bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive Mission Planning and Analysis for Complex Systems
Authors: DeStefano Charlie , Jensen David
Published: October 2016

This paper presents a new method for complex system failure analysis and adaptive mission planning that provides both an overall failure analysis on a system's performance as well as a mission-based failure analysis. The adaptive mission planning and analysis (AMPA) method presented here uses physics-based governing equations to identify the system's overall behavior during both nominal and faulty conditions. The AMPA method is unique, in which it first identifies a specific failure or combination of failures within a system and then determines how each failure scenario will affect the system's overall performance characteristics, i.e., its functionality. Then, AMPA uses this failure information to assess and optimize various missions that the system may be asked to perform. The AMPA method is designed to identify functional failures of a given system and then, depending on the types of failures that have occurred and what tasks the system will be asked to perform, identify the optimal functional approach needed for moving forward to successfully complete its mission. Ultimately, this method could be applied in situ to systems using sensor data rather than simulations to allow autonomous systems to automatically adapt to failures. That is, by using the remaining healthy components in a new or different way to compensate for the faulty components to extend the systems lifespan and optimize the chance of mission completion.
Heterogeneous Composition Adaptation With Material Convolution Control Features
Authors: Gupta Vikas , Tandon Puneet
Published: October 2016

Controlling and accomplishing the desired functional material composition in a heterogeneous object (HO) is a close loop process and requires frequent remodeling-and-analysis. Thus, flexibility and capability to efficiently modify the existing CAD model of a heterogeneous object are essential aspects of heterogeneous object modeling. The current work unfolds such capabilities of the developed material convolution surface approach. The geometric and material control features associated with the approach demonstrate the potential to modify existing material-distributions to remodel complex material variations and assure rapid heterogeneous composition adaptations. Convolution material primitives (CMPs), material potential functions, and heterogeneous and grading enclosure are manipulated to achieve desired material compositions across the heterogeneous region. The manipulation process for each control feature has been established. A few examples of modeling and modifying complex material-distributions have been reported for the validation of work.
Experimental and Numerical Study on Optimizing the Dry Low NOx Micromix Hydrogen Combustion Principle for Industrial Gas Turbine Applications
Authors: Funke Harald H. W. , Keinz Jan , Kusterer Karsten , Ayed Anis Haj , Kazari Masahide , Kitajima Junichi , Horikawa Atsushi , Okada Kunio
Published: October 2016

Combined with the use of renewable energy sources for its production, hydrogen represents a possible alternative gas turbine fuel for future low-emission power generation. Due to the difference in the physical properties of hydrogen compared to other fuels such as natural gas, well-established gas turbine combustion systems cannot be directly applied to dry low NOx (DLN) hydrogen combustion. The DLN micromix combustion of hydrogen has been under development for many years, since it has the promise to significantly reduce NOx emissions. This combustion principle for air-breathing engines is based on crossflow mixing of air and gaseous hydrogen. Air and hydrogen react in multiple miniaturized diffusion-type flames with an inherent safety against flashback and with low NOx emissions due to a very short residence time of the reactants in the flame region. The paper presents an advanced DLN micromix hydrogen application. The experimental and numerical study shows a combustor configuration with a significantly reduced number of enlarged fuel injectors with high-thermal power output at constant energy density. Larger fuel injectors reduce manufacturing costs, are more robust and less sensitive to fuel contamination and blockage in industrial environments. The experimental and numerical results confirm the successful application of high-energy injectors, while the DLN micromix characteristics of the design point, under part-load conditions, and under off-design operation are maintained. Atmospheric test rig data on NOx emissions, optical flame-structure, and combustor material temperatures are compared to numerical simulations and show good agreement. The impact of the applied scaling and design laws on the miniaturized micromix flamelets is particularly investigated numerically for the resulting flow field, the flame-structure, and NOx formation.
A Finite Difference Lattice Boltzmann Method to Simulate Multidimensional Subcontinuum Heat Conduction
Authors: Chen Cheng , Geer James , Sammakia Bahgat
Published: October 2016

In this paper, a lattice Boltzmann method (LBM)-based model is developed to simulate the subcontinuum behavior of multidimensional heat conduction in solids. Based on a previous study (Chen et al., 2014, “Sub-Continuum Thermal Modeling Using Diffusion in the Lattice Boltzmann Transport Equation,” Int. J. Heat Mass Transfer, 79, pp. 666–675), phonon energy transport is separated to a ballistic part and a diffusive part, with phonon equilibrium assumed at boundaries. Steady-state temperature/total energy density solutions from continuum scales to ballistic scales are considered. A refined LBM-based numerical approach is applied to a two-dimensional simplified transistor model proposed by (Sinha et al. 2006, “Non-Equilibrium Phonon Distributions in Sub-100 nm Silicon Transistors,” ASME J. Heat Transfer, 128(7), pp. 638–647), and the results are compared with the Fourier-based heat conduction model. The three-dimensional (3D) LBM model is also developed and verified at both the ballistic and continuous limits. The impact of film thickness on the cross-plane and in-plane thermal conductivities is analyzed, and a new model of the supplementary diffusion term is proposed. Predictions based on the finalized model are compared with the existing in-plane thermal conductivity measurements and cross-plane thermal conductivity molecular dynamics (MD) results.
Handling Actuator Saturation as Underactuation: Case Study With Acroboter Service Robot
Authors: Zelei Ambrus , Bencsik László , Stépán Gábor
Published: October 2016

