bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomics Analysis Reveals Abnormal Electron Transport and Excessive Oxidative Stress Cause Mitochondrial Dysfunction in Placental Tissues of Early‐Onset Preeclampsia
Authors: Xu Zhongwei , Jin Xiaohan , Cai Wei , Zhou Maobin , Shao Ping , Yang Zhen , Fu Rong , Cao Jin , Liu Yan , Yu Fang , Fan Rong , Zhang Yan , Zou Shuang , Zhou Xin , Yang Ning , Chen Xu , Li Yuming
Published: April 2018

Purpose

Early‐onset preeclampsia (EOS‐PE) refers to preeclampsia that occurred before 34 gestation weeks. This study is conducted to explore the relationship between mitochondrial dysfunction and the pathogenesis of EOS‐PE using proteomic strategy.

Experimental design

To identify altering expressed mitochondrial proteins between severe EOS‐PE and healthy pregnancies, enrichment of mitochondria coupled with iTRAQ‐based quantitative proteomic method is performed. Immunohistochemistry (IHC) and western blot are performed to detect the alteration of changing expression proteins, and confirmed the accuracy of proteomic results.

Results

A total of 1372 proteins were quantified and 132 altering expressed proteins were screened, including 86 downregulated expression proteins and 46 upregulated expression proteins (p < 0.05). Bioinformatics analysis showed that differentially expressed proteins participated in numerous biological processes, including oxidation–reduction process, respiratory electron transport chain, and oxidative phosphorylation. Especially, mitochondria‐related molecules, PRDX2, PARK7, BNIP3, BCL2, PDHA1, SUCLG1, ACADM, and NDUFV1, are involved in energy‐production process in the matrix and membrane of mitochondria.

Conclusions and clinical relevance

Results of the experiment show that abnormal electron transport, excessive oxidative stress, and mitochondrion disassembly might be the main cause of mitochondrial dysfunction, and is related to the pathogenesis of EOS‐PE.
Knowledge‐based intensity‐modulated radiotherapy plans for cervical cancer with overlap volume of target and organs at risk
Authors: Ma Changdong , Luo Judong , Zhang Zhongquan , Ma Changsheng
Published: April 2018

Objective

To compare the differences in the dose‐volume histograms between knowledge‐based intensity‐modulated radiotherapy (K‐IMRT) plans and conventional IMRT (C‐IMRT) plans of 20 patients with cervical cancer.

Methods

A total of 70 cervical cancer patients were selected in the present study. Of these, 60 patients were selected randomly as a model group. The remaining 10 patients with overlap volume of target and organs at risk were categorized as group E1 for open‐loop verification. A total of 10 patients from the model group were selected randomly as group E2 for closed‐loop verification.

Results

The dose parameters of the target in the K‐IMRT and C‐IMRT plans showed no significant difference. The maximum dose and homogeneity index of group E2 showed no significant difference (P > 0.05) in their K‐IMRT and C‐IMRT plans. The dose parameters in the K‐IMRT plans of organs at risk were superior to those in the C‐IMRT plans. For group E1, V20 of the rectum, and V15, V20, and V25 of the left and right femoral heads in the K‐IMRT plans decreased as compared with those in the C‐IMRT plans (P < 0.05). For group E2, V25, V30, V35, and D50 of the bladder; V25 and V30 of the rectum; and V15, V20, and V25 of the left and right femoral heads in the K‐IMRT plans decreased as compared with those in the C‐IMRT plans (P < 0.05).

Conclusion

It is feasible to optimize the IMRT plans for cervical cancer patients with the overlap volume of the target and organs at risk using knowledge‐based radiation treatment automatically.
Computational assessment of folding energy landscapes in heterodimeric coiled coils
Authors: André Ingemar , Bjelic Sinisa
Published: April 2018

The coiled coil structural motif consists of alpha helices supercoiling around each other to form staggered knobs‐into‐holes packing. Such structures are deceptively simple, especially as they often can be described with parametric equations, but are known to exist in various conformations. Even the simplest systems, consisting of 2 monomers, can assemble into a wide range of states. They can form canonical as well as noncanonical coiled coils, be parallel or antiparallel, where helices associate with different degrees of shift, tilt, and rotation. Here, we investigate the energy landscape of heterodimeric coiled coils by carrying out de novo folding simulations starting from amino acid sequence. We folded a diverse set of 22 heterodimers and demonstrate that the approach is capable of identifying the atomic details in the experimental structure in the majority of cases. Our methodology also enables exploration of alternative states that can be accessible in solution beyond the experimentally determined structure. For many systems, we observe folding energy landscapes with multiple energy minima and several isoenergetic states. By comparing coiled coils from single domains and those extracted from larger proteins, we find that standalone coiled coils have deeper energy wells at the experimentally determined conformation. By folding the competing homodimeric states in addition to the heterodimers, we observe that the structural specificity towards the heteromeric state is often small. Taken together, our results demonstrate that de novo folding simulations can be a powerful tool to characterize structural specificity of coiled coils when coupled to assessment of energy landscapes.
Physicochemical property guidelines for modern agrochemicals
Authors: Zhang Yu , Lorsbach Beth A , Castetter Scott , Lambert William T , Kister Jeremy , Wang Nick X , Klittich Carla J R , Roth Joshua , Sparks Thomas C , Loso Mike R
Published: April 2018

