bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and risk factors for functional bowel disorders in South China: a population based study using the Rome III criteria
Authors: Long Y. , Huang Z. , Deng Y. , Chu H. , Zheng X. , Yang J. , Zhu Y. , Fried M. , Fox M. , Dai N.
Published: July 2016

Background

Functional bowel disorders (FBDs) such as irritable bowel syndrome (IBS) impact on quality of life and health care resources. It is uncertain whether patients with functional digestive symptoms have similar characteristics in different populations. This population‐based study assessed the prevalence and identified risk factors for these disorders in South‐East China.

Methods

Five communities were selected at random and invitations distributed to a representative sample (block randomization). Questionnaires were completely supervised by investigators. Demographic and medical data with FBD symptoms (Rome III criteria), psychological condition, life event stress, and quality of life were collected.

Key Results

Functional bowel disorder prevalence was 41.6% in 1999/2115 (94.5%) completed questionnaires: 9.9% functional constipation (FC), 6.8% bloating (FB), 6.5% diarrhea (FD), 5.9% IBS (IBS‐D 47.1%, IBS‐M 23.9%, IBS‐C 12.8%, IBS‐U 16.2%), and 12.6% unspecified. Similar numbers of men and women had FBDs or IBS (overall; 51.3% male vs 48.7% female, P=.796); however, there was female predominance in FC (62.1%, P<.001) and FB (58.5%, P=.038). FBDs were associated with greater anxiety, depression, life event stress, and a lower quality of life compared with those without symptoms (all, P<.0001). Logistic regression identified medical co‐morbidity, anxiety/depression, and life event stress as independent risk factors for these disorders.

Conclusions & Inferences

Functional bowel disorders are as common in South China as in western populations. A similar number of men and women report FBDs and IBS. Only FC and FB are more prevalent in females. Independent risk factors associated with FBDs included physical and psychosocial stressors.
Temporal prediction modulates the evaluative processing of “good” action feedback: An electrophysiological study
Authors: Kimura Kenta , Kimura Motohiro , Iwaki Sunao
Published: July 2016

The present study aimed to investigate whether or not the evaluative processing of action feedback can be modulated by temporal prediction. For this purpose, we examined the effects of the predictability of the timing of action feedback on an ERP effect that indexed the evaluative processing of action feedback, that is, an ERP effect that has been interpreted as a feedback‐related negativity (FRN) elicited by “bad” action feedback or a reward positivity (RewP) elicited by “good” action feedback. In two types of experimental blocks, the participants performed a gambling task in which they chose one of two cards and received an action feedback that indicated monetary gain or loss. In fixed blocks, the time interval between the participant's choice and the onset of the action feedback was fixed at 0, 500, or 1,000 ms in separate blocks; thus, the timing of action feedback was predictable. In mixed blocks, the time interval was randomly chosen from the same three intervals with equal probability; thus, the timing was less predictable. The results showed that the FRN/RewP was smaller in mixed than fixed blocks for the 0‐ms interval trial, whereas there was no difference between the two block types for the 500‐ms and 1,000‐ms interval trials. Interestingly, the smaller FRN/RewP was due to the modulation of gain ERPs rather than loss ERPs. These results suggest that temporal prediction can modulate the evaluative processing of action feedback, and particularly good feedback, such as that which indicates monetary gain.
Patients with chronic insomnia have selective impairments in memory that are modulated by cortisol
Authors: Chen Gui‐hai , Xia Lan , Wang Fang , LI Xue‐Wei , Jiao Chuan‐an
Published: July 2016

Memory impairment is a frequent complaint in insomniacs; however, it is not consistently demonstrated. It is unknown whether memory impairment in insomniacs involves neuroendocrine dysfunction. The participants in this study were selected from the clinical setting and included 21 patients with chronic insomnia disorder (CID), 25 patients with insomnia and comorbid depressive disorder (CDD), and 20 control participants without insomnia. We evaluated spatial working and reference memory, object working and reference memory, and object recognition memory using the Nine Box Maze Test. We also evaluated serum neuroendocrine hormone levels. Compared to the controls, the CID patients made significantly more errors in spatial working and object recognition memory (p < .05), whereas the CDD patients performed poorly in all the assessed memory types (p < .05). In addition, the CID patients had higher levels (mean difference [95% CI]) of corticotrophin‐releasing hormone, cortisol (31.98 [23.97, 39.98] μg/l), total triiodothyronine (667.58 [505.71, 829.45] μg/l), and total thyroxine (41.49 [33.23, 49.74] μg/l) (p < .05), and lower levels of thyrotropin‐releasing hormone (‐35.93 [‐38.83, ‐33.02] ng/l), gonadotropin‐releasing hormone (‐4.50 [‐5.02, ‐3.98] ng/l) (p < .05), and adrenocorticotropic hormone compared to the CDD patients. After controlling for confounding variables, the partial correlation analysis revealed that the levels of cortisol positively correlated with the errors in object working memory (r = .534,p = .033) and negatively correlated with the errors in object recognition memory (r = ‐.659,p = .006) in the CID patients. The results suggest that the CID patients had selective memory impairment, which may be mediated by increased cortisol levels.
Gravitating toward the quadruple helix: international connections for the enhancement of a regional innovation system in Northeast Italy
Authors: Lew Yong Kyu , Khan Zaheer , Cozzio Sara
Published: July 2016

