| 1. |
- Carlsson, Tobias, et al.
(author)
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Algorithm for generating a Brownian motion on a sphere
- 2010
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In: Journal of physics A: Mathematical and theoretical. - : IOP Publishing. - 1751-8113 .- 1751-8121. ; 43:50, s. 505001-
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Journal article (peer-reviewed)abstract
- We present a new algorithm for generation of a random walk on a two-dimensional sphere. The algorithm is obtained by viewing the 2-sphere as the equator in the 3-sphere surrounded by an infinitesimally thin band with boundary which reflects Brownian particles and then applying known effective methods for generating Brownian motion on the 3-sphere. To test the method, the diffusion coefficient was calculated in computer simulations using the new algorithm and, for comparison, also using a commonly used method in which the particle takes a Brownian step in the tangent plane to the 2-sphere and is then projected back to the spherical surface. The two methods are in good agreement for short time steps, while the method presented in this paper continues to give good results also for larger time steps, when the alternative method becomes unstable.
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| 2. |
- Kamerlin, Natasha, et al.
(author)
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Construction of a closed polymer network for computer simulations
- 2014
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In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 141:15, s. 154113-
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Journal article (peer-reviewed)abstract
- Computer simulations are an important tool for linking the behaviour of polymer materials to the properties of the constituent polymer chains. In simulations, one normally uses periodic boundary conditions to mimic a macroscopic system. For a cross-linked polymer network, this will impose restrictions on the motion of the polymer chains at the borders of the simulation cell. We present a new method for constructing a three-dimensional closed network without periodic boundaries by embedding the system onto the surface of a sphere in four dimensions. This method can also be used to construct finite-sized gel particles for simulating the swelling of particles in a surrounding solvent. The method is described in algorithmic detail to allow the incorporation of the method into different types of simulation programs. We also present the results of Brownian dynamics simulations, analyzing the end-to-end distribution, radial distribution function, and the pore size distribution for different volume fractions and for chains with varying stiffness.
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| 3. |
- Alvarsson, Jonathan, et al.
(author)
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Ligand-Based Target Prediction with Signature Fingerprints
- 2014
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In: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 54:10, s. 2647-2653
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Journal article (peer-reviewed)abstract
- When evaluating a potential drug candidate it is desirable to predict target interactions in silico prior to synthesis in order to assess, e.g., secondary pharmacology. This can be done by looking at known target binding profiles of similar compounds using chemical similarity searching. The purpose of this study was to construct and evaluate the performance of chemical fingerprints based on the molecular signature descriptor for performing target binding predictions. For the comparison we used the area under the receiver operating characteristics curve (AUC) complemented with net reclassification improvement (NRI). We created two open source signature fingerprints, a bit and a count version, and evaluated their performance compared to a set of established fingerprints with regards to predictions of binding targets using Tanimoto-based similarity searching on publicly available data sets extracted from ChEMBL. The results showed that the count version of the signature fingerprint performed on par with well-established fingerprints such as ECFP. The count version outperformed the bit version slightly; however, the count version is more complex and takes more computing time and memory to run so its usage should probably be evaluated on a case-by-case basis. The NRI based tests complemented the AUC based ones and showed signs of higher power.
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| 4. |
- Carlsson, Axel C., et al.
(author)
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Country of birth-specific and gender differences in prevalence of diabetes in Sweden
- 2013
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In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 100:3, s. 404-408
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Journal article (peer-reviewed)abstract
- Objective: The aim was to investigate country or region of birth-specific prevalence and gender differences of diabetes in residents in Sweden, using Swedish-born men and women as referent. Methods: The Apolipoprotein MOrtality RISk (AMORIS) cohort was used (184,000 men and 151,453 women) aged between 20 and 80 years, with data from the CALAB laboratory, Stockholm, 1985-1996. Diabetes was defined as fasting glucose >= 7.0 mmol/L or a hospital diagnosis of diabetes. Country of birth was obtained by linkage to Swedish Censuses 1970-1990. Standardized prevalence rate ratios (SPRR) with 95% confidence intervals (95% CI) were estimated. Results: Five groups of women and one group of men had a significantly higher prevalence than Swedish-born (based on SPRR): women born in Iraq (6.0 (95% CI 1.3-28.9)), North Africa (6.9 (95% CI 3.1-15.3)), South Asia (3.1 (95% CI 1.0-10.0)), Syria (5.3 (95% CI 1.8-16.0)), Turkey (3.7 (95% CI 1.2-10.9)) and men born in other Middle Eastern countries (2.3 (95% CI 1.0-5.5)). Swedish-born men had a higher age-standardized prevalence of diabetes (3.9%) than Swedish born women ( 2.5%). A higher prevalence among men was also seen in other Western countries. In contrast, a higher age-standardized prevalence among women was observed in immigrants from Turkey (8.9% vs. 3.1%, p < 0.001), Syria (13.1% vs. 4.0%, p = 0.002), and North Africa (16.8% vs. 6.6%, p < 0.001). Conclusion: Female immigrants to Sweden from Iraq, North Africa, South Asia, Syria, and Turkey have an increased prevalence of diabetes of substantial public health concern.