The relentless need for the discovery and development of new agrochemicals continues as a result of driving forces such as loss of existing products through the development of resistance, the necessity for products with more favorable environmental and toxicological profiles, shifting pest spectra, and the changing agricultural needs and practices of the farming community. These new challenges underscore the demand for novel, high‐quality starting points to accelerate the discovery of new agrochemicals that address market challenges. This article discusses the efforts to identify the optimum ranges of physicochemical properties of agrochemicals through analysis of modern commercial products. Specifically, we reviewed literature studies examining physicochemical property effects and analyzed the properties typical of successful fungicides, herbicides, and insecticides (chewing and sap‐feeding pests). From the analysis, a new set of physicochemical property guidelines for each discipline, as well as building block class, are proposed. These new guidelines should significantly aid in the discovery of next‐generation agrochemicals. © 2018 Society of Chemical Industry
Using set invariance to design robust interval observers for discrete‐time linear systems
Authors: Meslem N. , Loukkas N. , Martinez J.J.
Published: April 2018

Based on interval and invariant set computation, an interval version of the Luenberger state observer for uncertain discrete‐time linear systems is proposed in this work. This new interval observer provides a punctual estimation of the state vector and guaranteed bounds on the estimation error. An off‐line and an on‐line approach to characterize, in a guaranteed way, the estimation error are introduced. Compared with the existing approaches, the proposed interval observer design method is not restrictive in terms of required assumptions, complexity, and on‐line computation time. Furthermore, the convergence issue of the estimation error is well established and to reduce the conservatism of the estimated state enclosure induced by the bounded additive state disturbance and noise measurement, an H∞ method to compute the optimal observer gain is proposed. The performance of the proposed state estimation approach are highlighted on different illustrative examples.
Stabilization of a class of cascade nonlinear switched systems with application to chaotic systems
Authors: Aghababa Mohammad Pourmahmood
Published: April 2018

In this study, the problem of finite‐time practical control of a class of nonlinear switched systems in the presence of input nonlinearities is investigated. The subsystems of the switched system are considered as complex nonlinear systems with a cascade structure. Each subsystem is fluctuated by lumped uncertainties. Moreover, some parts of the system's dynamics are considered to be unknown in advance. This paper sets no restrictive assumption on the switching logic of the system. Therefore, the aim is to propose a controller to work under any arbitrary switching signals. After providing a smooth sliding manifold, a simple adaptive control input is developed such that the system trajectories approach the prescribed sliding mode dynamics in finite‐time sense. The adopted control signal does not use the upper bounds of the lumped uncertainties, and it is robust against unknown nonlinear parts of the subsystems. It is proved that the origin is the (practical) finite‐time stable equilibrium point of the overall closed‐loop system. Subsequently, the proposed control rule is modified to handle the same switched system with no input nonlinearities. Computer simulations via 2 chaotic electric direct current machines demonstrate the robust performance of the derived variable structure control algorithm against system fluctuations and nonlinear inputs.
Nitrogen cycling in large temperate floodplain rivers of contrasting nutrient regimes and management
Authors: Richardson W.B. , Bartsch L.A. , Bartsch M.R. , Kiesling R. , Lafrancois B.M.
Published: April 2018

Hydraulic connection between channels and floodplains (“connectivity”) is a fundamental determinant of ecosystem function in large floodplain rivers. Factors controlling material processing in these rivers depend not only on the degree of connectivity but also on the sediment conditions, nutrient loads, and source. Nutrient cycling in the nutrient‐rich upper Mississippi River (MISS) is relatively well studied, whereas that of less eutrophic tributaries is not (e.g., St Croix River; SACN). We examined components of nitrogen cycling in 2 floodplain rivers of contrasting nutrient enrichment and catchment land use to test the hypothesis that N‐cycling rates will be greater in the MISS with elevated nutrient loads and productivity in contrast to the relatively nutrient‐poor SACN. Nitrate (NO3−‐N) concentrations were greatest in flowing habitats in the MISS and often undetectable in isolated backwaters except where groundwater inputs occurred. In the SACN, NO3−‐N concentrations were greatest in the flowing backwater where groundwater inputs were high. Ambient nitrification in the MISS was twice that in the SACN and tended to be lowest in the main channel. Denitrification was 3× greater in the MISS than that in the SACN, N‐limited in both rivers. Community production/respiration was >1 in the MISS and likely provisioned labile C to fuel microbial metabolism and dissimilatory NO3−‐N reduction, whereas the heterotrophic (production/respiration < 1) nature of the SACN likely limited microbial metabolism and NO3−‐N dissimilation. It appears that N‐cycling in the SACN was driven by groundwater, whereas that in the MISS was supported mainly by water column N‐sources.
Investigation of work function and chemical composition of thin films of borides and nitrides
Authors: Mezzi A. , Soltani P. , Kaciulis S. , Bellucci A. , Girolami M. , Mastellone M. , Trucchi D. M.
Published: April 2018

Thin films of various borides, nitrides, and barium fluorides were tentatively deposited by pulsed laser deposition and by magnetron sputtering in order to develop the components of thermionic‐photovoltaic devices for the high‐temperature thermal to electrical conversion by solid state. To improve the device performance, the materials characterized by a low work function were selected. In the present work, the chemical composition and work function of obtained films were investigated by X‐ray photoelectron spectroscopy and ultraviolet photoelectron spectroscopy techniques. The values of work function were determined from the cut‐off in the He I valence band spectra. Different films were compared and estimated on the basis of X‐ray photoelectron spectroscopy and ultraviolet photoelectron spectroscopy results.
Rollover Cyclopalladation via Remote C‐H Bond Activation of Br‐Pyridinbenzothiazole: An Experimental Study
Authors: Tovar‐Ramírez Martin E. , Ramírez‐Zúńiga Rosario , Nicasio‐Collazo Juan , Wrobel Katarzyna , Alvarado‐Rodríguez José G. , Wrobel Kazimierz , Serrano Oracio
Published: April 2018

Rollover palladacycles complexes containing pyridinebenzothiazole fragments were synthetized via remote C−H bond activation by PdCl2 in DMF. The structures of these compounds were proposed based on NMR analysis and high‐resolution mass spectrometry; in selected case of compound 1, its molecular structure was corroborated by single crystal X‐ray diffraction experiment. Upon solubilization in acetonitrile and using ESI‐QTOFMS, this complex was found as unusual tricoordinate cationic complex 1‐NCCH3 with acetonitrile attachment via Pd−Cl bond activation. Of note, synthesis success when PdCl2 was used as the starting material and mild heating (60 °C) of the reaction mixture was necessary to obtain the desired compound in a reasonable time (7 days). Evidence is provided that DMF solvent plays a key mechanistic role enabling the formation of organometallic rollover compounds; whereas using another solvent like DMSO, NCCH3 or acetone, a classic coordination complex is obtained.
Design, Synthesis, DNA Binding, and Docking Studies of Thiazoles and Thiazole‐Containing Triazoles as Antibacterials
Authors: Santosh Rangappa , Selvam Mukunthan K. , Kanekar Saptami U. , Nagaraja Gundibasappa K. , Kumar Madan
Published: April 2018

A series of thiazoles 4 a‐g and thiazole clubbed triazoles 5 a‐f were synthesized and showed good antibacterial activity against, Pseudomonas aeruginosa, Escherchia coli, Staphylococcus aureus and Bacillus subtilis. Particularly, 4 a (methyl), 5 b (nitro) and 5 d (fluoro) derivatives demonstrated a broad range of activity over other derivatized compounds. In addition, Computational interaction, ADMET (absorption, distribution, metabolism, and excretion ‐ toxicity in pharmacokinetics), Lipinski's rule and DNA binding studies of all the results stacked together indicated that 5 b can be further developed as lead molecule against bacterial pathogens.
Effects of Surgically Implanted Acoustic Tags on Body Condition, Growth, and Survival in a Small, Laterally Compressed Forage Fish
Authors: Klinard Natalie V. , Halfyard Edmund A. , Fisk Aaron T. , Stewart Thomas J. , Johnson Timothy B.
Published: April 2018

Telemetry studies often assume a lack of adverse effects caused by tag attachment and presence in various species and size‐classes, which may lead to inaccurate conclusions about fish behavior in field studies. Studies that examine the effects of tagging are typically performed on salmonids and adult fishes rather than on the small fishes that are increasingly becoming the focus of telemetry studies. The objectives of this study were to assess the effects of intracoelomic acoustic tagging on growth, condition, survival, and tag retention in subadult hatchery Bloaters Coregonus hoyi (a focal species for restoration efforts in the Laurentian Great Lakes) and to determine the maximum tag burden below which tag effects are reduced. Fish were either tagged with one of three dummy acoustic transmitters (Vemco V6: n = 50; V7: n = 50; V9: n = 50) or were followed as controls (n = 50; anesthesia, PIT‐tagging, and handling only) or sham individuals (n = 49; anesthesia, surgery, suturing, and PIT‐tagging but no acoustic tag implanted). Tags represented 1.3–9.0% of body mass. All fish received a PIT tag for individual identification throughout the 6‐month monitoring period (November 2014–May 2015). Survival exceeded 90% in all treatment groups, and the tag retention rate was 100%. All surviving fish appeared healthy and in excellent condition at the conclusion of the experiment. The results of this study suggest that acoustic transmitters with a tag mass : body mass ratio of 9% or less can be successfully implanted intracoelomically into subadult Bloaters—small, laterally compressed pelagic fish—with no adverse effects.
On the tails of the wind ramp distributions
Authors: DeMarco Adam , Basu Sukanta
Published: April 2018

We analyzed several multiyear wind speed datasets from 4 different geographical locations. The probability density functions of wind ramps from all these sites revealed remarkably similar shapes. The tails of the probability density functions are much heavier than a Gaussian distribution, and they also systematically depend on time increments. Quite interestingly, from a purely statistical standpoint, the characteristics of the extreme ramp‐up and ramp‐down events are found to be almost identical. With the aid of extreme value theory, we describe several other inherent features of extreme wind ramps in this paper.
Correction to: Interactions between β-adrenergic vasodilation and cervical sympathetic nerves are mediated by α2-adrenoceptors in the rat masseter muscle
Authors: Ishii Hisayoshi , Sato Toshiya
Published: April 2018

