bluuebunny/crossref_metadata_2025 huggingface dataset:
Event-Driven Control of a Speed Varying Digital Displacement Machine
Authors: Pedersen Niels H. , Johansen Per , Andersen Torben O.
Published: December 2017

The design and analysis of feedback controllers for digital displacement machines requires a control oriented model. The displacement throughput of a full stroke operated machine is altered on a stroke-by-stroke basis at fixed rotation angles. In the case of a fixed speed operation, it may be treated as a Discrete Linear Time Invariant control problem with synchronous sampling rate. To make synchronous linear control theory applicable for a variable speed digital displacement machine, a method based on event-driven control is presented. Using this method, the time domain differential equations are converted into the spatial (position) domain to obtain a constant sampling rate and thus allowing for use of classical control theory. The method is applied to a down scaled digital fluid power motor, where the motor speed is controlled at varying references under varying pressure and load torque conditions. The controller synthesis is carried out as a discrete optimal deterministic problem with full state feedback. Based on a linear analysis of the feedback control system, stability is proven in a pre-specified operation region. Simulation of a non-linear evaluation model with the controller implemented shows great performance, both with respect to tracking and disturbance rejection.
An Arbitrary Order Adaptive Control Structure With Application to a Hydraulic Winch Drive
Authors: Schmidt Lasse , Andersen Torben O. , Pedersen Henrik C. , Bech Michael M.
Published: December 2017

The dominant physical phenomena in hydraulic drives are generally well known, why the model equations describing the dominant dynamics may be established with a high level of certainty. To some extend, this is also the case for the model parameters when these are based on data sheet information. However, parameters such as the effective bulk modulus, leakage, external disturbances etc. may be difficult to evaluate, and may furthermore be varying. In regard to control design, linear methods may be difficult to apply and stability margins difficult to evaluate, unless dynamic models are established prior to the control design. This problem may be overcome using adaptive controllers, adjusting themselves to uncertainties/variations. This often shifts the problem from adjusting the controller parameters, to adjusting the parameters of the control parameter adaption mechanism, which in many cases involves a significant number of parameters. This paper considers a novel adaptive control algorithm, theoretically applicable to systems of arbitrary orders, and potentially only with three tuning parameters. The proposed algorithm is considered in relation to the position control of a hydraulic winch drive, and results imply that excellent motion tracking performance may be achieved utilizing only state feedback.
Innovative Solution of an Integrated Motor Pump Assembly
Authors: Fiebig Wieslaw , Cependa Piotr , Jedraszczyk Paulina , Kuczwara Hubert
Published: December 2017

In this paper an innovative design solution of a vane pump integrated with an electric motor is presented. In the proposed solution the double vane pump is embedded into the rotor of electric permanent magnets motor (BLDC). CFD simulations of the flow have been carried out to analyze the flow in the pump crossover areas and to avoid the cavitation phenomena at the inlet channel. Results of experimental investigations of the motor pump assembly prototype are presented.
Experimental Validation of a Time Domain Cavitation Model for Switched Inertance Circuits
Authors: Yudell Alexander C. , Van de Ven James D.
Published: December 2017

Switched inertance hydraulic systems are switch mode fluid power circuit topologies that allow the load pressure to be modulated in an efficient manner. A unique feature of these circuits is a long, small diameter, inertance tube, which stores energy in the fluid kinetic domain during a switching cycle. A barrier to application of these circuits is that current models require an elevated reservoir pressure, which is difficult to implement in practice. Research has focused on analyzing inertance tube wave delay effects in the frequency domain, which necessarily excludes non-linear physical phenomena such as cavitation and pressure dependent wave speed. A circuit with an ambient reservoir pressure exposes the fluid in the inertance tube to local pressure conditions where these non-ideal behaviors may have a strong effect on system dynamics. In this paper, a method of characteristics cavitation model with unsteady friction is presented that accurately captures the incidence and severity of cavitation in a long pipeline undergoing cyclic high and low pressure boundary conditions. This model is validated experimentally by examining the pressure response in a 3.95m steel pipeline with an upstream switching valve capable of 0.5ms transition at 120Hz. Experiments are conducted over a range of switching frequencies at 60% duty. The proposed pipeline model can be used to predict conditions leading to cavitation as well as help develop cavitation avoidance strategies, such as soft switching and utilization of line resonance.
Analysis of Leakage Flow Through the Flank Contacts in Transition Zone in Involute External Toothed Gear Pump
Authors: Sahoo Vineet , Roy Debanshu , Maiti Rathindranath
Published: December 2017

The leakage past the tooth flanks of the gears in transition contacts in involute external toothed gear pump is analyzed in details using CFD in Fluent®. Analytical results support the experimentally visualized flow patterns [1]. Extending the approach of an earlier investigation [2] more rigorous analyses are carried out considering actual gear data of a pump and a full cycle of contact. However, the relieve groove and cavitation are not considered. The basic purpose is to establish the flow pattern analyses using CFD in Fluent-Ansys® environment. The beginning and the end of entrapment, squeezing of fluid, pressure build up, separation and generation of gap at the active contact and instantaneous flow through the gap are estimated meticulously.
The Design of Powersplit Transmissions Using New Technologies of Hydrostatic Components
Authors: Göllner Wilhelm , Rahmfeld Robert , Hames Bernd
Published: December 2017

In powersplit systems, which are state-of-the-art in tractor transmissions, the efficiency is of much higher importance than in most other vehicles. Key for high efficiency is to transmit only some power hydrostically and a high amount mechanically (Fig. 1 and 2) because the mechanical path has higher efficiency than the hydrostatic path. The hydrostatic path is needed to get an infinitely variable transmission.

