3,076 research outputs found

    Associations of circulating fatty acids with incident coronary heart disease: a prospective study of 89,242 individuals in UK Biobank

    Get PDF
    Background: the role of fatty acids in coronary heart disease (CHD) remains uncertain. There is little evidence from large-scale epidemiological studies on the relevance of circulating fatty acids levels to CHD risk. This study aims to examine the independent associations of the major circulating types of fatty acids with CHD risk.Methods: UK Biobank is a prospective study of adults aged 40–69 in 2006–2010; in 2012–2013, a subset of the participants were resurveyed. Analyses were restricted to 89,242 participants with baseline plasma fatty acids (measured using nuclear magnetic resonance spectroscopy) and without prior CHD. Cox proportional hazards models were used to estimate hazard ratios (HRs) for the associations with incidence CHD, defined as the first-ever myocardial infarction, unstable angina pectoris, coronary-related death, or relevant procedure. And the major types of fatty acids were mutually adjusted to examine the independent associations. Hazard ratios were corrected for regression dilution using the correlation of baseline and resurvey fatty acids measures.Results: during a median follow-up of 11.8 years, 3,815 incident cases of CHD occurred. Independently of other fatty acids, CHD risk was positively associated with saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA), inversely associated with omega-3 polyunsaturated fatty acids (PUFA), but there was no strong evidence of an association with omega-6 PUFA: HR per standard deviation higher were 1.14 (95% CI, 1.09–1.20), 1.15 (1.10–1.21), 0.91 (0.87–0.94), and 1.04 (0.99–1.09) respectively. Independently of triglycerides and cholesterol, the inverse association with omega-3 PUFA was not materially changed, but the positive associations with SFA and MUFA attenuated to null after adjusting for triglycerides levels.Conclusions: this large-scale study has quantitated the independent associations of circulating fatty acids with CHD risk. Omega-3 PUFA was inversely related to CHD risk, independently of other fatty acids and major lipid fractions. By contrast, independently of other fatty acids, the positive associations of circulating SFA and MUFA with CHD risk were mostly attributed to their relationship with triglycerides

    Conceptual model for the formation of bedforms along subglacial meltwater corridors (SMCs) by variable ice‐water‐bed interactions

    Get PDF
    Subglacial meltwater landforms found on palaeo-ice sheet beds allow the properties of meltwater drainage to be reconstructed, informing our understanding of modern-day subglacial hydrological processes. In northern Canada and Fennoscandia, subglacial meltwater landforms are largely organized into continental-scale networks of subglacial meltwater corridors (SMCs), interpreted as the relics of subglacial drainage systems undergoing variations in meltwater input, effective pressure and drainage efficiency. We review the current state of knowledge of bedforms (hummocks, ridges, murtoos, ribbed bedforms) and associated landforms (channels, eskers) described along SMCs and use selected high-resolution DEMs in Canada and Fennoscandia to complete the bedform catalogue and categorize their characteristics, patterning and spatial distributions. We synthesize the diversity of bedform and formation processes occurring along subglacial drainage routes in a conceptual model invoking spatiotemporal changes in hydraulic connectivity, basal meltwater pressure and ice-bed coupling, which influences the evolution of subglacial processes (bed deformation, erosion, deposition) along subglacial drainage systems. When the hydraulic capacity of the subglacial drainage system is overwhelmed glaciofluvial erosion and deposition will dominate in the SMC, resulting in tracts of hummocks and ridges arising from both fragmentation of underlying pre-existing bedforms and downstream deposition of sediments in basal cavities and crevasses. Re-coupling of ice with the bed, when meltwater supply decreases, facilitates deformation, transforming existing and producing new bedforms concomitant with the wider subglacial bedform imprint. We finally establish a range of future research perspectives to improve understanding of subglacial hydrology, geomorphic processes and bedform diversity along SMCs. These perspectives include the new acquisition of remote-sensing and field-based sedimentological and geomorphological data, a better connection between the interpreted subglacial drainage configurations down corridors and the mathematical treatments studying their stability, and the quantification of the scaling, distribution and evolution of the hydraulically connected drainage system beneath present-day ice masses to test our bedform-related conceptual model

    Independent relevance of different measures of adiposity for carotid intima‐media thickness in 40 000 adults in UK Biobank

