bluuebunny/crossref_metadata_2025 huggingface dataset:
Maximum Power From Fluid Flow by Applying the First and Second Laws of Thermodynamics
Authors: Diaz German Amador , Forero Jorge Duarte , Garcia Jesus , Rincon Adriana , Fontalvo Armando , Bula Antonio , Padilla Ricardo Vasquez
Published: October 2016

The application of equilibrium thermodynamics in the study of thermal plant performance under real operating conditions is a constant challenge. In this paper, an analysis of a reservoir pressure piston working between two linear flow resistances is performed by considering the friction of the piston cylinder system on the walls. The proposed model is developed to obtain the optimum power output and speed of the piston in terms of first law efficiency. If the friction on the piston–cylinder assembly is neglected, the expressions obtained are consistent with those presented in the literature under laminar regime. It was also demonstrated that for both laminar and turbulent regimes with overall size constraints, the power delivered can be maximized by balancing the upstream and downstream flow resistances of the piston. This paper also evaluated the influence of the overall size constraints and flow regime on the performance of the piston cylinder. This analysis is equivalent to evaluate the irreversibilities in an endo-irreversible Carnot heat engine with heat loss resistance between the engine and its heat reservoirs. The proposed model introduced some modifications to the results obtained from the recent literature and led to important conclusions. Finally, the proposed model was applied to calculate the lost available work in a turbine operating at steady flow conditions with an ideal gas as working fluid.
An Experimental Study of Optimum Angle of Air Swirler Vanes in Liquid Fuel Burners
Authors: Pourhoseini S. H. , Asadi Rasoul
Published: October 2016

The present work shows that how the angle of an air swirler vane affects the combustion characteristics of liquid fuels such as flame temperature, radiation heat flux, combustion efficiency, and pollutants' emission. It finds out an optimum angle of vane based on flame characteristics. Three vanes with angles of 0 deg, 40 deg, and 80 deg which induced low and high-swirl intensities in air stream were investigated, and the combustion characteristics of flame were quantified. The flame temperature was measured by an S-type thermocouple, and a Testo 350 XL gas analyzer was used to determine the CO and NO pollutant concentrations. Also, gravity method was used to gauge the soot concentration along the furnace, and a SBG01 water cooled heat flux sensor determined the flame radiation. The results indicate that the angle of the swirler vane has significant effects on temperature, combustion efficiency, and NO and CO pollutants' emission. Most importantly, there is an optimum angle for the swirler vane. At the optimum angle, the optimum combination of the contact area and time maximizes the mixing rate of the inlet air and the fuel jet. Consequently, at the optimum angle, the mean temperature, radiation heat flux, and combustion efficiency are higher than at small and large swirl angles and soot, CO and NOx emissions are at their minimum states.
A Theoretical Tribological Comparison Between Soft and Hard Coatings of Spur Gear Pairs
Authors: Liu Huaiju , Zhu Caichao , Wang Zhanjiang , Zhou Ye , Zhang Yuanyuan
Published: October 2016

A thermal elastohydrodynamic lubrication (TEHL) model is developed for a coated spur gear pair to investigate the effect of soft coatings and hard coatings on the tribological behavior of such a gear pair during meshing. The coating properties, i.e., the ratio of the Young's modulus between the coating and the substrate, and the coating thickness, are represented in the calculation of the elastic deformation. Discrete convolution, fast Fourier transform (DC-FFT) is utilized for the fast calculation of the surface deformation. The variation of the radius of curvature, the rolling speed, the slide-to-roll ratio, and the tooth load along the line of action (LOA) during meshing is taken into account and the transient squeeze effect is considered in the Reynolds equation. Energy equations of the solids and the oil film are derived. The temperature field and the pressure field are solved iteratively. The tribological behavior is evaluated in terms of the minimum film thickness, the maximum pressure, the temperature rise, the coefficient of friction, and the frictional power loss of the tooth contact during meshing. The results show discrepancies between the soft coating results and hard coating results.
Increasing the Performance of a Rotary Piezoelectric Frequency Up-Converting Energy Harvester Under Weak Excitations
Authors: Ramezanpour Reza , Nahvi Hassan , Ziaei-Rad Saeed
Published: October 2016

In common rotary piezoelectric (PZT) frequency up-converting energy harvesters, impact or nonimpact frequency up-conversion technologies are used. For low separation distances between the magnets in nonimpact cases, when weak excitation is applied, depending on some parameters such as separation distance between the magnets, eccentric proof mass may be unable to overcome the magnetic potential between the magnets, and thus, the extracted power of the harvester lowers. To increase the harvester power output, the use of an additional pair of magnets, called the assisting part, is proposed in this paper. For different harmonic excitations, the generated powers of the harvester with and without assisting part have been compared to each other. It is found that by appropriately adjusting the separation distance, the use of such part can increase the generated power in most cases. Using a real-world multifrequency multi-amplitude excitation, the ability of the proposed idea to increase the extracted power is investigated. It is found that the maximum generated power of the device can effectively increase to more than two times. In order to check the accuracy of the applied mathematical modeling, some experiments have been conducted.
A New Microstructure-Sensitive Flow Stress Model for the High-Speed Machining of Titanium Alloy Ti–6Al–4V
Authors: Zhang X. P. , Shivpuri R. , Srivastava A. K.
Published: October 2016

