| 1. |
- Carlsson, Axel C, et al.
(författare)
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Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes : findings from two community based cohorts of elderly
- 2014
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 237:1, s. 236-242
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers.METHODS: The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years).RESULTS: In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatingsTNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation.CONCLUSIONS: An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.
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| 2. |
- Benaim, Andre, et al.
(författare)
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Building a pathway for innovation : Lessons learned from developing an online platform
- 2014
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Ingår i: Proceedings of NordDesign 2014 Conference, NordDesign 2014. - Eespo, Finland : Aalto University. - 9781904670582 ; , s. 662-669
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Konferensbidrag (refereegranskat)abstract
- Companies are constantly being pressured to innovate in order to stay competitive in the short run and have new offerings in the long run. One way of boosting innovation is to develop idea support systems that go beyond the traditional methods and tools. Through a qualitative study, this paper explores the lessons learned from developing an online platform for idea generation, and discusses it in terms of innovation process, climate, and capabilities. The results show that the platform itself is not enough for innovation. The structure and work processes around the platform are as important, which implies the need to design processes and procedures that allow an idea to develop, providing, focus, idea feedback and role clarity.
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| 3. |
- Carlsson, Axel C, et al.
(författare)
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Soluble TNF receptors and kidney dysfunction in the elderly
- 2014
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 25:6, s. 1313-1320
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Tidskriftsartikel (refereegranskat)abstract
- The importance of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in the development of kidney disease is being unraveled. Yet, community-based data regarding the role of sTNFRs are lacking. We assessed serum sTNFRs and aspects of kidney damage cross-sectionally in two independent community-based cohorts of elderly participants: Prospective Investigation of the Vasculature in Uppsala Seniors (n=815; mean age, 75 years; 51% women) and Uppsala Longitudinal Study of Adult Men (n=778; mean age, 78 years). Serum sTNFR1 correlated substantially with different aspects of kidney pathology in the Uppsala Longitudinal Study of Adult Men cohort (R=-0.52 for estimated GFR, R=0.22 for urinary albumin-to-creatinine ratio, and R=0.17 for urinary kidney injury molecule-1; P<0.001 for all), with similar correlations in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort. These associations remained significant after adjustment for age, sex, inflammatory markers, and cardiovascular risk factors and were also evident in participants without diabetes. Serum sTNFR2 was associated with all three markers in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort (P<0.001 for all). Our findings from two independent community-based cohorts confirm and extend results of previous studies supporting circulating sTNFRs as relevant biomarkers for kidney damage and dysfunction in elderly individuals, even in the absence of diabetes.
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| 4. |
- Carlsson, Axel C, et al.
(författare)
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Soluble tumor necrosis factor receptor 1 is associated with glomerular filtration rate progression and incidence of chronic kidney disease in two community-based cohorts of elderly individuals
- 2015
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Ingår i: CardioRenal Medicine. - : S. Karger AG. - 1664-3828 .- 1664-5502. ; 5:4, s. 278-288
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We aimed to explore and validate the longitudinal associations between soluble tumor necrosis factor receptor 1 (sTNFR1), glomerular filtration rate (GFR) progression, and chronic kidney disease (CKD) incidence in two independent community-based cohorts of elderly individuals with prespecified subgroup analyses in individuals without prevalent diabetes.Research design and methods: Two community-based cohorts of elderly individuals were used with 5-year follow-up data on estimated GFR: the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 437 men; mean age: 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 703; mean age: 70 years; 51% women). GFR categories were defined as >= 60, 30-60, and <30 ml/min/1.73 m(2).Results: In longitudinal multivariable logistic regression models adjusted for inflammatory markers and established cardiovascular risk factors, higher serum sTNFR1 was significantly associated with an increased risk to progress to a lower GFR category in both ULSAM and PIVUS [odds ratio (OR) per standard deviation (SD) increase 1.28 (95% CI 1.03-1.60) and OR 1.56 (95% CI 1.30-1.87), respectively]. Also, in subgroup analyses in individuals with a GFR >= 60 ml/min/1.73 m(2) at baseline, higher sTNFRs were associated with incident CKD after 5 years in both cohorts [ULSAM: OR per SD increase 1.49 (95% CI 1.16-1.9) and PIVUS: OR 1.84 (95% CI 1.50-2.26)]. Associations were similar in individuals without diabetes.Conclusions: Higher circulating sTNFR1 independently predicts the progression to a worse GFR category and CKD incidence in elderly individuals even in the absence of diabetes. Further studies are warranted to investigate the underlying mechanisms, and to evaluate the clinical relevance of our findings.
