bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of SC Walls and Connections in Nuclear Facilities
Authors: Varma Amit H. , Bhardwaj Saahastaranshu R. , Malushte Sanjeev R.
Published: October 2016

Steel-plate composite (SC) walls and associated connections can be designed based on the provisions of Appendix N9 to AISC N690s1. AISC N690s1 is Supplement No. 1 to AISC N690-12 specification for safety related steel structures in nuclear facilities and was published in October 2015. AISC is currently in the process of developing a design guide to further enable the use of this specification. This design guide will explore the provisions of this specification in detail and discuss different possible design methodologies.

SC wall details at the beginning of the design process are based on typical plant layouts, shielding requirements and prevalent practices. The spacing of tie bars and steel anchors in SC wall needs to ensure the faceplate does not undergo buckling before steel yielding. The steel anchor additionally need to be spaced to ensure that (i) interfacial shear failure does not occur before out-of-plane shear failure, and (ii) the yield strength of the faceplates is developed over the development length. The tie bars need to have sufficient tensile strength to prevent splitting failure of SC walls. The elastic analysis of the SC walls is performed using a finite element analysis. The analysis needs to consider cracked transformed stiffnesses and equivalent material properties. The analysis will be conducted for operating thermal and accident thermal load combinations. The individual demands and the combination of demands need to be compared with the available strengths. The SC walls need to be adequately detailed for openings, meet construction and fabrication tolerances, and satisfy the Quality Assurance and Quality Control requirements. The designed SC walls needs to be safe for impactive and impulsive loads.

SC wall panel may need to be (i) anchored to basemat, (ii) connected to another SC wall panel, or (iii) connected to RC slab. The SC connections can be designed as full strength connection or over strength connections. The connection needs to have a well-defined force transfer mechanism. The connection required strength is determined from the design demands of SC walls and the connection design philosophy. The available strength is determined from the individual strengths of connectors participating in the force transfer mechanism.
Development of New MHI LOCA Analysis Code: MCOBRA/RELAP5-GOTHIC
Authors: Katayama Masaaki , Teramae Tetsuya , Mizokami Masatsugu , Kosaka Shinya
Published: October 2016

Mitsubishi Heavy Industries, Ltd. (MHI) has developed the safety analysis code system, MCOBRA/RELAP5-GOTHIC, for large break LOCA, small break LOCA and containment integrity analyses of PWR. The code system contains three codes, MCOBRA code, M-RELAP5 code and GOTHIC code. MHI implemented some models and correlations to MCOBRA and M-RELAP5 code to improve prediction of important phenomena of LOCA event. MHI conducted a lot of analyses for separate effect tests and integral effect tests to confirm the applicability of the MHI’s safety analysis code to LOCA key phenomena, like core heat transfer, DNB, entrainment, break flow, counter-current flow limitation (CCFL), core froth level, and so on. The code model uncertainties are quantified to calculate core heat transfer break flow rate, loop seal phenomena; heat transfer in steam generators, and so on. The results show that the code system can predict the key phenomena well and can calculate LOCA event scenario. Consequently, it is confirmed that the new code system is applicable to the LOCA licensing analysis.
Application of Fuzzy Weighted Support Vector Regression to Accidents Condition Monitoring of Nuclear Power Plant
Authors: Jiang B. T. , Hines J. W. , Zhao F. Y.
Published: October 2016

Monitoring changes in important parameters has been suggested as a potentially useful condition monitoring (CM) method for the accidents occurred in nuclear power plants (NPPs). The reactor core power is believed to be an important parameter governing the performance of reactor during transient response. The accurate prediction of reactor behavior and power is very important for nuclear power plant operators, especially during the major severe accident scenarios following an initiating event such as rod ejection accident (REA) or rod drop accident (RDA). REA and RDA together are found to be the worst postulated power transients in reactor licensing and are referred to as reactivity-initiated accidents (RIAs). RIAs is a postulated event of very low probability and involves inadvertent removal of a control element from an operating reactor, leading to a rapid power excursion in nearby fuel elements. On the basis of our previous work, in which only REA scenario is analyzed, the primary objective of this study is to develop and implement fuzzy weighted support vector regression (FWSVR) for condition monitoring under REA and RDA in NPPs. FWSVR is an extension of support vector regression (SVR) which introduces fuzzy weights in traditional SVR formulation. The accidents simulated in this study are based on the same model used in our previous work. This model can be accomplished by two procedures. First, the neutron flux and enthalpy distributions of the core can be obtained from a solution to the three-dimensional nodal space time kinetics equations and energy equations for both single and two-phase flows respectively. Second, the reactivity effects of the moderator temperature, boron concentration, fuel temperature, coolant void, xenon worth, samarium worth, control element positions (CEAs) and core burnup status can be calculated and determined. For the purpose of condition monitoring, it’s a fundamental issue to acquire condition monitoring data for useful data representation. Otherwise, it’s hard to predict the power accurately if enough data is not available. The data used in this study is collected from computer generated accident scenarios. Then the obtained data is split into two subgroups, training and test. The training subgroup data is utilized to train the FWSVR model and the fuzzy weights introduced in FWSVR are employed to extract multiple linear structures in a training dataset and assign to each data point a cluster index determined by its trained kernel radius function. The test is employed to validate the model. Finally the results of FWSVR model are compared with that of other models such as traditional SVR and back propagation network (BPN) which is one type of artificial neural networks (ANNs). Comparison of results among the three methods indicates that FWSVR model not only outperforms traditional SVR and BPN, but also has a better agreement with the general understanding than them.
Study on Stability of Liquid Jet for Liquid Lithium Target of Boron Neutron Capture Therapy (BNCT)
Authors: Maehara Yuki , Kondo Masatoshi , Takahashi Minoru
Published: October 2016

