bluuebunny/crossref_metadata_2025 huggingface dataset:
Provocative testing of the esophagus and its future
Authors: Farmer Adam D. , Franchina Marianna , Gregersen Hans , Penagini Roberto , Shaker Anisa , Soffer Edy
Published: June 2016

Standard tests in clinical practice commonly fail to demonstrate a clear esophageal etiology for symptoms such as heartburn, dysphagia, or chest pain. Over the years, various provocative measures have been developed to provide a better understanding of the origins of such symptoms. Some measures, such as esophageal acid infusion or changing bolus consistency, can be easily incorporated into clinical practice. Others, such as multimodal stimulation systems, are more technically demanding. They have contributed to a better understanding of esophageal physiology in health and disease. Their role in clinical decision making is still evolving. This focused review provides a summary of the esophageal nociceptive pathways and how provocative testing can be used to interrogate their integrity.
Surveillance biopsies after paediatric kidney transplantation: A review
Authors: Rose Edward M. , Kennedy Sean E. , Mackie Fiona E.
Published: June 2016

Kidney transplantation is the most effective means of treating children with end‐stage kidney disease, and yet, there continues to be a limited “life span” of transplanted kidneys in paediatric recipients. Early graft monitoring, using the surveillance biopsy, has the potential to extend renal allograft survival in paediatric recipients. The surveillance biopsy provides important and timely information about acute and chronic graft pathology, particularly SCR and calcineurin inhibitor‐induced nephrotoxicity, which can subsequently guide management decisions and improve long‐term graft survival. The ostensible value of the surveillance biopsy is furthered by the limitations of conventional renal functional studies. However, there is still much debate surrounding the surveillance biopsy in paediatric recipients, particularly in regard to its overall utility, safety and timing. This review discusses the current literature regarding the utility, safety, and potential predictive value of surveillance biopsies for guiding post‐transplant management in paediatric renal allograft recipients, as well as the viability of other potentially newer non‐invasive strategies for renal allograft monitoring.
Thomas F. Mayer (1951–2014) and the Roman Inquisition: A Review Essay
Authors: Pattenden Miles
Published: June 2016

The Roman Inquisition: A Papal Bureaucracy and its Laws in the Age of Galileo, Thomas F. Mayer, University of Pennsylvania Press, 2013 (ISBN 978‐0‐8122‐4473‐1), 385 pp., hb £52

The Roman Inquisition on the Stage of Italy, c. 1590‐1640, Thomas F. Mayer, University of Pennsylvania Press, 2014 (ISBN 978‐0‐8122‐4573‐8), 361 pp., hb £52

The Roman Inquisition: Trying Galileo, Thomas F. Mayer, University of Pennsylvania Press, 2015 (ISBN: 978‐0‐8122‐4655‐1), 368 pp., hb £58.50

This review article appraises the recent trilogy of books on the Roman Inquisition written by the late Thomas F. Mayer. It explains the context in which Mayer came to write these works, the research questions which guided him and the nature of the outputs he delivered before his untimely death. Mayer's principal theme of the importance of process in guiding inquisitors' actions and activities, is traced through his three volumes: the first a general reconstruction of how the Holy Office operated, the second an application of his insights to specific cases of importance throughout late sixteenth‐ and early seventeenth‐century Italy, the third on the Galileo trial itself. Other scholars have received Mayer's work in a number of different ways, some favorable, others less so. Here, this essay summarizes parameters of the debate which Mayer catalyzed, in particular between scholars of Galileo and of the Inquisition; it also explains the further questions that has risen. Finally, it assesses how, as colleagues, we might extend Mayer's inquires and evaluates the wider impact his work deserves to have in historical studies and, indeed, in contemporary academic discourse. Mayer's insistance on the need to understand the methods and processes of censorship seems especially timely given the general assault on free speech which we currently face on many university campuses. On that basis, his scholarship should continue to resonate with all of us, perhaps in some uncomfortable ways.
ICT and Exporting: The Effects of Broadband on the Extensive Margin of Business Service Exports
Authors: Kneller Richard , Timmis Jonathan
Published: June 2016

Over the last three decades the global economy has witnessed rapid growth of international trade in services. This has been particularly true of service‐intensive countries such as the UK. Developments in information and communication technologies are an obvious explanation for this. We provide empirical evidence for the effects of broadband use on the firm‐extensive margin of UK service exports. To deal with the issue of causality we build a novel instrument that exploits exogenous variation in access to broadband technologies owing to the historic telephone network. We find evidence for a causal effect from the Internet on trade in business services, but no evidence for an effect on trade in services more generally.
The HOPS/Class C Vps Complex Tethers High‐Curvature Membranes via a Direct Protein–Membrane Interaction
Authors: Ho Ruoya , Stroupe Christopher
Published: June 2016

