bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcritical Crack Growth in Cementitious Materials Subject to Chemomechanical Deterioration—Experimental Test Using Specimens of Negative Geometry
Authors: Wang Weijin , Tong Teng , Tan Susheng , Yu Qiang
Published: December 2016

Knowledge of the subcritical crack growth (SCG) in cement-based materials subject to concurrent physical and chemical attacks is of great importance for understanding and mitigating the chemomechanical deterioration in concrete structural members. In this study, the SCG in hardened cement pastes is investigated experimentally by a novel test approach aided with microcharacterization. In the test, specimens of negative geometry are designed, which enable the use of load control to trigger stable crack propagation in hardened cement pastes. Multiple specimens, cast from the same batch of mixture, are exposed to the same chemical condition and loaded at the same age. With the aid of a high-resolution microscopy system, which is used to trace the crack tip, the average trend and the associated variation of the dependence of crack velocity v on the stress intensity factor K at the crack tip are obtained. Different from static fatigue, three distinctive regions are captured in the K–v curves of specimens experiencing chemomechanical deterioration. With the help of advanced techniques including scanning electron microscopy (SEM), atomic-force microscopy (AFM), and Raman spectroscopy, the microstructure destruction and chemical composition change induced by the imposed chemomechanical attack are characterized at different stages. In addition to the physical insights for deeper understanding of the coupled effect of chemomechanical attack, these experimental results provide important macro- and microscopic benchmarks for the theoretical modeling and numerical investigation in the future studies.
Post-Buckling Analysis of Curved Beams
Authors: Fan Zhichao , Wu Jian , Ma Qiang , Liu Yuan , Su Yewang , Hwang Keh-Chih
Published: December 2016

Stretchability of the stretchable and flexible electronics involves the post-buckling behaviors of internal connectors that are designed into various shapes of curved beams. The linear displacement–curvature relation is often used in the existing post-buckling analyses. Koiter pointed out that the post-buckling analysis needs to account for curvature up to the fourth power of displacements. A systematic method is established for the accurate post-buckling analysis of curved beams in this paper. It is shown that the nonlinear terms in curvature should be retained, which is consistent with Koiter's post-buckling theory. The stretchability and strain of the curved beams under different loads can be accurately obtained with this method.
Formulation of Generalized Mass Transfer Correlations for Blood Oxygenator Design
Authors: Low Kenny W. Q. , Van Loon Raoul , Rolland Samuel A. , Sienz Johann
Published: December 2016

This paper numerically investigates non-Newtonian blood flow with oxygen and carbon dioxide transport across and along an array of uniformly square and staggered arranged fibers at various porosity (ε) levels, focussing on a low Reynolds number regime (Re < 10). The objective is to establish suitable mass transfer correlations, expressed in the form of Sherwood number (Sh = f(ε, Re, Sc)), that identifies the link from local mass transfer investigations to full-device analyses. The development of a concentration field is initially investigated and expressions are established covering the range from a typical deoxygenated condition up to a full oxygenated condition. An important step is identified where a cut-off point in those expressions is required to avoid any under- or over-estimation on the Sherwood number. Geometrical features of a typical commercial blood oxygenator is adopted and results in general show that a balance in pressure drop, shear stress, and mass transfer is required to avoid potential blood trauma or clotting formation. Different definitions of mass transfer correlations are found for oxygen/carbon dioxide, parallel/transverse flow, and square/staggered configurations, respectively. From this set of correlations, it is found that transverse flow has better gas transfer than parallel flow which is consistent with reported literature. The mass transfer dependency on fiber configuration is observed to be pronounced at low porosity. This approach provides an initial platform when one is looking to improve the mass transfer performance in a blood oxygenator without the need to conduct any numerical simulations or experiments.
Analysis of a Cycloid Speed Reducer Considering Tooth Profile Modification and Clearance-Fit Output Mechanism
Authors: Li Xuan , Li Chaoyang , Wang Yawen , Chen Bingkui , Lim Teik C.
Published: December 2016

The load distribution analysis plays a significant role in the performance evaluation of cycloid speed reducer. However, current analytical models usually ignore elastic deformation, clearances, or assembly errors. These factors must be considered for realistic performance evaluation of cycloid speed reducer. This paper proposes an analytical model for cycloid speed reducer based on unloaded tooth contact and load distribution analyses. The proposed model can predict the loads on various components of the speed reducer in the presence of clearances and eccentricity errors. The results are compared with those predicted by the cycloid speed reducer model based on theoretical geometry. The effect of radial and pin-hole clearances as well as eccentricity errors, on some key design factors, such as contact stress, transmission error, gear ratio, and load on bearing, is investigated. This study can be used to assist the optimal design of cycloid speed reducers.
Analysis of Two Spherical Parallel Manipulators With Hidden Revolute Joints
Authors: Li Ju , Michael McCarthy J.
Published: December 2016

