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1.
  • 2021
  • swepub:Mat__t
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2.
  • 2021
  • swepub:Mat__t
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3.
  • Bravo, L, et al. (författare)
  • 2021
  • swepub:Mat__t
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4.
  • Tabiri, S, et al. (författare)
  • 2021
  • swepub:Mat__t
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5.
  • Glasbey, JC, et al. (författare)
  • 2021
  • swepub:Mat__t
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10.
  • Belov, Vladimir, et al. (författare)
  • Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures
  • 2024
  • Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.
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12.
  • Efe, C., et al. (författare)
  • Validation of Risk Scoring Systems in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis
  • 2019
  • Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 114:7, s. 1101-1108
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts. METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points. RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%). DISCUSSION: In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.
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13.
  • Ljungman, P, et al. (författare)
  • COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey
  • 2021
  • Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35:10, s. 2885-2894
  • Tidskriftsartikel (refereegranskat)abstract
    • This study reports on 382 COVID-19 patients having undergone allogeneic (n = 236) or autologous (n = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0–80.3) for allogeneic, and 60.6 years (7.7–81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2–292.7) in allogeneic and 24.6 months (−0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (p = 0.02), need for ICU (p < 0.0001) and moderate/high immunodeficiency index (p = 0.04) increased the risk while better performance status (p = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19.
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14.
  • Slimani, Y., et al. (författare)
  • Ultrasound-assisted synthesis and magnetic investigations of Ni0.4Cu0.4Zn0.2GaxGdxFe2-2xO4 (0.00 <= x <= 0.04) nanosized spinel ferrites
  • 2022
  • Ingår i: Applied Physics A. - : Springer Nature. - 0947-8396 .- 1432-0630. ; 128:7
  • Tidskriftsartikel (refereegranskat)abstract
    • This study focused on the impact of Ga-Gd co-substitution on the structural, magnetic features and hyperfine interactions of nanosized NiCuZn spinel ferrites [Ni0.4Cu0.4Zn0.2GaxGdxFe2-2xO4 (0.00 <= x <= 0.04) NSFs] synthesized via sonochemical approach using ultrasonic irradiation. X-ray powder pattern (XRD) analyses confirmed cubic spinel structures of products. Crystallites and particle sizes of all samples are found to be between 9-14 nm and 18-22 nm, respectively. The NSF morphology and chemical composition were investigated by transmission and scanning electron microscope (TEM and SEM) along with energy-dispersive X-ray (EDX). The cation distribution of all ions was evaluated by Mossbauer spectroscopy. The high spin Fe3+ ions determined the isomer shift (I.S.) values. For lower rare-earth dopant ratios, we found that Gd3+ ions occupy B sites, while Ga3+ ions reside in A sites, and thereafter, some Ga3+ ions start to enter B sites. Magnetometry measurements were used to evaluate the effect of magnetic field (H) and temperature (T) on the magnetization of products. For each sample, both coercivity (H-c) and saturation magnetization (M-s) increase when the T decreases below ambient temperature. All substituted samples display M-s values higher than those of non-substituted ones; however, H-c values diminish for x content up to 0.02 and thereafter enlarge. Different magnetization measurements revealed superparamagnetic-to-ferromagnetic transition below the blocking temperature (T-B).
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16.
  • Efe, C., et al. (författare)
  • Extrahepatic autoimmune diseases in primary biliary cholangitis: Prevalence and significance for clinical presentation and disease outcome
  • 2021
  • Ingår i: Journal of Gastroenterology and Hepatology. - : Wiley. - 0815-9319 .- 1440-1746. ; 36:4, s. 936-942
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aim The prevalence and clinical significance of extrahepatic autoimmune diseases (EHAIDs) have not been evaluated in a large cohort of primary biliary cholangitis (PBC). Methods The medical records of 1554 patients with PBC from 20 international centers were retrospectively reviewed. Development of decompensated cirrhosis (ascites, variceal bleeding, and/or hepatic encephalopathy) and hepatocellular carcinoma were considered clinical endpoints. Results A total of 35 different EHAIDs were diagnosed in 440 (28.3%) patients with PBC. Patients with EHAIDs were more often female (92.5%vs86.1%,P < 0.001) and seropositive for anti-mitochondrial antibodies (88%vs84%,P = 0.05) and antinuclear antibodies and/or smooth muscle antibodies (53.8%vs43.6%,P = 0.005). At presentation, patients with EHAIDs had significantly lower levels of alkaline phosphatase (1.76vs1.98 x upper limit of normal [ULN],P = 0.006), aspartate aminotransferase (1.29vs1.50 x ULN,P < 0.001), and total bilirubin (0.53vs0.58 x ULN,P = 0.002). Patients with EHAIDs and without EHAIDs had similar rates of GLOBE high-risk status (12.3%vs16.1%,P = 0.07) and Paris II response (71.4%vs69.4%,P = 0.59). Overall, event-free survival was not different in patients with and without EHAIDs (90.8%vs90.7%,P = 0.53, log rank). Coexistence of each autoimmune thyroid diseases (10.6%), Sjogren disease (8.3%), systemic sclerosis (2.9%), rheumatoid arthritis (2.7%), systemic lupus erythematosus (1.7%), celiac disease (1.7%), psoriasis (1.5%), and inflammatory bowel diseases (1.3%) did not influence the outcome. Conclusions Our study confirms that EHAIDs are frequently diagnosed in patients with PBC. The presence of EHAIDs may influence the clinical phenotype of PBC at presentation but has no impact on PBC outcome.
