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Carlsson, A. C., Ruge, T., Kjøller, E., Hilden, J., Kolmos, H. J., Sajadieh, A., . . . Ärnlöv, J. (2018). 10-year associations between tumor necrosis factor receptors 1 and 2 and cardiovascular events in patients with stable coronary heart disease: a CLARICOR (effect of clarithromycin on mortality and morbidity in patients with ischemic heart disease) trial substudy. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 7(9), Article ID e008299.
Open this publication in new window or tab >>10-year associations between tumor necrosis factor receptors 1 and 2 and cardiovascular events in patients with stable coronary heart disease: a CLARICOR (effect of clarithromycin on mortality and morbidity in patients with ischemic heart disease) trial substudy
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2018 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 9, article id e008299Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.

METHODS AND RESULTS: <0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).

CONCLUSIONS: Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.

CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.

Keywords
cohort study, coronary atherosclerosis, tumor necrosis factor‐α
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-27534 (URN)10.1161/JAHA.117.008299 (DOI)000432332800014 ()29686027 (PubMedID)2-s2.0-85046402672 (Scopus ID)
Available from: 2018-04-26 Created: 2018-04-26 Last updated: 2018-06-05Bibliographically approved
Mokdad, A., Azzopardi, P., Cini, K., Kennedy, E., Sawyer, S., El Bcheraoui, C., . . . Murray, C. J. L. (2018). Adolescent health in the Eastern Mediterranean Region: findings from the global burden of disease 2015 study. International Journal of Public Health, 63(S1), 79-96
Open this publication in new window or tab >>Adolescent health in the Eastern Mediterranean Region: findings from the global burden of disease 2015 study
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2018 (English)In: International Journal of Public Health, ISSN 1661-8556, E-ISSN 1661-8564, Vol. 63, no S1, p. 79-96Article in journal (Refereed) Published
Abstract [en]

The 22 countries of the East Mediterranean Region (EMR) have large populations of adolescents aged 10-24 years. These adolescents are central to assuring the health, development, and peace of this region. We described their health needs. Using data from the Global Burden of Disease Study 2015 (GBD 2015), we report the leading causes of mortality and morbidity for adolescents in the EMR from 1990 to 2015. We also report the prevalence of key health risk behaviors and determinants. Communicable diseases and the health consequences of natural disasters reduced substantially between 1990 and 2015. However, these gains have largely been offset by the health impacts of war and the emergence of non-communicable diseases (including mental health disorders), unintentional injury, and self-harm. Tobacco smoking and high body mass were common health risks amongst adolescents. Additionally, many EMR countries had high rates of adolescent pregnancy and unmet need for contraception. Even with the return of peace and security, adolescents will have a persisting poor health profile that will pose a barrier to socioeconomic growth and development of the EMR

Keywords
Adolescent health; Burden of disease; Eastern Mediterranean Region
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-28036 (URN)10.1007/s00038-017-1003-4 (DOI)000433519400010 ()28776253 (PubMedID)
Available from: 2018-06-28 Created: 2018-06-28 Last updated: 2018-06-28Bibliographically approved
Wändell, P., Carlsson, A. C., Holzmann, M. J., Ärnlöv, J., Sundquist, J. & Sundquist, K. (2018). Associations between relevant cardiovascular pharmacotherapies and incident heart failure in patients with atrial fibrillation: a cohort study in primary care. Journal of Hypertension
Open this publication in new window or tab >>Associations between relevant cardiovascular pharmacotherapies and incident heart failure in patients with atrial fibrillation: a cohort study in primary care
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2018 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVE: To study association between relevant cardiovascular pharmacotherapy and incident congestive heart failure (CHF) in patients with atrial fibrillation treated in primary health care.

METHODS: Study population included all adults (n = 7975) aged 45 years and older diagnosed with atrial fibrillation at 75 primary care centers in Sweden between 2001 and 2007. Outcome was defined as a first diagnosis of CHF post-atrial fibrillation diagnosis. Association between CHF and treatment with relevant cardiovascular pharmacotherapies (beta blockers, calcium blockers, digitalis, diuretics, RAS blockers, and statins) was explored using Cox regression analysis with hazard ratios and 95% CIs. Adjustments were made for age, sociodemographic variables, and comorbid conditions (with or without cardiovascular disorders).

