bluuebunny/crossref_metadata_2025 huggingface dataset:
VASA (DDX4) is a Putative Marker for Spermatogonia, Spermatocytes and Round Spermatids in Stallions
Authors: Kim JY , Jung HJ , Yoon MJ
Published: October 2015

Contents

Expression of the protein DDX4/MVH, or VASA, has been reported in germ cells of several species. The main objectives of this study were to (i) investigate VASA expression patterns in testicular cells of stallions at two different reproductive stages (pre‐pubertal and post‐pubertal) and (ii) evaluate the use of VASA antibody as a molecular marker for single germ cells from stallions. Testicular tissues were obtained from stallions and categorized as pre‐pubertal and post‐pubertal based on the formation of lumen and status of spermatogenesis on the cross section of seminiferous tubules. The results of Western blot showed a VASA protein band located at 76 kDa, indicating that the rabbit antibody has a cross‐reactivity with horse testicular tissues. The result of immunolabelling showed that VASA was expressed in the cytoplasm of spermatogonia at both reproductive stages and in spermatocytes and round spermatids at the post‐pubertal stage. GATA4‐positive Sertoli cells and Leydig cells located in the interstitial space were not immunolabelled with VASA. These results suggest that VASA can be utilized as a molecular marker for germ cells of stallions at pre‐pubertal and post‐pubertal stages. Interestingly, immunolabelling intensity was significantly higher in pachytene spermatocytes compared to spermatogonia and round spermatid. VASA antibody was also effective for staining of single germ cell preparations. In conclusion, VASA protein expression can be used as a marker for identification of spermatogonia, spermatocytes and round spermatids in testicular tissues of stallions.
Multinational Firms and Plant Divestiture
Authors: Norbäck Pehr‐Johan , Tekin‐Koru Ayça , Waldkirch Andreas
Published: October 2015

Multinational firms not only make acquisitions, but also frequently divest affiliates. Affiliate divestiture is the result of many factors, some internal and some external to the firm. Using detailed confidential survey data of Swedish multinationals, we are able to examine divestiture decisions within the context of the world‐wide affiliate network of the firm. In contrast, most existing studies of multinational exit focus on one country only. A model of mergers and acquisitions with financing constraints generates predictions regarding the correlation between affiliate size and the decision to sell. Consistent with this theory, we find that larger affiliates are more likely to be divested, but an increase in relative size of an affiliate reduces the probability of divestiture. Additional network characteristics, the presence of other affiliates nearby and sales of affiliates elsewhere, are also positively correlated with divestiture. We find no support for the notion of footloose multinationals.
Trade Frictions and Market Access of Developing Countries: A Product‐level Empirical Investigation
Authors: Bempong Nyantakyi Eugene , Husted Steven , Nishioka Shuichiro
Published: October 2015

This paper examines the effects of trade frictions on export market access at the product level and the role these frictions have on the ability of developing countries to access world markets. We find distance and trade frictions are determinants of the probability of success in entering foreign markets. We examine whether there are any systematic biases from these frictions that further limit market access for exporters from developing countries. Our results suggest that developing countries are not differentially impacted by these factors.
In the National Interest: Construction and Destruction in Gaza City
Authors: Thirkell Lucy
Published: October 2015

This article presents a case study of Gaza City as the product of various – and literally conflicting – attempts to ‘boost’ particular visions for the future of the city. It is an example of the complicated, globalized reality whereby competing nationalist efforts occupy the same urban space, which deserves a more prominent place in urban studies. In Gaza City, plans to construct, develop, or destroy speak over each other and produce results quite different from their stated aims. The ensuing cacophony has created an urban experience that has much to teach on the subject of multiple power sources and overstated urban plans in cities in the process of constructing for a developing national identity around the world.
Ethylene production in Botrytis cinerea‐ and oligogalacturonide‐induced immunity requires calcium‐dependent protein kinases
Authors: Gravino Matteo , Savatin Daniel Valentin , Macone Alberto , De Lorenzo Giulia
Published: October 2015