The majority of previous Regional Innovation System (RIS) studies generally provide a rather static overview of the roles of innovation‐creating actors. This article explores a single RIS in Trentino in Italy. The case shows that the roles of three actors (i.e., the provincial government, academia/research centers, and firms) are vital in creating the RIS, and that the provincial‐level government policy is important in supporting the innovation activities of regional research institutions and firms aimed at developing their international connections. The public‐private research collaboration and international connections of these actors are the key determinants of the development of an advanced RIS, but have largely been ignored in the extant RIS literature. This article extends the existing RIS and Triple Helix research to an international dimension, highlighting the complementary role of international connections within the RIS, thus reflecting a shift toward Quadruple Helix.
Development of REACH Generic Exposure Scenarios for Substances Used as Coformulants in Plant Protection Products
Authors: Dobe Christopher , Bonifay Sebastien , Fliege Ralph , Krass Joachim , Mostert Volker , Vosswinkel Renate , Wormuth Matthias
Published: July 2016

This article reviews the interactions between the REACH (Registration, Evaluation, Authorization and restriction of Chemicals) regulation and the plant protection product regulation for substances used as coformulants in the European Union, and describes generic exposure scenarios developed for their exposure and risk assessment. The REACH exposure scenarios describe the operational conditions and risk management measures used in the risk assessment of a coformulant, and as such these translate as the boundaries of safe use. The generic exposure scenarios are designed to be simple, and closely integrate with REACH use descriptors and customized exposure models. Clustering of application methods and exposure determinants resulted in four generic exposure scenarios, each covering professional workers or consumers, and application of products in liquid, granular form, or applied on seeds. When used in conjunction with appropriate exposure models, the generic exposure scenarios support efficient first‐tier risk assessment of coformulants by utilizing a higher level of abstraction and conservatism than typically used in plant protection product assessments.
Individual Characteristics, Behavioral Biases, and Trade Policy Preferences: Evidence from a Survey in Japan
Authors: Tomiura Eiichi , Ito Banri , Mukunoki Hiroshi , Wakasugi Ryuhei
Published: July 2016

Import liberalization is one of the most actively debated issues in trade policy. This paper examines how trade policy preferences are related to individual characteristics based on a survey in Japan. Among 10,000 surveyed individuals, people working in non‐agricultural sectors, those working in managerial occupations, or those above retirement age tend to favor freer imports. This paper also finds that people who are influenced by the status quo bias are likely to oppose import liberalization even after controlling for each individual's various characteristics, suggesting that neither income compensation nor insurance schemes are sufficient for expanding support for free trade.
Wave Propagation in a Shape Memory Alloy Bar Under an Impulsive Loading
Authors: Zhu Pingping , Dai Hui-Hui
Published: July 2016

We analyze wave propagation in a semi-infinite shape memory alloy (SMA) bar under a rectangular impulsive loading. Different trilinear up–down–up nominal stress–strain curves for loading and unloading processes are adopted to complete the dynamical system. The chord criterion (equivalent to maximally dissipative kinetics) is employed to single out the unique solution for the impact problem. The interactions among discontinuities (loading/unloading elastic shock waves and phase boundaries) can yield some complicated wave structure. In particular, it is found that the encounter of the unloading elastic shock wave and the loading phase boundary can yield three different wave patterns depending on the level of impact stress, which are different from those for a hardening response studied in the literature. Solutions in the whole temporal and spatial domain are obtained, which reveal interesting wave structures induced by two different levels of impact. Phase transformation regions and tension/compression regions are also determined. The results also suggest that the SMAs can be used for impact-protection purpose effectively.
Interfacial Delamination of Inorganic Films on Viscoelastic Substrates
Authors: Huang Yin , Yuan Jianghong , Zhang Yingchao , Feng Xue
Published: July 2016

The performance of flexible/stretchable electronics may be significantly reduced by the interfacial delamination due to the large mismatch at the interface between stiff films and soft substrates. Based on the theory of viscoelasticity, a cracked composite beam model is proposed in this paper to analyze the delamination of an elastic thin film from a viscoelastic substrate. The time-varying neutral plane of the composite beam is derived analytically, and then the energy release rate of the interfacial crack is obtained from the Griffith's theory. Further, three different states of the crack propagation under constant external loadings are predicted, which has potential applications on the structural design of inorganic flexible/stretchable electronics.
Numerical Investigation of the Three-Dimensional Elastic–Plastic Sloped Contact Between Two Hemispheric Asperities
Authors: Shi Xi , Zou Yunwu , Fang Huibo
Published: July 2016

For real engineering surfaces contact, most asperities come into contact in a configuration of shoulder-to-shoulder instead of aligned head-on. In this work, a three-dimensional (3D) model of two identical elastic–plastic spherical asperities in contact was developed which characterizes the initial contact offset with polar angle α and azimuthal angle β. The simulations with finite-element method (FEM) show that the adhesive coefficient of friction (COF) is only influenced by large initial azimuthal angle thus mainly depends on interfacial shear strength. The plowing COF is determined, however, by effective contact interference, which reflects the combined effects of α and β. Moreover, a detailed parametric study shows that the load ratio is significantly dependent on Young's modulus and interfacial shear strength, while the maximum elastic rebound force during the unloading phase is mainly dependent on polar angle.
Perspective on Materials Failure Theory and Applications
Authors: Christensen Richard M.
Published: July 2016

