Status Update of the Parkes Pulsar Timing Array

The Parkes Pulsar Timing Array project aims to make a direct detection of a gravitational-wave background through timing of millisecond pulsars. In this article, the main requirements for that endeavour are described and recent and ongoing progress is outlined. We demonstrate that the timing properties of millisecond pulsars are adequate and that technological progress is timely to expect a successful detection of gravitational waves within a decade, or alternatively to rule out all current predictions for gravitational wave backgrounds formed by supermassive black-hole mergers.Comment: 10 pages, 3 figures, Amaldi 8 conference proceedings, accepted by Classical & Quantum Gravit

Phenoloxidase activity acts as a mosquito innate immune response against infection with semliki forest virus

Several components of the mosquito immune system including the RNA interference (RNAi), JAK/STAT, Toll and IMD pathways have previously been implicated in controlling arbovirus infections. In contrast, the role of the phenoloxidase (PO) cascade in mosquito antiviral immunity is unknown. Here we show that conditioned medium from the Aedes albopictus-derived U4.4 cell line contains a functional PO cascade, which is activated by the bacterium Escherichia coli and the arbovirus Semliki Forest virus (SFV) (Togaviridae; Alphavirus). Production of recombinant SFV expressing the PO cascade inhibitor Egf1.0 blocked PO activity in U4.4 cell- conditioned medium, which resulted in enhanced spread of SFV. Infection of adult female Aedes aegypti by feeding mosquitoes a bloodmeal containing Egf1.0-expressing SFV increased virus replication and mosquito mortality. Collectively, these results suggest the PO cascade of mosquitoes plays an important role in immune defence against arboviruses

Failure Analysis of Flow-induced Vibration Problem of in-serviced Duplex Stainless Steel Piping System in Oil and Gas Industry

Failure of the duplex stainless steel piping system in oil and gas industry can have disastrous effects. In this study, a novel method of failure analysis of flow-induced vibration problem of in-serviced duplex stainless steel piping system is proposed. The proposed non-destructive technique is able to determine a suitable operating condition for continuous operation without failure. The technique relies on the combined operation of operational modal analysis, operating deflection shape analysis and linear elastic finite element analysis. The effect of different operating conditions for two distinct valve opening cases (i.e. fully opened and partially opened) on the dynamic stress is examined, and they are utilised for forecasting purpose in failure analysis. The result shows that maximum operating conditions are 360 and 400 mmscfd for fully opened and partially opened flow control valves, respectively. Beyond this limit, the piping system most likely will fail

The combined diabetes and renal control trial (C-DIRECT) - a feasibility randomised controlled trial to evaluate outcomes in multi-morbid patients with diabetes and on dialysis using a mixed methods approach

Background: This cluster randomised controlled trial set out to investigate the feasibility and acceptability of the “Combined Diabetes and Renal Control Trial” (C-DIRECT) intervention, a nurse-led intervention based on motivational interviewing and self-management in patients with coexisting end stage renal diseases and diabetes mellitus (DM ESRD). Its efficacy to improve glycaemic control, as well as psychosocial and self-care outcomes were also evaluated as secondary outcomes. Methods: An assessor-blinded, clustered randomised-controlled trial was conducted with 44 haemodialysis patients with DM ESRD and ≥ 8% glycated haemoglobin (HbA1c), in dialysis centres across Singapore. Patients were randomised according to dialysis shifts. 20 patients were assigned to intervention and 24 were in usual care. The C-DIRECT intervention consisted of three weekly chair-side sessions delivered by diabetes specialist nurses. Data on recruitment, randomisation, and retention, and secondary outcomes such as clinical endpoints, emotional distress, adherence, and self-management skills measures were obtained at baseline and at 12 weeks follow-up. A qualitative evaluation using interviews was conducted at the end of the trial. Results: Of the 44 recruited at baseline, 42 patients were evaluated at follow-up. One patient died, and one discontinued the study due to deteriorating health. Recruitment, retention, and acceptability rates of C-DIRECT were generally satisfactory HbA1c levels decreased in both groups, but C-DIRECT had more participants with HbA1c < 8% at follow up compared to usual care. Significant improvements in role limitations due to physical health were noted for C-DIRECT whereas levels remained stable in usual care. No statistically significant differences between groups were observed for other clinical markers and other patient-reported outcomes. There were no adverse effects. Conclusions: The trial demonstrated satisfactory feasibility. A brief intervention delivered on bedside as part of routine dialysis care showed some benefits in glycaemic control and on QOL domain compared with usual care, although no effect was observed in other secondary outcomes. Further research is needed to design and assess interventions to promote diabetes self-management in socially vulnerable patients

Evidence for the existence of powder sub-populations in micronized materials : Aerodynamic size-fractions of aerosolized powders possess distinct physicochemical properties