For the development of the liquid lithium (Li) jet target system for the boron neutron capture therapy (BNCT), the stability of the Li jet is important. The purpose of the present study is to investigate the characteristics of the disturbances and the droplet formation of a water jet flow at high velocity. The experimental studies for a water jet flow were performed to simulate the liquid Li jet flow. The nozzles in the experiment had a rectangular flow channel with the gap of 0.5 mm and the length of 10 mm and 70 mm. The water flow velocities in these nozzles were 5 m/s, 10 m/s or 15 m/s. The stability of the water jet flow was investigated by the observation of the surface disturbance using a high speed video camera. The formation of water droplet from the water jet flow was detected, and the characteristics of the droplet formation were analyzed using Phase Doppler Anemometry (PDA). Then, the surface disturbance of the jet flow was characterized by the characteristics of the droplet generation. In the experiment with 10mm length of nozzle, a lot of droplets are generated from the jet surface and the surface is considered to be unstable. On the other hand the smooth jet surface and the stable jet are made near nozzle outlet. In the experiment with 70mm length of nozzle, few droplets are generated from the surface of the jet and the surface of the jet is very smooth especially for the place near nozzle outlet. It was concluded that the droplet generation from the surface of the water jet was promoted by the distortion of the jet surface. Also the surfaces of the jet flow made by the nozzle having the length of 70 mm was smoother than those in the tests with the nozzle having the length of 10 mm. The large eddy in the flow must be dumped before the nozzle outlet because the turbulence was fully developed in the nozzle.
Numerical Simulation of Three Dimensional Internal Flow of a PWR Reactor
Authors: Ge Jian , Tian Wenxi , Xu Tingting , Min Jiesheng , Chen Guofei , Bellet Serge , Delepine Samuel
Published: October 2016

The coolant flow in the reactor pressure vessel (RPV) lower plenum is complex due to the presence of various internal structures, which has a great influence on the flow distribution at the core inlet. In order to study the thermal hydraulic characteristics in the RPV lower plenum, many scaled down test facilities have been built for different PWR reactors such as Juliette, ACOP, and ROCOM. Although the experimental study is still a main research method, it may be not economical in some situations due to the high cost and the long study period. Compared with the experimental method, Computational Fluid Dynamics (CFD) methodology can simulate three dimensional fluid flow in complex geometries and perform parametric studies more easily. The detailed and localized thermal hydraulic characteristics which are difficult to measure during experiments can be obtained. So CFD simulation has been widely used nowadays. One of the purposes of numerical simulations of the internal flow in a RPV is to get the flow distribution at the core inlet, then to make an optimization for the flow diffusor in the RPV lower plenum to improve the core inlet flow distribution homogeneity. Appropriate optimizations for the flow diffusor depends on fully understanding the flow phenomena in the RPV lower plenum. In this paper, Phenomenon Identification and Ranking Table (PIRT) is adopted to analyze the physical phenomenon that occurs in the RPV lower plenum with the typical 900MW reactor internal structures, and the importance of the various physical phenomena and the reference parameters are ranked through expert opinions and literature review. Then a preliminary three dimensional CFD simulation for the reactor vessel is conducted. The main phenomena identified by the PIRT can be observed from the simulation results.
A Hybrid Probabilistic Physics of Failure Pattern Recognition Based Approach for Assessment of Multi-Unit Causal Dependencies
Authors: Zhou Taotao , Droguett Enrique López , Modarres Mohammad
Published: October 2016

The recent dependencies studies have mainly been done in context of single unit, which means the failures involving components in different units are not explicitly treated. The major scopes are also limited to the simultaneous failures as the direct results of shared causes, namely the Common Cause Failures (CCFs). The causal relations among components or units are rarely addressed. Thus it’s the prime topic of this investigation that the dependencies among multiple units co-located at a site which is called multi-unit dependencies.

This paper seeks to propose a hybrid approach by combining physics-based models and supervised learning techniques. The essential idea is to account for the multi-unit dependencies by explicitly modeling the interactions of the underlying physical failure mechanisms. Ultimately a hybrid Dynamic Bayesian Belief Network is developed to model the possible dependencies, and supervised learning techniques are adopted to quantify the likelihood of failures due to dependency effects. Furthermore, an experiment has been designed and presented involving redundant pumping system, the performance of which are monitored by an advanced sensing system. The experiment is now operating and the gathered multi-sensor data will be used to illustrate the proposed approach as the next stage of this research. These sensor data should be of good quality to allow revealing the underlying failure behavior and dependent failures. This study provides an understanding of the inherent risk significance of dependencies among multiple units, and can also work as the basis for the reliability of multi-unit systems where causal dependencies play a relevant role.
An Initial Assessment of Minimum Film Boiling Temperature Correlations and Comparison to Experimental Data
Authors: Duarte Juliana P. , Corradini Michael L.
Published: October 2016

The minimum film boiling temperature (TMFB) separates the unstable transition boiling region, where the liquid can contact the heated surface, and the post-CHF regime, where vapor can prevent the liquid from contacting the heated wall. This paper presents a review of minimum film boiling temperature correlations and describes a new technique to measure TMFB. The experiment proposed was simulated by TRACE and the same behavior was observed experimentally.
Characterizing the United States Nuclear Used Fuel Inventory Using the Cyclus Fuel Cycle Simulator
Authors: Bagdatlioglu Cem , Flanagan Robert , Schneider Erich
Published: October 2016

The used fuel inventory of the United States commercial nuclear fleet has been accumulating since the inception of nuclear reactors. In order to understand the mass and composition of the used fuel inventory, a nuclear fuel cycle simulation package (Cyclus) is used with a reactor modeling tool (Bright-lite). The parameters for the simulation are obtained as historical operation and burnup data for every reactor in the US fleet, taken from the U.S. Energy Information Administration. The historical burnup data is used to calculate the fuel enrichment of every reactor at every refueling. Discharged uranium inventories calculated by the software are shown to closely match the reference data. The total mass of three major actinide groups are presented as they build up over time. In addition, the evolution of the plutonium composition in discharged fuel is also presented, illustrating Cyclus’ ability to track the composition of material flowing through a large, evolving reactor fleet over decades.
Predictive Modeling of Acoustic Signals From Thermoacoustic Power Sensors (TAPS)
Authors: Dumm Christopher M. , Vipperman Jeffrey S. , Carvajal Jorge V. , Walter Melissa M. , Czerniak Luke , Ruane Amy S. , Ferroni Paolo , Heibel Michael D.
Published: October 2016

Thermoacoustic Power Sensor (TAPS) technology offers the potential for self-powered, wireless measurement of nuclear reactor core operating conditions. TAPS are based on thermoacoustic engines, which harness thermal energy from fission reactions to generate acoustic waves by virtue of gas motion through a porous stack of thermally nonconductive material. TAPS can be placed in the core, where they generate acoustic waves whose frequency and amplitude are proportional to the local temperature and radiation flux, respectively. TAPS acoustic signals are not measured directly at the TAPS; rather, they propagate wirelessly from an individual TAPS through the reactor, and ultimately to a low-power receiver network on the vessel’s exterior. In order to rely on TAPS as primary instrumentation, reactor-specific models which account for geometric/acoustic complexities in the signal propagation environment must be used to predict the amplitude and frequency of TAPS signals at receiver locations. The reactor state may then be derived by comparing receiver signals to the reference levels established by predictive modeling. In this paper, we develop and experimentally benchmark a methodology for predictive modeling of the signals generated by a TAPS system, with the intent of subsequently extending these efforts to modeling of TAPS in a liquid sodium environment.
Enhanced Verification for RELAP5-3D Parameter and Sensitivity Studies
Authors: Mesina George L. , Anderson Nolan
Published: October 2016

The RELAP5-3D1 program solves a complex system of governing, closure and special process equations to model the underlying physics of nuclear power plants. For SQA (software quality assurance), the code must be verified and validated (V&V) to ensure proper performance before release to users. The physical models are validated against data from experiments and plants and verified against specifications for the computer code. In addition to physics, programs such as RELAP5-3D perform numerous other functions and processes that should also be checked to guarantee correct results. Functions include input, output, data management, and user interaction, while processes include restart, time-step backup, code coupling, and multi-case processing. Previous articles have covered the verification of the physical models, restart, and backup through extremely accurate and automated sequential verification applied on a comprehensive suite of test cases to ensure that code changes produced no unintended consequences. New developments have enabled the verification of multi-case and multi-deck processing. These features are frequently used in parameter and code sensitivity studies and therefore must be verified as working correctly. Both theory and application are presented.
Computational Fluid Dynamics Analysis of Two Parallel Rectangular Jets Using OpenFOAM
Authors: Li Han , Wang Huhu , Hassan Yassin A. , Anand N. K.
Published: October 2016

