| 1. |
- Lumbers, R. T., et al.
(författare)
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The genomics of heart failure: design and rationale of the HERMES consortium
- 2021
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Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
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Tidskriftsartikel (refereegranskat)abstract
- Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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| 2. |
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| 3. |
- Kaptoge, S., et al.
(författare)
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Life expectancy associated with different ages at diagnosis of type 2 diabetes in high-income countries: 23 million person-years of observation
- 2023
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Ingår i: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 11:10, s. 731-742
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prevalence of type 2 diabetes is increasing rapidly, particularly among younger age groups. Estimates suggest that people with diabetes die, on average, 6 years earlier than people without diabetes. We aimed to provide reliable estimates of the associations between age at diagnosis of diabetes and all-cause mortality, cause-specific mortality, and reductions in life expectancy. Methods: For this observational study, we conducted a combined analysis of individual-participant data from 19 high-income countries using two large-scale data sources: the Emerging Risk Factors Collaboration (96 cohorts, median baseline years 1961–2007, median latest follow-up years 1980–2013) and the UK Biobank (median baseline year 2006, median latest follow-up year 2020). We calculated age-adjusted and sex-adjusted hazard ratios (HRs) for all-cause mortality according to age at diagnosis of diabetes using data from 1 515 718 participants, in whom deaths were recorded during 23·1 million person-years of follow-up. We estimated cumulative survival by applying age-specific HRs to age-specific death rates from 2015 for the USA and the EU. Findings: For participants with diabetes, we observed a linear dose–response association between earlier age at diagnosis and higher risk of all-cause mortality compared with participants without diabetes. HRs were 2·69 (95% CI 2·43–2·97) when diagnosed at 30–39 years, 2·26 (2·08–2·45) at 40–49 years, 1·84 (1·72–1·97) at 50–59 years, 1·57 (1·47–1·67) at 60–69 years, and 1·39 (1·29–1·51) at 70 years and older. HRs per decade of earlier diagnosis were similar for men and women. Using death rates from the USA, a 50-year-old individual with diabetes died on average 14 years earlier when diagnosed aged 30 years, 10 years earlier when diagnosed aged 40 years, or 6 years earlier when diagnosed aged 50 years than an individual without diabetes. Using EU death rates, the corresponding estimates were 13, 9, or 5 years earlier. Interpretation: Every decade of earlier diagnosis of diabetes was associated with about 3–4 years of lower life expectancy, highlighting the need to develop and implement interventions that prevent or delay the onset of diabetes and to intensify the treatment of risk factors among young adults diagnosed with diabetes. Funding: British Heart Foundation, Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.
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| 4. |
- Bäcklund, Nils, et al.
(författare)
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Salivary cortisol and cortisone in diagnosis of Cushing's syndrome - a comparison of six different analytical methods
- 2023
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 61:10, s. 1780-1791
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Salivary cortisol and cortisone at late night and after dexamethasone suppression test (DST) are increasingly used for screening of Cushing's syndrome (CS). We aimed to establish reference intervals for salivary cortisol and cortisone with three liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques and for salivary cortisol with three immunoassays (IAs), and evaluate their diagnostic accuracy for CS.Methods: Salivary samples at 08:00 h, 23:00 h and 08:00 h after a 1-mg DST were collected from a reference population (n=155) and patients with CS (n=22). Sample aliquots were analyzed by three LC-MS/MS and three IA methods. After establishing reference intervals, the upper reference limit (URL) for each method was used to calculate sensitivity and specificity for CS. Diagnostic accuracy was evaluated by comparing ROC curves.Results: URLs for salivary cortisol at 23:00 h were similar for the LC-MS/MS methods (3.4-3.9 nmol/L), but varied between IAs: Roche (5.8 nmol/L), Salimetrics (4.3 nmol/L), Cisbio (21.6 nmol/L). Corresponding URLs after DST were 0.7-1.0, and 2.4, 4.0 and 5.4 nmol/L, respectively. Salivary cortisone URLs were 13.5-16.6 nmol/L at 23:00 h and 3.0-3.5 nmol/L at 08:00 h after DST. All methods had ROC AUCs =0.96.Conclusions: We present robust reference intervals for salivary cortisol and cortisone at 08:00 h, 23:00 h and 08:00 h after DST for several clinically used methods. The similarities between LC-MS/MS methods allows for direct comparison of absolute values. Diagnostic accuracy for CS was high for all salivary cortisol and cortisone LC-MS/MS methods and salivary cortisol IAs evaluated.