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17.
  • Kappos, Ludwig, et al. (författare)
  • Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
  • 2018
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 391, s. 1263-1273
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2018 Elsevier Ltd Background: No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatme nt arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation: Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding: Novartis Pharma AG.
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18.
  • Baykal, A., et al. (författare)
  • Synthesis and Characterization of Dendrimer-Encapsulated Iron and Iron-Oxide Nanoparticles
  • 2012
  • Ingår i: JOURNAL OF SUPERCONDUCTIVITY AND NOVEL MAGNETISM. - : Springer Science and Business Media LLC. - 1557-1939 .- 1557-1947. ; 25:5, s. 1541-1549
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper, a series of iron (Fe) containing nanoparticles were prepared by employing PAMAM (Poly(amidoamine), dendrimers with different generations (G0-G3) as templates and sodium borohydride as a reducing agent. The products have been characterized by TEM, FT-IR, XRD, VSM, TGA, and XPS. XRD analysis reveal low crystallinity of formed particles within the dendrimers, however, crystallinity of the nanoparticles was observed to increase with increasing generation of dendrimers. Dominant phases were determined as magnetite (Fe3O4 or maghemite, gamma-Fe2O3). XPS analysis revealed the chemical composition of nanoparticles as iron oxide which indicated the oxidation of Fe species subsequent to the reduction process, in agreement with XRD analysis. The magnetization curves have superparamagnetic nonhysteretic characteristic at lower fields and with nonsaturation characteristic at high fields. Magnetic evaluation of samples with the 20:1 molar ratio of Fe:PAMAM showed decreasing superparamagnetic character and decreasing saturation magnetisation with increasing generation of dendrimers.
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19.
  • Cilli, A., et al. (författare)
  • The diagnostic yield of exercise stress testing as a screening tool for subclinical coronary artery disease in patients with moderate to severe obstructive sleep apnea
  • 2011
  • Ingår i: Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. - 1550-9397. ; 7:1, s. 25-9
  • Tidskriftsartikel (refereegranskat)abstract
    • STUDY OBJECTIVE: To address the yield of routine exercise stress testing as a screening tool for subclinical coronary artery disease (CAD) in patients with moderate to severe obstructive sleep apnea (OSA). DESIGN AND SETTING: A cross-sectional study in a university hospital. PARTICIPANTS: Of 380 consecutive patients with OSA, data from 206 subjects (mean apnea-hypopnea index [AHI] 41 +/- 21 events/h) were studied; data from 78 with a history of CAD and 96 with mild OSA (AHI 5-15 events/h) were excluded. MEASUREMENTS: Routine exercise stress testing. RESULTS: Six subjects could not reach maximal exercise capacity. Of the remaining 200 patients, the results of exercise stress testing were normal in 189. Three had a positive stress test, with coronary angiography confirming the diagnosis of CAD. Eight patients had suspected positive findings on the stress test, but the results of the myocardial perfusion study were negative. CONCLUSION: The prevalence of subclinical CAD in this selected population with OSA was 1.5%, which is not higher than that in a general population. Our results do not support the routine use of exercise stress testing in patients with moderate to severe OSA who do not have symptoms of CAD.
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20.
