Energy flux and dissipation of inhomogeneous plane waves in hereditary viscoelasticity

Inhomogeneous small-amplitude plane waves of (complex) frequency ω are propagated through a linear dissipative material which displays hereditary viscoelasticity. The energy density, energy flux and dissipation are quadratic in the small quantities, namely, the displacement gradient, velocity and velocity gradient, each harmonic with frequency ω, and so give rise to attenuated constant terms as well as to inhomogeneous plane waves of frequency 2ω. The quadratic terms are usually removed by time averaging but we retain them here as they are of comparable magnitude with the time-averaged quantities of frequency ω. A new relationship is derived in hereditary viscoelasticity that connects the amplitudes of the terms of the energy density, energy flux and dissipation that have frequency 2ω. It is shown that the complex group velocity is related to the amplitudes of the terms with frequency 2ω rather than to the attenuated constant terms as it is for homogeneous waves in conservative materials

Joint Longitudinal Models for Dealing With Missing at Random Data in Trial-Based Economic Evaluations

OBJECTIVES: In trial-based economic evaluation, some individuals are typically associated with missing data at some time point, so that their corresponding aggregated outcomes (eg, quality-adjusted life-years) cannot be evaluated. Restricting the analysis to the complete cases is inefficient and can result in biased estimates, while imputation methods are often implemented under a missing at random (MAR) assumption. We propose the use of joint longitudinal models to extend standard approaches by taking into account the longitudinal structure to improve the estimation of the targeted quantities under MAR. METHODS: We compare the results from methods that handle missingness at an aggregated (case deletion, baseline imputation, and joint aggregated models) and disaggregated (joint longitudinal models) level under MAR. The methods are compared using a simulation study and applied to data from 2 real case studies. RESULTS: Simulations show that, according to which data affect the missingness process, aggregated methods may lead to biased results, while joint longitudinal models lead to valid inferences under MAR. The analysis of the 2 case studies support these results as both parameter estimates and cost-effectiveness results vary based on the amount of data incorporated into the model. CONCLUSIONS: Our analyses suggest that methods implemented at the aggregated level are potentially biased under MAR as they ignore the information from the partially observed follow-up data. This limitation can be overcome by extending the analysis to a longitudinal framework using joint models, which can incorporate all the available evidence

Solvation and surface effects on polymorph stabilities at the nanoscale

We explore the effects of particle size and solvent environment on the thermodynamic stability of two pairs of polymorphs subjected to ball-mill neat grinding (NG) and liquid assisted grinding (LAG). Two systems were studied: (i) forms I and II of a 1 : 1 theophylline : benzamide cocrystal and (ii) forms A and B of an aromatic disulfide compound. For both systems, the most stable-bulk polymorph converted to the metastable-bulk polymorph upon NG. LAG experiments yielded different outcomes depending on the amount of solvent used. This was further investigated by performing carefully controlled LAG experiments with increasing $\mu$L amounts of solvents of different nature. With these experiments, we were able to monitor form A to B and form I to II conversions as a function of solvent concentration and derive polymorph equilibrium curves. The concentration required for a switch in polymorphic outcome was found to be dependent on solvent nature. We propose that these experiments demonstrate a switch in thermodynamic stability of the polymorphs in the milling jar. Form B, the stable-bulk polymorph, has less stable surfaces than form A, thus becoming metastable at the nanoscale when surface effects become important. $\textit{Ex situ}$ diffraction and electron microscopy data confirm crystal sizes in the order of tens of nanometers after the ball mill grinding experiments reach equilibrium. DFT-d computations of the polymorph particles stabilities support these findings and were used to calculate cross-over sizes of forms A and B as a function of solvent. Attachment energies and surface stabilities of the various crystalline faces exposed were found to be very sensitive to the solvent environment. Our findings suggest that surface effects are significant in polymorphism at the nanoscale and that the outcomes of equilibrium ball-mill NG and LAG experiments are in general controlled by thermodynamics.Engineering and Physical Sciences Research Counci

Benchmarking 2D hydraulic models for urban flood simulations

This paper describes benchmark testing of six two-dimensional (2D) hydraulic models (DIVAST, DIVASTTVD, TUFLOW, JFLOW, TRENT and LISFLOOD-FP) in terms of their ability to simulate surface flows in a densely urbanised area. The models are applied to a 1·0 km × 0·4 km urban catchment within the city of Glasgow, Scotland, UK, and are used to simulate a flood event that occurred at this site on 30 July 2002. An identical numerical grid describing the underlying topography is constructed for each model, using a combination of airborne laser altimetry (LiDAR) fused with digital map data, and used to run a benchmark simulation. Two numerical experiments were then conducted to test the response of each model to topographic error and uncertainty over friction parameterisation. While all the models tested produce plausible results, subtle differences between particular groups of codes give considerable insight into both the practice and science of urban hydraulic modelling. In particular, the results show that the terrain data available from modern LiDAR systems are sufficiently accurate and resolved for simulating urban flows, but such data need to be fused with digital map data of building topology and land use to gain maximum benefit from the information contained therein. When such terrain data are available, uncertainty in friction parameters becomes a more dominant factor than topographic error for typical problems. The simulations also show that flows in urban environments are characterised by numerous transitions to supercritical flow and numerical shocks. However, the effects of these are localised and they do not appear to affect overall wave propagation. In contrast, inertia terms are shown to be important in this particular case, but the specific characteristics of the test site may mean that this does not hold more generally

