bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of the cathode grain size and substrate fixture movement on the evolution of arc evaporated Cr-cathodes and Cr-N coating synthesis
Authors: Zhu Jianqiang , Syed Bilal , Polcik Peter , Håkansson Greger , Johansson-Jöesaar Mats , Ahlgren Mats , Odén Magnus
Published: February 2014

The influence of the cathode grain size and the operation mode of the substrate fixture on the microstructure evolution of the Cr cathodes and the resulting Cr-N coating synthesis is studied. Hot isostatic pressed Cr cathodes with three different grain sizes were arc evaporated in a nitrogen atmosphere and Cr-N coatings were deposited on cemented carbide substrate at 2 and 4 Pa nitrogen pressure, respectively. The Cr cathodes before and after arc discharging are composed of polycrystalline α-Cr regardless of the grain size. A converted layer forms on the Cr cathode surface and its microstructure differs with the cathode grain size. A stationary mode of the substrate fixture results in ditches covering the cathode surface while a single rotating mode does not. The increased grain size of the virgin Cr cathodes enhances the quantities of the ditches. The possible causes are addressed. At 2 Pa nitrogen pressure, the Cr-N coatings deposited with the single rotating mode of the substrate fixture comprise only cubic CrN phase while the ones deposited with the stationary mode of the substrate fixture contain a mixture of hexagonal Cr2N and cubic CrN phases. By the increasing grain size of the Cr cathode, the droplet density of the Cr-N coatings increase somewhat while the hardness decreases for the Cr-N coatings deposited with stationary mode at 2 Pa nitrogen pressure. At the same stationary operation mode of the substrate fixture, the hardness of Cr-N coatings deposited at 4 Pa nitrogen pressure decreases ∼5 GPa in comparison to coatings at 2 Pa nitrogen pressure due to the decreased fraction of hex-Cr2N and the increased droplet density.
Human radiation dosimetry of 6‐[18F]FDG predicted from preclinical studies
Authors: Muzic Raymond F. , Chandramouli Visvanathan , Huang Hsuan‐Ming , Wu Chunying , Hatami Ahmad , Ismail‐Beigi Faramarz
Published: February 2014

Purpose:

The authors are developing 6‐[18F]fluoro‐6‐deoxy‐D‐glucose (6‐[18F]FDG) as an in vivo tracer of glucose transport. While 6‐[18F]FDG has the same radionuclide half‐life as 2‐[18F]fluoro‐2‐deoxy‐D‐glucose (2‐[18F]FDG) which is ubiquitously used for PET imaging, 6‐[18F]FDG has special biologic properties and different biodistributions that make it preferable to 2‐[18F]FDG for assessing glucose transport. In preparation for 6‐[18F]FDG use in human PET scanning, the authors would like to determine the amount of 6‐[18F]FDG to inject while maintaining radiation doses in a safe range.

Methods:

Rats were injected with 6‐[18F]FDG, euthanized at specified times, and tissues were collected and assayed for activity content. For each tissue sample, the percent of injected dose per gram was calculated and extrapolated to that for humans in order to construct predicted time‐courses. Residence times were calculated as areas under the curves and were used as inputs to OLINDA/EXM in order to calculate the radiation doses.

Results:

Unlike with 2‐[18F]FDG for which the urinary bladder wall receives the highest absorbed dose due to urinary excretion, with 6‐[18F]FDG there is little urinary excretion and osteogenic cells and the liver are predicted to receive the highest absorbed doses: 0.027 mGy/MBq (0.100 rad/mCi) and 0.018 mGy/MBq (0.066 rad/mCi), respectively. Also, the effective dose from 6‐[18F]FDG, i.e., 0.013 mSv/MBq (0.046 rem/mCi), is predicted to be approximately 30% lower than that from 2‐[18F]FDG.

Conclusions:

6‐[18F]FDG will be safe for use in the PET scanning of humans.
Long‐term stability of the Leksell Gamma Knife® Perfexion™ patient positioning system (PPS)
Authors: Novotny J. , Bhatnagar J. P. , Xu Y. , Huq M. S.
Published: February 2014

Purpose:

To assess the long‐term mechanical stability and accuracy of the patient positioning system (PPS) of the Leksell Gamma Knife® Perfexion™ (LGK PFX).

Methods:

The mechanical stability of the PPS of the LGK PFX was evaluated using measurements obtained between September 2007 and June 2011. Three methods were employed to measure the deviation of the coincidence of the radiological focus point (RFP) and the PPS calibration center point (CCP). In the first method, the onsite diode test tool with single diode detector was used together with the 4 mm collimator on a daily basis. In the second method, a service diode test tool with three diode detectors was used biannually at the time of the routine preventive maintenance. The test performed with the service diode test tool measured the deviations for all three collimators 4, 8, and 16 mm and also for three different positions of the PPS. The third method employed the conventional film pin‐prick method. This test was performed annually for the 4 mm collimator at the time of the routine annual QA. To estimate the effect of the patient weight on the performance of the PPS, the focus precision tests were also conducted with varying weights on the PPS using a set of lead bricks.

Results:

The average deviations measured from the 641 daily focus precision tests were 0.1 ± 0.1, 0.0 ± 0.0, and 0.0 ± 0.0 mm, respectively, for the 4 mm collimator in the X (left/right of the patient), Y (anterior/posterior of the patient), and Z (superior/inferior of the patient) directions. The average of the total radial deviations as measured during ten semiannual measurements with the service diode test tool were 0.070 ± 0.029, 0.060 ± 0.022, and 0.103 ± 0.028 mm, respectively for the central, long, and short diodes for the 4 mm collimator. Similarly, the average total radial deviations measured during the semiannual measurements for the 4, 8, and 16 mm collimators and using the central diode were 0.070 ± 0.029, 0.097 ± 0.025, 0.159 ± 0.028 mm, respectively. The average values of the deviations as obtained from the five annual film pin‐prick tests for the 4 mm collimator were 0.10 ± 0.06, 0.06 ± 0.09, and 0.03 ± 0.03 mm for the X, Y, Z stereotactic directions, respectively. Only a minor change was observed in the total radial deviations of the PPS as a function of the simulated patient weight up to 202 kg on the PPS.

Conclusions:

Excellent long‐term mechanical stability and high accuracy was observed for the PPS of the LGK PFX. No PPS recalibration or any adjustment in the PPS was needed during the monitored period of time. Similarly, the weight on the PPS did not cause any significant disturbance in the performance of the PPS for up to 202 kg simulated patient weight.
X‐ray scatter correction in breast tomosynthesis with a precomputed scatter map library
Authors: Feng Steve Si Jia , D'Orsi Carl J. , Newell Mary S. , Seidel Rebecca L. , Patel Bhavika , Sechopoulos Ioannis
Published: February 2014

Purpose:

To develop and evaluate the impact on lesion conspicuity of a software‐based x‐ray scatter correction algorithm for digital breast tomosynthesis (DBT) imaging into which a precomputed library of x‐ray scatter maps is incorporated.

Methods:

A previously developed model of compressed breast shapes undergoing mammography based on principal component analysis (PCA) was used to assemble 540 simulated breast volumes, of different shapes and sizes, undergoing DBT. A Monte Carlo (MC) simulation was used to generate the cranio‐caudal (CC) view DBT x‐ray scatter maps of these volumes, which were then assembled into a library. This library was incorporated into a previously developed software‐based x‐ray scatter correction, and the performance of this improved algorithm was evaluated with an observer study of 40 patient cases previously classified as BI‐RADS® 4 or 5, evenly divided between mass and microcalcification cases. Observers were presented with both the original images and the scatter corrected (SC) images side by side and asked to indicate their preference, on a scale from −5 to +5, in terms of lesion conspicuity and quality of diagnostic features. Scores were normalized such that a negative score indicates a preference for the original images, and a positive score indicates a preference for the SC images.

Results:

The scatter map library removes the time‐intensive MC simulation from the application of the scatter correction algorithm. While only one in four observers preferred the SC DBT images as a whole (combined mean score = 0.169 ± 0.37, p > 0.39), all observers exhibited a preference for the SC images when the lesion examined was a mass (1.06 ± 0.45, p < 0.0001). When the lesion examined consisted of microcalcification clusters, the observers exhibited a preference for the uncorrected images (−0.725 ± 0.51, p < 0.009).

Conclusions:

The incorporation of the x‐ray scatter map library into the scatter correction algorithm improves the efficiency of the algorithm. The observer study presented here is also the first test of the scatter correction algorithm with patient images and human observers, and demonstrates its potential to improve the clinical performance of DBT.
Diffraction by electronic components of everyday use
Authors: Barreiro Jesús J. , Pons Amparo , Barreiro Juan C. , Castro-Palacio Juan C. , Monsoriu Juan A.
Published: February 2014

We demonstrate the use of CCD image sensors and LCD screens from discarded electronic devices as elements for performing simple optical diffraction experiments. The experiments can determine the spatial structure of these components by analyzing diffraction patterns generated by their interaction with monochromatic light. This article presents the design and results of such experiments.
The Slinky Wilberforce pendulum: A simple coupled oscillator
Authors: Mewes Matthew
Published: February 2014

The Wilberforce pendulum is an effective classroom demonstration of coupled oscillations and the beat-like behavior that arises in weakly coupled tuned oscillators. We describe a simple and inexpensive version constructed from a Slinky spring toy and a soup can.
Impact behavior of hollow balls
Authors: Cross Rod
Published: February 2014

Measurements are presented of the force acting on ping-pong and squash balls impacting on a force plate. Both ball types are hollow and have the same diameter but deform in very different ways. Ping pong balls are relatively stiff and buckle inwards at high impact speeds, while squash balls are softer and tend to squash or flatten. The buckling process generates a large-amplitude, high-frequency oscillation of the force acting on a ping-pong ball. Squash balls are initially very stiff before they soften, with the result that the force on the ball rises to about half its maximum value in the first 20 μs. Ping-pong balls have a high coefficient of restitution (COR), while squash balls have a low COR. Results for both ball types are interpreted in terms of additional experimental observations.
Isotropic photon drag: Analytic expressions for velocity (3D) and position (1D) with applications to blackbody friction
Authors: West Joseph
Published: February 2014