  • Cordier, R., et al. (författare)
  • Evaluating the Psychometric Properties of the Eating Assessment Tool (EAT-10) Using Rasch Analysis
  • 2017
  • Ingår i: Dysphagia. - : Springer Science and Business Media LLC. - 0179-051X .- 1432-0460. ; 32:2, s. 250-260
  • Tidskriftsartikel (refereegranskat)abstract
    • Early and reliable screening for oropharyngeal dysphagia (OD) symptoms in at-risk populations is important and a crucial first stage in effective OD management. The Eating Assessment Tool (EAT-10) is a commonly utilized screening and outcome measure. To date, studies using classic test theory methodologies report good psychometric properties, but the EAT-10 has not been evaluated using item response theory (e.g., Rasch analysis). The aim of this multisite study was to evaluate the internal consistency and structural validity and conduct a preliminary investigation of the cross-cultural validity of the EAT-10; floor and ceiling effects were also checked. Participants involved 636 patients deemed at risk of OD, from outpatient clinics in Spain, Turkey, Sweden, and Italy. The EAT-10 and videofluoroscopic and/or fiberoptic endoscopic evaluation of swallowing were used to confirm OD diagnosis. Patients with esophageal dysphagia were excluded to ensure a homogenous sample. Rasch analysis was used to investigate person and item fit statistics, response scale, dimensionality of the scale, differential item functioning (DIF), and floor and ceiling effect. The results indicate that the EAT-10 has significant weaknesses in structural validity and internal consistency. There are both item redundancy and lack of easy and difficult items. The thresholds of the rating scale categories were disordered and gender, confirmed OD, and language, and comorbid diagnosis showed DIF on a number of items. DIF analysis of language showed preliminary evidence of problems with cross-cultural validation, and the measure showed a clear floor effect. The authors recommend redevelopment of the EAT-10 using Rasch analysis.
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24.
  • Kavas, H., et al. (författare)
  • ZnxCu(1-x)Fe2O4 Nanoferrites by Sol-Gel Auto Combustion Route : Cation Distribution and Microwave Absorption Properties
  • 2014
  • Ingår i: Journal of Inorganic and Organometallic Polymers and Materials. - : Springer Science and Business Media LLC. - 1574-1443 .- 1574-1451. ; 24:6, s. 963-970
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of Zn doping on magnetic properties and site preference of cations of CuFe2O4 has been investigated. Zn substituted Cu ferrite nanoparticles with general formula ZnxCu(1-x)Fe2O4 were synthesized by a sol-gel auto combustion method. Samples showed fine particle size with very strong aggregation, due to the high temperatures attained during the combustion process. All samples showed high phase purity assessed from X-ray diffraction analysis and do not have magnetization hysteresis, which reveals superparamagnetic character of the fabricated particles. It was found that a certain amount of Zn substitution in Cu ferrite (0.4 < x < 0.6) causes different site occupation of cations. XRD and magnetic hysteresis data of all samples were analyzed and the cation distribution in spinel ferrites was calculated by these two experimental techniques. It was found that the Neel antiferromagnetic aligned sublattice model is valid below this region (x < 0.4), and above it (x > 0.6) the canted spins at octahedral site are dominant according to the tetrahedral site spins.
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25.
  • Wilson, Stephanie J., et al. (författare)
  • Global subterranean estuaries modify groundwater nutrient loading to the ocean
  • 2024
  • Ingår i: Limnology And Oceanography Letters. - 2378-2242.
  • Tidskriftsartikel (refereegranskat)abstract
    • Terrestrial groundwater travels through subterranean estuaries before reaching the sea. Groundwater-derived nutrients drive coastal water quality, primary production, and eutrophication. We determined how dissolved inorganic nitrogen (DIN), dissolved inorganic phosphorus (DIP), and dissolved organic nitrogen (DON) are transformed within subterranean estuaries and estimated submarine groundwater discharge (SGD) nutrient loads compiling > 10,000 groundwater samples from 216 sites worldwide. Nutrients exhibited complex, nonconservative behavior in subterranean estuaries. Fresh groundwater DIN and DIP are usually produced, and DON is consumed during transport. Median total SGD (saline and fresh) fluxes globally were 5.4, 2.6, and 0.18 Tmol yr−1 for DIN, DON, and DIP, respectively. Despite large natural variability, total SGD fluxes likely exceed global riverine nutrient export. Fresh SGD is a small source of new nutrients, but saline SGD is an important source of mostly recycled nutrients. Nutrients exported via SGD via subterranean estuaries are critical to coastal biogeochemistry and a significant nutrient source to the oceans.
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26.
