Particle concentration measurement and flow regime identification in multiphase pipe flow using a generalised dual-frequency inversion method

An acoustic particle concentration measurement method, originally developed for marine sediment, in which the backscattered energy received by emitter-receiver transducers in the megahertz range is used to construct concentration profiles in suspensions of solid particles in a carrier fluid is applied to suspensions of general engineering interest. Four particle species with range of densities and sizes are used. Concentration profiles in horizontal, turbulent pipe flow at a Reynolds number of 50,000 and three nominal volume fractions are presented for each particle species, using experimentally determined acoustic coefficients, in order to isolate the influence of particle size and density on transport and settling in solid-liquid multiphase flows. It is clear from the results that the method allows the degree of segregation in real suspensions and slurries to be measured, and has a range of potential applications in the nuclear and minerals processing industries, for example. Lastly, the limiting conditions of the method are explored through the concept of an acoustic penetration depth

Multiscale modelling of ceramic nanoparticle interactions and their influence on the thermal conductivity of nanofluids

There is currently a lack of a reliable theory capable of making accurate predictions of the thermal enhancement in nanofluids (with relatively low solid volume fractions). The work described therefore assesses the thermal conductivity of nanoparticle suspensions in fluids using a Lagrangian particle tracking-based computational modelling technique. A 3D, multiphase fluid-solid model is developed which predicts the motion of suspended nanoparticles. The nanofluid is predicted using an Eulerian-Lagrangian hybrid approach with a constant timestep. This technique takes various multiscale forces into consideration in the calculations, whose characteristic scales are quite different, providing for the first time an analysis of all factors affecting the stability and thermal conductivity of nanofluids. The system considered consists of 71 nm diameter Al2O3 ceramic nanoparticles suspended in water, with homogeneous temperature distributions ranging from 25 °C to 85 °C, at various volume fractions between 1% and 5%. The results of the simulations demonstrate the effectiveness of the presented technique, with predictions elucidating the role of Brownian motion, fluid viscous drag, inter-particle collisions and DLVO attraction and repulsion forces on nanofluid stability. Results indicate that aggregated nanoparticles formed in the suspensions, at various particle concentrations, play an important role in the thermal behaviour of the nanofluids. Predictions are in agreement with theoretical and experimental results obtained in related studies. The thermal characteristics of nanofluids are also considered as a function of temperature, system chemistry and time (measured from an initially homogeneously dispersed state). The proven enhancement in the conductivity of fluids affected by the addition of nanoparticles has great potential to assist the development of commercial nanofluid technology aimed at energy efficient and sustainable processes

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events

Cost-effectiveness of adjunct non-pharmacological interventions for osteoarthritis of the knee

BACKGROUND: There is limited information on the costs and benefits of alternative adjunct non-pharmacological treatments for knee osteoarthritis and little guidance on which should be prioritised for commissioning within the NHS. This study estimates the costs and benefits of acupuncture, braces, heat treatment, insoles, interferential therapy, laser/light therapy, manual therapy, neuromuscular electrical stimulation, pulsed electrical stimulation, pulsed electromagnetic fields, static magnets and transcutaneous electrical nerve Stimulation (TENS), based on all relevant data, to facilitate a more complete assessment of value. METHODS: Data from 88 randomised controlled trials including 7,507 patients were obtained from a systematic review. The studies reported a wide range of outcomes. These were converted into EQ-5D index values using prediction models, and synthesised using network meta-analysis. Analyses were conducted including firstly all trials and secondly only trials with low risk of selection bias. Resource use was estimated from trials, expert opinion and the literature. A decision analytic model synthesised all evidence to assess interventions over a typical treatment period (constant benefit over eight weeks or linear increase in effect over weeks zero to eight and dissipation over weeks eight to 16). RESULTS: When all trials are considered, TENS is cost-effective at thresholds of £20-30,000 per QALY with an incremental cost-effectiveness ratio of £2,690 per QALY vs. usual care. When trials with a low risk of selection bias are considered, acupuncture is cost-effective with an incremental cost-effectiveness ratio of £13,502 per QALY vs. TENS. The results of the analysis were sensitive to varying the intensity, with which interventions were delivered, and the magnitude and duration of intervention effects on EQ-5D. CONCLUSIONS: Using the £20,000 per QALY NICE threshold results in TENS being cost-effective if all trials are considered. If only higher quality trials are considered, acupuncture is cost-effective at this threshold, and thresholds down to £14,000 per QALY