The understanding of powerloss characteristics of hydrostatic components helps to choose between swashplate and bent axis components. Best total efficiencies of 97% are key arguments for using 45° bent axis technology. This is the reason for a dominant use of 45° bent axis in powersplit transmissions.

The search for further reduction in powerloss shows the weak volumetric efficiency at small displacements and high pressure levels. The compression loss is now a dominant subject for improvement. The paper will explain a new design for reduced compression loss, which can be applied to 45° bent axis units. The powerloss reduction will be shown for a powersplit transmission with 2 and 3 modes, which are state of the art today [7].
Design of a Velocity Control System Using an Inlet Metered Pump
Authors: Ali Hasan H. , Fales Roger C. , Manring Noah D.
Published: December 2017

This work introduces a new way to control hydraulic cylinder velocity using an inlet metering pump system to control the hydraulic flow entering the cylinder. The inlet metering system consists of a fixed displacement pump and an inlet metering valve that adjusts the hydraulic fluid flow entering the pump as required. The energy losses associated with flow metering in the system are reduced because the pressure drop across the inlet metering valve can be arbitrarily small. The fluid is supplied to the inlet metering valve at a fixed pressure using a charge pump. A velocity control system is designed using the inlet metering system as means to control the fluid flow to a hydraulic cylinder. In addition to the inlet metering system, the velocity control system designed in this work includes a four-way directional valve to set the fluid flow direction according to the desired direction of the hydraulic cylinder velocity. Open-loop and closed-loop proportional and proportional derivative (P and PD) controllers are designed. Designs with the goals of stability and performance of the system are studied so that a precise and smooth velocity control system for the hydraulic cylinder is achieved. In addition to potentially high efficiency of this system, there is potential for other benefits including low cost, fast response, and less complicated dynamics compared to other systems. The results presented in this work show that the inlet metering velocity control system can be designed so that the system is stable, there is zero overshoot and no oscillation.
CFD Simulation and Experimental Investigation of Steady State Flow Force Reduction in a Hydraulic Spool Valve With Machined Back Angles
Authors: Jackson Randall S. , Belger Matthew M. , Cassaidy Kevin J. , Kokemoor Andrew R.
Published: December 2017

As the force output of an electromagnetic actuator is limited, achieving reliable operation of a direct-acting solenoid valve at high pressures and flow rates can be challenging. The major performance obstacle is the hydrodynamic flow force acting on the spool as it moves between energized and de-energized states. With trends in the fluid power industry requiring valves to operate at higher pressures and volumetric flow rates, while minimizing electrical power consumption, methods to reduce hydrodynamic flow forces become critical in developing functional products.

This paper presents CFD simulation and correlating experimental results in using back angles to reduce the hydrodynamic flow forces in a direct-acting, solenoid operated, cartridge-style, directional control valve. Traditional methods of calculating flow forces are discussed and a brief summary of prior research is presented. A commercially available CFD package, Fluent, was used to numerically estimate the flow forces using a realizable k-ε turbulence closure model. A parametric analysis of flow, pressure, and spool stroke showed sensitivity to the metering edge geometry. A special fixture was created to isolate and directly measure the forces acting on the spool. The addition of a +60° back-angle showed the largest flow force reduction of 36% compared to a spool with no back angle.
Dynamic Modeling of a Linear Electromagnetic Piston Pump
Authors: Hogan Paul H. , Van de Ven James D.
Published: December 2017

Due to recent advances in technologies ranging from hydraulically-assisted prostheses to human-scale robotics, there is a growing need for compact and efficient delivery of hydraulic power. Existing electric driven pumps require conversion from electric to rotational power before generating hydraulic output power. This work presents a dynamic model and experimental results of a linear pump that uses an electromagnetic force applied directly to the piston, resulting in a more direct conversion of electrical to hydraulic power in a compact package at the human power level. The model uses a quasi-steady state magnetic equivalent circuit model for the linear electromagnetic actuator coupled to a numerical time-domain piston pump model. The coupled model calculates the piston trajectory, cylinder pressures, and flowrates as a function of time. The modeled force generation and resulting mechanical dynamics match results generated from finite element analysis within 7%, with a predicted power density of 0.19 W/cc and efficiency of 73% for an unoptomized geometry. A multi-objective genetic algorithm is used to determine the geometry and operating parameters that give maximum power density and maximum efficiency, demonstrating that power densities of 0.7 W/cc and efficiencies of 85% are achievable.
An Approach to Visualize Lifetime Limiting Factors in the Cylinder Block/Valve Plate Gap in Axial Piston Pumps
Authors: Ivantysyn Roman , Shorbagy Ahmed , Weber Jürgen
Published: December 2017

The lifetime of axial piston pumps is depending on the application and it’s overall robustness to external loads, but even in ideal conditions pumps will fail eventually. The analytics to this problem are known to pump manufacturers. Bearing and shaft calculations paired with FEM models are invaluable tools, however the main questions remain with the rotating kit – cylinder block, pistons, and slippers. If properly designed these parts should theoretically outlast the finite lifetime parts, such as roller bearings due to their hydrostatic and hydrodynamic bearings. In reality however failures still occur due to fatigue or other factors such as contamination or wear.