The history of developing failure criteria is briefly examined. The cumulative result is found to be completely unsatisfactory and extremely misleading, to the point of crisis. The long time blockage of the materials failure field has had serious and retarding effects on all related technical areas that are dependent on reliable failure projections. A new and rationally different approach to failure theory formulation is outlined and fully documented. After summarizing recent research progress, a program for the recovery and revitalization of the field is given.
Analysis of a Two-Dimensional Aeroelastic System Using the Differential Transform Method
Authors: Wang Xuechuan , Yue Xiaokui , Dai Honghua , Yuan Jianping
Published: July 2016

This paper investigates the nonlinear responses of a typical two-dimensional airfoil with control surface freeplay and cubic pitch stiffness in an incompressible flow. The differential transform (DT) method is applied to the aeroelastic system. Due to the nature of this method, it is capable of providing analytical solutions in forms of Taylor series expansions in each subdomain between two adjacent sampling points. The results demonstrate that the DT method can successfully detect nonlinear aeroelastic responses such as limit cycle oscillations (LCOs), chaos, bifurcation, and flutter phenomenon. The accuracy and efficiency of this method are verified by comparing it with the RK (Henon) method. In addition to ordinary differential equations (ODEs), the DT method is also a powerful tool for directly solving integrodifferential equations. In this paper, the original aeroelastic system of integrodifferential equations is handled directly by the DT method. With no approximation or simplification imposed on the integral terms of aerodynamic function, the resulted solutions are closer to representing the real dynamical behavior.
Predicting Non-Stationary and Stochastic Activation of Saddle-Node Bifurcation
Authors: Kim Jinki , Harne R. L. , Wang K. W.
Published: July 2016

Accurately predicting the onset of large behavioral deviations associated with saddle-node bifurcations is imperative in a broad range of sciences and for a wide variety of purposes, including ecological assessment, signal amplification, and microscale mass sensing. In many such practices, noise and non-stationarity are unavoidable and ever-present influences. As a result, it is critical to simultaneously account for these two factors toward the estimation of parameters that may induce sudden bifurcations. Here, a new analytical formulation is presented to accurately determine the probable time at which a system undergoes an escape event as governing parameters are swept toward a saddle-node bifurcation point in the presence of noise. The double-well Duffing oscillator serves as the archetype system of interest since it possesses a dynamic saddle-node bifurcation. The stochastic normal form of the saddle-node bifurcation is derived from the governing equation of this oscillator to formulate the probability distribution of escape events. Non-stationarity is accounted for using a time-dependent bifurcation parameter in the stochastic normal form. Then, the mean escape time is approximated from the probability density function (PDF) to yield a straightforward means to estimate the point of bifurcation. Experiments conducted using a double-well Duffing analog circuit verifies that the analytical approximations provide faithful estimation of the critical parameters that lead to the non-stationary and noise-activated saddle-node bifurcation.
Modeling and Simulation of Flexible Needle Insertion Into Soft Tissue Using Modified Local Constraints
Authors: Gao Dedong , Lei Yong , Lian Bin , Yao Bin
Published: July 2016

Needle insertion is a widely used medical procedure in various minimally invasive surgeries. The estimation of the coupled needle deflection and tissue deformation during the needle insertion procedure is crucial to the success of the surgery. In this work, a novel needle deflection–tissue deformation coupling model is proposed for flexible needle insertion into soft tissue. Based on the assumption that the needle deflection is small comparing to the length of the insertion, the needle–tissue interaction model is developed based on the modified local constraint method, where the interactive forces between the needle and the tissue are balanced through integration of needle–force and tissue–force relationships. A testbed is constructed and the experiments are designed to validate the proposed method using artificial phantom with markers. Based on the experimental analysis, the cutting and friction forces are separated from the force–time curves and used as the inputs into the proposed model. The trajectories of the markers inside the soft tissue are recorded by a CCD camera to compare with the simulation trajectories. The errors between the experimental and simulation trajectories are less than 0.8 mm. The results demonstrate that the proposed method is effective to model the needle insertion procedure.
Fixturing Effects in the Thermal Modeling of Laser Cladding
Authors: Gouge M. F. , Michaleris P. , Palmer T. A.
Published: July 2016

Fixturing of components during laser cladding can incur significant conductive thermal losses. However, due to the surface roughness at contact, interfacial conduction is impeded. The effective contact conductivity, known as gap conductance, is much lower than the contacting material conductivities. This work investigates modeling conduction losses to fixturing bodies during laser cladding. Two laser cladding experiments are performed using contrasting fixturing schemes: one cantilevered substrate with a minimal substrate-fixture contact area and one with a substrate bolted to a work bench, with a significant substrate-fixture contact area. Using calibrated gap conductance values, error for the cantilevered fixture model decreases from 20.5% to 6.49% in the contact region, while the bench fixtured model error decreases from a range of 60–102% to 11–45%. The improvement in accuracy shows the necessity of accounting for conduction losses in the thermal modeling of laser cladding, particularly for fixturing setups with large areas of contact.
Moisture Desorption Studies on Polymer Hydrated and Vacuum Extruded Bentonite Clay Mat
Authors: Loh Eric Wooi Kee , Wijeyesekera Devapriya Chitral , Ciupala Mihaela Anca
Published: July 2016