Membrane tethering is a physical association of two membranes before their fusion. Many membrane tethering factors have been identified, but the interactions that mediate inter‐membrane associations remain largely a matter of conjecture. Previously, we reported that the homotypic fusion and protein sorting/Class C vacuolar protein sorting (HOPS/Class C Vps) complex, which has two binding sites for the yeast vacuolar Rab GTPase Ypt7p, can tether two low‐curvature liposomes when both membranes bear Ypt7p. Here, we show that HOPS tethers highly curved liposomes to Ypt7p‐bearing low‐curvature liposomes even when the high‐curvature liposomes are protein‐free. Phosphorylation of the curvature‐sensing amphipathic lipid‐packing sensor (ALPS) motif from the Vps41p HOPS subunit abrogates tethering of high‐curvature liposomes. A HOPS complex without its Vps39p subunit, which contains one of the Ypt7p binding sites in HOPS, lacks tethering activity, though it binds high‐curvature liposomes and Ypt7p‐bearing low‐curvature liposomes. Thus, HOPS tethers highly curved membranes via a direct protein–membrane interaction. Such high‐curvature membranes are found at the sites of vacuole tethering and fusion. There, vacuole membranes bend sharply, generating large areas of vacuole‐vacuole contact. We propose that HOPS localizes via the Vps41p ALPS motif to these high‐curvature regions. There, HOPS binds via Vps39p to Ypt7p in an apposed vacuole membrane.
Thermal-Acoustic Wave Generation and Propagation Using Suspended Carbon Nanotube Thin Film in Fluidic Environments
Authors: Jia P. , Lim C. W.
Published: June 2016

A simplified analytical pressure solution for thermal-acoustic wave response generated by using suspended multiwall carbon nanotube (MWCNT) thin film in different fluidic environments is developed. The solution consists of two independent portions: the near-field solution and the far-field solution. The electricity power input is a key element to control the thermal-acoustic wave pressure level. The dependence of the solution on axial distance from the source origin is investigated for different fluidic environments. Comparison between analytical solutions and published experimental results is presented, and excellent agreement is reported. A number of numerical examples for different parameters are studied for various liquids and gases including air, argon, water, and ethanol. Accurate analytical approximations for the thermal-acoustic wave response, and amplitude functions for different temperatures in fluids of varying densities are proposed here. The relation of Rayleigh distance and critical frequency has been determined in order to enhance and optimize the thermal-acoustic effect and wave behavior in fluids. These two parameters can be modified by suitable choices of the size of thin film, the properties of surrounding media, etc. The thermal-acoustic generation properties including the electric power input, frequency, and the suspended MWCNT thin film size significantly affect the acoustic pressure performance. It is concluded here that this extended analytical work not only agrees better with experiment but also offers more convincing analytical prediction for the generation and propagation of thermal-acoustic wave in different fluids.
Experimental and Numerical Validation of Digital, Electromechanical, Parametrically Excited Amplifiers
Authors: Dolev Amit , Bucher Izhak
Published: June 2016

A parametric amplifier having a tunable, dual-frequency pumping signal and a controlled cubic stiffness term is realized and investigated experimentally. This device can be tuned to amplify a desired, single frequency weak signal, well below resonance. The transition between a previously described theoretical model and a working prototype requires an additional effort in several areas: modeling, design, calibration, identification, verification, and adjustment of the theoretical model. The present paper describes these necessary steps and analyzes the results. Tunability is achieved here by adding a digitally controlled feedback, driving a linear mechanical oscillator with an electromechanical actuator. The main advantage of the present approach stems from the separation of the controlled parametric and nonlinear feedback terms which are linked to the resonating element. This separation allows for the realization of feedback in an electronic form where a digital implementation adds further advantages as the feedback coefficients can be tuned in situ. This arrangement benefits from the mechanical resonance of a structure and from the ability to set the parametric excitation such that it accommodates sinusoidal input signals over a wide range of frequencies. The importance of an in situ identification phase is made clear in this work, as the precise setting of model and feedback parameters was shown to be crucial for successful application of the amplifier. A detailed model-identification effort is described throughout this paper. It has been shown through identification that the approach is robust despite some modeling uncertainties and imperfections.
Fatigue Tests on Aluminum Specimens Subjected to Constant and Random Amplitude Loadings
Authors: Rahimi Abkenar Morteza , Kihl David P. , Manzari Majid T.
Published: June 2016

Increasing interest in using aluminum as the structural component of light-weight structures, mechanical devices, and ships necessitates further investigations on fatigue life of aluminum alloys. The investigation reported here focuses on characterizing the performance of cruciform-shaped weldments made of 5083 aluminum alloys in thickness of 9.53 mm (3/8 in.) under constant, random, and bilevel amplitude loadings. The results are presented as S/N curves that show cyclic stress amplitude versus the number of cycles to failure. Statistical procedures show good agreements between test results and predicted fatigue life of aluminum weldments. Moreover, the results are compared to the results obtained from previous experiments on aluminum specimens with thicknesses of 12.7 mm (1/2 in.) and 6.35 mm (1/4 in.).
Numerical Computation of a Fractional Model of Differential-Difference Equation
Authors: Kumar Devendra , Singh Jagdev , Baleanu Dumitru
Published: June 2016

In the present article, we apply a numerical scheme, namely, homotopy analysis Sumudu transform algorithm, to derive the analytical and numerical solutions of a nonlinear fractional differential-difference problem occurring in nanohydrodynamics, heat conduction in nanoscale, and electronic current that flows through carbon nanotubes. The homotopy analysis Sumudu transform method (HASTM) is an inventive coupling of Sumudu transform algorithm and homotopy analysis technique that makes the calculation very easy. The fractional model is also handled with the aid of Adomian decomposition method (ADM). The numerical results derived with the help of HASTM and ADM are approximately same, so this scheme may be considered an alternative and well-organized technique for attaining analytical and numerical solutions of fractional model of discontinued problems. The analytical and numerical results derived by the application of the proposed technique reveal that the scheme is very effective, accurate, flexible, easy to apply, and computationally very appropriate for such type of fractional problems arising in physics, chemistry, biology, engineering, finance, etc.
Temperature-Controlled Forming of 7075-T6 Aluminum Using Linearly Decaying Direct Electric Current
Authors: Ruszkiewicz Brandt J. , Mears Laine
Published: June 2016

7075-T6 aluminum suffers from limited elongation during tensile forming; electrically assisted forming (EAF), which uses direct current to improve formability, is a viable candidate process to improve this effect. In past electrical tension testing by various authors, two types of waveforms have been examined: continuous current and square waveforms. For tension, it was shown that the applying current using square waveforms was able to extend formability beyond what continuous current could do, due to reducing the overheating in the necking region. The goal of this paper is to model the temperature and flow stress effects of saw tooth waves by modifying an existing square wave temperature prediction model and combining it with a theoretical flow stress model. Nondecaying and linearly globally decaying saw tooth waveforms are used in an attempt to control the temperature of the necking zone to allow for increased strain at fracture. Comparisons between saw tooth waveforms and square waveforms are exhibited, and it is found that the saw tooth waveforms are inferior to square waves for increasing strain at fracture for 7075-T6.
Direct Printing and Electrical Characterization of Conductive Micro-Silver Tracks by Alternating Current-Pulse Modulated Electrohydrodynamic Jet Printing
Authors: Qin Hantang , Wei Chuang , Dong Jingyan , Lee Yuan-Shin
Published: June 2016

In this paper, a rapid prototyping method for fabrication of highly conductive micropatterns on insulating substrates was developed and evaluated. Sub-20 μm microstructures were printed on flexible insulating substrates using alternating current (AC) modulated electrohydrodynamic jet (e-jet) printing. The presented technique resolved the challenge of current rapid prototyping methods in terms of limited resolution and conductivity for microelectronic components for flexible electronics. Significant variables of fabrication process, including voltage, plotting speeds, curing temperature, and multilayer effect, were investigated to achieve reliable printing of silver tracks. Sub-20 μm silver tracks were successfully fabricated with resistivity about three times than bulk silver on flexible substrates, which indicates the potential applications of electrohydrodynamic printing in flexible electronics and medical applications, such as lab-on-chip systems.
Chip Formation and Force Responses in Linear Rock Cutting: An Experimental Study
Authors: Che Demeng , Zhang Weizhao , Ehmann Kornel
Published: June 2016

Polycrystalline diamond compact (PDC) cutters, as a major cutting tool, have been widely applied in oil and gas drilling processes. The understanding of the complex interactions at the rock and cutter interfaces is essential for the advancement of future drilling technologies; yet, these interactions are still not fully understood. Linear cutting of rock, among all the testing methods, avoids the geometric and process complexities and offers the most straightforward way to reveal the intrinsic mechanisms of rock cutting. Therefore, this paper presents an experimental study of the cutter’s cutting performance and the rock’s failure behaviors on a newly developed linear rock cutting facility. A series of rock cutting tests were designed and performed. The acquired experimental data was analyzed to investigate the influences of process parameters and the rock’s mechanical properties on chip formation and force responses.
Application of nitrogen plasma immersion ion implantation to titanium nasal implants with nanonetwork surface structure
Authors: Sun Ying-Sui , Zhang Lan , Zhu Hongqin , Yang Wei-En , Lan Ming-Ying , Lee Sheng-Wei , Huang Her-Hsiung
Published: June 2016

In nasal reconstruction, the response of cells to titanium (Ti) implants is mainly determined by surface features of the implant. In a pilot study, the authors applied electrochemical anodization to Ti surfaces in an alkaline solution to create a network of nanoscale surface structures. This nanonetwork was intended to enhance the responses of primary human nasal epithelial cell (HNEpC) to the Ti surface. In this study, the authors then treated the anodized, nanonetwork-structured Ti surface using nitrogen plasma immersion ion implantation (NPIII) in order to further improve the HNEpC response to the Ti surface. Subsequently, surface characterization was performed to elucidate morphology, roughness, wettability, and chemistry of specimens. Cytotoxicity, blood, and HNEpC responses were also evaluated. Our results demonstrate that NPIII treatment led to the formation of a noncytotoxic TiN-containing thin film (thickness <100 nm) on the electrochemically anodized Ti surface with a nanonetwork-structure. NPIII treatment was shown to improve blood clotting and the adhesion of platelets to the anodized Ti surface as well as the adhesion and proliferation of hNEpC. This research spreads our understanding of the fact that a TiN-containing thin film, produced using NPIII treatment, could be used to improve blood and HNEpC responses to anodized, nanonetwork-structured Ti surfaces in nasal implant applications.
Lipoprotein interactions with a polyurethane and a polyethylene oxide-modified polyurethane at the plasma–material interface
Authors: Cornelius Rena M. , Macri Joseph , Cornelius Katherine M. , Brash John L.
Published: June 2016

Lipoproteins [high density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL)] are present in blood in relatively high concentrations, and, given their importance in cardiovascular disease, the interactions of these species with blood contacting biomaterials and their possible role in thrombogenesis is of interest. In the present communication, quantitative data on the adsorption of apolipoprotein AI, apolipoprotein AII (the main protein components of HDL), and apolipoprotein B (the main protein component of LDL and VLDL), as well as the lipoproteins themselves from plasma to a biomedical grade polyurethane (PU) with and without a copolymer additive that contains polyethylene oxide (PEO) segments, were investigated. Adsorption from some binary solutions was also studied. Significant quantities of the apolipoproteins were found to adsorb from plasma to the PU, while adsorption to the PEO material was more than 90% lower, demonstrating strong protein resistance of the latter material. In contrast, significant quantities of the lipoproteins were found to adsorb to the PEO as well as to the PU material. From these and previously published results, it is concluded that the protein layer formed on the PU surface from plasma (and by extension from blood) contains apolipoproteins and lipoproteins in addition to other plasma proteins; the layer formed on the PEO surface, however, appears to contain minimal quantities of plasma proteins (including free apolipoproteins) but significant quantities of lipoproteins.
Effects of thickness and V/III ratio of low temperature capping layer growth to the optical properties of InAs quantum dots
Authors: Weir Nicholas , Yao Ruizhe , Lee Chi-Sen , Guo Wei
Published: June 2016

To achieve increased device performance, the authors systematically explored the dependence of the optical characteristics of InAs quantum dot (QD) ensembles grown via molecular beam epitaxy with different V/III ratios and thicknesses of the low temperature GaAs capping layers. In addition, the paper discusses the mechanism behind the dependence. Experiments showed the QD optical properties were significantly dependent on the GaAs capping layer V/III ratio and the initial GaAs capping layer thickness. An optimized V/III ratio and GaAs capping thickness is reported.
Dynamic Characteristic Analysis of Spinal Motor Control Between 11- and 15-Year-Old Children
Authors: Chow Daniel H.K. , Lau Newman M.L.
Published: June 2016

Spinal motor control can provide substantial insight for the causes of spinal musculoskeletal disorders. Its dynamic characteristics however, have not been fully investigated. The objective of this study is to explore the dynamic characteristics of spinal motor control via the fractional Brownian motion mathematical technique. Spinal curvatures and repositioning errors of different spinal regions in 64 children age 11- or 15-years old during upright stance were measured and compared for the effects of age and gender. With the application of the fractional Brownian motion analytical technique to the changes of spinal curvatures, distinct persistent movement behaviors could be determined, which could be interpreted physiologically as open-loop behaviors. Moreover, it was found that the spinal motor control of 15-year-old children was better than that of 11-year-old children with smaller repositioning error and less curvature variability as well as shorter response time and smaller curvature deformation.
LIGO detects another black hole crash
Authors: Cho Adrian
Published: June 2016

Second gravitational-wave detection augurs bumper crop of sightings.
Experts fear Zika's effects may be even worse than thought
Authors: Vogel Gretchen
Published: June 2016

Doctors and researchers are scrambling to define “Zika congenital syndrome.”
Expanding our mental maps
Authors: Underwood Emily
Published: June 2016

Grid cells that represent physical space in the human brain may also organize more conceptual forms of knowledge.
Tumors' do-it-yourself blood vessels
Authors: Leslie Mitch
Published: June 2016

The unusual supply lines built by cancer cells may explain why some treatments fail and offer new targets for drugs.
Ancient DNA divide
Authors: Gibbons Ann
Published: June 2016

While Europe forges ahead on a transformative technique, U.S. researchers struggle for funding.
Webinar | Analysis of extracellular vesicles including exosomes by imaging flow cytometry
Authors: Görgens André
Published: June 2016

Extracellular vesicles (EVs) such as exosomes (70 nm – 160 nm in diameter) and microvesicles (100 nm – 1,000 nm diameter) can be harvested from cell-culture supernatants and from all bodily fluids. Current standard techniques to visualize, quantify, and characterize EVs are electron microscopy, nanoparticle tracking analyses, and dynamic light scattering. To further characterize and discriminate EVs, more exact high-throughput technologies to analyze their surface are highly desired. Although conventional flow cytometry is limited to measuring particles down to approximately 300 nm – 500 nm, a relatively new flow-cytometric method—called "imaging flow cytometry"—allows for the analysis of EVs smaller than 300 nm. This webinar will introduce viewers to the challenges, limitations, and pitfalls of flow cytometry-based EV analysis, and to the imaging flow cytometry methodology. Also covered will be techniques for analyzing exosomes, microvesicles, and apoptotic bodies in unprocessed samples, how imaging flow cytometry can be used to evaluate or reevaluate EV isolation techniques, and the advantages and disadvantages of using this method.

View the Webinar
T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4
+
T cells
Authors: Arbore Giuseppina , West Erin E. , Spolski Rosanne , Robertson Avril A. B. , Klos Andreas , Rheinheimer Claudia , Dutow Pavel , Woodruff Trent M. , Yu Zu Xi , O’Neill Luke A. , Coll Rebecca C. , Sher Alan , Leonard Warren J. , Köhl Jörg , Monk Pete , Cooper Matthew A. , Arno Matthew , Afzali Behdad , Lachmann Helen J. , Cope Andrew P. , Mayer-Barber Katrin D. , Kemper Claudia
Published: June 2016

Innate immune crosstalk in T cells

The classical view of immune activation is that innate immune cells, such as macrophages and dendritic cells, recognize invading microbes and then alert adaptive immune cells, such as T cells, to respond. Arbore
et al.
now show that innate and adaptive immunity converge in human and mouse T cells. Activated T cells express components of the complement cascade, which in turn leads to the assembly of NLRP3 inflammasomes—both critical components of innate immunity that help hosts detect and eliminate microbes. In T cells, complement and inflammasomes work together to push T cells to differentiate into a specialized subset of T cells important for eliminating intracellular bacteria.

Science
, this issue p.
10.1126/science.aad1210
Organizing conceptual knowledge in humans with a gridlike code
Authors: Constantinescu Alexandra O. , O’Reilly Jill X. , Behrens Timothy E. J.
Published: June 2016

Coding abstract concepts in the brain

Grid cells are thought to provide the neuronal code that underlies spatial knowledge in the brain. Grid cells have mostly been studied in the context of path integration. However, recent theoretical studies have suggested that they may have a broader role in the organization of general knowledge. Constantinescu
et al.
investigated whether the neural representation of concepts follows a structure similar to the representation of space in the entorhinal cortex. Several brain regions, including the entorhinal cortex and the ventromedial prefrontal cortex, showed gridlike neural representation of conceptual space.

Science
, this issue p.
1464
Persistent pollutants, persistent threats
Authors: Jepson Paul D. , Law Robin J.
Published: June 2016

Polychlorinated biphenyls remain a major threat to marine apex predators such as orcas
The resurgence of NAD
+
Authors: Guarente Leonard
Published: June 2016

Restoring a mitochondrial metabolite slows stem cell loss and aging
Phenotypic H-Antigen Typing by Mass Spectrometry Combined with Genetic Typing of H Antigens, O Antigens, and Toxins by Whole-Genome Sequencing Enhances Identification of Escherichia coli Isolates
Authors: Cheng Keding , Chui Huixia , Domish Larissa , Sloan Angela , Hernandez Drexler , McCorrister Stuart , Robinson Alyssia , Walker Matthew , Peterson Lorea A. M. , Majcher Miles , Ratnam Sam , Haldane David J. M. , Bekal Sadjia , Wylie John , Chui Linda , Tyler Shaun , Xu Bianli , Reimer Aleisha , Nadon Celine , Knox J. David , Wang Gehua
Published: June 2016

Mass spectrometry-based phenotypic H-antigen typing (MS-H) combined with whole-genome-sequencing-based genetic identification of H antigens, O antigens, and toxins (WGS-HOT) was used to type 60 clinicalEscherichia coliisolates, 43 of which were previously identified as nonmotile, H type undetermined, or O rough by serotyping or having shown discordant MS-H and serotyping results. Whole-genome sequencing confirmed that MS-H was able to provide more accurate data regarding H antigen expression than serotyping. Further, enhanced and more confident O antigen identification resulted from gene cluster based typing in combination with conventional typing based on the gene pair comprisingwzxandwzyand that comprisingwzmandwzt. The O antigen was identified in 94.6% of the isolates when the two genetic O typing approaches (gene pair and gene cluster) were used in conjunction, in comparison to 78.6% when the gene pair database was used alone. In addition, 98.2% of the isolates showed the existence of genes for various toxins and/or virulence factors, among which verotoxins (Shiga toxin 1 and/or Shiga toxin 2) were 100% concordant with conventional PCR based testing results. With more applications of mass spectrometry and whole-genome sequencing in clinical microbiology laboratories, this combined phenotypic and genetic typing platform (MS-H plus WGS-HOT) should be ideal for pathogenicE. colityping.
The BD Onclarity HPV Assay on Samples Collected in SurePath Medium Meets the International Guidelines for Human Papillomavirus Test Requirements for Cervical Screening
Authors: Ejegod Ditte , Bottari Fabio , Pedersen Helle , Sandri Maria Teresa , Bonde Jesper
Published: June 2016

This study describes a validation of the BD Onclarity HPV (Onclarity) assay using the international guidelines for HPV test requirements for cervical cancer screening of women 30 years old and older using Danish SurePath screening samples. The clinical specificity (0.90, 95% confidence interval [CI] = 0.88 to 0.91) and sensitivity (0.97, 95% CI = 0.87 to 1.0) of the Onclarity assay were shown to be not inferior to the reference assay (specificity, 0.90 [95% CI = 0.88 to 0.92]; sensitivity, 0.98 [95% CI = 0.91 to 1.0]). The intralaboratory reproducibility of Onclarity was 97%, with a lower confidence bound of 96% (kappa value, 0.93). The interlaboratory agreement was 97%, with a lower confidence bound of 95% (kappa value, 0.92). The BD Onclarity HPV assay fulfills all the international guidelines for a new HPV test to be used in primarily screening. This is the first clinical validation of a new HPV assay using SurePath screening samples, and thus the Onclarity HPV assay is the first HPV assay to hold an international validation for both SurePath and ThinPrep.
Mycoplasma genitalium Prevalence, Coinfection, and Macrolide Antibiotic Resistance Frequency in a Multicenter Clinical Study Cohort in the United States
Authors: Getman Damon , Jiang Alice , O'Donnell Meghan , Cohen Seth
Published: June 2016