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| 5. |
- Carlsson, Axel C, et al.
(author)
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Soluble TNF receptors and kidney dysfunction in the elderly
- 2014
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In: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 25:6, s. 1313-1320
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Journal article (peer-reviewed)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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| 6. |
- Carlsson, Axel C, et al.
(author)
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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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In: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 237:1, s. 236-242
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Journal article (peer-reviewed)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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| 7. |
- Carlsson, Axel C, et al.
(author)
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Urinary kidney injury molecule 1 and incidence of heart failure in elderly men
- 2013
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In: European Journal of Heart Failure. - : Oxford University Press. - 1388-9842 .- 1879-0844. ; 15:4, s. 447-446
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Journal article (peer-reviewed)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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| 8. |
- Carlsson, Axel C, et al.
(author)
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Urinary kidney injury molecule-1 and the risk of cardiovascular mortality in elderly men
- 2014
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In: American Society of Nephrology. Clinical Journal. - 1555-9041 .- 1555-905X. ; 9:8, s. 1393-1401
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Journal article (peer-reviewed)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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| 9. |
- Carlsson, Jenny Rubensdotter, et al.
(author)
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Drug experts of the future, today? : Depiction of the pharmacist profession in Swedish professional and lay print media
- 2012
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In: Research in Social and Administrative Pharmacy. - : Elsevier BV. - 1551-7411 .- 1934-8150. ; 8:2, s. 133-144
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Journal article (peer-reviewed)abstract
- Background: The Swedish pharmacy market is presently being reregulated. The state-owned pharmacy monopoly company was divided and sold during 2009, and certain nonprescription medicines are now allowed in nonpharmacy settings. The changes will likely affect the pharmacist's role and the image of the community pharmacist in society. This change may affect how pharmacists are seen by society at large, and therefore, a baseline showing how pharmacists are depicted before the reregulation is of great value. Objectives: The aim of this study was to describe how the pharmacist profession is depicted in print media in Sweden, with a focus on community pharmacy. Methods: A deductive qualitative content analysis with material from print media was conducted, using professional criteria as a framework. Swedish print media from October 2005 to October 2008 were searched and all relevant articles included. Results: A total of 139 articles were included. Most articles came from professional journals, that is, journals directed toward pharmacist or related professions. The results show that the pharmacist profession is not highly visible and that this lack of visibility is disappointing to pharmacists. Conclusions: Society, as reflected in print media, does not display an awareness of the pharmacist role in Sweden. Although this is disappointing for the profession, it allows pharmacists to influence the depiction and hence their position in society.
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| 10. |
- Carlsson, Tobias, et al.
(author)
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Brownian dynamics of a compressed polymer brush model : Off-equilibrium response as a function of surface coverage and compression rate
- 2011
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In: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 13:35, s. 16084-16094
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Journal article (peer-reviewed)abstract
- We study the compressive behaviour of a polymer-covered surface (i.e., a "polymer brush'') using Brownian dynamics simulations. The model consists of grafted chains with variable flexibility, variable intra-and inter-chain interactions, as well as different surface coverage. We discuss the polymer brush response to confinement by considering variable rates of compression under a hard plane. Our results show a small degree of inter-chain entanglement, regardless of whether the interaction is attractive or merely excluded volume. We observe that the molecular shape depends strongly on the surface coverage. Dense brushes exhibit a limited degree of lateral deformation under compression; instead, chains undergo a transition that produces a local patch with near-solid packing. This effect due to surface density can be undone partially by increasing the attractive nature of the chain interaction, by modulating the rate of compression, or by allowing "soft anchoring'', i.e., the possible Brownian drift of the grafting bead on the surface. We have also studied the polymer brush relaxation while maintaining the compressing plane, as well as after its sudden removal. We find evidence that also the relaxation depends on surface density; dense brushes appear to be configurationally frustrated at high compression and are unable to undergo swelling, regardless of the pressure applied.
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