Moisture desorption observations from two bentonite clay mats subjected to ten environmental zones with individually different combinations of laboratory-controlled constant temperatures (between 20 °C and 40 °C) and relative humidity (between 15% and 70%) are presented. These laboratory observations are compared with predictions from mathematical models, such as thin-layer drying equations and kinetic drying models proposed by Page, Wang and Singh, and Henderson and Pabis. The quality of fit of these models is assessed using standard error (SE) of estimate, relative percent of error, and coefficient of correlation. The Page model was found to better predict the drying kinetics of the bentonite clay mats for the simulated tropical climates. Critical study on the drying constant and moisture diffusion coefficient helps to assess the efficacy of a polymer to retain moisture and control desorption through water molecule bonding. This is further substantiated with the Guggenheim–Anderson–De Boer (GAB) desorption isotherm model which is presented.
Why marine phytoplankton calcify
Authors: Monteiro Fanny M. , Bach Lennart T. , Brownlee Colin , Bown Paul , Rickaby Rosalind E. M. , Poulton Alex J. , Tyrrell Toby , Beaufort Luc , Dutkiewicz Stephanie , Gibbs Samantha , Gutowska Magdalena A. , Lee Renee , Riebesell Ulf , Young Jeremy , Ridgwell Andy
Published: July 2016

Calcification in coccolithophores has high energy demand but brings multiple benefits enabling diversity of ecology and form.
First farmers' motley roots
Authors: Gibbons Ann
Published: July 2016

Unrelated groups adopted farming at about the same time in different parts of the Fertile Crescent.
Brain scans are prone to false positives, study says
Authors: Miller Greg
Published: July 2016

Common software settings may have skewed the statistics for thousands of studies.
ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells
Authors: Lewis Samantha C. , Uchiyama Lauren F. , Nunnari Jodi
Published: July 2016

How the ER manages mitochondrial division

It has been unclear how mitochondrial DNA (mtDNA) replication is spatially controlled in mammalian cells and how the mitochondrial nucleoid—the protein-DNA structure that is the unit of mtDNA inheritance—is distributed at the cellular level. Lewis
et al.
now show that homeostatic mtDNA synthesis in mitochondrial nucleoids in mammalian cells is spatially linked to a small subset of endoplasmic reticulum (ER)-mitochondria contact sites that are specifically destined for mitochondrial division. Successive events of mtDNA replication, mitochondrial division, and mitochondrial motility function together to ensure the accurate distribution of mtDNA in cells. Furthermore, ER-mitochondria contacts coordinate the licensing of mtDNA replication with division to distribute newly replicated nucleoids to daughter mitochondria.

Science
, this issue p.
261
Shrinking light to allow forbidden transitions on the atomic scale
Authors: Rivera Nicholas , Kaminer Ido , Zhen Bo , Joannopoulos John D. , Soljačić Marin
Published: July 2016

Making the forbidden allowed

Spontaneous emission, in which an excited electron lowers its energy by emitting a photon, is a fundamental process in light-matter interactions. In principle, the electron can relax from the excited state to any unoccupied lower energy level. In practice, however, most of these transitions are too slow and so are effectively forbidden. Rivera
et al.
show theoretically that the plasmonic excitations associated with two-dimensional materials can be used to enhance and control the light-matter interaction. Transitions that were once considered forbidden can thus be accessed, opening up the entire spectrum of an optical emitter.

Science
, this issue p.
263
Big data meets human health
Self-Tracking
Gina Neff and Dawn Nafus
MIT Press, 2016. 233 pp.
Crowdsourced Health How What You Do on the Internet Will Improve Medicine
Elad Yom-Tov
MIT Press, 2016. 144 pp.
Authors: Farrington Conor
Published: July 2016

Internet searches and fitness trackers are poised to play a role in the future of health care
Ferroelectric chalcogenides—materials at the edge
Authors: Kooi Bart J. , Noheda Beatriz
Published: July 2016

Tin telluride becomes a more robust ferroelectric as an ultrathin film
A toxic timeline
Love Canal A Toxic History from Colonial Times to the Present
Richard S. Newman
Oxford University Press, 2016. 306 pp.
Authors: Hamblin Jacob Darwin
Published: July 2016

Lessons from Love Canal offer context for complacent environmental policies
Crisis informatics—New data for extraordinary times
Authors: Palen Leysia , Anderson Kenneth M.
Published: July 2016

Focus on behaviors, not on fetishizing social media tools
Diagnosis of Ebola Virus Disease: Past, Present, and Future
Authors: Broadhurst M. Jana , Brooks Tim J. G. , Pollock Nira R.
Published: July 2016

