Characterization of uncertainties in atmospheric trace gas inversions using hierarchical Bayesian methods

We present a hierarchical Bayesian method for atmospheric trace gas inversions. This method is used to estimate emissions of trace gases as well as "hyper-parameters" that characterize the probability density functions (PDFs) of the a priori emissions and model-measurement covariances. By exploring the space of "uncertainties in uncertainties", we show that the hierarchical method results in a more complete estimation of emissions and their uncertainties than traditional Bayesian inversions, which rely heavily on expert judgment. We present an analysis that shows the effect of including hyper-parameters, which are themselves informed by the data, and show that this method can serve to reduce the effect of errors in assumptions made about the a priori emissions and model-measurement uncertainties. We then apply this method to the estimation of sulfur hexafluoride (SF6) emissions over 2012 for the regions surrounding four Advanced Global Atmospheric Gases Experiment (AGAGE) stations. We find that improper accounting of model representation uncertainties, in particular, can lead to the derivation of emissions and associated uncertainties that are unrealistic and show that those derived using the hierarchical method are likely to be more representative of the true uncertainties in the system. We demonstrate through this SF6 case study that this method is less sensitive to outliers in the data and to subjective assumptions about a priori emissions and model-measurement uncertainties than traditional methods

Infarct size and left ventricular remodelling after preventive percutaneous coronary intervention

Objective: We hypothesised that, compared with culprit-only primary percutaneous coronary intervention (PCI), additional preventive PCI in selected patients with ST-elevation myocardial infarction with multivessel disease would not be associated with iatrogenic myocardial infarction, and would be associated with reductions in left ventricular (LV) volumes in the longer term. Methods: In the preventive angioplasty in myocardial infarction trial (PRAMI; ISRCTN73028481), cardiac magnetic resonance (CMR) was prespecified in two centres and performed (median, IQR) 3 (1, 5) and 209 (189, 957) days after primary PCI. Results: From 219 enrolled patients in two sites, 84% underwent CMR. 42 (50%) were randomised to culprit-artery-only PCI and 42 (50%) were randomised to preventive PCI. Follow-up CMR scans were available in 72 (86%) patients. There were two (4.8%) cases of procedure-related myocardial infarction in the preventive PCI group. The culprit-artery-only group had a higher proportion of anterior myocardial infarctions (MIs) (55% vs 24%). Infarct sizes (% LV mass) at baseline and follow-up were similar. At follow-up, there was no difference in LV ejection fraction (%, median (IQR), (culprit-artery-only PCI vs preventive PCI) 51.7 (42.9, 60.2) vs 54.4 (49.3, 62.8), p=0.23), LV end-diastolic volume (mL/m2, 69.3 (59.4, 79.9) vs 66.1 (54.7, 73.7), p=0.48) and LV end-systolic volume (mL/m2, 31.8 (24.4, 43.0) vs 30.7 (23.0, 36.3), p=0.20). Non-culprit angiographic lesions had low-risk Syntax scores and 47% had non-complex characteristics. Conclusions: Compared with culprit-only PCI, non-infarct-artery MI in the preventive PCI strategy was uncommon and LV volumes and ejection fraction were similar

Challenges in developing a solar powered stirling engine for domestic electricity generation

Paper presented at the 9th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Malta, 16-18 July, 2012.This paper investigates the challenges in developing a solar powered Stirling engine for domestic electricity generation. All the system components, the parabolic troughs, heat transfer fluid and the Stirling engine are individually analysed. The analysis includes a market survey and performance assessments of such components. A mathematical analysis for the Stirling engine is carried out in order to understand the affect of varies parameters with the work output per cycle and the engine efficiency. Such parameters are the phase angle between pistons, the diameter ratio of the power and displacer piston, and change in temperature.dc201

Dielectric spectra analysis: reliable parameter estimation using interval analysis

Dielectric spectroscopy is an extremely versatile method for characterizing the molecular dynamics over a large range of time scales. Unfortunately, the extraction of model parameters by data fitting is still a crucial problem which is now solved by our program S.A.D.E. S.A.D.E. is based on the algorithm S.I.V.I.A. which was proposed and implemented by Jaulin in order to solve constraint satisfaction problems. The problem of dielectric data analysis is reduced to a problem of choosing the appropriate physical model. In this article, Debye relaxations were used and validated to fit the relaxations of a DGEBA prepolymer and the polarization of the spectrometer electrodes. The conductivity was evaluated too

Challenges in developing a solar powered stirling engine for domestic electricity generation

This paper investigates the challenges in developing a solar powered Stirling engine for domestic electricity generation. All the system components, the parabolic troughs, heat transfer fluid and the Stirling engine are individually analysed. The analysis includes a market survey and performance assessments of such components. A mathematical analysis for the Stirling engine is carried out in order to understand the affect of varies parameters with the work output per cycle and the engine efficiency. Such parameters are the phase angle between pistons, the diameter ratio of the power and displacer piston, and change in temperature.peer-reviewe

