A novel method for predicting the response variability of friction-damped gas turbine blades

Predicting the response of gas turbine blades with underplatform friction dampers is challenging due to the combination of frictional nonlinearity and system uncertainty: a traditional Monte Carlo approach to predicting response distributions requires a large number of nonlinear simulations which is computationally expensive. This paper presents a new approach based on the principle of Maximum Entropy that provides an estimate of the response distribution that is approximately two orders of magnitude faster than Monte Carlo Harmonic Balance Method simulations. The premise is to include the concept of `computational uncertainty': incorporating lack of knowledge of the solution as part of the uncertainty, on the basis that there are diminishing returns in computing precise solutions to an uncertain system. To achieve this, the method uses a describing function approximation of the friction-damped part of the system; chooses an ignorance prior probability density function for the complex value of the describing function based on Coulombs friction law; updates the distribution using an estimate of the mean solution, the admissible domain of solutions, and the principle of Maximum Entropy; then carries out a linear Monte Carlo simulation to estimate the response distribution. The approach is validated by comparison with HBM simulations and experimental tests, using an idealised academic system consisting of a periodic array of beams (with controllable uncertainty) coupled by single-point friction dampers. Comparisons with two- and eight-blade systems show generally good agreement. Predicting the response statistics of the maximum blade amplitude reveals specific well-understood circumstances when the method is less effective. Predictions of the overall blade response statistics agree with Monte Carlo HBM extremely well across a wide range of excitation amplitudes and uncertainty levels. Critically, experimental comparisons reveal the care that is needed in accurately characterising uncertainty in order to obtain agreement of response percentiles. The new method allowed fast iteration of uncertainty parameters and correlations to achieve good agreement, which would not have been possible using traditional methods.Mitsubishi Heavy Industrie

Predicting response bounds for friction-damped gas turbine blades with uncertain friction coupling

Friction dampers are often used to reduce high amplitude vibration within gas turbines: they are a robust solution that are able to withstand extreme operating environments. Although the turbine blades are manufactured to tight tolerances, there can be significant variability in the overall response of the assembly. Uncertainties associated with the frictional contact properties are a major factor contributing to this variability. This paper applies a recently developed method for predicting response bounds to friction-damped gas turbines when the characteristics of the friction dampers are unknown, including uncertainty regarding the underlying functional form of the friction law. The approach taken is to represent the frictional contact using a describing function, and formulate an optimisation problem to seek upper and lower bounds on a chosen response metric, such as displacement amplitude. Constraints are chosen that describe known properties of the frictional nonlinearity, without needing to specify a particular constitutive law. The method was validated by comparison with numerical and experimental results from an idealised test system. The experimental test rig consisted of an array of eight beams coupled by pin-contact friction dampers. A modal description of this test rig formed the basis of a numerical model, which uses the Harmonic Balance Method (HBM) for nonlinear simulations. A set of Monte Carlo tests was carried out numerically and experimentally for both a two-beam sub-assembly as well as for the full eight-beam assembly. Comparisons with numerical results showed excellent agreement providing confident verification of the implementation, and comparisons with experimental results revealed that the bounds became less conservative as the system complexity increased. Overall the results are promising: upper and lower response bounds for an array of friction-damped systems can be computed at similar cost to a single HBM simulation, giving reliable bounds that are valid for both parametric and model uncertainties associated with the friction couplings.Mitsubishi Heavy Industrie

The multidisciplinary management of type 2 and gestational diabetes in pregnancy

The UK is experiencing a dramatic increase in the prevalence of type 2 diabetes mellitus (T2D). Consequently, there is a corresponding increase in diabetes in pregnancy, with 87.5% of pregnancies in the UK complicated by diabetes due to gestational diabetes mellitus (GDM), and 27% of those with pre-existing diabetes having T2D (National Centre for Health and Clinical Excellence (NICE), 2008a). Although the risks to mother and baby are similar to type 1 diabetes (T1D), the approach and management often differ. Women with GDM and T2D are more likely to be older, multiparous and live in deprived areas. Certain ethnic groups are more prone to GDM and T2D, and there is a strong association between being overweight or obese and diabetes. Women who develop GDM in pregnancy also have an increased risk of T2D in later life (Diabetes UK, 2011a). Some surveys, such as the Confidential Enquiry into Maternal and Child Health (CEMACH, 2007a) have shown that women with T2D often receive suboptimum care prior to conception and in early pregnancy. This paper presents an overview of the multidisciplinary management of T2D and GDM in pregnancy and identifies areas where care may be lacking for these women

The Epidemiology of Staphylococcus aureus and Panton-Valentine Leucocidin (pvl) in Central Australia, 2006-2010

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: The Central Australian Indigenous population has a high incidence of Staphylococcus aureus bacteremia (SAB) but little is known about the local molecular epidemiology. Methods: Prospective observational study of bacteremic and nasal colonizing S.aureus isolates between June 2006 to June 2010. All isolates underwent single nucleotide polymorphism (SNP) genotyping and testing for the presence of the Panton-Valentine Leucocidin (pvl) gene. Results: Invasive isolates (n = 97) were predominantly ST93 (26.6 %) and pvl positive (54.3 %), which was associated with skin and soft tissue infections (OR 4.35, 95 % CI 1.16, 16.31). Non-multiresistant MRSA accounted for 31.9 % of bacteremic samples and showed a trend to being healthcare associated (OR 2.16, 95 % CI 0.86, 5.40). Non-invasive isolates (n = 54) were rarely ST93 (1.9 %) or pvl positive (7.4 %). Conclusions: In Central Australia, ST93 was the dominant S.aureus clone, and was frequently pvl positive and associated with an aggressive clinical phenotype. Whether non-nasal carriage is more important with invasive clones or whether colonization occurs only transiently remains to be elucidated

A novel method for predicting the response variability of friction-damped gas turbine blades

Predicting the response of gas turbine blades with underplatform friction dampers is challenging due to the combination of frictional nonlinearity and system uncertainty: a traditional Monte Carlo approach to predicting response distributions requires a large number of nonlinear simulations which is computationally expensive. This paper presents a new approach based on the principle of Maximum Entropy that provides an estimate of the response distribution that is approximately two orders of magnitude faster than Monte Carlo Harmonic Balance Method simulations. The premise is to include the concept of ‘computational uncertainty’: incorporating lack of knowledge of the solution as part of the uncertainty, on the basis that there are diminishing returns in computing precise solutions to an uncertain system. To achieve this, the method uses a describing function approximation of the friction-damped part of the system; chooses an ignorance prior probability density function for the complex value of the describing function based on Coulombs friction law; updates the distribution using an estimate of the mean solution, the admissible domain of solutions, and the principle of Maximum Entropy; then carries out a linear Monte Carlo simulation to estimate the response distribution. The approach is validated by comparison with HBM simulations and experimental tests, using an idealised academic system consisting of a periodic array of beams (with controllable uncertainty) coupled by single-point friction dampers. Comparisons with two- and eight-blade systems show generally good agreement. Predicting the response statistics of the maximum blade amplitude reveals specific well-understood circumstances when the method is less effective. Predictions of the overall blade response statistics agree with Monte Carlo HBM extremely well across a wide range of excitation amplitudes and uncertainty levels. Critically, experimental comparisons reveal the care that is needed in accurately characterising uncertainty in order to obtain agreement of response percentiles. The new method allowed fast iteration of uncertainty parameters and correlations to achieve good agreement, which would not have been possible using traditional methods

Impact of an interatrial shunt device on survival and heart failure hospitalization in patients with preserved ejection fraction

Aims: Impaired left ventricular diastolic function leading to elevated left atrial pressures, particularly during exertion, is a key driver of symptoms and outcomes in heart failure with preserved ejection fraction (HFpEF). Insertion of an interatrial shunt device (IASD) to reduce left atrial pressure in HFpEF has been shown to be associated with short‐term haemodynamic and symptomatic benefit. We aimed to investigate the potential effects of IASD placement on HFpEF survival and heart failure hospitalization (HFH). Methods and results: Heart failure with preserved ejection fraction patients participating in the Reduce Elevated Left Atrial Pressure in Patients with Heart Failure study (Corvia Medical) of an IASD were followed for a median duration of 739 days. The theoretical impact of IASD implantation on HFpEF mortality was investigated by comparing the observed survival of the study cohort with the survival predicted from baseline data using the Meta‐analysis Global Group in Chronic Heart Failure heart failure risk survival score. Baseline and post‐IASD implant parameters associated with HFH were also investigated. Based upon the individual baseline demographic and cardiovascular profile of the study cohort, the Meta‐analysis Global Group in Chronic Heart Failure score‐predicted mortality was 10.2/100 pt years. The observed mortality rate of the IASD‐treated cohort was 3.4/100 pt years, representing a 33% lower rate (P = 0.02). By Kaplan–Meier analysis, the observed survival in IASD patients was greater than predicted (P = 0.014). Baseline parameters were not predictive of future HFH events; however, poorer exercise tolerance and a higher workload‐corrected exercise pulmonary capillary wedge pressure at the 6 months post‐IASD study were associated with HFH. Conclusions: The current study suggests IASD implantation may be associated with a reduction in mortality in HFpEF. Large‐scale ongoing randomized studies are required to confirm the potential benefit of this therapy

Predictors of non-cystic fibrosis bronchiectasis in Indigenous adult residents of central Australia: results of a case-control study

The human T-cell leukaemia virus type 1 (HTLV-1) is associated with pulmonary inflammation. Indigenous Australians in central Australia have a very high prevalence of HTLV-1 infection and we hypothesised that this might contribute to high rates of bronchiectasis in this population. 80 Indigenous adults with confirmed bronchiectasis, each matched by age, sex and language to two controls without bronchiectasis, were recruited. Case notes and chest imaging were reviewed, HTLV-1 serology and the number of peripheral blood leukocytes (PBLs) infected with HTLV-1 (pro-viral load (PVL)) were determined, and radiological abnormality scores were calculated. Participants were followed for a mean±sd of 1.14±0.86 years and causes of death were determined. Median (interquartile range) HTLV-1 PVL for cases was 8-fold higher than controls (cases 213.8 (19.7-3776.3) copies per 10⁵ PBLs versus controls 26.6 (0.9-361) copies per 10⁵ PBLs; p=0.002). Radiological abnormality scores were higher for cases with HTLV-1 PVL ≥1000 copies per 10⁵ PBLs and no cause of bronchiectasis other than HTLV-1 infection. Major predictors of bronchiectasis were prior severe lower respiratory tract infection (adjusted OR (aOR) 17.83, 95% CI 4.51-70.49; p<0.001) and an HTLV-1 PVL ≥1000 copies per 10⁵ PBLs (aOR 12.41, 95% CI 3.84-40.15; p<0.001). Bronchiectasis (aOR 4.27, 95% CI 2.04-8.94; p<0.001) and HTLV-1 PVL ≥1000 copies per 105 PBLs (aOR 3.69, 95% CI 1.11-12.27; p=0.033) predicted death. High HTLV-1 PVLs are associated with bronchiectasis and with more extensive radiological abnormalities, which may result from HTLV-1-mediated airway inflammation.Lloyd Einsiedel, Hai Pham, Virginia Au, Saba Hatami, Kim Wilson, Tim Spelman and Hubertus Jersman

Multiple sclerosis risk variants regulate gene expression in innate and adaptive immune cells