This paper describes an approach for the thermal analysis of the cylinder block / valve plate sealing interface. Using a state of the art test rig the temperature distribution, instantaneous gap height as well as particle wear have been analyzed across the entire operating range of an axial piston pump at the block / valve plate sealing interface. Simulations are done with cooperation of Purdue University by using their developed gap simulation model called Caspar FSTI. These simulations along with the measurements are used to locate potential lifetime reducing operating conditions and analyze them. The first results of the thermal behavior of this interface will be presented in this paper.
A Solution for an Electronically-Controlled Variable Delivery External Gear Pump
Authors: Tankasala Srinath , Vacca Andrea
Published: December 2017

This paper describes an innovative design concept to enable electronic control of the flow delivered by external spur gear pumps. The basic principle used to obtain flow variation relies on a variable timing concept previously demonstrated by the author’s research team. This principle permits to vary the flow within a certain range, without introducing additional sources of power loss. Previous work proved the applicability of the proposed concept in a pressure compensated design of an external gear pump for high pressure applications. This concept took advantage of the pressure differential acting on the “slider”, which is an internal element performing the flow regulation.

In this paper, a solution that permits to achieve balance of the pressure forces acting on the slider is proposed. This solution reduces the actuation forces, thus enabling direct flow control actuation through an electronic control system. The proposed solution is cost effective, it consists of a limited number of parts, and it is suitable for pumps without pressure compensation, i.e. for low or intermediate pressures.

The paper details the aspects of the pump design, which was performed by using a multi-objective algorithm that maximizes the flow operating range and at the same time the pump. The optimum design could achieve a flow variation of about 32% in simulation and this was also demonstrated in actual experiments on a prototype realized at the author’s Research Center.

The proposed design can impact several of the current applications of external gear pumps, introducing the additional “flow on demand” capability.
A Novel Digitalized Hydrostatic Drive Solution for Modern Wind Turbine
Authors: Chen Jincheng , Wang Feng , Stelson Kim A.
Published: December 2017

Gearbox is a concern in modern wind turbines, increasing the maintenance cost and therefore the cost of energy (COE). A hydrostatic transmission (HST) improves the turbine drivetrain reliability by using slightly compressible mineral oil as the working medium rather than a rigid gearbox. An HST eliminates the power converter since it is a continuous variable transmission (CVT), making the turbine simpler and more cost effective. The turbine operates below the rated wind speed for a considerable time in a year, making the variable hydraulic motor run at partial displacement for the most common configuration of a hydrostatic wind turbine, a fixed displacement pump and a variable displacement motor. This results in low drivetrain efficiency. Moreover, large variable displacement motors for megawatt turbine are commercially unavailable. A digitalized hydrostatic drive for a modern wind turbine is proposed to improve the drivetrain efficiency at low wind speeds. The digital coding method for hydrostatic wind turbine is studied. A dynamic simulation model of the digitalized hydrostatic (dHST) wind turbine has been developed in Simulink. A widely used efficiency model for the hydrostatic pump and motors is used in the simulation to make the study practical. The proposed digitalized hydrostatic solution has been compared with a conventional hydrostatic solution. Simulation results show the benefits of digitalized hydrostatic transmission over conventional hydrostatic transmission in drivetrain efficiency, system complexity and cost.
Residual stress measurements in electron beam evaporated yttria doped zirconia films deposited on Si (111) substrates
Authors: Amirtharaj Moses Kamalan Kirubaharan , Parasuraman Kuppusami , Chakravarty Sujay , Rabel Arul Maximus , Selvaraj Anandh Jesuraj , Singh Akash
Published: December 2017

Zirconia thin films with varying yttria concentrations (0, 4, and 10 mol. %) were grown on Si (111) substrates using electron beam physical vapor deposition technique. The residual stress as a function of depth on undoped and yttria doped zirconia films with different phases was determined using the modified sin2ψ technique by varying the x-ray angle of incidence. Surface profilometry was also used as a complementary technique for qualitative measurement of stress in these films. The residual stress profile revealed that tensile residual stress was present in the near-surface region and it decreased rapidly as a function of depth in all three films with different yttria concentration. The possible reasons for the film growth stress and stress gradient in the yttria doped zirconia films with different concentration of yttria are discussed.
Interpolation of the early part of the acoustic transfer functions using block sparse models
Authors: Feng Qipeng , Yang Feiran , Yang Jun
Published: December 2017

Two types of block sparse models are presented to interpolate the early part of the acoustic transfer functions (eATFs) between the loudspeakers and the target spatial regions in reverberant rooms. The desired eATFs are modeled as a superposition of sound fields generated by a dense grid of equivalent point sources, which exhibit two kinds of block sparse structures under the far-field and small target region assumptions. Simulation results in the two-dimensional case demonstrate that the proposed models can provide accurate eATF interpolation over a broad frequency range using a small number of microphones.
Limited Effect of Later-Generation Fluoroquinolones in the Treatment of Ofloxacin-Resistant and Moxifloxacin-Susceptible Multidrug-Resistant Tuberculosis
Authors: Lee Hyun , Ahn Soohyun , Hwang Na Young , Jeon Kyeongman , Kwon O Jung , Huh Hee Jae , Lee Nam Yong , Kim Chang-Ki , Koh Won-Jung
Published: December 2017

