bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystal structure and anti-inflammatory and anaphylactic effects of andrographlide sulphonate E in Xiyanping, a traditional Chinese medicine injection
Authors: Yang Qian-Wen , Li Qiao , Zhang Jie , Xu Qian , Yang Xin , Li Zhi-Yong , Xu Hui
Published: October 2018

Objectives

Andrographlide sulphonate E, namely sodium 9-dehydro-17-hydro-andrographolide-19-yl sulphate, was one of the major ingredients of Xiyanping injection. The present study aimed to demonstrate its suitability as a reference standard for use of quality control of this traditional Chinese medicine preparation made from andrographlide that has been widely used to treat various infectious diseases.

Methods

The stable crystals were prepared for unambiguous elucidation of the chemical structure by comprehensive spectral and thermal analysis. The anti-inflammatory effects were investigated using in vitro and in vivo methods, and the potential allergenic risk related with safety was evaluated by in silico molecular docking analysis.

Key findings

The dihydrated sulphonate derivative could be present as orthorhombic crystals with stable three-dimensional supramolecular structure, providing it the favourable physico-chemical stability as reference substance. It exhibited potent anti-inflammatory activity both in vitro and in vivo, suggesting the potency responsible for clinic efficacy of Xiyanping. Molecular docking further demonstrated its low risk of allergic reaction, as well as the proposed mechanism of anaphylactic effect of andrographolide analogues.

Conclusions

Dihydrated sodium 9-dehydro-17-hydro-andrographolide-19-yl sulphate may be the ideal reference standard for use in quality control of Xiyanping.
Intellectual property audit of an organization
Authors: Gargate Gouri , Siddiquee Qutbuddin , Wingkar Chaitanya
Published: October 2018

In this era of rapidly evolving Intellectual Property (IP) regimes, it is the need of the time to identify and efficiently utilize Intellectual Assets owned by an organization. It has now become a prerequisite for organizations to develop a expertise and capabilities not only to create IP through R&D, but also to manage it efficiently. There are various tools available for IP Management and IP audit is one such tool. In this paper, authors share IP audit experience of two leading Indian organizations operating in the electrical engineering sector. The analysis of the data provided various interesting observations and insights with reference to IP Management which may be useful to other organizations working in electrical engineering sector as well as organizations from the other sectors.
Introduction to a special feature issue – New insights into plant volatiles
Authors: Kessler André
Published: October 2018

This article is an Editorial on the special feature issue ‘New insights into plant volatiles’, which is published in this issue and which includes the following articles: Ameye et al., pp. 666–683; Sharifi et al. pp. 684–691; Moreira et al., pp. 703–713; Pichersky & Raguso, pp. 692–702; Chen et al., pp. 714–725; Danner et al., pp. 726–738; Junker et al., pp. 739–749; Rering et al., pp. 750–759; Eberl et al., pp. 760–772; Fernández‐Martínez et al., pp. 773–784; Glenny et al., pp. 785–798 and Visakorpi et al., pp. 799–810.
Fired Up by Morality: The Unique Physiological Response Tied to Moral Conviction in Politics
Authors: Garrett Kristin N.
Published: October 2018

Studies provide mounting evidence that morally convicted attitudes elicit passionate and unyielding political responses. Questions remain, however, whether these effects occur because moral conviction is another strong, versus a distinctly moral dimension of attitude strength. Building on work in moral psychology and neuroscience, I argue that moral conviction stems from a distinctive mode of mental processing that is tied to automatic affective reactions. Testing this idea using a lab experiment designed to capture self‐reported moral conviction and physiological arousal, I find that conviction about political objects positively predicts arousal evoked by the objects, while attitude extremity and importance do not. These findings suggest that moral conviction items do tap into moral processing, helping to validate the conviction measure. They also illustrate the value of using physiological indicators to study politics, help explain why morally convicted attitudes trigger such fervent responses, and raise normative questions about political conflict and compromise.
Effects of Humor on Intergroup Communication in Intractable Conflicts: Using Humor in an Intergroup Appeal Facilitates Stronger Agreement Between Groups and a Greater Willingness to Compromise
Authors: Nir Nimrod , Halperin Eran
Published: October 2018

Overcoming sociopsychological barriers within intergroup communications may bring forth new, practical methods for conflict resolution, particularly crucial for groups engulfed by intractable conflict. This article examines the use of humor—an extremely effective technique of persuasive communication—as one potential route whose potency in resolving intractable conflicts has thus far been neglected. In Study 1, Palestinians who read a message from an “Israeli representative” (conveying the Israeli narrative of the conflict) agreed more with the Israeli perspective once three short humorous asides were added to the original statement. When these humorous asides targeted Jewish‐Israelis, Palestinian‐Israeli participants were more willing to compromise on various aspects of the conflict. In Study 2, Jewish‐Israelis who read a message from a “Palestinian representative” were more agreeable to the Palestinian message (portraying the Palestinian narrative) once three short humorous asides were added to the original statement. When these humorous asides were general in nature (but not when they targeted Palestinian‐Israelis), Jewish‐Israeli participants were more willing to compromise on various aspects of this intractable conflict. These findings further demonstrate the power of psychological barriers in intractable conflicts and the potential of humor to overcome them. Implications and limitations of the current research are discussed.
Polycentricity and the Hollow State: Exploring Shared Personnel as a Source of Connectivity in Fragmented Urban Systems
Authors: Scott Tyler A. , Greer Robert A.
Published: October 2018

The Ecology of Games (EoG) theory couples institutional rational choice with social network theory, articulating how transaction costs, social capital, and collective action dilemmas shape networks and network outcomes in polycentric governance systems. EoG literature has often focused on social–relational ties across organizational boundaries. However, jurisdictional fragmentation and increased reliance on private contractors in local public service delivery foster another source of network connectivity—shared personnel who work for multiple service providers. Drawing upon novel data of organizational personnel from more than 500 special purpose entities responsible for delivering drinking water to local neighborhoods in the Houston metro area in the state of Texas (United States), we examine how managerial, technical, and financial service delivery personnel connect otherwise independent organizations. We find that districts regulated by a common groundwater management agency and districts which contract with one another are both more likely to share technical and managerial personnel. By studying special districts that have overlapping personnel, we broaden the scope of the EoG framework to include additional layers of governance network complexity. As individual bureaucrats and service professionals play a key role in information transfer and innovation diffusion across organizations, shared personnel networks merit consideration as a mechanism for coordination and collective problem solving in fragmented urban systems.
Role of pyrimidine salvage pathway in the maintenance of organellar and nuclear genome integrity
Authors: Pedroza‐García José‐Antonio , Nájera‐Martínez Manuela , Mazubert Christelle , Aguilera‐Alvarado Paulina , Drouin‐Wahbi Jeannine , Sánchez‐Nieto Sobeida , Gualberto José M. , Raynaud Cécile , Plasencia Javier
Published: October 2018

Nucleotide biosynthesis proceeds through a de novo pathway and a salvage route. In the salvage route, free bases and/or nucleosides are recycled to generate the corresponding nucleotides. Thymidine kinase (TK) is the first enzyme in the salvage pathway to recycle thymidine nucleosides as it phosphorylates thymidine to yield thymidine monophosphate. The Arabidopsis genome contains two TK genes −TK1a and TK1b− that show similar expression patterns during development. In this work, we studied the respective roles of the two genes during early development and in response to genotoxic agents targeting the organellar or the nuclear genome. We found that the pyrimidine salvage pathway is crucial for chloroplast development and genome replication, as well as for the maintenance of its integrity, and is thus likely to play a crucial role during the transition from heterotrophy to autotrophy after germination. Interestingly, defects in TK activity could be partially compensated by supplementation of the medium with sugar, and this effect resulted from both the availability of a carbon source and the activation of the nucleotide de novo synthesis pathway, providing evidence for a compensation mechanism between two routes of nucleotide biosynthesis that depend on nutrient availability. Finally, we found differential roles of the TK1a and TK1b genes during the plant response to genotoxic stress, suggesting that different pools of nucleotides exist within the cells and are required to respond to different types of DNA damage. Altogether, our results highlight the importance of the pyrimidine salvage pathway, both during plant development and in response to genotoxic stress.
Structural Breaks and Volatility Persistence of Stock Returns: Evidence from the US and UK Equity Markets
Authors: Tsuji Chikashi
Published: October 2018

This paper quantitatively investigates the effects of structural breaks on stock return volatility persistence by using the US and UK stock market index return data. Applying two kinds of representative univariate GARCH models of standard GARCH and EGARCH models, we derive the following interesting findings. (1) First, we find that for both the US and UK stock market returns, the volatility persistence parameter values of standard GARCH models decrease when structural breaks are taken into account. (2) Second, we further reveal that for both the US and UK stock market returns, the volatility persistence parameter values of EGARCH models again decline when structural breaks are taken into consideration.
Exercise training reduces the insulin‐sensitizing effect of a single bout of exercise in human skeletal muscle
Authors: Steenberg Dorte E. , Jørgensen Nichlas B. , Birk Jesper B. , Sjøberg Kim A. , Kiens Bente , Richter Erik A. , Wojtaszewski Jørgen F.P.
Published: October 2018

Key points

A single bout of exercise is capable of increasing insulin sensitivity in human skeletal muscle. Whether this ability is affected by training status is not clear.

Studies in mice suggest that the AMPK‐TBC1D4 signalling axis is important for the increased insulin‐stimulated glucose uptake after a single bout of exercise.

The present study is the first longitudinal intervention study to show that, although exercise training increases insulin‐stimulated glucose uptake in skeletal muscle at rest, it diminishes the ability of a single bout of exercise to enhance muscle insulin‐stimulated glucose uptake.

The present study provides novel data indicating that AMPK in human skeletal muscle is important for the insulin‐sensitizing effect of a single bout of exercise.

Not only chronic exercise training, but also a single bout of exercise, increases insulin‐stimulated glucose uptake in skeletal muscle. However, it is not well described how adaptations to exercise training affect the ability of a single bout of exercise to increase insulin sensitivity. Rodent studies suggest that the insulin‐sensitizing effect of a single bout of exercise is AMPK‐dependent (presumably via the α2β2γ3 AMPK complex). Whether this is also the case in humans is unknown. Previous studies have shown that exercise training decreases the expression of the α2β2γ3 AMPK complex and diminishes the activation of this complex during exercise. Thus, we hypothesized that exercise training diminishes the ability of a single bout of exercise to enhance muscle insulin sensitivity. We investigated nine healthy male subjects who performed one‐legged knee‐extensor exercise at the same relative intensity before and after 12 weeks of exercise training. Training increased and expression of mitochondrial proteins in muscle, whereas the expression of AMPKγ3 was decreased. Training also increased whole body and muscle insulin sensitivity. Interestingly, insulin‐stimulated glucose uptake in the acutely exercised leg was not enhanced further by training. Thus, the increase in insulin‐stimulated glucose uptake following a single bout of one‐legged exercise was lower in the trained vs. untrained state. This was associated with reduced signalling via confirmed α2β2γ3 AMPK downstream targets (ACC and TBC1D4). These results suggest that the insulin‐sensitizing effect of a single bout of exercise is also AMPK‐dependent in human skeletal muscle.
Baroreflex functionality in the eye of diffusion tensor imaging
Authors: Tsai Ching‐Yi , Poon Yan‐Yuen , Chan Julie Y. H. , Chan Samuel H. H.
Published: October 2018

By applying diffusion tensor imaging (DTI) as a physiological tool to evaluate changes in functional connectivity between key brainstem nuclei in the baroreflex neural circuits of mice and rats, recent work has revealed several hitherto unidentified phenomena regarding baroreflex functionality. (1) The presence of robust functional connectivity between nucleus tractus solitarii (NTS) and nucleus ambiguus (NA) or rostral ventrolateral medulla (RVLM) offers a holistic view on the moment‐to‐moment modus operandi of the cardiac vagal baroreflex or baroreflex‐mediated sympathetic vasomotor tone. (2) Under pathophysiological conditions (e.g. neurogenic hypertension), the disruption of functional connectivity between key nuclei in the baroreflex circuits is reversible. However, fatality ensues on progression from pathophysiological to pathological conditions (e.g. hepatic encephalopathy) when the functional connectivity between NTS and NA or RVLM is irreversibly severed. (3) The absence of functional connectivity between the NTS and caudal ventrolateral medulla (CVLM) necessitates partial rewiring of the classical neural circuit that includes CVLM as an inhibitory intermediate between the NTS and RVLM. (4) Sustained functional connectivity between the NTS and NA is responsible for the vital period between brain death and the inevitable cardiac death. (5) Reduced functional connectivity between the NTS and RVLM or NA points to inherent anomalous baroreflex functionality in floxed and Cre‐Lox mice. (6) Disrupted NTS‐NA functional connectivity in Flk‐1 (VEGFR2) deficient mice offers an explanation for the hypertensive side‐effect of anti‐vascular endothelial growth factor therapy (anti‐VEGF) therapy. These newly identified baroreflex functionalities revealed by DTI bear clinical and therapeutic implications.
Tribological and Nanomechanical Behavior of Liquid Wood
Authors: Broitman Esteban , Nedelcu Dumitru , Mazurchevici Simona , Glenat Hervè , Grillo Stefano
Published: October 2018

During the last decades, there has been an increased interest in the use of lignin-based composites following the ideas of developing green materials for fossil-based raw materials substitution. The biopolymer Arboform is a mixture of lignin, plant fibers, and additives, which is nowadays successfully used in many applications. As a thermoplastic, it can be molded and is therefore also called “liquid wood.” In this paper, we report a study comparing the nanomechanical and tribological properties of Arboform (AR), and Aramid-reinforced Arboform (AR-AF) composite biopolymers. The samples were produced in an industrial-scale injection molding machine. Nanoindentation experiments have revealed that, in both series of biopolymer samples, an increase in temperature or a change in the injection direction from 0 deg to 90 deg produces an increase in hardness. On the other hand, Young's modulus is slightly affected by the increase in temperature, and not affected by the injection angle. Tribological characterization has shown that all samples, except the AR-AF injected at 175 °C, present noticeable wear and have a similar friction coefficients μ ∼ 0.44–0.49 at Hertzian contact pressures p0 between 90 and 130 MPa. Interestingly, the reinforced polymer produced at 175 °C shows no wear and low friction of μ ∼ 0.19 at p0 = 90 MPa. Our results show that the reinforced Arboform biopolymers are a good candidate to replace other polymers in many mechanical and tribological applications.
Conceptual Design of Structures Using an Upper Bound of von Mises Stress
Authors: Kumar Ashok V.
Published: October 2018

Optimal layouts for structural design have been generated using topology optimization approach with a wide variety of objectives and constraints. Minimization of compliance is the most common objective but the resultant structures often have stress concentrations. Two new objective functions, constructed using an upper bound of von Mises stress, are presented here for computing design concepts that avoid stress concentration. The first objective function can be used to minimize mass while ensuring that the design is conservative and avoids stress concentrations. The second objective can be used to tradeoff between maximizing stiffness versus minimizing the maximum stress to avoid stress concentration. The use of the upper bound of von Mises stress is shown to avoid singularity problems associated with stress-based topology optimization. A penalty approach is used for eliminating stress concentration and stress limit violations which ensures conservative designs while avoiding the need for special algorithms for handling stress localization. In this work, shape and topology are represented using a density function with the density interpolated piecewise over the elements to obtain a continuous density field. A few widely used examples are utilized to study these objective functions.
Efficient Compliant Variation Simulation of Spot-Welded Assemblies
Authors: Lorin Samuel , Lindau Björn , Lindkvist Lars , Söderberg Rikard
Published: October 2018

During product development one important aspect is the geometric robustness of the design. This is due to the fact that all manufacturing processes lead to products with variation. Failing to properly account for the variability of the process in the design phase may lead to expensive redesign. One important tool during the design phase in many industries is variation simulation, which makes it possible to predict and optimize the geometric quality of the design. However, despite the increase in computer power, calculation time is still an obstacle for the wider use of variation simulation. In this article, we propose a new method for efficient compliant variation simulation of spot-welded sheet metal assemblies. The method is exact, and we show that the method leads to time savings in simulation of approximately 40–50% compared to current state-of-the-art variation simulation.
Discrete-Time Robust Control With an Anticipative Action for Preview Systems
Authors: Achnib Asma , Airimitoaie Tudor-Bogdan , Lanusse Patrick , Abrashov Sergey , Aoun Mohamed , Chetoui Manel
Published: October 2018

A discrete-time robust controller design method is proposed for optimal tracking of future references in preview systems. In the context of preview systems, it is supposed that future values of the reference signal are available a number of time steps ahead. The objective is to design a control algorithm that minimizes a quadratic error between the reference and the output of the system and at the same time achieves a good level of the control signal. The proposed solution combines a robust feedback controller with a feedforward anticipative filter. The feedback controller's purpose is to assure robustness of the closed-loop system to model uncertainties. Any robust control methodology can be used (such as μ-synthesis, qft, or crone control). The focus of this paper will be on the design of the feedforward action in order to introduce the anticipative effect with respect to known future values of the reference signal without hindering the robustness achieved through the feedback controller. As such, the model uncertainties are taken into account also in the design of the feedforward anticipative filter. The proposed solution is validated in simulation and on an experimental water tank level control system.
The Theoretical Volumetric Displacement of a Check-Valve Type, Digital Displacement Pump
Authors: Manring Noah , Williamson Christopher
Published: October 2018

This paper has been written to develop closed-form equations for describing the theoretical displacement of a check-valve type, digital displacement pump. In theory, the digital displacement pump is used to alter the apparent volumetric displacement of the machine by short circuiting the flow path for reciprocating pistons within the machine that would ordinarily deliver a full volumetric flow rate to the discharge side of the pump. The short circuiting for the pistons is achieved by opening and closing a digital valve connected to each piston chamber at a desired time during the kinematic cycle for each reciprocating piston. Experience with these machines has shown that the expected volumetric displacement for the machine tends to decrease with pressure. This paper presents a theoretical explanation for the reduced volumetric displacement of the pump and quantifies the expected behavior based upon the digital valve command, the residual volume of fluid within a single piston chamber, and the fluid bulk modulus-of-elasticity. In summary, it shown that the apparent volumetric displacement of the machine may be reduced by as much as 10% for high-displacement commands and by as much as 30% for low-displacement commands.
Study on BEOL Failures in a Chip by Shear Tests of Copper Pillar Bumps
Authors: Wang Lei , Wang Jun , Xiao Fei
Published: October 2018

A chip with 40 nm technology node and beyond generally incorporates low-k/ultra-low-k (LK/ULK) dielectric materials and copper traces in the back end of line (BEOL) to improve its electrical performance. Owing to the fragile low-k/ultra-low-k materials, the BEOL becomes vulnerable to external loads. When a copper pillar bump (CPB) above the BEOL sustains a shear force due to thermal mismatch between the components, failures occur in the microstructures of BEOL, especially in low-k materials. We fabricated CPBs on the chips and investigated fractures in the BEOL by a shear test approach. The shear speed and shear height are varied to examine their effects. The tested samples were analyzed via focused ion beam (FIB) and scanning electron microscope (SEM) to reveal the microstructures degradation or breaks in the BEOL, and they are classified into three kinds of failure modes. Assisted by a finite element analysis (FEA), the failure mechanism was explained and associated with the failure modes. The studies showed that the shear speed has a little influence on the maximum shear stress, but the increase of shear height leads to more fractures in the low-k materials. It indicated that decreasing the height of CPBs is helpful for reducing destruction risk of the BEOL under the thermomechanical loads. Based on a parametric study for shearing test simulation of a single CPB, the modulus and thickness of polyimide (PI) were found a larger impact on the stresses in the low-k material layer, but the modulus of low-k materials has a smaller effect on the stress. Generally, the shear test of a CPB can help to evaluate the integrity of BEOL in a chip.
Numerical and Experimental Investigation of the Cavitating Flow Within Venturi Tube
Authors: Kozák Jiří , Rudolf Pavel , Hudec Martin , Štefan David , Forman Matěj
Published: October 2018

Hydrodynamic cavitation represents complex physical phenomenon undesirably affecting operation as well as lifespan of many hydraulic machines from small valves to the large hydro power plants. On the other hand, the same phenomenon and its concomitants such as pressure pulsations can be exploited in many positive ways. One of them which seems to be very promising and perspective is the cavitation utilization for reduction of the microorganisms such as cyanobacteria within large bulks of water. Mutual effect of the swirl induced by the upstream mounted generator and flow constriction in converging–diverging nozzle has been experimentally investigated. The analysis of the hydraulic losses in the wide range of the cavitation regimes has been done as well as the investigation of the pipe wall acceleration induced by the fluctuations of the cavitating structures. The dynamics of the cavitation was studied using the proper orthogonal decomposition (POD) of the captured video records. The main scope of this paper is numerical investigation complementing the experimental results. The multiphase simulations were carried out using the OpenFOAM 1606+ and its interPhaseChangeFoam solver. The present study focuses on computational fluid dynamics results of the cavitating velocity field within the nozzle and analysis of the loss coefficient within the nozzle. The results of the numerical analysis were utilized for the further discussion of the experimental results.
Influence of Lubricant Pressure Response on Subsurface Stress in Elastohydrodynamically Lubricated Finite Line Contacts
Authors: Hultqvist Tobias , Vrcek Aleks , Prakash Braham , Marklund Pär , Larsson Roland
Published: October 2018

In order to adapt to increasingly stringent CO2 regulations, the automotive industry must develop and evaluate low cost, low emission solutions in the powertrain technology. This often implies increased power density and the use of low viscosity oils, leading to additional challenges related to the durability of various machine elements. Therefore, an increased understanding of lubricated contacts becomes important where oil viscosity–pressure and compressibility–pressure behavior have been shown to influence the film thickness and pressure distribution in elastohydrodynamic lubrication (EHL) contacts, further influencing the durability. In this work, a finite line EHL contact is analyzed with focus on the oil compressibility–pressure and viscosity–pressure response, comparing two oils with relatively different behavior and its influence on subsurface stress concentrations in the contacting bodies. Results indicate that increased pressure gradients and pressure spikes, and therefore increased localized stress concentrations, can be expected for stiffer, less compressible oils, which under transient loading conditions not only affect the outlet but also the edges of the roller.
Surface characterization of clean SrTiO3(100) substrates by x-ray photoelectron spectroscopy
Authors: Nono Tchiomo Arnaud P. , Babu-Geetha Ganga , Carleschi Emanuela , Ngabonziza Prosper , Doyle Bryan P.
Published: October 2018

The authors analyze the x-ray photoelectron spectra of SrTiO3(100) (STO) substrates to clarify the electronic structure characteristics induced by a sputter–anneal procedure. The survey spectra, the valence band spectra, and the relevant core level spectra, i.e., Sr 3s, Sr 3p, Sr 3d, Sr 4s, Sr 4p, Ti 2p, Ti 3s, Ti 3p, O 1s, and O 2s along with their satellite structures, of both pristine and sputtered and annealed STO have been measured. A comparison of spectra reveals the appearance of new features in the Ti 2p spectra of sputtered and annealed STO, corresponding to Ti3+ states and gap states near the Fermi energy. The presence of Ti3+ states points to the formation of a two-dimensional electron system at the STO surface generated by Ar+ sputtering and annealing in vacuum. Furthermore, the sputter-annealed surface shows only minor carbon contamination as compared to that of the pristine substrate.
Evaluation of the effectiveness of kINPen Med plasma jet and bioactive agent therapy in a rat model of wound healing
Authors: Breathnach Rory , McDonnell Kevin A. , Chebbi Ahmed , Callanan John J. , Dowling Denis P.
Published: October 2018

Chronic nonhealing wounds, particularly those complicated by multidrug resistant infections, represent a major health and economic challenge. Plasma treatment promotes wound repair due to its antimicrobial, angiogenic, and cell modulating properties. This study investigated the efficacy of the kINPen Med system in promoting healing and assessed if efficacy was enhanced by adding collagen or hyaluronic acid (HA). Two 6 mm diameter punch biopsy wounds were created on the lumbar spine of Sprague Dawley rats. Based on the results of a pilot study, operating process conditions involving 30 s plasma/day were selected for the pivotal study. In the pivotal study, six groups of rats (n = 28/group) received either control (1), plasma (2), HA (3), plasma and HA (4), collagen (5), or plasma and collagen (6). Wound measurements were obtained on Days 0, 4, 7, and 14. The mean reduction in wound size was significantly higher in all treatment groups compared to controls on Day 4; group 6 performed best. On Day 7, group 6 still performed significantly better compared to groups 1, 2, 3, and 4. Day 14 results were more comparable between groups. Histology (Day 14) revealed epidermal hyperplasia and serocellular crusts. Neutrophilic infiltrates in group 6 were significantly lower compared to group 2. Mononuclear infiltrates were highest in groups 3 and 5, while Langerhans cells were observed in all groups. These results underpin the clinical benefits of the kINPen Med plasma system, particularly when combined with collagen during early inflammatory phases, and support the conduct of future human clinical trials.
Minimal attachment of Pseudomonas aeruginosa to DNA modified surfaces
Authors: Pingle Hitesh , Wang Peng-Yuan , Cavaliere Rosalia , Whitchurch Cynthia B. , Thissen Helmut , Kingshott Peter
Published: October 2018

Extracellular deoxyribonucleic acid (eDNA) exists in biological environments such as those around medical implants since prokaryotic or eukaryotic cells can undergo processes such as autolysis, necrosis, and apoptosis. For bacteria, eDNA has been shown to be involved in biofilm formation and gene transfer and acts as a nutrient source. In terms of biofilm formation, eDNA in solution has been shown to be very important in increasing attachment; however, very little is known about the role played by surface immobilized eDNA in initiating bacterial attachment and whether the nature of a DNA layer (physically adsorbed or covalently attached, and molecular weight) influences biofilm formation. In this study, the authors shed light on the role that surface attached DNA plays in the early biofilm formation by using Si wafers (Si) and allylamine plasma polymer (AAMpp) coated Si wafers to adsorb and covalently immobilize salmon sperm DNA of three different molecular weights. Pseudomonas aeruginosa was chosen to study the bacterial interactions with these DNA functionalized surfaces. Characterization of surface chemistry and imaging of attached bacteria were performed via x-ray photoelectron spectroscopy (XPS), scanning electron microscopy, and epi-fluorescence microscopy. XPS results confirmed the successful grafting of DNA on the AAMpp and Si surfaces, and surprisingly the results showed that the surface attached DNA actually reduced initial bacterial attachment, which was contrary to the initial hypothesis. This adds speculation about the specific role played by DNA in the dynamics of how it influences biofilm formation, with the possibility that it could actually be used to make bacterial resistant surfaces.
Acquisition of Extended-Spectrum β-Lactamase GES-6 Leading to Resistance to Ceftolozane-Tazobactam Combination in
Pseudomonas aeruginosa
Authors: Poirel Laurent , Ortiz De La Rosa José-Manuel , Kieffer Nicolas , Dubois Véronique , Jayol Aurélie , Nordmann Patrice
Published: October 2018

A clinical
Pseudomonas aeruginosa
isolate resistant to all β-lactams, including ceftolozane-tazobactam and carbapenems, was recovered. It belonged to sequence type 235 and produced the extended-spectrum β-lactamase (ESBL) GES-6 differing from GES-1 by two amino acid substitutions (E104K and G170S).
Spectrum of choroidal neovascularisation associated with dome-shaped macula
Authors: Marchese Alessandro , Arrigo Alessandro , Sacconi Riccardo , Querques Lea , Prascina Francesco , Pierro Luisa , Bandello Francesco , Querques Giuseppe
Published: October 2018

Aims

To investigate the clinical spectrum of choroidal neovascularisation (CNV) in patients with dome-shaped macula with the aid of multimodal imaging.

Methods

In this cross-sectional, retrospective, observational study, we reviewed charts and imaging studies of 144 eyes of 79 consecutive patients with dome-shaped macula evaluated at a tertiary referral centre, including optical coherence tomography angiography (OCTA), fluorescein angiography (FA) and indocyanine green angiography (ICGA). Three masked graders evaluated the prevalence and type of CNV. Primary outcome measures were the diagnostic agreement between OCTA and FA±ICGA, the multimodal imaging characteristics and prevalence of CNV associated with dome-shaped macula.

Results

We identified 30 eyes with dome-shaped macula complicated by CNV with an estimated prevalence of 20.8% (95% CI 14.2 to 27.4). Twenty-two eyes (73%) showed a type 2 CNV while eight eyes (27%) showed a type 1 CNV. Serous macular detachment was present in 39 eyes (27%) and harboured a CNV in five cases (13%). The overall diagnostic agreement between OCTA and FA±ICGA was excellent (k=0.894, p<0.001), but only the use of both techniques allowed the identification of the whole pool of CNVs.

Conclusion

Eyes with dome-shaped macula may either develop typical myopic CNV (ie, type 2 CNV) or pachychoroid-associated CNV (ie, type 1 CNV), similar to those observed in central serous chorioretinopathy. Accordingly, in case of serous macular detachment complicating dome-shaped macula, the presence of an associated CNV should be considered. When suspecting a CNV associated with dome-shaped macula, the application of both OCTA and FA±ICGA is superior to the use of one technique alone.
Creation of the WHO Indicators of Infant and Young Child Development (IYCD): metadata synthesis across 10 countries
Authors: Lancaster Gillian A , McCray Gareth , Kariger Patricia , Dua Tarun , Titman Andrew , Chandna Jaya , McCoy Dana , Abubakar Amina , Hamadani Jena Derakhshani , Fink Günther , Tofail Fahmida , Gladstone Melissa , Janus Magdalena
Published: October 2018

Background

Renewed global commitment to the improvement of early child development outcomes, as evidenced by the focus of the United Nations Sustainable Development Goal 4, highlights an increased need for reliable and valid measures to evaluate preventive and interventional efforts designed to affect change. Our objective was to create a new tool, applicable across multicultures, to measure development from 0 to 3 years through metadata synthesis.

Methods

Fourteen cross-sectional data sets were contributed on 21 083 children from 10 low/middle-income countries (LMIC), assessed using seven different tools (caregiver reported or directly assessed). Item groups, measuring similar developmental skills, were identified by item mapping across tools. Logistic regression curves displayed developmental trajectories for item groups across countries and age. Following expert consensus to identify well-performing items across developmental domains, a second mapping exercise was conducted to fill any gaps across the age range. The first version of the tool was constructed. Item response analysis validated our approach by putting all data sets onto a common scale.

Results

789 individual items were identified across tools in the first mapping and 129 item groups selected for analysis. 70 item groups were then selected through consensus, based on statistical performance and perceived importance, with a further 50 items identified at second mapping. A tool comprising 120 items (23 fine motor, 23 gross motor, 20 receptive language, 24 expressive language, 30 socioemotional) was created. The linked data sets on a common scale showed a curvilinear trajectory of child development, highlighting the validity of our approach through excellent coverage by age and consistency of measurement across contributed tools, a novel finding in itself.

Conclusions

We have created the first version of a prototype tool for measuring children in the early years, developed using novel easy to apply methodology; now it needs to be feasibility tested and piloted across several LMICs.
Corporal punishment bans and physical fighting in adolescents: an ecological study of 88 countries
Authors: Elgar Frank J , Donnelly Peter D , Michaelson Valerie , Gariépy Geneviève , Riehm Kira E , Walsh Sophie D , Pickett William
Published: October 2018

Objective

To examine the association between corporal punishment bans and youth violence at an international level.

Design

Ecological study of low-income to high-income 88 countries.

Setting

School-based health surveys of students.

Participants

403 604 adolescents.

Interventions

National corporal punishment bans.

Primary outcome measure

Age-standardised prevalence of frequent physical fighting (ie, 4+ episodes in the previous year) for male and female adolescents in each country.

Results

Frequent fighting was more common in males (9.9%, 95% CI 9.1% to 10.7%) than females (2.8%, 95% CI 2.5% to 3.1%) and varied widely between countries, from 0.9% (95% CI 0.8% to 0.9%) in Costa Rican females to 34.8% (95% CI 34.7 to 35.0) in Samoan males. Compared with 20 countries with no ban, the group of 30 countries with full bans (in schools and in the home) experienced 69% the rate of fighting in males and 42% in females. Thirty-eight countries with partial bans (in schools but not in the home) experienced less fighting in females only (56% the rate found in countries without bans).

Conclusions

Country prohibition of corporal punishment is associated with less youth violence. Whether bans precipitated changes in child discipline or reflected a social milieu that inhibits youth violence remains unclear due to the study design and data limitations. However, these results support the hypothesis that societies that prohibit the use of corporal punishment are less violent for youth to grow up in than societies that have not.
Preferred learning modalities and practice for critical skills: a global survey of paediatric emergency medicine clinicians
Authors: Craig Simon S , Auerbach Marc , Cheek John Alexander , Babl Franz E , Oakley Ed , Nguyen Lucia , Rao Arjun , Dalton Sarah , Lyttle Mark D , Mintegi Santiago , Nagler Joshua , Mistry Rakesh D , Dixon Andrew , Rino Pedro , Kohn-Loncarica Guillermo , Dalziel Stuart R
Published: October 2018

Objective

To describe senior paediatric emergency clinician perspectives on the optimal frequency of and preferred modalities for practising critical paediatric procedures.

Methods

Multicentre multicountry cross-sectional survey of senior paediatric emergency clinicians working in 96 EDs affiliated with the Pediatric Emergency Research Network.

Results

1332/2446 (54%) clinicians provided information on suggested frequency of practice and preferred learning modalities for 18 critical procedures. Yearly practice was recommended for six procedures (bag valve mask ventilation, cardiopulmonary resuscitation (CPR), endotracheal intubation, laryngeal mask airway insertion, defibrillation/direct current (DC) cardioversion and intraosseous needle insertion) by at least 80% of respondents. 16 procedures were recommended for yearly practice by at least 50% of respondents. Two procedures (venous cutdown and ED thoracotomy) had yearly practice recommended by <40% of respondents. Simulation was the preferred learning modality for CPR, bag valve mask ventilation, DC cardioversion and transcutaneous pacing. Practice in alternative clinical settings (eg, the operating room) was the preferred learning modality for endotracheal intubation and laryngeal mask insertion. Use of models/mannequins for isolated procedural training was the preferred learning modality for all other invasive procedures. Free-text responses suggested the utility of cadaver labs and animal labs for more invasive procedures (thoracotomy, intercostal catheter insertion, open surgical airways, venous cutdown and pericardiocentesis).

Conclusions

Paediatric ED clinicians suggest that most paediatric critical procedures should be practised at least annually. The preferred learning modality depends on the skill practised; alternative clinical settings are thought to be most useful for standard airway manoeuvres, while simulation-based experiential learning is applicable for most other procedures.
Extended treatment of venous thromboembolism: a systematic review and network meta-analysis
Authors: Wang Kang-Ling , van Es Nick , Cameron Chris , Castellucci Lana A , Büller Harry R , Carrier Marc
Published: October 2018

Objective

To evaluate efficacy and safety of oral anticoagulant regimens and aspirin for extended venous thromboembolism (VTE) treatment.

Methods

We searched MEDLINE, Embase, CENTRAL and conference proceedings for randomised controlled trials studying vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or aspirin for secondary prevention of VTE beyond 3 months. ORs (95% credible intervals) between treatments were estimated using random-effects Bayesian network meta-analysis.

Results

Sixteen studies, totaling more than 22 000 patients, were included. Compared with placebo or observation and with aspirin, respectively, the risk of recurrent VTE was lower with standard-intensity VKAs (0.15 (0.08 to 0.24) and 0.23 (0.09 to 0.54)), low-dose factor Xa inhibitors (0.16 (0.06 to 0.38) and 0.25 (0.09 to 0.66)), standard-dose factor Xa inhibitors (0.17 (0.08 to 0.33) and 0.27 (0.11 to 0.65)) and the direct thrombin inhibitor (0.15 (0.04 to 0.37) and 0.23 (0.06 to 0.74)) although the risk of major bleeding was higher with standard-intensity VKAs (4.42 (1.99 to 12.24) and 4.14 (1.17 to 18.86)). Effect estimates were consistent in male patients and those with index pulmonary embolism or with unprovoked VTE and in sensitivity analyses. In addition, compared with placebo or observation, the risk of all-cause mortality was reduced with standard-intensity VKAs (0.44 (0.20 to 0.87)) and low-dose factor Xa inhibitors (0.38 (0.12 to 0.995)).

Conclusions

Standard-intensity VKAs and DOACs are more efficacious than aspirin for extended VTE treatment. Despite a higher risk of major bleeding, standard-intensity VKAs was associated with a lower risk of all-cause mortality. Since overall efficacy and safety of standard-intensity VKAs and DOACs are in equipoise, patient factors, costs and patient preferences should be considered when recommending extending anticoagulation treatment.
Severe sociopolitical stressors and preterm births in New York City: 1 September 2015 to 31 August 2017
Authors: Krieger Nancy , Huynh Mary , Li Wenhui , Waterman Pamela D , Van Wye Gretchen
Published: October 2018

Background

Severe stressors can induce preterm birth (PTB; gestation <37 weeks), with such stressors including social and economic threats, interpersonal violence, hate crimes and severe sociopolitical stressors (ie, arising from political leaders’ threatening rhetoric or from political legislation). We analysed temporal changes in risk of PTB among immigrant, Hispanic and Muslim populations targeted in the US 2016 presidential election and its aftermath.

Methods

Trend analysis of all singleton births in New York City from 1 September 2015 to 31 August 2017 (n=230 105).

Results

Comparing the period before the US presidential nomination (1 September 2015 to 31 July 2016) to the post-inauguration period (1 January 2017 to 31 August 2017), the overall PTB rate increased from 7.0% to 7.3% (relative risk (RR): 1.04; 95% CI 1.00 to 1.07). Among Hispanic women, the highest post-inauguration versus pre-inauguration increase occurred among foreign-born Hispanic women with Mexican or Central American ancestry (RR: 1.15; 95% CI 1.01 to 1.31). The post-inauguration versus pre-inauguration PTB rate also was higher for women from the Middle East/North Africa and from the travel ban countries, although non-significant due to the small number of events.

Conclusion

Severe sociopolitical stressors may contribute to increases in the risk of PTB among targeted populations.
Biallelic mutations in EXOC3L2 cause a novel syndrome that affects the brain, kidney and blood
Authors: Shalata Adel , Lauhasurayotin Supanun , Leibovitz Zvi , Li Hongbing , Hebert Diane , Dhanraj Santhosh , Hadid Yarin , Mahroum Mohammed , Bajar Jacob , Egenburg Sandro , Arad Ayala , Shohat Mordechai , Haddad Sami , Bakry Hassan , Moshiri Houtan , Scherer Stephen W , Tzur Shay , Dror Yigal
Published: October 2018

Background

Dandy-Walker malformation features agenesis/hypoplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle and enlargement of posterior fossa. Although Dandy-Walker malformation is relatively common and several genes were linked to the syndrome, the genetic cause in the majority of cases is unknown.

Objective

To identify the mutated gene responsible for Dandy-Walker malformation, kidney disease and bone marrow failure in four patients from two unrelated families.

Methods

Medical assessment, sonographic, MRI and pathological studies were used to define phenotype. Chromosomal microarray analysis and whole-exome sequence were performed to unravel the genotype.

Results

We report four subjects from two unrelated families with homozygous mutations in the Exocyst Complex Component 3-Like-2 gene (EXOC3L2).EXOC3L2 functions in trafficking of post-Golgi vesicles to the plasma membrane. In the first family a missense mutation in a highly conserved amino acid, p.Leu41Gln, was found in three fetuses; all had severe forms of Dandy-Walker malformation that was detectable by prenatal ultrasonography and confirmed by autopsy. In the second family, the affected child carried a nonsense mutation, p.Arg72*, and no detected protein. He had peritrigonal and cerebellar white matter abnormalities with enlargement of the ventricular trigones, developmental delay, pituitary hypoplasia, severe renal dysplasia and bone marrow failure.

Conclusion

We propose that biallelic EXOC3L2 mutations lead to a novel syndrome that affects hindbrain development, kidney and possibly the bone marrow.
British Army recruits with low serum vitamin D take longer to recover from stress fractures
Authors: Richards Thomas , Wright C
Published: October 2018

Background

Recruits undergoing military training experience a particularly high incidence of stress fractures. The role of combined calcium and vitamin D (25-OHD) deficiency and subsequent supplementation has been well described in the literature, but the role of 25-OHD deficiency alone is less well understood, particularly its influence on recovery once a stress fracture has been incurred.

Methods

Retrospective data of recruits who had incurred stress fractures were collected (n=37). Independent-samples t-tests were conducted in Microsoft Excel to investigate the association between serum-25 OHD and the time taken to recover.

Results

Significant differences (p<0.05) were found in the mean time taken to recover from stress fractures when participants were grouped according to serum 25-OHD level. Sufficient levels of serum 25-OHD (>50 nmol/L) at the time of injury resulted in shorter recovery times than all other groups.

Conclusion

The study demonstrated an association between serum 25-OHD level and the time taken to recover from a stress fracture. The sample population of this study was too small to contribute to the discussion about whether a minimum serum 25-OHD status should be met before entering British Army training, but a larger prospective study should be able to provide the data required for a cost benefit analysis to be conducted and a decision made.