The flow stress in the high-speed machining of titanium alloys depends strongly on the microstructural state of the material which is defined by the composition of the material, its starting microstructure, and the thermomechanical loads imposed during the machining process. In the past, researchers have determined the flow stress empirically as a function of mechanical state parameters, such as strain, strain rate, and temperature while ignoring the changes in the microstructural state such as phase transformations. This paper presents a microstructure-sensitive flow stress model based on the self-consistent method (SCM) that includes the effects of chemical composition, α phase and β phase, as well mechanical state imposed. This flow stress is developed to model the flow behavior of titanium alloys in machining at speed of higher than 5 m/s, characterized by extremely high strains (2–10 or higher), high strain rates (104–106 s−1 or higher), and high temperatures (600–1300 °C). The flow stress sensitivity to mechanical and material parameters is analyzed. A new SCM-based Johnson–Cook (JC) flow stress model is proposed whose constants and ranges are determined using experimental data from literature and the physical basis for SCM approach. This new flow stress is successfully implemented in the finite-element (FE) framework to simulate machining. The predicted results confirm that the new model is much more effective and reliable than the original JC model in predicting chip segmentation in the high-speed machining of titanium Ti–6Al–4V alloy.
Magnetohydrodynamics Mixed Convection Flow of a Nanofluid in an Isothermal Vertical Cone
Authors: Sudhagar Palani , Kameswaran Peri K. , Rushi Kumar B.
Published: October 2016

A boundary layer analysis is laid out for the steady, laminar, mixed convection flow past an isothermal vertical cone embedded in a porous medium filled with a nanofluid. The model used for the nanofluid is one which includes the effects of Brownian motion and thermophoresis. A parametric study is performed for different physical parameters, such as magnetic (M), cone angle (m), mixed convection (χ), Brownian motion (Nt), and thermophoresis (Nb), on the velocity, temperature, and nanoparticle concentration profiles. The local Nusselt, Sherwood, and nanoparticle Sherwood number have been laid out in a graphical way. The dependency of the rate of heat and mass transfer on the governing parameters has been discussed.
A Method for Dynamic Analysis of Three-Dimensional Solid Element Rotors With Uncertain Parameters
Authors: Zuo Yanfei , Wang Jianjun
Published: October 2016

Three-dimensional solid element models often with a great number of degrees-of-freedom (DOFs) are now widely used for rotor dynamic analysis. While without reduction, it will cost considerable calculating resources and time to solve the equations of motion, especially when Monte Carlo simulation (MCS) is needed for stochastic analysis. To improve the analysis efficiency, the DOFs are partly reduced to modal spaces, and the stochastic results (critical speeds or unbalance response) are expanded to polynomial spaces. First, a reduced rotor model is got by component mode synthesis (CMS), and the stochastic results are expanded by polynomial chaos basis with unknown coefficients. Then, the reduced rotor model is used to calculate the sample results to obtain the coefficients. At last, the expressions of the result by polynomial chaos basis are used as surrogate models for MCS. An aero-engine rotor system with uncertain parameters is analyzed. The accuracy of the method is validated by direct MCS, and the high efficiency makes it possible for stochastic dynamic analysis of complex engine rotor systems modeled by 3D solid element.
Biomimetic coat enables the use of sonoporation to assist delivery of silica nanoparticle-cargoes into human cells
Authors: Carrasco Giovana , López-Marín Luz M. , Fernández Francisco , Salas Pedro , Loske Achim M. , Millán-Chiu Blanca E.
Published: October 2016

Due to their biocompatibility and high adsorption properties, mesoporous silica nanoparticles (MSN) represent one of the most promising systems for drug delivery. Previous investigations have shown that both surface functionalization and external stimuli may act in a synergistic way to deliver drugs from nanoparticles. One such stimulus is underwater shock wave-induced sonoporation, a physical method known to transiently permeabilize cell membranes. However, there are some concerns regarding the feasibility to apply shock waves in the presence of dense nanoparticles. In this work, bioinspired supramolecular MSN were prepared by self-assembly of cationic liposomes with 200 nm MCM-41 type silica nanoparticles. The effects of the biomimetic coat on cargo stability, adherence to HEK-293 cells, and shock wave-mediated delivery of plasmid deoxyribonucleic acid were addressed. Compared to bare MSN, structures displaying a lipid coat showed higher cargo retention. Adherence to cell surface was only achieved with a cationic lipid surface, which was related to higher efficient delivery of MSN cargoes, including the release of a green fluorescent protein-codifying transgene. Unexpectedly, MSN covered with a biomimetic coat were found to protect cells from the exacerbated mortality observed after exposure of cells to shock waves in the presence of bare MSN. Further research will be required to understand the mechanisms involved in this combined strategy, which paves the way for the exploration of dense nanoparticles in the field of shock wave-mediated drug delivery.
Implementation of output prediction models for a passively double‐scattered proton therapy system
Authors: Ferguson Sven , Ahmad Salahuddin , Jin Hosang
Published: October 2016

Purpose

Two output (cGy/MU) prediction models (one existing and one newly developed) for a passively double‐scattered proton therapy system are implemented and investigated for clinical use. Variations of each model are tested for accuracy in order to determine the most viable prediction model.