Model-based control methods such as inverse dynamics control and computed torque control encounter difficulties if actuator saturation occurs. However, saturation is a common phenomenon in robotics leading to significant nonlinearity in system behavior. In this study, the saturation of the actuator torques is considered as a temporary reduction of the number of independent control inputs. The reduction of the number of actuators leads to an underactuated control problem which typically involves the handling of differential algebraic equation systems. The saturated system may become especially complex when intricate combinations of the actuator saturations appear. A servoconstraint-based inverse dynamics control method for underactuated multibody systems is applied for the treatment of actuator torque saturation. In case of human-friendly robots, the problem of saturation cannot be avoided on the level of trajectory planning because unexpected human perturbations may take place, which result in such abrupt changes in the desired trajectory that lead to saturation at some actuators. A case study for the service robot Acroboter shows the applicability of the proposed approach.
Comparison of Semirecursive and Subsystem Synthesis Algorithms for the Efficient Simulation of Multibody Systems
Authors: Callejo Alfonso , Pan Yongjun , Ricón José L. , Kövecses József , García de Jalón Javier
Published: October 2016

A great variety of formulations exist for the numerical simulation of rigid-body systems, particularly of medium-large systems such as vehicles. Topological formulations, which are considered to be the most efficient ones, are often cumbersome and not necessarily easy to implement. As a consequence, there is a lack of comparative evidence to support the performance of these formulations. In this paper, we present and compare three state-of-the-art topological formulations for multibody dynamics: generalized semirecursive, double-step semirecursive, and subsystem synthesis methods. We analyze the background, underlying principles, numerical efficiency, and accuracy of these formulations in a systematic way. A 28-degree-of-freedom, open-loop rover model and a 16-degree-of-freedom, closed-loop sedan car model are selected as study cases. Insight on the key aspects toward performance is provided.
A Recommended Correction to the kT−kL−ω Transition-Sensitive Eddy-Viscosity Model
Authors: Lopez Maurin , Keith Walters D.
Published: October 2016

A physics-based modification to the kT−kL−ω transition-sensitive eddy-viscosity model is presented. The modification corrects an anomaly related to the physical mechanism of production of laminar kinetic energy for regions far from the wall in fully turbulent flows, by limiting the production of natural modes in the large-scale eddy-viscosity term by a rescale of the wall-limited turbulent length scale. Round jet and backward facing step test cases are used to reveal the relevant issue and to demonstrate that the new modification successfully addresses the problem.
Synthesis of Constant Torque Compliant Mechanisms
Authors: Nair Prakashah Hari , Zhou Hong
Published: October 2016

Constant torque compliant mechanisms produce an output torque that does not change in a large range of input rotation. They have wide applications in aerospace, automobile, timing, gardening, medical, and healthcare devices. Unlike constant force compliant mechanisms, the synthesis of constant torque compliant mechanisms has not been extensively investigated yet. In this paper, a method is presented for synthesizing constant torque compliant mechanisms that have coaxial input rotation and output torque. The same shaft is employed for both input rotation and output torque. A synthesized constant torque compliant mechanism is modeled as a set of variable width spline curves within an annular design domain formed between a rotation shaft and a fixed ring. Interpolation circles are used to define variable width spline curves. The synthesis of constant torque compliant mechanisms is systematized as optimizing the control parameters of the interpolation circles of the variable width spline curves. The presented method is demonstrated by the synthesis of constant torque compliant mechanisms that have different number of variable width spline curves in this paper.
Failure Analysis of Composite-Based Lightweight Multimaterial Joints in Tensile-Shear Tests After Cyclic Heat at High-Relative Humidity
Authors: Sakai Kaori , Nassar Sayed A.
Published: October 2016

Failure analysis of tensile-shear tested bonded composite-based single lap joints (SLJs) that have been subjected to two different levels of cyclic environmental loading is provided. Each test joint has at least one composite adherend which is made of glass fiber-reinforced polymer (GFRP); the second adherend may be aluminum, magnesium, or GFRP composite, and structural epoxy adhesive is used to join two adherends together for creating test joints. Scanning electron microscope (SEM) and energy dispersive spectrometry (EDS) are utilized to investigate the root cause failure of fractured surfaces that gives an insight into the recently published data that showed a significant effect of the cyclic heat on the static load transfer capacity (LTC) of the same SLJs. The SEM and EDS inspections show that the failure mode shifts from interfacial adhesive failure (ADH) to fiber tear (FT) for the GFRP/GFRP joints that have been exposed to cyclic heat with and without high relative humidity as compared to that at ambient condition. Further, failure analysis and discussion are provided.
Machining Complex Three-Dimensional Nanostructures With an Atomic Force Microscope Through the Frequency Control of the Tip Reciprocating Motions
Authors: Geng Yanquan , Yan Yongda , Brousseau Emmanuel , Cui Xing , Yu Bowen , Zhao Xuesen , Hu Zhenjiang
Published: October 2016