The motion of objects traveling at relativistic speeds and subject only to isotropic photon drag (blackbody friction as a special case) is modeled. The objects are assumed to be perfectly absorbing. Analytic expressions for velocity and position as a function of time for objects subject to photon drag are obtained for the case in which the photons are constrained to one-dimensional motion. If the object is also assumed to be a perfect emitter of energy, analytic expressions are found for time as a function of velocity of the body for photons constrained to one-dimensional motion, and for a full three-dimensional isotropic photon background. The derivations are carried out entirely from the point of view of a reference frame at rest relative to the isotropic photon field, so that no changes of reference frame are involved. The results for the three-dimensional model do not agree with work by previous authors, and this discrepancy is discussed. The derivations are suitable for use in the undergraduate classroom. Example cases for a light sail and a micron-sized sand grain are examined for interactions with the cosmic background radiation, assuming a temperature of 3000 K, the temperature at the time the universe became transparent, and it is found that relativistic speeds would decay on a time scale of years.
Capacitance-voltage profiling: Research-grade approach versus low-cost alternatives
Authors: Reynolds Neal D. , Panda Cristian D. , Essick John M.
Published: February 2014

We describe an experiment that implements capacitance-voltage profiling on a reverse-biased Schottky barrier diode to determine the density of impurity dopants in its semiconductor layer as well as its built-in electric potential. Our sample is a commercially produced Schottky diode. Three different experimental setups, one using research-grade instrumentation, the other two using low-cost alternatives, are given and their results compared. In each of the low-cost setups, phase-sensitive detection required to measure the sample's capacitance is carried out using an inexpensive data acquisition (DAQ) device and a software program that implements a lock-in detection algorithm. The limitations of the DAQ device being used (e.g., restricted analog-to-digital conversion speed, inadequate waveform generation capabilities, lack of hardware triggering) are taken into account in each setup. Excellent agreement for the value of the doping density obtained by the all three setups is found and this value is shown to be consistent with the result of an independent method (secondary ion mass spectroscopy).
Cultivating Safe Space: Lessons for Sport-for-Development Projects and Events
Authors: Spaaij Ramon , Schulenkorf Nico
Published: February 2014

Recent research has examined how sports events and sport-for-development projects can create, sustain, and maximize positive social impacts for local communities. This article takes this debate forward by arguing that the cultivation of safe space is a key ingredient of sport-for-development management and community event leverage. Safe space is conceptualized as a multidimensional process that involves physical, psychological/affective, sociocultural, political, and experimental dimensions. Drawing on empirical findings from Sri Lanka, Israel, and Brazil, the article shows how these dimensions of safe space operate and interact in practice, and identifies practical strategies that sport managers, policymakers, and practitioners can use to cultivate safe spaces in and through sports projects and events.
Solar Synthesis: Prospects in Visible Light Photocatalysis
Authors: Schultz Danielle M. , Yoon Tehshik P.
Published: February 2014

Background

Interest in photochemical synthesis has been motivated in part by the realization that sunlight is effectively an inexhaustible energy source.Chemists have also long recognized distinctive patterns of reactivity that are uniquely accessible via photochemical activation. However, most simple organic molecules absorb only ultraviolet (UV) light and cannot be activated by the visible wavelengths that comprise most of the solar energy that reaches Earth’s surface. Consequently, organic photochemistry has generally required the use of UV light sources.

Advances

Over the past several years, there has been a resurgence of interest in synthetic photochemistry, based on the recognition that the transition metal chromophores that have been so productively exploited in the design of technologies for solar energy conversion can also convert visible light energy into useful chemical potential for synthetic purposes. Visible light enables productive photoreactions of compounds possessing weak bonds that are sensitive toward UV photodegradation. Furthermore, visible light photoreactions can be conducted by using essentially any source of white light, including sunlight, which obviates the need for specialized UV photoreactors. This feature has expanded the accessibility of photochemical reactions to a broader range of synthetic organic chemists. A variety of reaction types have now been shown to be amenable to visible light photocatalysis via photoinduced electron transfer to or from the transition metal chromophore, as well as energy-transfer processes. The predictable reactivity of the intermediates generated and the tolerance of the reaction conditions to a wide range of functional groups have enabled the application of these reactions to the synthesis of increasingly complex target molecules.

Outlook

This general strategy for the use of visible light in organic synthesis is already being adopted by a growing community of synthetic chemists. Much of the current research in this emerging area is geared toward the discovery of photochemical solutions for increasingly ambitious synthetic goals. Visible light photocatalysis is also attracting the attention of researchers in chemical biology, materials science, and drug discovery, who recognize that these reactions offer opportunities for innovation in areas beyond traditional organic synthesis. The long-term goals of this emerging area are to continue to improve efficiency and synthetic utility and to realize the long-standing goal of performing chemical synthesis using the sun.
Fighting Urban Scourges
Pests in the City
Flies, Bedbugs, Cockroaches, and Rats

by Dawn Day Biehler

University of Washington Press, Seattle, 2013. 359 pp. $34.95. ISBN 9780295993010.
Authors: Davis Frederick R.
Published: February 2014

Through her histories of efforts to control urban pests, Biehler develops the notion of "ecologies of social injustice."
Connecting Paradigms
The New Science of Cities

by Michael Batty

MIT Press, Cambridge, MA, 2013. 518 pp. $45, £31.95. ISBN 9780262019521.
Authors: Szell Michael
Published: February 2014

Batty demonstrates how applying mathematical modeling and complexity theory can improve our understanding of cities.
Meet the New Boss, Same as the Old Boss
Authors: Kaspari Michael , Weiser Michael D.
Published: February 2014

A chemical defense helps an invasive ant species to outcompete an earlier invader that originates from the same native region.

[Also see Report by

LeBrun
et al.

]
Signaling Shifts in Allergy Responses
Authors: Daëron Marc
Published: February 2014

A mechanism that senses antigen affinity shifts cell signaling and leads to qualitatively different inflammatory responses.

[Also see Report by

Suzuki
et al.

]
Festival Lessons
Authors: Borysiewicz Leszek , Buckley Nicola
Published: February 2014

For a university that is over 800 years old, 20th anniversaries are rather modest. Yet in March, the University of Cambridge will reflect on 20 years of organizing the Cambridge Science Festival in the United Kingdom. During this year's event, topics ranging from string theory to sustainability will be examined through talks, demonstrations, debates, theatre, music, exhibitions, and more. Hundreds of researchers and students will participate, and around 30,000 people are expected to attend. Over the past two decades, the festival has imparted many general lessons about how to successfully make science “public” and why this endeavor is important not only for the audience but for the research enterprise itself.
Commentary: The Role of the Clinical Laboratory in the Future of Health Care: Lean Microbiology
Authors: Samuel Linoj , Novak-Weekley Susan
Published: February 2014

This commentary will introduce lean concepts into the clinical microbiology laboratory. The practice of lean in the clinical microbiology laboratory can remove waste, increase efficiency, and reduce costs. Lean, Six Sigma, and other such management initiatives are useful tools and can provide dividends but must be accompanied by organizational leadership commitment to sustaining the lean culture in the laboratory setting and providing resources and time to work through the process.
Clinical Characteristics of Bacteremia Caused by Helicobacter cinaedi and Time Required for Blood Cultures To Become Positive
Authors: Araoka Hideki , Baba Masaru , Kimura Muneyoshi , Abe Masahiro , Inagawa Hiroko , Yoneyama Akiko
Published: February 2014

The aim of this study was to clarify the clinical characteristics of patients withHelicobacter cinaedibacteremia and the time required for blood cultures to become positive. The medical records of all patients withH. cinaedibacteremia at Toranomon Hospital and Toranomon Hospital Kajigaya between March 2009 and March 2013 were retrospectively reviewed. Sixty-three patients, 34 men and 29 women with a median age of 67 years (range, 37 to 88 years), were diagnosed withH. cinaedibacteremia. A total of 51,272 sets of blood cultures were obtained during the study period, of which 5,769 sets of blood cultures were positive for some organism and 126 sets wereH. cinaedipositive. The time required for blood cultures to become positive forH. cinaediwas ≤5 days in 69 sets (55%) and >5 days in 57 sets (45%). Most patients had an underlying disease, including chronic kidney disease (21 cases), solid tumor (19 cases), hematological malignancy (13 cases), diabetes mellitus (8 cases), chronic liver disease (6 cases), and postorthopedic surgery (3 cases). Only 1 patient had no apparent underlying disease. The clinical symptoms included cellulitis in 24 cases, colitis in 7 cases, and fever only in 27 cases, including 7 cases of febrile neutropenia. The 30-day mortality rate ofH. cinaedibacteremia was 6.3%. In conclusion, most cases ofH. cinaedibacteremia occurred in immunocompromised patients. We might have overlooked nearly half of theH. cinaedibacteremia cases if the duration of monitored blood culture samples had been within 5 days. Therefore, when clinicians suspectH. cinaedibacteremia, the observation period for blood cultures should be extended.
Identification of Polybacterial Communities in Patients with Postoperative, Posttraumatic, and Endogenous Endophthalmitis through 16S rRNA Gene Libraries
Authors: Jayasudha Rajagopalaboopathi , Narendran Venkatapathy , Manikandan Palanisamy , Prabagaran Solai Ramatchandirane
Published: February 2014

Endophthalmitis is a potential vision-threatening complication following surgical procedures (postoperative endophthalmitis [POE]), trauma (posttraumatic endophthalmitis [PTE]), and bacteremic seeding of the eye from a distant infection site (endogenous endophthalmitis [EE]). Several studies have revealed the polybacterial characteristics of endophthalmitis, which make the administration of antibiotics to treat the disease challenging. However, until now, the polybacterial communities of POE, PTE, and EE have not been precisely studied. Hence, the present study was designed to identify the bacterial community of endophthalmitis through 16S rRNA gene libraries. Of the 40 intraocular samples tested, 30 libraries were constructed with bacterial nested-PCR-positive samples. The obtained recombinant clones were screened through amplified rRNA gene restriction analysis (ARDRA) to identify unique clones. The multiple types of ARDRA patterns (
P
= 0.345) and diverse bacterial sequences (
P
= 0.277) within the libraries revealed the polybacterial nature of infection in POE, PTE, and EE. Moreover, to the best of our knowledge, this is the first report on polybacterial infection in EE. Gram-positive bacteria, including
Bacillus
spp. (
n
= 19),
Streptococcus
spp. (
n
= 18),
Staphylococcus
spp. (
n
= 6),
Exiguobacterium
spp. (
n
= 3),
Gemella
spp. (
n
= 2),
Enterococcus
spp. (
n
= 2), a
Lysinibacillus
sp. (
n
= 1), a
Clostridium
sp. (
n
= 1), and a
Nocardia
sp. (
n
= 1), and Gram-negative bacteria, including
Serratia
spp. (
n
= 18),
Pseudomonas
spp. (
n
= 10),
Enterobacter
spp. (
n
= 8),
Acinetobacter
spp. (
n
= 3),
Pantoea
spp. (
n
= 3), a
Haemophilus
sp. (
n
= 1), and a
Massilia
sp. (
n
= 1), were identified. Interestingly, among them, 10 bacterial species were not previously reported to be associated with endophthalmitis or other ocular infections. Besides, the presence of 4 unidentifiable clones suggests the possibility of novel organisms that might cause eye infections. Therefore, it is recommended that, in addition to the polybacterial nature of POE, PTE, and EE infections, the spectrum of the pathogenic bacterial community identified in this work should be considered while administering antibiotic therapy in suspected endophthalmitis cases.
Meta-Analysis of Sonication Fluid Samples from Prosthetic Components for Diagnosis of Infection after Total Joint Arthroplasty
Authors: Zhai Zanjing , Li Haowei , Qin An , Liu Guangwang , Liu Xuqiang , Wu Chuanlong , Li Huiwu , Zhu Zhenan , Qu Xinhua , Dai Kerong
Published: February 2014

This meta-analysis included 12 studies that evaluated sonication fluid cultures (SFC) for the diagnosis of prosthetic joint infection (PJI). The pooled sensitivity and specificity were 0.80 (95% confidence interval [CI], 0.74 to 0.84) and 0.95 (CI, 0.90 to 0.98), respectively. Subgroup analyses showed that a 14-day anaerobic culture may improve sensitivity, the use of centrifugation or vortexing may improve specificity, and the use of 400 to 500 ml of Ringer's solution for containers may improve sensitivity and specificity. The best SFC cutoff was ≥5 CFU. In conclusion, SFC has high sensitivity and very high specificity for diagnosing PJI.
Direct Detection of Macrolide Resistance in Mycoplasma genitalium Isolates from Clinical Specimens from France by Use of Real-Time PCR and Melting Curve Analysis
Authors: Touati Arabella , Peuchant Olivia , Jensen Jorgen S. , Bébéar Cécile , Pereyre Sabine
Published: February 2014

Mycoplasma genitalium
is a sexually transmitted organism commonly treated with azithromycin. However, macrolide resistance has been reported and is associated with point mutations in the 23S rRNA gene. To evaluate the prevalence of macrolide resistance in
M. genitalium
isolates from clinical specimens from France, we first used a previously reported high-resolution melting assay. Because susceptible and resistant
M. genitalium
isolates were hardly discriminated in
M. genitalium
-positive clinical specimens, we developed a new molecular assay for the rapid detection of macrolide resistance. An assay using real-time PCR based on fluorescence resonance energy transfer (FRET) coupled with melting curve analysis was designed. The assay was first validated on characterized macrolide-resistant
M. genitalium
isolates and then applied to 202 urogenital
M. genitalium
-positive specimens collected from 178 patients from France in 2011 and 2012. Resistant genotypes were confirmed by 23S rRNA gene sequencing. Among the 202
M. genitalium
-positive specimens, 155 were amplified, demonstrating a sensitivity of 76.7%. A substitution in the 23S rRNA gene was found in 14.2% of the patient samples. Nine and six patients had
M. genitalium
isolates with a substitution at positions 2059 and 2058, respectively. In four cases, a mixed population of wild-type and mutated
M. genitalium
isolates was observed. The prevalence of
M. genitalium
macrolide resistance has been stable in France since its detection in 2006. Our FRET PCR assay is able to discriminate between wild-type and resistant genotypes directly from clinical specimens. This assay will allow clinicians to shorten the time to the initiation of effective disease treatment.
Heat Shock Protein 70 Enhances Mucosal Immunity against Human Norovirus When Coexpressed from a Vesicular Stomatitis Virus Vector
Authors: Ma Yuanmei , Duan Yue , Wei Yongwei , Liang Xueya , Niewiesk Stefan , Oglesbee Michael , Li Jianrong
Published: February 2014

Human norovirus (NoV) accounts for 95% of nonbacterial gastroenteritis worldwide. Currently, there is no vaccine available to combat human NoV as it is not cultivable and lacks a small-animal model. Recently, we demonstrated that recombinant vesicular stomatitis virus (rVSV) expressing human NoV capsid protein (rVSV-VP1) induced strong immunities in mice (Y. Ma and J. Li, J. Virol. 85:2942–2952, 2011). To further improve the safety and efficacy of the vaccine candidate, heat shock protein 70 (HSP70) was inserted into the rVSV-VP1 backbone vector. A second construct was generated in which the firefly luciferase (Luc) gene was inserted in place of HSP70 as a control for the double insertion. The resultant recombinant viruses (rVSV-HSP70-VP1 and rVSV-Luc-VP1) were significantly more attenuated in cell culture and viral spread in mice than rVSV-VP1. At the inoculation dose of 1.0 × 106PFU, rVSV-HSP70-VP1 triggered significantly higher vaginal IgA than rVSV-VP1 and significantly higher fecal and vaginal IgA responses than rVSV-Luc-VP1, although serum IgG and T cell responses were similar. At the inoculation dose of 5.0 × 106PFU, rVSV-HSP70-VP1 stimulated significantly higher T cell, fecal, and vaginal IgA responses than rVSV-VP1. Fecal and vaginal IgA responses were also significantly increased when combined vaccination of rVSV-VP1 and rVSV-HSP70 was used. Collectively, these data indicate that (i) insertion of an additional gene (HSP70 or Luc) into the rVSV-VP1 backbone further attenuates the VSV-based vaccinein vitroandin vivo, thus improving the safety of the vaccine candidate, and (ii) HSP70 enhances the human NoV-specific mucosal and T cell immunities triggered by a VSV-based human NoV vaccine.

IMPORTANCEHuman norovirus (NoV) is responsible for more than 95% of acute nonbacterial gastroenteritis worldwide. Currently, there is no vaccine for this virus. Development of a live attenuated vaccine for human NoV has not been possible because it is uncultivable. Thus, a live vector-based vaccine may provide an alternative vaccine strategy. In this study, we developed a vesicular stomatitis virus (VSV)-based human NoV vaccine candidate. We constructed rVSV-HSP70-VP1, coexpressing heat shock protein (HSP70) and capsid (VP1) genes of human NoV, and rVSV-Luc-VP1, coexpressing firefly luciferase (Luc) and VP1 genes. We found that VSVs with a double gene insertion were significantly more attenuated than VSV with a single VP1 insertion (rVSV-VP1). Furthermore, we found that coexpression or coadministration of HSP70 from VSV vector significantly enhanced human NoV-specific mucosal immunity. Collectively, we developed an improved live vectored vaccine candidate for human NoV which will be useful for future clinical studies.
Local Control of Repeated-Dose Rectal Challenges in DNA/MVA-Vaccinated Macaques Protected against a First Series of Simian Immunodeficiency Virus Challenges
Authors: Kannanganant Sunil , Gangadhara Salaija , Lai Lilin , Lawson Benton , Kozlowski Pamela A. , Robinson Harriet L. , Amara Rama Rao
Published: February 2014

Here, we report the results of a late boost and three additional series of simian immunodeficiency virus (SIV) challenges in seven DNA/modified vaccinia virus Ankara (MVA)-vaccinated rhesus macaques who resisted a first series of rectal challenges. During 29 additional challenges delivered over 2.3 years, all animals became infected. However, 13 blips of virus in six macaques and anamnestic Env-specific rectal IgA responses in three of the six suggested that local control of infections was occurring during the serial challenge.
Varicella-Zoster Virus and Herpes Simplex Virus 1 Can Infect and Replicate in the Same Neurons whether Co- or Superinfected
Authors: Sloutskin Anna , Yee Michael B. , Kinchington Paul R. , Goldstein Ronald S.
Published: February 2014

The two human neurotropic alphaherpesviruses varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV1) both establish latency in sensory ganglia. Human trigeminal ganglia are known to frequently harbor both viruses, and there is evidence to suggest the presence of both VZV and HSV1 DNA in the same neuron. We ask here whether VZV and HSV1 can exclude themselves and each other and whether they can productively infect the same cells in human neurons and human foreskin fibroblasts (HFF). Simultaneous infection (coinfection) or consecutive infection (superinfection) was assessed using cell-free HSV1 and VZV expressing fluorescent reporter proteins. Automated analysis was carried out to detect singly and dually infected cells. We demonstrate that VZV and HSV1 both display efficient superinfection exclusion (SE) in HFF, with each virus excluding either itself or the other virus. While SE also occurred in neurons, it was with much lower efficiency. Both alphaherpesviruses productively infected the same neurons, whether applied simultaneously or even consecutively, albeit at lower frequencies.

IMPORTANCE
Superinfection exclusion by VZV for itself or the related neurotropic alphaherpesvirus HSV1 has been studied here for the first time. We find that while these viruses display classic SE in fibroblasts, SE is less efficient for both HSV1 and VZV in human neurons. The ability of multiple VZV strains to productively infect the same neurons has important implications in terms of recombination of both wild-type and vaccine strains in patients.
A Critical Determinant of Neurological Disease Associated with Highly Pathogenic Tick-Borne Flavivirus in Mice
Authors: Yoshii Kentaro , Sunden Yuji , Yokozawa Kana , Igarashi Manabu , Kariwa Hiroaki , Holbrook Michael R , Takashima Ikuo
Published: February 2014

Tick-borne encephalitis virus (TBEV) and Omsk hemorrhagic fever virus (OHFV) are highly pathogenic tick-borne flaviviruses; TBEV causes neurological disease in humans, while OHFV causes a disease typically identified with hemorrhagic fever. Although TBEV and OHFV are closely related genetically, the viral determinants responsible for these distinct disease phenotypes have not been identified. In this study, chimeric viruses incorporating components of TBEV and OHFV were generated using infectious clone technology, and their pathological characteristics were analyzed in a mouse model to identify virus-specific determinants of disease. We found that only four amino acids near the C terminus of the NS5 protein were primarily responsible for the development of neurological disease. Mutation of these four amino acids had no effect on viral replication or histopathological features, including inflammatory responses, in mice. These findings suggest a critical role for NS5 in stimulating neuronal dysfunction and degeneration following TBEV infection and provide new insights into the molecular mechanisms underlying the pathogenesis of tick-borne flaviviruses.

IMPORTANCE
Tick-borne encephalitis virus (TBEV) and Omsk hemorrhagic fever virus (OHFV) belong to the tick-borne encephalitis serocomplex, genus
Flavivirus
, family
Flaviviridae
. Although TBEV causes neurological disease in humans while OHFV causes a disease typically identified with hemorrhagic fever. In this study, we investigated the viral determinants responsible for the different disease phenotypes using reverse genetics technology. We identified a cluster of only four amino acids in nonstructural protein 5 primarily involved in the development of neurological disease in a mouse model. Moreover, the effect of these four amino acids was independent of viral replication property and did not affect the formation of virus-induced lesions in the brain directly. These data suggest that these amino acids may be involved in the induction of neuronal dysfunction and degeneration in virus-infected neurons, ultimately leading to the neurological disease phenotype. These findings provide new insight into the molecular mechanisms of tick-borne flavivirus pathogenesis.
The Stability of Herpes Simplex Virus 1 ICP0 Early after Infection Is Defined by the RING Finger and the U
L
13 Protein Kinase
Authors: Zhu Zhi , Du Te , Zhou Guoying , Roizman Bernard
Published: February 2014

Herpes simplex virus 1 (HSV-1)-infected cell protein 0 (ICP0) is a multifunctional protein that plays a key role in overcoming numerous facets of host innate immunity. A key function of ICP0 that requires an intact RING finger domain is that of an ubiquitin E3 ligase: ICP0 interacts with at least three ubiquitin-conjugating enzymes of which one, UbcH5a, is required for degradation of PML and SP100. A preceding report showed that ICP0 is highly unstable at very early times after infection but becomes stable at later times. We report here that (i) the degradation of ICP0 is not infected cell specific, (ii) the degradation does not require the interaction of ICP0 with either UbcH5a, UbcH6, or UbcH9, (iii) ICP0 is degraded both early and late in cells infected with a mutant lacking the U
L
13 protein kinase, (iv) ICP0 encoded by wild-type virus or the ΔU
L
13 mutant is stable in cells transfected with a plasmid encoding U
L
13 before infection, (v) ICP0 carrying mutations in the RING finger domain is stable both early and late in infection, and, finally, (vi) in cells infected with both wild type and RING finger mutant only the wild-type ICP0 is rapidly degraded at early times. The results suggest that the stability of ICP0 is mediated by the U
L
13 protein kinase and that the target of proteolysis is a site at or near the RING domain of ICP0.

IMPORTANCE
ICP0, a major regulatory protein of HSV-1, turns over rapidly early in infection but becomes stable at late times. We report that stabilization requires the presence of U
L
13 protein kinase and that an ICP0 with mutations in RING finger is stable. In mixed infections mutant ICP0 is stable, whereas the wild-type ICP0 is degraded. Our findings suggest that the lifestyle of HSV-1 requires an ICP0 that turns over rapidly if late proteins are absent.
Defective Interfering Influenza Virus RNAs: Time To Reevaluate Their Clinical Potential as Broad-Spectrum Antivirals?
Authors: Dimmock Nigel J. , Easton Andrew J.
Published: February 2014

Defective interfering (DI) RNAs are highly deleted forms of the infectious genome that are made by most families of RNA viruses. DI RNAs retain replication and packaging signals, are synthesized preferentially over infectious genomes, and are packaged as DI virus particles which can be transmitted to susceptible cells. Their ability to interfere with the replication of infectious virus in cell culture and their potential as antivirals in the clinic have long been known. However, until now, no realistic formulation has been described. In this review, we consider the early evidence of antiviral activity by DI viruses and, using the example of DI influenza A virus, outline developments that have led to the production of a cloned DI RNA that is highly active in preclinical studies not only against different subtypes of influenza A virus but also against heterologous respiratory viruses. These data suggest the timeliness of reassessing the potential of DI viruses as a novel class of antivirals that may have general applicability.
Nelfinavir Inhibits Maturation and Export of Herpes Simplex Virus 1
Authors: Kalu Nene N. , Desai Prashant J. , Shirley Courtney M. , Gibson Wade , Dennis Phillip A. , Ambinder Richard F.
Published: February 2014

Nelfinavir (NFV) is an HIV-1 protease inhibitor with demonstrated antiviral activity against herpes simplex virus 1 (HSV-1) and several other herpesviruses. However, the stages of HSV-1 replication inhibited by NFV have not been explored. In this study, we investigated the effects of NFV on capsid assembly and envelopment. We confirmed the inhibitory effects of NFV on HSV-1 replication by plaque assay and found that treatment with NFV did not affect capsid assembly, activity of the HSV-1 maturational protease, or formation of DNA-containing capsids in the nucleus. Confocal and electron microscopy studies showed that these capsids were transported to the cytoplasm but failed to complete secondary envelopment and subsequent exit from the cell. Consistent with the microscopy results, a light-scattering band corresponding to enveloped virions was not evident following sucrose gradient rate-velocity separation of lysates from drug-treated cells. Evidence of a possibly related effect of NFV on viral glycoprotein maturation was also discovered. NFV also inhibited the replication of an HSV-1 thymidine kinase mutant resistant to nucleoside analogues such as acyclovir. Given that NFV is neither a nucleoside mimic nor a known inhibitor of nucleic acid synthesis, this was expected and suggests its potential as a coinhibitor or alternate antiviral therapeutic agent in cases of resistance.