Plant immunity against pathogens is achieved through rapid activation of defense responses that occur upon sensing of microbe‐ or damage‐associated molecular patterns, respectively referred to as MAMPs and DAMPs. Oligogalacturonides (OGs), linear fragments derived from homogalacturonan hydrolysis by pathogen‐secreted cell wall‐degrading enzymes, and flg22, a 22‐amino acid peptide derived from the bacterial flagellin, represent prototypical DAMPs and MAMPs, respectively. Both types of molecules induce protection against infections. In plants, like in animals, calcium is a second messenger that mediates responses to biotic stresses by activating calcium‐binding proteins. Here we show that simultaneous loss of calcium‐dependent protein kinases CPK5, CPK6 and CPK11 affects Arabidopsis thaliana basal as well as elicitor‐ induced resistance to the necrotroph Botrytis cinerea, by affecting pathogen‐induced ethylene production and accumulation of the ethylene biosynthetic enzymes 1‐aminocyclopropane‐1‐carboxylic acid (ACC) synthase 2 (ACS2) and 6 (ACS6). Moreover, ethylene signaling contributes to OG‐triggered immunity activation, and lack of CPK5, CPK6 and CPK11 affects the duration of OG‐ and flg22‐induced gene expression, indicating that these kinases are shared elements of both DAMP and MAMP signaling pathways.
Re‐inhabiting no‐man's land: genealogies, political life and critical agendas
Authors: Leshem Noam , Pinkerton Alasdair
Published: October 2015

This article sets out to answer a seemingly simple question: what is no‐man's land? By positing this question, we aim to problematise the taken‐for‐granted status of no‐man's land and its proliferation as a convenient colloquialism that is applied to a vast set of spaces, material conditions and socio‐political circumstances. Despite its popular association with the killing fields of the First World War, no‐man's land is considered here as a rich analytical category, which resonates in a broader historical and intellectual corpus. We present a conceptual framework for the study of no‐man's land as a space produced by simultaneous forces of abandonment and enclosure. The analysis explores the function of no‐man's lands as a critical quality that bears on concrete spatio‐political realities. In doing so, we aim to open up future research avenues that will further deepen the conceptual and analytical challenges of no‐man's lands in the 21st century.
Cross‐country Services Versus Manufacturing Activity of Multinational Firms in Response to Services Versus Goods Policy
Authors: Egger Peter , Merlo Valeria , Wamser Georg
Published: October 2015

This paper assesses the consequences of trade costs on goods and services for the distribution of foreign direct investment (FDI) across goods and services as well as across countries. The paper employs data on the universe of German FDI abroad which are collected at the firm level and aggregated for the purpose of this paper to two sectors – goods and services – and 79 countries, using data for the year 2005. Key findings are that services trade costs as reflected in the services trade restrictiveness index and bilateral investment treaty membership are the most important policy drivers of the activity of German‐owned multinational firms in both goods and services. An increase in services trade restrictions raises goods activity at the expense of services activity. This effect is more pronounced the more important host countries in terms of the German FDI are.
When an Importer's Protection of IPR Interacts with an Exporter's Level of Technology: Comparing the Impacts on the Exports of the North and South
Authors: Shin Wonkyu , Lee Keun , Park Walter G.
Published: October 2015

Using bilateral trade data of countries from 2000 to 2007, this paper contributes to the empirical literature on the role of intellectual property rights (IPRs) in global trade. The existing literature has focused on how IPRs in the destination country affect exports from a source country. In this paper, we add an additional dimension: the level of technology of the exporting country (LT). This is quite important for distinguishing the impact of IPRs on the exports of developed and developing countries, since the technology levels vary across countries at different stages of development and intellectual property rights better protect exports that are technologically advanced than exports that are imitative and potentially infringing. By factoring in the level of technology (LT), our empirical analysis makes the case that IPRs can act as a barrier to the exports from the South, especially the rapidly catching‐up economies, and thus be a source for the middle‐income trap phenomenon.
EU Trade Preferences and Export Diversification
Authors: Persson Maria , Wilhelmsson Fredrik
Published: October 2015