  • Ai, Jiaoyu, et al. (författare)
  • Bcl3 Couples Cancer Stem Cell Enrichment With Pancreatic Cancer Molecular Subtypes
  • 2021
  • Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 161:1, s. 318-332
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: The existence of different subtypes of pancreatic ductal adenocarcinoma (PDAC) and their correlation with patient outcome have shifted the emphasis on patient classification for better decision-making algorithms and personalized therapy. The contribution of mechanisms regulating the cancer stem cell (CSC) population in different subtypes remains unknown.Methods: Using RNA-seq, we identified B-cell CLL/lymphoma 3 (BCL3), an atypical nf-κb signaling member, as differing in pancreatic CSCs. To determine the biological consequences of BCL3 silencing in vivo and in vitro, we generated bcl3-deficient preclinical mouse models as well as murine cell lines and correlated our findings with human cell lines, PDX models, and 2 independent patient cohorts. We assessed the correlation of bcl3 expression pattern with clinical parameters and subtypes.Results: Bcl3 was significantly down-regulated in human CSCs. Recapitulating this phenotype in preclinical mouse models of PDAC via BCL3 genetic knockout enhanced tumor burden, metastasis, epithelial to mesenchymal transition, and reduced overall survival. Fluorescence-activated cell sorting analyses, together with oxygen consumption, sphere formation, and tumorigenicity assays, all indicated that BCL3 loss resulted in CSC compartment expansion promoting cellular dedifferentiation. Overexpression of BCL3 in human PDXs diminished tumor growth by significantly reducing the CSC population and promoting differentiation. Human PDACs with low BCL3 expression correlated with increased metastasis, and BCL3-negative tumors correlated with lower survival and nonclassical subtypes.Conclusions: We demonstrate that bcl3 impacts pancreatic carcinogenesis by restraining CSC expansion and by curtailing an aggressive and metastatic tumor burden in PDAC across species. Levels of BCL3 expression are a useful stratification marker for predicting subtype characterization in PDAC, thereby allowing for personalized therapeutic approaches.
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27.
  • Baykal, A., et al. (författare)
  • Synthesis, Characterization, and Dielectric Properties of BaFe10(Mn2+Zn2+Zn2+)O-19 Hexaferrite
  • 2016
  • Ingår i: Journal of Superconductivity and Novel Magnetism. - : Springer. - 1557-1939 .- 1557-1947. ; 29:1, s. 199-205
  • Tidskriftsartikel (refereegranskat)abstract
    • Barium hexaferrite with nominal chemical composition BaMnZn2Fe10O19 has been synthesized by sol-gel method, using polymethyl methacrylate (PMMA) as a template. Fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffraction (XRD) were used for approving the formation of barium hexaferrites. In addition, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were performed to investigate the structural and morphological properties of BaM. The dielectric properties were studied by impedance measurements as a function of frequency (in the range 0.1 Hz-1 MHz). The XRD patterns confirmed the formation of single-phase magnetoplumbite with crystallite size around 73 nm. The results of dielectric parameters and conductivity measurements showed three regions with different behaviors in electrical conduction mechanism.
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29.
  • Daelman, Bo, et al. (författare)
  • Frailty and cognitive function in middle-aged and older adults with congenital heart disease
  • 2024
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 83:12, s. 1149-1159
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Life expectancy of patients with congenital heart disease (CHD) has increased rapidly, resulting in a growing and aging population. Recent studies have shown that older people with CHD have higher morbidity, health care use, and mortality. To maintain longevity and quality of life, understanding their evolving medical and psychosocial challenges is essential.Objectives: The authors describe the frailty and cognitive profile of middle-aged and older adults with CHD to identify predictor variables and to explore the relationship with hospital admissions and outpatient visits.Methods: Using a cross-sectional, multicentric design, we included 814 patients aged ≥40 years from 11 countries. Frailty phenotype was determined using the Fried method. Cognitive function was assessed by the Montreal Cognitive Assessment.Results: In this sample, 52.3% of patients were assessed as robust, 41.9% as prefrail, and 5.8% as frail; 38.8% had cognitive dysfunction. Multinomial regression showed that frailty was associated with older age, female sex, higher physiologic class, and comorbidities. Counterintuitively, patients with mild heart defects were more likely than those with complex lesions to be prefrail. Patients from middle-income countries displayed more prefrailty than those from higher-income countries. Logistic regression demonstrated that cognitive dysfunction was related to older age, comorbidities, and lower country-level income.Conclusions: Approximately one-half of included patients were (pre-)frail, and more than one-third experienced cognitive impairment. Frailty and cognitive dysfunction were identified in patients with mild CHD, indicating that these concerns extend beyond severe CHD. Assessing frailty and cognition routinely could offer valuable insights into this aging population.
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30.
