| 1. |
- Sundström, Johan, Professor, 1971-, et al.
(author)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
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In: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
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Journal article (peer-reviewed)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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| 2. |
- Sundin, Per-Ola, 1971-, et al.
(author)
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Measured glomerular filtration rate does not improve prediction of mortality by cystatin C and creatinine
- 2017
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In: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 32:4, s. 663-670
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Journal article (peer-reviewed)abstract
- Background: Cystatin C may add explanatory power for associations with mortality in combination with other filtration markers, possibly indicating pathways other than glomerular filtration rate (GFR). However, this has not been firmly established since interpretation of associations independent of measured GFR (mGFR) is limited by potential multicollinearity between markers of GFR. The primary aim of this study was to assess associations between cystatin C and mortality, independent of mGFR. A secondary aim was to evaluate the utility of combining cystatin C and creatinine to predict mortality risk.Methods: Cox regression was used to assess the associations of cystatin C and creatinine with mortality in 1157 individuals referred for assessment of plasma clearance of iohexol.Results: Since cystatin C and creatinine are inversely related to mGFR, cystatin C - 1 and creatinine - 1 were used. After adjustment for mGFR, lower cystatin C - 1 (higher cystatin C concentration) and higher creatinine - 1 (lower creatinine concentration) were independently associated with increased mortality. When nested models were compared, avoiding the potential influence of multicollinearity, the independence of the associations was supported. Among models combining the markers of GFR, adjusted for demographic factors and comorbidity, cystatin C - 1 and creatinine - 1 combined explained the largest proportion of variance in associations with mortality risk ( R 2 = 0.61). Addition of mGFR did not improve the model.Conclusions: Our results suggest that both creatinine and cystatin C have independent associations with mortality not explained entirely by mGFR and that mGFR does not offer a more precise mortality risk assessment than these endogenous filtration markers combined.
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| 3. |
- Ahlin, Sofie, 1985, et al.
(author)
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Macrophage Gene Expression in Adipose Tissue is Associated with Insulin Sensitivity and Serum Lipid Levels Independent of Obesity.
- 2013
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In: Obesity (Silver Spring, Md.). - : Wiley. - 1930-739X .- 1930-7381. ; 21:12
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Journal article (peer-reviewed)abstract
- Objective: Obesity is linked to both increased metabolic disturbances and increased adipose tissue macrophage infiltration. However, whether macrophage infiltration directly influences human metabolism is unclear. The aim of this study was to investigate if there are obesity-independent links between adipose tissue macrophages and metabolic disturbances. Design and Methods: Expression of macrophage markers in adipose tissue was analyzed by DNA microarrays in the SOS Sib Pair study and in patients with type 2 diabetes and a BMI-matched healthy control group. Results: The expression of macrophage markers in adipose tissue was increased in obesity and associated with several metabolic and anthropometric measurements. After adjustment for BMI, the expression remained associated with insulin sensitivity, serum levels of insulin, C-peptide, high density lipoprotein cholesterol (HDL-cholesterol) and triglycerides. In addition, the expression of most macrophage markers was significantly increased in patients with type 2 diabetes compared to the control group. Conclusion: Our study shows that infiltration of macrophages in human adipose tissue, estimated by the expression of macrophage markers, is increased in subjects with obesity and diabetes and associated with insulin sensitivity and serum lipid levels independent of BMI. This indicates that adipose tissue macrophages may contribute to the development of insulin resistance and dyslipidemia.
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| 4. |
- Bäcklund, Nils, et al.