RESULTS: During a mean of 5.7 years (SD 2.3) of follow-up, totally 1552 patients (19.5%; 803 women and 749 men) had a recorded CHF diagnosis. Thiazides (hazard ratio 0.74, 95% CI 0.65-0.84), vessel-active calcium channel blockers (hazard ratio 0.76, 95% CI 0.67-0.86), and nonselective beta blockers (hazard ratio 0.84, 95% CI 0.72-0.98), with specifically sotalol representing 80% of nonselective beta blockers (hazard ratio 0.81, 95% CI 0.69-0.97), were associated with lower CHF risk in fully adjusted models. Loop diuretics (hazard ratio 1.41, 95% CI 1.25-1.57) were associated with a higher risk. Findings for thiazides and vessel-active channel blockers were consistent in the tested subgroups.

CONCLUSION: In this clinical setting, we found that thiazides, vessel-active calcium channel blockers, and nonselective beta blockers (specifically sotalol) were associated with a lower risk of incident CHF among patients with atrial fibrillation. The findings of the present study need to be confirmed in other settings.

National Category
Health Sciences
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-27774 (URN)10.1097/HJH.0000000000001813 (DOI)29870433 (PubMedID)
Available from: 2018-06-07 Created: 2018-06-07 Last updated: 2018-06-07Bibliographically approved
Mokdad, A., Tehrani-Banihashemi, A., Moradi-Lakeh, M., El Bcheraoui, C., Charara, R., Afshin, A., . . . Murray, C. (2018). Burden of cardiovascular diseases in the Eastern Mediterranean Region, 1990-2015: findings from the Global Burden of Disease 2015 study. International Journal of Public Health, 63(S1), 137-149
Open this publication in new window or tab >>Burden of cardiovascular diseases in the Eastern Mediterranean Region, 1990-2015: findings from the Global Burden of Disease 2015 study
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2018 (English)In: International Journal of Public Health, ISSN 1661-8556, E-ISSN 1661-8564, Vol. 63, no S1, p. 137-149Article in journal (Refereed) Published
Abstract [en]

To report the burden of cardiovascular diseases (CVD) in the Eastern Mediterranean Region (EMR) during 1990-2015. We used the 2015 Global Burden of Disease study for estimates of mortality and disability-adjusted life years (DALYs) of different CVD in 22 countries of EMR. A total of 1.4 million CVD deaths (95% UI: 1.3-1.5) occurred in 2015 in the EMR, with the highest number of deaths in Pakistan (465,116) and the lowest number of deaths in Qatar (723). The age-standardized DALY rate per 100,000 decreased from 10,080 in 1990 to 8606 in 2015 (14.6% decrease). Afghanistan had the highest age-standardized DALY rate of CVD in both 1990 and 2015. Kuwait and Qatar had the lowest age-standardized DALY rates of CVD in 1990 and 2015, respectively. High blood pressure, high total cholesterol, and high body mass index were the leading risk factors for CVD. The age-standardized DALY rates in the EMR are considerably higher than the global average. These findings call for a comprehensive approach to prevent and control the burden of CVD in the region.

Keywords
Cardiovascular disease; Burden of disease; Eastern Mediterranean Region
National Category
Clinical Medicine
Research subject
Health and Welfare; Health and Welfare
Identifiers
urn:nbn:se:du-28043 (URN)10.1007/s00038-017-1012-3 (DOI)
Available from: 2018-06-28 Created: 2018-06-28 Last updated: 2018-06-28Bibliographically approved
Mokdad, A., El Bcheraoui, C., Afshin, A., Charara, R., Khalil, I., Moradi-Lakeh, M., . . . Murray, C. (2018). Burden of obesity in the Eastern Mediterranean Region: findings from the Global Burden of Disease 2015 study. International Journal of Public Health, 63(S1), 165-176
Open this publication in new window or tab >>Burden of obesity in the Eastern Mediterranean Region: findings from the Global Burden of Disease 2015 study
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2018 (English)In: International Journal of Public Health, ISSN 1661-8556, E-ISSN 1661-8564, Vol. 63, no S1, p. 165-176Article in journal (Refereed) Published
Abstract [en]