Recent data conflict on the clinical efficacy of later-generation fluoroquinolones, such as moxifloxacin or levofloxacin, for the treatment of multidrug-resistant tuberculosis (MDR-TB) that is resistant to ofloxacin but susceptible to moxifloxacin. The purpose of the present study was to evaluate whether later-generation fluoroquinolones can improve treatment outcomes in patients with ofloxacin-resistant, moxifloxacin-susceptible MDR-TB. A retrospective cohort study was performed on 208 patients with moxifloxacin-susceptible MDR-TB who were treated between 2006 and 2011. Later-generation fluoroquinolones were used for all patients. Overall, 171 patients (82%) had ofloxacin-susceptible, moxifloxacin-susceptible MDR-TB (ofloxacin-susceptible group), and 37 (18%) had ofloxacin-resistant, moxifloxacin-susceptible MDR-TB (ofloxacin-resistant group). Compared to the ofloxacin-susceptible group, the ofloxacin-resistant group was more likely to have a history of MDR-TB treatment (
P
< 0.001) and cavitary lesions on chest radiography (
P
< 0.001). In addition, the ofloxacin-resistant group was more likely than the ofloxacin-susceptible group to have resistance to the drugs pyrazinamide (
P
= 0.003), streptomycin (
P
= 0.015), prothionamide (
P
< 0.001), and para-aminosalicylic acid (
P
< 0.001). Favorable outcomes were more frequently achieved for the ofloxacin-susceptible group than for the ofloxacin-resistant group (91% [156/171] versus 57% [21/37], respectively [
P
< 0.001]). In multivariable regression logistic analysis, the ofloxacin-susceptible group was about 5.36 (95% confidence interval, 1.55 to 18.53) times more likely than the ofloxacin-resistant group (
P
< 0.001) to have favorable outcomes. Despite
in vitro
moxifloxacin susceptibility, the frequency of favorable treatment outcomes for ofloxacin-resistant MDR-TB was significantly lower than that for ofloxacin-susceptible MDR-TB, even when later-generation fluoroquinolones were used, indicating that more-aggressive therapies may be needed for ofloxacin-resistant MDR-TB.
Intermittent Antibiotic Therapy for Recurrent Nodular Bronchiectatic Mycobacterium avium Complex Lung Disease
Authors: Jhun Byung Woo , Moon Seong Mi , Kim Su-Young , Park Hye Yun , Jeon Kyeongman , Kwon O Jung , Huh Hee Jae , Ki Chang-Seok , Lee Nam Yong , Chung Myung Jin , Lee Kyung Soo , Shin Sung Jae , Daley Charles L. , Koh Won-Jung
Published: December 2017

Intermittent, three-times-weekly oral antibiotic therapy is recommended for the initial treatment of noncavitary nodular bronchiectatic (NB)
Mycobacterium avium
complex (MAC) lung disease. However, intermittent therapy is not recommended for patients who have been previously treated. We evaluated 53 patients with recurrent noncavitary NB MAC lung disease who underwent antibiotic treatment for ≥12 months with daily therapy (
n
= 26) or intermittent therapy (
n
= 27) between January 2008 and December 2015. Baseline characteristics were comparable between daily therapy and intermittent therapy groups. Sputum culture conversion rates did not differ between daily therapy (21/26, 81%) and intermittent therapy (22/27, 82%) groups. Compared to the etiologic organism at the time of previous treatment, recurrent MAC lung disease was caused by the same MAC species in 38 patients (72%) and by a different MAC species in 15 patients (28%). Genotype analysis in patients with sequenced paired isolates revealed that 86% (12/14) of cases with same species recurrence were due to reinfection with a new MAC genotype. In conclusion, most recurrent noncavitary NB MAC lung disease cases were caused by reinfection rather than relapse. Intermittent antibiotic therapy is a reasonable treatment strategy for recurrent noncavitary NB MAC lung disease.
Evaluation of Activity and Emergence of Resistance of Polymyxin B and ZTI-01 (Fosfomycin for Injection) against KPC-Producing Klebsiella pneumoniae
Authors: Diep John K. , Sharma Rajnikant , Ellis-Grosse Evelyn J. , Abboud Cely S. , Rao Gauri G.
Published: December 2017

ZTI-01 (fosfomycin for injection) is a broad-spectrum antibiotic with a novel mechanism of action and is currently under development in the United States for treatment of complicated urinary tract infections. Globally, fosfomycin and polymyxin B are increasingly being used to treat multidrug-resistant Gram-negative infections. The objectives were to evaluate the pharmacodynamic activity of polymyxin B and fosfomycin alone and in combination against KPC-producing
Klebsiella pneumoniae
and to assess the rate and extent of emergence of resistance to different antibiotic regimens. Two clinical isolates, BRKP26 (MIC of polymyxin B[MIC
PMB
], 0.5 mg/liter; MIC of fosfomycin [MIC
FOF
], 32 mg/liter) and BRKP67 (MIC
PMB
, 8 mg/liter; MIC
FOF
, 32 mg/liter) at an initial inoculum of 10
7
CFU/ml, were evaluated over 168 h in a hollow-fiber infection model simulating clinically relevant polymyxin B (2.5-mg/kg loading dose as a 2 h-infusion followed by 1.5-mg/kg dose every 12 h [q12h] as a 1-h infusion) and fosfomycin (6 g q6h as a 1-h or 3-h infusion) regimens alone and in combination. Population analysis profiles (PAPs) and MIC testing were performed to assess emergence of resistance. Polymyxin B or fosfomycin monotherapy was ineffective and selected for resistance by 24 h. Polymyxin B plus a fosfomycin 1-h infusion demonstrated sustained bactericidal activity by 4 h, with undetectable colony counts beyond 144 h. Polymyxin B plus a fosfomycin 3-h infusion demonstrated bactericidal activity at 4 h, followed by regrowth similar to that of the control by 144 h. PAPs revealed resistant subpopulations by 120 h. The combination of polymyxin B and a fosfomycin 1-h infusion is a promising treatment option for KPC-producing
K. pneumoniae
and suppresses the emergence of resistance. Further evaluation of novel dosing strategies is warranted to optimize therapy.
In Vitro
and
In Vivo
Studies of the Trypanocidal Effect of Novel Quinolines
Authors: Nefertiti A. S. G. , Batista M. M. , Da Silva P. B. , Batista D. G. J. , Da Silva C. F. , Peres R. B. , Torres-Santos E. C. , Cunha-Junior E. F. , Holt E. , Boykin D. W. , Brun R. , Wenzler T. , Soeiro M. N. C.
Published: December 2017