(author)
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Salivary cortisol and cortisone in diagnosis of Cushing's syndrome - a comparison of six different analytical methods
- 2023
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In: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 61:10, s. 1780-1791
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Journal article (peer-reviewed)abstract
- Objectives: Salivary cortisol and cortisone at late night and after dexamethasone suppression test (DST) are increasingly used for screening of Cushing's syndrome (CS). We aimed to establish reference intervals for salivary cortisol and cortisone with three liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques and for salivary cortisol with three immunoassays (IAs), and evaluate their diagnostic accuracy for CS.Methods: Salivary samples at 08:00 h, 23:00 h and 08:00 h after a 1-mg DST were collected from a reference population (n=155) and patients with CS (n=22). Sample aliquots were analyzed by three LC-MS/MS and three IA methods. After establishing reference intervals, the upper reference limit (URL) for each method was used to calculate sensitivity and specificity for CS. Diagnostic accuracy was evaluated by comparing ROC curves.Results: URLs for salivary cortisol at 23:00 h were similar for the LC-MS/MS methods (3.4-3.9 nmol/L), but varied between IAs: Roche (5.8 nmol/L), Salimetrics (4.3 nmol/L), Cisbio (21.6 nmol/L). Corresponding URLs after DST were 0.7-1.0, and 2.4, 4.0 and 5.4 nmol/L, respectively. Salivary cortisone URLs were 13.5-16.6 nmol/L at 23:00 h and 3.0-3.5 nmol/L at 08:00 h after DST. All methods had ROC AUCs =0.96.Conclusions: We present robust reference intervals for salivary cortisol and cortisone at 08:00 h, 23:00 h and 08:00 h after DST for several clinically used methods. The similarities between LC-MS/MS methods allows for direct comparison of absolute values. Diagnostic accuracy for CS was high for all salivary cortisol and cortisone LC-MS/MS methods and salivary cortisol IAs evaluated.
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| 5. |
- Olofsson, Louise, 1977, et al.
(author)
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Preliminary report: Zn-alpha2-glycoprotein genotype and serum levels are associated with serum lipids.
- 2010
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In: Metabolism. - : Elsevier BV. - 1532-8600 .- 0026-0495. ; 59:9, s. 1316-1318
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Journal article (peer-reviewed)abstract
- Zn-alpha2-glycoprotein (ZAG) is a serum protein implicated in cancer cachexia and lipolysis. Our aim was to investigate serum levels of ZAG and polymorphisms in the ZAG gene in relation to serum lipids in man. Serum levels of ZAG correlated with serum levels of cholesterol (P = .00088) in healthy subjects and during weight loss (P = .059). The ZAG genotype was associated with total cholesterol (P = .014) and low-density lipoprotein cholesterol (P = .026) in healthy subjects, and the associations were replicated in an additional cohort (P = .0017 and P = .060, respectively). Our data indicate that ZAG plays a role in lipid metabolism.
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| 6. |
- Saiki, Atsuhito, et al.
(author)
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Tenomodulin is highly expressed in adipose tissue, increased in obesity, and down-regulated during diet-induced weight loss.
- 2009
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94:10, s. 3987-94
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Journal article (peer-reviewed)abstract
- CONTEXT: Tenomodulin (TNMD), a putative angiogenesis inhibitor, is expressed in hypovascular connective tissues. Global gene expression scans show that the TNMD gene also is expressed in human adipose tissue and that its expression is regulated in response to weight reduction; however, more detailed information is lacking. OBJECTIVE: The aim of this study was to investigate TNMD tissue distribution and TNMD gene expression in human adipose tissue in relation to obesity and metabolic disease. DESIGN, PATIENTS, AND INTERVENTIONS: TNMD gene expression, tissue distribution, and TNMD gene expression in adipose tissue from different depots, from lean and obese subjects, and during diet-induced weight reduction were analyzed by DNA microarray and real-time PCR. MAIN OUTCOME MEASURE: We primarily measured TNMD gene expression. RESULTS: The TNMD gene was predominantly expressed in sc adipose tissue. TNMD gene expression was higher in sc than omental adipose tissue both in lean (P = 0.002) and obese subjects (P = 0.014). In both women and men, TNMD gene expression was significantly higher in the obese subjects compared to the lean subjects (P = 1.1 x 10(-26) and P = 0.010, respectively). In a multiple linear regression analysis, BMI was a significant independent predictor of TNMD gene expression. TNMD gene expression was down-regulated during diet-induced weight loss, with a 65% decrease after 18 wk of diet (P < 0.0001). CONCLUSIONS: We conclude that human adipose tissue TNMD gene expression is highly affected by obesity, adipose tissue location, and weight loss, indicating that TNMD may play a role in adipose tissue function.
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| 7. |
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| 10. |
- Olsson, Per-Anders, 1971, et al.