In this paper, we examine two spherical parallel manipulators (SPMs) constructed with legs that include planar and spherical subchains that combine to impose constraints equivalent to hidden revolute joints. The first has supporting serial chain legs constructed from three revolute joints with parallel axes, denoted R∥R∥R, followed by two revolute joints that have intersecting axes, denoted RR̂. The leg has five degrees-of-freedom and is denoted R∥R∥R-RR̂. Three of these legs can be assembled so the spherical chains all share the same point of intersection to obtain a spherical parallel manipulator denoted as 3-R∥R∥R-RR̂. The second spherical parallel manipulator has legs constructed from three revolute joints that share one point of intersection, denoted RRR̂, and a second pair of revolute joints with axes that intersect in a different point. This five-degree-of-freedom leg is denoted RRR̂-RR̂. The spherical parallel manipulator constructed from these legs is 3-RRR̂-RR̂. We show that the internal constraints of these two types of legs combine to create hidden revolute joints that can be used to analyze the kinematics and singularities of these spherical parallel manipulators. A quaternion formulation provides equations for the quartic singularity varieties some of which decompose into pairs of quadric surfaces which we use to classify these spherical parallel manipulators.
Data Communication Pathway for Sensing Guidewire at Proximal Side: A Review
Authors: Sharei Hoda , Stoute Ronald , van den Dobbelsteen John J. , Siebes Maria , Dankelman Jenny
Published: December 2016

As the connection at the proximal tip plays an important role for sensing guidewires, we compared various sensing guidewires with regard to their proximal connectors. The strengths and weaknesses of each are discussed and recommendations for future development are provided. A literature search limited to the English language for the time period from the 1960s to the 2010s has been performed on the USPTO database, Espacenet, and Web of Science. The results have been categorized on the basis of the connector design. A comprehensive overview and classification of proximal connectors for sensing guidewires used for cardiovascular interventions is presented. The classification is based on both the type of connector (fixed or removable) and the type of connection (physical, wireless, or a combination). Considering the complexity of the currently prototyped and tested connectors, future connector development will necessitate an easy and cost-effective manufacturing process that can ensure safe and robust connections.
Particulate Release From Nanoparticle-Loaded Shape Memory Polymer Foams
Authors: Nathan Adam L. , Fletcher Grace K. , Monroe Mary Beth B. , Hwang Wonjun , Herting Scott M. , Hasan Sayyeda M. , Keller Brandis K. , Maitland Duncan J.
Published: December 2016

Highly porous, open-celled shape memory polymer (SMP) foams are being developed for a number of vascular occlusion devices. Applications include abdominal aortic and neurovascular aneurysm or peripheral vascular occlusion. A major concern with implanting these high surface area materials in the vasculature is the potential to generate unacceptable particulate burden, in terms of number, size, and composition. This study demonstrates that particulate numbers and sizes in SMP foams are in compliance with limits stated by the most relevant standard and guidance documents. Particulates were quantified in SMP foams as made, postreticulation, and after incorporating nanoparticles intended to increase material toughness and improve radiopacity. When concentrated particulate treatments were administered to fibroblasts, they exhibited high cell viability (100%). These results demonstrate that the SMP foams do not induce an unacceptable level of risk to potential vascular occlusion devices due to particulate generation.
Hydraulic Robotic Surgical Tool Changing Manipulator
Authors: Pourghodrat Abolfazl , Nelson Carl A. , Oleynikov Dmitry
Published: December 2016

Natural orifice transluminal endoscopic surgery (NOTES) is a surgical technique to perform “scarless” abdominal operations. Robotic technology has been exploited to improve NOTES and circumvent its limitations. Lack of a multitasking platform is a major limitation. Manual tool exchange can be time consuming and may lead to complications such as bleeding. Previous multifunctional manipulator designs use electric motors. These designs are bulky, slow, and expensive. This paper presents design, prototyping, and testing of a hydraulic robotic tool changing manipulator. The manipulator is small, fast, low-cost, and capable of carrying four different types of laparoscopic instruments.
Benchmarking the Real-Time Core Model for VVER-1000 Simulator Application on Asymmetric Core Load
Authors: Georgieva Emiliya , Dinkov Yavor , Ivanov Kostadin
Published: December 2016

The aim of this paper is to summarize authors' experience in adaptation of an existing plant-specific VVER-1000/V320 model for simulation of a rare example of a Kalinin 3 nuclear power plant (NPP) transient of “switching-off of one of the four operating main circulation pumps at nominal reactor power” with an asymmetric core configuration. The fidelity and accuracy of simulation with emphasis on reactor core model is illustrated through comparison with plant-specific data. Simulation results concerning fuel assembly (FA) power and axial power distribution during the transient are compared with records from Kalinin 3 in-core monitoring system (ICMS). Main operating parameters of nuclear steam supply system of a VVER-1000/V320 series units vary to a considerable degree. While Kalinin 3 benchmark specification contains very good description of the transient, as well as record of many parameters of the unit, the document provides only superficial description of the reference unit. In such a case, an approach based on a “generic” V320 model by default introduces deviations which are difficult to quantify. There are several examples which warrant discussion. Some of the most important lessons learned are as follows. (1) individual characteristics of all the main circulation pumps and the reactor coolant loops are quite important for the quality of simulation and should be accounted for in the model; (2) variations in fuel assembly characteristics should be accounted for not only in terms of macroscopic cross section library but also in terms of local pressure loss coefficients and mixing factors in the case of mixed core loads; (3) comprehensive plant-specific model of dynamic response of instrumentation and control (I&C) systems is a necessity; dynamic characteristics of individual measurement channels (nuclear instrumentation, pressure, temperature) should be accounted for; and (4) comprehensive plant-specific model of balance-of-plant equipment, instrumentation, and control is a necessity. Above requirements impose a difficult task to comply with. Nevertheless, any individual nuclear power unit is supposed to maintain a detailed design database and data requirements for plant-specific model development should be considered.
Biomechanical Phenotyping of the Murine Aorta: What Is the Best Control?
Authors: Bellini C. , Caulk A. W. , Li G. , Tellides G. , Humphrey J. D.
Published: December 2016