Methods

The first output prediction model [model (1)] is a semianalytical model proposed by Kooy et al. [Phys. Med. Biol. 50, 5847–5856 (2005)], which employs three main factors. The first factor (basic output prediction) uses a unique combined parameter [r = (R − M)/M] of range (R) and modulation [M; spread‐out Bragg peak (SOBP) width] along with option specific fitting parameters. The second factor takes into account minor source shifts using a linear fit due to varying beamline configurations for different options. The final factor accounts for a condition where the point of measurement is not at the isocenter or away from the middle of the SOBP based on an inverse‐square correction. The second model [model (2)] is a novel quartic polynomial fit of the basic output prediction whose idea was inspired by the first model. Different variations in the definition of R and M at distal (D) and proximal (P) ends resulted in the exploration of three variations of r for both models: r1 = (RD90 − MD90−P95)/MD90−P95, r2 = [(RD90 + ΔR1) − m × (MD90−P95 + ΔR1)]/[m × (MD90−P95 + ΔR1)], where ΔR1 is an offset between RD80 and RD90 and m is a ratio between MD90−P95 and theoretical , and r3 = [(RD90 − 0.305) − 0.801 × MD90−P95]/(0.801 × MD90−P95), where 0.305 (ΔR2) is an offset between RD90 and RD100 and 0.801 is a ratio between MD90−P95 and measured MD100−P100. Output measurements for 177 sets of R and M from all 24 options are compared to outputs predicted by both the models of three variations of r.

Results

The mean differences between measurements and predictions ([predicted − measured]/measured × 100%) were −0.41% ± 1.78% (r1), 0.03% ± 1.53% (r2), and 0.05% ± 1.20% (r3) for model (1), and 0.27% ± 1.36% (r1), 0.71% ± 1.51% (r2), and −0.05% ± 1.20% (r3) for model (2). For a passing prediction rate with a difference threshold of ±3%, model (1) showed slightly worse results than model (2) using r1 (91.5% vs 94.4%). In general, small (M < 4 g/cm2) and close‐to‐full modulations produced larger discrepancies. However, 100% output predictions using r3 were confined within ±3% of measurements for both models and the difference between the models was not substantial (mean difference: 0.05% vs −0.05%).

Conclusions

The first existing model has proven to be a successful predictor of output for our compact double‐scattering proton therapy system. The new model performed comparably to the first model and showed better performance in some options due to a great degree of flexibility of a polynomial fit. Both models performed well using r3. Either model with r3 thus can serve well as an output prediction calculator.
Levels and Patterns of Objectively Measured Physical Activity and Sedentary Time in 4-Year-Old Swedish Children
Authors: Berglind Daniel , Hansson Lena , Tynelius Per , Rasmussen Finn
Published: October 2016

Background:

Levels of physical activity (PA) affect health already at 4 years of age. The aims of this study were to describe levels and patterns of PA and sedentary time (ST) in a sample of 4-year-old Swedish children and to assess the number of children achieving PA guidelines throughout the week.

Methods:

Data from 540 4-year-old children enrolled in the population-based PRIMROSE trial was used. PA was measured for a period of 1 week by the Actigraph GT3X+ accelerometer. Average PA, time spent in light PA, moderate-to-vigorous PA (MVPA) and ST were assessed.

Results:

On average children spent 6.7% of the day in MVPA and 45% of the day being sedentary and 33% (n = 178) of the children met the PA guidelines of 60 minutes of MVPA per day. Boys spent 56.8 (SD 21.8) minutes/day in MVPA, while girls spent 43.0 (SD 18.1) minutes/day in MVPA (P < .001).

Conclusions:

Four-year-old children spent almost half of the day being sedentary and only one-third meet the recommended PA guidelines. This finding is alarming as higher levels of PA, already at 4 years of age, seem to reduce the risk of childhood obesity and provides long-term health benefits.
Park Use and Physical Activity Among Mostly Low-to-Middle Income, Minority Parents and Their Children
Authors: Greer Anna E. , Castrogivanni Brianna , Marcello Richard
Published: October 2016

Background:

Limited research has examined park use and physical activity among economically and ethnically diverse families. This study fills that gap.

Methods:

Parents (n = 326) completed a questionnaire about their park use (yes/no, parks visited, reasons for nonuse) and physical activity (Godin Leisure Time questionnaire). Geographical Information Systems was used to calculate the distance from respondents’ home address to their nearest park. The number of activity features (eg, playgrounds) in parks was determined objectively using the Community Park Audit Tool.

Results:

Half of respondents were sufficiently active; 87.6% reported park use in the prior 6 months. Among sufficiently active respondents, 92.4% reported park use (P = .011). We found no difference in park proximity between respondents who did and did not report distance as a park use barrier. An objective assessment confirmed fewer activity features in parks near the homes of respondents reporting few activity features as a barrier to park use. The most often visited parks were significantly larger than the less-often visited parks.

Conclusion:

Parks might best support physical activity for families when activity features are carefully planned and equitably distributed across parks. Efforts to promote families’ awareness of park locations might be warranted to reduce perceived proximity barriers.
How Self-Objectification Impacts Physical Activity Among Adolescent Girls in Costa Rica
Authors: Monge-Rojas Rafael , Fuster-Baraona Tamara , Garita-Arce Carlos , Sánchez-López Marta , Colon-Ramos Uriyoán , Smith-Castro Vanessa
Published: October 2016

Background:

In Latin America, more than 80% of adolescent girls are physically inactive. Inactivity may be reinforced by female stereotypes and objectification in the Latin American sociocultural context.

Methods:

We examined the influence of objectification on the adoption of an active lifestyle among 192 adolescents (14 and 17 years old) from urban and rural areas in Costa Rica. Analyses of 48 focus-groups sessions were grounded in Objectification Theory.

