| 1. |
- Bentham, James, et al.
(författare)
-
A century of trends in adult human height
- 2016
-
Ingår i: eLIFE. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
|
|
| 2. |
- Bentham, James, et al.
(författare)
-
A century of trends in adult human height
- 2016
-
Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
|
|
| 3. |
- Brante, Thomas, et al.
(författare)
-
Profession och vetenskap : idéer och strategier för ett professionslärosäte
- 2009
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Förord av Björn Brorström, Prorektor Högskolan i Borås Ett professionslärosäte bedriver utbildning och forskning på vetenskaplig grund. Vetenskapliga metoder tillämpas och framkomna resultat prövas för att säkra tillförlitlighet och relevans. Förmågan att problematisera, formulera frågor och välja lämpliga metoder för att besvara frågor är egenskaper för god forskning och utmärkande för en stark utbildnings- och forskningsmiljö. Vid ett professionslärosäte finns samtidigt en stark strävan efter att i utbildning och forskning ta till vara den kunskap och de erfarenheter som professioner besitter och därigenom säkra en hög grad av praktisk relevans. Växelverkan mellan teori och praktik och erfarenhetsutbyte mellan forskare och praktiker är ständigt pågående. Det finns ingen avslutning på processen utan den pågår utan avbrott. En nödvändig förutsättning för ett fruktbart samarbete är en ömsesidig respekt och vilja att stödja och ifrågasätta varandra. Forskaren måste vara beredd på kritik för bristen på praktisk relevans och professionsföreträdaren måste vara beredd på att förtrogenhetskunskapens lämplighet ifrågasätts. Det är en fråga om med- och mothåll från båda håll i syfte att långsiktigt utveckla teori och praktik. Det är en utmaning att utveckla, etablera och därefter kontinuerligt försvara och förbättra professionslärosätet. Ett led i utvecklingen är att inom ramen för Högskolan i Borås föra en debatt om innebörden av ett professionslärosäte och vad vi behöver göra för att förbättra verksamheten. På uppdrag av rektor Lena Nordholm har medarbetare vid Bibliotekshögskolan utvecklat och ansvarat för en seminarieserie benämnd Profession och vetenskap. Seminarierna spände över ett brett fält. En av många viktiga frågor som diskuterades flitigt var huruvida vi ska forska om professioner, i för eller med, eller kanske alltihop samtidigt. Bidragen publiceras nu i denna antologi som ges ut inom ramen för Högskolan i Borås rapportserie Vetenskap för profession. Rapporten Profession och vetenskap – idéer och strategier för ett professionslärosäte, som redigerats av universitetsadjunkt Maria Lindh, kommer att få stor betydelse inom lärosätet och i vårt samarbete med företrädare för näringsliv, kulturliv och offentlig verksamhet. Jag ser det som en intressant fortsättning att anordna ett antal seminarier med inbjudna representanter för professioner där artiklarna i denna rapport kan ligga till grund för erfarenhetsutbyte och diskussioner.
|
|
| 4. |
|
|
| 5. |
- Fridén, Michael, et al.
(författare)
-
Effects of a low-carbohydrate high polyunsaturated fat diet or a healthy Nordic diet versus usual care on liver fat content and cardiometabolic risk factors in people with type 2 diabetes and prediabetes: a randomized controlled trial (NAFLDiet)
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Previous trials have shown that plant-derived polyunsaturated fatty acids (PUFA) in place of saturated fat reduces liver fat, a prerequisite for non-alcoholic fatty liver disease (NAFLD). The effect on liver fat from a novel “anti-lipogenic diet” replacing carbohydrates with PUFA or a healthy Nordic diet (HND) higher in whole-grains but lower in saturated fat has not yet been examined. Objectives: To investigate the effects on changes in liver fat (primary outcome) and other cardiometabolic risk factors after 12 months of follow-up in individuals with prediabetes or T2D from three different diet comparisons: a low carbohydrate high PUFA (LCPUFA) diet versus a HND, a LCPUFA diet versus usual care (UC) and a HND versus UC. Methods: A three-arm parallel ad libitum randomized trial was conducted. Adult men and women (n=148) were randomized to one of the three diet groups. Participants in all groups received key food items on a monthly/bimonthly basis. Liver fat and cardiometabolic risk factors were assessed at baseline and after 12 months. Dietary adherence was assessed using weighed food diaries and objective biomarkers. General linear models were employed to estimate the intention-to-treat (ITT) effect. Results: Dietary adherence was high for all diet groups. Liver fat was reduced to a similar extent in the LCPUFA and the HND group compared to UC (-1.46% (95% CI: -2.42, -0.51)) and -1.76 % (95% CI: -2.96, -0.57), respectively. No difference in liver fat between LCPUFA and HND was observed. Body weight and HbA1c decreased more in the HND compared to the other diet groups whereas no differences were observed between LCPUFA and UC. Similar reductions in LDL-cholesterol were observed for the HND and the LCPUFA group compared to UC, but only the HND reduced triglycerides and C-reactive protein (CRP) compared with UC. No differences were observed for any other secondary outcomes.Conclusions: A LCPUFA diet and a HND both reduced liver fat as compared with UC. Given the sustained weight loss after the HND compared to the other groups, together with improvements in other cardiometabolic markers, the HND in particular seems to be useful for the treatment of T2D and NAFLD.
|
|
| 6. |
- Hagberg, Johan, et al.
(författare)
-
Nordic retail research : An introduction
- 2012
-
Ingår i: Nordic Retail Research: Emerging Diversity. - : BAS Publishers. - 9789172463110 ; , s. 19-32
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- A presentation of retailing in the Nordic countries together with an introduction to the anthology and the co-authors.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Eggers, Kai M, et al.