Intraoperative contrast-enhanced sonography of bowel blood flow: preliminary experience

The potential to predict, and therefore avoid, anastomotic failure has eluded generations of colon and rectal surgeons to date. A reliable, reproducible method of assessing bowel blood flow therefore would be of enormous potential clinical relevance. To our knowledge, intraoperative contrast-enhanced sonography of the bowel has not been performed previously. We present our study assessing the feasibility of using contrast-enhanced sonography to study bowel perfusion intraoperatively. We studied 8 patients (4 male and 4 female) with an age range of 52 to 81 years who underwent colorectal surgery (right hemicolectomies, n = 3; Hartmann procedure, n = 1; anterior resections, n = 2; and bowel resections with ileocolic anastomoses, n = 2). A 5-mL bolus of a sulfur hexafluoride contrast agent solution was injected before and after vascular ligation with simultaneous noncompression ultrasound scanning directly over the large bowel. The patients were followed clinically to assess for leaks. Contrast-enhanced sonographic time-intensity curves were generated for the time to peak and maximum amplitude. Moderate interobserver agreement was shown for the time to peak (κ = 0.50) and maximum amplitude (κ = 0.42), and moderate intraobserver agreement was shown for the time to peak (κ= 0.53) and maximum amplitude (κ= 0.53). No significant differences were shown between the time to peak (P = .28) and maximum amplitude (P = .49) for the preligation and postligation scans. To our knowledge, intraoperative contrast-enhanced sonography of the bowel has not been performed previously. We have shown the technique to be feasible with good intraobserver and interobserver agreement. Further work is ongoing to optimize the technique and assess its use in predicting anastomotic breakdown.published_or_final_versio

Listening Difficulties in Children: Behavior and Brain Activation Produced by Dichotic Listening of CV Syllables

Listening difficulties (LiD) are common in children with and without hearing loss. Impaired interactions between the two ears have been proposed as an important component of LiD when there is no hearing loss, also known as auditory processing disorder (APD). We examined the ability of 6–13 year old (y.o.) children with normal audiometric thresholds to identify and selectively attend to dichotically presented CV syllables using the Bergen Dichotic Listening Test (BDLT; www.dichoticlistening.com). Children were recruited as typically developing (TD; n = 39) or having LiD (n = 35) based primarily on composite score of the ECLiPS caregiver report. Different single syllables (ba, da, ga, pa, ta, ka) were presented simultaneously to each ear (6 × 36 trials). Children reported the syllable heard most clearly (non-forced, NF) or the syllable presented to the right [forced right (FR)] or left [forced left (FL)] ear. Interaural level differences (ILDs) manipulated bottom-up perceptual salience. Dichotic listening (DL) data [correct responses, laterality index (LI)] were analyzed initially by group (LiD, TD), age, report method (NF, FR, FL), and ILD (0, ± 15 dB) and compared with speech-in-noise thresholds (LiSN-S) and cognitive performance (NIH Toolbox). fMRI measured brain activation produced by a receptive speech task that segregated speech, phonetic, and intelligibility components. Some activated areas [planum temporale (PT), inferior frontal gyrus (IFG), and orbitofrontal cortex (OFC)] were correlated with dichotic results in TD children only. Neither group, age, nor report method affected the LI of right/left recall. However, a significant interaction was found between ear, group, and ILD. Laterality indices were small and tended to increase with age, as previously reported. Children with LiD had significantly larger mean LIs than TD children for stimuli with ILDs, especially those favoring the left ear. Neural activity associated with Speech, Phonetic, and Intelligibility sentence cues did not differ significantly between groups. Significant correlations between brain activity level and BDLT were found in several frontal and temporal locations for the TD but not for the LiD group. Overall, the children with LiD had only subtle differences from TD children in the BDLT, and correspondingly minor changes in brain activation

Amniotic fluid volume: Rapid MR-based assessment at 28-32 weeks gestation.