Results:

Vigorous exercises were gender-typed as masculine while girls had to maintain an aesthetic appearance at all times. Adolescents described how girls were anxious around the prospect of being shamed and sexually objectified during exercises. This contributed to a decrease in girls’ desire to engage in physical activities. Among males, there is also a budding tolerance of female participation in vigorous sports, as long as girls maintained a feminine stereotype outside their participation.

Conclusion:

Self-objectification influenced Costa Rican adolescent girls’ decisions to participate in physical activities. Interventions may include: procuring safe environments for physical activity where girls are protected from fear of ridicule and objectification; sensitizing boys about girl objectification and fostering the adoption of a modern positive masculine and female identities to encourage girls’ participation in sports.
Inferring propagation paths for sparsely observed perturbations on complex networks
Authors: Massucci Francesco Alessandro , Wheeler Jonathan , Beltrán-Debón Raúl , Joven Jorge , Sales-Pardo Marta , Guimerà Roger
Published: October 2016

Tackling the challenge of reconstructing the state of a perturbed system from a single sparse observation.
The Influence of the Host Plant Is the Major Ecological Determinant of the Presence of Nitrogen-Fixing Root Nodule Symbiont Cluster II Frankia Species in Soil
Authors: Battenberg Kai , Wren Jannah A. , Hillman Janell , Edwards Joseph , Huang Liujing , Berry Alison M.
Published: October 2016

The actinobacterial genus
Frankia
establishes nitrogen-fixing root nodule symbioses with specific hosts within the nitrogen-fixing plant clade. Of four genetically distinct subgroups of
Frankia
, cluster I, II, and III strains are capable of forming effective nitrogen-fixing symbiotic associations, while cluster IV strains generally do not. Cluster II
Frankia
strains have rarely been detected in soil devoid of host plants, unlike cluster I or III strains, suggesting a stronger association with their host. To investigate the degree of host influence, we characterized the cluster II
Frankia
strain distribution in rhizosphere soil in three locations in northern California. The presence/absence of cluster II
Frankia
strains at a given site correlated significantly with the presence/absence of host plants on the site, as determined by glutamine synthetase (
glnA
) gene sequence analysis, and by microbiome analysis (16S rRNA gene) of a subset of host/nonhost rhizosphere soils. However, the distribution of cluster II
Frankia
strains was not significantly affected by other potential determinants such as host-plant species, geographical location, climate, soil pH, or soil type. Rhizosphere soil microbiome analysis showed that cluster II
Frankia
strains occupied only a minute fraction of the microbiome even in the host-plant-present site and further revealed no statistically significant difference in the α-diversity or in the microbiome composition between the host-plant-present or -absent sites. Taken together, these data suggest that host plants provide a factor that is specific for cluster II
Frankia
strains, not a general growth-promoting factor. Further, the factor accumulates or is transported at the site level, i.e., beyond the host rhizosphere.

IMPORTANCE
Biological nitrogen fixation is a bacterial process that accounts for a major fraction of net new nitrogen input in terrestrial ecosystems. Transfer of fixed nitrogen to plant biomass is especially efficient via root nodule symbioses, which represent evolutionarily and ecologically specialized mutualistic associations.
Frankia
spp. (
Actinobacteria
), especially cluster II
Frankia
spp., have an extremely broad host range, yet comparatively little is known about the soil ecology of these organisms in relation to the host plants and their rhizosphere microbiomes. This study reveals a strong influence of the host plant on soil distribution of cluster II
Frankia
spp.
Gamma Interferon-Regulated Chemokines in Leishmania donovani Infection in the Liver
Authors: Murray Henry W. , Luster Andrew D. , Zheng Hua , Ma Xiaojing
Published: October 2016

In the livers of C57BL/6 mice, gamma interferon (IFN-γ) controls intracellularLeishmania donovaniinfection and the efficacy of antimony (Sb) chemotherapy. Since both responses usually correlate with granulomatous inflammation, we tested six prominently expressed, IFN-γ-regulated chemokines—CXCL9, CXCL10, CXCL13, CXCL16, CCL2, and CCL5—for their roles in (i) mononuclear cell recruitment and granuloma assembly and maturation, (ii) initial control of infection and self-cure, and (iii) responsiveness to Sb treatment. Together, the results for theL. donovani-infected livers of chemokine-deficient mice (CXCR6−/−mice were used as CXCL16-deficient surrogates) indicated that individual IFN-γ-induced chemokines have diverse affects and (i) may be entirely dispensable (CXCL13, CXCL16), (ii) may promote (CXCL10, CCL2, CCL5) or downregulate (CXCL9) initial granuloma assembly, (iii) may enhance (CCL2, CCL5) or hinder (CXCL10) early parasite control, (iv) may promote granuloma maturation (CCL2, CCL5), (v) may exert a granuloma-independent action that enables self-cure (CCL5), and (vi) may have no role in responsiveness to chemotherapy. Despite the near absence of tissue inflammation in early-stage infection, parasite replication could be controlled (in CXCL10−/−mice) and Sb was fully active (in CXCL10−/−, CCL2−/−, and CCL5−/−mice). These results characterize chemokine action in the response toL. donovaniand also reemphasize that (i) recruited mononuclear cells and granulomas are not required to control infection or respond to Sb chemotherapy, (ii) granuloma assembly, control of infection, and Sb's efficacy are not invariably linked expressions of the same T cell-dependent, cytokine-mediated antileishmanial mechanism, and (iii) granulomas are not necessarily hallmarks of protective antileishmanial immunity.
Association between VEGF-A and VEGFR-2 polymorphisms and response to treatment of neovascular AMD with anti-VEGF agents: a meta-analysis
Authors: Wu Mingxing , Xiong Haibo , Xu Yan , Xiong Xiaojing , Zou Hongmi , Zheng Minming , Wang Xiuqing , Zhou Xiyuan
Published: October 2016

Aims

The purpose of this study is to investigate whether gene polymorphisms of the vascular endothelial growth factor A (VEGF-A) and its receptor (VEGFR-2) have a pharmacogenetics effect on the anti-VEGF treatment for neovascular age-related macular degeneration (nAMD).