A novel method relying on atomic force microscope (AFM) tip based nanomachining is presented to enable the fabrication of microchannels that exhibit complex three-dimensional (3D) nanoscale floor surface geometries. To achieve this, reciprocating lateral displacements of the tip of an AFM probe are generated, while a high-precision stage is also actuated to move in a direction perpendicular to such tip motions. The width and length of microchannels machined in this way are determined by the amplitude of the tip motion and the stage displacement, respectively. Thus, the processing feed can be changed during the process as it is defined by the combined control of the frequency of the tip reciprocating motions and the stage speed. By employing the built-in force feedback loop of conventional AFM systems during such operations, the variation of the feed leads to different machined depths. Thus, this results in the capability to generate complex 3D nanostructures, even for a given normal load, which is set by the AFM user prior to the start of the process. In this paper, the fabrication of different microchannels with floor surfaces following half triangular, triangular, sinusoidal, and top-hat waveforms is demonstrated. It is anticipated that this method could be employed to fabricate complex nanostructures more readily compared to traditional vacuum-based lithography processes.
Milling Stability Interrogation by Subharmonic Sampling
Authors: Honeycutt Andrew , Schmitz Tony L.
Published: October 2016

This paper describes the use of subharmonic sampling to distinguish between different instability types in milling. It is demonstrated that sampling time-domain milling signals at integer multiples of the tooth period enables secondary Hopf and period-n bifurcations to be automatically differentiated. A numerical metric is applied, where the normalized sum of the absolute values of the differences between successively sampled points is used to distinguish between the potential bifurcation types. A new stability map that individually identifies stable and individual bifurcation zones is presented. The map is constructed using time-domain simulation and the new subharmonic sampling metric.
A Single Nucleotide Change in the Promoter
mutp
Enhances Fluoride Resistance of Streptococcus mutans
Authors: Liao Ying , Brandt Bernd W. , Zhang Min , Li Jiyao , Crielaard Wim , van Loveren Cor , Deng Dong Mei
Published: October 2016

Previously, we identified a single nucleotide mutation in the promoter (
mutp
) of the fluoride antiporter-coding genes in a naturally fluoride-resistant
Streptococcus mutans
strain. Here, we studied the role of this mutation in a defined genetic background. The results confirmed that this mutation alone confers fluoride resistance on
S. mutans
, as shown by growth and lactic acid production assays. This resistance was explained by constitutively higher
mutp
promoter activity and upregulation of the fluoride antiporter-coding genes.
Population Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Children
Authors: Lestner Jodi M. , Groll Andreas H. , Aljayyoussi Ghaith , Seibel Nita L. , Shad Aziza , Gonzalez Corina , Wood Lauren V. , Jarosinski Paul F. , Walsh Thomas J. , Hope William W.
Published: October 2016

Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited pharmacokinetic (PK) data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults. Our objective was to describe the pharmacokinetics of LAmB in children aged 1 to 17 years with suspected or documented IFD. Thirty-five children were treated with LAmB at doses of 2.5 to 10 mg kg
−1
daily. Samples were taken at baseline and at 0.5- to 2.0-h intervals for 24 h after receipt of the first dose (
n
= 35 patients) and on the final day of therapy (
n
= 25 patients). LAmB was measured using high-performance liquid chromatography (HPLC). The relationship between drug exposure and development of toxicity was explored. An evolution in PK was observed during the course of therapy, resulting in a proportion of patients (
n
= 13) having significantly higher maximum serum concentrations (
C
max
) and areas under the concentration-time curve from 0 to 24 h (AUC
0–24
) later in the course of therapy, without evidence of drug accumulation (trough plasma concentration accumulation ratio of <1.2). The fit of a 2-compartment model incorporating weight and an exponential decay function describing volume of distribution best described the data. There was a statistically significant relationship between mean AUC
0–24
and probability of nephrotoxicity (odds ratio, 2.37; 95% confidence interval, 1.84 to 3.22;
P
= 0.004). LAmB exhibits nonlinear pharmacokinetics. A third of children appear to experience a time-dependent change in PK, which is not explained by weight, maturation, or observed clinical factors.
Pharmacokinetic Interactions between Tafenoquine and Dihydroartemisinin-Piperaquine or Artemether-Lumefantrine in Healthy Adult Subjects
Authors: Green Justin A. , Mohamed Khadeeja , Goyal Navin , Bouhired Samia , Hussaini Azra , Jones Siôn W. , Koh Gavin C. K. W. , Kostov Ivan , Taylor Maxine , Wolstenholm Allen , Duparc Stephan
Published: October 2016