Laboratory diagnosis of Ebola virus disease plays a critical role in outbreak response efforts; however, establishing safe and expeditious testing strategies for this high-biosafety-level pathogen in resource-poor environments remains extremely challenging. Since the discovery of Ebola virus in 1976 via traditional viral culture techniques and electron microscopy, diagnostic methodologies have trended toward faster, more accurate molecular assays. Importantly, technological advances have been paired with increasing efforts to support decentralized diagnostic testing capacity that can be deployed at or near the point of patient care. The unprecedented scope of the 2014-2015 West Africa Ebola epidemic spurred tremendous innovation in this arena, and a variety of new diagnostic platforms that have the potential both to immediately improve ongoing surveillance efforts in West Africa and to transform future outbreak responses have reached the field. In this review, we describe the evolution of Ebola virus disease diagnostic testing and efforts to deploy field diagnostic laboratories in prior outbreaks. We then explore the diagnostic challenges pervading the 2014-2015 epidemic and provide a comprehensive examination of novel diagnostic tests that are likely to address some of these challenges moving forward.
Modulation of Host Immunity by the Human Metapneumovirus
Authors: Céspedes Pablo F. , Palavecino Christian E. , Kalergis Alexis M. , Bueno Susan M.
Published: July 2016

Globally, as a leading agent of acute respiratory tract infections in children <5 years of age and the elderly, the human metapneumovirus (HMPV) has gained considerable attention. As inferred from studies comparing vaccinated and experimentally infected mice, the acquired immune response elicited by this pathogen fails to efficiently clear the virus from the airways, which leads to an exaggerated inflammatory response and lung damage. Furthermore, after disease resolution, there is a poor development of T and B cell immunological memory, which is believed to promote reinfections and viral spread in the community. In this article, we discuss the molecular mechanisms that shape the interactions of HMPV with host tissues that lead to pulmonary pathology and to the development of adaptive immunity that fails to protect against natural infections by this virus.
Species Distribution and
In Vitro
Azole Susceptibility of Aspergillus Section
Nigri
Isolates from Clinical and Environmental Settings
Authors: Iatta Roberta , Nuccio Federica , Immediato Davide , Mosca Adriana , De Carlo Carmela , Miragliotta Giuseppe , Parisi Antonio , Crescenzo Giuseppe , Otranto Domenico , Cafarchia Claudia
Published: July 2016

Aspergillus
section
Nigri
includes species of interest for animal and human health, although studies on species distribution are limited to human cases. Data on the antifungal susceptibilities and the molecular mechanism of triazole resistance in strains belonging to this section are scant. Forty-two black
Aspergillus
strains from human patients (16 isolates), animals (14 isolates), and the environment (12 isolates) were molecularly characterized and their
in vitro
triazole susceptibilities investigated.
Aspergillus tubingensis
was isolated from humans, animals, and environmental settings, whereas
Aspergillus awamori
and
Aspergillus niger
were isolated exclusively from humans. Phylogenetic analyses of β-tubulin and calmodulin gene sequences were concordant in differentiating
A. tubingensis
from
A. awamori
and
A. niger
. Voriconazole and posaconazole (PSZ) were the most active triazoles. One
A. tubingensis
strain was resistant to itraconazole and PSZ and one
A. niger
strain to PSZ. Sequence analysis of the
cyp51A
gene revealed different sequence types within a species, and
A. tubingensis
strains were also phylogenetically distinct from
A. awamori
/
A. niger
strains according to the strain origin and susceptibility profile. Genetic analysis of the
cyp51A
sequences suggests that two nonsynonymous mutations resulting in amino acid substitutions in the CYP51A protein (changes of L to R at position 21 [L21R] and of Q to R at position 228 [Q228R]) might be involved in azole resistance. Though azole resistance in black
Aspergillus
isolates from animals and rural environments does not represent a threat to public health in Southern Italy, the use of triazoles in the clinical setting needs to better monitored. The
cyp51A
sequence is useful for the molecular identification of black
Aspergillus
, and point mutations in protein sequences could be responsible for azole resistance phenomena.
Moraxella catarrhalis Might Be More Common than Expected in Acute Otitis Media in Young Finnish Children
Authors: Sillanpää Saara , Oikarinen Sami , Sipilä Markku , Kramna Lenka , Rautiainen Markus , Huhtala Heini , Aittoniemi Janne , Laranne Jussi , Hyöty Heikki , Cinek Ondrej
Published: July 2016

According to studies based on bacterial cultures of middle ear fluids,
Streptococcus pneumoniae
,
Haemophilus influenzae
, and
Moraxella catarrhalis
have been the most common pathogens in acute otitis media. However, bacterial culture can be affected by reduced viability or suboptimal growth of bacteria. PCR detects bacterial DNA from samples with greater sensitivity than culture. In the present study, we analyzed the middle ear pathogens with both conventional culture and semiquantitative real-time PCR in 90 middle ear fluid samples obtained from children aged 5 to 42 months during acute otitis media episodes. Samples were tested for the presence of
S. pneumoniae
,
H. influenzae
,
M. catarrhalis
,
Alloiococcus
otitidis
,
Staphylococcus aureus
, and
Pseudomonas aeruginosa
. One or more bacterial pathogens were detected in 42 (47%) samples with culture and in 69 (77%) samples with PCR. According to PCR analysis,
M. catarrhalis
results were positive in 42 (47%) samples,
H. influenzae
in 30 (33%),
S. pneumoniae
in 27 (30%),
A. otitidis
in 6 (6.7%),
S. aureus
in 5 (5.6%), and
P. aeruginosa
in 1 (1.1%). Multibacterial etiology was seen in 34 (38%) samples, and
M. catarrhalis
was detected in most (85%) of those cases. Fifteen signals for
M. catarrhalis
were strong, suggesting a highly probable etiological role of the pathogen. In conclusion, even though
M. catarrhalis
is often a part of mixed flora in acute otitis media, a considerable proportion of cases may be primarily attributable to this pathogen.
Biochemical and Structural Insights into the Preference of Nairoviral DeISGylases for Interferon-Stimulated Gene Product 15 Originating from Certain Species
Authors: Deaton M. K. , Dzimianski J. V. , Daczkowski C. M. , Whitney G. K. , Mank N. J. , Parham M. M. , Bergeron E. , Pegan S. D.
Published: July 2016