The availability of diverse mouse models is revealing increasingly greater information on arterial mechanics, including homeostatic adaptations and pathologic maladaptations to genetic, pharmacological, and surgical manipulations. Fundamental to understanding such biomechanical changes, however, is reliable information on appropriate control vessels. In this paper, we contrast 15 different geometrical and mechanical metrics of biaxial wall mechanics for the ascending aorta across seven different types of possible control mice. We show that there is a comforting similarity across these multiple controls for most, though not all, metrics. In particular, three potential controls, namely, noninduced conditional mice, exhibit higher values of distensibility, an important clinical metric of structural stiffness, and two of these potential controls also have higher values of intrinsic circumferential material stiffness. There is motivation, therefore, to understand better the biomechanical changes that can arise with noninduced Cre-lox or similar approaches for generating mutations conditionally. In cases of germline mutations generated by breeding heterozygous +/− mice, however, the resulting homozygous +/+ mice tend to exhibit properties similar to traditional (C57BL/6) controls.
Solute segregation and deviation from bulk thermodynamics at nanoscale crystalline defects
Authors: Titus Michael S. , Rhein Robert K. , Wells Peter B. , Dodge Philip C. , Viswanathan Gopal Babu , Mills Michael J. , Van der Ven Anton , Pollock Tresa M.
Published: December 2016

Atomistic processes governing the high-temperature strength of structural materials were accurately characterized and modeled.
Scientists flag new causes for surge in methane levels
Authors: Voosen Paul
Published: December 2016

Swelling tropical wetlands and a decline in a natural atmospheric detergent are
leading suspects.
Critics assail paper claiming harm from cancer vaccine
Authors: Normile Dennis
Published: December 2016

Vaccination rates fall as antivax campaigns gather steam.
Mineral Types and Tree Species Determine the Functional and Taxonomic Structures of Forest Soil Bacterial Communities
Authors: Colin Y. , Nicolitch O. , Turpault M.-P. , Uroz S.
Published: December 2016

Although minerals represent important soil constituents, their impact on the diversity and structure of soil microbial communities remains poorly documented. In this study, pure mineral particles with various chemistries (i.e., obsidian, apatite, and calcite) were considered. Each mineral type was conditioned in mesh bags and incubated in soil below different tree stands (beech, coppice with standards, and Corsican pine) for 2.5 years to determine the relative impacts of mineralogy and mineral weatherability on the taxonomic and functional diversities of mineral-associated bacterial communities. After this incubation period, the minerals and the surrounding bulk soil were collected to determine mass loss and to perform soil analyses, enzymatic assays, and cultivation-dependent and -independent analyses. Notably, our 16S rRNA gene pyrosequencing analyses revealed that after the 2.5-year incubation period, the mineral-associated bacterial communities strongly differed from those of the surrounding bulk soil for all tree stands considered. When focusing only on minerals, our analyses showed that the bacterial communities associated with calcite, the less recalcitrant mineral type, significantly differed from those that colonized obsidian and apatite minerals. The cultivation-dependent analysis revealed significantly higher abundances of effective mineral-weathering bacteria on the most recalcitrant minerals (i.e., apatite and obsidian). Together, our data showed an enrichment of
Betaproteobacteria
and effective mineral-weathering bacteria related to the
Burkholderia
and
Collimonas
genera on the minerals, suggesting a key role for these taxa in mineral weathering and nutrient cycling in nutrient-poor forest ecosystems.

IMPORTANCE
Forests are usually developed on nutrient-poor and rocky soils, while nutrient-rich soils have been dedicated to agriculture. In this context, nutrient recycling and nutrient access are key processes in such environments. Deciphering how soil mineralogy influences the diversity, structure, and function of soil bacterial communities in relation to the soil conditions is crucial to better understanding the relative role of the soil bacterial communities in nutrient cycling and plant nutrition in nutrient-poor environments. The present study determined in detail the diversity and structure of bacterial communities associated with different mineral types incubated for 2.5 years in the soil under different tree species using cultivation-dependent and -independent analyses. Our data showed an enrichment of specific bacterial taxa on the minerals, specifically on the most weathered minerals, suggesting that they play key roles in mineral weathering and nutrient cycling in nutrient-poor forest ecosystems.
Transcriptomic Responses in the Bloom-Forming Cyanobacterium Microcystis Induced during Exposure to Zooplankton
Authors: Harke Matthew J. , Jankowiak Jennifer G. , Morrell Brooke K. , Gobler Christopher J.
Published: December 2016