    No full text
    Background Uncertainty persists about carotid intima–media thickness (CIMT) as a marker of subclinical atherosclerosis and the independent relevance of different measures of adiposity for CIMT. We assessed the independent relevance of general adiposity (body mass index), central adiposity (waist circumference), and body composition (fat mass index and fat‐free mass index) with CIMT among adults in the United Kingdom. Methods and Results Multivariable linear regression of cross‐sectional analyses of UK Biobank assessed the mean percentage difference in CIMT associated with equivalent differences in adiposity measures. To assess independent associations, body mass index and waist circumference were mutually adjusted, as were fat mass index and fat‐free mass index. Among 39 367 participants (mean [SD] age 64 [8] years, 52% female, 97% White), median (interquartile range) CIMT was 0.65 (0.14) mm in women and 0.69 (0.18) mm in men. All adiposity measures were linearly and positively associated with CIMT after adjusting for confounders. Fat‐free mass index was most strongly associated with CIMT after adjustment for fat mass index (% difference in CIMT: 1.23 [95% CI 0.93–1.53] women; 3.44 [3.01–3.86] men), while associations of fat mass index were attenuated after adjustment for fat‐free mass index (0.28 [−0.02, 0.58] women; −0.59 [−0.99, −0.18] men). After mutual adjustment, body mass index remained positively associated with CIMT, but waist circumference was completely attenuated. Conclusions Fat‐free mass index was the adiposity measure most strongly associated with CIMT, suggesting that CIMT may reflect vascular compensatory remodeling rather than atherosclerosis. Hence, screening for subclinical atherosclerosis should evaluate carotid plaques in addition to CIMT

    Clinical Characteristics and Outcomes of Drug-Induced Acute Kidney Injury Cases

    Get PDF
    Introduction Drug-induced acute kidney injury (DI-AKI) is a frequent adverse event. The identification of DI-AKI is challenged by competing etiologies, clinical heterogeneity among patients, and a lack of accurate diagnostic tools. Our research aims to describe the clinical characteristics and predictive variables of DI-AKI. Methods We analyzed data from the DIRECT study (NCT02159209), an international, multi-center, observational cohort study of enriched clinically adjudicated DI-AKI cases. Cases met the primary inclusion criteria if the patient was exposed to at least one nephrotoxic drug for a minimum of 24 hours prior to acute kidney injury (AKI) onset. Cases were clinically adjudicated and inter-rater reliability (IRR) was measured using Krippendorff's alpha. Variables associated with DI-AKI were identified using L1 regularized multivariable logistic regression. Model performance was assessed using the area under the receiver operating characteristic curve (ROC AUC). Results 314 AKI cases met the eligibility criteria for this analysis, and 271 (86%) cases were adjudicated as DI-AKI. The majority of the AKI cases were recruited from the United States (68%). The most frequent causal nephrotoxic drugs were vancomycin (48.7%), non-steroidal anti-inflammatory drugs (18.2%), and piperacillin/tazobactam (17.8%). The IRR for DI-AKI adjudication was 0.309. The multivariable model identified age, vascular capacity, hyperglycemia, infections, pyuria, serum creatinine trends, and contrast media as significant predictors of DI-AKI with good performance, ROC AUC 0.86. Conclusions The identification of DI-AKI is challenging even with comprehensive adjudication by experienced nephrologists. Our analysis identified key clinical characteristics and outcomes of DI-AKI compared to other AKI etiologies

    Predictive value of metabolic profiling in cardiovascular risk scores: analysis of 75 000 adults in UK Biobank

    Get PDF
    Background: metabolic profiling (the extensive measurement of circulating metabolites across multiple biological pathways) is increasingly employed in clinical care. However, there is little evidence on the benefit of metabolic profiling as compared with established atherosclerotic cardiovascular disease (CVD) risk scores.Methods: UK Biobank is a prospective study of 0.5 million participants, aged 40–69 at recruitment. Analyses were restricted to 74 780 participants with metabolic profiling (measured using nuclear magnetic resonance) and without CVD at baseline. Cox regression was used to compare model performance before and after addition of metabolites to QRISK3 (an established CVD risk score used in primary care in England); analyses derived three models, with metabolites selected by association significance or by employing two different machine learning approaches.Results: we identified 5097 incident CVD events within the 10-year follow-up. Harrell’s C-index of QRISK3 was 0.750 (95% CI 0.739 to 0.763) for women and 0.706 (95% CI 0.696 to 0.716) for men. Adding selected metabolites did not significantly improve measures of discrimination in women (Harrell’s C-index of three models are 0.759 (0.747 to 0.772), 0.759 (0.746 to 0.770) and 0.759 (0.748 to 0.771), respectively) or men (0.710 (0.701 to 0.720), 0.710 (0.700 to 0.719) and 0.710 (0.701 to 0.719), respectively), and neither did it improve reclassification or calibration.Conclusion: this large-scale study applied both conventional and machine learning approaches to assess the potential benefit of metabolic profiling to well-established CVD risk scores. However, there was no evidence that metabolic profiling improved CVD risk prediction in this population

    Scientific Business Abstracts

    No full text

    Multicenter Diagnostic Evaluation of OnSite COVID-19 Rapid Test (CTK Biotech) among Symptomatic Individuals in Brazil and the United Kingdom

    Get PDF
    Evaluating rapid diagnostic tests in diverse populations is essential to improving diagnostic responses as it gives an indication of the accuracy in real-world scenarios. In the case of rapid diagnostic testing within this pandemic, lateral flow tests that meet the minimum requirements for sensitivity and specificity can play a key role in increasing testing capacity, allowing timely clinical management of those infected, and protecting health care systems

    A high-resolution melt curve toolkit to identify lineage-defining SARS-CoV-2 mutations

    Get PDF
    The emergence of severe acute respiratory syndrome 2 (SARS-CoV-2) variants of concern (VOCs), with mutations linked to increased transmissibility, vaccine escape and virulence, has necessitated the widespread genomic surveillance of SARS-CoV-2. This has placed a strain on global sequencing capacity, especially in areas lacking the resources for large scale sequencing activities. Here we have developed three separate multiplex high-resolution melting assays to enable the identification of Alpha, Beta, Delta and Omicron VOCs. The assays were evaluated against whole genome sequencing on upper-respiratory swab samples collected during the Alpha, Delta and Omicron [BA.1] waves of the UK pandemic. The sensitivities of the eight individual primer sets were all 100%, and specificity ranged from 94.6 to 100%. The multiplex HRM assays have potential as a tool for high throughput surveillance of SARS-CoV-2 VOCs, particularly in areas with limited genomics facilities

    Body Fat Distribution, Fat-Free Mass and Cardiovascular Function in the UK Biobank

    No full text
    Abstract Background We evaluated the independent associations of body composition measures on left ventricular ejection fraction (LVEF) and pulse wave arterial stiffness index (PWASI). Methods The present analysis included 23,258 individuals (mean age 63 years, 53% women) who participated in the whole body imaging sub-study of the UK Biobank. Associations of body composition measures with each of LVEF and PWASI, after mutual adjustment for one another and potential confounders, were determined using multivariable linear regression. Results Among regional body fat measures, higher visceral fat (VAT) was associated with lower LVEF (β = − 0.45; 95% CI − 0.60, − 0.31 per SD) and higher PWASI (β = 0.51; 95% CI 0.38–0.65 per SD). The association between VAT and LVEF was negatively linear but positively linear for PWASI throughout the range of VAT measured. Other regional fat measures and fat-free mass were not significantly associated with either LVEF or PWASI. Central adiposity measures (waist circumference [WC] and waist–hip ratio [WHR]) showed significant inverse association with LVEF (WC: β = − 0.11; 95% CI − 0.21, − 0.01 per SD; WHR β = − 0.25; 95% CI − 0.38, − 0.12 per SD) but positive association with PWASI (WC: β = 0.37; 95% CI 0.28–0.47 per SD; WHR β = 0.39; 95% CI 0.27 − 0.51 per SD) while BMI was not significantly associated with LVEF (β = 0.05; 95% CI − 0.04, 0.14 per SD) but showed weaker positive association with PWASI (β = 0.27; 95% CI 0.18–0.35 per SD). Conclusions Excess visceral fat and central adiposity are associated with impaired LV function and increased arterial stiffness which may predispose to heart failure
    corecore