Methods

We carried out a meta-analysis focusing on the relationship between VEGF-related gene polymorphisms and treatment response of nAMD.

Results

For the single nucleotide polymorphisms (SNPs) withinVEGF-AandVEGFR-2, anti-VEGF treatment was much more effective in patients with nAMD having rs833061 (CC vs TT:OR=2.222, 95% CI 1.252 to 3.944, p=0.006; CT vs TT: OR=2.537,95% CI 1.478 to 4.356, p=0.001 and CC vs CT+TT: OR=2.362, 95% CI 1.414 to 3.946, p=0.001), particularly for Asians (CC vs TT: OR=2.903, 95% CI 1.150 to 7.330, p=0.024; CT vs TT: OR=3.849, 95% CI 1.522 to 9.733, p=0.004 and CC vs CT+TT: OR=3.339, 95% CI 1.369 to 8.145, p=0.008, respectively). In subgroup analysis, rs833061 was more likely to be a predictor of response to anti-VEGF therapy specifically when ranibizumab (RBZ) only regime was adopted or visual acuity (VA) was taken as the standardised assessment of outcome. No association with response to anti-VEGF treatment was detected for the other eight polymorphisms.

Conclusions

Pharmacogenetics ofVEGF-Apolymorphism rs833061 may play a positive role in response to anti-VEGF therapy for nAMD.
World Hip Trauma Evaluation (WHiTE): framework for embedded comprehensive cohort studies
Authors: Costa Matthew L , Griffin Xavier L , Achten Juul , Metcalfe David , Judge Andrew , Pinedo-Villanueva Rafael , Parsons Nicholas
Published: October 2016

Introduction

Osteoporotic hip fractures present a significant global challenge to patients, clinicians and healthcare systems. It is estimated that hip fracture accounts for 1.4% of total social and healthcare costs in the established market economies.

Methods and analysis

The World Hip Trauma Evaluation (WHiTE) was set up to measure outcome in a comprehensive cohort of UK patients with hip fracture. All patients in the cohort are treated under a single comprehensive treatment pathway. A core outcome set, including health-related quality of life, is collected on all the patients. This protocol describes the current multicentre project that will be used as a vehicle to deliver a series of embedded observational studies.

Ethics and dissemination

Research Ethics Committee approval was granted (Rec reference 11/LO/0927, approved 18/8/2011) and each hospital trust provided National Health Service (NHS) approvals.

Trial registration number

The study is registered with National Institute of Health Research Portfolio (UKCRN ID 12351) and the ISRCTN registry (ISRCTN63982700).
Stepped-wedge cluster randomised controlled trial to assess the effectiveness of an electronic medication management system to reduce medication errors, adverse drug events and average length of stay at two paediatric hospitals: a study protocol
Authors: Westbrook J I , Li L , Raban M Z , Baysari M T , Mumford V , Prgomet M , Georgiou A , Kim T , Lake R , McCullagh C , Dalla-Pozza L , Karnon J , O'Brien T A , Ambler G , Day R , Cowell C T , Gazarian M , Worthington R , Lehmann C U , White L , Barbaric D , Gardo A , Kelly M , Kennedy P
Published: October 2016

Introduction

Medication errors are the most frequent cause of preventable harm in hospitals. Medication management in paediatric patients is particularly complex and consequently potential for harms are greater than in adults. Electronic medication management (eMM) systems are heralded as a highly effective intervention to reduce adverse drug events (ADEs), yet internationally evidence of their effectiveness in paediatric populations is limited. This study will assess the effectiveness of an eMM system to reduce medication errors, ADEs and length of stay (LOS). The study will also investigate system impact on clinical work processes.

Methods and analysis

A stepped-wedge cluster randomised controlled trial (SWCRCT) will measure changes pre-eMM and post-eMM system implementation in prescribing and medication administration error (MAE) rates, potential and actual ADEs, and average LOS. In stage 1, 8 wards within the first paediatric hospital will be randomised to receive the eMM system 1 week apart. In stage 2, the second paediatric hospital will randomise implementation of a modified eMM and outcomes will be assessed. Prescribing errors will be identified through record reviews, and MAEs through direct observation of nurses and record reviews. Actual and potential severity will be assigned. Outcomes will be assessed at the patient-level using mixed models, taking into account correlation of admissions within wards and multiple admissions for the same patient, with adjustment for potential confounders. Interviews and direct observation of clinicians will investigate the effects of the system on workflow. Data from site 1 will be used to develop improvements in the eMM and implemented at site 2, where the SWCRCT design will be repeated (stage 2).

Ethics and dissemination

The research has been approved by the Human Research Ethics Committee of the Sydney Children's Hospitals Network and Macquarie University. Results will be reported through academic journals and seminar and conference presentations.

Trial registration number

Australian New Zealand Clinical Trials Registry (ANZCTR) 370325.
Core requirements for successful data linkage: an example of a triangulation method
Authors: Hopf Y M , Francis J , Helms P J , Haughney J , Bond C
Published: October 2016

Objectives

The aim was to explore the views of professional stakeholders and healthcare professionals (HCPs) on the linkage of UK National Health Service (NHS) data for paediatric pharmacovigilance purposes and to make recommendations for such a system.