IMPORTANCE
Nelfinavir (NFV) is a clinically important antiviral drug that inhibits production of infectious HIV. It was reported to inhibit herpesviruses in cell culture. Herpes simplex virus 1 (HSV-1) infections are common and often associated with several diseases. The studies we describe here confirm and extend earlier findings by investigating how NFV interferes with HSV-1 replication. We show that early steps in virus formation (e.g., assembly of DNA-containing capsids in the nucleus and their movement into the cytoplasm) appear to be unaffected by NFV, whereas later steps (e.g., final envelopment in the cytoplasm and release of infectious virus from the cell) are severely restricted by the drug. Our findings provide the first insight into how NFV inhibits HSV-1 replication and suggest that this drug may have applications for studying the herpesvirus envelopment process. Additionally, NFV may have therapeutic value alone or in combination with other antivirals in treating herpesvirus infections.
Very late stent thrombosis following the placement of a crossing Y-stent with dual closed-cell stents for the coiling of a wide-necked aneurysm
Authors: Lee Chang-Young , Kim Chang-Hyun
Published: February 2014

The crossing Y-stent technique is a viable option for coiling of wide-necked bifurcation aneurysms. However, little is known about the long-term impact of this technique. Very late (>1 year) stent thrombosis following the placement of a crossing Y-stent with dual closed-cell stents for the coiling of a wide-necked basilar tip aneurysm, which has not been reported to date, is described.
Safe Handover : Safe Patients - The Electronic Handover System
Authors: Till Alex , Sall Hanish , Wilkinson Jonathan
Published: February 2014

Failure of effective handover is a major preventable cause of patient harm. We aimed to promote accurate recording of high-quality clinical information using an Electronic Handover System (EHS) that would contribute to a sustainable improvement in effective patient care and safety. Within our hospital the human factors associated with poor communication were compromising patient care and unnecessarily increasing the workload of staff due to the poor quality of handovers. Only half of handovers were understood by the doctors expected to complete them, and more than half of our medical staff felt it posed a risk to patient safety. We created a standardised proforma for handovers that contained specific sub-headings, re-classified patient risk assessments, and aided escalation of care by adding prompts for verbal handover. Sources of miscommunication were removed, accountability for handovers provided, and tasks were re-organised to reduce the workload of staff. Long-term, three-month data showed that each sub-heading achieved at least 80% compliance (an average improvement of approximately 40% for the overall quality of handovers). This translated into 91% of handovers being subjectively clear to junior doctors. 87% of medical staff felt we had reduced a risk to patient safety and 80% felt it increased continuity of care. Without guidance, doctors omit key information required for effective handover. All organisations should consider implementing an electronic handover system as a viable, sustainable and safe solution to handover of care that allows patient safety to remain at the heart of the NHS.
Overenthusiastic stroke risk factor modification in the over-80s: Are we being disingenuous to ourselves, and to our oldest patients?
Authors: Byatt Kit
Published: February 2014

Statins and antihypertensive therapy are widely used in our oldest patients (ie, those aged over 80 years). The epidemiology suggests that, by this age, hypertension is not an attributable risk factor for stroke, and hypercholesterolaemia has little effect on stroke risk overall. The largest trials of antihypertensive therapy and statins in this age group show at best a marginal clinical reduction in stroke and very modest clinical reductions in other cardiovascular end points. Older patients have very diverse views on the relative importance of stroke and death as end points, and these differ from physicians’ views. Informed consent principles (full relevant information in an accessible form, and autonomy of decision-making) suggest that these medications are greatly over-prescribed in the healthy elderly and largely irrelevant in the frail elderly, but require that the patient should be actively involved in the process.
The mental health of the UK Armed Forces in the 21st century: resilience in the face of adversity
Authors: MacManus Deirdre , Jones N , Wessely S , Fear N T , Jones E , Greenberg N
Published: February 2014

The recent conflicts in Iraq and Afghanistan have attracted considerable political and media interest in the mental health of UK military personnel. As a result of the close operational collaboration between US and UK forces, there have inevitably been many comparisons drawn between the mental health status of the two forces. Considerable research activity suggests that the mental health of UK forces appear to have remained relatively resilient in spite of their considerable exposure to traumatic events; one stark exception to this is the high rates of alcohol misuse which seem to be related to deployment. This paper explores the recently published literature relating to UK military forces and attempts to draw conclusions about the reasons for the apparent resilience shown by the majority of the regular forces.
Lenticulostriate aneurysms: a case series and review of the literature
Authors: Vargas Jan , Walsh Kevin , Turner Raymond , Chaudry Imran , Turk Aquilla , Spiotta Alejandro
Published: February 2014

Introduction

Aneurysms of lenticulostriate artery (LSA) perforators are uncommon. There are few data on their natural history, and opinions differ on the treatment strategies.

Objective

We report a case series and summarize the most recent literature with current treatment recommendations. We propose an anatomical classification for these entities.

Methods

A retrospective review of all patients who were diagnosed with an LSA aneurysm on cerebral angiogram was performed. An extensive online literature search was performed to identify other studies reporting on the diagnosis and management of ruptured and unruptured lenticulostriate aneurysms.

Results

48 cases were identified in the literature and reviewed: 27 patients were treated surgically; five cases were treated with endovascular therapy; two cases underwent gamma knife radiosurgery; and 13 cases were managed conservatively. We classified these aneurysms into three types: type 1 describes aneurysms arising from the middle cerebral artery next to a perforating LSA; type 2 is an LSA aneurysm from which the perforating artery or arteries arise—the type 2A subtype is one in which the aneurysm neck incorporates the origin of the perforating arteries and the type 2B describes perforating arteries arising from the dome of the aneurysm; and type 3 describes a fusiform aneurysm beyond the first loop or turn of an LSA.

Conclusions

LSA aneurysms are rare entities that present several treatment challenges. We have summarized the cumulative experience with these lesions and proposed a classification scheme that has treatment implications.