(författare)
-
Relations of growth-differentiation factor-15 to biomarkers reflecting vascular pathologies in a population-based sample of elderly subjects
- 2012
-
Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 72:1, s. 45-51
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Growth-differentiation factor-15 (GDF-15) has recently emerged as a risk predictor in patients with cardiac diseases. GDF-15 is commonly related to cardiovascular risk factors, inflammatory activity and cardiac abnormalities. However, it is not clear whether it might be an indicator of vascular pathologies as well.Methods.Circulating levels of GDF-15 were measured in 1004 elderly community dwellers participating in the PIVUS study. The relations of GDF-15 to biomarkers of endothelial activation (E-selectin, P-selectin, ICAM-1, VCAM-1), extracellular matrix degradation (MMP-9, TIMP-1), coagulatory activity (D-dimer, von Willebrand factor, prothrombin fragment 1 + 2, factor VIIa), and fibrinolytic activity (PAI-1 activity, tPA-antigen) were assessed by multiple linear regressions.Results. The median GDF-15 level was 1135 ng/L. By linear correlation analysis, GDF-15 exhibited a moderate relation to von Willebrand factor (r = 0.30), and weak, albeit significant relations (r = 0.13-0.29) to E-selectin, P-selectin, ICAM-1, VCAM-1, MMP-9, TIMP-1, D-dimer, PAI-1 activity and tPA-antigen. The relations to the assessed biomarkers of endothelial activation, TIMP-1, D-dimer and von Willebrand factor remained significant applying multiple linear regression models adjusted for clinical covariates and echocardiographic data. There were no significant relations between GDF-15 and biomarkers solely reflecting coagulatory activity.Conclusions.In the elderly, GDF-15 reflects endothelial activation and vascular inflammation and thus, multiple pathways involved in the development and progression of atherosclerosis.
|
|
| 10. |
- Engström, Gunnar, et al.
(författare)
-
The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
-
Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
|
|
| 11. |
- Eriksdotter-Jönhagen, Maria, et al.
(författare)
-
Encapsulated cell biodelivery of nerve growth factor to the Basal forebrain in patients with Alzheimer's disease.
- 2012
-
Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 33:1, s. 18-28
-
Tidskriftsartikel (refereegranskat)abstract
- Degeneration of cholinergic neurons in the basal forebrain correlates with cognitive decline in patients with Alzheimer's disease (AD). Targeted delivery of exogenous nerve growth factor (NGF) has emerged as a potential AD therapy due to its regenerative effects on the basal forebrain cholinergic neurons in AD animal models. Here we report the results of a first-in-man study of encapsulated cell (EC) biodelivery of NGF to the basal forebrain of AD patients with the primary objective to explore safety and tolerability.
|
|
| 12. |
- Folkersen, Lasse, et al.
(författare)
-
Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
-
Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
-
Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
|
|
| 13. |
- Folkersen, Lasse, et al.
(författare)
-
Integration of known DNA, RNA and protein biomarkers provides prediction of anti-TNF response in rheumatoid arthritis : results from the COMBINE study.
- 2016
-
Ingår i: Molecular Medicine. - : Springer Science and Business Media LLC. - 1076-1551 .- 1528-3658. ; 22, s. 322-328
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In rheumatoid arthritis (RA) several recent efforts have sought to discover means of predicting which patients would benefit from treatment. However, results have been discrepant with few successful replications. Our objective was to build a biobank with DNA, RNA and protein measurements to test the claim that the current state-of-the-art precision medicine will benefit RA patients.METHODS: We collected 451 blood samples from 61 healthy individuals and 185 RA patients initiating treatment, before treatment initiation and at a 3 month follow-up time. All samples were subjected to high-throughput RNA sequencing, DNA genotyping, extensive proteomics and flow cytometry measurements, as well as comprehensive clinical phenotyping. Literature review identified 2 proteins, 52 single-nucleotide polymorphisms (SNPs) and 72 gene-expression biomarkers that had previously been proposed as predictors of TNF inhibitor response (∆DAS28-CRP).RESULTS: From these published TNFi biomarkers we found that 2 protein, 2 SNP and 8 mRNA biomarkers could be replicated in the 59 TNF initiating patients. Combining these replicated biomarkers into a single signature we found that we could explain 51% of the variation in ∆DAS28-CRP. This corresponds to a sensitivity of 0.73 and specificity of 0.78 for the prediction of three month ∆DAS28-CRP better than -1.2.CONCLUSIONS: The COMBINE biobank is currently the largest collection of multi-omics data from RA patients with high potential for discovery and replication. Taking advantage of this we surveyed the current state-of-the-art of drug-response stratification in RA, and identified a small set of previously published biomarkers available in peripheral blood which predicts clinical response to TNF blockade in this independent cohort.
|
|
| 14. |
- Hagström, Emil, et al.
(författare)
-
Plasma parathyroid hormone and risk of congestive heart failure in the community
- 2010
-
Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 12:11, s. 1186-1192
-
Tidskriftsartikel (refereegranskat)abstract
- In experimental studies parathyroid hormone (PTH) has been associated with underlying causes of heart failure (HF) such as atherosclerosis, left ventricular hypertrophy, and myocardial fibrosis. Individuals with increased levels of PTH, such as primary or secondary hyperparathyroidism patients, have increased risk of ischaemic heart disease and HF. Moreover, increasing PTH is associated with worse prognosis in patients with overt HF. However, the association between PTH and the development HF in the community has not been reported. In a prospective, community-based study of 864 elderly men without HF or valvular disease at baseline (mean age 71 years, the ULSAM study) the association between plasma (P)-PTH and HF hospitalization was investigated adjusted for established HF risk factors (myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and hypercholesterolaemia) and variables reflecting mineral metabolism (S-calcium, S-phosphate, P-vitamin D, S-albumin, dietary calcium and vitamin D intake, physical activity, glomerular filtration rate, and blood draw season). During follow-up (median 8 years), 75 individuals were hospitalized due to HF. In multivariable Cox-regression analyses, higher P-PTH was associated with increased HF hospitalization (hazard ratio for 1-SD increase of PTH, 1.41, 95% CI 1.12-1.77, P = 0.003). Parathyroid hormone also predicted hospitalization in participants without apparent ischaemic HF and in participants with normal P-PTH. In a large community-based sample of elderly men, PTH predicted HF hospitalizations, also after accounting for established risk factors and mineral metabolism variables. Our data suggest a role for PTH in the development of HF even in the absence of overt hyperparathyroidism.
|
|
| 15. |
- Hagström, Emil, et al.