(author)
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Effects on gravity from non-tidal sea level variations in the Baltic Sea
- 2009
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In: Journal of Geodynamics. - : Elsevier BV. - 0264-3707. ; 48:3-5, s. 151-156
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Journal article (peer-reviewed)abstract
- The main purpose of this paper is to investigate numerically the effects of non-tidal sea level variations in the Baltic Sea on gravity with special emphasis on the Swedish stations in the Nordic Absolute Gravity Project.To calculate the ocean loading effect on gravity the method described by Farrell (1972) is widely used. This method is based on convolution of a Green's function for gravity with the ocean load, but does not include the direct attraction depending on the height of the observation point. It is described how this effect is included in the Green's functions and how numerical integration is performed over a dense grid bounded by a very high resolution coastline. The importance of this high resolution is shown. The major part of the direct attraction for stations close to the coast comes from relatively small water masses close to the station. The total effect from the Baltic Sea, crustal loading and direct attraction, is calculated for 12 Swedish and one Finnish absolute gravity stations. The distance from the coast for these stations varies from 10 m to 150 km. It is shown that the total non-tidal gravity effect is significant, easily reaching values of 2–3 μgal for stations with high elevation close to the coast.In modelling the Glacial Isostatic Adjustment (GIA), the relation between the change of gravity and the absolute land uplift ((dg/dt) / (dh/dt)) contains information about the viscoelastic properties of the upper mantle. The Baltic Sea is located in the Fennoscandian postglacial land uplift area and experiences therefore a long-term sea level decrease. It is also shown that the magnitude of this long-term effect is not negligible for determination of the unknown part of (dg/dt) / (dh/dt).
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| 11. |
- Olsson, Per-Anders, 1971, et al.
(author)
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Modelling of the GIA-induced surface gravity change over Fennoscandia
- 2012
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In: Journal of Geodynamics. - : Elsevier BV. - 0264-3707. ; 61, s. 12-22
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Journal article (peer-reviewed)abstract
- This paper deals with the modelling of surface gravity change in Fennoscandia, induced by postglacial rebound or Glacial Isostatic Adjustment (GIA). The theoretical foundation is based on the theory introduced by [Peltier, 1974] and [Peltier, 1976] for a spherical, non-rotating, laterally homogenous, viscoelastic, Maxwell Earth and the solution of the Sea Level Equation, originally introduced by Farrel and Clark (1976), with time-dependent coastline geometry. The ice history is defined by the ice model ICE-5G. Rotational feedback is not included.The sensitivity of predictions of present day gravity rates View the MathML source, with respect to a selection of assumptions and approximations, is investigated numerically. Six model variants are defined: (i) linear relation between View the MathML source and the vertical deformation rate View the MathML source, (ii) direct attraction expressed in terms of internal and (iii) external harmonic series expansions as well as by (iv) analytical integration over rectangular prisms. For the most rigorous treatment of the direct attraction, the effect of simplified modelling of the sea level is also investigated. These modelling approximations of the sea level change include (v) fixed shorelines and (vi) eustatic sea level change. Predictions of View the MathML source for the model variants are plotted, compared and discussed.The most rigorous model (iv) and the linear model (i) differ less than 0.03 μGal yr−1 over land and close to, or over, the ocean the difference reaches maximally ∼0.5 μGal yr−1. Due to truncation at 180°, the high frequent nature of the direct attraction is not properly described by models (ii) and (iii). The two simplified sea level modelling approximations (v) and (vi) induce differences, compared to the most rigorous model exceeding 0.2 μGal yr−1 over land, i.e. about one order of magnitude worse than the linear model.
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| 12. |
- Olsson, Per-Anders, 1971
(author)
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On modelling of postglacial gravity change
- 2013
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Doctoral thesis (other academic/artistic)abstract
- Glacial isostatic adjustment (GIA) is the Earth's response to glacial-induced load variations on its surface. This phenomenon can today be observed in, for example, North America and Fennoscandia. Different observables, such as vertical and horizontal deformation of the crust, relative sea level change and disturbances in the gravity field, contribute different and complemental information on the phenomenon. Knowledge of the gravitational component is important for understanding the underlying geodynamical processes. Further, accurate predictions of the gravity change are important for e.g. reductions of geodetic observations to a reference epoch. During the last decade, efforts to observe the surface gravity change in Fennoscandia have been intensified and the observational accuracy successively improved. This offers new possibilities at the same time as it puts new demands on modelling. The purpose of this thesis is to study some aspects of the modelling of GIA-induced gravity change. We show that gravity stations close to the sea are affected by non-tidal sea level variations and that the direct attraction from the sea water constitutes a crucial contribution. Accurate modelling of the direct attraction from sea water is an intricate matter. We use different methods to model the direct attraction from GIA-induced sea level change and show that standard methods are not adequate. Further we solve the forward GIA modelling problem and show numerically how predictions of the gravity change are affected using different approximate methods. We also investigate the relation between gravity change and vertical displacement as they are predicted with the earth model depending on different sets of structural and rheological parameters. A linear relation is used as a reference. Deviations from the linear approximation are small, especially in Fennoscandia. The relation differs more between different regions included in the study than between different earth models within each region. The thesis also includes an overview of observational efforts to determine the postglacial land uplift and gravity change in Fennoscandia, as well as a general discussion on some modelling issues that form the background for the motivation of the thesis.