Therapies for human African trypanosomiasis and Chagas disease, caused by
Trypanosoma brucei
and
Trypanosoma cruzi
, respectively, are limited, providing minimal therapeutic options for the millions of individuals living in very poor communities. Here the effects of 10 novel quinolines are evaluated
in silico
and by phenotypic studies using
in vitro
and
in vivo
models. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties revealed that most molecules did not infringe on Lipinski's rules, which is a prediction of good oral absorption. These quinolines showed high probabilities of Caco2 permeability and human intestinal absorption and low probabilities of mutagenicity and of hERG1 inhibition.
In vitro
screens against bloodstream forms of
T. cruzi
demonstrated that all quinolines were more active than the reference drug (benznidazole [Bz]), except for DB2171 and DB2192, with five (DB2187, DB2131, DB2186, DB2191, and DB2217) displaying 50% effective concentrations (EC
50
s) of <3 μM (4-fold lower than that of Bz). Nine quinolines were more effective than Bz (2.7 μM) against amastigotes, showing EC
50
s ranging from 0.6 to 0.1 μM. All quinolines were also highly active
in vitro
against African trypanosomes, showing EC
50
s of ≤0.25 μM. The most potent and highly selective candidates for each parasite species were tested in
in vivo
models. Results for DB2186 were promising in mice with
T. cruzi
and
T. brucei
infections, reaching a 70% reduction of the parasitemia load for
T. cruzi
, and it cured 2 out of 4 mice infected with
T. brucei
. DB2217 was also active
in vivo
and cured all 4 mice (100% cure rate) with
T. brucei
infection.
Pharmacodynamics of a Long-Acting Echinocandin, CD101, in a Neutropenic Invasive-Candidiasis Murine Model Using an Extended-Interval Dosing Design
Authors: Lepak Alexander J. , Zhao Miao , VanScoy Brian , Ambrose Paul G. , Andes David R.
Published: December 2017

Echinocandins are important in the prevention and treatment of invasive candidiasis but limited by current dosing regimens that include daily intravenous administration. The novel echinocandin CD101 has a prolonged half-life of approximately 130 h in humans, making it possible to design once-weekly dosing strategies. The present study examined the pharmacodynamic activity of CD101 using the neutropenic invasive candidiasis mouse model against select
Candida albicans
(
n
= 4),
C. glabrata
(
n
= 3), and
C. parapsilosis
(
n
= 3) strains. The CD101 MIC ranged from 0.03 to 1 mg/liter. Plasma pharmacokinetic measurements were performed using uninfected mice after intraperitoneal administration of 1, 4, 16, and 64 mg/kg. The elimination half-life was prolonged at 28 to 41 h. Neutropenic mice were infected with each strain by lateral tail vein injection, treated with a single dose of CD101, and monitored for 7 days, at which time the organism burden was enumerated from the kidneys. Dose-dependent activity was observed for each organism. The pharmacokinetic/pharmacodynamic (PK/PD) index of the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC index) correlated well with efficacy (
R
2
, 0.74 to 0.93). The median stasis 24-h free-drug AUC/MIC targets were as follows: for
C. albicans
, 2.92; for
C. glabrata
, 0.07; and for
C. parapsilosis
, 2.61. The PK/PD targets for 1-log
10
kill endpoint were 2- to 4-fold higher. Interestingly, the aforementioned PK/PD targets of CD101 were numerically lower for all three species than those of other echinocandins. In summary, CD101 is a promising, novel echinocandin with advantageous pharmacokinetic properties and potent
in vivo
pharmacodynamic activity.
Distribution and Molecular Characterization of Acinetobacter baumannii International Clone II Lineage in Japan
Authors: Matsui Mari , Suzuki Masato , Suzuki Masahiro , Yatsuyanagi Jun , Watahiki Masanori , Hiraki Yoichi , Kawano Fumio , Tsutsui Atsuko , Shibayama Keigo , Suzuki Satowa
Published: December 2017