(författare)
-
Plasma parathyroid hormone and the risk of cardiovascular mortality in the community
- 2009
-
Ingår i: Circulation. - : American Heart Association. - 0009-7322 .- 1524-4539. ; 119:21, s. 2765-2771
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Diseases with elevated levels of parathyroid hormone (PTH) such as primary and secondary hyperparathyroidism are associated with increased incidence of cardiovascular disease and death. However, data on the prospective association between circulating PTH levels and cardiovascular mortality in the community are lacking. METHODS AND RESULTS: The Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men (mean age, 71 years; n=958), was used to investigate the association between plasma PTH and cardiovascular mortality. During follow-up (median, 9.7 years), 117 participants died of cardiovascular causes. In Cox proportional-hazards models adjusted for established cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease), higher plasma PTH was associated with higher risk for cardiovascular mortality (hazard ratio for 1-SD increase in PTH, 1.38; 95% confidence interval, 1.18 to 1.60; P<0.001). This association remained essentially unaltered in participants without previous cardiovascular disease and in participants with normal PTH (<6.8 pmol/L) with no other signs of a disturbed mineral metabolism (normal serum calcium, 2.2 to 2.6 mmol/L; normal glomerular filtration rate, >50 mL . min(-1) . 1.73 m(-2) and without vitamin D deficiency, plasma 25-OH vitamin D >37.5 nmol/L). Interestingly, elevated plasma PTH (>5.27 pmol/L) accounted for 20% (95% confidence interval, 10 to 26) of the population-attributable risk proportion for cardiovascular mortality. CONCLUSIONS: Plasma PTH levels predict cardiovascular mortality in the community, even in individuals with PTH within the normal range. Further studies are warranted to evaluate the clinical implications of measuring PTH in cardiovascular risk prediction and to elucidate whether PTH is a modifiable risk factor.
|
|
| 16. |
- Hagström, Emil, et al.
(författare)
-
Plasma-parathyroid hormone is associated with subclinical and clinical atherosclerotic disease in 2 community-based cohorts
- 2014
-
Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 34:7, s. 1567-1579
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Cardiovascular risk factors have different impact on different arterial territories. Diseases with elevated circulating parathyroid hormone (PTH) such as primary hyperparathyroidism and chronic renal failure have been shown to be associated with an increased risk of cardiovascular disease, predominantly heart or cerebrovascular diseases. However, data on the associations between circulating PTH and peripheral atherosclerosis are limited.APPROACH AND RESULTS: Two prospective, community-based studies were used. In 306 men and women, who were 70 years old, from the Prospective investigation of the vasculature in Uppsala seniors (PIVUS) study, cross-sectional relations between PTH and atherosclerotic burden assessed by whole-body magnetic resonance angiography were investigated. In 998 men, who were 71 years old, from the Uppsala longitudinal study of adult men (ULSAM) study, the association between PTH concentration and risk of subsequent nonfatal atherosclerotic disease (excluding coronary or cerebrovascular disease) was investigated. Adjusting for established vascular risk factors, PTH was associated with burden of atherosclerosis (increase in total atherosclerotic score per SD PTH increase: 0.04, 0.003-0.08; P=0.03) in the PIVUS study. During follow-up in the ULSAM study (median 16.7 years), 89 men were diagnosed with nonfatal atherosclerotic disease. In Cox-regression analyses adjusting for established vascular risk factors and mineral metabolism, higher PTH was associated with an increased risk of nonfatal atherosclerotic disease (hazard ratio for 1 SD increase of PTH: 1.55, 1.33-1.88; P<0.0001). Results were similar when including fatal atherosclerotic disease in the outcome.CONCLUSIONS: In 2 independent community-based cohorts, PTH was associated to the degree of atherosclerosis and risk of clinically overt atherosclerotic disease, respectively. Our data confirm and extend previous studies supporting a role for PTH in the development of atherosclerotic disease.
|
|
| 17. |
- Herlitz, Johan, et al.
(författare)
-
Suspicion and treatment of severe sepsis : An overview of the prehospital chain of care
- 2012
-
Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : BioMed Central. - 1757-7241. ; 20:42
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundSepsis is a life-threatening condition where the risk of death has been reported to be even higher than that associated with the major complications of atherosclerosis, i.e. myocardial infarction and stroke. In all three conditions, early treatment could limit organ dysfunction and thereby improve the prognosis.AimTo describe what has been published in the literature a/ with regard to the association between delay until start of treatment and outcome in sepsis with the emphasis on the pre-hospital phase and b/ to present published data and the opportunity to improve various links in the pre-hospital chain of care in sepsis.MethodsA literature search was performed on the PubMed, Embase (Ovid SP) and Cochrane Library databases.ResultsIn overall terms, we found a small number of articles (n=12 of 1,162 unique hits) which addressed the prehospital phase. For each hour of delay until the start of antibiotics, the prognosis appeared to become worse. However, there was no evidence that prehospital treatment improved the prognosis.Studies indicated that about half of the patients with severe sepsis used the emergency medical service (EMS) for transport to hospital. Patients who used the EMS experienced a shorter delay to treatment with antibiotics and the start of early goal-directed therapy (EGDT). Among EMS-transported patients, those in whom the EMS staff already suspected sepsis at the scene had a shorter delay to treatment with antibiotics and the start of EGDT.There are insufficient data on other links in the prehospital chain of care, i.e. patients, bystanders and dispatchers.ConclusionSevere sepsis is a life-threatening condition. Previous studies suggest that, with every hour of delay until the start of antibiotics, the prognosis deteriorates. About half of the patients use the EMS. We need to know more about the present situation with regard to the different links in the prehospital chain of care in sepsis.
|
|
| 18. |
|
|
| 19. |
- Hermes, Andreas, et al.
(författare)
-
Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial.
- 2008
-
Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 26:26, s. 4261-7
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: A Japanese randomized trial showed superior survival for patients with extensive-disease (ED) small-cell lung cancer (SCLC) receiving irinotecan plus cisplatin compared with etoposide plus cisplatin. The present trial evaluated the efficacy of irinotecan plus carboplatin (IC) compared with oral etoposide plus carboplatin (EC). PATIENTS AND METHODS: Patients with ED SCLC were randomly assigned to receive either IC, which consisted of carboplatin (area under the curve = 4; Chatelut formula) and irinotecan (175 mg/m2) intravenously both on day 1, or EC, which consisted of carboplatin as in IC and etoposide (120 mg/m(2)/d) orally on days 1 through 5. Courses were repeated every 3 weeks with four cycles planned. Doses were reduced by one third in patients with a WHO performance status (PS) of 3 to 4 and/or age older than 70 years. Primary end point was overall survival (OS). Secondary end points were quality of life (QOL) and complete response (CR) rate. RESULTS: Of 220 randomly assigned patients, 209 were eligible for analysis (IC, n = 105; EC, n = 104). Thirty-five percent were older than 70 years, and 47% had a PS of 2 to 4. The groups were well balanced with respect to prognostic factors. OS was inferior in the EC group (hazard ratio = 1.41; 95% CI, 1.06 to 1.87; P = .02). Median survival time was 8.5 months for IC compared with 7.1 months for EC. One-year survival rate was 34% for IC and 24% for EC. CR was seen in 18 IC patients compared with seven EC patients (P = .02). There were no statistically significant differences in hematologic grade 3 or 4 toxicity. Grade 3 or 4 diarrhea was more common in the IC group. QOL differences were small, with a trend toward prolonged palliation with the IC regimen. CONCLUSION: IC prolongs survival in ED SCLC with slightly better scores for QOL.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Johansson, Carolina, et al.