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| 5. |
- Engström, Rebecka Ericsdotter, et al.
(författare)
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Corrigendum : Multi-functionality of nature-based and other urban sustainability solutions: New York City study
- 2022
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Ingår i: Land Degradation and Development. - : Wiley. - 1085-3278 .- 1099-145X. ; 33:5, s. 813-814
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In the referenced article, Engström R, et al. (2018), the authors would like to report a calculation error. Correcting this error does not alter any of the overarching results or conclusions of the article, but changes the results in the original Table 3 and Figure 3. Two typographical errors were also found in the main article, and are corrected here. The supplementary material has also been updated to reflect these corrections.
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| 6. |
- Engström, Rebecka Ericsdotter, et al.
(författare)
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Corrigendum to “Connecting the resource nexus to basic urban service provision – with a focus on water-energy interactions in New York City” [31 (May) (2017) 83–94] (Sustainable Cities and Society (2017) 31 (83–94), (S2210670716305947), (10.1016/j.scs.2017.02.007))
- 2021
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Ingår i: Sustainable cities and society. - : Elsevier BV. - 2210-6707. ; 72, s. 103002-
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Tidskriftsartikel (refereegranskat)abstract
- The authors regret two instances of misinterpretation of input data and one formatting error in the previously published paper as titled above. First, the numerical estimates for water use in NYC electricity and natural gas supply were found to be incorrect due to a conversion error in a data file. This error has now been corrected and the estimates have been changed to correctly correspond to the references on which they are based on. These changes have led to a recalculation of indirect water use reduction potentials in the interventions studied in the paper. Second, two errors due to primary data misinterpretation related to the studied green roof intervention have been found and corrected. The first led to an overestimation of the green roofs’ energy use reduction potential in the previously published paper. The second led to an underestimation of their installation cost. These errors have also been corrected and all numerical results for the green roof intervention have been recalculated. In the updated sections 3 and 4 of the original publication (below), Table 2, Table 3, Fig. 2 and Fig. 3 are updated with the new results related to both indirect water use reductions and green roof performance and costs. The text in the below sections have been given minor adjustments to clarify this update. These changes make green roofs a less economically favourable intervention in comparison to the previously published results. It also makes indirect water use reductions relatively smaller compared to direct water use reductions. All other results as well as the conclusions of this paper are still valid and unchanged. Lastly, a typo in writing of Eq. (7) in the manuscript text has been corrected. There was no error in the equation used in the analysis; hence, no numerical results have been effected by this correction. The authors would like to apologise for any inconvenience caused. Corrected writing of Eq. (7), section 2.3.1: [Formula presented] Updated sections of the original publication.
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| 7. |
- Engström, Rebecka Ericsdotter, 1984-
(författare)
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Exploring cross-resource impacts of urban sustainability measures : an urban climate-land-energy-water nexus analysis
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In an increasingly urban world, cities' global resource uses grow. Two fundamental resources for making cities liveable are water and energy. These resources are also closely interlinked – systems that convert and deliver energy to cities require water, and urban water systems use energy. In addition, these two resource systems affect and are affected by land use and climate change. This ‘nexus’ between climate, land use, energy and water (CLEW) systems has been extensively studied in the past decade, mainly with a focus on national and transboundary CLEW systems. This doctoral thesis develops the CLEW nexus research from an urban perspective.Two quantitative analyses examine how different types of sustainability measures in cities affect intended and unintended CLEW systems. First, the CLEW impacts of a set of sustainability measures in New York City are assessed - from water conservation to emission reductions. Results show that every measure affects (to varying degrees) all studied sustainability dimensions - water, energy and climate - and that the impacts can be quantified through a reference-resource-to-service-system (RRSS).The second quantitative study focuses on how CLEW impacts from a city's sustainability efforts spread