Correlations and forecast of death tolls in the Syrian conflict

The Syrian armed conflict has been ongoing since 2011 and has already caused thousands of deaths. The analysis of death tolls helps to understand the dynamics of the conflict and to better allocate resources and aid to the affected areas. In this article, we use information on the daily number of deaths to study temporal and spatial correlations in the data, and exploit this information to forecast events of deaths. We found that the number of violent deaths per day in Syria varies more widely than that in England in which non-violent deaths dominate. We have identified strong positive auto-correlations in Syrian cities and non-trivial cross-correlations across some of them. The results indicate synchronization in the number of deaths at different times and locations, suggesting respectively that local attacks are followed by more attacks at subsequent days and that coordinated attacks may also take place across different locations. Thus the analysis of high temporal resolution data across multiple cities makes it possible to infer attack strategies, warn potential occurrence of future events, and hopefully avoid further deaths

Effect of Care Guided by Cardiovascular Magnetic Resonance, Myocardial Perfusion Scintigraphy, or NICE Guidelines on Subsequent Unnecessary Angiography Rates : The CE-MARC 2 Randomized Clinical Trial

Importance Among patients with suspected coronary heart disease (CHD), rates of invasive angiography are considered too high. Objective To test the hypothesis that among patients with suspected CHD, cardiovascular magnetic resonance (CMR)–guided care is superior to National Institute for Health and Care Excellence (NICE) guidelines–directed care and myocardial perfusion scintigraphy (MPS)–guided care in reducing unnecessary angiography. Design, Setting, and Participants Multicenter, 3-parallel group, randomized clinical trial using a pragmatic comparative effectiveness design. From 6 UK hospitals, 1202 symptomatic patients with suspected CHD and a CHD pretest likelihood of 10% to 90% were recruited. First randomization was November 23, 2012; last 12-month follow-up was March 12, 2016. Interventions Patients were randomly assigned (240:481:481) to management according to UK NICE guidelines or to guided care based on the results of CMR or MPS testing. Main Outcomes and Measures The primary end point was protocol-defined unnecessary coronary angiography (normal fractional flow reserve >0.8 or quantitative coronary angiography [QCA] showing no percentage diameter stenosis ≥70% in 1 view or ≥50% in 2 orthogonal views in all coronary vessels ≥2.5 mm diameter) within 12 months. Secondary end points included positive angiography, major adverse cardiovascular events (MACEs), and procedural complications. Results Among 1202 symptomatic patients (mean age, 56.3 years [SD, 9.0]; women, 564 [46.9%] ; mean CHD pretest likelihood, 49.5% [SD, 23.8%]), number of patients with invasive coronary angiography after 12 months was 102 in the NICE guidelines group (42.5% [95% CI, 36.2%-49.0%])], 85 in the CMR group (17.7% [95% CI, 14.4%-21.4%]); and 78 in the MPS group (16.2% [95% CI, 13.0%-19.8%]). Study-defined unnecessary angiography occurred in 69 (28.8%) in the NICE guidelines group, 36 (7.5%) in the CMR group, and 34 (7.1%) in the MPS group; adjusted odds ratio of unnecessary angiography: CMR group vs NICE guidelines group, 0.21 (95% CI, 0.12-0.34, P < .001); CMR group vs the MPS group, 1.27 (95% CI, 0.79-2.03, P = .32). Positive angiography proportions were 12.1% (95% CI, 8.2%-16.9%; 29/240 patients) for the NICE guidelines group, 9.8% (95% CI, 7.3%-12.8%; 47/481 patients) for the CMR group, and 8.7% (95% CI, 6.4%-11.6%; 42/481 patients) for the MPS group. A MACE was reported at a minimum of 12 months in 1.7% of patients in the NICE guidelines group, 2.5% in the CMR group, and 2.5% in the MPS group (adjusted hazard ratios: CMR group vs NICE guidelines group, 1.37 [95% CI, 0.52-3.57]; CMR group vs MPS group, 0.95 [95% CI, 0.46-1.95]). Conclusions and Relevance In patients with suspected angina, investigation by CMR resulted in a lower probability of unnecessary angiography within 12 months than NICE guideline–directed care, with no statistically significant difference between CMR and MPS strategies. There were no statistically significant differences in MACE rates. Trial Registration Clinicaltrials.gov Identifier: NCT01664858

Large-Scale Evidence for the Effect of the COLIA1 Sp1 Polymorphism on Osteoporosis Outcomes: The GENOMOS Study.

Background Osteoporosis and fracture risk are considered to be under genetic control. Extensive work is being performed to identify the exact genetic variants that determine this risk. Previous work has suggested that a G/T polymorphism affecting an Sp1 binding site in the COLIA1 gene is a genetic marker for low bone mineral density (BMD) and osteoporotic fracture, but there have been no very-large-scale studies of COLIA1 alleles in relation to these phenotypes. Methods and Findings Here we evaluated the role of COLIA1 Sp1 alleles as a predictor of BMD and fracture in a multicenter study involving 20,786 individuals from several European countries. At the femoral neck, the average (95% confidence interval [CI]) BMD values were 25 mg/cm2 (CI, 16 to 34 mg/cm2) lower in TT homozygotes than the other genotype groups ( p &lt; 0.001), and a similar difference was observed at the lumbar spine; 21 mg/cm2 (CI, 1 to 42 mg/cm2), ( p = 0.039). These associations were unaltered after adjustment for potential confounding factors. There was no association with fracture overall (odds ratio [OR] = 1.01 [CI, 0.95 to 1.08]) in either unadjusted or adjusted analyses, but there was a non-significant trend for association with vertebral fracture and a nominally significant association with incident vertebral fractures in females (OR = 1.33 [CI, 1.00 to 1.77]) that was independent of BMD, and unaltered in adjusted analyses. Conclusions Allowing for the inevitable heterogeneity between participating teams, this study—which to our knowledge is the largest ever performed in the field of osteoporosis genetics for a single gene—demonstrates that the COLIA1 Sp1 polymorphism is associated with reduced BMD and could predispose to incident vertebral fractures in women, independent of BMD. The associations we observed were modest however, demonstrating the importance of conducting studies that are adequately powered to detect and quantify the effects of common genetic variants on complex diseases

Coronary microvascular dysfunction in patients with stable coronary artery disease: The CE-MARC 2 coronary physiology sub-study

Background: In patients with angina undergoing invasive management, no obstructive coronary artery disease (NOCAD) is a common finding, and angina may persist following percutaneous coronary intervention (PCI). Coronary microvascular dysfunction may be relevant. We aimed to assess the proportion of patients presenting with suspected CAD who had coronary microvascular dysfunction. Methods: Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 (CE-MARC 2) was a prospective multicenter randomised controlled trial of functional imaging versus guideline-based management in patients with suspected CAD. Invasive coronary angiography was protocol-directed. Fractional flow reserve (FFR) and parameters of microvascular function (coronary flow reserve (CFR), index of microcirculatory resistance (IMR), resistance reserve ratio (RRR)) were measured in major epicardial coronary arteries with ≥40–≤90% diameter stenosis. An FFR value ≤0.80 indicated the presence of obstructive CAD. Results: 267/1202 (22.2%) patients underwent angiography and 81 (30%) patients had FFR measured. 63 (78%) of these patients had microvascular function assessed in 85 arteries (mean age 58.5 ± 8.2 years; 47 (75%) male). 25/63 (40%) patients had NOCAD, and of these, 17 (68%) had an abnormality ≥1 parameter of microvascular function (abnormal IMR (≥25), abnormal CFR (<2.0), and abnormal RRR (<2.0) occurred in 10 (40%), 12 (48%), and 11 (44%), respectively). 38/63 (60%) patients had obstructive epicardial CAD. Of these patients, 15/38 (39%), 20/38 (53%), and 12/38 (32%) had an abnormal IMR, CFR and RRR, respectively. Conclusions: Coronary microvascular dysfunction is common in patients with angina. Invasive assessment of microvascular function may be informative and relevant for decision-making in patients with both NOCAD and obstructive epicardial CAD

Rationale and design of the Medical Research Council precision medicine with Zibotentan in microvascular angina (PRIZE) trial

Background: Microvascular angina is caused by cardiac small vessel disease and dysregulation of the endothelin system is implicated. The minor G allele of the non-coding single nucleotide polymorphism (SNP) rs9349379 enhances expression of the endothelin 1 gene in human vascular cells, increasing circulating concentrations of ET-1. The prevalence of this allele is higher in patients with ischemic heart disease. Zibotentan is a potent, selective inhibitor of the ETA receptor. We have identified zibotentan as a potential disease-modifying therapy for patients with microvascular angina. Methods: We will assess the efficacy and safety of adjunctive treatment with oral zibotentan (10 mg daily) in patients with microvascular angina and assess whether rs9349379 (minor G allele; population prevalence ~36%) acts as a theragnostic biomarker of the response to treatment with zibotentan. The Precision medicine with Zibotentan in microvascular angina (PRIZE) trial is a prospective, randomized, double-blind, placebo-controlled, sequential cross-over trial. The study population will be enriched to ensure a G-allele frequency of 50% for the rs9349379 SNP. The participants will receive a single-blind placebo run-in followed by treatment with either 10 mg of zibotentan daily for 12 weeks then placebo for 12 weeks, or vice versa, in random order. The primary outcome is treadmill exercise duration using the Bruce protocol. The primary analysis will assess the within-subject difference in exercise duration following treatment with zibotentan versus placebo. Conclusion: PRIZE invokes precision medicine in microvascular angina. Should our hypotheses be confirmed, this developmental trial will inform the rationale and design for undertaking a larger multicenter trial