(författare)
-
Mutagenesis and homology modelling of the Tn21 integron integrase IntI1
- 2009
-
Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 48:8, s. 1743-1753
-
Tidskriftsartikel (refereegranskat)abstract
- Horizontal DNA transfer between bacteria is widespread and a major cause of antibiotic resistance. For logistic reasons, single or combined genes are shuttled between vectors such as plasmids and bacterial chromosomes. Special elements termed integrons operate in such shuttling and are therefore vital for horizontal gene transfer. Shorter elements carrying genes, cassettes, are integrated in the integrons, or excised from them, by virtue of a recombination site, attC, positioned in the 3' end of each unit. It is a remarkable and possibly restricting elementary feature of attC that it must be single-stranded while the partner target site, attI, may be double-stranded. The integron integrases belong to the tyrosine recombinase family, and this work reports mutations of the integrase IntI1 from transposon Tn21, chosen within a well-conserved region characteristic of the integron integrases. The mutated proteins were tested for binding to a bottom strand of an attC substrate, by using an electrophoresis mobility shift assay. To aid in interpreting the results, a homology model was constructed on the basis of the crystal structure of integron integrase VchIntIA from Vibrio cholerae bound to its cognate attC substrate VCRbs. The local stability and hydrogen bonding network of key domains of the modeled structure were further examined using molecular dynamics simulations. The homology model allowed us to interpret the roles of several amino acid residues, four of which were clearly binding assay responsive upon mutagenesis. Notably, we also observed features indicating that IntI1 may be more prone to base-specific contacts with VCRbs than VchIntIA.
|
|
| 23. |
- Järhult, Susann J, 1971-, et al.
(författare)
-
Brachial artery hyperemic blood flow velocity in relation to established indices of vascular function and global atherosclerosis
- 2012
-
Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961 .- 1475-097X. ; 32:3, s. 227-233
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundSystolic to diastolic blood flow velocity (SDFV) ratio in the Brachial artery recently proved to be related to cardiovascular risk and Carotid atherosclerosis. We hypothesized that the SDFV ratio was related to established markers of vascular function and global atherosclerosis. MethodsEstablished markers of endothelial function in forearm resistance vessels, flow-mediated vasodilation and arterial stiffness were assessed in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study including 1016 individuals aged 70. Whole body magnetic resonance angiography was performed in a random 306 of the participants. Atherosclerotic lesions were summarized in a total atherosclerotic score (TAS). Before and during hyperemia of the Brachial artery, systolic and diastolic blood flow velocities were measured by Doppler. Results The SDFV ratio was positively related to endothelium-independent vasodilatation, while inverse relations to flow-mediated dilation, common carotid artery distensibility and the stroke volume to pulse pressure ratio were found. Endothelium-dependent vasodilatation and total peripheral resistance index were not significantly related to the SDFV ratio.The SDFV ratio (p=0.015) and the blood flow increase during hyperemia (p= 0.020) were both significantly related to TAS after gender adjustment. When adjusted for the Framingham risk score, both the SDFV ratio (p= 0.057) and blood flow increase (p= 0.078) lost somewhat in significance. ConclusionThe SDFV ratio was related to established markers of both vasodilation and arterial compliance, and to global atherosclerosis. Future larger studies have to evaluate if the SDFV ratio is related to global atherosclerosis independently of traditional risk factors.
|
|
| 24. |
- Lind, Lars, et al.
(författare)
-
Endothelial Function in Resistance and Conduit Arteries and 5-Year Risk of Cardiovascular Disease
- 2011
-
Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 123:14, s. 1545-1551
-
Tidskriftsartikel (refereegranskat)abstract
- Background-Impaired endothelial function has been implicated as a cause of cardiovascular disease. Little is known of the relations of measures of endothelial function in resistance and conduit arteries to incident cardiovascular disease in the general population, and available techniques have not been compared. Methods and Results-In 1016 participants (70 years of age) of the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (52% women), we measured endothelium-dependent vasodilation using the invasive forearm technique with acetylcholine given in the brachial artery, the brachial artery ultrasound technique with measurement of flow-mediated dilatation, and the pulse-wave analysis-based method with beta-2-agonist terbutaline provocation. During 5 years of follow-up, 101 participants experienced a composite end point of myocardial infarction, stroke, or death, excluding the 85 persons with a history of myocardial infarction or stroke at baseline. In logistic regression models adjusted for several established and novel cardiovascular disease risk factors and medications, endothelium-dependent vasodilation by the invasive forearm technique with acetylcholine was associated with risk of the end point (odds ratio, 0.72 per SD; 95% confidence interval, 0.56 to 0.93; P = 0.01). Endothelial function by the other 2 methods was not related to risk of the end point. Addition of endothelium-dependent vasodilation to the Framingham risk score improved discrimination of risk of the end point. Conclusions-Endothelium-dependent vasodilation in resistance arteries, but not in the brachial conduit artery (flow-mediated dilatation), was associated with 5-year risk of a composite end point of death, myocardial infarction, or stroke independently of major cardiovascular disease risk factors. This vascular measurement improved risk discrimination when added to an established risk score in an elderly population.
|
|
| 25. |
- Lind, Lars, et al.
