bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear dynamics of turbulence driven magnetic islands. I. Theoretical aspects
Authors: Agullo O. , Muraglia M. , Benkadda S. , Poyé A. , Dubuit N. , Garbet X. , Sen A.
Published: April 2017

The nonlinear properties of a turbulence driven magnetic island (TDMI) are investigated. Starting from a minimal magnetohydrodynamic fluid model that provides for the generation of a TDMI and using scale separation arguments along with numerical simulation findings, we elucidate the links between the nonlinear transport properties of such magnetic islands and the characteristic features of the small scale turbulence. We also explain the phenomenon of partial pressure flattening inside the TDMI.
Magnetization reversal in ferromagnetic wires patterned with antiferromagnetic gratings
Authors: Sani S. R. , Liu F. , Ross C. A.
Published: April 2017

The magnetic reversal behavior is examined for exchange-biased ferromagnetic/antiferromagnetic nanostructures consisting of an array of 10 nm thick Ni80Fe20 stripes with width 200 nm and periodicity 400 nm, underneath an orthogonal array of 10 nm thick IrMn stripes with width ranging from 200 nm to 500 nm and periodicity from 400 nm to 1 μm. The Ni80Fe20 stripes show a hysteresis loop with one step when the IrMn width and spacing are small. However, upon increasing the IrMn width and spacing, the hysteresis loops showed two steps as the pinned and unpinned sections of the Ni80Fe20 stripes switch at different fields. Micromagnetic modeling reveals the influence of geometry on the reversal behavior.
Note: An improved low-frequency correction technique for piezoelectric force sensors in high-speed nanopositioning systems
Authors: Yong Yuen K. , Fleming Andrew J.
Published: April 2017

Piezoelectric force and position sensors provide high sensitivity but are limited at low frequencies due to their high-pass response which complicates the direct application of integral control. To overcome this issue, an additional sensor or low-frequency correction method is typically employed. However, these approaches introduce an additional first-order response that must be higher than the high-pass response of the piezo and interface electronics. This article describes a simplified method for low-frequency correction that uses the piezoelectric sensor as an electrical component in a filter circuit. The resulting response is first-order, rather than second-order, with a cut-off frequency equal to that of a buffer circuit with the same input resistance. The proposed method is demonstrated to allow simultaneous damping and tracking control of a high-speed vertical nanopositioning stage.
Enhancement in electrical and magnetic properties with Ti-doping in Bi0.5La0.5Fe0.5Mn0.5O3
Authors: Singh Rahul , Gupta Prince Kumar , Kumar Shiv , Joshi Amish G. , Ghosh A. K. , Patil S. , Chatterjee Sandip
Published: April 2017

In this investigation, we have synthesized Bi0.5La0.5Fe0.5Mn0.5-xTixO3 (where x = 0 and 0.05) samples. The Rietveld refinement of X-ray diffraction (XRD) patterns shows that the systems crystallize in the orthorhombic phase with the Pnma space group. The observed Raman modes support the XRD results. The appearance of prominent A1-3 and weak E-2 modes in Bi0.5La0.5Fe0.5Mn0.45Ti0.05O3 indicates the presence of chemically more active Bi-O covalent bonds. Ferromagnetism of Bi0.5La0.5Fe0.5Mn0.5O3 is enhanced by Ti doping at the Mn-site, indicating that these particular samples might be interesting for device applications.
Vector beams generated by tunable liquid crystal polarization holograms
Authors: Ruiz U. , Pagliusi P. , Provenzano C. , Cipparrone G.
Published: April 2017

Two optically coupled nematic liquid crystal (NLC) polarization holograms (PHs) enable nearly 100% generation efficiency for vector beams (VBs) with spatially variant phase and polarization. Adopting a spatial light modulator assisted holographic approach, the PHs are recorded in the photoaligning substrates of the NLC cell and amplified by the NLC bulk. Owing to negligible NLC absorption at the visible and near infrared wavelengths and the ability to electrically adjust its optical birefringence, a single device allows us to generate VBs with the highest possible efficiency at any wavelength in the transparency range. In particular, we report the generation of VBs with an efficiency of 96% at a wavelength of 633 nm.
Pulse wake-up and breakdown investigation of ferroelectric yttrium doped HfO2
Authors: Starschich S. , Menzel S. , Böttger U.
Published: April 2017

The wake-up effect in yttrium doped hafnium oxide is investigated by pulse measurements, revealing the initial distribution of oxygen vacancies within symmetrical and asymmetrical layer stacks. It is shown that single pulses are sufficient to achieve a significant wake-up, whereby additional pulses lead to a stronger wake-up. Further cycling induces a degradation of the devices, which is explained by generation of oxygen vacancies and results in an electroforming step where subsequently resistive valence change mechanism switching is observed. The degradation and therefore the generation of oxygen vacancies show a strong frequency dependence, whereby the device lifetime is strongly increased for increasing frequencies.
Broad band optical band-reject filters in near-infrared regime utilizing bilayer Ag metasurface
Authors: Hu X. L. , Sun L. B. , Wu Q. J. , Wang L. S. , Bai S. A. , Li Q. , Yang S. M. , Tai R. Z. , Mohr M. , Fecht H. J. , Wang L. Q. , Zhang D. X. , Jiang J. Z.
Published: April 2017

A band-reject filter working in a near-infrared regime employing a bilayer Ag metasurface was demonstrated numerically and experimentally. This band-reject filter exhibited a broad rejection band (more than 500 nm), simple structure (including an ultrathin metal film, a dielectric layer, and substrate), and high tunability in the near-infrared spectral region, superior to previously reported filters with band-reject features. Simulations of optical reflection spectra under different conditions were carried out and revealed that the filtering behavior strongly depends on structural parameters. Three band-reject filters were experimentally fabricated and proved to be in good agreement with simulations.
On–off intermittency in coupled chaotic thermoacoustic oscillations
Authors: Delage Rémi , Takayama Yusuke , Biwa Tetsushi
Published: April 2017

This paper documents on-off intermittency observed in coupled thermoacoustic chaotic oscillations. Mode competition between two or three oscillation modes engenders chaotic oscillations through quasiperiodic oscillations introduced by a local cross-sectional change in a gas-filled tube. Complete synchronization is then obtained by connecting two thermoacoustic chaotic oscillators via a rigid plate with an orifice. From the analysis of pressure fluctuations, theoretical statistical scaling laws related to the laminar phases, spectral density, and amplitude probability distribution are found to be satisfied in the coupled thermoacoustic oscillators, when the thermoacoustic complete synchronization breaks down through an on-off intermittency route with the decreased orifice size.
Spatially resolved modeling and measurements of metastable argon atoms in argon-helium microplasmas
Authors: Hoskinson Alan R. , Gregório José , Hopwood Jeffrey , Galbally-Kinney Kristin L. , Davis Steven J. , Rawlins Wilson T.
Published: April 2017

Microwave-driven plasmas operating near atmospheric pressure have been shown to be a promising technique for producing the high density of argon metastable atoms required for optically pumped rare gas laser systems. Stable microwave-driven plasmas can be generated at high pressures using microstrip-based resonator circuits. We present results from computational modeling and laser absorption measurements of argon metastable densities in such plasmas operating in argon-helium gas mixtures at pressures up to 300 Torr. The model and measurements resolve the plasma characteristics both perpendicular to the substrate surface and along the resonator length. The measurements qualitatively and in many aspects quantitatively confirm the accuracy of the model. The plasmas exhibit distinct behaviors depending on whether the operating gas is mostly argon or mostly helium. In high-argon plasmas, the metastable density has a large peak value but is confined very closely to the electrode surfaces as well as being reduced near the discharge gap itself. In contrast, metastable densities in high helium-fraction mixtures extend through most of the plasma. In all systems, increasing the power extends the region of metastable along the resonator length, while the extent away from the substrate surface remains approximately constant.
Suppressing the memory state of floating gate transistors with repeated femtosecond laser backside irradiations
Authors: Chambonneau Maxime , Souiki-Figuigui Sarra , Chiquet Philippe , Della Marca Vincenzo , Postel-Pellerin Jérémy , Canet Pierre , Portal Jean-Michel , Grojo David
Published: April 2017

We demonstrate that infrared femtosecond laser pulses with intensity above the two-photon ionization threshold of crystalline silicon induce charge transport through the tunnel oxide in floating gate Metal-Oxide-Semiconductor transistor devices. With repeated irradiations of Flash memory cells, we show how the laser-produced free-electrons naturally redistribute on both sides of the tunnel oxide until the electric field of the transistor is suppressed. This ability enables us to determine in a nondestructive, rapid and contactless way the flat band and the neutral threshold voltages of the tested device. The physical mechanisms including nonlinear ionization, quantum tunneling of free-carriers, and flattening of the band diagram are discussed for interpreting the experiments. The possibility to control the carriers in memory transistors with ultrashort pulses holds promises for fast and remote device analyses (reliability, security, and defectivity) and for considerable developments in the growing field of ultrafast microelectronics.
Large, scalable dispersion engineering using cladding-modulated Bragg gratings on a silicon chip
Authors: Sahin E. , Ooi K. J. A. , Png C. E. , Tan D. T. H.
Published: April 2017

A cladding-modulated 1D photonic crystal is realized for creating ultra-large dispersion on a silicon chip. Both normal dispersion and anomalous dispersion are realized on the same waveguide device. The design, fabrication, and characterization of the devices are demonstrated. The device exploits adjacent pillars' positioning to engineer the dispersion, as well as the variation of the distance between the pillar and waveguide to realize apodization. Devices achieving a group delay dispersion coefficient of −3.61 ps/nm and 3.28 ps/nm are demonstrated with a footprint of 1.27 × 1.7 mm2. The demonstrated devices possess a group delay dispersion coefficient × bandwidth product as large as 72 ps on a silicon, CMOS-compatible chip.
Dielectric metasurfaces for quantum weak measurements
Authors: Chen Shizhen , Zhou Xinxing , Mi Chengquan , Liu Zhenxing , Luo Hailu , Wen Shuangchun
Published: April 2017

Metasurfaces have shown extraordinary abilities to manipulate the phase and polarization of light and thus hold great promise for applications in photonics and optoelectronics. Here, we propose a unique application of the dielectric metasurface for quantum weak measurements. In our scheme, the dielectric metasurface introduces a tiny phase gradient in the procedure of measurements and keeps the measured system almost undisturbed. The dielectric metasurface may improve and simplify already existing schemes in quantum weak measurements and thereby provide potential applications in precise measurements of phase, polarization, and frequency of light.
New shielding material development for compact accelerator-driven neutron source
Authors: Hu Guang , Hu Huasi , Wang Sheng , Han Hetong , Otake Y. , Pan Ziheng , Taketani A. , Ota H. , Hashiguchi Takao , Yan Mingfei
Published: April 2017

The Compact Accelerator-driven Neutron Source (CANS), especially the transportable neutron source is longing for high effectiveness shielding material. For this reason, new shielding material is researched in this investigation. The component of shielding material is designed and many samples are manufactured. Then the attenuation detection experiments were carried out. In the detections, the dead time of the detector appeases when the proton beam is too strong. To grasp the linear range and nonlinear range of the detector, two currents of proton are employed in Pb attenuation detections. The transmission ratio of new shielding material, polyethylene (PE), PE + Pb, BPE + Pb is detected under suitable current of proton. Since the results of experimental neutrons and γ-rays appear as together, the MCNP and PHITS simulations are applied to assisting the analysis. The new shielding material could reduce of the weight and volume compared with BPE + Pb and PE + Pb.
On using distributional analysis techniques for determining the onset of the influence of experimental variables
Authors: Reingold Eyal M , Sheridan Heather
Published: April 2017

Much of the investigation of eye movement control in visual cognition has focused on the influence of experimental variables on mean fixation durations. In this article, we explored the convergence between two distributional analysis techniques that were recently introduced in this domain. First, Staub, White, Drieghe, Hollway and Rayner, proposed fitting the ex-Gaussian distribution to individual participants’ data in order to ascertain whether a variable has a rapid or a slow influence on fixation durations. Second, the divergence point analysis (DPA) procedure was introduced by Reingold, Reichle, Glaholt and Sheridan in order to determine more precisely the earliest discernible impact of a variable on the distribution of fixation durations by contrasting survival curves across two experimental conditions and determining the point at which the two curves begin to diverge. In this article, we introduced a new version of the DPA procedure which is based on ex-Gaussian fitting. We evaluated this procedure by re-analyzing data obtained in previous empirical investigations as well as by conducting a simulation study. We demonstrated that the new ex-Gaussian DPA technique produced estimates that were consistent with estimates produced by prior versions of DPA procedure, and in the present simulation, the ex-Gaussian DPA procedure produced somewhat more accurate individual participant divergence point estimates. Based on the present findings, we also suggest guidelines for best practices in the use of DPA techniques.
Unique molecular profile of exosomes derived from primary human proximal tubular epithelial cells under diseased conditions
Authors: Wang Xiangju , Wilkinson Ray , Kildey Katrina , Potriquet Jeremy , Mulvenna Jason , Lobb Richard J. , Möller Andreas , Cloonan Nicole , Mukhopadhyay Pamela , Kassianos Andrew J. , Healy Helen
Published: April 2017

Human proximal tubular epithelial cells (PTEC) of the kidney are known to respond to and mediate the disease process in a wide range of kidney diseases, yet their exosomal production and exosome molecular cargo remain a mystery. Here we investigate, for the first time, the production and molecular content of exosomes derived from primary human PTEC cultured under normal and diseased conditions representing a spectrum of in vivo disease severity from early inflammation, experienced in multiple initial kidney disease states, through to hypoxia, frequently seen in late stage chronic kidney disease (CKD) due to fibrosis and vascular compromise. We demonstrate a rapid reproducible methodology for the purification of PTEC‐derived exosomes, identify increased numbers of exosomes from disease‐state cultures and identify differential expression levels of both known and unique miRNA and protein species from exosomes derived from different disease‐culture conditions. The validity of our approach is supported by the identification of miRNA, proteins and pathways with known CKD associations, providing a rationale to further evaluate these novel and known pathways as targets for therapeutic intervention.
Regulation of microtubule-associated motors drives intermediate filament network polarization
Authors: Leduc Cécile , Etienne-Manneville Sandrine
Published: April 2017

Intermediate filaments (IFs) are key players in the control of cell morphology and structure as well as in active processes such as cell polarization, migration, and mechanoresponses. However, the regulatory mechanisms controlling IF dynamics and organization in motile cells are still poorly understood. In this study, we investigate the mechanisms leading to the polarized rearrangement of the IF network along the polarity axis. Using photobleaching and photoconversion experiments in glial cells expressing vimentin, glial fibrillary acidic protein, and nestin, we show that the distribution of cytoplasmic IFs results from a continuous turnover based on the cooperation of an actin-dependent retrograde flow and anterograde and retrograde microtubule-dependent transports. During wound-induced astrocyte polarization, IF transport becomes directionally biased from the cell center toward the cell front. Such asymmetry in the transport is mainly caused by a Cdc42- and atypical PKC–dependent inhibition of dynein-dependent retrograde transport. Our results show how polarity signaling can affect the dynamic turnover of the IF network to promote the polarization of the network itself.
Phagocytosis imprints heterogeneity in tissue-resident macrophages
Authors: A-Gonzalez Noelia , Quintana Juan A. , García-Silva Susana , Mazariegos Marina , González de la Aleja Arturo , Nicolás-Ávila José A. , Walter Wencke , Adrover Jose M. , Crainiciuc Georgiana , Kuchroo Vijay K. , Rothlin Carla V. , Peinado Héctor , Castrillo Antonio , Ricote Mercedes , Hidalgo Andrés
Published: April 2017

Tissue-resident macrophages display varying phenotypic and functional properties that are largely specified by their local environment. One of these functions, phagocytosis, mediates the natural disposal of billions of cells, but its mechanisms and consequences within living tissues are poorly defined. Using a parabiosis-based strategy, we identified and isolated macrophages from multiple tissues as they phagocytosed blood-borne cellular material. Phagocytosis was circadianally regulated and mediated by distinct repertoires of receptors, opsonins, and transcription factors in macrophages from each tissue. Although the tissue of residence defined the core signature of macrophages, phagocytosis imprinted a distinct antiinflammatory profile. Phagocytic macrophages expressed CD206, displayed blunted expression of Il1b, and supported tissue homeostasis. Thus, phagocytosis is a source of macrophage heterogeneity that acts together with tissue-derived factors to preserve homeostasis.
Tissue adaptation: Implications for gut immunity and tolerance
Authors: Faria Ana M.C. , Reis Bernardo S. , Mucida Daniel
Published: April 2017

Tissue adaptation is an intrinsic component of immune cell development, influencing both resistance to pathogens and tolerance. Chronically stimulated surfaces of the body, in particular the gut mucosa, are the major sites where immune cells traffic and reside. Their adaptation to these environments requires constant discrimination between natural stimulation coming from harmless microbiota and food, and pathogens that need to be cleared. This review will focus on the adaptation of lymphocytes to the gut mucosa, a highly specialized environment that can help us understand the plasticity of leukocytes arriving at various tissue sites and how tissue-related factors operate to shape immune cell fate and function.
A novel physiological role for ARF1 in the formation of bidirectional tubules from the Golgi
Authors: Bottanelli Francesca , Kilian Nicole , Ernst Andreas M. , Rivera-Molina Felix , Schroeder Lena K. , Kromann Emil B. , Lessard Mark D. , Erdmann Roman S. , Schepartz Alanna , Baddeley David , Bewersdorf Joerg , Toomre Derek , Rothman James E.
Published: April 2017

Capitalizing on CRISPR/Cas9 gene-editing techniques and super-resolution nanoscopy, we explore the role of the small GTPase ARF1 in mediating transport steps at the Golgi. Besides its well-established role in generating COPI vesicles, we find that ARF1 is also involved in the formation of long (∼3 µm), thin (∼110 nm diameter) tubular carriers. The anterograde and retrograde tubular carriers are both largely free of the classical Golgi coat proteins coatomer (COPI) and clathrin. Instead, they contain ARF1 along their entire length at a density estimated to be in the range of close packing. Experiments using a mutant form of ARF1 affecting GTP hydrolysis suggest that ARF1[GTP] is functionally required for the tubules to form. Dynamic confocal and stimulated emission depletion imaging shows that ARF1-rich tubular compartments fall into two distinct classes containing 1) anterograde cargoes and clathrin clusters or 2) retrograde cargoes and coatomer clusters.
SigSeeker: a peak-calling ensemble approach for constructing epigenetic signatures
Authors: Lichtenberg Jens , Elnitski Laura , Bodine David M
Published: April 2017

Motivation

Epigenetic data are invaluable when determining the regulatory programs governing a cell. Based on use of next-generation sequencing data for characterizing epigenetic marks and transcription factor binding, numerous peak-calling approaches have been developed to determine sites of genomic significance in these data. Such analyses can produce a large number of false positive predictions, suggesting that sites supported by multiple algorithms provide a stronger foundation for inferring and characterizing regulatory programs associated with the epigenetic data. Few methodologies integrate epigenetic based predictions of multiple approaches when combining profiles generated by different tools.

Results

The SigSeeker peak-calling ensemble uses multiple tools to identify peaks, and with user-defined thresholds for peak overlap and signal strength it retains only those peaks that are concordant across multiple tools. Peaks predicted to be co-localized by only a very small number of tools, discovered to be only marginally overlapping, or found to represent significant outliers to the approximation model are removed from the results, providing concise and high quality epigenetic datasets. SigSeeker has been validated using established benchmarks for transcription factor binding and histone modification ChIP-Seq data. These comparisons indicate that the quality of our ensemble technique exceeds that of single tool approaches, enhances existing peak-calling ensembles, and results in epigenetic profiles of higher confidence.

Availability and implementation

http://sigseeker.org

Supplementary information

Supplementary data are available at Bioinformatics online.
What does a Deductible Do? The Impact of Cost-Sharing on Health Care Prices, Quantities, and Spending Dynamics*
Authors: Brot-Goldberg Zarek C. , Chandra Amitabh , Handel Benjamin R. , Kolstad Jonathan T.
Published: April 2017

Measuring consumer responsiveness to medical care prices is a central issue in health economics and a key ingredient in the optimal design and regulation of health insurance markets. We leverage a natural experiment at a large self-insured firm that required all of its employees to switch from an insurance plan that provided free health care to a nonlinear, high-deductible plan. The switch caused a spending reduction between 11.8% and 13.8% of total firm-wide health spending. We decompose this spending reduction into the components of (i) consumer price shopping, (ii) quantity reductions, and (iii) quantity substitutions and find that spending reductions are entirely due to outright reductions in quantity. We find no evidence of consumers learning to price shop after two years in high-deductible coverage. Consumers reduce quantities across the spectrum of health care services, including potentially valuable care (e.g., preventive services) and potentially wasteful care (e.g., imaging services). To better understand these changes, we study how consumers respond to the complex structure of the high-deductible contract. Consumers respond heavily to spot prices at the time of care, reducing their spending by 42% when under the deductible, conditional on their true expected end-of-year price and their prior year end-of-year marginal price. There is no evidence of learning to respond to the true shadow price in the second year post-switch.
The spo0A-sinI-sinR Regulatory Circuit Plays an Essential Role in Biofilm Formation, Nematicidal Activities, and Plant Protection in Bacillus cereus AR156
Authors: Xu Sunde , Yang Nan , Zheng Shiyu , Yan Fang , Jiang Chunhao , Yu Yiyang , Guo Jianhua , Chai Yunrong , Chen Yun
Published: April 2017

The rhizosphere bacterium Bacillus cereus AR156 is capable of forming biofilms, killing nematodes, and protecting plants. However, the underlying molecular mechanisms of these processes are not well understood. In this study, we found that the isogenic mutants ΔBcspo0A and ΔBcsinI have significantly reduced colonization and nematicidal activity in vitro and biological control efficacy on the tomato plant under greenhouse conditions. We further investigated the role of the spo0A-sinI-sinR regulatory circuit in biofilm formation, killing against nematodes, and biological control in AR156. Results from mutagenesis of those regulatory genes in AR156 and their heterologous expression in B. subtilis suggested that the spo0A-sinI-sinR genetic circuit is not only essential for biofilm formation and cell differentiation in AR156 but also able to functionally replace their counterparts in B. subtilis in a nearly indistinguishable fashion. Genome-wide transcriptional profiling in the wild type and the ΔBcspo0A and ΔBcsinI mutants further revealed hundreds of differentially expressed genes, likely positively regulated by both Spo0A and SinI (via SinR) in AR156. Among them, 29 genes are predicted to be directly controlled by SinR, whose counterpart in B. subtilis is a biofilm master repressor. Collectively, our studies demonstrated the essential role of the spo0A-sinI-sinR regulatory circuit in biofilm formation, cell differentiation, and bacteria–host interactions in B. cereus AR156.
Harnessing Effector-Triggered Immunity for Durable Disease Resistance
Authors: Zhang Meixiang , Coaker Gitta
Published: April 2017

Genetic control of plant diseases has traditionally included the deployment of single immune receptors with nucleotide-binding leucine-rich repeat (NLR) domain architecture. These NLRs recognize corresponding pathogen effector proteins inside plant cells, resulting in effector-triggered immunity (ETI). Although ETI triggers robust resistance, deployment of single NLRs can be rapidly overcome by pathogen populations within a single or a few growing seasons. In order to generate more durable disease resistance against devastating plant pathogens, a multitiered strategy that incorporates stacked NLRs combined with other sources of disease resistance is necessary. New genetic and genomic technologies have enabled advancements in identifying conserved pathogen effectors, isolating NLR repertoires from diverse plants, and editing plant genomes to enhance resistance. Significant advancements have also been made in understanding plant immune perception at the receptor level, which has promise for engineering new sources of resistance. Here, we discuss how to utilize recent scientific advancements in a multilayered strategy for developing more durable disease resistance.
Iron Loading Exaggerates the Inflammatory Response to the Toll-like Receptor 4 Ligand Lipopolysaccharide by Altering Mitochondrial Homeostasis
Authors: Hoeft Konrad , Bloch Donald B. , Graw Jan A. , Malhotra Rajeev , Ichinose Fumito , Bagchi Aranya
Published: April 2017

Background

Perioperative and critically ill patients are often exposed to iron (in the form of parenteral-iron administration or blood transfusion) and inflammatory stimuli, but the effects of iron loading on the inflammatory response are unclear. Recent data suggest that mitochondrial reactive oxygen species have an important role in the innate immune response and that increased mitochondrial reactive oxygen species production is a result of dysfunctional mitochondria. We tested the hypothesis that increased intracellular iron potentiates lipopolysaccharide-induced inflammation by increasing mitochondrial reactive oxygen species levels.

Methods

Murine macrophage cells were incubated with iron and then stimulated with lipopolysaccharide. C57BL/6 wild-type mice were intraperitoneally injected with iron and then with lipopolysaccharide. Markers of inflammation and mitochondrial superoxide production were examined. Mitochondrial homeostasis (the balance between mitochondrial biogenesis and destruction) was assessed, as were mitochondrial mass and the proportion of nonfunctional to total mitochondria.

Results

Iron loading of mice and cells potentiated the inflammatory response to lipopolysaccharide. Iron loading increased mitochondrial superoxide production. Treatment with MitoTEMPO, a mitochondria-specific antioxidant, blunted the proinflammatory effects of iron loading. Iron loading increased mitochondrial mass in cells treated with lipopolysaccharide and increased the proportion of nonfunctional mitochondria. Iron loading also altered mitochondrial homeostasis to favor increased production of mitochondria.

Conclusions

Acute iron loading potentiates the inflammatory response to lipopolysaccharide, at least in part by disrupting mitochondrial homeostasis and increasing the production of mitochondrial superoxide. Improved understanding of iron homeostasis in the context of acute inflammation may yield innovative therapeutic approaches in perioperative and critically ill patients.
Evidence-based Recommendations for Pediatric Orthopaedic Practice
Authors: Mulpuri Kishore , Schaeffer Emily K. , Graham H. Kerr , Kocher Mininder S. , Sanders James , Zaltz Ira
Published: April 2017

Background:

Evidence-based medicine has become the cornerstone to guide clinical practice decision-making. Evidence-based medicine integrates the strongest available evidence with clinical expertise to make decisions about clinical care. The quality of the evidence depends upon the soundness of the study methodology to allow for meaningful interpretation of the clinical results. The purpose of this review is to analyze the methodological design and clinical findings of published pediatric orthopaedic studies to determine their ability to change or influence clinical practice.

Methods:

This is the first in a series of evidence-based reviews in pediatric orthopaedics. The pediatric orthopaedic literature was reviewed for randomized controlled trials (RCTs) published in 2013 to 2014. Two RCTs were selected from the Journal of Bone and Joint Surgery for in depth methodological review and analysis. Methodological reviews were performed by 2 orthopaedic surgeons with advanced research degrees. Following this, 2 clinical experts reviewed the articles to rate the clinical impact or value of each study. Methodological and clinical reviews were compiled, and a final recommendation on impact to change clinical practice was made based on both review components at the consensus of the panel.

Results:

The first study reviewed investigated the impact of physical therapy on function following supracondylar humeral fractures in children. The reviewers deemed the superiority study to of sound design, and conclusions appropriate for the methodology used and clinical findings. The results do not compel a recommendation to change clinical practice. The second study investigated the impact of Botulinum Toxin A with casting for the treatment of idiopathic toe-walking in children. Although of relatively sound design, the sample size was too small to appropriately perform some statistical comparisons. No recommendation to change clinical practice could be made.

Conclusion:

Both RCTs reviewed were superiority studies with a negative result. No recommendation to change clinical practice could be made.

Significance:

Interpretation of superiority studies with nonsignificant findings must be done with caution. The findings of both of these RCTs highlight the need for more noninferiority trials in the pediatric orthopaedic literature in order to appropriately demonstrate no difference between 2 treatment options.
Intraoperative Change in Defect Size during Maxillary Reconstruction Using Surgical Guides Created by CAD/CAM
Authors: Morita Daiki , Numajiri Toshiaki , Nakamura Hiroko , Tsujiko Shoko , Sowa Yoshihiro , Yasuda Makoto , Hirano Shigeru
Published: April 2017

Surgical osteotomy guides created by computer-aided design/computer-aided manufacturing (CAD/CAM) have been developed and are now widely used in maxillofacial reconstruction. However, there are no standard procedures for dealing with an intraoperative change in defect size. We report on a case in which we used our CAD/CAM guides to deal with an intraoperative change in defect size in a maxillary reconstruction. We planned the maxillary reconstruction using a free fibula flap because of left maxillary sinus cancer in a 73-year-old man. In Japan, we cannot use commercially supplied CAD/CAM guides because these have not been approved by the government. We created novel CAD/CAM guides by using free software and a low-cost 3D printer. We performed model surgery to check the accuracy of the design and to prebend the titanium plates before the operation. The actual defect in the maxilla was found to be smaller than that used in preoperative planning. It was therefore necessary to rearrange the fibular segments and to rebend the plates. Comparison between the preoperative and postoperative 3D images showed that the deviation was 2–4 mm. In case that the CAD/CAM guides become inapplicable because of an intraoperative change in defect size, rearranging both the ends of set-up fibular segments and rebending the plates in situ allows us to deal with the situation. However, because extra time is needed to rearrange and rebend, the total operation and flap ischemic times are not shortened.
Impact of Chlorhexidine Cord Cleansing on Mortality, Omphalitis and Cord Separation Time Among Facility-Born Babies in Nepal and Bangladesh
Authors: Mullany Luke C. , Arifeen Shams El , Khatry Subarna K. , Katz Joanne , Shah Rashed , Baqui Abdullah H. , Tielsch James M.
Published: April 2017

Guidance is needed regarding potential extension of the World Health Organization recommendation for cord cleansing with chlorhexidine to babies born in facilities. Among 3223 facility-born babies from Nepal and Bangladesh, mortality was approximately halved among those allocated to the intervention clusters [10.5/1000 vs. 19.4/1000; relative risk (RR): 0.54; 95% confidence interval: 0.30–0.97]. In high-mortality settings, a single policy for home and facility births is warranted.
Antimicrobial Resistant Streptococcus pneumoniae: Prevalence, Mechanisms, and Clinical Implications
Authors: Cherazard Regine , Epstein Marcia , Doan Thien-Ly , Salim Tanzila , Bharti Sheena , Smith Miriam A.
Published: April 2017

Background:

Streptococcus pneumoniae is a major cause of pneumonia, meningitis, sepsis, bacteremia, and otitis media. S. pneumoniae has developed increased resistance to multiple classes of antibiotics.

Study Design:

Systematic literature review of prevalence, mechanisms, and clinical implications in S. pneumoniae resistance.

Areas of Uncertainty:

Since S. pneumoniae resistance to penicillin was first reported with subsequent development of resistance to other classes of drugs, selection of appropriate antibiotic treatment is challenging.

Data Sources:

We searched PubMed (English language) for citations to antibiotic resistance in S. pneumoniae published before March 1, 2016.

Results:

We present a review of S. pneumoniae resistance to beta-lactams, macrolides, lincosamides, fluoroquinolones, tetracyclines, and trimethoprim-sulfamethoxazole (TMP-SMX). There has been a steady decline in susceptibility of S. pneumoniae to commonly used beta-lactams. Phenotypic expression of penicillin resistance occurs as a result of a genetic structural modification in penicillin-binding proteins. Between 20% and 40% of S. pneumoniae isolates are resistant to macrolides. Macrolide resistance mechanisms include ribosomal target site alteration, alteration in antibiotic transport, and modification of the antibiotic. Approximately 22% of S. pneumoniae isolates are resistant to clindamycin. Similar to macrolide resistance, clindamycin involves a target site alteration. The prevalence of fluoroquinolone resistance is low, although increasing. S. pneumoniae resistance to fluoroquinolones occurs by accumulated mutations within the bacterial genome, increased efflux, or acquisition of plasmid-encoded genes. S. pneumoniae resistance has also increased for the tetracyclines. The primary mechanism is mediated by 2 genes that confer ribosomal protection. The prevalence of TMP-SMX resistance is around 35%. As with fluoroquinolones, resistance to TMP-SMX is secondary to mutations in the bacterial genome.

Conclusions:

Effective treatment of resistant S. pneumoniae is a growing concern. New classes of drugs, newer formulations of older drugs, combination antibiotic therapy, nonantibiotic modalities, better oversight of antibiotic usage, and enhanced preventive measures hold promise.
Prescriber Compliance With Liver Monitoring Guidelines for Pazopanib in the Postapproval Setting: Results From a Distributed Research Network
Authors: Shantakumar Sumitra , Nordstrom Beth L. , Hall Susan A. , Djousse Luc , van Herk-Sukel Myrthe P.P. , Fraeman Kathy H. , Gagnon David R. , Chagin Karen , Nelson Jeanenne J.
Published: April 2017

Objectives

Pazopanib received US Food and Drug Administration approval in 2009 for advanced renal cell carcinoma. During clinical development, liver chemistry abnormalities and adverse hepatic events were observed, leading to a boxed warning for hepatotoxicity and detailed label prescriber guidelines for liver monitoring. As part of postapproval regulatory commitments, a cohort study was conducted to assess prescriber compliance with liver monitoring guidelines.

Methods

Over a 4-year period, a distributed network approach was used across 3 databases: US Veterans Affairs Healthcare System, a US outpatient oncology community practice database, and the Dutch PHARMO Database Network. Measures of prescriber compliance were designed using the original pazopanib label guidelines for liver monitoring.

Results

Results from the VA (n = 288) and oncology databases (n = 283) indicate that prescriber liver chemistry monitoring was less than 100%: 73% to 74% compliance with baseline testing and 37% to 39% compliance with testing every 4 weeks. Compliance was highest near drug initiation and decreased over time. Among patients who should have had weekly testing, the compliance was 56% in both databases. The more serious elevations examined, including combinations of liver enzyme elevations meeting the laboratory definition of Hy’s law were infrequent but always led to appropriate discontinuation of pazopanib. Only 4 patients were identified for analysis in the Dutch database; none had recorded baseline testing.

Conclusions

In this population-based study, prescriber compliance was reasonable near pazopanib initiation but low during subsequent weeks of treatment. This study provides information from real-world community practice settings and offers feedback to regulators on the effectiveness of label monitoring guidelines.
Multilateral Functional Alterations of Human Neutrophils in Sepsis: From the Point of Diagnosis to the Seventh Day
Authors: Endo Akira , Okamura Miko , Yoshikawa Shunsuke , Otomo Yasuhiro , Morio Tomohiro
Published: April 2017

Neutrophil functional changes caused by sepsis itself and their time-course variation have not been fully elucidated because previous studies targeted patients who had received therapeutic interventions. We explored the multilateral functions of circulating neutrophils in patients with severe sepsis or septic shock who had not yet undergone interventions, and followed their changes. Patients were treated based on the Surviving Sepsis Campaign Guidelines 2012. Neutrophil functions were evaluated on days 0 (before therapeutic intervention), 3, and 7 in 59 septic patients. The clinical severity score (APACHE II and SOFA) and serum pro-/anti-inflammatory cytokine concentrations of the patients were significantly increased on day 0 and normalized on day 3. However, neutrophil priming state, estimated by measuring the fMLP-stimulated reactive oxygen species, was significantly elevated on day 0, further augmented on day 3, and then returned to day 0 levels on day 7 despite general resolution of the inflammatory response. The expression of CXC chemokine receptor 2 and paired immunoglobulin-like receptor α, assessed as surrogate markers of transmigration and adhesion potency, was suppressed most strongly on day 0 and gradually recovered. To conclude, contrary to the patient's clinical course, neutrophil priming state was augmented most strongly at 3 days after diagnosis of sepsis. Impaired transmigration and excessive adhesion potency were observed most prominently at diagnosis. These observations would partially explain the mechanism of development of multiple organ dysfunction of the host who is subjected to a secondary insult, and may provide an important perspective for the implementation of additional immune-modulating therapy in sepsis.
The Impact of a Dedicated Robotic Team on Robotic-Assisted Sacrocolpopexy Outcomes
Authors: Carter-Brooks Charelle M. , Du Angela L. , Bonidie Michael J. , Shepherd Jonathan P.
Published: April 2017

Background

Robotic-assisted sacrocolpopexy has been criticized for high cost. A strategy to increase operating room efficiency and decrease cost is implementation of a dedicated robotic team. Our objective was to determine if a dedicated robotic team decreases operative time.

Study Design

This institutional review board–approved retrospective cohort study included all robotic-assisted sacrocolpopexy performed from June 2010 to August 2015 by a single surgeon at 2 institutions in 1 health system. One hospital had a dedicated robotic team, whereas the other did not. To assess baseline differences, χ2 and t tests were used. Multivariable linear regression identified factors impacting operative time.

Results

Eighty-eight robotic-assisted sacrocolpopexy cases met inclusion criteria. Subjects were primarily white (92.8%) and postmenopausal (85.5%) with stage III prolapse (71.1%). Mean age was 60.6 ± 9.0 years, and BMI was 28.5 ± 5.1 kg/m2. Seventeen cases (19.3%) had a dedicated team. In the 71 cases without a dedicated team, there were 16 different surgical technologist and no advanced practice providers. Groups had similar baseline characteristics (all P > 0.05).

Mean operative time for the dedicated team was significantly less (131.8 vs 160.2 minutes, P < 0.001), a 17.7% time reduction. The decrease persisted on multivariable regression (β = −25.98 minutes, P < 0.001) after adjusting for case order on the day (β = −8.6 minutes, P = 0.002) and prior to hysterectomy (β = −36.1 minutes, P < 0.001). Operative complications and prolapse recurrence were low overall and not different between the dedicated and nondedicated teams (0% vs 2.9%, P = 0.50; 0% vs 7.5%, P = 0.29).

Conclusions

A dedicated robotic team during robotic-assisted sacrocolpopexy significantly decreased operative time by 26 minutes, a 17.7% reduction at our institution.
Awareness Regarding Perineal Protection, Obstetric Anal Sphincter Injury, and Episiotomy Among Obstetrics and Gynecology Residents; Effects of an Educational Workshop
Authors: Stecher Anna M. , Yeung Jennifer , Crisp Catrina C. , Pauls Rachel N.
Published: April 2017

Objectives

Appropriate perineal protection may reduce rates of obstetric anal sphincter injuries (OASIS). We sought to investigate the knowledge and attitudes of obstetrics and gynecology residents concerning perineal protection, OASIS, and episiotomy before and after an educational workshop.

Methods

This was an institutional review board–approved cross-sectional survey study of obstetrics and gynecology residents. Two experts in perineal protection, whose methods have been shown to reduce OASIS by 50%, provided 1 week of education. Residents were taught in hands-on workshops and labor and delivery wards. Residents were surveyed regarding experiences, knowledge, and opinions of perineal protection, OASIS, and episiotomy. Surveys were administered immediately before and after the workshop and at 3 months following.

Results

All 31 residents participated. Almost all (97%) felt it was possible to reduce the incidence of OASIS prior to the workshop. Statistically significant increases were noted following training in the number that felt it was “very effective” to use the 2-handed technique taught in the workshop (P = 0.002), as well as those that reported most commonly performing a mediolateral episiotomy (protective against OASIS, if used selectively) when episiotomy was indicated (P = 0.001). The percent that reported feeling “comfortable” or “very comfortable” performing episiotomies increased from 45% to 77% immediately after the workshop (P = 0.002); this declined to 55% at 3 months. A large majority (77%) reported that the workshop was beneficial; 65% described an impact to patient care.

Conclusions

A workshop targeting perineal protection improved awareness and changed clinical practice in this group of residents. Ongoing education regarding perineal protection and episiotomy may reinforce behavior modifications.
The Effect of Lithotomy Position on Nerve Stretch: A Cadaveric Study
Authors: Deveneau Nicolette E. , Forbis Courtney , Lipetskaia Lioudmilla , Kinman Casey L. , Agrawal Anubhav , Herring Nicole R. , Francis Sean L.
Published: April 2017

Objective

The objective of our study was to design a method to measure nerve stretch in cadaveric subjects and then use the method to assess femoral nerve stretch in the lithotomy position with varying degrees of flexion and extension.

Methods

A university-based, cadaveric observational study of femoral nerve stretch was conducted. In 6 cadaveric subjects, femoral nerve near the inguinal ligament was dissected in each cadaveric subject. The nerve was marked, and digital images of the nerve were obtained in the supine position and lithotomy position in both flexion and extension. Distances were calculated using the ratio of pixels to millimeter specific for each image. The average distance for each set of images was then used to calculate the percent change from supine for each position.

Results

We were able to assess nerve stretch using photo-editing software. For extended position, all nerves showed some degree of stretch with the mean percent change in nerve length being 10.35%. For all other positions, most showed a decrease of nerve length. There was not a significant relation between degree of extension and stretch (Pearson r, P < 0.05).

Conclusions

Hip extension between 10 and 20 degrees consistently stretches the femoral nerve greater than 5%. The potential for femoral nerve stretch and avoiding hip extension should be considered when positioning a patient in lithotomy for surgical procedures.