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| 5. |
- Carlsson, Axel C, et al.
(författare)
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Urinary kidney injury molecule 1 and incidence of heart failure in elderly men
- 2013
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Ingår i: European Journal of Heart Failure. - : Oxford University Press. - 1388-9842 .- 1879-0844. ; 15:4, s. 447-446
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: There is growing recognition of the clinical importance of cardiorenal syndrome-the bidirectional interplay between kidney and cardiac dysfunction. Yet, the role of kidney tubular damage in the development of heart failure is less studied. The objective of this study was to investigate whether urinary kidney injury molecule (KIM)-1, a specific marker of tubular damage, predisposes to an increased heart failure risk.METHODS AND RESULTS: This was a community-based cohort study [Uppsala Longitudinal study of Adult Men (ULSAM)] of 565, 77-year-old men free from heart failure at baseline. Heart failure hospitalizations were used as outcome. During follow-up (median 8.0 years), 73 participants were hospitalized for heart failure. In models adjusted for cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, LDL/HDL ratio, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, LV hypertrophy, and prevalent cardiovascular disease) and markers of kidney dysfunction and damage [cystatin C-based glomerular filtration rate (GFR) and urinary albumin/creatinine ratio], a higher urinary KIM-1/creatinine ratio was associated with higher risk for heart failure (hazard ratio upper vs. lower tertile, 1.81; 95% confidence interval 1.01-3.29; P < 0.05). Participants with a combination of low GFR (<60 mL/min/1.72 m(2)) and high KIM-1/creatinine (>128 ng/mmol) had a 3-fold increase in heart failure risk compared with participants with normal GFR and KIM-1 (P < 0.001).CONCLUSION: Our findings suggest that kidney tubular damage predisposes to an increased risk for heart failure in the community. Further studies are needed to clarify the causal role of KIM-1 in the development of heart failure, and to evaluate the clinical utility of urinary KIM-1 measurements.
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| 6. |
- Carlsson, Axel C, et al.
(författare)
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Urinary kidney injury molecule-1 and the risk of cardiovascular mortality in elderly men
- 2014
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Ingår i: American Society of Nephrology. Clinical Journal. - 1555-9041 .- 1555-905X. ; 9:8, s. 1393-1401
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Kidney injury molecule-1 (KIM-1) has been suggested as a clinically relevant highly specific biomarker of acute kidney tubular damage. However, community-based data on the association between urinary levels of KIM-1 and the risk for cardiovascular mortality are lacking. This study aimed to investigate the association between urinary KIM-1 and cardiovascular mortality.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a prospective study, using the community-based Uppsala Longitudinal Study of Adult Men (N=590; mean age 77 years; baseline period, 1997-2001; median follow-up 8.1 years; end of follow-up, 2008).RESULTS: During follow-up, 89 participants died of cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models were adjusted for cardiovascular risk factors (age, systolic BP, diabetes, smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, and history of cardiovascular disease) and for markers of kidney dysfunction and damage (cystatin C-based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM-1/creatinine (from 24-hour urine collections) was associated with a higher risk for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high KIM-1/creatinine (upper quintile, ≥175 ng/mmol), low eGFR (≤60 ml/min per 1.73 m(2)), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio≥3 g/mol) had a >8-fold increased risk compared with participants with low KIM-1/creatinine (<175 ng/mmol), normal eGFR (>60 ml/min per 1.73 m(2)), and normoalbuminuria (albumin/creatinine ratio<3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56; P<0.001).CONCLUSIONS: These findings suggest that higher urinary KIM-1 may predispose to a higher risk of cardiovascular mortality independently of established cardiovascular risk factors, eGFR, and albuminuria. Additional studies are needed to further assess the utility of measuring KIM-1 in the clinical setting.
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| 7. |
- Filla, Reno, 1973-
(författare)
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Operator and Machine Models for Dynamic Simulation of Construction Machinery
- 2005
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- VIRTUAL PROTOTYPING has been generally adopted in product development in order to minimise the traditional reliance on testing of physical prototypes. It thus constitutes a major step towards solving the conflict of actual increasing development cost and time due to increasing customer demands on one side, and the need to decrease development cost and time due to increasing competition on the other. Particularly challenging for the off-road equipment industry is that its products, working machines, are complex in architecture. Tightly coupled, non-linear sub-systems of different technical domains make prediction and optimisation of the complete system’s dynamic behaviour difficult.Furthermore, in working machines the human operator is essential for the performance of the total system. Properties such as productivity, fuel efficiency, and operability are all not only dependent on inherent machine properties and working place conditions, but also on how the operator uses the machine. This is an aspect that is traditionally neglected in dynamic simulations, because the modelling needs to be extended beyond the technical system.The research presented in this thesis focuses on wheel loaders, which are representative for working machines. The technical system and the influence of the human operator is analysed, and so-called short loading cycles are described in depth. Two approaches to rule-based simulation models of a wheel loader operator are presented and used in simulations. Both operator models control the machine model by means of engine throttle, lift and tilt lever, steering wheel, and brake only – just as a human operator does. Also, only signals that a human operator can sense are used in the models. It is demonstrated that both operator models are able to adapt to basic variations in workplace setup and machine capability. Thus, a “human element” can be introduced into dynamic simulation of working machines, giving more relevant answers with respect to operator-influenced complete-machine properties such as productivity, fuel efficiency, and operability already in the concept phase of the product development process.
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| 8. |
- Ruge, Toralph, et al.
(författare)
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Endostatin Level is Associated with Kidney Injury in the Elderly : Findings from Two Community-Based Cohorts
- 2014
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Ingår i: American Journal of Nephrology. - : S. Karger AG. - 0250-8095 .- 1421-9670. ; 40:5, s. 417-424
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to investigate the associations between circulating endostatin and the different aspects of renal dysfunction, namely, estimated (cystatin C) glomerular filtration rate (GFR) and urine albumin-creatinine ratio (ACR). Methods: Two independent longitudinal community-based cohorts of elderly. ULSAM, n = 786 men; age 78 years; median GFR 74 ml/min/1.73 m(2); median ACR 0.80 mg/mmol); and PIVUS, n = 815; age 75 years; 51% women; median GFR; 67 ml/min/1.73 m(2); median ACR 1.39 mg/mmol. Cross-sectional associations between the endostatin levels and GFR as well as ACR, and longitudinal association between endostatin at baseline and incident CKD (defined as GFR <60 ml/min/1.73 m(2)) were assessed. Results: In cross-sectional regression analyses adjusting for age, gender, inflammation, and cardiovascular risk factors, serum endostatin was negatively associated with GFR (ULSAM: B-coefficient per SD increase -0.51, 95% CI (-0.57, -0.45), p < 0.001; PIVUS -0.47, 95% CI (-0.54, -0.41), p < 0.001) and positively associated with ACR (ULSAM: B-coefficient per SD increase 0.24, 95% CI (0.15, 0.32), p < 0.001; PIVUS 0.13, 95% CI (0.06-0.20), p < 0.001) in both cohorts. Moreover, in longitudinal multivariable analyses, higher endostatin levels were associated with increased risk for incident CKD defined as GFR < 60 ml/min/1.73 m(2) at re-investigations in both ULSAM (odds ratio per SD increase of endostatin 1.39 (95% CI 1.01-1.90) and PIVUS 1.68 (95% CI 1.36-2.07)). Conclusions: Higher circulating endostatin is associated with lower GFR and higher albuminuria and independently predicts incident CKD in elderly subjects. Further studies are warranted to investigate the underlying mechanisms linking endostatin to kidney pathology, and to evaluate the clinical relevance of our findings. (C) 2014 S. Karger AG, Basel
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| 9. |
- Ärnlöv, Johan, et al.
(författare)
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Higher fibroblast growth factor-23 increases the risk of all-cause and cardiovascular mortality in the community
- 2013
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Ingår i: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 83, s. 160-166
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Tidskriftsartikel (refereegranskat)abstract
- Fibroblast growth factor-23 (FGF23), a regulator of mineral metabolism, has been linked to cardiovascular disease in chronic kidney disease. As community-based data of the longitudinal association between FGF23 and cardiovascular events are lacking, we investigated a possible relationship in 727 men of the Uppsala Longitudinal Study of Adult Men population-based cohort (mean age 77 years). During a median follow-up of 9.7 years, 110 participants died of cardiovascular causes. In Cox regression models adjusted for age and established cardiovascular risk factors, higher serum FGF23 was associated with a significantly increased risk for cardiovascular mortality (hazard ratio (HR) per increased s.d. of 1.36). This relationship remained significant, albeit attenuated, after adjustment for glomerular filtration rate (GFR) (HR 1.21). FGF23 was also associated with all-cause mortality, although the association was weaker than that with cardiovascular mortality, and it was nonsignificant in fully adjusted multivariate models. Spline analysis suggested a log-linear relationship between FGF23 and outcome. Participants with a combination of high FGF23 (>60 pg/ml), low GFR (<60 ml/min), and micro-/macro-albuminuria (albumin/creatinine ratio above 3 mg/ml) had an almost eightfold increased risk compared with participants without these abnormalities. Thus, a higher FGF23 level is associated with an increased cardiovascular mortality risk in the community. Clinical trials are needed to determine whether FGF23 is a modifiable risk factor.Kidney International advance online publication, 5 September 2012; doi:10.1038/ki.2012.327.
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| 10. |
- Ärnlöv, Johan, et al.
(författare)
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Serum FGF23 and risk of cardiovascular events in relation to mineral metabolism and cardiovascular pathology
- 2013
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Ingår i: American Society of Nephrology. Clinical Journal. - : American Society of Nephrology. - 1555-9041 .- 1555-905X. ; 8:5, s. 781-786
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives Circulating fibroblast growth factor-23 is associated with adverse cardiovascular outcomes in CKD and non-CKD individuals, but the underlying mechanism remains unclear. This study tested whether this association is independent of mineral metabolism and indices of subclinical cardiovascular pathology. Design, setting, participants, & measurements The prospective association between fibroblast growth factor-23 and major cardiovascular events (a composite of hospital-treated myocardial infarction, hospital-treated stroke, or all-cause mortality) was investigated in the community-based Prospective Investigation of the Vasculature in Uppsala Seniors (n=973; mean age=70 years, 50% women) using multivariate logistic regression. Subjects were recruited between January of 2001 and June of 2004. Results During follow-up (median=5.1 years), 112 participants suffered a major cardiovascular event. In logistic regression models adjusted for age, sex, and estimated GFR, higher fibroblast growth factor-23 was associated with increased risk for major cardiovascular events (odds ratio for tertiles 2 and 3 versus tertile 1=1.92, 95% confidence interval=1.19-3.09, P<0.01). After additional adjustments in the model, adding established cardiovascular risk factors, confounders of mineral metabolism (calcium, phosphate, parathyroid hormone, and 25 (OH)-vitamin D), and indices of subclinical pathology (flow-mediated vasodilation, endothelial-dependent and -independent vasodilation, arterial stiffness, and atherosclerosis and left ventricular mass) attenuated this relationship, but it remained significant (odds ratio for tertiles 2 and 3 versus tertile 1=1.69, 95% confidence interval=1.01-2.82, P<0.05). Conclusions Fibroblast growth factor-23 is an independent predictor of cardiovascular events in the community, even after accounting for mineral metabolism abnormalities and subclinical cardiovascular damage. Circulating fibroblast growth factor-23 may reflect novel and important aspects of cardiovascular risk yet to be unraveled. Clin J Am Soc Nephrol 8: 781-786, 2013. doi: 10.2215/CJN.09570912
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