The bloom-forming, toxic cyanobacterium
Microcystis
synthesizes multiple secondary metabolites and has been shown to deter zooplankton grazing. However, the biochemical and/or molecular basis by which
Microcystis
deters zooplankton remains unclear. This global transcriptomic study explored the response of
Microcystis
to direct and indirect exposures to multiple densities of two cladoceran grazers,
Daphnia pulex
and
D. magna
. Higher densities of both daphnids significantly reduced
Microcystis
cell densities and elicited a stronger transcriptional response in
Microcystis
. While many putative grazer deterrence genes (encoding microcystin, aeruginosin, cyanopeptolin, and microviridin) were largely unaffected by zooplankton, transcripts for heat shock proteins (
hsp
) increased in abundance. Beyond metabolites and
hsp
, large increases in the abundances of transcripts from photosynthetic processes were observed, evidencing energy acquisition pathways were stimulated by grazing. In addition, transcripts of genes associated with the production of extracellular polysaccharides and gas vesicles significantly increased in abundance. These genes have been associated with colony formation and may have been invoked to deter grazers. Collectively, this study demonstrates that daphnid grazers induce a significant transcriptomic response in
Microcystis
, suggesting this cyanobacterium upregulates specific biochemical pathways to adapt to predation.

IMPORTANCE
This work explores the transcriptomic responses of
Microcystis aeruginosa
following exposure to grazing by two cladocerans,
Daphnia magna
and
D. pulex
. Contrary to previous hypotheses,
Microcystis
did not employ putative grazing deterrent secondary metabolites in response to the cladocerans, suggesting they may have other roles within the cell, such as oxidative stress protection. The transcriptional metabolic signature during intense grazing was largely reflective of a growth and stress response, although increasing abundances of transcripts encoding extracellular polysaccharides and gas vesicles were potentially related to predator avoidance.
Genomic Variation in IbA10G2 and Other Patient-Derived Cryptosporidium hominis Subtypes
Authors: Sikora Per , Andersson Sofia , Winiecka-Krusnell Jadwiga , Hallström Björn , Alsmark Cecilia , Troell Karin , Beser Jessica , Arrighi Romanico B. G.
Published: December 2016

In order to improve genotyping and epidemiological analysis of
Cryptosporidium
spp., genomic data need to be generated directly from a broad range of clinical specimens. Utilizing a robust method that we developed for the purification and generation of amplified target DNA, we present its application for the successful isolation and whole-genome sequencing of 14 different
Cryptosporidium hominis
patient specimens. Six isolates of subtype IbA10G2 were analyzed together with a single representative each of 8 other subtypes: IaA20R3, IaA23R3, IbA9G3, IbA13G3, IdA14, IeA11G3T3, IfA12G1, and IkA18G1. Parasite burden was measured over a range of more than 2 orders of magnitude for all samples, while the genomes were sequenced to mean depths of between 17× and 490× coverage. Sequence homology-based functional annotation identified several genes of interest, including the gene encoding
Cryptosporidium
oocyst wall protein 9 (COWP9), which presented a predicted loss-of-function mutation in all the sequence subtypes, except for that seen with IbA10G2, which has a sequence identical to the
Cryptosporidium parvum
reference Iowa II sequence. Furthermore, phylogenetic analysis showed that all the IbA10G2 genomes form a monophyletic clade in the
C. hominis
tree as expected and yet display some heterogeneity within the IbA10G2 subtype. The current report validates the aforementioned method for isolating and sequencing
Cryptosporidium
directly from clinical stool samples. In addition, the analysis demonstrates the potential in mining data generated from sequencing multiple whole genomes of
Cryptosporidium
from human fecal samples, while alluding to the potential for a higher degree of genotyping within
Cryptosporidium
epidemiology.
Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry for Combined Species Identification and Drug Sensitivity Testing in Mycobacteria
Authors: Ceyssens Pieter-Jan , Soetaert Karine , Timke Markus , Van den Bossche An , Sparbier Katrin , De Cremer Koen , Kostrzewa Markus , Hendrickx Marijke , Mathys Vanessa
Published: December 2016

Species identification and drug susceptibility testing (DST) of mycobacteria are important yet complex processes traditionally reserved for reference laboratories. Recent technical improvements in matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) has started to facilitate routine mycobacterial identifications in clinical laboratories. In this paper, we investigate the possibility of performing phenotypic MALDI-based DST in mycobacteriology using the recently described MALDI Biotyper antibiotic susceptibility test rapid assay (MBT-ASTRA). We randomly selected 72 clinical
Mycobacterium tuberculosis
and nontuberculous mycobacterial (NTM) strains, subjected them to MBT-ASTRA methodology, and compared its results to current gold-standard methods. Drug susceptibility was tested for rifampin, isoniazid, linezolid, and ethambutol (
M. tuberculosis
,
n
= 39), and clarithromycin and rifabutin (NTM,
n
= 33). Combined species identification was performed using the Biotyper Mycobacteria Library 4.0.
Mycobacterium
-specific MBT-ASTRA parameters were derived (calculation window,
m/z
5,000 to 13,000, area under the curve [AUC] of >0.015, relative growth [RG] of <0.5; see the text for details). Using these settings, MBT-ASTRA analyses returned 175/177
M. tuberculosis
and 65/66 NTM drug resistance profiles which corresponded to standard testing results. Turnaround times were not significantly different in
M. tuberculosis
testing, but the MBT-ASTRA method delivered on average a week faster than routine DST in NTM. Databases searches returned 90.4% correct species-level identifications, which increased to 98.6% when score thresholds were lowered to 1.65. In conclusion, the MBT-ASTRA technology holds promise to facilitate and fasten mycobacterial DST and to combine it directly with high-confidence species-level identifications. Given the ease of interpretation, its application in NTM typing might be the first in finding its way to current diagnostic workflows. However, further validations and automation are required before routine implementation can be envisioned.
Progress towards Rapid Detection of Measles Vaccine Strains: a Tool To Inform Public Health Interventions
Authors: Hacker Jill K.
Published: December 2016