(författare)
-
On the association between body fat and left ventricular mass
- 2019
-
Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 37:8, s. 1699-1704
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: As intervention studies have shown a reduction in body weight to be paralleled with a reduction in left ventricular mass (LVM), we quantified a hypothesized causal relationship between fat mass and LVM, and how much of these effects that was mediated by blood pressure (BP), diabetes and adipokines. Also visceral and subcutaneous adipose tissue (VAT and SAT) were explored in the same fashion.Methods: In the Prospective Study of the Vasculature in Uppsala Seniors study (n = 1016, 50% women, all aged 70 years), LVM was measured by echocardiography (indexed for lean mass, LVMI), fat and lean mass by dual-energy X-ray. VAT and SAT were measured by abdominal MRI (in n = 275).Results: In a structural equation model adjusting for sex, the total effect of fat mass on LVMI was large (standardized coefficient 0.280, P = 3.2 × 10−15, 95% confidence interval 0.210–0.349). Out of the total effect of fat mass on LVMI, 29.0% was mediated by BP and glucose (P = 2.4 × 10−12). The BP pathway was most important, mediating 24.4% of the total effect of fat mass on LVMI (P = 4.6 × 10−7), while the glucose pathway accounted for 4.6% (P = 0.033). The association of VAT with LVMI (0.202, P = 2.4 × 10−4) was slightly weaker than that of SAT with LVMI (0.283, P = 1.0 × 10−6). Of several measured adipokines, leptin was a significant mediator of the effect of fat mass on LVMI (P = 3.0 × 10−3).Conclusion: One-third of the hypothesized association between body fat and LVMI was mediated by BP and glucose in this population-based cohort. Leptin was also an important mediator. Visceral adipose tissue was not more closely related to LVMI than subcutaneous abdominal fat.
|
|
| 26. |
- Michaëlsson, Karl, et al.
(författare)
-
Plasma vitamin D and mortality in older men : a community-based prospective cohort study
- 2010
-
Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 92:4, s. 841-848
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Vitamin D status is known to be important for bone health but may also affect the development of several chronic diseases, including cancer and cardiovascular diseases, which are 2 major causes of death. Objective: We aimed to examine how vitamin D status relates to overall and cause-specific mortality. Design: The Uppsala Longitudinal Study of Adult Men, a community-based cohort of elderly men (mean age at baseline: 71 y; n = 1194), was used to investigate the association between plasma 25-hydroxyvitamin D [25(OH)D] and mortality. Total plasma 25(OH)D was determined with HPLC atmospheric pressure chemical ionization mass spectrometry. Proportional hazards regression was used to compute hazard ratios (HRs). Results: During follow-up (median: 12.7 y), 584 (49%) participants died. There was a U-shaped association between vitamin D concentrations and total mortality. An approximately 50% higher total mortality rate was observed among men in the lowest 10% (<46 nmol/L) and the highest 5% (>98 nmol/L) of plasma 25(OH)D concentrations compared with intermediate concentrations. Cancer mortality was also higher at low plasma concentrations (multivariable-adjusted HR: 2.20; 95% CI: 1.44, 3.38) and at high concentrations (HR: 2.64; 95% CI: 1.46, 4.78). For cardiovascular death, only low (HR: 1.89; 95% CI: 1.21, 2.96) but not high (HR: 1.33; 95% CI: 0.69, 2.54) concentrations indicated higher risk. Conclusions: Both high and low concentrations of plasma 25(OH)D are associated with elevated risks of overall and cancer mortality. Low concentrations are associated with cardiovascular mortality.
|
|
| 27. |
- Nilsson, Magnus, et al.
(författare)
-
A 9-band WCDMA/EDGE transceiver supporting HSPA evolution
- 2011
-
Ingår i: [Host publication title missing]. - 0193-6530. ; , s. 366-368
-
Konferensbidrag (refereegranskat)abstract
- The future of cellular radio ICs lies in the integration of an ever-increasing number of bands and channel bandwidths. This paper presents a transceiver together with the associated discrete front-end components. The transceiver supports 4 EDGE bands and 9 WCDMA bands (l-VI and Vlll-X), while the radio can be configured to simultaneously support the 4 EDGE bands and up to 5 WCDMA bands: 3 high bands (HB) and 2 low bands (LB). The RX is a SAW-less homodyne composed of a main RX and a diversity RX. To reduce package complexity with so many bands, we chose to minimize the number of ports by using single-ended RF interfaces for both RX and TX. This saves seve ral package pins, but requires careful attention to grounding. The main RX has 8 LNA ports and the diversity RX has 5, with some LNAs supporting multiple bands. On the TX side, 2 ports are used for all EDGE bands and 4 for the WCDMA bands.
|
|
| 28. |
- Pennells, Lisa, et al.
(författare)
-
Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
|
|
| 29. |
- Simard, Julia F., et al.
(författare)
-
Ten years with biologics : to whom do data on effectiveness and safety apply?
- 2011
-
Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 50:1, s. 204-213
-
Tidskriftsartikel (refereegranskat)abstract
- Methods. We identified all adult patients with RA (n = 9612), PsA (n = 1417) and other SpA (n = 1652) initiating a first biologic therapy between 1 January 1999 and 31 December 2008, registered in the Swedish Biologics Register (ARTIS), including information on demographics, disease characteristics and 1-year risk of first-line treatment discontinuation. Results. Over calendar time, measures of disease activity at start declined substantially for all indications, and diminished between first-, second- and third-line therapy starts. One-year risks of first-line therapy discontinuation increased. Switchers to anti-TNF and non-TNF biologics had different comorbidities. Despite < 50% drug retention at 5 years, most patients remained exposed to some biologic. Conclusions. The trends in baseline characteristics and drug retention underscores that any effects of biologics, including comparison between different biologics, must be interpreted in light of the characteristics of the population treated. The observed differences further call for continued vigilance to properly evaluate the safety profiles of biologic treatments as they are currently used. Exposure to multiple biologics presents a challenge for attribution of long-term effects.
|
|
| 30. |
- Soveri, Inga, et al.
(författare)
-
Kidney function and discrimination of cardiovascular risk in middle-aged men
- 2009
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 266:4, s. 406-413
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo define the optimal glomerular filtration rate (GFR) cut off for discriminating the risk of myocardial infarction or cardiovascular death.DesignProspective longitudinal observational study.SettingA community-based cohort.ParticipantsA total of 2176 nondiabetic 50-year-old men without cardiovascular disease.MethodsThe men were followed until age 70. GFR was estimated at baseline using the Cockcroft–Gault formula. The optimal GFR cut-off points for discriminating risk of a fatal or nonfatal myocardial infarction and cardiovascular death were defined as the GFR levels maximizing integrated discrimination improvement (IDI).Main outcome measuresFatal or nonfatal myocardial infarction, cardiovascular death.ResultsDuring follow-up, 264 men experienced a fatal or nonfatal myocardial infarction, and 218 died of cardiovascular disease. The IDI-defined optimal GFR cut offs in this study were 98 mL min−1 for discriminating myocardial infarction risk and 92 mL min−1 for discriminating risk of cardiovascular death. In Cox proportional hazard models adjusting for established risk factors, the myocardial infarction risk was substantially higher in men with GFR below versus above 98 mL min−1 [hazard ratio (HR) 1.7, 95% confidence interval (CI) 1.3–2.3, P < 0.001], and the risk of cardiovascular death was doubled in men with GFR below versus above 92 mL min−1 (HR 2.1, 95% CI 1.5–3.0, P < 0.001).ConclusionThe GFR cut-off point for optimal discrimination of cardiovascular risk in the general population may be higher than previously suggested.
|
|
| 31. |
- Sundström, Anna, et al.