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| 13. |
- Olsson, Per-Anders, 1971, et al.
(author)
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The relation between gravity rate of change and vertical displacement in previously glaciated areas
- 2015
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In: Journal of Geodynamics. - : Elsevier BV. - 0264-3707. ; 83, s. 76-84
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Journal article (peer-reviewed)abstract
- The rate of change of surface gravity, dg/dt, and vertical deformation rate of the solid surface, du/dt, are two observables of glacial isostatic adjustment (GIA). They contribute with different information on the same phenomenon. Their relation contains information of the underlying physics and a trustworthy relation allows to combine these observations to strengthen the overall observational accuracy of the phenomenon. In this paper we investigate the predicted relation between dg/dt and du/dt in previously glaciated areas. We use the normal mode approach for one dimensional earth models and solutions of the sea level equation with time-dependent coastline geometry. Numerical predictions of dg/dt and du/dt are computed for Laurentia, Fennoscandia and the British Isles respectively, using six different earth models. Within each region a linear trend is then fitted using the relation dg/dt = C du/dt + dg_0/dt. The estimated C and dg_0/dt differ more between the regions than between different earth models within each region. For Fennoscandia C ≈ −0.163 μGal/mm and for Laurentia C ≈ −0.152 μGal/mm. Maximum residuals between the linear trend and spatially varying model predictions of dg/dt are 0.04 μGal/yr in Fennoscandia and 0.17 μGal/yr in Laurentia. For the British Isles the results are harder to interpret, mainly since this region is located on the zero uplift isoline of Fennoscandia. In addition, we show temporal variation of the relation since the last glacial maximum till present-day. The temporal and spatial variation of the relation between dg/dt and du/dt can be explained by (i) the elastic respectively viscous proportion of the total signal and (ii) the spectral composition of the regional signal. Additional local effects, such as the Newtonian attraction and elastic deformation from local sea level changes, are examined in a case study for six stations in the Nordic absolute gravity network. The influence of these local effects on the relation between View the dg/dt and du/dt is negligible except for extreme locations close to the sea.
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| 14. |
- Sundström, Johan, Professor, 1971-, et al.
(author)
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Rationale for a Swedish cohort consortium
- 2019
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In: Upsala Journal of Medical Sciences. - : Taylor & Francis Group. - 0300-9734 .- 2000-1967. ; 124:1, s. 21-28
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Journal article (peer-reviewed)abstract
- We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.
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| 15. |
- Åsberg, Dennis, 1988-, et al.
(author)
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A quality control method enhancement concept : Continual improvement of regulatory approved QC methods
- 2016
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In: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier. - 0731-7085 .- 1873-264X. ; 129, s. 273-281
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Journal article (peer-reviewed)abstract
- Quality Control methods (QC-methods) play an important role in the overall control strategy for drug manufacturing. However, efficient life-cycle management and continual improvement are hindered due to a variety of post-approval variation legislations across territories and a lack of harmonization of the requirements. As a result, many QC-methods fall behind the technical development. Developing the QC-method in accordance with the Quality by Design guidelines gives the possibility to do continual improvements inside the original Method Operable Design Region (MODR). However, often it is necessary to do changes outside the MODR, e.g. to incorporate new technology that was not available at the time the original method was development. Here, we present a method enhancement concept which allows minor adjustments, within the same measuring principle, outside the original MODR without interaction with regulatory agencies. The feasibility of the concept is illustrated by a case study of a QC-method based on HPLC, assumed to be developed before the introduction of UHPLC, where the switch from HPLC to UHPLC is necessary as a continual improvement strategy. The concept relies on the assumption that the System Suitability Test (SST) and failure modes are relevant for other conditions outside the MODR as well when the same measuring principle is used. It follows that it should be possible to move outside the MODR as long as the SST has passed. All minor modifications of the original, approved QC-method must be re-validated according to a template given in the original submission and a statistical equivalence should be shown between the original and modified QC-methods. To summarize, revalidation is handled within the pharmaceutical quality control system according to internal change control procedures, but without interaction with regulating agencies.
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