The prevalence rates of
Mycoplasma genitalium
infections and coinfections with other sexually transmitted organisms and the frequency of a macrolide antibiotic resistance phenotype were determined in urogenital specimens collected from female and male subjects enrolled in a multicenter clinical study in the United States. Specimens from 946 subjects seeking care from seven geographically diverse clinical sites were tested for
M. genitalium
and for
Chlamydia trachomatis
,
Neisseria gonorrhoeae
, and
Trichomonas vaginalis
. Sequencing was used to assess macrolide antibiotic resistance among
M. genitalium
-positive subjects.
M. genitalium
prevalence rates were 16.1% for females and 17.2% for males. Significant risk factors for
M. genitalium
infections were black race, younger age, non-Hispanic ethnicity, and female symptomatic status. Female
M. genitalium
infections were significantly more prevalent than
C. trachomatis
and
N. gonorrhoeae
infections, while the
M. genitalium
infection rate in males was significantly higher than the
N. gonorrhoeae
and
T. vaginalis
infection rates. The macrolide-resistant phenotype was found in 50.8% of females and 42% of males. These results show a high prevalence of
M. genitalium
single infections, a lower prevalence of coinfections with other sexually transmitted organisms, and high rates of macrolide antibiotic resistance in a diverse sample of subjects seeking care across a wide geographic area of the United States.
Commentary: The Future of Whole-Genome Sequencing for Public Health and the Clinic
Authors: Allard Marc W.
Published: June 2016

An American Society for Microbiology (ASM) conference titled the Conference on Rapid Next-Generation Sequencing and Bioinformatic Pipelines for Enhanced Molecular Epidemiological Investigation of Pathogens provided a venue for discussing how technologies surrounding whole-genome sequencing (WGS) are advancing microbiology. Several applications in microbial taxonomy, microbial forensics, and genomics for public health pathogen surveillance were presented at the meeting and are reviewed. All of these studies document that WGS is revolutionizing applications in microbiology and that the impact of these technologies will be profound. ASM is providing support mechanisms to promote discussions of WGS techniques to foster applications and interpretations.
Antiviral Activity of Myticin C Peptide from Mussel: an Ancient Defense against Herpesviruses
Authors: Novoa Beatriz , Romero Alejandro , Álvarez Ángel L. , Moreira Rebeca , Pereiro Patricia , Costa María M. , Dios Sonia , Estepa Amparo , Parra Francisco , Figueras Antonio
Published: June 2016

Little is known about the antiviral response in mollusks. As in other invertebrates, the interferon signaling pathways have not been identified, and in fact, there is a debate about whether invertebrates possess antiviral immunity similar to that of vertebrates. In marine bivalves, due to their filtering activity, interaction with putative pathogens, including viruses, is very high, suggesting that they should have mechanisms to address these infections. In this study, we confirmed that constitutively expressed molecules in naive mussels confer resistance in oysters to ostreid herpesvirus 1 (OsHV-1) when oyster hemocytes are incubated with mussel hemolymph. Using a proteomic approach, myticin C peptides were identified in both mussel hemolymph and hemocytes. Myticins, antimicrobial peptides that have been previously characterized, were constitutively expressed in a fraction of mussel hemocytes and showed antiviral activity against OsHV-1, suggesting that these molecules could be responsible for the antiviral activity of mussel hemolymph. For the first time, a molecule from a bivalve has shown antiviral activity against a virus affecting mollusks. Moreover, myticin C peptides showed antiviral activity against human herpes simplex viruses 1 (HSV-1) and 2 (HSV-2). In summary, our work sheds light on the invertebrate antiviral immune response with the identification of a molecule with potential biotechnological applications.

IMPORTANCE
Several bioactive molecules that have potential pharmaceutical or industrial applications have been identified and isolated from marine invertebrates. Myticin C, an antimicrobial peptide from the Mediterranean mussel (
Mytilus galloprovincialis
) that was identified by proteomic techniques in both mussel hemolymph and hemocytes, showed potential as an antiviral agent against ostreid herpesvirus 1 (OsHV-1), which represents a major threat to the oyster-farming sector. Both hemolymph from mussels and a myticin C peptide inhibited OsHV-1 replication in oyster hemocytes. Additionally, a modified peptide derived from myticin C or the nanoencapsulated normal peptide also showed antiviral activity against the human herpesviruses HSV-1 and HSV-2. Therefore, myticin C is an example of the biotechnological and therapeutic potential of mollusks.
The K1 Protein of Kaposi's Sarcoma-Associated Herpesvirus Augments Viral Lytic Replication
Authors: Zhang Zhigang , Chen Wuguo , Sanders Marcia K. , Brulois Kevin F. , Dittmer Dirk P. , Damania Blossom
Published: June 2016

The K1 gene product of Kaposi's sarcoma-associated herpesvirus (KSHV) is encoded by the first open reading frame (ORF) of the viral genome. To investigate the role of the K1 gene during the KSHV life cycle, we constructed a set of recombinant viruses that contained either wild-type (WT) K1, a deleted K1 ORF (KSHVΔK1), stop codons within the K1 ORF (KSHV-K1
5×STOP
), or a revertant K1 virus (KSHV-K1
REV
). We report that the recombinant viruses KSHVΔK1 and KSHV-K1
5×STOP
displayed significantly reduced lytic replication compared to WT KSHV and KSHV-K1
REV
upon reactivation from latency. Additionally, cells infected with the recombinant viruses KSHVΔK1 and KSHV-K1
5×STOP
also yielded smaller amounts of infectious progeny upon reactivation than did WT KSHV- and KSHV-K1
REV
-infected cells. Upon reactivation from latency, WT KSHV- and KSHV-K1
REV
-infected cells displayed activated Akt kinase, as evidenced by its phosphorylation, while cells infected with viruses deleted for K1 showed reduced phosphorylation and activation of Akt kinase. Overall, our results suggest that K1 plays an important role during the KSHV life cycle.

IMPORTANCE
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of three human malignancies, and KSHV K1 is a signaling protein that has been shown to be involved in cellular transformation and to activate the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway. In order to investigate the role of the K1 protein in the life cycle of KSHV, we constructed recombinant viruses that were deficient for K1. We found that K1 deletion viruses displayed reduced lytic replication compared to the WT virus and also yielded smaller numbers of infectious progeny. We report that K1 plays an important role in the life cycle of KSHV.
Klebsiella pneumoniae: Going on the Offense with a Strong Defense
Authors: Paczosa Michelle K. , Mecsas Joan
Published: June 2016

Klebsiella pneumoniaecauses a wide range of infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Historically,K. pneumoniaehas caused serious infection primarily in immunocompromised individuals, but the recent emergence and spread of hypervirulent strains have broadened the number of people susceptible to infections to include those who are healthy and immunosufficient. Furthermore,K. pneumoniaestrains have become increasingly resistant to antibiotics, rendering infection by these strains very challenging to treat. The emergence of hypervirulent and antibiotic-resistant strains has driven a number of recent studies. Work has described the worldwide spread of one drug-resistant strain and a host defense axis, interleukin-17 (IL-17), that is important for controlling infection. Four factors, capsule, lipopolysaccharide, fimbriae, and siderophores, have been well studied and are important for virulence in at least one infection model. Several other factors have been less well characterized but are also important in at least one infection model. However, there is a significant amount of heterogeneity inK. pneumoniaestrains, and not every factor plays the same critical role in all virulentKlebsiellastrains. Recent studies have identified additionalK. pneumoniaevirulence factors and led to more insights about factors important for the growth of this pathogen at a variety of tissue sites. Many of these genes encode proteins that function in metabolism and the regulation of transcription. However, much work is left to be done in characterizing these newly discovered factors, understanding how infections differ between healthy and immunocompromised patients, and identifying attractive bacterial or host targets for treating these infections.
Bacterial Sphingomyelinases and Phospholipases as Virulence Factors
Authors: Flores-Díaz Marietta , Monturiol-Gross Laura , Naylor Claire , Alape-Girón Alberto , Flieger Antje
Published: June 2016

Bacterial sphingomyelinases and phospholipases are a heterogeneous group of esterases which are usually surface associated or secreted by a wide variety of Gram-positive and Gram-negative bacteria. These enzymes hydrolyze sphingomyelin and glycerophospholipids, respectively, generating products identical to the ones produced by eukaryotic enzymes which play crucial roles in distinct physiological processes, including membrane dynamics, cellular signaling, migration, growth, and death. Several bacterial sphingomyelinases and phospholipases are essential for virulence of extracellular, facultative, or obligate intracellular pathogens, as these enzymes contribute to phagosomal escape or phagosomal maturation avoidance, favoring tissue colonization, infection establishment and progression, or immune response evasion. This work presents a classification proposal for bacterial sphingomyelinases and phospholipases that considers not only their enzymatic activities but also their structural aspects. An overview of the main physiopathological activities is provided for each enzyme type, as are examples in which inactivation of a sphingomyelinase- or a phospholipase-encoding gene impairs the virulence of a pathogen. The identification of sphingomyelinases and phospholipases important for bacterial pathogenesis and the development of inhibitors for these enzymes could generate candidate vaccines and therapeutic agents, which will diminish the impacts of the associated human and animal diseases.
Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4, the First Example of a GC-Rich Branch Proboscivirus
Authors: Ling Paul D. , Long Simon Y. , Fuery Angela , Peng Rong-Sheng , Heaggans Sarah Y. , Qin Xiang , Worley Kim C. , Dugan Shannon , Hayward Gary S.
Published: June 2016

Multiple species of herpesviruses from three different lineages of the
Proboscivirus
genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. Milder disease caused by EEHV5 or EEHV4 is being increasingly recognized as well, but little is known about the latter, which is estimated to have diverged at least 35 million years ago from the others within a distinctive GC-rich branch of the
Proboscivirus
genus. Here, we have determined the complete genomic DNA sequence of a strain of EEHV4 obtained from a trunk wash sample collected from a surviving Asian elephant calf undergoing asymptomatic shedding during convalescence after an acute hemorrhagic disease episode. This represents the first example from among the three known GC-rich branch
Proboscivirus
species to be assembled and fully annotated. Several distinctive features of EEHV4 compared to AT-rich branch genomes are described
Candida albicans Gene Deletion with a Transient CRISPR-Cas9 System
Authors: Min Kyunghun , Ichikawa Yuichi , Woolford Carol A. , Mitchell Aaron P.
Published: June 2016

The fungus
Candida albicans
is a major pathogen. Genetic analysis of this organism has revealed determinants of pathogenicity, drug resistance, and other unique biological features, as well as the identities of prospective drug targets. The creation of targeted mutations has been greatly accelerated recently through the implementation of CRISPR genome-editing technology by Vyas et al. [Sci Adv 1(3):e1500248, 2015,
http://dx.doi.org/10.1126/sciadv.1500248
]. In this study, we find that CRISPR elements can be expressed from genes that are present only transiently, and we develop a transient CRISPR system that further accelerates
C. albicans
genetic manipulation.
Insights into cyanobacterial fossilization in Ediacaran siliciclastic environments
Authors: Newman Sharon A. , Mariotti Giulio , Pruss Sara , Bosak Tanja
Published: June 2016

Ediacaran sedimentary successions are noted for the preservation of microbes and microbial textures on the surfaces of sandstones and siltstones. Although microorganisms have been preserved in coarse-grained siliciclastic sand throughout geologic history, the exceptional preservation of microbes in Ediacaran sediments suggests the potential for a unique taphonomic window. Here, we identify conditions conducive to the fossilization of filamentous cyanobacteria growing in the presence of siliciclastic sand and demonstrate that the sheaths of filamentous cyanobacteria can become coated by clay minerals within days under oxic conditions. Smooth, extensive mineral coatings develop in the presence of 5.6 to 55.6 mg/L of suspended clay and 0.1 mM or greater concentrations of dissolved silica. Thus, elevated concentrations of seawater silica and the delivery of suspended clays promote microbial preservation on sandy and silty surfaces. These factors likely facilitated microbial fossilization in coarse-grained siliciclastic sand throughout the Ediacaran Period and may have also contributed to microbial fossilization in siliciclastic deposits at other times throughout Earth’s history.
Republished: Spontaneous subarachnoid hemorrhage due to ruptured cavernous internal carotid artery aneurysm after medical prolactinoma treatment
Authors: Khalsa Siri Sahib , Hollon Todd C , Shastri Ravi , Trobe Jonathan D , Gemmete Joseph J , Pandey Aditya S
Published: June 2016

Aneurysms of the cavernous segment of the internal carotid artery (ICA) are believed to have a low risk of subarachnoid haemorrhage (SAH), given the confines of the dural rings and the anterior clinoid process. The risk may be greater when the bony and dural protection has been eroded. We report a case of spontaneous SAH from rupture of a cavernous ICA aneurysm in a patient whose large prolactinoma had markedly decreased in size as the result of cabergoline treatment. After passing a balloon test occlusion, the patient underwent successful endovascular vessel deconstruction. This case suggests that an eroding skull base lesion may distort normal anterior cranial base anatomy and allow communication between the cavernous ICA and subarachnoid space. The potential for SAH due to cavernous ICA aneurysm rupture should be recognised in patients with previous pituitary or other skull base lesions adjacent to the cavernous sinus.
The value of emergency medicine placements for postgraduate doctors: views of Foundation Year 2 doctors and training leads in the emergency department (ED)
Authors: O’Keeffe Colin , Carter Angela , Mason Suzanne
Published: June 2016

Objectives

To examine the delivery of postgraduate training in the emergency medicine setting and its impact on postgraduate doctor (Foundation Year 2) performance and competence.

Methods

A national study in four emergency departments (EDs) in England between 2009 and 2010 was undertaken. Semistructured interviews with ED training leads (TLs) and focus groups with Foundation Year 2 (F2) doctors were carried out in each ED. Interviews and focus group data were analysed to compare the perspectives of F2 doctors and TLs on the delivery of training and performance and confidence of F2 doctors.

Results

Interviews were carried out with eight TLs and focus groups with 30 F2s. F2 doctors and EDTLs agreed that ED was a valuable environment for F2 doctors to develop their competence, with exposure to a broad range of patients and the opportunity to make decisions about clinical care. Diverging views existed around competence and performance of F2s. F2 doctors had anxieties about decision-making (particularly discharging patients) and required regular feedback to feel confident in their care. TLs recognised a need for more supervision and support for F2 doctors but this was challenging in a busy, performance-led service.

Conclusions

Emergency medicine placements were important in the development of confident and competent F2 doctors, particularly in the context of less clinical exposure in other specialty placements. However, there are competing tensions between elements of postgraduate learning and service delivery within emergency medicine that require addressing to enable trainees to optimally develop knowledge and skills in this environment.
Stress in new graduates: can the profession do more to help?
Authors: Halliwell R. E. W. , Downes M. , Adams V. J. , Allister R. , Harrison W. , Mellanby R. J. , Dean R. S.
Published: June 2016

Richard Halliwell and colleagues believe that it can, on the basis of a survey they conducted to assess the incidence of poor mental health and wellbeing in recent veterinary graduates, and workplace factors that might be associated with this.