We used the Global Burden of Disease (GBD) 2015 study results to explore the burden of high body mass index (BMI) in the Eastern Mediterranean Region (EMR). We estimated the prevalence of overweight and obesity among children (2-19 years) and adults (20 years) in 1980 and 2015. The burden of disease related to high BMI was calculated using the GBD comparative risk assessment approach. The prevalence of obesity increased for adults from 15.1% (95% UI 13.4-16.9) in 1980 to 20.7% (95% UI 18.8-22.8) in 2015. It increased from 4.1% (95% UI 2.9-5.5) to 4.9% (95% UI 3.6-6.4) for the same period among children. In 2015, there were 417,115 deaths and 14,448,548 disability-adjusted life years (DALYs) attributable to high BMI in EMR, which constitute about 10 and 6.3% of total deaths and DALYs, respectively, for all ages. This is the first study to estimate trends in obesity burden for the EMR from 1980 to 2015. We call for EMR countries to invest more resources in prevention and health promotion efforts to reduce this burden.

Keywords
Obesity; Burden of disease; Eastern Mediterranean Region
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-28041 (URN)10.1007/s00038-017-1002-5 (DOI)000433519400016 ()
Available from: 2018-06-28 Created: 2018-06-28 Last updated: 2018-06-28Bibliographically approved
Ruge, T., Carlsson, A. C., Ingelsson, E., Risérus, U., Sundström, J., Larsson, A., . . . Ärnlöv, J. (2018). Circulating endostatin and the incidence of heart failure. Scandinavian Cardiovascular Journal, 1-6
Open this publication in new window or tab >>Circulating endostatin and the incidence of heart failure
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2018 (English)In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, p. 1-6Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVE:

Circulating levels of endostatin are elevated in many underlying conditions leading to heart failure such as hypertension, diabetes, chronic kidney disease and ischemic heart disease. Yet, the association between endostatin and the incidence of heart failure has not been reported previously in the community.

DESIGN:

We investigated the longitudinal association between serum endostatin levels and incident heart failure in two community-based cohorts of elderly: Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 966; mean age 70 years, 51% women, 81 events, mean follow-up 10 years) and Uppsala Longitudinal Study of Adult Men (ULSAM, n = 747 men; mean age 78 years, 98 heart failure events, mean follow-up 8 years). We also investigated the cross-sectional association between endostatin and echocardiographic left ventricular systolic function and diastolic function (ejection fraction and E/A-ratio, respectively).

RESULTS:

Higher serum endostatin was associated with an increased risk for heart failure in both cohorts after adjustment for established heart failure risk factors, glomerular filtration rate and N-terminal pro-brain natriuretic peptide (NT-proBNP) (PIVUS: multivariable hazard ratio (HR) per 1-standard deviation (SD) increase, HR 1.46 (95%CI, 1.17-1.82, p < .001); ULSAM: HR 1.29 (95%CI, 1.00-1.68, p < .05). In cross-sectional analyses at baseline, higher endostatin was significantly associated with both worsened left ventricular systolic and diastolic function in both cohorts. Conclusion Higher serum endostatin was associated with left ventricular dysfunction and an increased heart failure risk in two community-based cohorts of elderly. Our findings encourage further experimental studies that investigate the role of endostatin in the development of heart failure.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
Keywords
Heart failure; angiogenesis; anti-angiogenesis; epidemiology; left ventricular systolic function; population based studies; remodelling of extracellular matrix
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-27933 (URN)10.1080/14017431.2018.1483080 (DOI)29893146 (PubMedID)2-s2.0-85048355578 (Scopus ID)
Available from: 2018-06-18 Created: 2018-06-18 Last updated: 2018-06-25Bibliographically approved
Stenemo, M., Nowak, C., Byberg, L., Sundström, J., Giedraitis, V., Lind, L., . . . Ärnlöv, J. (2018). Circulating proteins as predictors of incident heart failure in the elderly.. European Journal of Heart Failure, 20(1), 55-62
Open this publication in new window or tab >>Circulating proteins as predictors of incident heart failure in the elderly.
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2018 (English)In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 20, no 1, p. 55-62Article in journal (Refereed) Published
Abstract [en]

AIMS: To identify novel risk markers for incident heart failure using proteomic profiling of 80 proteins previously associated with cardiovascular pathology.