(författare)
-
Amalgam-related complaints and cognition
- 2011
-
Ingår i: Dental Abstracts. - : Elsevier. - 0011-8486. ; 56:2, s. 83-83
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 32. |
- Sundström, Anna, et al.
(författare)
-
Amalgam-related complaints and life events
- 2011
-
Ingår i: Dental Abstracts. - : Elsevier. - 0011-8486. ; 56:5, s. 261-262
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 33. |
- Sundström, Anna, 1969-, et al.
(författare)
-
APOE influences on neurosychological function after mild head injury : within-person comparisons
- 2004
-
Ingår i: Neurology. - Minneapolis, Minn : Lancet Publications Inc.. - 0028-3878 .- 1526-632X. ; 62:11, s. 1963-1966
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the relationship between neuropsychological outcome following mild head injury (MHI) and APOE genotype. Methods: Data from a population-based longitudinal study (n = 3,500) were used to identify 34 adults who experienced MHI during the course of the study. Their pre- and postinjury performances on a battery of nine neuropsychological tests were compared within person, and the postinjury performance was compared with that of age- and gender-matched control subjects. Results: The within-person comparisons showed that participants with at least oneAPOE ε4 allele (n = 11) had a significantly decreased postinjury performance on three of the tests, whereas the postinjury performance for APOE ε4-negative participants (n = 23) was unchanged. There was no significant difference in postinjury performance between participants with/without the ε4 allele, and neither group was impaired relative to controls. Conclusions: APOE genotype may influence the outcome following an MHI. Pre/postinjury within-person comparisons seem more sensitive than control group comparisons for detecting injury-related effects.
|
|
| 34. |
|
|
| 35. |
- Sundström, Anna, 1969-, et al.
(författare)
-
Cognitive Status in Persons with Amalgam-related Complaints
- 2010
-
Ingår i: Journal of Dental Research. - : SAGE Publications. - 0022-0345 .- 1544-0591. ; 89:11, s. 1236-1240
-
Tidskriftsartikel (refereegranskat)abstract
- Self-reported cognitive symptoms are frequent in persons with amalgam-related complaints, but few studies have focused on their cognitive function. The aim was to examine a symptom profile and whether participants with amalgam-related complaints have cognitive deficits in comparison with control individuals. We drew 342 participants with amalgam-related complaints and 342 one-to-one matched control individuals from a longitudinal population-based study. For 81 of the participants with amalgam-related complaints and controls, data were available approximately five years before the onset of complaints, making a longitudinal analysis possible. All participants were assessed by a self-reported health questionnaire and a comprehensive cognitive test battery. The participants with amalgam-related complaints reported more symptoms, mainly musculoskeletal and neuropsychological, compared with control individuals (p < 0.001). The results revealed no significant difference between the amalgam and control group, either cross-sectionally or longitudinally, for any of the cognitive tests. These results suggest that cognitive decline is not associated with amalgam-related complaints.
|
|
| 36. |
- Sundström, Anna, 1969-, et al.
(författare)
-
Fatigue before and after mild traumatic brain injury: Pre- and post-comparisons in relation to ApolipoproteinE
- 2007
-
Ingår i: Brain Injury. - London : Informa UK Limited. - 0269-9052 .- 1362-301X. ; 21:10, s. 1049-1054
-
Tidskriftsartikel (refereegranskat)abstract
- Primary objective: To assess the incidence of fatigue for persons following a mild traumatic brain injury (MTBI) and to evaluate the relationship between fatigue and APOE genotype. As fatigue is often found to be influenced by anxiety, depression and sleep disturbance, these factors were also measured. Methods and procedures: Thirty-one persons who sustained a MTBI were drawn from a population-based longitudinal study. Each person who sustained a MTBI was matched by age, gender, education and APOE genotype with two non-head injury controls. Self-reported pre- and post-injury incidence of fatigue, anxiety, depression and sleep disturbance was compared within-group and between groups. Results: For the MTBI group, incidence of fatigue was almost twice as common post- than pre-injury, whereas there was no corresponding change in a non-injured control group. Within the MTBI-group, post-injury fatigue was particularly common for carriers of the APOE ε4 allele. Conclusions: Fatigue is common sequela after a MTBI and especially pronounced for carriers of the APOE ε4 allele.
|
|
| 37. |
- Sundström, Anna, et al.
(författare)
-
Increased risk of dementia following mild head injury for carriers but not for non-carriers of the APOE ε4 allele.
- 2007
-
Ingår i: International Psychgeriatrics. ; 19
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Background: The є4-allele of Apolipoprotein-E (APOE) and head injury are risk factors for dementia diseases, and these factors may act synergistically to further increase the risk. The aim of the present study was to examine the association between mild head injury, APOE, and dementia.Methods: Data were obtained from the Betula prospective population-based study of aging, memory, and health. The study included 543 participants in the age range 40-85 years, free of dementia at baseline, who were followed-up within a 5-year interval. Dementia was classified using the Diagnostic and Statistical Manual of Mental Disorders Criteria. Information of previous head injury was done through screening of the participants’ answers to health questionnaires both at baseline and at following test occasions.Results: We found that subjects with head injury but without APOE є4 had no increased risk of dementia. Subjects with APOE є4 had elevated risk and those with both APOE є4 and head injury had the highest risk (OR = 5.2).Conclusions: This study confirms that APOE ε4 constitutes a risk factor of dementia, that mild injury in isolation does not increase the risk, but that head injury in combination with the APOE ε4 lead to increased risk of dementia.
|
|
| 38. |
- Sundström, Anna, 1969-, et al.