Tafenoquine is in development as a single-dose treatment for relapse prevention in individuals with
Plasmodium vivax
malaria. Tafenoquine must be coadministered with a blood schizonticide, either chloroquine or artemisinin-based combination therapy (ACT). This open-label, randomized, parallel-group study evaluated potential drug interactions between tafenoquine and two ACTs: dihydroartemisinin-piperaquine and artemether-lumefantrine. Healthy volunteers of either sex aged 18 to 65 years without glucose-6-phosphate dehydrogenase deficiency were randomized into five cohorts (
n
= 24 per cohort) to receive tafenoquine on day 1 (300 mg) plus once-daily dihydroartemisinin-piperaquine on days 1, 2, and 3 (120 mg/960 mg for 36 to <75 kg of body weight and 160 mg/1,280 mg for ≥75 to 100 kg of body weight), or plus artemether-lumefantrine (80 mg/480 mg) in two doses 8 h apart on day 1 and then twice daily on days 2 and 3, or each drug alone. The pharmacokinetic parameters of tafenoquine, piperaquine, lumefantrine, artemether, and dihydroartemisinin were determined by using noncompartmental methods. Point estimates and 90% confidence intervals were calculated for area under the concentration-time curve (AUC) and maximum observed plasma concentration (
C
max
) comparisons of tafenoquine plus ACT versus tafenoquine or ACT. All subjects receiving dihydroartemisinin-piperaquine experienced QTc prolongation (a known risk with this drug), but tafenoquine coadministration had no clinically relevant additional effect. Tafenoquine coadministration had no clinically relevant effects on dihydroartemisinin, piperaquine, artemether, or lumefantrine pharmacokinetics. Dihydroartemisinin-piperaquine coadministration increased the tafenoquine
C
max
by 38% (90% confidence interval, 25 to 52%), the AUC from time zero to infinity (AUC
0–∞
) by 12% (1 to 26%), and the half-life (
t
1/2
) by 29% (19 to 40%), with no effect on the AUC from time zero to the time of the last nonzero concentration (AUC
0–last
). Artemether-lumefantrine coadministration had no effect on tafenoquine pharmacokinetics. Tafenoquine can be coadministered with dihydroartemisinin-piperaquine or artemether-lumefantrine without dose adjustment for any of these compounds. (This study has been registered at ClinicalTrials.gov under registration no. NCT02184637.)
Liver Fatty Acid Binding Protein Deficiency Provokes Oxidative Stress, Inflammation, and Apoptosis-Mediated Hepatotoxicity Induced by Pyrazinamide in Zebrafish Larvae
Authors: Zhang Yun , Liu Kechun , Hassan Hozeifa M. , Guo Hongli , Ding Pingping , Han Liwen , He Qiuxia , Chen Weiyun , Hsiao Chung-Der , Zhang Luyong , Jiang Zhenzhou
Published: October 2016

Pyrazinamide (PZA) is an essential antitubercular drug, but little is still known about its hepatotoxicity potential. This study examined the effects of PZA exposure on zebrafish (
Danio rerio
) larvae and the mechanisms underlying its hepatotoxicity. A transgenic line of zebrafish larvae that expressed enhanced green fluorescent protein (EGFP) in the liver was incubated with 1, 2.5, and 5 mM PZA from 72 h postfertilization (hpf). Different endpoints such as mortality, morphology changes in the size and shape of the liver, histological changes, transaminase analysis and apoptosis, markers of oxidative and genetic damage, as well as the expression of certain genes were selected to evaluate PZA-induced hepatotoxicity. Our results confirm the manner of PZA dose-dependent hepatotoxicity. PZA was found to induce marked injury in zebrafish larvae, such as liver atrophy, elevations of transaminase levels, oxidative stress, and hepatocyte apoptosis. To further understand the mechanism behind PZA-induced hepatotoxicity, changes in gene expression levels in zebrafish larvae exposed to PZA for 72 h postexposure (hpe) were determined. The results of this study demonstrated that PZA decreased the expression levels of liver fatty acid binding protein (L-FABP) and its target gene, peroxisome proliferator-activated receptor α (PPAR-α), and provoked more severe oxidative stress and hepatitis via the upregulation of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and transforming growth factor β (TGF-β). These findings suggest that L-FABP-mediated PPAR-α downregulation appears to be a hepatotoxic response resulting from zebrafish larva liver cell apoptosis, and L-FABP can be used as a biomarker for the early detection of PZA-induced liver damage in zebrafish larvae.
RalF-Mediated Activation of Arf6 Controls Rickettsia typhi Invasion by Co-Opting Phosphoinositol Metabolism
Authors: Rennoll-Bankert Kristen E. , Rahman M. Sayeedur , Guillotte Mark L. , Lehman Stephanie S. , Beier-Sexton Magda , Gillespie Joseph J. , Azad Abdu F.
Published: October 2016

Rickettsiae are obligate intracellular pathogens that induce their uptake into nonphagocytic cells; however, the events instigating this process are incompletely understood. Importantly, diverse
Rickettsia
species are predicted to utilize divergent mechanisms to colonize host cells, as nearly all adhesins and effectors involved in host cell entry are differentially encoded in diverse
Rickettsia
species. One particular effector, RalF, a Sec7 domain-containing protein that functions as a guanine nucleotide exchange factor of ADP-ribosylation factors (Arfs), is critical for
Rickettsia typhi
(typhus group rickettsiae) entry but pseudogenized or absent from spotted fever group rickettsiae. Secreted early during
R. typhi
infection, RalF localizes to the host plasma membrane and interacts with host ADP-ribosylation factor 6 (Arf6). Herein, we demonstrate that RalF activates Arf6, a process reliant on a conserved Glu within the RalF Sec7 domain. Furthermore, Arf6 is activated early during infection, with GTP-bound Arf6 localized to the
R. typhi
entry foci. The regulation of phosphatidylinositol 4-phosphate 5-kinase (PIP5K), which generates PI(4,5)P
2
, by activated Arf6 is instrumental for bacterial entry, corresponding to the requirement of PI(4,5)P
2
for
R. typhi
entry. PI(3,4,5)P
3
is then synthesized at the entry foci, followed by the accumulation of PI(3)P on the short-lived vacuole. Inhibition of phosphoinositide 3-kinases, responsible for the synthesis of PI(3,4,5)P
3
and PI(3)P, negatively affects
R. typhi
infection. Collectively, these results identify RalF as the first bacterial effector to directly activate Arf6, a process that initiates alterations in phosphoinositol metabolism critical for a lineage-specific
Rickettsia
entry mechanism.
Macrophages Promote Oxidative Metabolism To Drive Nitric Oxide Generation in Response to Trypanosoma cruzi
Authors: Koo Sue-jie , Chowdhury Imran H. , Szczesny Bartosz , Wan Xianxiu , Garg Nisha J.
Published: October 2016

Trypanosoma cruziis the causative agent of chronic chagasic cardiomyopathy. Why macrophages (mφs), the early responders to infection, fail to achieve parasite clearance is not known. Mouse (RAW 264.7) and human (THP-1 and primary) mφs were infected for 3 h and 18 h withT. cruziTcI isolates, SylvioX10/4 (SYL, virulent) and TCC (nonpathogenic), which represent mφ stimulation and infection states, respectively. Mφs incubated with lipopolysaccharide and gamma interferon (LPS/IFN-γ) and with interleukin-4 (IL-4) were used as controls. We monitored the cytokine profile (using enzyme-linked immunosorbent assay [ELISA]), reactive oxygen species (ROS; fluorescent probes), nitric oxide (·NO; Griess assay), and metabolic state using a custom-designed mitoxosome array and Seahorse XF24 Analyzer. LPS/IFN-γ treatment of mφs elicited a potent increase in production of tumor necrosis alpha (TNF-α) at 3 h and of ROS and ·NO by 18 h. Upon SYL infection, murine mφs elicited an inflammatory cytokine profile (TNF-α ≫ TGF-β + IL-10) and low levels of ·NO and ROS production. LPS/IFN-γ treatment resulted in the inhibition of oxidative metabolism at the gene expression and functional levels and a switch to the glycolytic pathway in mφs, while IL-4-treated mφs utilized oxidative metabolism to meet energy demands. SYL infection resulted in an intermediate functional metabolic state with increased mitoxosome gene expression and glycolysis, and IFN-γ addition shut down the oxidative metabolism in SYL-infected mφs. Further, TCC- and SYL-stimulated mφs exhibited similar levels of cell proliferation and production of TNF-α and ROS, while TCC-stimulated mφs exhibited up to 2-fold-higher levels of oxidative metabolism and ·NO production than SYL-infected mφs. Inhibiting ATP-coupled O2consumption suppressed the ·NO generation in SYL-infected mφs. Mitochondrial oxygen consumption constitutes a mechanism for stimulating ·NO production in mφs duringT. cruziinfection. Enhancing the oxidative metabolism provides an opportunity for increased ·NO production and pathogen clearance by mφs to limit disease progression.
The Phosphorolytic Exoribonucleases Polynucleotide Phosphorylase and RNase PH Stabilize sRNAs and Facilitate Regulation of Their mRNA Targets
Authors: Cameron Todd A. , De Lay Nicholas R.
Published: October 2016

Gene regulation by base pairing between small noncoding RNAs (sRNAs) and their mRNA targets is an important mechanism that allows bacteria to maintain homeostasis and respond to dynamic environments. In Gram-negative bacteria, sRNA pairing and regulation are mediated by several RNA-binding proteins, including the sRNA chaperone Hfq and polynucleotide phosphorylase (PNPase). PNPase and its homolog RNase PH together represent the two 3′ to 5′ phosphorolytic exoribonucleases found in
Escherichia coli
; however, the role of RNase PH in sRNA regulation has not yet been explored and reported. Here, we have examined in detail how PNPase and RNase PH interact to support sRNA stability, activity, and base pairing in exponential and stationary growth conditions. Our results indicate that these proteins facilitate the stability and regulatory function of the sRNAs RyhB, CyaR, and MicA during exponential growth. PNPase further appears to contribute to pairing between RyhB and its mRNA targets. During stationary growth, each sRNA responded differently to the absence or presence of PNPase and RNase PH. Finally, our results suggest that PNPase and RNase PH stabilize only Hfq-bound sRNAs. Taken together, these results confirm and extend previous findings that PNPase participates in sRNA regulation and reveal that RNase PH serves a similar, albeit more limited, role as well. These proteins may, therefore, act to protect sRNAs from spurious degradation while also facilitating regulatory pairing with their targets.