beyond local and international borders. It investigates how global water and land use are affected in alternative scenarios to achieve climate neutrality in 2030 in the town of Oskarshamn, Sweden, using an energy systems simulation model. The study finds that both the magnitude and the geographical distribution of land and water requirements vary between scenarios. A strategy to achieve climate neutrality that invests in electrification leads to increased national water use, while a strategy that relies on biofuels has a greater impact on water and land use internationally. When results are translated to interactions between the UN's sustainable development goals (SDGs), they reveal that SDG synergies and trade-offs are 'strategy-dependent': different options for achieving SDGs on energy, sustainable cities and climate action have varying consequences for the advancement of SDGs on sustainable water, food production and biodiversity.To shed light on how data challenges affect quantitative urban nexus studies, uncertainty assessments of selected thesis’ results are conducted and complemented with a thematic analysis of a set of recently published urban nexus papers. Together, they indicate that analytical choices, uncertainties in results and - as a consequence - research foci are influenced by data limitations in both this thesis and in other urban nexus studies.Lastly, the finding from the Oskarshamn analysis – that SDG interactions are strategy-dependent – is deliberated with experts within sustainability sciences and SDG interaction research. From this, a research agenda is proposed with measures to make SDG 'spillovers' visible in local level decision-making.Taken together, the thesis contributes to filling several knowledge gaps on how urban sustainability measures within the CLEW systems interact within and beyond city limits, and proposes analytical approaches to quantify these interactions. It further points out how current data challenges constrain quantitative urban nexus analyses and highlights research needs to improve data management as well as other key efforts to enable consideration of nexus interactions, including SDG 'spillovers', in cities' sustainability work.
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| 8. |
- Gyldenkerne, Christine, et al.
(författare)
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Coronary Artery Lesion Lipid Content and Plaque Burden in Diabetic and Nondiabetic Patients : PROSPECT II
- 2023
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 147:6, s. 469-481
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with diabetes have increased rates of major adverse cardiac events (MACEs). We hypothesized that this is explained by diabetes-associated differences in coronary plaque morphology and lipid content.METHODS: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), 898 patients with acute myocardial infarction with or without ST-segment elevation underwent 3-vessel quantitative coronary angiography and coregistered near-infrared spectroscopy and intravascular ultrasound imaging after successful percutaneous coronary intervention. Subsequent MACEs were adjudicated to either treated culprit lesions or untreated nonculprit lesions. This substudy stratified patients by diabetes status and assessed baseline culprit and nonculprit prevalence of high-risk plaque characteristics defined as maximum plaque burden ≥70% and maximum lipid core burden index ≥324.7. Separate covariate-adjusted multivariable models were performed to identify whether diabetes was associated with nonculprit lesion-related MACEs and high-risk plaque characteristics.RESULTS: Diabetes was present in 109 of 898 patients (12.1%). During a median 3.7-year follow-up, MACEs occurred more frequently in patients with versus without diabetes (20.1% versus 13.5% [odds ratio (OR), 1.94 (95% CI, 1.14-3.30)]), primarily attributable to increased risk of myocardial infarction related to culprit lesion restenosis (4.3% versus 1.1% [OR, 3.78 (95% CI, 1.12-12.77)]) and nonculprit lesion-related spontaneous myocardial infarction (9.3% versus 3.8% [OR, 2.74 (95% CI, 1.25-6.04)]). However, baseline prevalence of high-risk plaque characteristics was similar for patients with versus without diabetes concerning culprit (maximum plaque burden ≥70%: 90% versus 93%, P=0.34; maximum lipid core burden index ≥324.7: 66% versus 70%, P=0.49) and nonculprit lesions (maximum plaque burden ≥70%: 23% versus 22%, P=0.37; maximum lipid core burden index ≥324.7: 26% versus 24%, P=0.47). In multivariable models, diabetes was associated with MACEs in nonculprit lesions (adjusted OR, 2.47 [95% CI, 1.21-5.04]) but not with prevalence of high-risk plaque characteristics (adjusted OR, 1.21 [95% CI, 0.86-1.69]).CONCLUSIONS: Among patients with recent myocardial infarction, both treated and untreated lesions contributed to the diabetes-associated ≈2-fold increased MACE rate during the 3.7-year follow-up. Diabetes-related plaque characteristics that might underlie this increased risk were not identified by multimodality imaging.
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| 9. |
- Hamada-Kawaguchi, Noriko, 1978-, et al.