The regulation of the interferon type I (IFN-I) response has been shown to rely on posttranslational modification by ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15) to stabilize, or activate, a variety of IFN-I signaling and downstream effector proteins. Unlike Ub, which is almost perfectly conserved among eukaryotes, ISG15 is highly divergent, even among mammals. Since zoonotic viruses rely on viral proteins to recognize, or cleave, ISG15 conjugates in order to evade, or suppress, innate immunity, the impact of ISG15 biodiversity on deISGylating proteases of the ovarian tumor family (vOTU) from nairoviruses was evaluated. The enzymatic activities of vOTUs originating from the Crimean-Congo hemorrhagic fever virus, Erve virus, and Nairobi sheep disease virus were tested against ISG15s from humans, mice, shrews, sheep, bats, and camels, which are mammalian species known to be infected by nairoviruses. This along with investigation of binding by isothermal titration calorimetry illustrated significant differences in the abilities of nairovirus deISGylases to accommodate certain species of ISG15. To investigate the molecular underpinnings of species preferences of these vOTUs, a structure was determined to 2.5 Å for a complex of Erve virus vOTU protease and a mouse ISG15 domain. This structure revealed the molecular basis of Erve virus vOTU's preference for ISG15 over Ub and the first structural insight into a nonhuman ISG15. This structure also revealed key interactions, or lack thereof, surrounding three amino acids that may drive a viral deISgylase to prefer an ISG15 from one species over that of another.

IMPORTANCE
Viral ovarian tumor domain proteases (vOTUs) are one of the two principal classes of viral proteases observed to reverse posttranslational modification of host proteins by ubiquitin and interferon-stimulated gene product 15 (ISG15), subsequently facilitating downregulation of IFN-I signaling pathways. Unlike the case with ubiquitin, the amino acid sequences of ISG15s from various species are notably divergent. We illustrate that vOTUs have clear preferences for ISG15s from certain species. In addition, these observations are related to the molecular insights acquired via the first X-ray structure of the vOTU from the Erve nairovirus in complex with the first structurally resolved nonhuman ISG15. This information implicates certain amino acids that drive the preference of vOTUs for ISG15s from certain species.
High-Throughput Small Interfering RNA Screening Identifies Phosphatidylinositol 3-Kinase Class II Alpha as Important for Production of Human Cytomegalovirus Virions
Authors: Polachek William S. , Moshrif Hanan F. , Franti Michael , Coen Donald M. , Sreenu Vattipally B. , Strang Blair L.
Published: July 2016

High-throughput small interfering RNA (siRNA) screening is a useful methodology to identify cellular factors required for virus replication. Here we utilized a high-throughput siRNA screen based on detection of a viral antigen by microscopy to interrogate cellular protein kinases and phosphatases for their importance during human cytomegalovirus (HCMV) replication and identified the class II phosphatidylinositol 3-kinase class II alpha (PI3K-C2A) as being involved in HCMV replication. Confirming this observation, infected cells treated with either pooled or individual siRNAs targeting
PI3K-C2A
mRNA produced approximately 10-fold less infectious virus than the controls. Western blotting and quantitative PCR analysis of infected cells treated with siRNAs indicated that depletion of PI3K-C2A slightly reduced the accumulation of late but not immediate early or early viral antigens and had no appreciable effect on viral DNA synthesis. Analysis of siRNA-treated cells by electron microscopy and Western blotting indicated that PI3K-C2A was not required for the production of viral capsids but did lead to increased numbers of enveloped capsids in the cytoplasm that had undergone secondary envelopment and a reduction in the amount of viral particles exiting the cell. Therefore, PI3K-C2A is a factor important for HCMV replication and has a role in the production of HCMV virions.

IMPORTANCE
There is limited information about the cellular factors required for human cytomegalovirus (HCMV) replication. Therefore, to identify proteins involved in HCMV replication, we developed a methodology to conduct a high-throughput siRNA screen of HCMV-infected cells. From our screening data, we focused our studies on the top hit from our screen, the lipid kinase phosphatidylinositol 3-kinase class II alpha (PI3K-C2A), as its role in HCMV replication was unknown. Interestingly, we found that PI3K-C2A is important for the production of HCMV virions and is involved in virion production after secondary envelopment of viral capsids, the encapsidation of HCMV capsids by a lipid bilayer that occurs before virions exit the cell.
Complexities in Ferret Influenza Virus Pathogenesis and Transmission Models
Authors: Belser Jessica A. , Eckert Alissa M. , Tumpey Terrence M. , Maines Taronna R.
Published: July 2016