IMPORTANCE
In many bacteria, Hfq-dependent base-pairing sRNAs facilitate rapid changes in gene expression that are critical for maintaining homeostasis and responding to stress and environmental changes. While a role for Hfq in this process was identified more than 2 decades ago, the identity and function of the other proteins required for Hfq-dependent regulation by sRNAs have not been resolved. Here, we demonstrate that PNPase and RNase PH, the two phosphorolytic RNases in
E. coli
, stabilize sRNAs against premature degradation and, in the case of PNPase, also accelerate regulation by sRNA-mRNA pairings for certain sRNAs. These findings are the first to demonstrate that RNase PH influences and supports sRNA regulation and suggest shared and distinct roles for these phosphorolytic RNases in this process.
Host Responses to Urinary Tract Infections and Emerging Therapeutics: Sensation and Pain within the Urinary Tract
Authors: Birder Lori A. , Klumpp David J.
Published: October 2016

Urinary tract infection (UTI) pathogenesis is understood increasingly at the level of the uropathogens and the cellular and molecular mediators of host inflammatory responses. However, little is known about the mediators of symptoms during UTI and what distinguishes symptomatic events from asymptomatic bacteriuria. Here, we review bladder physiology and sensory pathways in the context of an emerging literature from murine models dissecting the host and pathogen factors mediating pain responses during UTI. The bladder urothelium is considered a mediator of sensory responses and appears to play a role in UTI pain responses. Virulence factors of uropathogens induce urothelial damage that could trigger pain due to compromised bladder-barrier function. Instead, bacterial glycolipids are the major determinants of UTI pain independent of urothelial damage, and the O-antigen of lipopolysaccharide modulates pain responses. The extent of pain modulation by O-antigen can have profound effects, from abolishing pain responses to inducing chronic pain that results in central nervous system features reminiscent of neuropathic pain. Although these effects are largely dependent upon Toll-like receptors, pain is independent of inflammation. Surprisingly, some bacteria even possess analgesic properties, suggesting that bacteria exhibit a wide range of pain phenotypes in the bladder. In summary, UTI pain is a complex form of visceral pain that has significant potential to inform our understanding of bacterial pathogenesis and raises the specter of chronic pain resulting from transient infection, as well as novel approaches to treating pain.
Massive iatrogenic orbital cysts following glaucoma drainage implant and strabismus surgery
Authors: Demirkilinc Biler Elif , Yagci Ayse , Uretmen Onder , Palamar Melis
Published: October 2016

We describe 2 paediatric patients who developed large orbital conjunctival epithelium-lined inclusion cysts postsurgery. Case 1 underwent Ahmed glaucoma valve implant surgery 8 months ago and case 2 underwent strabismus surgery 7 years ago. Both cases had either symptomatic strabismus or a mass causing some degree of proptosis or incomitance due to lesions in the intraorbital space. Following total excision of the cysts all associated symptoms were resolved. Conjunctival cysts following ocular surgery can develop anywhere in the anterior segment; however, large orbital cysts following anterior segment surgery are quite rare. We think that implantation cysts should be considered in the differential diagnosis of patients that have signs of orbital mass with a history of previous anterior segment surgery. Complete excision of the cysts results in resolution of all associated signs and symptoms.
Efficacy of extracorporeal ultrafiltration in patients with diuretic-resistant heart failure
Authors: Nakazawa Naomi , Nakabayashi Keisuke , Oka Toshiaki
Published: October 2016

Renal congestion contributes to the cardiorenal syndrome. There are some heart failure cases that are refractory to diuretic therapy. If the dose of diuretics is titrated, it leads to irreversible renal dysfunction. Early administration of tolvaptan is effective in treating fluid retention and congestion. However, in case of tolvaptan resistance, starting extracorporeal ultrafiltration (ECUM) at an early stage should be considered. Tolvaptan has been proven efficient, and we believe it should be incorporated with the classical method, ECUM. Herein, we present a case of successful application of ECUM to a heart failure patient refractory to any diuretics and tolvaptan.
Evidence from prospective cohort studies does not support current dietary fat guidelines: a systematic review and meta-analysis
Authors: Harcombe Zoë , Baker Julien S , Davies Bruce
Published: October 2016

Objectives

National dietary guidelines were introduced in 1977 and 1983, by the US and UK governments to reduce coronary heart disease (CHD) mortality by reducing dietary fat intake. Our 2016 systematic review examined the epidemiological evidence available to the dietary committees at the time; we found no support for the recommendations to restrict dietary fat. The present investigation extends our work by re-examining the totality of epidemiological evidence currently available relating to dietary fat guidelines.

Methods

A systematic review and meta-analysis of prospective cohort studies currently available, which examined the relationship between dietary fat, serum cholesterol and the development of CHD, were undertaken.

Results

Across 7 studies, involving 89 801 participants (94% male), there were 2024 deaths from CHD during the mean follow-up of 11.9±5.6 years. The death rate from CHD was 2.25%. Eight data sets were suitable for inclusion in meta-analysis; all excluded participants with previous heart disease. Risk ratios (RRs) from meta-analysis were not statistically significant for CHD deaths and total or saturated fat consumption. The RR from meta-analysis for total fat intake and CHD deaths was 1.04 (95% CI 0.98 to 1.10). The RR from meta-analysis for saturated fat intake and CHD deaths was 1.08 (95% CI 0.94 to 1.25).

Conclusions

Epidemiological evidence to date found no significant difference in CHD mortality and total fat or saturated fat intake and thus does not support the present dietary fat guidelines. The evidence per se lacks generalisability for population-wide guidelines.
Prevalence, discomfort and self-relief behaviours of painful diabetic neuropathy in Taiwan: a cross-sectional study
Authors: Jane Sui-Whi , Lin Ming-Shyan , Chiu Wen-Nan , Beaton Randal D , Chen Mei-Yen
Published: October 2016

Objectives

To explore the prevalence, discomfort, and self-relief behaviours of painful diabetic neuropathy (PDN) among rural community residents with type 2 diabetes.