OBJECTIVES: This work evaluates rapid magnetic resonance projection hydrography (PH) based amniotic fluid volume (AFV) estimates against established routine ultrasound single deepest vertical pocket (SDVP) and amniotic fluid index (AFI) measurements, in utero at 28-32 weeks gestation. Manual multi-section planimetry (MSP) based measurement of AFV is used as a proxy reference standard. METHODS: Thirty-five women with a healthy singleton pregnancy (20-41 years) attending routine antenatal ultrasound were recruited. SDVP and AFI were measured using ultrasound, with same day MRI assessing AFV with PH and MSP. The relationships between the respective techniques were assessed using linear regression analysis and Bland-Altman method comparison statistics. RESULTS: When comparing estimated AFV, a highly significant relationship was observed between PH and the reference standard MSP (R(2) = 0.802, p < 0.001). For the US measurements, SDVP measurement related most closely to amniotic fluid volume, (R(2) = 0.470, p < 0.001), with AFI demonstrating a weaker relationship (R(2) = 0.208, p = 0.007). CONCLUSION: This study shows that rapid MRI based PH measurement is a better predictor of AFV, relating more closely to our proxy standard than established US techniques. Although larger validation studies across a range of gestational ages are required this approach could form part of MR fetal assessment, particularly where poly- or oligohydramnios is suspected. KEY POINTS: • MR projection hydrography can be used to estimate amniotic fluid volume. • MR projection hydrography relies on the T2w signal from amniotic fluid. • Amniotic fluid volume (AFV) is more accurately assessed than with ultrasound.This study was supported by the National Institute of Health Research, Cambridge Biomedical Research Centre. The authors also acknowledge the support of Addenbrooke’s Charitable Trust and thank the participants for their contribution to the study.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00330-015-4179-

Methods for estimating between-study variance and overall effect in meta-analysis of odds-ratios

In random-effects meta-analysis the between-study variance (τ 2) has a key role in assessing heterogeneity of study-level estimates and combining them to estimate an overall effect. For odds ratios the most common methods suffer from bias in estimating τ 2 and the overall effect and produce confidence intervals with below-nominal coverage. An improved approximation to the moments of Cochran's Q statistic, suggested by Kulinskaya and Dollinger (KD), yields new point and interval estimators of τ 2 and of the overall log-odds-ratio. Another, simpler approach (SSW) uses weights based only on study-level sample sizes to estimate the overall effect. In extensive simulations we compare our proposed estimators with established point and interval estimators for τ 2 and point and interval estimators for the overall log-odds-ratio (including the Hartung-Knapp-Sidik-Jonkman interval). Additional simulations included three estimators based on generalized linear mixed models and the Mantel-Haenszel fixed-effect estimator. Results of our simulations show that no single point estimator of τ 2 can be recommended exclusively, but Mandel-Paule and KD provide better choices for small and large numbers of studies, respectively. The KD estimator provides reliable coverage of τ 2. Inverse-variance-weighted estimators of the overall effect are substantially biased, as are the Mantel-Haenszel odds ratio and the estimators from the generalized linear mixed models. The SSW estimator of the overall effect and a related confidence interval provide reliable point and interval estimation of the overall log-odds-ratio

Health research improves healthcare: now we have the evidence and the chance to help the WHO spread such benefits globally

There has been a dramatic increase in the body of evidence demonstrating the benefits that come from health research. In 2014, the funding bodies for higher education in the UK conducted an assessment of research using an approach termed the Research Excellence Framework (REF). As one element of the REF, universities and medical schools in the UK submitted 1,621 case studies claiming to show the impact of their health and other life sciences research conducted over the last 20 years. The recently published results show many case studies were judged positively as providing examples of the wide range and extensive nature of the benefits from such research, including the development of new treatments and screening programmes that resulted in considerable reductions in mortality and morbidity. Analysis of specific case studies yet again illustrates the international dimension of progress in health research; however, as has also long been argued, not all populations fully share the benefits. In recognition of this, in May 2013 the World Health Assembly requested the World Health Organization (WHO) to establish a Global Observatory on Health Research and Development (R&D) as part of a strategic work-plan to promote innovation, build capacity, improve access, and mobilise resources to address diseases that disproportionately affect the world’s poorest countries. As editors of Health Research Policy and Systems (HARPS), we are delighted that our journal has been invited to help inform the establishment of the WHO Global Observatory through a Call for Papers covering a range of topics relevant to the Observatory, including topics on which HARPS has published articles over the last few months, such as approaches to assessing research results, measuring expenditure data with a focus on R&D, and landscape analyses of platforms for implementing R&D. Topics related to research capacity building may also be considered. The task of establishing a Global Observatory on Health R&D to achieve the specified objectives will not be easy; nevertheless, this Call for Papers is well timed – it comes just at the point where the evidence of the benefits from health research has been considerably strengthened

The effectiveness of public health interventions to reduce the health impact of climate change:a systematic review of systematic reviews

Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases