Summary
Background
Validated diagnostic tools that are accurate, cost effective and acceptable to patients are required for disease stratification and monitoring in NAFLD.
Aims
To investigate the ...performance and cost of multiparametric MRI alongside existing biomarkers in the assessment of NAFLD.
Methods
Adult patients undergoing standard of care liver biopsy for NAFLD were prospectively recruited at two UK liver centres and underwent multiparametric MRI, blood sampling and transient elastography withing 2 weeks of liver biopsy. Non‐invasive markers were compared to histology as the gold standard.
Results
Data were obtained in 50 patients and 6 healthy volunteers. Corrected T1 (cT1) correlated with NAFLD activity score (ρ = 0.514, P < .001). cT1, enhanced liver fibrosis (ELF) test and liver stiffness differentiated patients with simple steatosis and NASH with AUROC (95% CI) of 0.69 (0.50‐0.88), 0.87 (0.77‐0.79) and 0.82 (0.70‐0.94) respectively and healthy volunteers from patients with AUROC (95% CI) of 0.93 (0.86‐1.00), 0.81 (0.69‐0.92) and 0.89 (0.77‐1.00) respectively. For the risk stratification of NAFLD, multiparametric MRI could save £150,218 per 1000 patients compared to biopsy. Multiparametric MRI did not discriminate between individual histological fibrosis stages in this population (P = .068).
Conclusions
Multiparametric MRI accurately identified patients with steatosis, stratifies those with NASH or simple steatosis and reliably excludes clinically significant liver disease with superior negative predictive value (83.3%) to liver stiffness (42.9%) and ELF (57.1%). For the risk stratification of NAFLD, multiparametric MRI was cost effective and, combined with transient elastography, had the lowest cost per correct diagnosis.
Linked content
This article is linked to Ferraioli paper. To view this article visit https://doi.org/10.1111/apt.14501.
Myocardial fibrosis can arise from a range of pathological processes and its presence correlates with adverse clinical outcomes. Cardiac magnetic resonance (CMR) can provide a non-invasive assessment ...of cardiac structure, function, and tissue characteristics, which includes late gadolinium enhancement (LGE) techniques to identify focal irreversible replacement fibrosis with a high degree of accuracy and reproducibility. Importantly the presence of LGE is consistently associated with adverse outcomes in a range of common cardiac conditions; however, LGE techniques are qualitative and unable to detect diffuse myocardial fibrosis, which is an earlier form of fibrosis preceding replacement fibrosis that may be reversible. Novel T1 mapping techniques allow quantitative CMR assessment of diffuse myocardial fibrosis with the two most common measures being native T1 and extracellular volume (ECV) fraction. Native T1 differentiates normal from infarcted myocardium, is abnormal in hypertrophic cardiomyopathy, and may be particularly useful in the diagnosis of Anderson–Fabry disease and amyloidosis. ECV is a surrogate measure of the extracellular space and is equivalent to the myocardial volume of distribution of the gadolinium-based contrast medium. It is reproducible and correlates well with fibrosis on histology. ECV is abnormal in patients with cardiac failure and aortic stenosis, and is associated with functional impairment in these groups. T1 mapping techniques promise to allow earlier detection of disease, monitor disease progression, and inform prognosis; however, limitations remain. In particular, reference ranges are lacking for T1 mapping values as these are influenced by specific CMR techniques and magnetic field strength. In addition, there is significant overlap between T1 mapping values in healthy controls and most disease states, particularly using native T1, limiting the clinical application of these techniques at present.
Manganese-enhanced magnetic resonance imaging can provide a surrogate measure of myocardial calcium handling. Its repeatability and reproducibility are currently unknown. Sixty-eight participants: 20 ...healthy volunteers, 20 with acute myocardial infarction, 18 with hypertrophic and 10 with non-ischemic dilated cardiomyopathy underwent manganese-enhanced magnetic resonance imaging. Ten healthy volunteers were re-scanned at 3 months. Native T1 values and myocardial manganese uptake were assessed for intra and inter-observer repeatability. Scan-rescan reproducibility was assessed in ten healthy volunteers. Intra-observer and inter-observer correlation was excellent in healthy volunteers for mean native T1 mapping Lin's correlation coefficient (LCC) 0.97 and 0.97 respectively and myocardial manganese uptake (LCC: 0.99 and 0.96 respectively). Scan-rescan correlation for native T1 and myocardial manganese uptake was also excellent. Similarly, intra-observer correlations for native T1 and myocardial manganese uptake in patients with acute myocardial infarction (LCC: 0.97 and 0.97 respectively), hypertrophic (LCC: 0.98 and 0.97 respectively) and dilated cardiomyopathy (LCC: 0.99 and 0.95 respectively) were excellent. Limits of agreement were broader in patients with dilated cardiomyopathy. Manganese-enhanced magnetic resonance imaging has high repeatability and reproducibility in healthy myocardium and high repeatability in diseased myocardium. However, further study is needed to establish robustness in pathologies with diffuse myocardial fibrosis.
...the chemical may pass through the skin and contribute to the systemic load. ...the chemical can evoke allergic skin reactions through complex immune system responses that can subsequently trigger ...responses in the skin at both the point of contact and at skin sites remote to the contact.
Over half the world is exposed daily to the smoke from combustion of solid fuels. Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease and can ...be caused by biomass smoke exposure. However, studies of biomass exposure and COPD show a wide range of effect sizes. The aim of this systematic review was to quantify the impact of biomass smoke on the development of COPD and define reasons for differences in the reported effect sizes.
A systematic review was conducted of studies with sufficient statistical power to calculate the health risk of COPD from the use of solid fuel, which followed standardised criteria for the diagnosis of COPD and which dealt with confounding factors. The results were pooled by fuel type and country to produce summary estimates using a random effects model. Publication bias was also estimated.
There were positive associations between the use of solid fuels and COPD (OR=2.80, 95% CI 1.85 to 4.0) and chronic bronchitis (OR=2.32, 95% CI 1.92 to 2.80). Pooled estimates for different types of fuel show that exposure to wood smoke while performing domestic work presents a greater risk of development of COPD and chronic bronchitis than other fuels.
Despite heterogeneity across the selected studies, exposure to solid fuel smoke is consistently associated with COPD and chronic bronchitis. Efforts should be made to reduce exposure to solid fuel by using either cleaner fuel or relatively cleaner technology while performing domestic work.
Offspring exposed to maternal diabetes are at increased risk of neurocognitive impairment, but its origins are unknown. With MR imaging, we investigated the feasibility of comprehensive assessment of ...brain metabolism (
H-MRS), microstructure (DWI), and macrostructure (structural MRI) in third-trimester fetuses in women with diabetes and determined normal ranges for the MR imaging parameters measured.
Women with singleton pregnancies with diabetes (
= 26) and healthy controls (
= 26) were recruited prospectively for MR imaging studies between 34 and 38 weeks' gestation.
Data suitable for postprocessing were obtained from 79%, 71%, and 46% of women for
H-MRS, DWI, and structural MRI, respectively. There was no difference in the NAA/Cho and NAA/Cr ratios (mean SD) in the fetal brain in women with diabetes compared with controls (1.74 0.79 versus 1.79 0.64,
= .81; and 0.78 0.28 versus 0.94 0.36,
= .12, respectively), but the Cho/Cr ratio was marginally lower (0.46 0.11 versus 0.53 0.10,
= .04). There was no difference in mean SD anterior white, posterior white, and deep gray matter ADC between patients and controls (1.16 0.12 versus 1.16 0.08,
= .96; 1.54 0.16 versus 1.59 0.20,
= .56; and 1.49 0.23 versus 1.52 0.23,
= .89, respectively) or volume of the cerebrum (243.0 mL 22.7 mL versus 253.8 mL 31.6 mL,
= .38).
Acquiring multimodal MR imaging of the fetal brain at 3T from pregnant women with diabetes is feasible. Further study of fetal brain metabolism in maternal diabetes is warranted.
•Existing approaches to EPCs in Europe reviewed.•Limitations to current and future applications highlighted.•New forms of modelling for future EPCs documented.•A framework of criteria for evaluating ...new assessment approaches proposed.
As our need for energy information of buildings evolves, and the tools and methods at our disposal increase in scale and complexity, it is perhaps reasonable to expect a similar level of change in the way energy in buildings is assessed within national energy compliance frameworks. By comparing the available opportunities for building energy modelling with the current methodologies underlying Energy Performance Certificates, this study proposes future directions for standardised energy assessment of residential buildings and the impact this could have on different facets of energy policy. In carrying out this exercise, a number of criteria are proposed that could be used to appraise methodologies that align with future requirements of energy assessment, with two potential candidates for future energy assessment considered as part of this appraisal. An argument is thus proposed for better aligning future forms of standardised energy assessment with directions and requirements of future low-carbon energy policy.
Abstract
Aims
The aim of this study is to quantify altered myocardial calcium handling in non-ischaemic cardiomyopathy using magnetic resonance imaging.
Methods and results
Patients with dilated ...cardiomyopathy (n = 10) or hypertrophic cardiomyopathy (n = 17) underwent both gadolinium and manganese contrast-enhanced magnetic resonance imaging and were compared with healthy volunteers (n = 20). Differential manganese uptake (Ki) was assessed using a two-compartment Patlak model. Compared with healthy volunteers, reduction in T1 with manganese-enhanced magnetic resonance imaging was lower in patients with dilated cardiomyopathy mean reduction 257 ± 45 (21%) vs. 288 ± 34 (26%) ms, P < 0.001, with higher T1 at 40 min (948 ± 57 vs. 834 ± 28 ms, P < 0.0001). In patients with hypertrophic cardiomyopathy, reductions in T1 were less than healthy volunteers mean reduction 251 ± 86 (18%) and 277 ± 34 (23%) vs. 288 ± 34 (26%) ms, with and without fibrosis respectively, P < 0.001. Myocardial manganese uptake was modelled, rate of uptake was reduced in both dilated and hypertrophic cardiomyopathy in comparison with healthy volunteers (mean Ki 19 ± 4, 19 ± 3, and 23 ± 4 mL/100 g/min, respectively; P = 0.0068). In patients with dilated cardiomyopathy, manganese uptake rate correlated with left ventricular ejection fraction (r2 = 0.61, P = 0.009). Rate of myocardial manganese uptake demonstrated stepwise reductions across healthy myocardium, hypertrophic cardiomyopathy without fibrosis and hypertrophic cardiomyopathy with fibrosis providing absolute discrimination between the healthy myocardium and fibrosed myocardium (mean Ki 23 ± 4, 19 ± 3, and 13 ± 4 mL/100 g/min, respectively; P < 0.0001).
Conclusion
The rate of manganese uptake in both dilated and hypertrophic cardiomyopathy provides a measure of altered myocardial calcium handling. This holds major promise for the detection and monitoring of dysfunctional myocardium, with the potential for early intervention and prognostication.
Scientific understanding of indoor air pollution is predominately based on research carried out in cities in high-income countries (HICs). Less is known about how pollutant concentrations change over ...the course of a typical day in cities in low- and middle-income countries (LMICs).
To understand how concentrations of fine particulate matter smaller than 2.5 microns in diameter (PM
) change over the course of the day outdoors (across a range of countries) and indoors (using measurements from Dhaka, Bangladesh).
Data on PM
concentrations were gathered from 779 households in Dhaka as part of the MCLASS II (Muslim Communities Learning About Second-hand Smoke in Bangladesh) project, and compared to outdoor PM
concentrations to determine the temporal variation in exposure to air pollution. Hourly PM
data from 23 cities in 14 LMICs, as well as London (UK), Paris (France) and New York (NY, USA), were extracted from publicly available sources for comparison.
PM
in homes in Dhaka demonstrated a similar temporal pattern to outdoor measurements, with greater concentrations at night than in the afternoon. This pattern was also evident in 19 of 23 LMIC cities.
PM
concentrations are greater at night than during the afternoon in homes in Dhaka. Diurnal variations in PM
in LMICs is substantial and greater than in London, Paris or New York. This has implications for public health community approaches to health effects of air pollution in LMICs.
Despite increased global interest in Chinook salmon aquaculture, little is known of their viral immune defenses. This study describes the establishment and characterization of a continuous cell line ...derived from Chinook salmon spleen, CHSS, and its use in innate immune studies. Optimal growth was seen at 14–18 °C when grown in Leibovitz's L-15 media with 20% fetal bovine serum. DNA analyses confirmed that CHSS was Chinook salmon and genetically different from the only other available Chinook salmon cell line, CHSE-214. Unlike CHSE-214, CHSS could bind extracellular dsRNA, resulting in the rapid and robust expression of antiviral genes. Receptor/ligand blocking assays confirmed that class A scavenger receptors (SR-A) facilitated dsRNA binding and subsequent gene expression. Although both cell lines expressed three SR-A genes: SCARA3, SCARA4, and SCARA5, only CHSS appeared to have functional cell-surface SR-As for dsRNA. Collectively, CHSS is an excellent cell model to study dsRNA-mediated innate immunity in Chinook salmon.
•Development of a novel Chinook salmon cell line, CHSS.•CHSS can bind extracellular dsRNA, unlike CHSE-214.•Both CHSE-214 and CHSS express scavenger receptors.•CHSS can be used to study Chinook salmon antiviral responses in vitro.