Two or multiple parallel jets are an important shear flow that widely existing in many industrial applications. The interaction between turbulence jets enables fast and thorough mixing of two fluids. The mixing feature of parallel jets has many engineering applications, such as, in Generation IV conceptual nuclear reactors, the coolants merge in upper or lower plenum after passing through the reactor core. While study of parallel jets mixing phenomenon, numerical experiments such as Computational Fluid Dynamics (CFD) simulations are extensively incorporated. Validation of varied turbulent models is of importance to make sure that the numerical results could be trusted and served as a guideline further design purpose. Many commercial CFD packages in the market such as FLUENT and Star CCM+ can provide the ability to simulate turbulent flow with predefined turbulence model, however, such commercial solvers may lack the flexibility that allow users build their own models for R&D purpose. The existing solvers in OpenFOAM are developed to fulfill both academic and industrial needs by achieving large-scale computational capability with a variety of physical models. Moreover, as an open source CFD toolbox, OpenFOAM grants users full control of the source code with complete freedom of customization. The purpose of this study is to perform CFD simulation using OpenFOAM for two submerged parallel jets issuing from two rectangular channels. Fully hexahedron multi-density mesh is generated using blockMesh utility to ensure velocity gradients are properly evaluated. A generalized-multi-grid solver is used to enhance convergence. Based on Reynolds-Averaged Navier-Stokes Equations (RANS), the realizable k-ε and k-ε shear stress transport (SST) are selected to model turbulent flow. Steady state Finite Volume solver simpleFoam is used to perform the simulation. In addition, data from experiments run in Thermal-Hydraulic Lab at Texas A&M University using particle image velocity (PIV) and Laser Doppler Anemometry (LDA) methods are considered in order to compare and validate simulation results. A number of turbulence characteristic such as mean velocities, turbulent intensities, z-component vorticity were compared with experiments. It was found that for stream-wise mean velocity profile as well as shear stresses, the realizable k-ε model exhibits a good agreement with experimental data. However, velocity fluctuation and turbulence intensities, simulation results showed a certain discrepancy.
IAEA Guidance on Enhancing the Safety of Electrical Power Systems
Authors: Duchac Alexander , Knutsson Magnus
Published: October 2016

An open phase condition is a known phenomenon in the power industry and is now recognized to have adverse impact on the electrical power systems in several nuclear power plants. An open phase condition may result in challenging plant safety. Operating experience in different countries has shown that the currently installed instrumentation and protective schemes have not been adequate to detect this condition and take appropriate action. An open phase condition, if not detected and disconnected in a timely manner, represents design vulnerability for many nuclear power plants. It may lead to a condition where neither the offsite power system nor the onsite power system is able to support the safety functions, and could propagate to station blackout. The design of electrical power systems needs to be evaluated systematically and improved, where necessary, to minimize the probability of losing electric power from any of the remaining supplies as a result of single or double open phase conditions. The improved design should be coordinated with existing measures to ensure that the electrical power system is able to support the safety functions after the open phase condition is detected and disconnected. In this regard, the IAEA has developed a safety publication dealing with design vulnerability of open phase conditions. This paper summarizes the contents of the report, the rationale and criteria to enhance the safety of nuclear power plants by providing technical guidance to address an open phase condition vulnerability in electrical systems used to start up, operate, maintain and shutdown the nuclear power plant.
The Influence of Microstructures on the Thermal Conductivity of Polycrystalline UO2
Authors: Jin Enze , Liu Chen , He Heming
Published: October 2016

The thermal conductivity is one of the most important properties for UO2. The influences of microstructure are especially important for UO2 due to the severe structural changes under irradiation conditions. In this study, we have investigated the thermal conductivity of UO2 with different microstructures using Finite Element Method. The thermal conductivity increases with increasing grain size. The grain size distribution has obvious influence on the thermal conductivity especially when there are pores in the polycrystal. The influences of porosity and pore size are very sensitive to the position of the pores. The results obtained in this study are useful for prediction of property changes of UO2 fuel in pile and important to gain some design guidance to tune the properties through the control of the microstructure.
Integrity Assessment of Mechanical Components Subjected to Mixed Mode Cracking
Authors: Zeng Lingfu , Luo Chouping , Jansson Lennart G.
Published: October 2016

This paper addresses a mixed mode driven cracking and its integrity assessment for applications in aging nuclear power piping. Following our earlier discussion on the use of mode-I based criteria in the current R6-method-based practice of integrity assessment, case studies conducted using finite element analysis are conducted and examined: (1) A plate with a single and multiple central crack(s) under tension; (2) A full-scale laboratory test of a straight pipe with an obliquely inserted crack in a dissimilar metal weld. Our results confirm the following earlier observations: For cases when mixed mode loading conditions are significant, (i) the fracture initiation predicted by using J-integral based mixed mode cracking criteria can approximately be achieved by an “effective stress intensity factor” based approach; (ii) it is not conservative to use a purely mode-I based criterion for the evaluation of the fracture failure assessment for typical problems of mixed mode driven cracking; (iii) The effect of multiple cracks can be significant and an assessment by only examining one crack, which is a common practice today, may not be fully conservative.
Three Dimensional Numerical Simulation of Atmospheric Dispersion Influenced by Complex Underlying Surface Surrounding Nuclear Power Plant
Authors: Wang Bo , Zhang Qiong , Guo Ruiping
Published: October 2016

An accurate simulation of radioactive plume dispersion in a geometrically complex plant region is a prerequisite in emergency preparedness for regulators to design effective policies. The influences of typical complex underlying surface in inland nuclear power plants, such as huge cooling towers, on the atmospheric dispersion have been simulated by commercial Computational Fluid Dynamics (CFD) software and compared with wind tunnel tests by Statistical performance measures under four fixed wind directions considering the relation between dominant wind directions and main structures. The simulation results show that, the influences of cooling towers on local wind field are closely related to the relative position of the release source and the building groups. The mechanical disturbance of cooling towers increased the turbulence intensity significantly, leading to the distribution expansion of pollutants; while the wake zone changed the vertical movement, leading to the increase in the ground concentration near release point and the decrease in distance of maximum ground concentration from release point. The objective of this study was to simulate the wake structure and its effects on mean flow and turbulence of the atmospheric boundary layer (ABL) under the action of the mechanical disturbance with the combination of the terrain and the buildings for given key wind directions, and to analyze the flow characteristics around the building groups and to provide a visual quantitative analysis method for the transport and dispersion of near field in the inland nuclear power plant.
Predictive Methods in the Assessment of Alloy 600 PWSCC Failures in Operating Pressurized Water Reactors
Authors: Rao Gutti V.
Published: October 2016

This paper reviews the role of fundamental factors such as stress, temperature and material microstructure in contributing to the PWSCC susceptibility in Alloy 600 components of operating PWRs. The effect of residual stresses from fabrication, cold work and welding as well as cyclic work hardening are considered. The influence of fabrication practice and the resulting microstructural parameters such as grain size, carbide distribution and ghost boundaries are considered. The paper considers the development of deterministic and probabilistic PWSCC susceptibility models to predict failures in the components and explain how these are applied to operating units. Investigation of service failures in the base metal and welds are considered.
Study on Typical Initial Event of ATWS for Small Modular Reactor
Authors: Dan Zhang , Xu Ran , Zhifang Qiu , Ke Zhou , Li Feng
Published: October 2016

The method for ATWS (anticipated transient without scram) analysis was completely developed for commercial pressurized water (PWR) reactor plants, especially for selecting of typical initial events. For accident analysis of ATWS, it is different between PWR and small modular reactor (SMR), as different structures and characters, and it is necessary to study the typical initial events for these reactors. Based on the standard of PWR, the demanding for ATWS analysis was studied and the consequences for typical anticipated transient was calculated using RELAP5/MOD3.2 code, “maintain reactor coolant pressure boundary integrity” was selected as limiting criterion. The results shows for SMR, anticipated transient with the most serious consequence for ATWS are loss of offsite power and inadvertent control rod withdraw event, this conclusion will support to prepare the safety analysis report and optimum design of diversity activation system (DAS) for SMR.
A statistical background noise correction sensitive to the steadiness of background noise
Authors: Oppenheimer Charles H.
Published: October 2016

A statistical background noise correction is developed for removing background noise contributions from measured source levels, producing a background noise-corrected source level. Like the standard background noise corrections of ISO 3741, ISO 3744, ISO 3745, and ISO 11201, the statistical background correction increases as the background level approaches the measured source level, decreasing the background noise-corrected source level. Unlike the standard corrections, the statistical background correction increases with steadiness of the background and is excluded from use when background fluctuation could be responsible for measured differences between the source and background noise levels. The statistical background noise correction has several advantages over the standard correction: (1) enveloping the true source with known confidence, (2) assuring physical source descriptions when measuring sources in fluctuating backgrounds, (3) reducing background corrected source descriptions by 1 to 8 dB for sources in steady backgrounds, and (4) providing a means to replace standardized background correction caps that incentivize against high precision grade methods.
Combinatorial interaction network of transcriptomic and phenotypic responses to nitrogen and hormones in the
Arabidopsis thaliana
root
Authors: Ristova Daniela , Carré Clément , Pervent Marjorie , Medici Anna , Kim Grace Jaeyoon , Scalia Domenica , Ruffel Sandrine , Birnbaum Kenneth D. , Lacombe Benoît , Busch Wolfgang , Coruzzi Gloria M. , Krouk Gabriel
Published: October 2016

Multivariate analysis reveals a hormone- and nutrient-regulated network that shapes root architecture.
Science Signaling
Podcast for 25 October 2016: How glucocorticoids stimulate fat
Authors: Feldman Brian J. , VanHook Annalisa M.
Published: October 2016

A secreted protease inhibits diet- and glucocorticoid-induced differentiation of adipocytes (Wong
et al
., in 25 October 2016 issue).
Papers of note in
Science
Authors: VanHook Annalisa M.
Published: October 2016

This week’s articles highlight dysregulation of a tissue repair–promoting cytokine in IBD, the generation of peptides for antigen presentation, a signaling system that promotes the exchange of DNA between mycobacteria, a feedback loop that resets a plant’s response to blue light, and the structural basis for activation of a calcium channel.
Improving the health of newborns of obese mothers
Authors: Gough Nancy R.
Published: October 2016

AMPK activators may rescue brown adipose tissue development in neonates of obese mothers.
A tauopathy kinase
Authors: Ferrarelli Leslie K.
Published: October 2016

Inhibiting the kinase NUAK1 could slow the accumulation of tau in Alzheimer’s disease and progressive supranuclear palsy.
Papers of note in
Science Immunology
Authors: Foley John F.
Published: October 2016

This week’s articles describe ways in which type I interferons lead to depletion of B cells and loss of antibody responses during chronic viral infections.
Population Pharmacokinetics and Dosing Considerations for Gentamicin in Newborns with Suspected or Proven Sepsis Caused by Gram-Negative Bacteria
Authors: Bijleveld Yuma A. , van den Heuvel Maria E. , Hodiamont Caspar J. , Mathôt Ron A. A. , de Haan Timo R.
Published: October 2016

The aim of this study was to describe the population pharmacokinetics (PK) of gentamicin in neonates with suspected or proven Gram-negative sepsis and determine the optimal dosage regimen in relation to the bacterial MICs found in this population. Data were prospectively collected between October 2012 and January 2013 in the Neonatal Intensive Care Unit (NICU) at the Academic Medical Center (AMC), Amsterdam, The Netherlands. A single nonlinear mixed-effects regression analysis (NONMEM) was performed to describe the population PK of gentamicin. Dosage regimens based upon gestational age (GA) were generated using Monte Carlo simulations with the final model. Target values were based on the MIC distribution in our patient population. In total, 136 gentamicin concentrations from 65 (pre)term neonates were included. The PK was best described by an allometric 2-compartment model with postmenstrual age (PMA) as a covariate on clearance (Cl). The MIC distribution (median, 0.75 [range, 0.5 to 1.5] mg/liter) justified a gentamicin target peak concentration of 8 to 12 mg/liter. This study describes the PK of gentamicin in (pre)term neonates. Dosage regimens of 5 mg/kg of body weight every 48 h, 5 mg/kg every 36 h, and 5 mg/kg every 24 h for patients with GAs of <37 weeks, 37 to 40 weeks, and ≥40 weeks, respectively, are recommended.
Comparative Evaluation of Etest, EUCAST, and CLSI Methods for Amphotericin B, Voriconazole, and Posaconazole against Clinically Relevant Fusarium Species
Authors: Al-Hatmi Abdullah M. S. , Normand Anne-Cécile , Ranque Stephane , Piarroux Renaud , de Hoog G. Sybren , Meletiadis Joseph , Meis Jacques F.
Published: October 2016

We compared EUCAST and CLSI methods versus Etest for antifungal susceptibility testing of 20 clinically relevant
Fusarium
species against amphotericin B, posaconazole, and voriconazole. The median Etest amphotericin B and posaconazole MICs were 1 dilution higher than the median EUCAST and the CLSI MICs. The essential agreement (within ±1/±2 dilutions) was 60/90%, 80/95%, and 70/85% between the Etest and EUCAST methods and 80/95%, 75/95%, and 45/100% between the Etest and CLSI methods for amphotericin B, voriconazole, and posaconazole, respectively. The categorical agreement was >85%. Etest can be used for antifungal susceptibility testing of
Fusarium
species.
Multimerization of the Virulence-Enhancing Group A Streptococcus Transcription Factor RivR Is Required for Regulatory Activity
Authors: Ramalinga Anupama , Danger Jessica L. , Makthal Nishanth , Kumaraswami Muthiah , Sumby Paul
Published: October 2016

Group A
Streptococcus
(GAS) (
Streptococcus pyogenes
) causes more than 700 million human infections each year. The significant morbidity and mortality rates associated with GAS infections are in part a consequence of the ability of this pathogen to coordinately regulate virulence factor expression during infection. RofA-like protein IV (RivR) is a member of the Mga-like family of transcriptional regulators, and previously we reported that RivR negatively regulates transcription of the
hasA
and
grab
virulence factor-encoding genes. Here, we determined that RivR inhibits the ability of GAS to survive and to replicate in human blood. To begin to assess the biochemical basis of RivR activity, we investigated its ability to form multimers, which is a characteristic of Mga-like proteins. We found that RivR forms both dimers and a higher-molecular-mass multimer, which we hypothesize is a tetramer. As cysteine residues are known to contribute to the ability of proteins to dimerize, we created a library of expression plasmids in which each of the four cysteines in RivR was converted to serine. While the C68S RivR protein was essentially unaffected in its ability to dimerize, the C32S and C377S proteins were attenuated, while the C470S protein completely lacked the ability to dimerize. Consistent with dimerization being required for regulatory activity, the C470S RivR protein was unable to repress
hasA
and
grab
gene expression in a
rivR
mutant. Thus, multimer formation is a prerequisite for RivR activity, which supports recent data obtained for other Mga-like family members, suggesting a common regulatory mechanism.

IMPORTANCE
The modulation of gene transcription is key to the ability of bacterial pathogens to infect hosts to cause disease. Here, we discovered that the group A
Streptococcus
transcription factor RivR negatively regulates the ability of this pathogen to survive in human blood, and we also began biochemical characterization of this protein. We determined that, in order for RivR to function, it must self-associate, forming both dimers (consisting of two RivR proteins) and higher-order complexes (consisting of more than two RivR proteins). This functional requirement for RivR is shared by other regulators in the same family of proteins, suggesting a common regulatory mechanism. Insight into how these transcription factors function may facilitate the development of novel therapeutic agents targeting their activity.
Monocyte, Macrophage, and Dendritic Cell Development: the Human Perspective
Authors: Collin Matthew , Bigley Venetia
Published: October 2016

The maintenance of monocytes, macrophages, and dendritic cells (DCs) involves manifold pathways of ontogeny and homeostasis that have been the subject of intense study in recent years. The concept of a peripheral mononuclear phagocyte system continually renewed by blood-borne monocytes has been modified to include specialized DC pathways of development that do not involve monocytes, and longevity through self-renewal of tissue macrophages. The study of development remains difficult owing to the plasticity of phenotypes and misconceptions about the fundamental structure of hematopoiesis. However, greater clarity has been achieved in distinguishing inflammatory monocyte-derived DCs from DCs arising in the steady state, and new concepts of conjoined lymphomyeloid hematopoiesis more easily accommodate the shared lymphoid and myeloid phenotypes of some DCs. Cross-species comparisons have also yielded coherent systems of nomenclature for all mammalian monocytes, macrophages, and DCs. Finally, the clear relationships between ontogeny and functional specialization offer information about the regulation of immune responses and provide new tools for the therapeutic manipulation of myeloid mononuclear cells in medicine.
Coordinated Regulation of Signaling Pathways during Macrophage Activation
Authors: Lawrence Toby
Published: October 2016

The functional and phenotypic diversity of macrophages has long been appreciated, and it is now clear that it reflects a complex interplay between hard-wired differentiation pathways and instructive signals in specific tissues (Lawrence T, Natoli G. 2011,
Nat Rev Immunol
11:
750–761). Recent studies have begun to unravel the molecular basis for the integration of these intrinsic developmental pathways with extracellular signals from the tissue microenvironment that confer the distinct phenotypes of tissue-resident macrophages (Lavin Y et al. 2014.
Cell
159:
1312–1326; Gosselin D et al. 2014.
Cell
159:
1327–1340). Macrophage phenotype and function is particularly dynamic during inflammation or infection, as blood monocytes are recruited into tissues and differentiate into macrophages, and depending on the nature of the inflammatory stimulus, they may acquire distinct functional phenotypes (Xue J et al. 2014.
Immunity
40:
274–288; Murray PJ et al. 2014.
Immunity
41:
14–20). Furthermore, these functional activation states can be rapidly modified in response to a changing microenvironment. Here we will discuss several key signaling pathways that drive macrophage activation during the inflammatory response and discuss how these pathways are integrated to “fine-tune” macrophage phenotype and function.
Murine Monocytes: Origins, Subsets, Fates, and Functions
Authors: Mildner Alexander , Marinkovic Goran , Jung Steffen
Published: October 2016

Monocytes are short-lived mononuclear phagocytes that circulate in the bloodstream and comprise two main subpopulations that in the mouse are best defined by the Ly6C marker. Intravascular functions of “classical” Ly6C
+
monocytes and their interactions with other lymphoid and myeloid leukocytes in the circulation remain poorly understood. Rather, these cells are known to efficiently extravasate into tissues. Indeed, Ly6C
+
monocytes and their descendants have emerged as a third, highly plastic and dynamic cellular system that complements the two classical, tissue-resident mononuclear phagocyte compartments, i.e., macrophages and dendritic cells, on demand. Following recruitment to injured tissue, Ly6C
+
monocytes respond to local cues and can critically contribute to the initiation and resolution of inflammatory reactions. The second main murine monocyte subset, Ly6C
–
cells, derive in steady state from Ly6C
+
monocytes and remain in the vasculature, where the cells act as scavengers. Moreover, a major fraction of Ly6C
–
monocytes adheres to the capillary endothelium and patrols the vessel wall for surveillance. Given the central role of monocytes in homeostasis and pathology, in-depth study of this cellular compartment can be highly informative on the health state of the organism and provides an attractive target for therapeutic intervention.
Where did the clot go? An unusual complication of mechanical thrombectomy caused by malignancy related subclavian steal phenomenon in a patient with acute basilar artery occlusion
Authors: Randhawa Nikkie , Squires Jonathan P , Heran Manraj Kanwal Singh , Mann Sharanpal K
Published: October 2016

Subclavian steal is a relatively common vascular phenomenon usually caused by atherosclerotic disease. While symptoms are rare, arm claudication of the ipsilateral limb is most common, with paroxysmal symptoms of vertebrobasilar insufficiency (often exercise induced) being relatively uncommon. Here we present a case of brachial artery embolism during mechanical thrombectomy for basilar artery thrombosis, secondary to subclavian steal phenomenon. This atypical and potentially irreversible complication should be considered in patients with acute ischemic stroke undergoing neurointerventional management when subclavian steal is discovered angiographically.
Paraurethral cysts in newborn girls
Authors: Costantino Eliana , Ganesan George S
Published: October 2016

The Skene's glands are located in the distal urethral floor, and they are the largest paraurethral glands. Skene's gland cysts are unusual at any age, but specially newborns. However, due to lack of systematic reporting, true incidence is probably higher than the one described in the literature. We present a newborn girl found to have a paraurethral cyst at birth. Characteristic displacement of the urethral opening was revealed on catheterisation. Review of literature, and comparison to a similar case of interlabial mass previously evaluated, were carried out. We suggest a prenatal development possibly due to maternal oestrogen exposure, although further studies are necessary to determine the exact aetiology. Treatment options include observation, needle aspiration and incisional drainage, partial excision, unroofing and marsupialisation. Expectant management is preferred in asymptomatic cases, particularly in newborns, since spontaneous resolution can occur without long-term sequalae or recurrence. Cases with acute obstruction require immediate surgical management.
Ventricular fibrillation via torsade des pointes of cardiac sarcoidosis with preserved left ventricular ejection fraction
Authors: Sekihara Takayuki , Nakane Eisaku , Nakasone Kazutaka , Inoko Moriaki
Published: October 2016

Generally, low left ventricular ejection fraction (LVEF) is a risk for ventricular arrhythmia in patients with cardiac sarcoidosis. We present a case of cardiac sarcoidosis with preserved LVEF that evoked ventricular fibrillation (VF). A 73-year-old woman with VF presented to our emergency department. She had a history of ocular sarcoidosis, with gradual thinning of the basal intraventricular septum. LVEF was 62% on the most recent echocardiography. The electrocardiogram after defibrillation showed complete atrioventricular block (CAVB) with QT segment prolongation and frequent ventricular premature beats. VF via torsade des pointes (TdP) was suspected, and temporary intravenous ventricular pacing and magnesium sulfate infusion suppressed her VF. Cardiac sarcoidosis was diagnosed, and an implantable cardioverter defibrillator was implanted. Patients with cardiac sarcoidosis with CAVB are at risk of evoking VF via TdP regardless of LVEF. If cardiac sarcoidosis is suspected, early diagnosis and risk stratification of ventricular arrhythmia are important.
Coronary artery bypass grafting with internal thoracic arteries may cause bilateral brachiocephalic vein occlusion, complicating pacemaker implantation
Authors: Nakabayashi Keisuke , Kato Hiroko , Sugiura Ryo , Oka Toshiaki
Published: October 2016

The number of patients with arrhythmia and ischaemic heart diseases is increasing. Patients with pacemaker implantation sometimes have brachiocephalic vein occlusion, and several aetiologies have been reported. However, coronary artery bypass grafting using the internal thoracic arteries is not fully discussed in the literature. We present a case of failed percutaneous pacemaker implantation due to bilateral brachiocephalic vein occlusion 8 years after coronary artery bypass grafting using the bilateral internal thoracic arteries. There were rich collateral veins consisting of hemiazygos and azygos veins. We then performed surgical implantation instead. Contrast CT or venography for such patients might be considered.
Lasting impact: insights from a surgical mission-based mentoring training programme in the Republic of Congo
Authors: White Michelle , Close Kristin
Published: October 2016

The global shortage of surgeons, anaesthetists and obstetricians is significant, especially in low and middle income countries (LMICs). A significant amount of LMIC surgical volume is provided by surgical missions and non-governmental organisations (NGOs) who are often well resourced, making them ideal environments for training. However, there are few publications addressing how to train in this setting, or the long-term impact of such training. Mercy Ships operates the largest non-governmental hospital ship in the world, theAfrica Mercy, serving LMICs at the invitation of their President by providing free surgery and training for the surgical workforce. Mercy Ships developed and offered a comprehensive training programme across surgical specialties and disciplines in the Republic of Congo, 2013–2014. In this analysis paper, we present our experiences in developing and implementing the training portion of the programme. We also present the findings of an evaluation of the programme, which show a sustained positive impact and lasting change on personal and organisational practice 12–18 months post-training. We also make recommendations to NGOs and surgical mission organisations seeking to augment the impact of surgical missions with effective surgical training programmes.
Screen time of infants in Sydney, Australia: a birth cohort study
Authors: Chandra Meena , Jalaludin Bin , Woolfenden Susan , Descallar Joseph , Nicholls Laura , Dissanayake Cheryl , Williams Katrina , Murphy Elisabeth , Walter Amelia , Eastwood John , Eapen Valsamma
Published: October 2016

Objectives

To determine the amount of daily screen time in children 18 months of age and ascertain correlations that may be contributing to excessive screen use.

Design

A birth cohort was followed with telephone interviews at 6, 12 and 18 months of age. Information about screen time was collected at 18 months.

Setting

Parents were recruited from postnatal wards of 2 major public hospitals and at home visits conducted for new mothers within 4 weeks of birth in South Western Sydney (SWS).

Participants

Parents of 500 children with infants 18 months of age residing in SWS.

Primary and secondary outcomes

Screen time in infants 18 months of age and associated correlations.

Results

A large percentage of children 18 months of age (40%) had screen times >2 hours daily. There were significant associations between more than 2 hours of screen time daily and mothers without a partner (OR 4.32 (95% CI 1.67 to 11.15)); having <3 siblings (no siblings: OR 2.44 (95% CI 1.20 to 4.94); 1–2 siblings: OR 2.08 (95% CI 1.06 to 4.08)); an employed father (OR 1.96 (95% CI 1.09 to 3.52)); no outdoor equipment at home (OR 1.89 (95% CI 1.08 to 3.34)) and fewer than 5 outings per week (OR 2.08 (95% CI 1.37 to 3.17)).

Conclusions

There is emerging evidence that excess screen time in children causes adverse cognitive, developmental and health outcomes. This study has shown that a large proportion of very young children residing in SWS have screen exposures for >2 hours per day. Factors contributing to excess screen time have also been identified in this study; however, a greater understanding of risk factors needs to be ascertained in order to facilitate greater public health efforts to reduce screen exposure.