  • Dahlberg, Jakob, 1969, et al. (författare)
  • Incidence, detection and outcome of differentiated thyroid cancer in Western Sweden
  • 2021
  • Ingår i: BJS open. - : Oxford University Press (OUP). - 2474-9842. ; 5:5
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: It is unclear whether the increasing incidence of thyroid cancer (TC) due to increased diagnosis of small and indolent tumours might mask a real increase of clinically significant cancers. The aim of this study was to correlate surgery, pathology and outcome data of individual patients to the mode of primary detection (palpation, by imaging or incidental) to assess if TC incidence has increased. METHODS: The Swedish Cancer Registry identified all patients with TC in Västra Götaland County representing approximately 1.6 million inhabitants. Clinical information was retrieved from medical records of patient cohorts from three study intervals (2001-2002, 2006-2007 and 2011-2014) comprising 60 per cent of all TC patients. Data were also obtained from the NORDCAN registry to compare of TC incidence with other Nordic countries. RESULTS: Between 2001 and 2014, the annualized standard incidence rate/100 000 population (ASR) of TC increased from 3.14 to 10.71 in women and from 1.12 to 3.77 in men. This was higher than the mean incidence for Sweden but similar to that in Norway and Finland. Differentiated TC (DTC) increased more than threefold. The majority of tumours (64 per cent) were detected by palpation. Larger tumours (10-20, 21-40 and greater than 40 mm) increased as much as microcarcinomas (less than 10 mm). Only 5 per cent of the tumours were detected by imaging. All disease-specific deaths (8.5 per cent of DTC in the first two cohorts) and most patients with recurrent or persistent disease (6.6 per cent of DTC cases) were diagnosed due to tumour-related symptoms. CONCLUSION: DTC in Western Sweden gradually increased between 2001 and 2014. The majority of tumours were detected by palpation suggesting a real increase in the incidence of clinically significant thyroid malignancies. © The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.
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31.
  • Demir, A., et al. (författare)
  • First Morning Voided Urinary Gonadotropin Measurements as an Alternative to the GnRH Test
  • 2016
  • Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 85:5, s. 301-308
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: We studied whether first morning voided ( FMV) urinary gonadotropin measurements could be used as a noninvasive alternative to the GnRH test in the assessment of the hypothalamic-pituitary-gonadal function in children. Methods: In a single-center study, we compared FMV urinary gonadotropin concentrations with basal and GnRH-stimulated serum gonadotropin levels in 274 children and adolescents (78 girls, 196 boys) aged 5-17 years referred for growth and pubertal disorders. The concordance between FMV urinary gonadotropin concentrations and GnRH test results was assessed. Results: FMV urinary LH (U-LH), urinary FSH (U-FSH) and their ratios correlated well with the corresponding basal and GnRH-stimulated serum parameters (r = 0.66, p < 0.001). Receiver operating characteristic curve analyses using urinary and serum LH and FSH concentrations showed that FMV U-LH and U-LH/U-FSH performed equally well as the GnRH test in the differentiation of early puberty (Tanner stage 2) from prepuberty (Tanner stage 1) (area under the curve 0.768-0.890 vs. 0.712-0.858). FMV U-LH and U-LH/UFSH performed equally well as basal serum LH in predicting a pubertal GnRH test result (area under the curve 0.90-0.93). Conclusion: FMV U-LH determination can be used for the evaluation of pubertal development and its disorders, reducing the need for invasive GnRH stimulation tests. (C) 2016 S. Karger AG, Basel
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  • Djekic, Demir, et al. (författare)
  • Body Mass Index in Adolescence and Long-Term Risk of Early Incident Atrial Fibrillation and Subsequent Mortality, Heart Failure, and Ischemic Stroke
  • 2022
  • Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 11:21
  • Tidskriftsartikel (refereegranskat)abstract
    • Background We sought to determine the role of obesity in adolescent men on development of atrial fibrillation (AF) and subsequent associated clinical outcomes in subjects diagnosed with AF. Methods and Results We conducted a nationwide, register-based, cohort study of 1 704 467 men (mean age, 18.3 +/- 0.75 years) enrolled in compulsory military service in Sweden from 1969 through 2005. Height and weight, blood pressure, fitness, muscle strength, intelligence quotient, and medical disorders were recorded at baseline. Records obtained from the National Inpatient Registry and the Cause of Death Register were used to determine incidence and clinical outcomes of AF. During a median follow-up of 32 years (interquartile range, 24-41 years), 36 693 cases (mean age at diagnosis, 52.4 +/- 10.6 years) of AF were recorded. The multivariable-adjusted hazard ratio (HR) for AF increased from 1.06 (95% CI, 1.03-1.10) in individuals with body mass index (BMI) of 20.0 to <22.5 kg/m(2) to 3.72 (95% CI, 2.44-5.66) among men with BMI of 40.0 to 50.0 kg/m(2), compared with those with BMI of 18.5 to <20.0 kg/m(2). During a median follow-up of approximate to 6 years in patients diagnosed with AF, we identified 3767 deaths, 3251 cases of incident heart failure, and 921 cases of ischemic stroke. The multivariable-adjusted HRs for all-cause mortality, incident heart failure, and ischemic stroke in AF-diagnosed men with baseline BMI >30 kg/m(2) compared with those with BMI <20 kg/m(2) were 2.86 (95% CI, 2.30-3.56), 3.42 (95% CI, 2.50-4.68), and 2.34 (95% CI, 1.52-3.61), respectively. Conclusions Increasing BMI in adolescent men is strongly associated with early AF, and with subsequent worse clinical outcomes in those diagnosed with AF with respect to all-cause mortality, incident heart failure, and ischemic stroke.