Methods

A mixed methods approach including a literature review, interviews, focus groups and a three-round Delphi survey with HCPs in Scotland was followed by a triangulation process using a systematic protocol. The survey was structured using the Theoretical Domains Framework of behaviour change. Items retained after applying the matrix-based triangulation process were thematically coded. Ethical approval was granted by the North of Scotland Research Ethics Service.

Results

Results from 18 papers, 23 interviewees, 23 participants of focus groups and 61 completed questionnaires in the Delphi survey contributed to the triangulation process. A total of 25 key findings from all four studies were identified during triangulation. There was good convergence; 21 key findings were agreed and remained to inform recommendations. The items were coded as practical/technical (eg, decision about the unique patient identifier to use), mandatory (eg, governed by statute), essential (consistently mentioned in all studies and therefore needed to ensure professional support) or preferable.

Conclusions

The development of a paediatric linked database has support from professional stakeholders and HCPs in Scotland. The triangulation identified three sets of core requirements for a new system of data linkage. An additional fourth set of ‘preferable’ requirements might increase engagement of HCPs and their support for the new system.
The Environmental footprint of morphine: a life cycle assessment from opium poppy farming to the packaged drug
Authors: McAlister Scott , Ou Yanjun , Neff Elise , Hapgood Karen , Story David , Mealey Philip , McGain Forbes
Published: October 2016

Objective

To examine the environmental life cycle from poppy farming through to production of 100 mg in 100 mL of intravenous morphine (standard infusion bag).

Design

‘Cradle-to-grave’ process-based life cycle assessment (observational).

Settings

Australian opium poppy farms, and facilities for pelletising, manufacturing morphine, and sterilising and packaging bags of morphine.

Main outcome measures

The environmental effects (eg, CO2equivalent (‘CO2e’) emissions and water use) of producing 100 mg of morphine. All aspects of morphine production from poppy farming, pelletising, bulk morphine manufacture through to final formulation. Industry-sourced and inventory-sourced databases were used for most inputs.

Results

Morphine sulfate (100 mg in 100 mL) had a climate change effect of 204 g CO2e (95% CI 189 to 280 g CO2e), approximating the CO2e emissions of driving an average car 1 km. Water use was 7.8 L (95% CI 6.7– to 9.0 L), primarily stemming from farming (6.7 L). All other environmental effects were minor and several orders of magnitude less than CO2e emissions and water use. Almost 90% of CO2e emissions occurred during the final stages of 100 mg of morphine manufacture. Morphine's packaging contributed 95 g CO2e, which accounted for 46% of the total CO2e (95% CI 82 to 155 g CO2e). Mixing, filling and sterilisation of 100 mg morphine bags added a further 86 g CO2e, which accounted for 42% (95% CI 80 to 92 g CO2e). Poppy farming (6 g CO2e, 3%), pelletising and manufacturing (18 g CO2e, 9%) made smaller contributions to CO2emissions.

Conclusions

The environmental effects of growing opium poppies and manufacturing bulk morphine were small. The final stages of morphine production, particularly sterilisation and packaging, contributed to almost 90% of morphine's carbon footprint. Focused measures to improve the energy efficiency and sources for drugsterilisationandpackagingcould be explored as these are relevant toall drugs. Comparisons of the environmental effects of the production of other drugs and between oral and intravenous preparations are required.
Effect of simple, targeted diet in pregnant women with metabolic risk factors on maternal and fetal outcomes (ESTEEM): study protocol for a pragmatic multicentre randomised trial
Authors: Al Wattar Bassel H , Dodds Julie , Placzek Anna , Spyreli Eleni , Moore Amanda , Hooper Richard , Beresford Lee , Roseboom Tessa J , Bes-Rastrollo Maira , Hitman Graham , Khan Khalid S , Thangaratinam Shakila
Published: October 2016

Introduction

Women with metabolic risk factors are at higher risk of adverse pregnancy outcomes. Mediterranean-based dietary interventions have the potential to minimise these risks. We aim to evaluate the effectiveness of a simple, targeted intervention modelled on Mediterranean diet in preventing maternal and fetal complications in pregnant women with metabolic risk factors.

Methods and analysis

Pregnant women with a singleton pregnancy <18 weeks gestation, and without pre-existing diabetes, chronic renal disease and autoimmune diseases will be recruited. Women with metabolic risk factors will be randomised to receive a dietary intervention based on a Mediterranean pattern, supplemented with extra virgin olive oil and mixed nuts until delivery. The intervention will be delivered through a series of one to one and group sessions. The primary outcome is a composite maternal outcome of pre-eclampsia or gestational diabetes and a composite fetal outcome of stillbirth, small for gestational age fetus or admission to the neonatal intensive care unit. Secondary outcomes include maternal, fetal, dietary and laboratory outcomes. We aim to randomise 1230 eligible women with metabolic risk factors. We will also compare the outcomes in women with and without these risk factors. The sample size will provide us with 80% power at 5% significance, assuming a 20% loss to follow-up to detect a 30% reduction in maternal and fetal complications.

Ethics and dissemination

The ESTEEM trial is designed to provide a definitive estimate of the effects of Mediterranean dietary pattern in pregnancy on maternal and fetal outcomes. The pragmatic nature of ESTEEM ensures the applicability of its findings into clinical practice. The findings of the study will be published in peer-reviewed journals and presented at national and international scientific meetings and congresses. Ethical approval was granted by the NHS Research Ethics Committees (14/EE/1048).