At least 200 single-nucleotide polymorphisms (SNPs) are associated with multiple sclerosis (MS) risk. A key function that could mediate SNP-encoded MS risk is their regulatory effects on gene expression. We performed microarrays using RNA extracted from purified immune cell types from 73 untreated MS cases and 97 healthy controls and then performed Cis expression quantitative trait loci mapping studies using additive linear models. We describe MS risk expression quantitative trait loci associations for 129 distinct genes. By extending these models to include an interaction term between genotype and phenotype, we identify MS risk SNPs with opposing effects on gene expression in cases compared with controls, namely, rs2256814 MYT1 in CD4 cells (q = 0.05) and rs12087340 RF00136 in monocyte cells (q = 0.04). The rs703842 SNP was also associated with a differential effect size on the expression of the METTL21B gene in CD8 cells of MS cases relative to controls (q = 0.03). Our study provides a detailed map of MS risk loci that function by regulating gene expression in cell types relevant to MS

Common and low frequency variants in MERTK are independently associated with multiple sclerosis susceptibility with discordant association dependent upon HLA-DRB1*15:01 status

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The risk of developing MS is strongly influenced by genetic predisposition, and over 100 loci have been established as associated with susceptibility. However, the biologically relevant variants underlying disease risk have not been defined for the vast majority of these loci, limiting the power of these genetic studies to define new avenues of research for the development of MS therapeutics. It is therefore crucial that candidate MS susceptibility loci are carefully investigated to identify the biological mechanism linking genetic polymorphism at a given gene to the increased chance of developing MS. MERTK has been established as an MS susceptibility gene and is part of a family of receptor tyrosine kinases known to be involved in the pathogenesis of demyelinating disease. In this study we have refined the association of MERTK with MS risk to independent signals from both common and low frequency variants. One of the associated variants was also found to be linked with increased expression of MERTK in monocytes and higher expression of MERTK was associated with either increased or decreased risk of developing MS, dependent upon HLA-DRB1*15:01 status. This discordant association potentially extended beyond MS susceptibility to alterations in disease course in established MS. This study provides clear evidence that distinct polymorphisms within MERTK are associated with MS susceptibility, one of which has the potential to alter MERTK transcription, which in turn can alter both susceptibility and disease course in MS patients

QTL detection for milk production traits in goats using a longitudinal model

Summary Eight paternal half-sib families were used to identify chromosomal regions associated with variation in the lactation curves of dairy goats. DNA samples from 162 animals were amplified by PCR for 37 microsatellite markers, from Capra hircus autosomes CHI3, CHI6, CHI14 and CHI20. Milk samples were collected during 6 years, and there were 897 records for milk yield (MY) and 814 for fat (FP) and protein percentage (PP). The analysis was conducted in two stages. First, a random regression model with several fixed effects was fitted to describe the lactation function, using a scale (α) plus four shape parameters: β and γ, both associated with a decrease in the slope of the curve, and δ and φ that are related to the increase in slope. Predictions of α, β, γ, δ and φ were regressed using an interval mapping model, and F-tests were used to test for quantitative trait loci (QTL) effects. Significant (p < 0.05) QTLs were found for: (i) MY: CHI6 at 70-80 cM for all parameters; CHI14 at 14 cM for δ and φ; (ii) FP: CHI14, at 63 cM was associated with β; CHI20, at 72 cM, showed association with α; (iii) PP: chromosomal regions associated with β were found at 59 cM in CHI3 and at 55 cM in CHI20 with α and γ. Analyses using more families and more animals will be useful to confirm or to reject these findings. © 2008 Blackwell Verlag, Berlin.Fil: Roldán, D.L.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Genética; ArgentinaFil: Rabasa, Alicia Elvira. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; ArgentinaFil: Saldaño, S.. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; ArgentinaFil: Holgado, F.. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Tucuman-santiago del Estero. Campo Experimental Regional Leales; ArgentinaFil: Poli, M. A.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Genética; ArgentinaFil: Cantet, Rodolfo Juan Carlos. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal; Argentin