Ferrets are widely employed to study the pathogenicity, transmissibility, and tropism of influenza viruses. However, inherent variations in inoculation methods, sampling schemes, and experimental designs are often overlooked when contextualizing or aggregating data between laboratories, leading to potential confusion or misinterpretation of results. Here, we provide a comprehensive overview of parameters to consider when planning an experiment using ferrets, collecting data from the experiment, and placing results in context with previously performed studies. This review offers information that is of particular importance for researchers in the field who rely on ferret data but do not perform the experiments themselves. Furthermore, this review highlights the breadth of experimental designs and techniques currently available to study influenza viruses in this model, underscoring the wide heterogeneity of protocols currently used for ferret studies while demonstrating the wealth of information which can benefit risk assessments of emerging influenza viruses.
Acute Whiplash Injury Study (AWIS): a protocol for a cluster randomised pilot and feasibility trial of an Active Behavioural Physiotherapy Intervention in an insurance private setting
Authors: Wiangkham Taweewat , Duda Joan , Haque M Sayeed , Price Jonathan , Rushton Alison
Published: July 2016

Introduction

Whiplash-associated disorder (WAD) causes substantial social and economic burden internationally. Up to 60% of patients with WAD progress to chronicity. Research therefore needs to focus on effective management in the acute stage to prevent the development of chronicity. Approximately 93% of patients are classified as WADII (neck complaint and musculoskeletal sign(s)), and in the UK, most are managed in the private sector. In our recent systematic review, a combination of active and behavioural physiotherapy was identified as potentially effective in the acute stage. An Active Behavioural Physiotherapy Intervention (ABPI) was developed through combining empirical (modified Delphi study) and theoretical (social cognitive theory focusing on self-efficacy) evidence. This pilot and feasibility trial has been designed to inform the design of an adequately powered definitive randomised controlled trial.

Methods and analysis

Two parallel phases. (1) An external pilot and feasibility cluster randomised double-blind (assessor and participants), parallel two-arm (ABPI vs standard physiotherapy) clinical trial to evaluate procedures and feasibility. Six UK private physiotherapy clinics will be recruited and cluster randomised by a computer-generated randomisation sequence. Sixty participants (30 each arm) will be assessed at recruitment (baseline) and at 3 months postbaseline. The planned primary outcome measure is the neck disability index. (2) An embedded exploratory qualitative study using semistructured indepth interviews (n=3–4 physiotherapists) and a focus group (n=6–8 patients) and entailing the recruitment of purposive samples will explore perceptions of the ABPI. Quantitative data will be analysed descriptively. Qualitative data will be coded and analysed deductively (identify themes) and inductively (identify additional themes).

Ethics and dissemination

This trial is approved by the University of Birmingham Ethics Committee (ERN_15-0542).

Trial registration number

ISRCTN84528320.
A surgeon's guide to anticoagulant and antiplatelet medications part one: warfarin and new direct oral anticoagulant medications
Authors: McBeth Paul B , Weinberg Jordan A , Sarani Babak , Yeung Louise Y Y , May Addison K
Published: July 2016

An increasing number of potent antiplatelet and anticoagulant medications are being used for the long-term management of cardiac, cerebrovascular, and peripheral vascular conditions. Management of these medications in the perioperative and peri-injury settings can be challenging for surgeons, mandating an understanding of these agents and the risks and benefits of various management strategies. In this two-part review, agents commonly encounter by surgeons in the perioperative and peri-injury settings are discussed and management strategies for patients on long-term antiplatelet and anticoagulant therapy reviewed. In part I, we review warfarin and the new direct oral anticoagulants. In part II, we review antiplatelet agents and assessment of platelet function and the perioperative management of long-term anticoagulant and antiplatelet therapy.
Vitamin D3 protects against prednisolone-induced liver injury associated with the impairment of the hepatic NF-κB/iNOS/NO pathway
Authors: Lisakovska Olha , Shymanskyy Ihor , Mazanova Anna , Khomenko Anna , Veliky Mykola
Published: July 2016

The study was carried out to define whether prednisolone-induced damage to hepatic cells is accompanied by excessive nitric oxide (NO) levels associated with nuclear factor kappa B (NF-κB)/inducible NO synthase (iNOS) activation and evaluate the efficacy of the treatment with vitamin D3. Histopathological examination, activities of liver transaminases (alanine aminotransferase and aspartate aminotransferase), and cell death assays consistently showed that prednisolone (5 mg/kg body weight, 30 days) induces chronic liver injury in female Wistar rats. Specifically, increased hepatocellular necrosis and caspase-3-dependent apoptosis were observed. Prednisolone enhanced iNOS protein expression, NO generation, and tyrosine nitration in liver cells. Despite unchanged hepatic level of the NF-κB/p65 protein, prednisolone increased inhibitory κB-α (IκB-α) degradation, nuclear translocation, and phosphorylation of NF-κB/p65 at Ser311, indicating that NF-κB activation can be involved in the induction of iNOS/NO. All changes were associated with a 2.9-fold decrease in the serum content of 25-hydroxyvitamin D3 and significant reduction of hepatic vitamin D3 receptor (VDR) expression that points reliably to vitamin D3 deficiency and failures in VDR signaling. Vitamin D3 co-administration (100 IU/rat, 30 days) prevented glucocorticoid-evoked abnormalities in hepatic tissue. In conclusion, prednisolone-induced liver disturbances were associated with the impairment of NF-κB/iNOS/NO responses that can be ameliorated by vitamin D3 treatment through VDR-mediated mechanisms.
Prediction of water content and normalized evaporation from oil sands soft tailings surface using hyperspectral observations
Authors: Entezari Iman , Rivard Benoit , Lipsett Michael G. , Wilson G. Ward
Published: July 2016