Trial registration number

NCT02218931; Pre-results.
IL-6 and PD-L1 antibody blockade combination therapy reduces tumour progression in murine models of pancreatic cancer
Authors: Mace Thomas A , Shakya Reena , Pitarresi Jason R , Swanson Benjamin , McQuinn Christopher W , Loftus Shannon , Nordquist Emily , Cruz-Monserrate Zobeida , Yu Lianbo , Young Gregory , Zhong Xiaoling , Zimmers Teresa A , Ostrowski Michael C , Ludwig Thomas , Bloomston Mark , Bekaii-Saab Tanios , Lesinski Gregory B
Published: October 2016

Objective

Limited efficacy of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) has prompted investigation into combination therapy. We hypothesised that interleukin 6 (IL-6) blockade would modulate immunological features of PDAC and enhance the efficacy of anti-programmed death-1-ligand 1 (PD-L1) checkpoint inhibitor therapy.

Design

Transcription profiles and IL-6 secretion from primary patient-derived pancreatic stellate cells (PSCs) were analyzed via Nanostring and immunohistochemistry, respectively. In vivo efficacy and mechanistic studies were conducted with antibodies (Abs) targeting IL-6, PD-L1, CD4 or CD8 in subcutaneous or orthotopic models using Panc02, MT5 or KPC-luc cell lines; and the aggressive, genetically engineered PDAC model (KrasLSL−G12D, Trp53LSL−R270H, Pdx1-cre, Brca2F/F (KPC-Brca2 mice)). Systemic and local changes in immunophenotype were measured by flow cytometry or immunohistochemical analysis.

Results

PSCs (n=12) demonstrated prominent IL-6 expression, which was localised to stroma of tumours. Combined IL-6 and PD-L1 blockade elicited efficacy in mice bearing subcutaneous MT5 (p<0.02) and Panc02 tumours (p=0.046), which was accompanied by increased intratumoural effector T lymphocytes (CD62L−CD44−). CD8-depleting but not CD4-depleting Abs abrogated the efficacy of combined IL-6 and PD-L1 blockade in mice bearing Panc02 tumours (p=0.0016). This treatment combination also elicited significant antitumour activity in mice bearing orthotopic KPC-luc tumours and limited tumour progression in KPC-Brca2 mice (p<0.001). Histological analysis revealed increased T-cell infiltration and reduced α-smooth muscle actin cells in tumours from multiple models. Finally, IL-6 and PD-L1 blockade increased overall survival in KPC-Brca2 mice compared with isotype controls (p=0.0012).

Conclusions

These preclinical results indicate that targeted inhibition of IL-6 may enhance the efficacy of anti-PD-L1 in PDAC.
Thermal properties of oil sands fluid fine tailings: laboratory and in situ testing methods
Authors: Dompierre Kathryn A. , Barbour S. Lee
Published: October 2016

Fluid fine tailings (FFT) are soft tailings produced by the bitumen extraction process associated with open-pit oil sands mining. Oil sands mine operators have proposed the use of end pit lakes (EPLs) to contain soft tailings and Syncrude Canada Ltd. has developed the first EPL in the industry. This EPL, referred to as Base Mine Lake, contains FFT transferred from an above-ground tailings facility in a mined-out pit. The FFT was placed at elevated temperatures relative to natural groundwater temperatures in the region, so the FFT will act as a long-term source of heat. Evaluation of the thermal regime within the EPL requires the characterization of the thermal properties of FFT. Laboratory testing was undertaken to measure the thermal properties (thermal conductivity and volumetric heat capacity) of the FFT over a range of water contents and to evaluate the effect of bitumen content on the thermal properties. Field testing was also undertaken to verify that these properties were similar in the undisturbed FFT, measured at a larger scale.
Physics at a Higgs factory
Authors: Reece Matthew
Published: October 2016

I give an overview of the physics potential at possible future [Formula: see text] colliders, including the ILC, FCC-ee, and CEPC. The goal is to explain some of the measurements that can be done in the context of electroweak precision tests and Higgs couplings, to compare some of the options under consideration, and to put the measurements in context by summarizing their implications for some new physics scenarios. This is a writeup of a plenary talk at the Hong Kong University of Science and Technology Jockey Club Institute for Advanced Study Program on High Energy Physics Conference, 18–21 January 2016. Some previously unpublished electroweak precision results for FCC-ee and CEPC are included.
Probing the nonunitarity of the leptonic mixing matrix at the CEPC
Authors: Antusch Stefan , Fischer Oliver
Published: October 2016

The nonunitarity of the leptonic mixing matrix is a generic signal of new physics aiming at the generation of the observed neutrino masses. We discuss the Minimal Unitarity Violation (MUV) scheme, an effective field theory framework which represents the class of extensions of the Standard Model (SM) by heavy neutral leptons, and discuss the present bounds on the nonunitarity parameters as well as estimates for the sensitivity of the CEPC, based on the performance parameters from the preCDR.
Theoretical study of some electrical parameters of graphene
Authors: Das D. K. , Roy S. , Sahoo S.
Published: October 2016