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34.
  • Djekic, Demir, 1989-, et al. (författare)
  • Replication of LC-MS untargeted lipidomics results in patients with calcific coronary disease : an interlaboratory reproducibility study
  • 2016
  • Ingår i: International Journal of Cardiology. - : Elsevier. - 0167-5273 .- 1874-1754. ; 222, s. 1042-1048
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Recently a lipidomics approach was able to identify perturbed fatty acyl chain (FAC) and sphingolipid moieties that could stratify patients according to the severity of coronary calcification, a form of subclinical atherosclerosis. Nevertheless, these findings have not yet been reproduced before generalising their application. The aim of this study was to evaluate the reproducibility of lipidomics approaches by replicating previous lipidomic findings in groups of patients with calcific coronary artery disease (CCAD).METHODS: Patients were separated into the following groups based on their calcium score (CS); no calcification (CS: 0; n=26), mild calcification (CS: 1-250; n=27) and severe calcification (CS: >250; n=17). Two serum samples were collected from each patient and used for comparative analyses by 2 different laboratories, in different countries and time points using liquid chromatography coupled to mass spectrometry untargeted lipidomics methods.RESULTS: Six identical metabolites differentiated patients with severe coronary artery calcification from those with no calcification were found by both laboratories independently. Additionally, relative intensities from the two analyses demonstrated high correlation coefficients. Phosphatidylcholine moieties with 18-carbon FAC were identified in lower intensities and 20:4 FAC in higher intensities in the serum of diseased group. Moreover, 3 common sphingomyelins were detected.CONCLUSION: This is the first interlaboratory reproducibility study utilising lipidomics applications in general and specifically in patients with CCAD. Lipid profiling applications in patients with CCAD are very reproducible in highly specialised and experienced laboratories and could be applied in clinical practice in order to spare patients diagnostic radiation.
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35.
  • Donis, Daphne, et al. (författare)
  • Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer
  • 2021
  • Ingår i: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590. ; 66:12, s. 4314-4333
  • Tidskriftsartikel (refereegranskat)abstract
    • To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L-1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4 degrees C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature.
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36.
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37.
  • Hedenström, Per, et al. (författare)
  • EUS-guided reverse bevel fine-needle biopsy sampling and open tip fine-needle aspiration in solid pancreatic lesions - a prospective, comparative study
  • 2018
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 53:2, s. 231-237
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Different diagnostic entities can present as solid pancreatic lesions (SPL). This study aimed to explore the utility of endoscopic ultrasound-guided reverse bevel fine-needle biopsy sampling (EUS-FNB) in SPLs.Material and methods: In 2012-2015, consecutive patients with SPLs were prospectively included in a tertiary center setting and subjected to dual needle sampling with a 22 gauge reverse bevel biopsy needle and a conventional 25 gauge open tip aspiration needle (EUS-FNA). The outcome measures were the diagnostic accuracy of sampling, calculated for each modality separately and for the modalities combined (EUS-FNA+FNB), and the adverse event rate related to sampling.Results: In 68 unique study subjects, the most common diagnostic entities were pancreatic neuroendocrine tumor, PNET, (34%), pancreatic ductal adenocarcinoma, PDAC, (32%), pancreatitis (15%) and metastasis (6%). The overall diagnostic accuracy of EUS-FNB was not significantly different from that of EUS-FNA, (69% vs. 78%, p=.31). EUS-FNA+FNB, compared with EUS-FNA alone, had a higher sensitivity for tumors other than PDAC (89% vs. 69%, p=.02) but not for PDACs (95% vs. 85%, p=.5). No adverse event was recorded after the study dual-needle sampling procedures.Conclusions: Endoscopic ultrasound-guided tissue acquisition performed with a 22 gauge reverse bevel biopsy needle is safe but not superior to conventional fine-needle aspiration performed with a 25 gauge open tip needle in diagnosing solid pancreatic lesions. However, the performance of both these modalities may facilitate the diagnostic work-up in selected patients, such as cases suspicious for pancreatic neuroendocrine tumors and metastases. NCT02360839.