(författare)
-
Increased risk of dementia following mild head injury for carriers but not for non-carriers of the APOE ε4 allele
- 2007
-
Ingår i: International psychogeriatrics. - New York : Springer. - 1041-6102 .- 1741-203X. ; 19:1, s. 159-165
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The ε4 allele of apolipoprotein E (APOE) and head injury are risk factors for dementia diseases, and may act synergistically to further increase the risk. The aim of this study was to examine the association between mild head injury, APOE and dementia.Methods: Data were obtained from the Betula prospective population-based study of aging, memory, and health. The study included 543 participants in the age range 40–85 years, free of dementia at baseline, who were followed up within a 5-year interval. Dementia was classified using DSM-IV criteria. Information on previous head injury was obtained through screening of the participants' answers to health questionnaires at baseline and at follow-up.Results: Subjects with head injury but without APOE ε4 had no increased risk of dementia. Subjects with APOE ε4 had an increased risk and those with both APOE ε4 and head injury had the highest risk of dementia (odds ratio = 5.2).Conclusions: APOE ε4 constitutes a risk factor for dementia, mild injury in isolation does not increase the risk, but head injury in combination with the APOE ε4 leads to increased risk of dementia.
|
|
| 39. |
- Sundström, Anna, 1969-, et al.
(författare)
-
Stressful negative life events and amalgam-related complaints
- 2011
-
Ingår i: Community Dentistry and Oral Epidemiology. - : Wiley. - 0301-5661 .- 1600-0528. ; 39:1, s. 12-18
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The role of stressful life events in the onset of self-reported amalgam-related complaints is unclear. The aim of this study was to examine the relationship between life events and amalgam-related complaints. Method: The participants were selected from a longitudinal population-based study. One-to-one matching of 337 participants with amalgam-related complaints to 337 participants without such complaints was performed. For 81 of the participants with amalgam-related complaints and their matched controls, data was also available approximately 5 years before the onset of complaints, making longitudinal analysis possible. All participants completed questionnaires assessing the occurrence of 55 life events. Results: The results showed that many participants with amalgam-related complaints experienced negative life events before and at the onset of amalgam-related complaints. They also reported more unexpected and uncontrollable events difficult to adjust to in comparison with controls. The groups did not differ on positive or neutral life events. Somatic illness or surgical operation was the most common life event. Death of a very close family member and a major change in financial situation were also commonly reported. Conclusions: This study indicates that adverse negative life events could play a vital role in understanding and explaining amalgam-related complaints.
|
|
| 40. |
|
|
| 41. |
- Sundström, Johan, et al.
(författare)
-
Cardiac troponin-I and risk of heart failure : a community-based cohort study
- 2009
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 30:7, s. 773-781
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: We examined if circulating levels of cardiac troponin-I (cTnI) predict subsequent heart failure in the community. METHODS AND RESULTS: Using Cox proportional hazards models, we examined the risk of a first hospitalization for heart failure during a maximum of 11.4 years in a community-based sample of 1089 70-year-old men without heart failure, valvular disease, or electrocardiographic left ventricular hypertrophy. Adjusting for smoking, systolic blood pressure, antihypertensive medication use, diabetes, body mass index, serum cholesterol, and myocardial infarction before baseline or during follow-up, 0.01 microg/L higher cTnI conferred a hazard ratio (HR) of 1.26 (95% confidence interval 1.15-1.38) for subsequent heart failure. Persons with cTnI > or =0.03 microg/L had an HR of 5.25 (2.00-13.77) compared with persons with cTnI <0.01 microg/L. Adjusting additionally for serum NTproBNP attenuated the estimates somewhat [HR 1.22 (1.11-1.34) per 0.01 microg/L of cTnI]. Excluding persons with myocardial infarction before baseline and censoring at time of myocardial infarction during follow-up, 0.01 microg/L higher cTnI was associated with a multivariable-adjusted HR of 1.31 (1.16-1.47) for heart failure. CONCLUSION: In a community-based sample, a direct measure of cardiomyocyte damage, cTnI, indicated a substantially increased risk of heart failure, accounting for other risk factors. Studies investigating the clinical utility of measuring cTnI in asymptomatic individuals are warranted.
|
|
| 42. |
|
|
| 43. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
-
Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 44. |
- Sundström, Lars, 1967-
(författare)
-
Det hotade kollektivet : Neolitiseringsprocessen ur ett östmellansvenskt perspektiv
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation questions the established view on the social process in connection with Neolithisation. Therefore it has been necessary to discuss more general principles, on how to understand this process of change, when iterant hunter-gatherers became settled farmers. The dissertation begins with a theoretical discussion on the foundations for the interpretation and most important a discussion on differences between the interpretations presented and the treatment of the empirical material on which they are based. A necessary point of departure for understanding the implications an incorporation of domesticates in prehistoric society, i.e. emergence of Funnel Beaker Culture in Sweden, is a principal discussion, social mechanisms of hunters-gatherers on one hand and peoples reactions to changes threatening the social ideology, on the other. Four case studies are used to discuss people’s reaction to change. They clearly indicate that the reaction involved the lifting up of blurred and semiconscious structures to a conscious, ideological level. Inherent in this awareness process has been an active use of material culture, both in the production of symbols and in communication. The most important reason for stating that the Neolithisation must have meant a clear break with the earlier existence is the abandonment of itinerant way of life, both geographically and socially. This abandonment resulted in reactionary process involving material culture. Thus the material culture of the Funnel-Beaker period can be perceived as instruments of reproduction of a historically well-anchored egalitarian ideology. In the dispersed settlement system of autonomous individual farmsteads the collective aggregation sites are given a focal role of the discussion on social reproduction. The social mechanisms of the Early Neolithic society of Eastern Central Sweden are investigated on a local settlement level by an analysis of the production of locally available raw material. This study involve a petrological investigation showed a system of local management in relation to raw material extraction, production and consumption. This system is considered as one way of upholding the social ideology historically situated in the life style of hunters and gatherers.
|
|
| 45. |
- Surendran, Praveen, et al.
(författare)
-
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
|
|
| 46. |
- Wohlin, Martin, et al.