Graphene, due to its numerous unique properties, is addressed as miraculous material by Novoselov et al. [Nature 490 (2012) 192]. It has ultrahigh heat and thermal conductivity. Several researchers over the globe are working on electrical properties of graphene like electrical resistance, electrical conductivity etc. In this paper, we estimate electrical resistivity, electrical conductivity and Lorenz number for graphene within the temperature range from 300 K to 500 K. Variation of these parameters with respect to temperature and sample size is also reported.
Symmetries and generalized higher order conserved vectors of the wave equation on Bianchi I spacetime
Authors: Abdulwahhab Muhammad Alim , Jhangeer Adil
Published: October 2016

Conservation laws of various systems have been studied for decades due to their unparalleled importance in unraveling systems’ intricacies without having to go into microscopic details of the physical process involved. Their association with symmetries has not only had a stupendous impact in the formulation of the fundamental laws of physics, but also open doors to further explorations and unifications of others. In this study, we present the Lie symmetries and nonlinearly self-adjoint classifications of the wave equation on Bianchi I spacetime. For different forms of the metric potentials, generalized higher order non-trivial conserved vectors are constructed. Some exact invariant solutions are also exhibited.
Toll-like receptor 9 prevents cardiac rupture after myocardial infarction in mice independently of inflammation
Authors: Omiya Shigemiki , Omori Yosuke , Taneike Manabu , Protti Andrea , Yamaguchi Osamu , Akira Shizuo , Shah Ajay M. , Nishida Kazuhiko , Otsu Kinya
Published: October 2016

We have reported that the Toll-like receptor 9 (TLR9) signaling pathway plays an important role in the development of pressure overload-induced inflammatory responses and heart failure. However, its role in cardiac remodeling after myocardial infarction has not been elucidated. TLR9-deficient and control C57Bl/6 wild-type mice were subjected to left coronary artery ligation. The survival rate 14 days postoperation was significantly lower in TLR9-deficient mice than that in wild-type mice with evidence of cardiac rupture in all dead mice. Cardiac magnetic resonance imaging showed no difference in infarct size and left ventricular wall thickness and function between TLR9-deficient and wild-type mice. There were no differences in the number of infiltrating inflammatory cells and the levels of inflammatory cytokine mRNA in infarct hearts between TLR9-deficient and wild-type mice. The number of α-smooth muscle actin (αSMA)-positive myofibroblasts and αSMA/Ki67-double-positive proliferative myofibroblasts was increased in the infarct and border areas in infarct hearts compared with those in sham-operated hearts in wild-type mice, but not in TLR9-deficient mice. The class B CpG oligonucleotide increased the phosphorylation level of NF-κB and the number of αSMA-positive and αSMA/Ki67-double-positive cells and these increases were attenuated by BAY1-7082, an NF-κB inhibitor, in cardiac fibroblasts isolated from wild-type hearts. The CpG oligonucleotide showed no effect on NF-κB activation or the number of αSMA-positive and αSMA/Ki67-double-positive cells in cardiac fibroblasts from TLR9-deficient hearts. Although the TLR9 signaling pathway is not involved in the acute inflammatory response in infarct hearts, it ameliorates cardiac rupture possibly by promoting proliferation and differentiation of cardiac fibroblasts.

Listen to this article’s corresponding podcast @ http://ajpheart.podbean.com/e/tlr9-in-post-infarct-cardiac-rupture/ .
Cardiomyopathy-related mutation (A30V) in mouse cardiac troponin T divergently alters the magnitude of stretch activation in α- and β-myosin heavy chain fibers
Authors: Mickelson Alexis V. , Gollapudi Sampath K. , Chandra Murali
Published: October 2016

The present study investigated the functional consequences of the human hypertrophic cardiomyopathy (HCM) mutation A28V in cardiac troponin T (TnT). The A28V mutation is located within the NH2terminus of TnT, a region known to be important for full activation of cardiac thin filaments. The functional consequences of the A28V mutation in TnT remain unknown. Given how α- and β-myosin heavy chain (MHC) isoforms differently alter the functional effect of the NH2terminus of TnT, we hypothesized that the A28V-induced effects would be differently modulated by α- and β-MHC isoforms. Recombinant wild-type mouse TnT (TnTWT) and the mouse equivalent of the human A28V mutation (TnTA30V) were reconstituted into detergent-skinned cardiac muscle fibers extracted from normal (α-MHC) and transgenic (β-MHC) mice. Dynamic and steady-state contractile parameters were measured in reconstituted muscle fibers. Step-like length perturbation experiments demonstrated that TnTA30Vdecreased the magnitude of the muscle length-mediated recruitment of new force-bearing cross bridges ( ER) by 30% in α-MHC fibers. In sharp contrast, TnTA30Vincreased ERby 55% in β-MHC fibers. Inferences drawn from other dynamic contractile parameters suggest that directional changes in ERin TnTA30V+ α-MHC and TnTA30V+ β-MHC fibers result from a divergent impact on cross bridge-regulatory unit (troponin-tropomyosin complex) cooperativity. TnTA30V-mediated effects on Ca2+-activated maximal tension and instantaneous muscle fiber stiffness ( ED) were also divergently affected by α- and β-MHC. Our study demonstrates that TnTA30V+ α-MHC and TnTA30V+ β-MHC fibers show contrasting contractile phenotypes; however, only the observations from β-MHC fibers are consistent with the clinical data for A28V in humans.

NEW & NOTEWORTHY The differential impact of α- and β-myosin heavy chain (MHC) on contractile dynamics causes a mutant cardiac troponin T (TnTA30V) to differently modulate cardiac contractile function. TnTA30Vattenuated Ca2+-activated maximal tension and length-mediated cross-bridge recruitment against α-MHC but augmented these parameters against β-MHC, suggesting divergent contractile phenotypes.