Design

A community-based, cross-sectional study.

Setting

This study was part of a longitudinal cohort study of a nurse-led health promotion programme for preventing foot ulceration in Chiayi County, Taiwan.

Participants

Six hundred and twenty-eight community adults with type 2 diabetes participated in this study.

Outcome measures

Parameters assessed included peripheral neuropathy, peripheral vasculopathy, glycaemic control and metabolic biomarkers. Statistical analyses included descriptive statistics and a multivariate logistic regression model.

Results

About 30.6% of participants (192/628) had PDN. Factors associated with PDN included an abnormal ankle brachial index (ABI; OR=3.4; 95% CI 1.9 to 6.2; p<0.001), Michigan neuropathy screening index (OR=1.69; 95% CI 1.0 to 2.6; p=0.021), triglyceride level (OR=1.61; 95% CI 1.0 to 2.4; p=0.036) and being female (OR=1.68; 95% CI 1.1 to 2.4; p=0.022). PDN was characterised by uncomfortable feelings of prickling, stinging or burning pain and inexplicable dullness around the base or dorsal areas of the feet, but received little attention or treatment from primary healthcare providers.

Conclusions

A high prevalence of PDN was found in rural community residents with type 2 diabetes and the healthcare workers provided little attention to, or treatment of, discomfort. It is important to identify high-risk groups with PDN early in order to prevent foot ulceration and reduce the incidence of amputation of the extremities. It is also urgent to develop appropriate treatment and self-relief behaviours to halt or reverse the progression of PDN for this population living in rural areas.
Current practices in patient-reported outcome (PRO) data collection in clinical trials: a cross-sectional survey of UK trial staff and management
Authors: Kyte Derek , Ives Jonathan , Draper Heather , Calvert Melanie
Published: October 2016

Objectives

Patient-reported outcome measures (PROMs) collected in clinical trials should be administered in a standardised way across sites and routinely screened for avoidable missing data in order to maximise data quality/minimise risk of bias. Recent qualitative findings, however, have raised concerns about the consistency of PROM administration in UK trials. The purpose of this study was to determine the generalisability of these findings across the wider community of trial personnel.

Design

Online cross-sectional survey.

Setting

Participants were recruited from 55 UK Clinical Research Collaboration Registered Clinical Trials Units and 19 Comprehensive Local Research Networks.

Participants

Research nurses, data managers/coordinators, trial managers and chief/principal investigators involved in clinical trials collecting PROMs.

Analysis

We undertook descriptive analyses of the quantitative data and directed thematic analysis of free-text comments. Factors associated with the management of missing PRO data were explored using logistic regression.

Results

Survey data from 767 respondents supported the generalisability of qualitative study findings, suggesting inconsistencies in PROM administration with regard to: the level of assistance given to trial participants; the timing of PROM completion in relation to the clinical consultation; and the management of missing data. Having ≥10 years experience in a research role was significantly associated with the appropriate management of missing PROM data (OR 2.26 (95% CI 1.06 to 4.82), p=0.035). There was a consensus that more PROM guidance was needed in future trials and agreement between professional groups about the necessary components.

Conclusions

There are inconsistencies in the way PROMs are administered by trial staff. Such inconsistencies may reduce the quality of data and have the potential to introduce bias. There is a need for improved guidance in future trials that support trial personnel in conducting optimal PROM data collection to inform patient care.
Community-based Rehabilitation Training after stroke: protocol of a pilot randomised controlled trial (ReTrain)
Authors: Dean Sarah G , Poltawski Leon , Forster Anne , Taylor Rod S , Spencer Anne , James Martin , Allison Rhoda , Stevens Shirley , Norris Meriel , Shepherd Anthony I , Calitri Raff
Published: October 2016

Introduction

The Rehabilitation Training (ReTrain) intervention aims to improve functional mobility, adherence to poststroke exercise guidelines and quality of life for people after stroke. A definitive randomised controlled trial (RCT) is required to assess the clinical and cost-effectiveness of ReTrain, which is based on Action for Rehabilitation from Neurological Injury (ARNI). The purpose of this pilot study is to assess the feasibility of such a definitive trial and inform its design.

Methods and analysis

A 2-group, assessor-blinded, randomised controlled external pilot trial with parallel mixed-methods process evaluation and economic evaluation. 48 participants discharged from clinical rehabilitation despite residual physical disability will be individually randomised 1:1 to ReTrain (25 sessions) or control (exercise advice booklet). Outcome assessment at baseline, 6 and 9 months include Rivermead Mobility Index; Timed Up and Go Test; modified Patient-Specific Functional Scale; 7-day accelerometry; Stroke Self-efficacy Questionnaire, exercise diary, Fatigue Assessment Scale, exercise beliefs and self-efficacy questionnaires, SF-12, EQ-5D-5L, Stroke Quality of Life, Carer Burden Index and Service Receipt Inventory. Feasibility, acceptability and process outcomes include recruitment and retention rates; with measurement burden and trial experiences being explored in qualitative interviews (20 participants, 3 intervention providers). Analyses include descriptive statistics, with 95% CI where appropriate; qualitative themes; intervention fidelity from videos and session checklists; rehearsal of health economic analysis.