This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Purpose: To investigate the agglomeration behaviour of the fine ( 12.8 µm) particle fractions of salmeterol xinafoate (SX) and fluticasone propionate (FP) by isolating aerodynamic size fractions and characterising their physicochemical and re-dispersal properties. Methods: Aerodynamic fractionation was conducted using the Next Generation Impactor (NGI). Re-crystallized control particles, unfractionated and fractionated materials were characterized for particle size, morphology, crystallinity and surface energy. Re-dispersal of the particles was assessed using dry dispersion laser diffraction and NGI analysis. Results: Aerosolized SX and FP particles deposited in the NGI as agglomerates of consistent particle/agglomerate morphology. SX particles depositing on Stages 3 and 5 had higher total surface energy than unfractionated SX, with Stage 5 particles showing the greatest surface energy heterogeneity. FP fractions had comparable surface energy distributions and bulk crystallinity but differences in surface chemistry. SX fractions demonstrated higher bulk disorder than unfractionated and re-crystallized particles. Upon aerosolization, the fractions differed in their intrinsic emission and dispersion into a fine particle fraction (< 5.0 µm). Conclusions: Micronized powders consisted of sub-populations of particles displaying distinct physicochemical and powder dispersal properties compared to the unfractionated bulk material. This may have implications for the efficiency of inhaled drug deliveryPeer reviewe

Intrapulmonary Pharmacokinetics of First-line Anti-tuberculosis Drugs in Malawian Patients With Tuberculosis

BACKGROUND: Further work is required to understand the intrapulmonary pharmacokinetics of first-line anti-tuberculosis drugs. This study aimed to describe the plasma and intrapulmonary pharmacokinetics of rifampicin, isoniazid, pyrazinamide, and ethambutol, and explore relationships with clinical treatment outcomes in patients with pulmonary tuberculosis. METHODS: Malawian adults with a first presentation of microbiologically-confirmed pulmonary tuberculosis received standard 6-month first-line therapy. Plasma and intrapulmonary samples were collected 8 and 16 weeks into treatment and drug concentrations measured in plasma, lung/airway epithelial lining fluid, and alveolar cells. Population pharmacokinetic modelling generated estimates of drug exposure (Cmax and AUC) from individual-level post-hoc Bayesian estimates of plasma and intrapulmonary pharmacokinetics. RESULTS: One-hundred-and-fifty-seven patients (58% HIV co-infected) participated. Despite standard weight-based dosing, peak plasma concentrations of first-line drugs were below therapeutic drug monitoring targets. Rifampicin concentrations were low in all three compartments. Isoniazid, pyrazinamide, and ethambutol achieved higher concentrations in epithelial lining fluid and alveolar cells than plasma. Isoniazid and pyrazinamide concentrations were 14.6 (95% CI: 11.2-18.0) and 49.8-fold (95% CI: 34.2-65.3) higher in lining fluid than plasma respectively. Ethambutol concentrations were highest in alveolar cells (alveolar cells:plasma ratio 15.0, 95% CI 11.4-18.6). Plasma or intrapulmonary pharmacokinetics did not predict clinical treatment response. CONCLUSIONS: We report differential drug concentrations between plasma and the lung. While plasma concentrations were below therapeutic monitoring targets, accumulation of drugs at the site of disease may explain the success of the first-line regimen. The low rifampicin concentrations observed in all compartments lend strong support for ongoing clinical trials of high-dose rifampicin regimens

High intrapulmonary rifampicin and isoniazid concentrations are associated with rapid sputum bacillary clearance in patients with pulmonary tuberculosis