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38.
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39.
  • Hoff, Erik, et al. (författare)
  • Carbonic anhydrase, obstructive sleep apnea and hypertension: Effects of intervention
  • 2020
  • Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 29:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Whole blood carbonic anhydrase activity (CAa) is increased in patients with obstructive sleep apnea (OSA). Our study investigated the influence of positive airway pressure (PAP) or CA inhibitor acetazolamide (ACT) therapy on CAa, OSA and blood pressure. Thirty‐three OSA patients (21 hypertensive, body mass index (BMI) 37 ± 7 kg/m2 and apnea–hypopnea index (AHI) of 47 ± 31 events/hr) were followed‐up after PAP treatment (compliance, 4.7 ± 1.5 hr/day; duration, median 6 [IQR 6,6] months) (Cohort A). A second OSA Cohort (B) contained nine hypertensive patients (BMI, 29 ± 4 kg/m2; AHI, 39 ± 20 events/hr) with 2‐week treatment of ACT, PAP or ACT + PAP in an open crossover study. CAa was assessed at baseline and at the end of each treatment period. In Cohort A, baseline CAa was higher in hypertensive, compared with normotensive, patients (1,033 ± 204 versus 861 ± 201 units, p = .028). PAP treatment reduced systolic/diastolic blood pressure but not CAa (−9 ± 11/−5 ± 7 mmHg and −20 ± 289 units, p < .001, <.001 and .70). In Cohort B, blood pressure was reduced in both ACT‐treated groups (−10 ± 10/−5 ± 7 mmHg, p = .043 and .019; and −5 ± 5/−13 ± 13 mmHg, p < .001 and .009). AHI was reduced in both groups: ACT only, −17 ± 9 events/hr p = .001; and ACT + PAP, −39 ± 19 events/hr, p < .001. PAP did not change CAa (p = .98) but activity tended to decrease after ACT with or without PAP (p = .081 and .056). CAa is elevated in hypertensive OSA patients. Long‐term PAP reduced blood pressure without affecting CAa. ACT reduced blood pressure and CAa. Increased CAa may constitute a physiological characteristic in OSA, contributing to comorbid hypertension.
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40.
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41.
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42.
  • Molin, Mikael, 1973, et al. (författare)
  • Linking peroxiredoxin and vacuolar-ATPase functions in calorie restriction-mediated life span extension
  • 2014
  • Ingår i: International Journal of Cell Biology. - : Hindawi Limited. - 1687-8876 .- 1687-8884.
  • Forskningsöversikt (refereegranskat)abstract
    • Calorie restriction (CR) is an intervention extending the life spans of many organisms. The mechanisms underlying CR-dependent retardation of aging are still poorly understood. Despite mechanisms involving conserved nutrient signaling pathways proposed, few target processes that can account for CR-mediated longevity have so far been identified. Recently, both peroxiredoxins and vacuolar-ATPases were reported to control CR-mediated retardation of aging downstream of conserved nutrient signaling pathways. In this review, we focus on peroxiredoxin-mediated stress-defence and vacuolar-ATPase regulated acidification and pinpoint common denominators between the two mechanisms proposed for how CR extends life span. Both the activities of peroxiredoxins and vacuolar-ATPases are stimulated upon CR through reduced activities in conserved nutrient signaling pathways and both seem to stimulate cellular resistance to peroxide-stress. However, whereas vacuolar-ATPases have recently been suggested to control both Ras-cAMP-PKA- and TORC1-mediated nutrient signaling, neither the physiological benefits of a proposed role for peroxiredoxins in H 2O2-signaling nor downstream targets regulated are known. Both peroxiredoxins and vacuolar-ATPases do, however, impinge on mitochondrial iron-metabolism and further characterization of their impact on iron homeostasis and peroxide-resistance might therefore increase our understanding of the beneficial effects of CR on aging and age-related diseases. © 2014 Mikael Molin and Ayse Banu Demir.
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43.
  • Nilsson, Lisa M, 1976, et al. (författare)
  • Cancer Differentiating Agent Hexamethylene Bisacetamide Inhibits BET Bromodomain Proteins
  • 2016
  • Ingår i: Cancer Research. - : American Association for Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 76:8, s. 2376-2383
  • Tidskriftsartikel (refereegranskat)abstract
    • Agents that trigger cell differentiation are highly efficacious in treating certain cancers, but such approaches are not generally effective in most malignancies. Compounds such as DMSO and hexamethylene bisacetamide (HMBA) have been used to induce differentiation in experimental systems, but their mechanisms of action and potential range of uses on that basis have not been developed. Here, we show that HMBA, a compound first tested in the oncology clinic over 25 years ago, acts as a selective bromodomain inhibitor. Biochemical and structural studies revealed an affinity of HMBA for the second bromodomain of BET proteins. Accordingly, both HMBA and the prototype BET inhibitor JQ1 induced differentiation of mouse erythroleukemia cells. As expected of a BET inhibitor, HMBA displaced BET proteins from chromatin, caused massive transcriptional changes, and triggered cell-cycle arrest and apoptosis in Myc-induced B-cell lymphoma cells. Furthermore, HMBA exerted anticancer effects in vivo in mouse models of Myc-driven B-cell lymphoma. This study illuminates the function of an early anticancer agent and suggests an intersection with ongoing clinical trials of BET inhibitor, with several implications for predicting patient selection and response rates to this therapy and starting points for generating BD2-selective BET inhibitors. (C) 2016 AACR.
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44.
  • Ostaszewski, Marek, et al. (författare)
  • COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms
  • 2021
  • Ingår i: Molecular Systems Biology. - : John Wiley & Sons. - 1744-4292 .- 1744-4292. ; 17:10
  • Tidskriftsartikel (refereegranskat)abstract
    • We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.
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45.
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46.
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47.
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48.
  • Willatt, Rosemary, et al. (författare)
  • Retrieval of Snow Depth on Arctic Sea Ice From Surface-Based, Polarimetric, Dual-Frequency Radar Altimetry
  • 2023
  • Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 50:20
  • Tidskriftsartikel (refereegranskat)abstract
    • Snow depth on sea ice is an Essential Climate Variable and a major source of uncertainty in satellite altimetry-derived sea ice thickness. During winter of the MOSAiC Expedition, the “KuKa” dual-frequency, fully polarized Ku- and Ka-band radar was deployed in “stare” nadir-looking mode to investigate the possibility of combining these two frequencies to retrieve snow depth. Three approaches were investigated: dual-frequency, dual-polarization and waveform shape, and compared to independent snow depth measurements. Novel dual-polarization approaches yielded r2 values up to 0.77. Mean snow depths agreed within 1cm, even for data sub-banded to CryoSat-2 SIRAL and SARAL AltiKa bandwidths. Snow depths from co-polarized dual-frequency approaches were at least a factor of four too small and had a r2 0.15 or lower. r2 for waveform shape techniques reached 0.72 but depths were underestimated. Snow depth retrievals using polarimetric information or waveform shape may therefore be possible from airborne/satellite radar altimeters.
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49.
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50.
  • Åberg, Maria A I, 1972, et al. (författare)
  • Body Weight in Adolescent Men in Sweden and Risk of an Early Acute Coronary Event: A Prospective Population-Based Study
  • 2023
  • Ingår i: Journal of the American Heart Association (JAHA). - 2047-9980. ; 12:12
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundCoronary heart disease remains the dominant cause of death worldwide. To improve cardiovascular disease prevention, knowledge of early key risk factors, especially those that are modifiable, is essential. The ongoing global obesity epidemic is of particular concern. We aimed to determine whether body mass index at conscription predicts early acute coronary events among men in Sweden. Methods and ResultsThis was a population-based Swedish cohort study of conscripts (n=1 668 921; mean age, 18.3 years; 1968-2005), with follow-up through linkage to the nationwide Swedish patient and death registries. Risk of a first acute coronary event (hospitalization for acute myocardial infarction or coronary death) during follow-up (1-48 years) was calculated with generalized additive models. Objective baseline measures of fitness and cognition were included in the models in secondary analyses. During follow-up, there were 51 779 acute coronary events, of which 6457 (12.5%) were fatal within 30 days. Compared with men at the lowest end of the normal body mass index spectrum (body mass index, 18.5 kg/m(2)), an increasing risk for a first acute coronary event was observed, with hazard ratios (HRs) peaking at 40 years of age. After multivariable adjustments, men with a body mass index of 35 kg/m(2) had an HR of 4.84 (95% CI, 4.29-5.46) for an event before the age of 40 years. ConclusionsAn increased risk of an early acute coronary event was detectable within normal levels of body weight at the age of 18 years, increasing to almost 5-fold in the highest weight category at 40 years of age. Given increasing levels of body weight and prevalence of overweight and obesity in young adults, the current decrease in coronary heart disease incidence in Sweden may flatten or even reverse in the near future.
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