The article Interactions between β-adrenergic vasodilation and cervical sympathetic nerves are mediated by α2-adrenoceptors in the rat masseter muscle, written by Hisayoshi Ishii and Toshiya Sato, was originally published Online First without open access.
Berufliche und private Standortfaktoren für die Niederlassung von Hausärzten in ländlichen Räumen
Authors: Küpper Patrick , Mettenberger Tobias
Published: April 2018

The safeguarding of primary health care in rural regions is broadly discussed in science, politics and practice. Thereby the knowledge about current location factors is insufficient, because existing studies focus on professional factors or on locational imaginations of future doctors instead of analysing effective locational decisions. Thus, this study asks which professional and private location factors influence the settling decisions of general practitioners in rural regions. Therefore two regional case studies are conducted with overall 21 interviews with regional experts and newly settled doctors, working out crucial location factors. Building on that, the influence of chosen location factors for regional unequal practitioner concentrations as well as for the development of practitioner numbers are nationwide quantified by multiple regression models. The results show, that professional aspects, like economic security, close patient contacts and organisational freedom, as well as biographical relations are especially decisive criteria for the doctors’ location decisions. Furthermore, family-friendly everyday environments are very important for many of them. Other soft location factors as high standard cultural and leisure facilities are negligible. Furthermore, there is a relationship between inpatient and outpatient care. Many general practitioners worked in a regional hospital, before they switched to the ambulant sector, due to better working conditions and an easier compatibility with family life. The results point to a change of location factors, whereby further needs for research and concrete policy recommendations arise.
In Vitro Determination of the Main Effects in the Design of High-Flow Nasal Therapy Systems with Respect to Aerosol Performance
Authors: Bennett Gavin , Joyce Mary , Sweeney Louise , MacLoughlin Ronan
Published: April 2018

Introduction

The use of concurrent aerosol delivery during high-flow nasal therapy (HFNT) may be exploited to facilitate the delivery of a variety of prescribed medications for inhalation. Until now, a systematic approach to determine the conditions required to yield an optimal emitted dose has not been reported. The aim of this study was to establish the effects of gas flow rate, input droplet size, and nebulizer position on the amount of aerosol exiting the nasal cannula during HFNT and thus becoming available for inhalation.

Methods

Testing was completed according to a factorial statistical design of experiments (DOE) approach. Emitted dose was characterized with a vibrating mesh nebulizer (Aerogen Solo, Aerogen Ltd) for an adult model of HFNT at three clinically relevant gas flow rates, using three nebulizers producing varying input droplet sizes and placed at two different nebulizer positions.

Results

Increasing the gas flow rate significantly lowered the emitted dose, with a dose of 7.10% obtained at 10 LPM, 2.67% at 25 LPM, and 1.30% at 40 LPM (p < 0.0001). There was a significant difference in emitted dose between nebulizers with different input droplet sizes, with increasing input droplet size associated with a reduced emitted dose (6.11% with an input droplet size of 3.22 µm, 2.76% with 4.05 µm, and 2.38% with 4.88 µm, p  = 0.0002, Pearson’s r = − 0.2871). In addition, the droplet size exiting the nasal cannula interface was lower than that produced by the aerosol generator for all devices under test. Positioning the nebulizer immediately after the humidification chamber yielded a marginally greater emitted dose (3.79%) than when the nebulizer was placed immediately upstream of the nasal cannula (3.39%). Flow rate, input droplet size, and nebulizer position were at the 0.10 level of significance, indicating that all three factors had significant effects on emitted dose. According to the DOE model, flow rate had the greatest influence on emitted dose, followed by input droplet size and then nebulizer position.

Conclusion

Our findings indicate that in order to optimize the amount of aerosol exiting the nasal cannula interface during HFNT, it is necessary for gas flow rate to be low and the input droplet size to be small, while the nebulizer should be positioned immediately after the humidification chamber.

Funding

Aerogen Limited.
Queensland Teachers’ Relationship With the Sustainability Cross-Curriculum Priority
Authors: Nicholls Jennifer , Thorne Marcia
Published: April 2018

Sustainability is a Cross-Curriculum Priority (SCCP) in the Australian Curriculum and is intended to be integrated into teaching and learning where deemed appropriate by teachers. This article explores teachers’ knowledge, understanding, and beliefs about curriculum priorities and the situational context of teaching and learning in Queensland schools. In this article we discuss the ways in which teachers describe their relationship with sustainability education and the SCCP. Data were collected from interviews with 26 Queensland teachers, teaching across all year levels from early childhood to Year 12, as part of two different PhD research projects. Queensland teachers participating in both studies indicated strong support for the inclusion of sustainability within formal curriculum; however, this strong support did not translate into practice in most cases. As a result of curriculum and policy pressures, teachers indicated that despite their belief that Education for Sustainability (EfS) is important, few believe they have the time or support for teaching EfS. The current educational context teachers have described offers limited opportunity for teachers to integrate sustainability in ways that are meaningful and relevant to their students. The SCCP did not influence planning or teaching decisions, and many teachers were unaware of its existence. Data from both studies question the adequacy of current educational policy and curriculum documents for supporting teachers to engage with sustainability education.
Internal wave attractors in three-dimensional geometries: trapping by oblique reflection
Authors: Pillet G. , Ermanyuk E. V. , Maas L. R. M. , Sibgatullin I. N. , Dauxois T.
Published: April 2018