Multidrug-resistant (MDR)
Acinetobacter
spp. have been globally disseminated in association with the successful clonal lineage
Acinetobacter baumannii
international clone II (IC II). Because the prevalence of MDR
Acinetobacter
spp. in Japan remains very low, we characterized all
Acinetobacter
spp. (
n
= 866) from 76 hospitals between October 2012 and March 2013 to describe the entire molecular epidemiology of
Acinetobacter
spp. The most prevalent species was
A. baumannii
(
n
= 645; 74.5%), with
A. baumannii
IC II (
n
= 245) accounting for 28.3% of the total. Meropenem-resistant isolates accounted for 2.0% (
n
= 17) and carried IS
Aba1-bla
OXA-23-like
(
n
= 10),
bla
IMP
(
n
= 4), or IS
Aba1-bla
OXA-51-like
(
n
= 3). Multilocus sequence typing of 110 representative
A. baumannii
isolates revealed the considerable prevalence of domestic sequence types (STs).
A. baumannii
IC II isolates were divided into the domestic sequence type 469 (ST469) (
n
= 18) and the globally disseminated STs ST208 (
n
= 14) and ST219 (
n
= 4). ST469 isolates were susceptible to more antimicrobial agents, while ST208 and ST219 overproduced the intrinsic AmpC β-lactamase.
A. baumannii
IC II and some
A. baumannii
non-IC II STs (e.g., ST149 and ST246) were associated with fluoroquinolone resistance. This study revealed that carbapenem-susceptible
A. baumannii
IC II was moderately disseminated in Japan. The low prevalence of acquired carbapenemase genes and presence of domestic STs could contribute to the low prevalence of MDR
A. baumannii
. A similar epidemiology might have appeared before the global dissemination of MDR epidemic lineages. In addition, fluoroquinolone resistance associated with
A. baumannii
IC II may provide insight into the significance of
A. baumannii
epidemic clones.
Bordetella pertussis Adenylate Cyclase Toxin Disrupts Functional Integrity of Bronchial Epithelial Layers
Authors: Hasan Shakir , Kulkarni Nikhil Nitin , Asbjarnarson Arni , Linhartova Irena , Osicka Radim , Sebo Peter , Gudmundsson Gudmundur H.
Published: December 2017

The airway epithelium restricts the penetration of inhaled pathogens into the underlying tissue and plays a crucial role in the innate immune defense against respiratory infections. The whooping cough agent,Bordetella pertussis, adheres to ciliated cells of the human airway epithelium and subverts its defense functions through the action of secreted toxins and other virulence factors. We examined the impact ofB. pertussisinfection and of adenylate cyclase toxin-hemolysin (CyaA) action on the functional integrity of human bronchial epithelial cells cultured at the air-liquid interface (ALI).B. pertussisadhesion to the apical surface of polarized pseudostratified VA10 cell layers provoked a disruption of tight junctions and caused a drop in transepithelial electrical resistance (TEER). The reduction of TEER depended on the capacity of the secreted CyaA toxin to elicit cAMP signaling in epithelial cells through its adenylyl cyclase enzyme activity. Both purified CyaA and cAMP-signaling drugs triggered a decrease in the TEER of VA10 cell layers. Toxin-produced cAMP signaling caused actin cytoskeleton rearrangement and induced mucin 5AC production and interleukin-6 (IL-6) secretion, while it inhibited the IL-17A-induced secretion of the IL-8 chemokine and of the antimicrobial peptide beta-defensin 2. These results indicate that CyaA toxin activity compromises the barrier and innate immune functions ofBordetella-infected airway epithelia.
Takeaway meal consumption and risk markers for coronary heart disease, type 2 diabetes and obesity in children aged 9–10 years: a cross-sectional study
Authors: Donin Angela S , Nightingale Claire M , Owen Chris G , Rudnicka Alicja R , Cook Derek G , Whincup Peter H
Published: December 2017

Objective

To investigate associations between takeaway meal consumption and risk markers for coronary heart disease, type 2 diabetes and obesity risk markers in children.

Design

A cross-sectional, school-based observational study.

Setting

85 primary schools across London, Birmingham and Leicester.

Participants

1948 UK primary school children in year 5, aged 9–10 years.

Main outcome measures

Children reported their frequency of takeaway meal consumption, completed a 24-hour dietary recall, had physical measurements and provided a fasting blood sample.

Results

Among 1948 participants with complete data, 499 (26%) never/hardly ever consumed a takeaway meal, 894 (46%) did so <1/week and 555 (28%) did ≥1/week. In models adjusted for age, sex, month, school, ethnicity and socioeconomic status, more frequent takeaway meal consumption was associated with higher dietary intakes of energy, fat % energy and saturated fat % energy and higher energy density (all P trend <0.001) and lower starch, protein and micronutrient intakes (all P trend <0.05). A higher frequency of takeaway meal consumption was associated with higher serum total cholesterol and low-density lipoprotein (LDL) cholesterol (P trend=0.04, 0.01, respectively); children eating a takeaway meal ≥1/week had total cholesterol and LDL cholesterol 0.09 mmol/L (95% CI 0.01 to 0.18) and 0.10 mmol/L (95% CI 0.02 to 0.18) higher respectively than children never/hardly ever eating a takeaway meal; their fat mass index was also higher.

Conclusions

More frequent takeaway meal consumption in children was associated with unhealthy dietary nutrient intake patterns and potentially with adverse longer term consequences for obesity and coronary heart disease risk.
Effectiveness of preoperative medical consultations by internal medicine physicians: a systematic review
Authors: Pham Clarabelle T , Gibb Catherine L , Fitridge Robert A , Karnon Jonathan D
Published: December 2017

Objective

Clinics have been established to provide preoperative medical consultations, and enable the anaesthetist and surgeon to deliver the best surgical outcome for patients. However, there is uncertainty regarding the effect of such clinics on surgical, in-hospital and long-term outcomes. A systematic review of the literature was conducted to determine the effectiveness of preoperative medical consultations by internal medicine physicians for patients listed for elective surgery.

Design

Systematic searches of MEDLINE, EMBASE, CINAHL, PubMed, Current Contents and the NHS Centre for Reviews and Dissemination were conducted up to 30 April 2017.

Setting

Elective surgery.

Study selection

Randomised controlled trials and non-randomised comparative studies conducted in adults.

Outcome measures

Length of hospital stay, perioperative morbidity and mortality, costs and quality of life.

Results

The one randomised trial reported that preadmission preoperative assessment was more effective than the option of an inpatient medical assessment in reducing the frequency of unnecessary admissions with significantly fewer surgical cancellations following admission for surgery. A small reduction in length of stay in patients was also observed. The three non-randomised studies reported increased lengths of stay, costs and postoperative complications in patients who received preoperative assessment. The timing and delivery of the preoperative medical consultation in the intervention group differed across the included studies.

Conclusion

Further research is required to inform the design and implementation of coordinated involvement of physicians and surgeons in the provision of care for high-risk surgical patients. A standardised approach to perioperative decision-making processes should be developed with a clear protocol or guideline for the assessment and management of surgical patients.
The short-term health and economic burden of gestational diabetes mellitus in China: a modelling study
Authors: Xu Tingting , Dainelli Livia , Yu Kai , Ma Liangkun , Silva Zolezzi Irma , Detzel Patrick , Fang Hai
Published: December 2017

Objectives

Gestational diabetes mellitus (GDM) is associated with a higher risk for adverse health outcomes during pregnancy and delivery for both mothers and babies. This study aims to assess the short-term health and economic burden of GDM in China in 2015.

Design

Using TreeAge Pro, an analytical decision model was built to estimate the incremental costs and quality-of-life loss due to GDM, in comparison with pregnancy without GDM from the 28th gestational week until and including childbirth. The model was populated with probabilities and costs based on current literature, clinical guidelines, price lists and expert interviews. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results.

Participants

Chinese population who gave birth in 2015.

Results

On average, the cost of a pregnancy with GDM was ¥6677.37 (in 2015 international $1929.87) more (+95%) than a pregnancy without GDM, due to additional expenses during both the pregnancy and delivery: ¥4421.49 for GDM diagnosis and treatment, ¥1340.94 (+26%) for the mother’s complications and ¥914.94 (+52%) for neonatal complications. In China, 16.5 million babies were born in 2015. Given a GDM prevalence of 17.5%, the number of pregnancies affected by GDM was estimated at 2.90 million in 2015. Therefore, the annual societal economic burden of GDM was estimated to be ¥19.36 billion (international $5.59 billion). Sensitivity analyses were used to confirm the robustness of the results. Incremental health losses were estimated to be approximately 260 000 quality-adjusted life years.

Conclusion

In China, the GDM economic burden is significant, even in the short-term perspective and deserves more attention and awareness. Our findings indicate a clear need to implement GDM prevention and treatment strategies at a national level in order to reduce the economic and health burden at both the population and individual levels.
Ultimate capacity of barrier–deck anchorage in MTQ TL-5 barrier reinforced with headed-end, high-modulus, sand-coated GFRP bars
Authors: Rostami Michael , Sennah Khaled , Afefy Hamdy M.
Published: December 2017

This paper presents an experimental program to justify the barrier design at the barrier–deck junction when compared to the factored applied transverse vehicular loading specified in the Canadian Highway Bridge Design Code (CHBDC). Compared to the dimensioning and the glass fibre reinforced polymer (GFRP) bar detailing of a recently crash-tested GFRP-reinforced barrier, the adopted barrier configurations in this paper were similar to those specified by Ministry of Transportation of Québec (MTQ) for TL-5 barrier except that the base of the barrier was 40 mm narrower and the deck slab is of 200 mm thickness, leading to reduction in the GFRP embedment depth into the deck slab. Four full-scale TL-5 barrier specimens were tested to collapse. Correlation between the experimental findings and the factored applied moments from CHBDC equivalent vehicle impact forces resulting from the finite-element modelling of the barrier–deck system was conducted followed by recommendations for use of the proposed design in highway bridges in Québec.
Shear deformable hybrid finite element formulation for buckling analysis of composite columns
Authors: Niki Vida , Erkmen R. Emre
Published: December 2017

The objective of this study is to develop a shear deformable hybrid finite element formulation for the flexural buckling analysis of fiber-reinforced laminate composite columns with doubly symmetric cross sections. The hybrid finite element formulation is developed by using the Hellinger-Reissner functional which is obtained by introducing the conditions of compatibility as auxiliary conditions to the potential energy functional. The shear deformation effects due to bending are included by equilibrating shear stress. In comparison to the displacement-based formulations the current hybrid formulation has the advantage of incorporating the shear deformation effects easily by using the strain energy of the shear stress field without modifying the basic kinematic assumptions of the beam theory. The agreement with Engesser formulation for flexural buckling analysis of columns with shear-weak cross sections shows the applicability and accuracy of the current hybrid finite element method for composite structural elements. The applicability of the developed method herein to sandwich and built-up columns are also illustrated.
EFFECT OF HIGH DOSES OF AMYTAL ON SKELETAL MUSCLE
Authors: Riedel Bernard E. , Huston Mervyn J.
Published: December 2017

Sodium amytal, 350 mgm. per kgm., injected intraperitoneally into rats caused a marked depression in the response of normal and denervated striated muscle to electrical stimulus. It is believed that the effect is due primarily to a direct action on the muscle. Sodium amytal and curare have a synergistic effect in depression of muscle fibers.
THE INFLUENCE OF ORAL ASCORBIC ACID ADMINISTRATION ON THE ADRENAL CORTICAL RESPONSE TO ACTH
Authors: Skelton F. R. , Fortier C.
Published: December 2017

The effect of orally administered ascorbic acid (as sodium ascorbate) on the adrenal cortical response to ACTH was studied in the hypophysectomized male rat. Plasma and adrenal ascorbic acid and adrenal cholesterol levels were determined three and six hours after ACTH injection. The depletion of adrenal ascorbic acid following such treatment was partially inhibited by the adminis tration of sodium ascorbate while the decrease in cholesterol was unaffected. These results suggest that the uptake of ascorbic acid from the increased quantity available in the plasma was sufficient to partially overcome the depleting effect of ACTH.
STUDIES ON THE RELATIONSHIP BETWEEN VIRUS AND HOST CELL
Authors: Lesley S. M. , French R. C. , Graham A. F. , van Rooyen C. E.
Published: December 2017

Infection of E. coli with P32 labelled T2r+ bacteriophage resulted in the con version of a part of the isotope to a form soluble in 5% trichloroacetic acid. This acid soluble phosphorus was used as a measure of the breakdown of the virus. When the phage to cell ratio was less than unity a two step breakdown curve was obtained corresponding to the two cycles of infection in this type of experi ment. The heights of the steps represented 5 and 32% breakdown, the second rise commencing after about 25 min. Multiple infection of cells yielded a curve which rose without inflection to about 23% breakdown at 20 min. after which there was little further increase. When the addition of radioactive phage was preceded by sufficient nonradioactive phage to infect most of the cells in the culture, the amount of breakdown of labelled virus increased to about 55% within 20 min. at which time breakdown practically ceased. Control experi ments indicated that dead phage in the labelled preparations contributed little to the acid soluble P32 fraction in these experiments and that the breakdown resulted from infection of the cells by virus. It is suggested that infection of cells by phage stimulates some mechanism whereby phage adsorbed to the cell at a later time is broken down extensively at the cell surface. The experimental results are interpreted in the light of this concept.
STUDIES ON THE RELATIONSHIP BETWEEN VIRUS AND HOST CELL
Authors: French R. C. , Lesley S. M. , Graham A. F. , van Rooyen C. E.
Published: December 2017

Infection of E. coli with T2r, T4r+, T4r, T5, T6r+, or T6r phages induces the formation of a mechanism which extensively degrades P32 labelled T2r+ phage adsorbed to the cell shortly afterwards, about 50% of the P32 being converted to a form soluble in 5% trichloroacetic acid. Each of the above viruses is as effi cient in this respect as a preliminary infection with T2r+ phage itself. Previous infection of the cells with Tl, T3, or T7 phages does not stimulate this mechanism to break down labelled T2r+ virus. When Tl, T3, or T7 phage, then T2r+ phage, and finally P32 labelled T2r+ phage were added to cells, with an interval of several minutes between each addition, the results indicated that adsorption of T2r+ to the cell was not sufficient per se to stimulate the breakdown of labelled phage. Apparently actual infection of the cell by T2r+ virus was required before the breakdown mechanism was induced.
PLASMA ASCORBIC ACID AND PITUITARY-ADRENAL ACTIVITY
Authors: Skelton F. R. , Fortier C.
Published: December 2017

In a study of the relationship of ascorbic acid metabolism to pituitaryadrenal function in the rat, the effect of stress, adrenalectomy, hypophysectomy, and administration of an adrenal cortical extract on the plasma ascorbic acid concentration was determined. Surgical trauma and cold elicited a triphasic, and scalding a biphasic, response in both intact and adrenalectomized animals. The plasma ascorbic acid concentration decreased after adrenalectomy and hypophysectomy but returned to normal or above normal level following the administration of an adrenal cortical extract. It is suggested that the pituitary–adrenal system plays a facilitating role in the increased synthesis of ascorbic acid elicited by stress.
SOME THEORETICAL ASPECTS OF RADIOAUTOGRAPHY
Authors: Nadler N. J.
Published: December 2017

The purpose of radioautography (also called autoradiography or autography) is to identify the presence of radio-elements within microscopic structures by the action of the emitted radiations on photographic emulsions. Since the quality of the photographic image depends on its resolution and density, a theoretical study of these two characteristics was made. For resolution studies, a theory based on an inverse square law relationship for β-ray intensity is expanded to include various geometric shapes of radioactive sources encountered in microscopical preparations. The formulae provide a means to calculate the resultant distri bution of photographic blackening (density), from which it is possible to deter mine how the resolving power is influenced by the geometrical relations between the tissue preparation and photographic emulsion. For density studies, a theory is presented whereby it has been possible to arrive at the average number of impacts of given β-particles required to render a medium contrast emulsion grain developable. The basis of the theory rests on calculating the mean energy dissipated by a β-particle in traversing a silver bromide grain, and determining from this the number of reduced silver atoms deposited per grain. Realizing the average number of silver atoms necessary to render a grain developable, the required number of impacts by a β-particle may then be calculated. An example is given in which j8-particles of a mean energy equal to that given off by radioiodine are made to react with the so-called medium contrast emulsion.