Ethics and dissemination

National Health Service (NHS) National Research Ethics Service approval granted in April 2015; recruitment started in June. Preliminary studies suggested low risk of serious adverse events; however (minor) falls, transitory muscle soreness and high levels of postexercise fatigue are expected. Outputs include pilot data to inform whether to proceed to a definitive RCT and support a funding application; finalised Trainer and Intervention Delivery manuals for multicentre replication of ReTrain; presentations at conferences, public involvement events; internationally recognised peer-reviewed journal publications, open access sources and media releases.

Trial registration number

NCT02429180; Pre-results.
Study protocol of the YP Face IT feasibility study: comparing an online psychosocial intervention versus treatment as usual for adolescents distressed by appearance-altering conditions/injuries
Authors: Williamson Heidi , Hamlet Claire , White Paul , Marques Elsa M R , Cadogan Julia , Perera Rohan , Rumsey Nichola , Hayward Leighton , Harcourt Diana
Published: October 2016

Introduction

A significant number of adolescents suffer extensive and enduring difficulties such as social anxiety, body image dissatisfaction, low self-esteem and bullying as a result of conditions or injuries that affect their appearance (eg, craniofacial and skin conditions, treatment side effects and scarring). Evidence-based psychosocial interventions to meet their specific needs are currently lacking. YP Face IT, developed by the UK's Centre for Appearance Research in collaboration with clinical experts and young people, is an innovative online psychosocial intervention designed to offer this group immediate support, advice and coping strategies. It has been endorsed by young people, their parents/carers, GPs, clinical psychologists and health professionals working with those affected by appearance-related conditions.

Methods and analysis

Young people aged 12–17 with an appearance-altering condition/injury that self-identify as experiencing appearance-related distress, teasing or bullying will be invited to participate via GP practices and UK charities. Consenting participants will be randomised to the intervention (YP Face IT) or the treatment as usual (TAU) control group. Outcome measures will be completed by young people and their parents/carers at baseline, 13, 26 and 52 weeks. Primary outcome measures will be the Body Esteem Scale and the Social Anxiety Scale for Adolescents. Participants will complete other health-related outcome measures and resource use questionnaires for health economic analysis. We will assess recruitment rates, acceptability of the YP Face IT programme, adherence and retention to treatment, questionnaire completion rates, variation of TAU in Primary Care and the feasibility of GP practice staff supervising young people's use of YP Face IT.

Ethics and dissemination

This feasibility trial protocol (V.1, 3 March 2014), received a favourable ethical opinion from the NRES Committee South West-Frenchay (reference number 14/SW/0058). Findings will be disseminated through academic peer-reviewed publications, conferences and to participating GP practices and charities supporting those with conditions affecting appearance.

Trial registration number

ISRCTN40650639; Pre-results.
Developing Quality Improvement capacity and capability across the Children in Fife partnership
Authors: Morris Craig , Alexander Ingrid
Published: October 2016

A Project Manager from the Fife Early Years Collaborative facilitated a large-scale Quality Improvement (herein QI) project to build organisational capacity and capability across the Children in Fife partnership through three separate, eight month training cohorts.

This 18 month QI project enabled 32 practitioners to increase their skills, knowledge, and experiences in a variety of QI tools including the Model for Improvement which then supported the delivery of high quality improvement projects and improved outcomes for children and families. Essentially growing the confidence and capability of practitioners to deliver sustainable QI.

27 respective improvement projects were delivered, some leading to service redesign, reduced waiting times, increased uptake of health entitlements, and improved accessibility to front-line health services. 13 improvement projects spread or scaled beyond the initial site and informal QI mentoring took place with peers in respective agencies. Multiple PDSA cycles were conducted testing the most efficient and effective support mechanisms during and post training, maintaining regular contact, and utilising social media to share progress and achievements.
Presentation of neurogenic shock within the emergency department
Authors: Taylor Matthew Pritam , Wrenn Paul , O'Donnell Andrew David
Published: October 2016

Background

Injury to the spinal cord can result in loss of sympathetic innervation causing a drop in BP and HR, this condition is known as neurogenic shock. There is debate among the literature on how and when neurogenic shock presents and what values of HR and BP should be used to define it. Previous studies do not take into account multiple prehospital and emergency department recordings.

Objective

To improve understanding of how neurogenic shock presents in humans, allowing better identification and treatment.

Methods

The Trauma Audit and Research Network database for an adult major trauma centre was used to isolate patients with a spinal cord injury. Qualifying patients had all available BPs and HRs collated into a database. Patients with neurogenic shock were isolated, allowing data analysis.

Results

Out of 3069 trauma patients, 33 met the inclusion criteria, of which 15 experienced neurogenic shock. 87% of the patients who had neurogenic shock experienced it within 2 hours of injury. Neurogenic shock below the T6 level was less common (p=0.009); however, there were still four cases in the cohort. More patients with complete spinal cord injury had neurogenic shock (p=0.039).

Conclusions

Neurogenic shock is variable and unpredictable. It can present in the prehospital environment and without warning in a patient with previously normal vital signs. The medical team should be aware of it in all patients with spinal cord injury regardless of injury level.