We study experimentally the propagation of internal waves in two different three-dimensional (3D) geometries, with a special emphasis on the refractive focusing due to the 3D reflection of obliquely incident internal waves on a slope. Both studies are initiated by ray tracing calculations to determine the appropriate experimental parameters. First, we consider a 3D geometry, the classical set-up to get simple, two-dimensional (2D) parallelogram-shaped attractors in which waves are forced in a direction perpendicular to a sloping bottom. Here, however, the forcing is of reduced extent in the along-slope, transverse direction. We show how the refractive focusing mechanism explains the formation of attractors over the whole width of the tank, even away from the forcing region. Direct numerical simulations confirm the dynamics, emphasize the role of boundary conditions and reveal the phase shifting in the transverse direction. Second, we consider a long and narrow tank having an inclined bottom, to simply reproduce a canal. In this case, the energy is injected in a direction parallel to the slope. Interestingly, the wave energy ends up forming 2D internal wave attractors in planes that are transverse to the initial propagation direction. This focusing mechanism prevents indefinite transmission of most of the internal wave energy along the canal.
Investigation of the second-mode instability at Mach 14 using calibrated schlieren
Authors: Kennedy Richard E. , Laurence Stuart J. , Smith Michael S. , Marineau Eric C.
Published: April 2018

Second-mode wave growth within the hypersonic boundary layer of a slender cone is investigated experimentally using high-speed schlieren visualizations. Experiments were performed in AEDC Tunnel 9 over a range of unit Reynolds number conditions at a Mach number of approximately 14. A thin lens with a known density profile placed within the field of view enables calibration of the schlieren set-up, and the relatively high camera frame rates employed allow for the reconstruction of time-resolved pixel intensities at discrete streamwise locations. The calibration in conjunction with the reconstructed signals enables integrated spatial amplification rates ($N$ factors) to be calculated for each unit Reynolds number condition and compared to $N$ factors computed from both pressure transducer measurements and linear parabolized stability equation (PSE) solutions. Good agreement is observed between $N$ factors computed from the schlieren measurements and those computed from the PSE solutions for the most-amplified second-mode frequencies. The streamwise development of $N$ factors calculated from the schlieren measurements compares favourably to that calculated from the pressure measurements with slight variations in the $N$ factor magnitudes calculated for harmonic frequencies. Finally, a bispectral analysis is carried out to identify nonlinear phase-coupled quadratic interactions present within the boundary layer. Multiple interactions are identified and revealed to be associated with the growth of disturbances at higher harmonic frequencies.
The Key Role of Banks in the Lifecycle of Bordeaux Wine Cooperatives
Authors: Cadot Julien , Ugaglia Adeline Alonso
Published: April 2018

In this article, we investigate a possible conflict between two core objectives of cooperatives, members’ income, and continuity, by examining the link between debt and the price paid to producers for Bordeaux wine cooperatives, according to their downstream strategies: (1) the traditional strategy, which is to sell wine in bulk to négociants; (2) joining a federation of cooperatives which blends and puts the wine in the retail market; and (3) vertical integration. We show that downstream strategies are related to different lending regimes, making the relationship between banks and cooperatives a key issue for the lifecycle of cooperatives. (JEL Classifications: D230, G320, Q130)
Style, Substance, and Philosophical Methodology: A Cross-Cultural Case Study
Authors: CHUNG JULIANNE
Published: April 2018

One challenge involved in integrating so-called ‘non-Western’ philosophies into ‘Western’ philosophical discourse concerns the fact that non-Western philosophical texts frequently differ significantly in style and approach from Western ones, especially those in contemporary analytic philosophy. But how might one bring texts that are written, for example, in a literary, non-expository style, and which do not clearly advance philosophical positions or arguments, into constructive dialogue with those that do? Also, why might one seek to do this in the first place? This paper addresses these questions by means of a case study involving the Daoist classic, theZhuangzi.
The Shame of Not Belonging: Navigating Failure in the Colonial Petition, South Africa 1910–1961
Authors: Jackson Will
Published: April 2018

This essay examines letters of petition sent by failed white settlers in South Africa to the British Governor General. These letters comprise a particular discursive genre that combine aspects of both private and public. The key to their success was controlled emotion: petitioners had to present their distress in such a way as to excite the exercise of compassion. Allowing subversive or stray emotions to enter a letter was bound to undermine a petitioner’s appeal. Reading this epistolary corpus critically allows us to understand the discursive strategies by which colonials claimed a sentimental attachment to Britain, the empire and, indeed, the Governor General himself.
Application of multiblock modelling to identify key drivers for antimicrobial use in pig production in four European countries
Authors: Collineau L. , Bougeard S. , Backhans A. , Dewulf J. , Emanuelson U. , Grosse Beilage E. , Lehébel A. , Lösken S. , Postma M. , Sjölund M. , Stärk K. D. C. , Visschers V. H. M. , Belloc C.
Published: April 2018

Antimicrobial use in pig farming is influenced by a range of risk factors, including herd characteristics, biosecurity level, farm performance, occurrence of clinical signs and vaccination scheme, as well as farmers’ attitudes and habits towards antimicrobial use. So far, the effect of these risk factors has been explored separately. Using an innovative method called multiblock partial least-squares regression, this study aimed to investigate, in a sample of 207 farrow-to-finish farms from Belgium, France, Germany and Sweden, the relative importance of the six above mentioned categories or ‘blocks’ of risk factors for antimicrobial use in pig production. Four country separate models were developed; they showed that all six blocks provided useful contribution to explaining antimicrobial use in at least one country. The occurrence of clinical signs, especially of respiratory and nervous diseases in fatteners, was one of the largest contributing blocks in all four countries, whereas the effect of the other blocks differed between countries. In terms of risk management, it suggests that a holistic and country-specific mitigation strategy is likely to be more effective. However, further research is needed to validate our findings in larger and more representative samples, as well as in other countries.
US Emergency Medical Services Fellows
Authors: Clemency Brian , Martin-Gill Christian , Rall Nicole , Patel Dipesh , Myers Jeffery
Published: April 2018

Introduction

The 2015-2016 academic year was the fourth year since the Accreditation Council for Graduate Medical Education (ACGME; Chicago, Illinois USA) accredited Emergency Medical Services (EMS) fellowships, and the first year an in-training examination was given. Soon, ACGME-accredited fellowship education will be the sole path to EMS board certification when the practice pathway closes after 2019. This project aimed to describe the current class of EMS fellows at ACGME-accredited programs and their current educational opportunities to better understand current and future needs in EMS fellowship education.

Methods

This was a cross-sectional survey of EMS fellows in ACGME-accredited programs in conjunction with the first EMS In-Training Examination (EMSITE) between April and June 2016. Fellows completed a 14-question survey composed of multiple-choice and free-response questions. Basic frequency statistics were performed on their responses.

Results

Fifty fellows from 35 ACGME-accredited programs completed the survey. The response rate was 100%. Forty-eight (96%) fellows reported previous training in emergency medicine. Twenty (40%) were undergoing fellowship training at the same institution as their prior residency training. Twenty-five (50%) fellows performed direct patient care aboard a helicopter during their fellowship. Thirty-three (66%) fellows had a dedicated physician response vehicle for fellows. All fellows reported using the National Association of EMS Physicians (NAEMSP; Overland Park, Kansas USA) textbooks as their primary reference. Fellows felt most prepared for the Clinical Aspects questions and least prepared for Quality Management and Research questions on the board exam.

Conclusion

These data provide insight into the characteristics of EMS fellows in ACGME-accredited programs.

ClemencyB, Martin-GillC, RallN, PatelD, MyersJ. US Emergency Medical Services fellows. Prehosp Disaster Med. 2018;33(3):339–341.
Antagonist treatment is just as effective as replacement therapy for opioid addiction but neither is used often enough
Authors: Stahl Stephen M.
Published: April 2018

One of the most malignant illnesses in psychiatry is opioid addiction. This disorder has resulted in a current epidemic of addiction, overdose, and death that continues in large part because of the lack of robust treatments and the surprising lack of utilization of the treatments that are available.
Effects of antibiotic resistance (AR) and microbiota shifts onCampylobacter jejuni-mediated diseases
Authors: Brooks Phillip T. , Mansfield Linda S.
Published: April 2018

Campylobacter jejuniis an important zoonotic pathogen recently designated a serious antimicrobial resistant (AR) threat. While most patients withC. jejuniexperience hemorrhagic colitis, serious autoimmune conditions can follow including inflammatory bowel disease (IBD) and the acute neuropathy Guillain Barré Syndrome (GBS). This review examines inter-relationships among factors mediatingC. jejunidiarrheal versus autoimmune disease especially ARC. jejuniand microbiome shifts. Because both susceptible and ARC. jejuniare acquired from animals or their products, we consider their role in harboring strains. Inter-relationships among factors mediatingC. jejunicolonization, diarrheal and autoimmune disease includeC. jejunivirulence factors and AR, the enteric microbiome, and host responses. Because ARC. jejunihave been suggested to affect the severity of disease, length of infections and propensity to develop GBS, it is important to understand how these interactions occur when strains are under selection by antimicrobials. More work is needed to elucidate host–pathogen interactions of ARC. jejunicompared with susceptible strains and how ARC. jejuniare maintained and evolve in animal reservoirs and the extent of transmission to humans. These knowledge gaps impair the development of effective strategies to prevent the emergence of ARC. jejuniin reservoir species and human populations.
The English Version of the Attitudes Toward Homosexuality Scale
Authors: Anderson Joel R. , Koc Yasin , Falomir-Pichastor Juan Manuel
Published: April 2018

Abstract. The present study reports the psychometric properties of the English version of the short form of the Attitudes Toward Homosexuality Scale (ATHS; Falomir-Pichastor & Mugny, 2009 ). Workers from Amazon’s MTurkTM (n = 235 for validation, n = 60 for test-retest) completed the short form of the ATHS, translated from French, and the Attitudes Toward Lesbians and Gay Men Scale (ATLG; Herek, 1998 ) and responded to a series of demographic questions. In this paper, we present evidence for a single-factor structure of the scale, along with evidence for the validity, internal consistency, and test-retest reliability of the measure. The data revealed distinct patterns in participants’ ATHS scores as a function of their religious affiliation and political conservatism. Finally, positive ATHS scores predicted support for gay rights over and above that predicted by ATLG scores ( Herek, 1984 ). The evidence presented suggests that the ATHS is a psychometrically reliable and valid tool for assessing attitudes toward homosexuality.
Multiphase Structural Evolution and Geodynamic Implications of Messinian Salt‐Related Structures, Levant Basin, Offshore Israel
Authors: Kartveit K. H. , Omosanya K. O. , Johansen S. E. , Eruteya O. E. , Reshef M. , Waldmann N. D.
Published: April 2018

Speculations surround salt deformation in the Mediterranean Basins, both related to the deformation history and the triggers for halokinesis since the onset of the Messinian Salinity Crisis. This work presents a detailed description of the mechanisms driving internal and external deformation of a salt giant from the Levant Basin, offshore Israel. The intrasalt siliciclastic layers generate good internal reflectivity within the Messinian evaporites, allowing a thorough elucidation of the complex evolution and nature of syn‐Messinian and post‐Messinian structures. We have identified three distinct phases of deformation in the deep basin, based on the orientation, timing, and geometry of their related structures: The first phase is characterized by small‐scaled, gravity‐driven, contractional faults and folds oriented N‐S that have been overprinted by a second syn‐Messinian, NW‐SE trending, deformation phase affecting the clastic bundles. This latter deformation phase is the cause of truncation of the intrasalt stringers on the intra‐Messinian truncation surface. The third deformation phase occurred in the Pleistocene and affected all strata from the Messinian salt to the seabed. This deformational phase produced thrust, strike‐slip, and normal faults, but the dominant orientation of the thrust faults and folds is NNW‐SSE. Our study demonstrates that the first deformation phase was caused by regional uplift along the Levant margin during the Messinian, the second is a response to basin subsidence toward the Cyprus Arc, also syn‐Messinian, and the third phase is likely related to the reorganization of the African‐Eurasian plate boundary and activity along the Dead Sea Transform after the Messinian Salinity Crisis.
Common Reflection Surface Stack Imaging of the Proterozoic Chambal Valley Vindhyan Basin and Its Boundary Fault in the Northwest India: Constraints on Crustal Evolution and Basin Formation
Authors: Mandal Biswajit , Vaidya Vijaya Rao , Sen Mrinal K. , Periyasamy Karuppannan , Sarkar Dipankar
Published: April 2018

The Vindhyan basin of northwestern and central India is one of the largest undeformed Meso‐Neoproterozoic basins in the world with likely potential of hydrocarbons. Crustal seismic reflection data along a 165‐km long Chandli‐Bundi‐Kota‐Kunjer profile of the Chambal Valley Vindhyan basin processed using common reflection surface stack method brought out new crustal features, which were missing in earlier images. A gently dipping structure of the basin is imaged with a maximum of 7.5‐km thick Proterozoic sediments, 1.5‐km thick volcanic sequence, and the granitic basement at 9.0‐km depth. The Great Boundary Thrust, a NW dipping crustal‐scale regional tectonic feature outcropping at Bundi, and a new NW dipping reflection band from 9‐ to 30‐km depth, named here as the Chambal thrust, are imaged beneath Bundi‐Kota segment. Subduction and collision are responsible for evolution of these thrusts implying horizontal crustal growth. Seismic images of compression on one side and extension on another side along with differences in the Moho characteristics and other constraints from geophysical data around Kota indicate the presence of a new tectonic boundary with a strong lateral discontinuity and strike‐slip features. The Moho topography is delineated for the first time revealing a crustal thickness ranging from 40 to 44 km. A 9‐ to 12‐km thick mafic underplating at the lower crust suggests an important postcollisional process indicating vertical crustal growth. Based on the images from the present reflection study, a geodynamic model of the region is suggested in a plate tectonic framework, which may apply to similar Paleoproterozoic collisional areas and associated basin formation.
Bifunctional gap-plasmon metasurfaces for visible light: polarization-controlled unidirectional surface plasmon excitation and beam steering at normal incidence
Authors: Ding Fei , Deshpande Rucha , Bozhevolnyi Sergey I
Published: April 2018

Integration of multiple diversified functionalities into a single, planar and ultra-compact device has become an emerging research area with fascinating possibilities for realization of very dense integration and miniaturization in photonics that requires addressing formidable challenges, particularly for operation in the visible range. Here we design, fabricate and experimentally demonstrate bifunctional gap-plasmon metasurfaces for visible light, allowing for simultaneous polarization-controlled unidirectional surface plasmon polariton (SPP) excitation and beam steering at normal incidence. The designed bifunctional metasurfaces, consisting of anisotropic gap-plasmon resonator arrays, produce two different linear phase gradients along the same direction for respective linear polarizations of incident light, resulting in distinctly different functionalities realized by the same metasurface. The proof-of-concept fabricated metasurfaces exhibit efficient (>25% on average) unidirectional (extinction ratio >20 dB) SPP excitation within the wavelength range of 600–650 nm when illuminated with normally incident light polarized in the direction of the phase gradient. At the same time, broadband (580–700 nm) beam steering (30.6°–37.9°) is realized when normally incident light is polarized perpendicularly to the phase gradient direction. The bifunctional metasurfaces developed in this study can enable advanced research and applications related to other distinct functionalities for photonics integration.
APR-246 reactivates mutant p53 by targeting cysteines 124 and 277
Authors: Zhang Qiang , Bykov Vladimir J. N. , Wiman Klas G. , Zawacka-Pankau Joanna
Published: April 2018

The TP53 tumor suppressor gene is frequently inactivated in human tumors by missense mutations in the DNA binding domain. TP53 mutations lead to protein unfolding, decreased thermostability and loss of DNA binding and transcription factor function. Pharmacological targeting of mutant p53 to restore its tumor suppressor function is a promising strategy for cancer therapy. The mutant p53 reactivating compound APR-246 (PRIMA-1Met) has been successfully tested in a phase I/IIa clinical trial. APR-246 is converted to the reactive electrophile methylene quinuclidinone (MQ), which binds covalently to p53 core domain. We identified cysteine 277 as a prime binding target for MQ in p53. Cys277 is also essential for MQ-mediated thermostabilization of wild-type, R175H and R273H mutant p53, while both Cys124 and Cys277 are required for APR-246-mediated functional restoration of R175H mutant p53 in living tumor cells. These findings may open opportunities for rational design of novel mutant p53-targeting compounds.
Upregulation of neuronal astrocyte elevated gene-1 protects nigral dopaminergic neurons in vivo
Authors: Leem Eunju , Kim Hyung-Jun , Choi Minji , Kim Sehwan , Oh Yong-Seok , Lee Kea Joo , Choe Young-Shik , Um Jae-Young , Shin Won-Ho , Jeong Jae Yeong , Jin Byung Kwan , Kim Dong Woon , McLean Catriona , Fisher Paul B. , Kholodilov Nikolai , Ahn Kwang Seok , Lee Jae Man , Jung Un Ju , Lee Seok-Geun , Kim Sang Ryong
Published: April 2018

The role of astrocyte elevated gene-1 (AEG-1) in nigral dopaminergic (DA) neurons has not been studied. Here we report that the expression of AEG-1 was significantly lower in DA neurons in the postmortem substantia nigra of patients with Parkinson’s disease (PD) compared to age-matched controls. Similarly, decreased AEG-1 levels were found in the 6-hydroxydopamine (6-OHDA) mouse model of PD. An adeno-associated virus-induced increase in the expression of AEG-1 attenuated the 6-OHDA-triggered apoptotic death of nigral DA neurons. Moreover, the neuroprotection conferred by the AEG-1 upregulation significantly intensified the neurorestorative effects of the constitutively active ras homolog enriched in the brain [Rheb(S16H)]. Collectively, these results demonstrated that the sustained level of AEG-1 as an important anti-apoptotic factor in nigral DA neurons might potentiate the therapeutic effects of treatments, such as Rheb(S16H) administration, on the degeneration of the DA pathway that characterizes PD.
Preliminary molecular evidence associating a novel BRCA1 synonymous variant with hereditary ovarian cancer syndrome
Authors: Minucci Angelo , Concolino Paola , De Bonis Maria , Costella Alessandra , Paris Ida , Scambia Giovanni , Capoluongo Ettore
Published: April 2018

Extensive molecular screening of the BRCA1/2 (BRCA) genes by massively parallel sequencing (MPS) identified variants of uncertain (or unknown) significance (VUS) and novel variants. We performed a molecular characterization of a novel BRCA1 synonymous variant discovered in a family with hereditary ovarian cancer (HOC) syndrome. We showed that the BRCA1 c.5073 A > T variant might play a pathogenic role in HOC syndrome in this family.
Analysis of predicted loss-of-function variants in UK Biobank identifies variants protective for disease
Authors: Emdin Connor A. , Khera Amit V. , Chaffin Mark , Klarin Derek , Natarajan Pradeep , Aragam Krishna , Haas Mary , Bick Alexander , Zekavat Seyedeh M. , Nomura Akihiro , Ardissino Diego , Wilson James G. , Schunkert Heribert , McPherson Ruth , Watkins Hugh , Elosua Roberto , Bown Matthew J. , Samani Nilesh J. , Baber Usman , Erdmann Jeanette , Gupta Namrata , Danesh John , Chasman Daniel , Ridker Paul , Denny Joshua , Bastarache Lisa , Lichtman Judith H. , D’Onofrio Gail , Mattera Jennifer , Spertus John A. , Sheu Wayne H.-H. , Taylor Kent D. , Psaty Bruce M. , Rich Stephen S. , Post Wendy , Rotter Jerome I. , Chen Yii-Der Ida , Krumholz Harlan , Saleheen Danish , Gabriel Stacey , Kathiresan Sekar
Published: April 2018

Less than 3% of protein-coding genetic variants are predicted to result in loss of protein function through the introduction of a stop codon, frameshift, or the disruption of an essential splice site; however, such predicted loss-of-function (pLOF) variants provide insight into effector transcript and direction of biological effect. In >400,000 UK Biobank participants, we conduct association analyses of 3759 pLOF variants with six metabolic traits, six cardiometabolic diseases, and twelve additional diseases. We identified 18 new low-frequency or rare (allele frequency < 5%) pLOF variant-phenotype associations. pLOF variants in the gene GPR151 protect against obesity and type 2 diabetes, in the gene IL33 against asthma and allergic disease, and in the gene IFIH1 against hypothyroidism. In the gene PDE3B, pLOF variants associate with elevated height, improved body fat distribution and protection from coronary artery disease. Our findings prioritize genes for which pharmacologic mimics of pLOF variants may lower risk for disease.