METHODS AND RESULTS: Proteomic profiling (proximity extension assay) was performed in two community-based prospective cohorts of elderly individuals without heart failure at baseline: the Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS, n = 901, median age 70.2 (interquartile range 70.0-70.3) years, 80 events]; and the Uppsala Longitudinal Study of Adult Men [ULSAM, n = 685, median age 77.8 (interquartile range 76.9-78.1) years, 90 events]. Twenty-nine proteins were associated with incident heart failure in the discovery cohort PIVUS after adjustment for age and sex, and correction for multiple testing. Eighteen associations replicated in ULSAM. In pooled analysis of both cohorts, higher levels of nine proteins were associated with incident heart failure after adjustment for established risk factors: growth differentiation factor 15 (GDF-15), T-cell immunoglobulin and mucin domain 1 (TIM-1), tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), spondin-1 (SPON1), matrix metalloproteinase-12 (MMP-12), follistatin (FS), urokinase-type plasminogen activator surface receptor (U-PAR), osteoprotegerin (OPG), and suppression of tumorigenicity 2 (ST2). Of these, GDF-15, U-PAR, MMP-12, TRAIL-R2, SPON1 and FS were associated with worsened echocardiographic left ventricular systolic function at baseline, while only TIM-1 was positively associated with worsened diastolic function (P < 0.02 for all).

CONCLUSION: Proteomic profiling identified several novel associations between proteins involved in apoptosis, inflammation, matrix remodelling, and fibrinolysis with incident heart failure in elderly individuals. Our results encourage additional studies investigating the underlying mechanisms and the clinical utility of our findings.

Keywords
Biomarkers, Epidemiology, Heart failure, Left ventricular dysfunction, Proteomics, Risk prediction
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-26378 (URN)10.1002/ejhf.980 (DOI)000423809700007 ()28967680 (PubMedID)
Available from: 2017-10-05 Created: 2017-10-05 Last updated: 2018-02-22Bibliographically approved
Stattin, K., Hållmarker, U., Ärnlöv, J., James, S., Michaelsson, K. & Byberg, L. (2018). Decreased hip, lower leg and humeral fractures but increased forearm fractures in highly active individuals. Journal of Bone and Mineral Research
Open this publication in new window or tab >>Decreased hip, lower leg and humeral fractures but increased forearm fractures in highly active individuals
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2018 (English)In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681Article in journal (Refereed) Epub ahead of print
Abstract [en]

It is not known how physical exercise affects the risk of different types of fractures, especially in highly active individuals. To investigate this association, we studied a cohort of 118,204 men and 71,757 women who from 1991 to 2009 participated in Vasaloppet, a long-distance cross-country skiing race in Sweden, and 505,194 nonparticipants frequency-matched on sex, age, and county of residence from the Swedish population. Participants ranged from recreational exercisers to world-class skiers. Race participation, distance of race run, number of races participated in, and finishing time were used as proxies for physical exercise. Incident fractures from 1991 to 2010 were obtained from national Swedish registers. Over a median follow-up of 8.9 years, 53,175 fractures of any type, 2929 hip, 3107 proximal humerus, 11,875 lower leg, 11,733 forearm, and 2391 vertebral fractures occurred. In a Cox proportional hazard regression analysis using time-updated exposure and covariate information, participation in the race was associated with an increased risk of any type of fracture (hazard ratio [HR], 1.02; 95% CI, 1.00 to 1.05); forearm fractures had an HR, 1.11 with a 95% CI, 1.06 to 1.15. There was a lower risk of hip (HR, 0.75; 95% CI, 0.67 to 0.83), proximal humerus (HR, 0.90; 95% CI, 0.82 to 0.98), and lower leg fractures (HR, 0.93; 95% CI, 0.89 to 0.97), whereas the HR of vertebral fracture was 0.97 with a 95% CI, 0.88 to 1.07. Among participants, the risk of fracture was similar irrespective of race distance and number of races run. Participants close to the median finishing time had a lower risk of fracture compared with faster and slower participants. In summary, high levels of physical exercise were associated with a slightly higher risk of fractures of any type, including forearm fractures, but a lower risk of hip, proximal humerus, and lower leg fractures.