The paper addresses the challenge of measuring water content and evaporative fluxes from oil sands soft tailings surfaces using hyperspectral observations. Hyperspectral time-series laboratory observations were collected from four different mature fine tailings (MFT) samples displaying variations in swelling potential and bitumen concentration. The samples were allowed to evaporate from an initial state of water saturation to an air-dried state. From these data, several spectral features were evaluated to predict water content and normalized evaporation rate from the optically sensed portion of the tailings surface (less than a few hundred micrometres). For the samples tested, the best estimate of moisture content was achieved using the normalized soil moisture index (NSMI) index (coefficient of determination R2 = 0.97). The absolute reflectance at 1920 nm was found to be the best spectral estimator of normalized evaporation (R2 = 0.97), with the NSMI index also being valuable (R2 = 0.95). In both instances, the NSMI index may be of value for estimations attempted in the field. Remote estimation of moisture content and evaporation could help tailings managers assess the drying process to determine when the deposit has stopped drying at the surface and decide when the next lift should be deposited. In future efforts, the models obtained from this laboratory investigation will be assessed for their applicability in field settings and validated using concurrent sampling.
A membrane-spanning macrocyclic bolaamphiphile lipid mimic of archaeal lipids
Authors: Mitchell Gavin M. , Hesketh Amelia , Lombardi Christie , Ho Cally , Fyles Thomas M.
Published: July 2016

The synthesis of a 72-membered macrocyclic tetraester bolaamphiphile is accomplished in six chemical steps from commercially available starting materials using copper-accelerated azide–alkyne coupling to close the macrocycle in high yield. Related diester amphiphiles and an acyclic tetraester bolaamphiphile were also prepared. The set of lipids bearing nitrophenyl phosphate head groups were incorporated into phospholipid vesicles but failed to undergo phosphate hydrolysis in basic conditions, undergoing efficient elimination in competition. The same lipid cores bearing phosphate-linked nitrobenzoxadiazole (NBD) head groups also incorporated into phospholipid vesicles and the NBD fluorescence was quenched with cobalt ions. The proportion of membrane-spanning bolaamphiphiles was determined from the ratio of cobalt quenching in the presence and in the absence of a detergent. The macrocyclic bolaamphiphile is incorporated into phospholipid vesicles such that 48 ± 4% of the NBD head groups are in the outer leaflet, consistent with a membrane-spanning orientation. The acyclic bolaamphiphile is incorporated with 75 ± 3% of the NBD head groups accessible to quencher in the absence of a detergent suggesting U-shaped incorporation in the outer leaflet of the bilayer membrane. In ring size and spanning ability, the macrocyclic bolaamphiphile mimics naturally occurring macrocyclic archaeal lipids.
Bonding analysis of ylidone complexes EL2 (E = C–Pb) with phosphine and carbene ligands L
Authors: Andrada Diego M. , Holzmann Nicole , Frenking Gernot
Published: July 2016

Quantum chemical calculations using DFT and ab initio methods have been carried out of the compounds EL2 with atoms E = C–Pb and the ligands L = PPh3, N-heterocyclic carbene (NHC), bicyclic NHC, and cyclic alkyl-amino carbene (cAAC). The equilibrium structures are reported and the bonding situation was analyzed with a variety of charge- and energy decomposition methods. Some of the molecules are experimentally known, but most molecules have not yet been prepared. The bonding analysis suggests that all but one molecule should be considered as ylidones that possess dative bonds L→E←L. The sole exception is C(cAAC)2, which has a linear structure and classical double bonds (cAAC)=C=(cAAC). The ylidones EL2 have two lone-pair orbitals at atom E with σ and π symmetry. The π lone pair is somewhat delocalized due to L←E→L π-backdonation. The contribution of L←E→L π-backdonation relative to L→E←L σ-donation increases for the heavier elements. The compounds have rather large first and second proton affinities, which is a characteristic feature of ylidones. They are thus double Lewis bases that could be utilized in chemical reactions.
The Hamiltonian structure and quasi-periodic solutions for the generalized associated Camassa–Holm equation
Authors: Luo Lin , Zhao Peng
Published: July 2016

In this paper, we study a integrable generalization of the associated Camassa–Holm equation. This equation is shown to be completely integrable and possesses bi-Hamiltonian structure. The bilinear equation and its solition solution are presented through the Bell polynomial technique. Meanwhile, the quasi-periodic wave solution is obtained by Riemann theta-function, and we show the asymptotic properties of the quasi-periodic wave solutions.
Hybrid Finite Element Method and Variational Theory of Complex Rays for Helmholtz Problems
Authors: Li Hao , Ladevèze Pierre , Riou Hervé
Published: July 2016

In this paper, we consider the Weak Trefftz Discontinuous Galerkin (WTDG) method, which enables one to use at the same time the Finite Element Method (FEM) or Variational Theory of Complex Rays (VTCR) discretizations (polynoms and waves), for vibration problems. It has already been developed such that the FEM and the VTCR can be used in different adjacent subdomains in the same problem. Here, it is revisited and extended in order to allow one to use the two discretizations in the same subdomain, at the same time. Numerical examples illustrate the performances of such an approach.