteins. Irradiation caused normal posttranslational modifications of TP53 and induced P21 expression in two of these cell lines. Transfection experiments showed that the FUS-DDIT3 fusion protein had no effects on irradiation induced TP53 responses. Ion Torrent AmpliSeq screening, using the Cancer Hotspot panel, showed no dysfunctional or disease associated alleles/mutations. In conclusion, our results suggest that most MLS/RCLS cases carry functional TP53 genes and this is consistent with the low numbers of secondary mutations observed in this tumor entity.
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| 34. |
- Søvik, T T, et al.
(författare)
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Randomized clinical trial of laparoscopic gastric bypass versus laparoscopic duodenal switch for superobesity.
- 2010
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 97:2, s. 160-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:: Laparoscopic Roux-en-$\font\ss=cmss10 scaled 1000 \hbox{Y}$ gastric bypass (LRYGB) and laparoscopic biliopancreatic diversion with duodenal switch (LDS) are surgical options for superobesity. A randomized trial was conducted to evaluate perioperative (30-day) safety and 1-year results. METHODS:: Sixty patients with a body mass index (BMI) of 50-60 kg/m(2) were randomized to LRYGB or LDS. BMI, percentage of excess BMI lost, complications and readmissions were compared between groups. RESULTS:: Patient characteristics were similar in the two groups. Mean operating time was 91 min for LRYGB and 206 min for LDS (P < 0.001). One LDS was converted to open surgery. Early complications occurred in four patients undergoing LRYGB and seven having LDS (P = 0.327), with no deaths. Median stay was 2 days after LRYGB and 4 days after LDS (P < 0.001). Four and nine patients respectively had late complications (P = 0.121). Mean BMI at 1 year decreased from 54.8 to 38.5 kg/m(2) after LRYGB and from 55.2 to 32.5 kg/m(2) after LDS; percentage of excess BMI lost was greater after LDS (74.8 versus 54.4 per cent; P < 0.001). CONCLUSION:: LRYGB and LDS can be performed with comparable perioperative safety in superobese patients. LDS provides greater weight loss in the first year. Registration number: NCT00327912 (http://www.clinicaltrials.gov). Copyright (c) 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
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| 35. |
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