Since at least the 1960s, the European Union (EU) has offered various kinds of non‐reciprocal trade preferences for developing countries. Originally, these trade preferences had at least two policy goals: (i) to increase export volumes for developing countries and thereby boost their export earnings and (ii) to facilitate export diversification. While extensive research has confirmed that the first of these goals is typically met, the second goal seems to have been largely forgotten by researchers as well as in policy circles. The aim of this paper was therefore to analyse the impact of the EU's non‐reciprocal trade preferences for developing countries on export diversification. Our estimation results suggest that some trade preference programmes, such as the Generalised Scheme of Preferences (GSP), lead to increasing ranges of export products. By contrast, preferences offered to Mediterranean countries typically have no significant effects, and African, Caribbean and Pacific (ACP) preferences actually have negative effects towards the end of our time period, suggesting that ACP countries may respond to preferences by specialising into fewer goods.
The Fiscal Framework in a Currency Union: Lessons from a Comparison between the Euro Area and the Eastern Caribbean Currency Union
Authors: Hughes Hallett Andrew , Jensen Svend E. Hougaard
Published: October 2015

This paper draws out lessons from the euro area (EA) that are transferable to the Eastern Caribbean Currency Union (ECCU) and other Caribbean economies with fixed exchange rates. Based on observations from both the EA and the ECCU, we present a new policy framework which is capable of imposing fiscal discipline, with the aim of avoiding the risk of unsustainable fiscal policies reappearing and of preventing monetary policy from being undermined by undisciplined national governments. In the ECCU case, we find that fiscal deficits are more a result of financial and trade imbalances than fiscal indiscipline per se. Consequently, constraints on overall debt, public and private, rather than direct limits on endogenous public deficits, appear to be the appropriate response.
Biological variation of thromboelastrography variables in 10 clinically healthy horses
Authors: Scruggs Jennifer L. , Flatland Bente , McCormick Karen A. , Reed Ann
Published: October 2015

Objective

To assess the utility of population‐based reference intervals (PRIs) for interpreting thromboelastography (TEG) variables in horses using biological variation data.

Design

Prospective cohort biologic variation study conducted over a 5‐week period.

Setting

Veterinary teaching hospital and research facility.

Animals

Ten clinically healthy horses randomly selected from a veterinary school research and teaching herd.

Interventions

Horse health was determined using physical examination, CBC, and biochemical and coagulation profiles prior to the start of the study. Subsequently, once weekly blood sampling for TEG testing was performed for 5 weeks.

Measurements and Main Results

The 4 TEG variables reaction time (R), clot formation time (K), angle, and maximum amplitude (MA) were measured, and coefficient of variation representing within‐ and between‐horse biological variation (CVi and CVg, respectively) and coefficient of variation representing analytical variation (CVa) were calculated using a nested ANOVA after removing outlier data. The CVi, CVg, and CVa for R were 26.8%, 5.2%, and 5.9%; for K were 31.0%, 0.0%, and 5.9%; for angle were 9.4%, 6.2%, and 21.7%; and for MA were 3.4%, 4.1%, and 4.4%, respectively. Index of individuality (IOI) was then calculated for each variable using the formula IOI for R was 5.3, for angle was 3.8, and for MA was 1.4; IOI was not assessed for K.

Conclusions

PRIs are appropriate for TEG variables, R, angle, and MA when interpreting results from individual horses based on calculated IOI values equal to or greater than 1.4. PRIs are likely appropriate when interpreting K, but IOI could not be calculated for this variable.
Transition Curve Analysis of Linear Fractional Periodic Time-Delayed Systems Via Explicit Harmonic Balance Method
Authors: Butcher Eric A. , Dabiri Arman , Nazari Morad
Published: October 2015

This paper presents a technique to obtain the transition curves of fractional periodic time-delayed (FPTD) systems based on a proposed explicit harmonic balance (EHB) method. This method gives the analytical Hill matrix of FPTD systems explicitly with a symbolic computation-free algorithm. Furthermore, all linear operations on Fourier basis vectors including fractional order derivative operators and time-delayed operators for a linear FPTD system are obtained. This technique is illustrated with parametrically excited simple and double pendulum systems, with both time-delayed states and fractional damping.
Improvement in Boundary Lubrication Characteristics of SAE20W40 Oil Using Aluminum Oxide Nanoparticles
Authors: Thakre Avinash A. , Shinde Ananta , Mundhe Ganesh
Published: October 2015