Rapid differentiation of vaccine from wild-type strains in suspect measles cases is a valuable epidemiological tool that informs the public health response to this highly infectious disease. Few public health laboratories sequence measles virus-positive specimens to determine genotype, and the vaccine-specific real-time reverse transcriptase PCR (rRT-PCR) assay described by F. Roy et al. (J. Clin. Microbiol. 55:735–743, 2017,
https://doi.org/10.1128/JCM.01879-16
) offers a rapid, easily adoptable method to identify measles vaccine strains in suspect cases.
Nonstructural Protein 4 of Porcine Reproductive and Respiratory Syndrome Virus Modulates Cell Surface Swine Leukocyte Antigen Class I Expression by Downregulating β2-Microglobulin Transcription
Authors: Qi Pengfei , Liu Ke , Wei Jianchao , Li Yuming , Li Beibei , Shao Donghua , Wu Zhuanchang , Shi Yuanyuan , Tong Guangzhi , Qiu Yafeng , Ma Zhiyong
Published: December 2016

Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of PRRS, which has important impacts on the pig industry. PRRSV infection results in disruption of the swine leukocyte antigen class I (SLA-I) antigen presentation pathway. In this study, highly pathogenic PRRSV (HP-PRRSV) infection inhibited transcription of the β2-microglobulin (β2M) gene (
B2M
) and reduced cellular levels of β2M, which forms a heterotrimeric complex with the SLA-I heavy chain and a variable peptide and plays a critical role in SLA-I antigen presentation. HP-PRRSV nonstructural protein 4 (Nsp4) was involved in the downregulation of β2M expression. Exogenous expression of Nsp4 downregulated β2M expression at both the mRNA and the protein level and reduced SLA-I expression on the cell surface. Nsp4 bound to the porcine
B2M
promoter and inhibited its transcriptional activity. Domain III of Nsp4 and the enhancer
PAM
element of the porcine
B2M
promoter were identified as essential for the interaction between Nsp4 and
B2M
. These findings demonstrate a novel mechanism whereby HP-PRRSV may modulate the SLA-I antigen presentation pathway and provide new insights into the functions of HP-PRRSV Nsp4.

IMPORTANCE
PRRSV modulates the host response by disrupting the SLA-I antigen presentation pathway. We show that HP-PRRSV downregulates SLA-I expression on the cell surface via transcriptional inhibition of
B2M
expression by viral Nsp4. The interaction between domain III of Nsp4 and the enhancer
PAM
element of the porcine
B2M
promoter is essential for inhibiting
B2M
transcription. These observations reveal a novel mechanism whereby HP-PRRSV may modulate SLA-I antigen presentation and provide new insights into the functions of viral Nsp4.
Disruption of Stress Granule Formation by the Multifunctional Cricket Paralysis Virus 1A Protein
Authors: Khong Anthony , Kerr Craig H. , Yeung Clarence H. L. , Keatings Kathleen , Nayak Arabinda , Allan Douglas W. , Jan Eric
Published: December 2016

Stress granules (SGs) are cytosolic ribonucleoprotein aggregates that are induced during cellular stress. Several viruses modulate SG formation, suggesting that SGs have an impact on virus infection. However, the mechanisms and impact of modulating SG assembly in infected cells are not completely understood. In this study, we identify the dicistrovirus cricket paralysis virus 1A (CrPV-1A) protein that functions to inhibit SG assembly during infection. Moreover, besides inhibiting RNA interference, CrPV-1A also inhibits host transcription, which indirectly modulates SG assembly. Thus, CrPV-1A is a multifunctional protein. We identify a key R146A residue that is responsible for these effects, and mutant CrPV(R146A) virus infection is attenuated in
Drosophila melanogaster
S2 cells and adult fruit flies and results in increased SG formation. Treatment of CrPV(R146A)-infected cells with actinomycin D, which represses transcription, restores SG assembly suppression and viral yield. In summary, CrPV-1A modulates several cellular processes to generate a cellular environment that promotes viral translation and replication.

IMPORTANCE
RNA viruses encode a limited set of viral proteins to modulate an array of cellular processes in order to facilitate viral replication and inhibit antiviral defenses. In this study, we identified a viral protein, called CrPV-1A, within the dicistrovirus cricket paralysis virus that can inhibit host transcription, modulate viral translation, and block a cellular process called stress granule assembly. We also identified a specific amino acid within CrPV-1A that is important for these cellular processes and that mutant viruses containing mutations of CrPV-1A attenuate virus infection. We also demonstrate that the CrPV-1A protein can also modulate cellular processes in human cells, suggesting that the mode of action of CrPV-1A is conserved. We propose that CrPV-1A is a multifunctional, versatile protein that creates a cellular environment in virus-infected cells that permits productive virus infection.
Recent Outbreaks of Shigellosis in California Caused by Two Distinct Populations of Shigella sonnei with either Increased Virulence or Fluoroquinolone Resistance
Authors: Kozyreva Varvara K. , Jospin Guillaume , Greninger Alexander L. , Watt James P. , Eisen Jonathan A. , Chaturvedi Vishnu
Published: December 2016

Shigellosis is an acute diarrheal disease causing nearly half a million infections, 6,000 hospitalizations, and 70 deaths annually in the United States.
S. sonnei
caused two unusually large outbreaks in 2014 and 2015 in California. We used whole-genome sequencing to understand the pathogenic potential of bacteria involved in these outbreaks. Our results suggest the persistence of a local
S. sonnei
SDi/SJo clone in California since at least 2008. Recently, a derivative of the original clone acquired the ability to produce Shiga toxin (STX) via exchanges of bacteriophages with other bacteria. STX production is connected with more severe disease, including bloody diarrhea. A second population of
S. sonnei
that caused an outbreak in the San Francisco area was resistant to fluoroquinolones and showed evidence of connection to a fluoroquinolone-resistant lineage from South Asia. These emerging trends in
S. sonnei
populations in California must be monitored for future risks of the spread of increasingly virulent and resistant clones.
Systematic review and meta-analysis of the effects of football heading
Authors: Kontos Anthony P , Braithwaite Rock , Chrisman Sara P D , McAllister-Deitrick Jamie , Symington Larissa , Reeves Valerie L , Collins Michael W
Published: December 2016

Aim/objective

The objective of this study was to provide a meta-analysis examining the effects of football heading.

Design

Meta-analytical review on football heading effects on neurocognitive performance, cognition and symptom reports.

Data sources

Combinations of the key terms were entered into the following electronic database search engines: Cochrane Libraries, PyscARTICLE, PyscINFO, PubMed, ProQuest, SPORTDiscus and Web of Science on 7 July 2016.

Eligibility criteria for selecting studies

The following inclusion criteria were used to determine eligibility for studies: (1) the study examined and reported on soccer athletes; (2) the population's age, sex and sport position was described; (3) cognitive function, symptoms, balance or other outcomes were quantitatively measured; (4) football heading exposure was quantitatively measured between at least two groups and (5) the study was written in the English language after December 1979.

Results

The literature search process identified 467 unique studies. After applying exclusion criteria, 28 studies remained. Included studies had a total of 2288 participants (female participants =933, male participants =1355), aged 13–70 years. The overall results of random effects modelling of football heading were found to be inconclusive across all outcomes, groups and time points. No moderating variables related to methodological, sample or study characteristics were supported in the analysis; age was a potential moderating variable.

Summary/conclusions

We provide the first meta-analytical review of football heading effects aggregated from multiple studies and extended findings from a recent systematic review of the effects of football heading. Our analysis indicates no overall effect for heading a football on adverse outcomes.
Calculating acute:chronic workload ratios using exponentially weighted moving averages provides a more sensitive indicator of injury likelihood than rolling averages
Authors: Murray Nicholas B , Gabbett Tim J , Townshend Andrew D , Blanch Peter
Published: December 2016

Objective

To determine if any differences exist between the rolling averages and exponentially weighted moving averages (EWMA) models of acute:chronic workload ratio (ACWR) calculation and subsequent injury risk.

Methods

A cohort of 59 elite Australian football players from 1 club participated in this 2-year study. Global positioning system (GPS) technology was used to quantify external workloads of players, and non-contact ‘time-loss’ injuries were recorded. The ACWR were calculated for a range of variables using 2 models: (1) rolling averages, and (2) EWMA. Logistic regression models were used to assess both the likelihood of sustaining an injury and the difference in injury likelihood between models.

Results

There were significant differences in the ACWR values between models for moderate (ACWR 1.0–1.49; p=0.021), high (ACWR 1.50–1.99; p=0.012) and very high (ACWR >2.0; p=0.001) ACWR ranges. Although both models demonstrated significant (p<0.05) associations between a very high ACWR (ie, >2.0) and an increase in injury risk for total distance ((relative risk, RR)=6.52–21.28) and high-speed distance (RR=5.87–13.43), the EWMA model was more sensitive for detecting this increased risk. The variance (R2) in injury explained by each ACWR model was significantly (p<0.05) greater using the EWMA model.

Conclusions

These findings demonstrate that large spikes in workload are associated with an increased injury risk using both models, although the EWMA model is more sensitive to detect increases in injury risk with higher ACWR.
Top-down Infliximab Study in Kids with Crohn's disease (TISKids): an international multicentre randomised controlled trial
Authors: Cozijnsen M A , van Pieterson M , Samsom J N , Escher J C , de Ridder L
Published: December 2016

Introduction

Crohn's disease (CD) is a chronic inflammatory disease predominantly affecting the gastrointestinal tract. CD usually requires lifelong medication and is accompanied by severe complications, such as fistulae and strictures, resulting in surgery. Infliximab (IFX) is very effective for treating paediatric patients with CD, but is currently only registered for therapy refractory patients—the so-called step-up strategy. We hypothesise that using IFX first-line, that is, top-down, will give more mucosal healing, fewer relapses, less complications, need for surgery and hospitalisation.

Methods and analysis

This international multicentre open-label randomised controlled trial includes children, aged 3–17 years, with new-onset, untreated CD with moderate-to-severe disease activity (weighted Paediatric Crohn's Disease Activity Index (wPCDAI)>40). Eligible patients will be randomised to top-down or step-up treatment. Top-down treatment consists of 5 IFX infusions combined with azathioprine (AZA). After these 5 infusions, patients will continue AZA. Patients randomised to step-up will receive standard induction treatment, either oral prednisolone or exclusive enteral nutrition, combined with AZA as maintenance treatment. The primary outcome is clinical remission (wPCDAI<12.5) at 52 weeks without need for additional CD-related therapy or surgery. Total follow-up is 5 years. Secondary outcomes include clinical disease activity, mucosal healing by endoscopy (at week 10 and optionally week 52), faecal calprotectin, growth, quality of life, medication use and adverse events.

Ethics and dissemination

Conducted according to the Declaration of Helsinki and Good Clinical Practice. Medical-ethical approval will be obtained for each site.

Trial registration number

NCT02517684; Pre-results.
Association between reported sleep need and sleepiness at the wheel: comparative study on French highways between 1996 and 2011
Authors: Quera-Salva M A , Hartley S , Sauvagnac-Quera R , Sagaspe P , Taillard J , Contrand B , Micoulaud J A , Lagarde E , Barbot F , Philip P
Published: December 2016

Objective

To investigate the evolution over 15 years of sleep schedules, sleepiness at the wheel and driving risk among highway drivers.

Methods

Comparative survey including questions on usual sleep schedules and before the trip, sleepiness at the wheel, the Epworth sleepiness scale, Basic Nordic Sleep Questionnaire (BNSQ) and a travel questionnaire.

Results

80% of drivers stopped by the highway patrol agreed to participate in both studies with a total of 3545 drivers in 2011 and 2196 drivers in 1996 interviewed. After standardisation based on sex, age and mean annual driving distance, drivers in 2011 reported shorter sleep time on week days (p<0.0001), and week-ends (p<0.0001) and shorter optimal sleep time (p<0.0001) compared to 1996 drivers. There were more drivers sleepy at the wheel in 2011 than in 1996 (p<0.0001) and 2.5 times more drivers in 2011 than in 1996 had an Epworth sleepiness score >15 indicating severe sleepiness.

Conclusions

Even if drivers in 2011 reported good sleep hygiene prior to a highway journey, drivers have reduced their mean weekly sleep duration over 15 years and have a higher risk of sleepiness at the wheel. Sleep hygiene for automobile drivers remains an important concept to address.
Prescription of renin–angiotensin system blockers and risk of acute kidney injury: a population-based cohort study
Authors: Mansfield Kathryn E , Nitsch Dorothea , Smeeth Liam , Bhaskaran Krishnan , Tomlinson Laurie A
Published: December 2016

Objective

To investigate whether there is an association between use of ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB) and risk of acute kidney injury (AKI).

Study design

We conducted a new-user cohort study of the rate of AKI among users of common antihypertensives.

Setting

UK primary care practices contributing to the Clinical Practice Research Datalink (CPRD) eligible for linkage to hospital records data from the Hospital Episode Statistics (HES) database between April 1997 and March 2014.

Participants

New users of antihypertensives: ACEI/ARB, β-blockers, calcium channel blockers and thiazide diuretics.

Outcomes

The outcome was first episode of AKI. We estimated incidence rate ratio (RR) for AKI during time exposed to ACEI/ARB compared to time unexposed, adjusting for age, sex, comorbidities, use of other antihypertensive drugs and calendar period using Poisson regression. Covariates were time updated.

Results

Among 570 445 participants, 303 761 were prescribed ACEI/ARB with a mean follow-up of 4.1 years. The adjusted RR of AKI during time exposed to ACEI/ARB compared to time unexposed was 1.12 (95% CI 1.07 to 1.17). This relative risk varied depending on absolute risk of AKI, with lower or no increased relative risk from the drugs among those at greatest absolute risk. For example, among people with stage 4 chronic kidney disease (who had 6.69 (95% CI 5.57 to 8.03) times higher rate of AKI compared to those without chronic kidney disease), the adjusted RR of AKI during time exposed to ACEI/ARB compared to time unexposed was 0.66 (95% CI 0.44 to 0.97) in contrast to 1.17 (95% CI 1.09 to 1.25) among people without chronic kidney disease.