Keywords
epidemiology, exercise, fracture prevention, orthopedics, osteoporosis
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-27987 (URN)10.1002/jbmr.3476 (DOI)29933501 (PubMedID)
Available from: 2018-06-25 Created: 2018-06-25 Last updated: 2018-06-25Bibliographically approved
Mokdad, A., Moradi-Lekeh, M., El Bcheraoui, C., Khalil, I., Charara, R., Afshin, A., . . . Murray, C. (2018). Diabetes mellitus and chronic kidney disease in the Eastern Mediterranean Region: findings from the Global Burden of Disease 2015 study. International Journal of Public Health, 63(S1), 177-186
Open this publication in new window or tab >>Diabetes mellitus and chronic kidney disease in the Eastern Mediterranean Region: findings from the Global Burden of Disease 2015 study
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2018 (English)In: International Journal of Public Health, ISSN 1661-8556, E-ISSN 1661-8564, Vol. 63, no S1, p. 177-186Article in journal (Refereed) Published
Abstract [en]

We used findings from the Global Burden of Disease 2015 study to update our previous publication on the burden of diabetes and chronic kidney disease due to diabetes (CKD-DM) during 1990-2015. We extracted GBD 2015 estimates for prevalence, mortality, and disability-adjusted life years (DALYs) of diabetes (including burden of low vision due to diabetes, neuropathy, and amputations and CKD-DM for 22 countries of the EMR from the GBD visualization tools. In 2015, 135,230 (95% UI 123,034-148,184) individuals died from diabetes and 16,470 (95% UI 13,977-18,961) from CKD-DM, 216 and 179% increases, respectively, compared to 1990. The total number of people with diabetes was 42.3 million (95% UI 38.6-46.4 million) in 2015. DALY rates of diabetes in 2015 were significantly higher than the expected rates based on Socio-demographic Index (SDI). Our study showed a large and increasing burden of diabetes in the region. There is an urgency in dealing with diabetes and its consequences, and these efforts should be at the forefront of health prevention and promotion.

Keywords
Diabetes; Chronic kidney disease; Burden of disease; Eastern Mediterranean Region
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-28039 (URN)10.1007/s00038-017-1014-1 (DOI)000433519400017 ()
Available from: 2018-06-28 Created: 2018-06-28 Last updated: 2018-06-28Bibliographically approved
Corsonello, A., Roller-Wirnsberger, R., Di Rosa, M., Fabbietti, P., Wirnsberger, G., Kostka, T., . . . Lattanzio, F. (2018). Estimated glomerular filtration rate and functional status among older people: A systematic review.. European journal of internal medicine, Article ID S0953-6205(18)30226-7.
Open this publication in new window or tab >>Estimated glomerular filtration rate and functional status among older people: A systematic review.
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2018 (English)In: European journal of internal medicine, ISSN 0953-6205, E-ISSN 1879-0828, article id S0953-6205(18)30226-7Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND: The association between chronic kidney disease (CKD) and functional status may change as a function of the equation used to estimate glomerular filtration rate (eGFR). We reviewed the predictive value of different eGFR equations in regard to frailty and disability outcomes.

METHODS: We searched Pubmed from inception to March 2018 for studies investigating the association between eGFR and self-reported and/or objective measures of frailty or disability. Cross-sectional and longitudinal studies were separately analysed.

RESULTS: We included 16 studies, one of which reporting both cross-sectional and longitudinal data. Three out of 7 cross-sectional studies compared different eGFR equations in regard to their association with functional status: two studies showed that cystatin C-based, but not creatinine-based eGFR may be associated with hand-grip strength or frailty; another study showed that two different creatinine-based eGFR equations may be similarly associated with disability. Four out of 10 longitudinal studies provided comparative data: two studies reported similar association with disability for different creatinine-based eGFR equations; one study showed that creatinine-based eGFR was not associated with frailty, but a not significant trend for association was observed with cystatin C-based eGFR; one study showed that cystatin C-based but not creatinine-based eGFR may predict incident mobility disability, while both methods may predict gait speed decline. High heterogeneity was observed in regard to confounders included in reviewed studies. None of them included the most recently published equations.

CONCLUSION: Available data do not support the superiority of one of the eGFR equations in terms of measuring or predicting functional decline.

Keywords
Creatinine, Cystatin C, Disability, Estimated glomerular filtration rate (eGFR), Frailty
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-27990 (URN)10.1016/j.ejim.2018.05.030 (DOI)29936073 (PubMedID)2-s2.0-85048772858 (Scopus ID)
Available from: 2018-06-25 Created: 2018-06-25 Last updated: 2018-07-04Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-6933-4637

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