(författare)
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Exposure to Therapeutic BTK Inhibitors Induces Phenocopying of Btk29A Mutants in the Fruit Fly Drosophila melanogaster
- 2023
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Ingår i: Frontiers in Bioscience-Landmark. - 2768-6701 .- 2768-6698. ; 28:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bruton’s tyrosine kinase (BTK) is a non-receptor type tyrosine kinase originally identified as the genetic signature responsible for X-linked agammaglobulinemia (XLA) when mutated. Its functional form is required for B lymphocyte maturation in both humans and mice, whereas loss-of-function causes a different form of developmental defect in the fruit fly, Drosophila melanogaster. Methods: Ibrutinib and other therapeutic inhibitors of BTK have been extensively used to successfully treat various leukemias and lymphomas. Btk29A type 2 is the ortholog of BTK in the fruit fly. We show that feeding wild-type flies an ibrutinib-containing diet induces phenocopying of Btk29A mutants, i.e., failure in the fusion of left and right halves of the dorsal cuticles, partial loss of wing tissues and dysregulation of germ cell production. Results: We have previously reported that Btk29A phosphorylates Drosophila Arm (β?-catenin), and ibrutinib reduces phosphorylation at Tyrosine142 of endogenously expressed β?-catenin in Cos7 cells transfected with Btk29A type 2 cDNA. Conclusions: Thus, Drosophila is suitable for screens of novel BTK inhibitor candidates and offers a unique in vivo system in which the mode of action of BTK inhibitors can be examined at the molecular, cellular, and organismal levels.
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| 10. |
- Johnson, Linda S.B., et al.
(författare)
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LVS-HARMED Risk Score for Incident Heart Failure in Patients With Atrial Fibrillation Who Present to the Emergency Department : Data from a World-Wide Registry
- 2021
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Ingår i: Journal of the American Heart Association. - : Wolters Kluwer. - 2047-9980. ; 10:18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heart failure (HF) is a common complication to atrial fibrillation (AF), leading to rehospitalization and death. Early identification of patients with AF at risk for HF might improve outcomes. We aimed to derive a score to predict 1-year risk of new-onset HF after an emergency department (ED) visit with AF.Methods and Results: The RE-LY AF (Randomized Evaluation of Long-Term Anticoagulant Therapy) registry enrolled patients with AF presenting to an ED in 47 countries, and followed them for a year. The end point was HF hospitalization and/or HF death. Among 15 400 ED patients, 9765 had no prior HF (mean age, 64.9 +/- 14.9 years). Within 1 year, new-onset HF developed in 6.8% of patients, of whom 21% died of HF. Independent predictors of HF included left ventricular hypertrophy (odds ratio [OR], 1.47; 95% CI, 1.19-1.82), valvular heart disease (OR, 1.55; 95% CI, 1.18-2.04), smoking (OR, 1.42; 95% CI, 1.12-1.78), height (OR, 0.93; 95% CI, 0.90-0.95 per 3 cm), age (OR, 1.11; 95% CI, 1.07-1.15 per 5 years), rheumatic heart disease (OR, 1.77, 95% CI, 1.24-2.51), prior myocardial infarction (OR, 1.85; 95% CI, 1.45-2.36), remaining in AF at ED discharge (OR, 1.86; 95% CI, 1.46-2.36), and diabetes (OR, 1.33; 95% CI, 1.09-1.64). A continuous risk prediction score (LVS-HARMED [left ventricular, valvular heart disease, smoking or other tobacco use, height, age, rheumatic heart disease, myocardial infarction, emergency department discharge rhythm, and diabetes]) had good discrimination (C statistic, 0.735; 95% CI, 0.716-0.755). Validation was conducted internally using bootstrapping (optimism-corrected C statistic, 0.705) and externally (C statistic, 0.699). The 1-year incidence of HF hospitalization and/or HF death across quartile groups of the score was 1.1%, 4.5%, 6.9%, and 14.4%, respectively. LVS-HARMED also predicted incident stroke (C statistic, 0.753; 95% CI, 0.728-0.778).Conclusions: The LVS-HARMED score predicts new-onset HF after an ED visit for AF. Preventative strategies should be considered in patients with high LVS-HARMED HF risk.
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