This work was supported by a Wellcome Trust Clinical PhD Fellowship [grant number 105392/B/14/Z to A.D.M. and L69AGB to JM]. ELC was supported by Wellcome [200901/Z/16/Z]. The Malawi-Liverpool-Wellcome Clinical Research Programme is supported by a strategic award from the Wellcome Trust [206545/Z/17/Z]. We also acknowledge infrastructural support for bioanalysis from the Liverpool Biomedical Research Centre funded by Liverpool Health Partners.Background Intrapulmonary pharmacokinetics may better explain response to tuberculosis (TB) treatment than plasma pharmacokinetics. We explored these relationships by modelling bacillary clearance in sputum in adult patients on first-line treatment in Malawi. Methods Bacillary elimination rates (BER) were estimated using linear mixed-effects modelling of serial time-to-positivity in mycobacterial growth indicator tubes for sputum collected during the intensive phase of treatment (weeks 0 to 8) for microbiologically confirmed TB. Population pharmacokinetic models used plasma and intrapulmonary drug levels at 8 and 16 weeks. Pharmacokinetic-pharmacodynamic relationships were investigated using individual-level measures of drug exposure (AUC and Cmax) for rifampicin, isoniazid, pyrazinamide, and ethambutol, in plasma, epithelial lining fluid, and alveolar cells as covariates in the bacillary elimination models. Results Among 157 participants (58% HIV co-infected), drug exposure in plasma or alveolar cells was not associated with sputum bacillary clearance. Higher peak concentrations (Cmax) or exposure (AUC) to rifampicin or isoniazid in epithelial lining fluid was associated with more rapid bacillary elimination and shorter time to sputum negativity. More extensive disease on baseline chest radiograph was associated with slower bacillary elimination. Clinical outcome was captured in 133 participants, with 15 (11%) unfavourable outcomes recorded (recurrent TB, failed treatment, or death). No relationship between BER and late clinical outcome was identified. Conclusions Greater intrapulmonary drug exposure to rifampicin or isoniazid in the epithelial lining fluid was associated with more rapid bacillary clearance. Higher doses of rifampicin and isoniazid may result in sustained high intrapulmonary drug exposure, rapid bacillary clearance, shorter treatment duration and better treatment outcomes.Publisher PDFPeer reviewe

A novel investigation into the application of non-destructive evaluation for vibration assessment and analysis of in-service pipes

Flow induced vibrations that are close to resonance frequencies are a major problem in all oil and gas processing industries, so all piping systems require regular condition monitoring and inspection to assess changes in their dynamic characteristics and structural integrity in order to prevent catastrophic failures. One of the main causes of pipe failure is weak support causing low frequency high amplitude flow-induced vibration. This causes wear and tear, especially near joints due to their dissimilar stiffness resulting in fatigue failure of joints caused by vibration-induced high cyclic stress. Other contributing factors in pipe failure are poor or inadequate design, poor workmanship during installation or maintenance and inadequate or weak and flexible support. These pipes are usually required to work non-stop for 24 hours a day 7 days a week for weeks, months or years at a time. Regular monitoring and in-service dynamic analysis should ensure continuous and safe operation. A novel method of non-destructive testing and evaluation of these pipes, while in service, is proposed in this paper. This technique will enable early detection and identification of the root causes of any impending failure due to excess vibration as a result of cyclic force induced by the flow. The method pinpoints the location of the impending failure prior to condition-based maintenance procedures. The technique relies on the combined application of Operating Deflection Shapes (ODS) analysis and computational mechanics utilizing Finite Element Analysis (FEA), i.e. linear elastic stress analysis. Any structural modification to the pipes and their supports can then be applied virtually and their effects on the system can be analysed. The effect on vibration levels is assessed and verified. The effect of any change in the forces corresponding to changes in the Differential Pressure (DP) at constant flow rate through the pipes can then be estimated. It was concluded that maintaining the differential pressure above some “critical” threshold ensures the pipe operates under the allowable dynamic stress for a theoretically “indefinite” life cycle

Energy Gaps and Stark Effect in Boron Nitride Nanoribbons

A first-principles investigation of the electronic properties of boron nitride nanoribbons (BNNRs) having either armchair or zigzag shaped edges passivated by hydrogen with widths up to 10 nm is presented. Band gaps of armchair BNNRs exhibit family-dependent oscillations as the width increases and, for ribbons wider than 3 nm, converge to a constant value that is 0.02 eV smaller than the bulk band gap of a boron nitride sheet owing to the existence of very weak edge states. The band gap of zigzag BNNRs monotonically decreases and converges to a gap that is 0.7 eV smaller than the bulk gap due to the presence of strong edge states. When a transverse electric field is applied, the band gaps of armchair BNNRs decrease monotonically with the field strength. For the zigzag BNNRs, however, the band gaps and the carrier effective masses either increase or decrease depending on the direction and the strength of the field.Comment: 5 pages, 5 figure

A rough set-based association rule approach implemented on exploring beverages product spectrum

[[abstract]]When items are classified according to whether they have more or less of a characteristic, the scale used is referred to as an ordinal scale. The main characteristic of the ordinal scale is that the categories have a logical or ordered relationship to each other. Thus, the ordinal scale data processing is very common in marketing, satisfaction and attitudinal research. This study proposes a new data mining method, using a rough set-based association rule, to analyze ordinal scale data, which has the ability to handle uncertainty in the data classification/sorting process. The induction of rough-set rules is presented as method of dealing with data uncertainty, while creating predictive if—then rules that generalize data values, for the beverage market in Taiwan. Empirical evaluation reveals that the proposed Rough Set Associational Rule (RSAR), combined with rough set theory, is superior to existing methods of data classification and can more effectively address the problems associated with ordinal scale data, for exploration of a beverage product spectrum.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]紙本[[booktype]]電子