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

High diversity of picornaviruses in rats from different continents revealed by deep sequencing

Outbreaks of zoonotic diseases in humans and livestock are not uncommon, and an important component in containment of such emerging viral diseases is rapid and reliable diagnostics. Such methods are often PCR-based and hence require the availability of sequence data from the pathogen. Rattus norvegicus (R. norvegicus) is a known reservoir for important zoonotic pathogens. Transmission may be direct via contact with the animal, for example, through exposure to its faecal matter, or indirectly mediated by arthropod vectors. Here we investigated the viral content in rat faecal matter (n=29) collected from two continents by analyzing 2.2 billion next-generation sequencing reads derived from both DNA and RNA. Among other virus families, we found sequences from members of the Picornaviridae to be abundant in the microbiome of all the samples. Here we describe the diversity of the picornavirus-like contigs including near-full-length genomes closely related to the Boone cardiovirus and Theiler's encephalomyelitis virus. From this study, we conclude that picornaviruses within R. norvegicus are more diverse than previously recognized. The virome of R. norvegicus should be investigated further to assess the full potential for zoonotic virus transmission

Identification of additional risk loci for stroke and small vessel disease: a meta-analysis of genome-wide association studies

BACKGROUND: Genetic determinants of stroke, the leading neurological cause of death and disability, are poorly understood and have seldom been explored in the general population. Our aim was to identify additional loci for stroke by doing a meta-analysis of genome-wide association studies. METHODS: For the discovery sample, we did a genome-wide analysis of common genetic variants associated with incident stroke risk in 18 population-based cohorts comprising 84 961 participants, of whom 4348 had stroke. Stroke diagnosis was ascertained and validated by the study investigators. Mean age at stroke ranged from 45·8 years to 76·4 years, and data collection in the studies took place between 1948 and 2013. We did validation analyses for variants yielding a significant association (at p<5 × 10(-6)) with all-stroke, ischaemic stroke, cardioembolic ischaemic stroke, or non-cardioembolic ischaemic stroke in the largest available cross-sectional studies (70 804 participants, of whom 19 816 had stroke). Summary-level results of discovery and follow-up stages were combined using inverse-variance weighted fixed-effects meta-analysis, and in-silico lookups were done in stroke subtypes. For genome-wide significant findings (at p<5 × 10(-8)), we explored associations with additional cerebrovascular phenotypes and did functional experiments using conditional (inducible) deletion of the probable causal gene in mice. We also studied the expression of orthologs of this probable causal gene and its effects on cerebral vasculature in zebrafish mutants. FINDINGS: We replicated seven of eight known loci associated with risk for ischaemic stroke, and identified a novel locus at chromosome 6p25 (rs12204590, near FOXF2) associated with risk of all-stroke (odds ratio [OR] 1·08, 95% CI 1·05-1·12, p=1·48 × 10(-8); minor allele frequency 21%). The rs12204590 stroke risk allele was also associated with increased MRI-defined burden of white matter hyperintensity-a marker of cerebral small vessel disease-in stroke-free adults (n=21 079; p=0·0025). Consistently, young patients (aged 2-32 years) with segmental deletions of FOXF2 showed an extensive burden of white matter hyperintensity. Deletion of Foxf2 in adult mice resulted in cerebral infarction, reactive gliosis, and microhaemorrhage. The orthologs of FOXF2 in zebrafish (foxf2b and foxf2a) are expressed in brain pericytes and mutant foxf2b(-/-) cerebral vessels show decreased smooth muscle cell and pericyte coverage. INTERPRETATION: We identified common variants near FOXF2 that are associated with increased stroke susceptibility. Epidemiological and experimental data suggest that FOXF2 mediates this association, potentially via differentiation defects of cerebral vascular mural cells. Further expression studies in appropriate human tissues, and further functional experiments with long follow-up periods are needed to fully understand the underlying mechanisms

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation