bluuebunny/crossref_metadata_2025 huggingface dataset:
Mixed Electroosmotic Pressure Driven Flow and Heat Transfer of Power Law Fluid in a Hydrophobic Microchannel
Authors: Haque Ainul , Nayak Ameeya Kumar
Published: October 2017

In this paper, a mathematical model has been developed to analyze the combined electroosmotic and pressure driven flow of power law fluids in a micro channel in the presence of Joule heating effects. The effects of Navier slip boundary condition and thermal radiation is examined for effective heat transfer in a hydrophobic microchannel. The analytical treatment has been performed for fluid flow and heat transfer effects in terms of flow governing parameters. This study highlights the effect of channel height to the electric double layer thickness and observed the flow variation due to heat transfer effect with the available scientific data. For a pure EOF, velocity slip have more significant role to get a maximum flow rate as expected. For both pseudo-plastic and dilatent fluids Nusselt number is decreased with the increment of the hydrophobic parameter and dimensionless pressure gradient where as increment in Joule heating effect enhance the heat transfer rate.
Instantaneous Turbulent Structure Relating to Momentum and Scalar Transport in a Reducing Channel Flow With Surfactant Additives
Authors: Matsumoto Takuya , Hara Shumpei , Tsukahara Takahiro , Kawaguchi Yasuo
Published: October 2017

Turbulent surfactant solution flows dramatically suppress turbulent scalar and momentum transports with changes to turbulent structures near the wall. In this study, particle image velocimetry and planar laser induced fluorescence concentration measurement method were used simultaneously to analyze turbulent mass transfer experimentally in surfactant channel flows at high Reynolds number. When compared against the instantaneous flow fields of the water case, the results showed a decrease in the magnitude of elementary vortices in the near-wall region. Momentum and scalar transports are caused by the combination of elementary vortices that are irregularly arranged at the outer edge of the shear layer. A conceptual vortex model is proposed for turbulent scalar transfer that provides a partial explanation for the turbulence statistics of a surfactant solution flow, such as the Reynolds shear stress, turbulent mass flux, and mean concentration distribution.
The Effect of Temperature on Water Cavitation Phenomena in Converging-Diverging Nozzle Flow
Authors: Ahmed Zayed , Beck B. Terry , Hosni Mohammad H.
Published: October 2017

A vapor-compression refrigeration cycle typically uses standard refrigerants as the working fluid. Traditional refrigerants, however, have been associated with Ozone level Depletion Potential (ODP) and significant Global Warming Potential (GWP). An innovative cooling technology has been investigated using sonic multi-phase flow in a critical-flow nozzle to create a low-pressure and low-temperature region for heat absorption. The strength of the new technology is its potential to produce cooling using water and/or other working fluids with low ODP and GWP. While the full potential for using water as the working fluid may not be fully-realized, because of property limitations still under investigation, water still provides a very useful media for investigating the underlying cavitation phenomena for the development of the new technology.

As part of ongoing research into the potential cooling capacity of the cavitation phenomena, cavitation in a converging-diverging nozzle is being investigated using water as the working fluid. Cavitation in a fluid is the formation of the vapor phase from the liquid phase by reduction in the pressure of the fluid below its saturated vapor pressure. Due to the constricting nature of the throat of a converging-diverging nozzle, the liquid water velocity at the throat is increased and the local absolute pressure can drop to values below the saturated vapor pressure of water at a given temperature; thus, causing the fluid to cavitate.

The effect of water temperature on both the onset of the cavitation within the nozzle, and the resulting length of the cavitation region within the nozzle, are the subject of the current paper. Flow Visualization using a high speed digital camera under these different operating conditions was aimed at investigating the region of cavitation onset, which also appears to be associated with the region of boundary layer separation just downstream of the throat of the nozzle. The length of the two phase region at different operating temperatures was measured and it was observed that as the temperature of the fluid was increased, the length of two-phase region before it condensed into single-phase liquid became longer. Experimental results and analysis are presented which also show that near the onset of cavitation, the flowrate can likely go well beyond a choking condition without cavitating, and can remain in this metastable state for an extended amount of time before nucleating (cavitating) into a stable state. In particular, analysis indicates that significantly negative absolute pressures can likely be achieved within the nozzle, suggesting the presence of tension in the liquid phase just prior to cavitation.
Design of a Controllable One-Meter Scale Research Wind Turbine
Authors: Cole Samuel , Hess Gavin , Wosnik Martin
Published: October 2017

A research wind turbine of one meter diameter was designed for the UNH Flow Physics Facility (FPF), a very large flow physics quality turbulent boundary layer wind tunnel (W 6m, H 2.7m, L 72m), which provides excellent spatial and temporal resolution, low flow blockage and allows measurements of turbine wakes far downstream due its long fetch.

The initial turbine design was carried out as an aero-servo model of the NREL 5MW reference turbine, with subsequent modifications to both the hub to accommodate blade mounting and pitch-adjustment, and increases in model blade chord to achieve sufficiently high Reynolds numbers. A trade-off study of turbine design parameters in scale space was conducted.

Several candidate airfoil profiles were evaluated numerically with the goal to reach Reynolds-number independence in turbine performance in the target operating range. The model turbine will achieve Reynolds numbers based on blade chord, an important consideration for airfoil performance and near-wake evolution, greater than 100,000, and Reynolds numbers based on turbine diameter, important for far-wake transport, on the order of 1,000,000. The blockage ratio is less than 5% based on swept area.

A motor and controller combination was implemented that allows to precisely prescribe the turbine tip-speed ratio (at maximum power coefficient for optimum blade chord), which can remain stable and absorb the generated electric power for long periods of time. The turbine nacelle was designed with a blade mounting mechanism which allows for precise manual adjustment of blade pitch angle, while allowing for future implementation of actuated pitch control.

The O(1m) turbine scale is viewed as a cost-effective compromise between size, driven by the need for sufficiently high Reynolds number, and the need for detailed measurements for significant distances downstream of the turbine under controlled conditions.
Interaction of a Shock Wave With a Dense Corrugated Particle Curtain
Authors: Rollin Bertrand , Desenlis Marie
Published: October 2017

A numerical experiment studying the gas-particle variant of the Richtmyer-Meshkov instability is presented. Using an Eulerian-Lagrangian approach, namely point particle simulations, we track trajectories of computational particles composing an initially corrugated particle curtain, after the curtain’s interaction with a shock wave. We solve the compressible multiphase Euler equations in a two-dimensional planar geometry and use state-of-the-art particle force models, including unsteady forces, for the gas-particle coupling. However, additional complexities associated with compaction of the curtain of particles to random close packing limit and beyond are avoided by limiting the simulations to relatively modest initial volume fraction of particles. At a fixed Mach number, we explore the effects of the initial perturbation amplitude, initial particle volume fraction and initial shape on the dispersal of the particle curtain. For this shock strength, our simulations suggests that the amplitude of the initial perturbation does not play a significant role in the late time particle dispersal, contrary to the volume fraction. Higher initial particle volume fraction tend to faster particles dispersal. Finally, higher frequency initial perturbations seem to be absorbed by lower frequency initial perturbations.
Computational Study of High Temperature Liquid Metal Infusion
Authors: Schiaffino Arturo , Chattopadhyay Ashesh , Hossain Shaikh Tanveer , Kumar Vinod , Kotteda V. M. K. , Bronson Arturo
Published: October 2017

Liquid metal infiltration, or liquid method infusion, consists of impregnating porous media composed of woven, ceramic particles, or fibers with a molten metal matrix, which fills the pores and occupies the void space within. Understanding the infiltration process is crucial to optimize the properties of the recently formed material and avoid or minimize the formation of fabrication defects. Given the fact that the flow of molten metal differs from organic flows, since molten metal possess a higher interface energy than organic flows, and modifies the wetting dynamics of the molten metal over surfaces, creating a flow driven by capillary and viscous forces. In addition, flow through porous media presents an extraordinary challenge to simulate efficiently, due to the presence of multiple scales far apart participating in the governing dynamics. For this reason, an in-house pore network simulator (EXPNS) was used. EXPNS was designed on a next generation computing framework using Sandia National Lab’s Trilinos and Kokkos library to perform high-resolution computing to generate data for the infiltration model and improve the general understanding of this process.
Aeromechanical Analysis of Two-Bladed Downwind Turbine Using a Nacelle Tilt Control
Authors: Zhao Qiuying , Sheng Chunhua , Al-Khalifin Yousuf , Afjeh Abdollah
Published: October 2017

The structural dynamics and response of a two-bladed downwind wind turbine using a new nacelle tilt control are numerically investigated based on a coupled Computational Fluid Dynamics and Computational Structural Dynamics analysis. The new wind turbine tilt control method is investigated to regulate the power output under a varying wind speed environment for offshore wind turbines. The high fidelity aerodynamic loads obtained from CFD computations are used as input in a CSD code to perform a structural dynamics analysis in order to predict the system response and structural deformation of the two-bladed downwind turbine. The coupled CFD and CSD analysis provide high fidelity assessments of the aeromechanical performance with increased accuracy to evaluate the new nacelle tilt control concept, which may lead to an alternative wind turbine control strategy with reduced costs for offshore wind turbine operations.
Computational Aerodynamic Analysis of Downwind Turbine Using a New Tilt Control Concept
Authors: Zhao Qiuying , Sheng Chunhua
Published: October 2017

Aerodynamic performance of a two-bladed downwind turbine using a new nacelle tilt control concept is numerically investigated based on a Computational Fluid Dynamics analysis. High fidelity, unsteady full Navier-Stoke viscous flow simulations are performed for wind turbines at different nacelle tilt angles to investigate the mean and unsteady aerodynamic loads under two operating conditions: (1) a power-unregulated mode at a rated wind speed of 11.4 m/s, and (2) a power-regulated mode at a rated power of 5 MW. The rotor power, blade and tower bending moments are among the key parameters to evaluate the effect of this new wind turbine control method. A dynamic moving grid method is used to simulate the relative motion and unsteady interaction between the rotor and the tower. Computational results indicate favorable mean bending moments obtained on the turbine blades and tower. However, increased unsteady loadings are experienced by wind turbines at high nacelle tilt angles. The current investigation provides quantitative assessments of the aerodynamic loads and performance of downwind turbines, as well as insight into reducing the costs of offshore horizontal axis wind turbines using an alternative power control method.
Effect of vocal fold stiffness on voice production in a three-dimensional body-cover phonation model
Authors: Zhang Zhaoyan
Published: October 2017

Although stiffness conditions in the multi-layered vocal folds are generally considered to have a large impact on voice production, their specific role in controlling vocal fold vibration and voice acoustics is unclear. Using a three-dimensional body-cover continuum model of phonation, this study shows that changes in vocal fold stiffness have a large effect on F0 and the means and amplitudes of the glottal area and flow rate. However, varying vocal fold stiffness, particularly along the anterior−posterior direction, has a much smaller effect on the closed quotient, vertical phase difference, and the spectral shape of the output acoustics, which are more effectively controlled by changes in the vertical thickness of the medial surface. These results suggest that although changes in vocal fold stiffness are often correlated with production of different voice types, there is no direct cause−effect relation between vocal fold stiffness and voice types, and the correlation may simply result from the fact that both vocal fold stiffness and geometry are regulated by the same set of laryngeal muscles. These results also suggest the possibility of developing reduced-order models of phonation in which the vocal fold is simplified to a one-layer structure.
The Effect of Functional Movement Training After Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial
Authors: Chao Wei-Cheng , Shih Jui-Chi , Chen Kuan-Chung , Wu Ching-Lin , Wu Nai-Yuan , Lo Chien-Sheng
Published: October 2017

Objectives:To evaluate the effect of functional movement screen (FMS)-based functional exercise in patients after anterior cruciate ligament reconstruction (ACLR).Design:Randomized, controlled, single-blind trial.Setting:Institutional, single center.Patients:A total of 38 patients who underwent ACLR were recruited and randomly assigned to group 1 (n = 19) or group 2 (n = 19).Interventions:Both groups received 6-month routine rehabilitation immediately after surgery. From the postoperative fourth to sixth month, group 1 received FMS-based functional exercise plus routine rehabilitation and group 2 received routine rehabilitation only. The FMS-based functional exercise was individualized and customized functional corrective exercise, which was designed based on the 3-month postoperative FMS results. The frequency of rehabilitation was 1 hour per session, twice a week, for a total duration of 6 months.Main Outcome Measures:At 3 and 6 months postoperatively, patients were evaluated by FMS scoring, Lysholm Knee Score, and International Knee Documentation Committee 2000 Score.Results:After the intervention, both groups had significantly increased FMS, Lysholm Knee Score, and International Knee Documentation Committee 2000 score. Group 1 had significantly greater changes in FMS (median: 4 vs 3,P < .001), Lysholm Knee Score (median: 24 vs 16,P = .001), and International Knee Documentation Committee 2000 Score (median: 22 vs 8,P < .001) than group 2.Conclusion:The application of FMS-based functional exercise to patients after ACLR resulted in significant improvement in knee function and movements. The authors suggested integrating FMS evaluation and FMS-based training into routine post-ACLR rehabilitation programs.
Developing Leadership Skills and a Commitment to Civic Engagement During an Undergraduate Community-Based Service Learning Class
Authors: Graber Kim C. , Chodzko-Zajko Wojtek , O’Connor Jamie A. , Linker Jenny M.
Published: October 2017

Civic engagement and service learning opportunities provide students with unique real-world experiences they are unable to acquire in a traditional in-class setting. Students develop a commitment to the community in which they live, exposure to other populations, leadership abilities, skills to work successfully within a team, and a chance to learn from failure. The Carnegie Foundation for the Advancement of Teaching has recognized the importance of such opportunities and has added the Community Engagement Classification to the restructured Carnegie Classifications of Institutions of Higher Education. The purpose of this paper is to provide a synthesis of the literature that addresses civic engagement and service learning opportunities and to describe a university class that was designed to provide undergraduate students with a capstone service learning experience promoting wellness for older adults in the community. Data that were collected to evaluate the success of the class are also described.
A Multi-Disciplinary Approach to Establishing a Community Wellness Program
Authors: Wohl Royal E. , Lockwood Park , Ure Kathy
Published: October 2017

Chronic disease is a leading cause of morbidity and mortality in the United States. One-half of U.S. adults have at least one chronic disease condition and 25% have multiple chronic conditions that can lead to a restriction in an ability to do basic daily living activities. Low-income adults have a high incidence of chronic disease that increases with aging due to ongoing psychological stress, higher risk exposure, less healthy living conditions, and limited access to health services. Community-based wellness programs, in collaboration with academic institutions, can serve this population by providing access to health services, quality educational and activity-based experiences, and continual assessment and support. Using a multidisciplinary approach, the expertise of numerous faculty, students, and staff can be used to help mitigate a myriad of health conditions presented by this population. This article shares one university’s creation, development, and delivery of an on-campus, multidisciplinary community wellness program for low-income adults.
3 WINS Fitness—Student-Delivered Free and Sustainable Exercise Programming in Public Parks:A Scalable Public Health Solution
Authors: Loy Steven
Published: October 2017

3 WINS Fitness is a student-delivered free exercise program for the community delivered in public parks. We believe this program, which operates without external funding and has been sustained for 6 years, is one significant solution to reducing the level of physical inactivity in the United States. The operative 3 WINS in our program are participant health, community health, and student professional development. The primary focus has been underserved communities, and our current eight programs in Los Angeles, serve over 300 participants regularly. Three challenges to the program are student empowerment, faculty understanding and involvement, and establishing the relationship between university and parks, which represent a vital partnership. However, the accomplishment of undergraduate students having such a dynamic impact on public health underscores the need for encouraging this sustainable and innovative strategy to increase the physical activity levels of communities across America.
Creating Interinstitutional Collaboration to Enhance Student Learning Outcomes and Potential Kinesiology Professionalization
Authors: Duke Lara M. , Piletic Cindy K.
Published: October 2017

This paper explores the use of collaboration theory and the consensus building framework to develop institutional strategic alliances at two North American postsecondary institutions. Collaboration between institutional and/or external partners offers rich opportunities to develop creative programming that provides students with opportunities for service learning situated in a well-planned curriculum. The collaboration development capitalizes on mutually beneficial outcomes for all partners and affords more informed decision making and impact than if partners were working individually. This paper highlights two successful partnerships and outlines the future direction of those collaborative alliances.
Improving Student Learning and Professional Preparation in Health Promotion Utilizing Partnerships
Authors: Barnes Jeremy T. , Pujol Thomas J.
Published: October 2017

Partnerships have been developed between faculty in the Department of Health, Human Performance and Recreation at Southeast Missouri State University and professionals from several organizations. These include on-campus partnerships with other academic departments, Recreation Services, Counseling and Disability Services, and a wide variety of off-campus partnerships including those with hospitals, fitness centers, county health departments, local coalitions, not-for-profits, schools K–12, and local corporations. All of these partnerships have resulted in substantial experiential learning opportunities for the students in the BS in Health Management: Health Promotion Option Program. Some of the skills students have acquired include improved written and oral communication skills, public speaking, program planning, program implementation, data collection, program evaluation, exercise testing, and prescription and health screening. The experiential learning activities students completed in two of the required classes in the major are described in this article.
Sustained Engagement Experiences in Kinesiology: An Engaged Department Initiative
Authors: Clocksin Brian D. , Greicar Margo B.
Published: October 2017

Community engagement is commonly imbedded in the ethos of institutions of higher education and has been identified as a High Impact Practice for student learning and retention. The Sustained Engagement Experiences in Kinesiology (SEEK) program at the University of La Verne is a curriculum-wide approach that moves students through four stages of community engagement: Respect, Participating with Effort, Self-Directions, and Leadership. The stages are developmentally sequenced across the curriculum and provide opportunities for learners to move from passive participants to active engagement scholars. The engagement experiences serve to enhance students’ abilities to transfer what they learn in the classroom to real-life problems, foster an asset-based approach to community engagement, and facilitate a transition from surface-to deep-learning.
In Vitro
Activity and MIC of Sitafloxacin against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis Isolated in Thailand
Authors: Leechawengwongs Manoon , Prammananan Therdsak , Jaitrong Sarinya , Billamas Pamaree , Makhao Nampueng , Thamnongdee Nongnard , Thanormchat Arirat , Phurattanakornkul Arisa , Rattanarangsee Somcharn , Ratanajaraya Chate , Disratthakit Areeya , Chaiprasert Angkana
Published: October 2017

New fluoroquinolones (FQs) have been shown to be more active against drug-resistant
Mycobacterium tuberculosis
strains than early FQs, such as ofloxacin. Sitafloxacin (STFX) is a new fluoroquinolone with
in vitro
activity against a broad range of bacteria, including
M. tuberculosis
. This study aimed to determine the
in vitro
activity of STFX against all groups of drug-resistant strains, including multidrug-resistant
M. tuberculosis
(MDR
M. tuberculosis
), MDR
M. tuberculosis
with quinolone resistance (pre-XDR), and extensively drug-resistant (XDR) strains. A total of 374 drug-resistant
M. tuberculosis
strains were tested for drug susceptibility by the conventional proportion method, and 95 strains were randomly submitted for MIC determination using the microplate alamarBlue assay (MABA). The results revealed that all the drug-resistant strains were susceptible to STFX at a critical concentration of 2 μg/ml. Determination of the MIC
90
s of the strains showed different MIC levels; MDR
M. tuberculosis
strains had a MIC
90
of 0.0625 μg/ml, whereas pre-XDR and XDR
M. tuberculosis
strains had identical MIC
90
s of 0.5 μg/ml. Common mutations within the quinolone resistance-determining region (QRDR) of
gyrA
and/or
gyrB
did not confer resistance to STFX, except that double mutations of GyrA at Ala90Val and Asp94Ala were found in strains with a MIC of 1.0 μg/ml. The results indicated that STFX had potent
in vitro
activity against all the groups of drug-resistant
M. tuberculosis
strains and should be considered a new repurposed drug for treatment of multidrug-resistant and extensively drug-resistant TB.
Methionine Ameliorates Polymyxin-Induced Nephrotoxicity by Attenuating Cellular Oxidative Stress
Authors: Azad Mohammad A. K. , Sivanesan Sivashangarie , Wang Jiping , Chen Ke , Nation Roger L. , Thompson Philip E. , Roberts Kade D. , Velkov Tony , Li Jian
Published: October 2017

Polymyxins are a last line of defense against multidrug-resistant Gram-negative pathogens. Recent pharmacological data show that intravenous polymyxins can cause nephrotoxicity in up to 60% of patients, and the plasma concentrations of polymyxins achieved with the currently recommended dosage regimens are suboptimal in a large proportion of patients. Simply increasing the daily dose of polymyxins is not possible due to nephrotoxicity. This study aimed to examine the protective effect of methionine against polymyxin-induced nephrotoxicity. Methionine (400 mg/kg of body weight), polymyxin B (35 mg/kg), a combination of methionine (100 or 400 mg/kg) and polymyxin B, and saline were administered to mice twice daily over 3.5 days. Kidneys were collected immediately at the end of the experiment for histological examination. The effect of methionine on the pharmacokinetics of polymyxin B was investigated in rats. The attenuation of polymyxin B (0.75 mM)-induced mitochondrial superoxide production by methionine (10.0 mM) was examined in rat kidney (NRK-52E) cells. Histological results revealed that the polymyxin-induced nephrotoxicity in mice was ameliorated by methionine in a dose-dependent manner. The methionine doses were well tolerated in the mice and rats, and the pharmacokinetics of polymyxin B in rats were not affected by methionine. In the group receiving polymyxin B-methionine, the total body clearance of polymyxin B was very similar to that in the group receiving polymyxin B alone (3.71 ± 0.57 versus 3.12 ± 1.66 ml/min/kg,
P
> 0.05). A substantial attenuation of polymyxin-induced mitochondrial superoxide production in NRK-52E cells was observed following pretreatment with methionine. Our results demonstrate that coadministration of methionine significantly ameliorated polymyxin-induced nephrotoxicity and decreased mitochondrial superoxide production in renal tubular cells.
Dissemination and Characteristics of a Novel Plasmid-Encoded Carbapenem-Hydrolyzing Class D β-Lactamase, OXA-436, Found in Isolates from Four Patients at Six Different Hospitals in Denmark
Authors: Samuelsen Ørjan , Hansen Frank , Aasnæs Bettina , Hasman Henrik , Lund Bjarte Aarmo , Leiros Hanna-Kirsti S. , Lilje Berit , Janice Jessin , Jakobsen Lotte , Littauer Pia , Søes Lillian M. , Holzknecht Barbara J. , Andersen Leif P. , Stegger Marc , Andersen Paal S. , Hammerum Anette M.
Published: October 2017

The diversity of OXA-48-like carbapenemases is continually expanding. In this study, we describe the dissemination and characteristics of a novel carbapenem-hydrolyzing class D β-lactamase (CHDL) named OXA-436. In total, six OXA-436-producing
Enterobacteriaceae
isolates, including
Enterobacter asburiae
(
n
= 3),
Citrobacter freundii
(
n
= 2), and
Klebsiella pneumoniae
(
n
= 1), were identified in four patients in the period between September 2013 and April 2015. All three species of OXA-436-producing
Enterobacteriaceae
were found in one patient. The amino acid sequence of OXA-436 showed 90.4 to 92.8% identity to the amino acid sequences of other acquired OXA-48-like variants. Expression of OXA-436 in
Escherichia coli
and kinetic analysis of purified OXA-436 revealed an activity profile similar to that of OXA-48 and OXA-181, with activity against penicillins, including temocillin; limited or no activity against extended-spectrum cephalosporins; and activity against carbapenems. The
bla
OXA-436
gene was located on a conjugative ∼314-kb IncHI2/IncHI2A plasmid belonging to plasmid multilocus sequence typing sequence type 1 in a region surrounded by chromosomal genes previously identified to be adjacent to
bla
OXA
genes in
Shewanella
spp. In conclusion, OXA-436 is a novel CHDL with functional properties similar to those of OXA-48-like CHDLs. The described geographical spread among different
Enterobacteriaceae
and the plasmid location of
bla
OXA-436
illustrate its potential for further dissemination.
In Vitro
Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria
Authors: Ito Akinobu , Sato Takafumi , Ota Merime , Takemura Miki , Nishikawa Toru , Toba Shinsuke , Kohira Naoki , Miyagawa Satoshi , Ishibashi Naoki , Matsumoto Shuhei , Nakamura Rio , Tsuji Masakatsu , Yamano Yoshinori
Published: October 2017

Cefiderocol (CFDC; S-649266), a novel parenteral siderophore cephalosporin conjugated with a catechol moiety, has a characteristic antibacterial spectrum with a potent activity against a broad range of aerobic Gram-negative bacterial species, including carbapenem-resistant strains of
Enterobacteriaceae
and nonfermenting bacteria such as
Pseudomonas aeruginosa
and
Acinetobacter baumannii
. Cefiderocol has affinity mainly for penicillin-binding protein 3 (PBP3) of
Enterobacteriaceae
and nonfermenting bacteria similar to that of ceftazidime. A deficiency of the iron transporter PiuA in
P. aeruginosa
or both CirA and Fiu in
Escherichia coli
caused 16-fold increases in cefiderocol MICs, suggesting that these iron transporters contribute to the permeation of cefiderocol across the outer membrane. The deficiency of OmpK35/36 in
Klebsiella pneumoniae
and the overproduction of efflux pump MexA-MexB-OprM in
P. aeruginosa
showed no significant impact on the activity of cefiderocol.
A Drug Repositioning Approach Reveals that Streptococcus mutans Is Susceptible to a Diverse Range of Established Antimicrobials and Nonantibiotics
Authors: Saputo S. , Faustoferri R. C. , Quivey R. G.
Published: October 2017

Streptococcus mutans
is the primary causative agent of dental caries and contributes to the multispecies biofilm known as dental plaque. An adenylate kinase-based assay was optimized for
S. mutans
to detect cell lysis when exposed to the Selleck library (Selleck Chemical, Houston, TX) of 853 FDA-approved drugs in, to our knowledge, the first high-throughput drug screen in
S. mutans
. We found 126 drugs with activity against
S. mutans
planktonic cultures, and they were classified into six categories: antibacterials (61), antineoplastics (23), ion channel effectors (9), other antimicrobials (7), antifungals (6), and other (20). These drugs were also tested for activity against
S. mutans
biofilm cultures, and 24 compounds were found to inhibit biofilm formation, 6 killed preexisting biofilms, 84 exhibited biofilm inhibition and killing activity, and 12 had no activity against biofilms. The activities of 9 selected compounds that exhibited antimicrobial activity were further characterized for their activity against
S. mutans
planktonic and biofilm cultures. Together, our results suggest that
S. mutans
exhibits a susceptibility profile to a diverse array of established and novel antibacterials.
Assessing Noninferiority in Treatment Trials for Severe Infectious Diseases: an Extension to the Entire Follow-Up Period Using a Cure-Death Multistate Model
Authors: Sommer Harriet , Bluhmki Tobias , Beyersmann Jan , Schumacher Martin
Published: October 2017

In current and former clinical trials for the development of antibacterial drugs, various primary endpoints have been used, and treatment effects are evaluated mostly in noninferiority analyses at the end of follow-up, which varies between studies. A more convincing and highly patient-relevant statement would be a noninferiority assessment over the entire follow-up period with cure and death as coprimary endpoints, while preserving the desired alpha level for statistical testing. To account for the time-dynamic pattern of cure and death, we apply a cure-death multistate model. The endpoint of interest is “get cured and stay alive over time.” Noninferiority between treatments over the entire follow-up period is studied by means of one-sided confidence bands provided by a flexible resampling technique. We illustrate the technique by applying it to a recently published study and establish noninferiority in being cured and alive over a time frame of interest for the entire population, patients with hospital-acquired pneumonia, but not for the subset of patients with ventilator-associated pneumonia. Our analysis improves the original results in the sense that our endpoint is more patient benefiting, a stronger noninferiority statement is demonstrated, and the time dependency of cure and death, competing events, and different follow-up times is captured. Multistate methodology combined with confidence bands adds a valuable statistical tool for clinical trials in the context of infection control. The framework is not restricted to the cure-death model but can be adapted to more complex multistate endpoints and equivalence or superiority analyses.
Intrapulmonary Pharmacokinetics of Laninamivir, a Neuraminidase Inhibitor, after a Single Nebulized Administration of Laninamivir Octanoate in Healthy Japanese Subjects
Authors: Toyama Kaoru , Furuie Hidetoshi , Ishizuka Hitoshi
Published: October 2017

A single dose of laninamivir octanoate (LO) inhaled using a dry powder inhaler (DPI) is effective for the treatment and prophylaxis of influenza. Nebulizers are an option for pediatric and elderly patients who may have difficulty in using a DPI. A single-center, open-label study was conducted to evaluate the plasma and intrapulmonary pharmacokinetics (PK) of laninamivir after a single nebulized administration of LO in healthy male Japanese subjects for identifying a safe and effective dosage regimen for a nebulizer. A single dose of LO (40 to 320 mg) was administered using a nebulizer, and plasma concentrations of LO and laninamivir were analyzed up to 168 h after inhalation by validated liquid chromatography-tandem mass spectrometry methods. Subgroups of 6 subjects each underwent bronchoalveolar lavage at specified time intervals over 4 to 168 h following a single nebulized administration of LO (160 mg), and the concentrations in epithelial lining fluid (ELF) were calculated by the urea diffusion method. PK parameters were determined by noncompartment analysis. Inhaled nebulized LO was found to be safe and well tolerated up to the highest dose evaluated (320 mg). Plasma laninamivir concentrations increased almost dose proportionally. Laninamivir concentrations in ELF exceeded the 50% inhibitory concentrations for viral neuraminidase up to 168 h after the nebulized inhalation of 160 mg LO. Thus, similarly to the DPI, ELF concentration profiles of laninamivir after a single nebulized administration support its long-lasting effect against influenza virus infection. This study has been registered at JAPIC Clinical Trials Information (
http://www.clinicaltrials.jp/
) under registration no. JAPIC CTI-152996.
Cell Invasion and Pyruvate Oxidase-Derived H
2
O
2
Are Critical for Streptococcus pneumoniae-Mediated Cardiomyocyte Killing
Authors: Brissac Terry , Shenoy Anukul T. , Patterson LaDonna A. , Orihuela Carlos J.
Published: October 2017

Streptococcus pneumoniae
(the pneumococcus) is the leading cause of community-acquired pneumonia and is now recognized to be a direct contributor to adverse acute cardiac events. During invasive pneumococcal disease,
S. pneumoniae
can gain access to the myocardium, kill cardiomyocytes, and form bacterium-filled “microlesions” causing considerable acute and long-lasting cardiac damage. While the molecular mechanisms responsible for bacterial translocation into the heart have been elucidated, the initial interactions of heart-invaded
S. pneumoniae
with cardiomyocytes remain unclear. In this study, we used a model of low multiplicity of
S. pneumoniae
infection with HL-1 mouse cardiomyocytes to investigate these early events. Using adhesion/invasion assays and immunofluorescent and transmission electron microscopy, we showed that
S. pneumoniae
rapidly adhered to and invaded cardiomyocytes. What is more, pneumococci existed as intravacuolar bacteria or escaped into the cytoplasm. Pulse-chase assays with BrdU confirmed intracellular replication of pneumococci within HL-1 cells. Using endocytosis inhibitors, bacterial isogenic mutants, and neutralizing antibodies against host proteins recognized by
S. pneumoniae
adhesins, we showed that
S. pneumoniae
uptake by cardiomyocytes is not through the well-studied canonical interactions identified for vascular endothelial cells. Indeed,
S. pneumoniae
invasion of HL-1 cells occurred through clathrin-mediated endocytosis (CME) and independently of choline binding protein A (CbpA)/laminin receptor, CbpA/polymeric immunoglobulin receptor, or cell wall phosphorylcholine/platelet-activating factor receptor. Subsequently, we determined that pneumolysin and streptococcal pyruvate oxidase-derived H
2
O
2
production were required for cardiomyocyte killing. Finally, we showed that this cytotoxicity could be abrogated using CME inhibitors or antioxidants, attesting to intracellular replication of
S. pneumoniae
as a key first step in pneumococcal pathogenesis within the heart.
Polyphenol- and Caffeine-Rich Postfermented Pu-erh Tea Improves Diet-Induced Metabolic Syndrome by Remodeling Intestinal Homeostasis in Mice
Authors: Gao Xiaoyu , Xie Qiuhong , Kong Ping , Liu Ling , Sun Sheng , Xiong Boyu , Huang Baojia , Yan Liang , Sheng Jun , Xiang Hongyu
Published: October 2017

Postfermented Pu-erh tea (PE) protects against metabolic syndrome (MS), but little is known regarding its underlying mechanisms. Animal experiments were performed to determine whether the gut microbiota mediated the improvement in diet-induced MS by PE and its main active components (PEAC). We confirmed that PE altered the body composition and energy efficiency, attenuated metabolic endotoxemia and systemic and multiple-tissue inflammation, and improved the glucose and lipid metabolism disorder in high-fat diet (HFD)-fed mice via multiple pathways. Notably, PE promoted the lipid oxidation and browning of white adipose tissue (WAT) in HFD-fed mice. Polyphenols and caffeine (CAF) played critical roles in improving these parameters. Meanwhile, PE remodeled the disrupted intestinal homeostasis that was induced by the HFD. Many metabolic changes observed in the mice were significantly correlated with alterations in specific gut bacteria.
Akkermansia muciniphila
and
Faecalibacterium prausnitzii
were speculated to be the key gut bacterial links between the PEAC treatment and MS at the genus and species levels. Interestingly,
A. muciniphila
administration altered body composition and energy efficiency, promoted the browning of WAT, and improved the lipid and glucose metabolism disorder in the HFD-fed mice, whereas
F. prausnitzii
administration reduced the HFD-induced liver and intestinal inflammatory responses. In summary, polyphenol- and CAF-rich PE improved diet-induced MS, and this effect was associated with a remodeling of the gut microbiota.
DksA and ppGpp Regulate the σ
S
Stress Response by Activating Promoters for the Small RNA DsrA and the Anti-Adapter Protein IraP
Authors: Girard Mary E. , Gopalkrishnan Saumya , Grace Elicia D. , Halliday Jennifer A. , Gourse Richard L. , Herman Christophe
Published: October 2017

σ
S
is an alternative sigma factor, encoded by the
rpoS
gene, that redirects cellular transcription to a large family of genes in response to stressful environmental signals. This so-called σ
S
general stress response is necessary for survival in many bacterial species and is controlled by a complex, multifactorial pathway that regulates σ
S
levels transcriptionally, translationally, and posttranslationally in
Escherichia coli
. It was shown previously that the transcription factor DksA and its cofactor, ppGpp, are among the many factors governing σ
S
synthesis, thus playing an important role in activation of the σ
S
stress response. However, the mechanisms responsible for the effects of DksA and ppGpp have not been elucidated fully. We describe here how DksA and ppGpp directly activate the promoters for the anti-adaptor protein IraP and the small regulatory RNA DsrA, thereby indirectly influencing σ
S
levels. In addition, based on effects of DksA
N88I
, a previously identified DksA variant with increased affinity for RNA polymerase (RNAP), we show that DksA can increase σ
S
activity by another indirect mechanism. We propose that by reducing rRNA transcription, DksA and ppGpp increase the availability of core RNAP for binding to σ
S
and also increase transcription from other promoters, including P
dsrA
and P
iraP
. By improving the translation and stabilization of σ
S
, as well as the ability of other promoters to compete for RNAP, DksA and ppGpp contribute to the switch in the transcription program needed for stress adaptation.

IMPORTANCE
Bacteria spend relatively little time in log phase outside the optimized environment found in a laboratory. They have evolved to make the most of alternating feast and famine conditions by seamlessly transitioning between rapid growth and stationary phase, a lower metabolic mode that is crucial for long-term survival. One of the key regulators of the switch in gene expression that characterizes stationary phase is the alternative sigma factor σ
S
. Understanding the factors governing σ
S
activity is central to unraveling the complexities of growth, adaptation to stress, and pathogenesis. Here, we describe three mechanisms by which the RNA polymerase binding factor DksA and the second messenger ppGpp regulate σ
S
levels.
Bone protective agents in children
Authors: Wood Claire Louise , Ahmed S Faisal
Published: October 2017

Evaluation of bone health in childhood is important to identify children who have inadequate bone mineralisation and who may benefit from interventions to decrease their risk of osteoporosis and subsequent fracture. There are no bone protective agents that are licensed specifically for the prevention and treatment of osteoporosis in children. In this review, we discuss the mechanism of action and use of bisphosphonates and other new and established bone protective agents in children.
Non-operative management of appendicitis in children
Authors: Hall Nigel J , Eaton Simon
Published: October 2017

While appendicectomy has been considered the mainstay of treatment for children with acute appendicitis for many decades, there has been a great deal of recent interest in non-operative treatment (NOT) with antibiotics alone. Initial results suggest that many children with appendicitis can indeed be safely treated with NOT and can be spared the surgeon’s knife. Many as yet unanswered questions remain, however, before NOT can be considered a realistic and reliable alternative to surgery. This review summaries current knowledge and understanding of the role of NOT in children with appendicitis and outlines and discusses the outstanding knowledge gaps.
Identification of health risk behaviours among adolescent refugees resettling in Western Australia
Authors: Hirani Kajal , Cherian Sarah , Mutch Raewyn , Payne Donald N
Published: October 2017

Objective

Adolescent refugees encounter traumatic stressors and are at risk of developing psychosocial health problems; limited research data exist internationally. This study aims to identify health risk behaviours among adolescent refugees resettling in Western Australia and assess the feasibility of using a standardised adolescent health questionnaire for this purpose.

Design

Refugees aged 12 years and above attending a tertiary Refugee Health Service (RHS) were recruited over 12 months. Sociodemographic data were collected. Psychosocial assessments based on the ‘Home, Education/Eating, Activities, Drugs, Sexuality, Suicide/mental health’ (HEADSS) framework were undertaken utilising interpreters where required. Health concerns identified were managed through the RHS.

Results

A total of 122 adolescents (20 ethnicities) participated; 65% required interpreters. Median age (range) was 14 (12–17) years. Most (80%) had nuclear family separation. Almost half (49%) had a deceased/missing family member. A third (37%) had lived in refugee camps and 20% had experienced closed detention. The median time (range) since arrival in Australia was 11 (2–86) months. Every adolescent had at least one health concern identified during the psychosocial assessment. Frequency of health concerns identified in each domain were 87% for home, 66% for education, 23% for eating, 93% for activities, 5% for drugs, 88% for sexuality and 61% for suicide/mental health. Most adolescents (75%) required intervention, consisting of counselling for health risk behaviours and/or referral to health or community services.

Conclusion

It is feasible to use a standardised adolescent health questionnaire to identify health risk behaviours among a cohort of ethnically diverse adolescent refugees. Use of the questionnaire identified a large burden of psychosocial health issues requiring multidisciplinary intervention.
Giant mediastinal parathyroid adenoma presenting as bilateral brown tumour of mandible: a rare presentation of primary hyperparathyroidism
Authors: Talukder Shibojit , Behera Arunanshu , Bhadada Sanjay K , Mitra Suvradeep
Published: October 2017

Hyperparathyroidism (HPT) is becoming increasingly common endocrinopathy in clinical practice. Nowadays, it is mostly diagnosed in subclinical or early clinical stage. Bony involvement in HPT has seen significant fall in incidence. Brown tumour of bone is exceptionally rare as a first manifestation of primary HPT (PHPT). Its radiological and histopathological features may be mistaken for other bony pathologies. If possibility of underlying HPT is overlooked the disease is bound to recur after surgery adding to morbidity of the patient. Here we present a case of bilateral brown tumour of mandible which was mistakenly treated as giant cell granuloma by surgical curettage. That the patient was harbouring an ectopic parathyroid adenoma with hypercalcemia causing non-specific symptoms was missed by the referring physician. This led to recurrence of the lesion. On subsequent evaluation, a giant mediastinal parathyroid adenoma causing PHPT was detected at our centre and was removed via mini sternotomy approach.
Effect of soft soil layer on local dynamic response of floating pile under harmonic lateral loading
Authors: Tantayopin Kullachai , Thammarak Punchet
Published: October 2017

Full-scale experiments of long floating piles under lateral harmonic excitation at the pile head were conducted to examine local resonant effects caused by the soft soil layer’s dynamic characteristic. Three 0.35 m diameter concrete piles with different lengths — 6, 10, and 15 m — in 19 m thick soft Bangkok clay were studied. Small-amplitude sweep excitations were applied in the frequency range that triggers resonance of the top soft soil layer, but will not reach the first fundamental frequency of the pile–soil system. The experiments show that the top soft soil layer produced local peaks of pile response at frequencies associated with predominant frequencies of the soil layer that agree well with the previous study of the dynamic characteristic of a soil layer in the Bangkok basin area by microtremor measurement. A comparison of experimental results with numerical solutions, i.e., the reduced dimension finite element model (RDFEM) and Winkler’s beam on spring and dashpot foundation (WBSDF), to evaluate their ability to simulate local resonance effects was carried out. Dynamic moduli of soil at different depths, to be used in numerical simulations, were measured by crosshole seismic test. Satisfactory matches between experimental results and numerical simulations by RDFEM were observed whereas WBSDF predictions are not close because the soft soil layer cannot be incorporated in WBSDF.