(författare)
-
Apolipoprotein E epsilon 4 genotype is independently associated with increased intima-media thickness in a recessive pattern
- 2007
-
Ingår i: Lipids. - : Wiley. - 0024-4201 .- 1558-9307. ; 42:5, s. 451-456
-
Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms in the apolipoprotein E (Apo E) gene have been associated with lipid levels, carotid intima media thickness (CCA-IMT), inflammation and cardiovascular disease (CVD). Earlier findings suggested an association of the Apo E alleles with increased CCA-IMT following a recessive pattern. Whether associations might be independent of C-reactive protein (CRP), lipid levels and other CVD risk factors is not known. We investigated the relationships between Apo E (epsilon2, epsilon3 and epsilon4 alleles) and CCA-IMT, measured by B-mode ultrasound, in dominant and recessive models in a community-based sample of 437 men 75 years of age. In men homozygous for the epsilon4 allele CCA-IMT was significantly increased by 0.13 mm to 0.86 +/- 0.16 mm compared to 0.73 +/- 0.19 mm in non- epsilon4-carriers (P = 0.0012) and 0.73 +/- 0.21 mm in epsilon4 heterozygous (P = 0.0044) in unadjusted recessive models. The association between Apo E epsilon4 genotype and CCA-IMT was independent of Apo E epsilon2 and Apo E epsilon3 alleles, CRP, lipid variables (TG, LDL, HDL) and other CVD risk factors (smoking, hypertension, body mass index, diabetes) (P = 0.018). No relations between Apo E genotype and CCA-IMT were observed in dominant models. No significant associations between the Apo E epsilon2 and epsilon3 alleles and CCA-IMT were found. In this study, men homozygous with the ApoE epsilon4 allele had thicker CCA-IMT, independently of Apo E epsilon2 and epsilon3 alleles, CRP, lipid variables (TG, LDL, HDL) and other CVD risk factors (smoking, hypertension, body mass index, diabetes), suggesting CCA-IMT to be modified by the ApoE epsilon4 genotype in a recessive pattern.
|
|
| 47. |
- Wormser, David, et al.
(författare)
-
Adult height and the risk of cause-specific death and vascular morbidity in 1 million people : individual participant meta-analysis
- 2012
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 41:5, s. 1419-1433
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.MethodsWe calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.ResultsFor people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.ConclusionAdult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
|
|
| 48. |
- Agarwal, Anubha, et al.
(författare)
-
Toward a Universal Definition of Etiologies in Heart Failure : Categorizing Causes and Advancing Registry Science
- 2024
-
Ingår i: Circulation Heart Failure. - : American Heart Association. - 1941-3289 .- 1941-3297. ; 17:4
-
Forskningsöversikt (refereegranskat)abstract
- Heart failure (HF) is a well-described final common pathway for a broad range of diseases however substantial confusion exists regarding how to describe, study, and track these underlying etiologic conditions. We describe (1) the overlap in HF etiologies, comorbidities, and case definitions as currently used in HF registries led or managed by members of the global HF roundtable; (2) strategies to improve the quality of evidence on etiologies and modifiable risk factors of HF in registries; and (3) opportunities to use clinical HF registries as a platform for public health surveillance, implementation research, and randomized registry trials to reduce the global burden of noncommunicable diseases. Investment and collaboration among countries to improve the quality of evidence in global HF registries could contribute to achieving global health targets to reduce noncommunicable diseases and overall improvements in population health.
|
|
| 49. |
- Ahlmanner, Filip, et al.
(författare)
-
CD39+ regulatory T cells accumulate in colon adenocarcinomas and display markers of increased suppressive function
- 2018
-
Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:97, s. 36993-37007
-
Tidskriftsartikel (refereegranskat)abstract
- Increasing knowledge of the function and regulation of tumor-infiltrating lymphocytes has led to new insights in cancer immunotherapy. Regulatory T cells (Treg) accumulate in colon tumors, and we recently showed that CD39+ Treg from cancer patients inhibit transendothelial migration of conventional T cells. CD39 mediates the hydrolysis of ATP to immunosuppressive adenosine and adds to the immunosuppressive effects of Treg. Here, we further investigated the regulatory features of intratumoral CD39+ Treg in colon cancer. Using flow cytometry analyses of cells from 46 colon cancer patients, we confirm the accumulation of CD39+ Treg in the tumor tissue compared to unaffected colon tissue, and also show that tumor-infiltrating Treg express more CD39 and Foxp3 on a per cell basis. Furthermore, CD39+ Treg in tumors express markers indicating increased turnover and suppressive ability. In particular, tumor-infiltrating CD39+ Treg have high expression of surface molecules related to immunosuppression, such as ICOS, PD-L1 and CTLA-4. Functional suppression assays also indicate potent suppressive capacity of CD39+ Treg on proliferation and IFN-γ secretion by conventional T cells. In conclusion, our results identify tumor-infiltrating CD39+ Treg as a numerous and potentially important immunosuppressive subset, and suggest that immunotherapy aimed at reducing the activity of CD39+ Treg may be particularly useful in the setting of colon cancer. © 2018 Ahlmanner et al.
|
|
| 50. |
- Ahmad, Shafqat, et al.
(författare)
-
Effect of General Adiposity and Central Body Fat Distribution on the Circulating Metabolome : A Multi-Cohort Nontargeted Metabolomics Observational and Mendelian Randomization Study
- 2022
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 71:2, s. 329-339
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity with circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data was generated by non-targeted ultra-performance liquid-chromatography coupled to time-of-flight mass-spectrometry in plasma and serum from three population-based Swedish cohorts: ULSAM (N=1,135), PIVUS (N=970), and TwinGene (N=2,059). We assessed associations between general adiposity measured as body mass index (BMI) and central body fat distribution measured as waist-to-hip ratio adjusted for BMI (WHRadjBMI) with 210 annotated metabolites. We employed MR analysis to assess causal effects. Lastly, we attempted to replicate the MR findings in the KORA and TwinsUK cohorts (N=7,373), the CHARGE consortium (N=8,631), the Framingham Heart Study (N=2,076) and the DIRECT consortium (N=3,029). BMI was associated with 77 metabolites, while WHRadjBMI was associated with 11 and 3 metabolites in women and men, respectively. The MR analyses in the Swedish cohorts suggested a causal association (p-value <0.05) of increased general adiposity and reduced levels of arachidonic acid, dodecanedioic acid and lysophosphatidylcholine (P-16:0) as well as with increased creatine levels. The replication effort provided support for a causal association of adiposity on reduced levels of arachidonic acid (p-value 0.03). Adiposity is associated with variation of large parts of the circulating metabolome, however causality needs further investigation in well-powered cohorts.
|
|