Conclusions

Treatment with ACEI/ARB is associated with only a small increase in AKI risk while individual patient characteristics are much more strongly associated with the rate of AKI. The degree of increased risk varies between patient groups.
Maternal Malaria and Malnutrition (M3) initiative, a pooled birth cohort of 13 pregnancy studies in Africa and the Western Pacific
Authors: Unger Holger W , Cates Jordan E , Gutman Julie , Briand Valerie , Fievet Nadine , Valea Innocent , Tinto Halidou , d'Alessandro Umberto , Landis Sarah H , Adu-Afarwuah Seth , Dewey Kathryn G , Ter Kuile Feiko , Dellicour Stephanie , Ouma Peter , Slutsker Laurence , Terlouw Dianne J , Kariuki Simon , Ayisi John , Nahlen Bernard , Desai Meghna , Madanitsa Mwayi , Kalilani-Phiri Linda , Ashorn Per , Maleta Kenneth , Mueller Ivo , Stanisic Danielle , Schmiegelow Christentze , Lusingu John , Westreich Daniel , van Eijk Anna Maria , Meshnick Steven , Rogerson Stephen
Published: December 2016

Purpose

The Maternal Malaria and Malnutrition (M3) initiative has pooled together 13 studies with the hope of improving understanding of malaria–nutrition interactions during pregnancy and to foster collaboration between nutritionists and malariologists.

Participants

Data were pooled on 14 635 singleton, live birth pregnancies from women who had participated in 1 of 13 pregnancy studies. The 13 studies cover 8 countries in Africa and Papua New Guinea in the Western Pacific conducted from 1996 to 2015.

Findings to date

Data are available at the time of antenatal enrolment of women into their respective parent study and at delivery. The data set comprises essential data such as malaria infection status, anthropometric assessments of maternal nutritional status, presence of anaemia and birth weight, as well as additional variables such gestational age at delivery for a subset of women. Participating studies are described in detail with regard to setting and primary outcome measures, and summarised data are available from each contributing cohort.

Future plans

This pooled birth cohort is the largest pregnancy data set to date to permit a more definite evaluation of the impact of plausible interactions between poor nutritional status and malaria infection in pregnant women on fetal growth and gestational length. Given the current comparative lack of large pregnancy cohorts in malaria-endemic settings, compilation of suitable pregnancy cohorts is likely to provide adequate statistical power to assess malaria–nutrition interactions, and could point towards settings where such interactions are most relevant. The M3 cohort may thus help to identify pregnant women at high risk of adverse outcomes who may benefit from tailored intensive antenatal care including nutritional supplements and alternative or intensified malaria prevention regimens, and the settings in which these interventions would be most effective.
Protocol for a multicentre study to assess feasibility, acceptability, effectiveness and direct costs of TRIumPH (Treatment and Recovery In PsycHosis): integrated care pathway for psychosis
Authors: Rathod Shanaya , Garner Christie , Griffiths Alison , Dimitrov Borislav D , Newman-Taylor Katherine , Woodfine Chris , Hansen Lars , Tabraham Paul , Ward Karen , Asher Carolyn , Phiri Peter , Naeem Farooq , North Pippa , Munshi Tariq , Kingdon David
Published: December 2016

Introduction

Duration of untreated psychosis (time between the onset of symptoms and start of treatment) is considered the strongest predictor of symptom severity and outcome. Integrated care pathways that prescribe timeframes around access and interventions can potentially improve quality of care.

Methods and analysis

A multicentre mixed methods study to assess feasibility, acceptability, effectiveness and analysis of direct costs of an integrated care pathway for psychosis. A pragmatic, non-randomised, controlled trial design is used to compare the impact of Treatment and Recovery In PsycHosis (TRIumPH; Intervention) by comparison between NHS organisations that adopt TRIumPH and those that continue with care as usual (Control). Quantitative and qualitative methods will be used. We will use routinely collected quantitative data and study-specific questionnaires and focus groups to compare service user outcomes, satisfaction and adherence to intervention between sites that adopt TRIumPH versus sites that continue with usual care pathways.

Setting

4 UK Mental health organisations. Two will implement TRIumPH whereas two will continue care as usual.

Participants

Staff, carers, individuals accepted to early intervention in psychosis teams in participating organisations for the study period.

Intervention

TRIumPH—Integrated Care Pathway for psychosis that has a holistic approach and prescribes time frames against interventions; developed using intelligence from data; co-produced with patients, carers, clinicians and other stakeholders.

Outcomes

Feasibility will be assessed through adherence to the process measures. Satisfaction and acceptability will be assessed using questionnaires and focus groups. Effectiveness will be assessed through data collection and evaluation of patient outcomes, including clinical, functional and recovery outcomes, physical health, acute care use. Outcome measures will be assessed at baseline, 12 and 24 months to measure whether there is an effect and if so, whether this is sustained over time. Outcomes measures at the adopter sites will be compared to their own baseline and against comparator sites.

Ethics and dissemination

Ethics approval was obtained from East of Scotland Research Ethics Service (REC Ref no: LR/15/ES/0091). The results will be disseminated through publications, conference presentations, reports to the organisation.

Study registration

UK Clinical Research Network Portfolio: 19187.