The present work includes the study of boundary lubrication properties of SAE20W40 lubricating oil added with aluminum oxide nanoparticles. Pin-on-disk tribometer is employed to study the effects of nanoparticles in different sizes (40–80 nm) and concentrations (0–1% by weight) on the friction coefficient. The experimental design consists of L18 orthogonal array involving six levels for nanoparticles concentration and three levels for nanoparticles size, sliding speed, and normal load. The presence of nanoparticles has significantly improved the lubrication properties of oil. Minimum friction coefficient is recorded at 1200 rpm rotational speed and 160 N normal load for 0.8% concentration of 60 nm sized nanoparticles. Scanning electron microscopy (SEM) and electron diffraction spectrometry (XRD) are employed to understand the friction reduction mechanism.
The Effects of Small Sinusoidal Load Variations in Elastohydrodynamic Line Contacts
Authors: Hooke C. J. , Morales-Espejel G. E.
Published: October 2015

A method of determining the response of elastohydrodynamic line contacts to low amplitude, sinusoidal variations in load is presented. It is shown that the load variations alter the Hertz width, cyclically increasing and reducing the effective entrainment velocity. This produces clearance variations in the inlet, which are transported through the conjunction altering the pressure distribution as they pass. The resulting pressure and clearance changes can be many times greater than when the load changes slowly. The results are used to determine the flexibility and damping of the conjunctions. These vary depending on the number of transported waves inside the contact. It is shown that a Maxwell model rather than the usual Voigt model is required to define the contact's behavior. While the Voigt model may be used at low frequencies, it has a damping coefficient that is not unique to the contact but depends on the total system stiffness.
On modeling and nanoanalysis of caries-affected dentin surfaces restored with Zn-containing amalgam and in vitro oral function
Authors: Toledano Manuel , Aguilera Fátima S. , Osorio Estrella , López-López Modesto T. , Cabello Inmaculada , Toledano-Osorio Manuel , Osorio Raquel
Published: October 2015

The aim of this research was to assess the influence of mechanical loading on the ability of Zn-free versus Zn-containing amalgams to promote remineralization at the dentin interface. Sound and caries-affected dentin surfaces (CAD) were restored using Zn-free or Zn-containing dental amalgams. Midcoronal dentin surfaces were studied by (1) atomic force microscopy analysis (including plot and phase imaging, nanoindentation test [modulus of Young (Ei), nanoroughness measurements, and fibril diameter assessment], (2) Raman spectroscopy/cluster analysis, (3) x-ray diffraction, (4) field emission electron microscope and energy-dispersive analysis, for morphological, mechanical, and physicochemical characterization. Analyses were performed before amalgam placement and after amalgam removal, at 24 h and 3 weeks of load cycling. Zn-free and Zn-containing amalgams restorations promoted an increase in the modulus of Young of CAD surfaces, after 3 weeks of load cycling; at this time, Zn-containing amalgams attained higher Ei than Zn-free restorations. Zn-containing amalgams induced tubular occlusion after load cycling, in both sound and CAD. Zn free-amalgams promoted remineralization of both intertubular and peritubular dentin in CAD substrata. These minerals were identified as calcium–phosphate deposits and crystals as hydroxyl-apatite with augmented crystallographic maturity but with some components of lattice distortion. Crosslinking of collagen diminished and secondary structure of collagen increased in CAD substrate restored with Zn-containing amalgam after 3 weeks of load cycling, indicating an advanced preservation, molecular organization, and orientation of collagen fibrils after load cycling. Plot and phase images permitted to observe the topographical changes which were promoted by the mineral deposits; in general, the indexes related to higher remineralization gave rise to a decrease of nanoroughness and an augmentation of the bandwidth of the collagen fibrils. Zn-containing amalgam restorations submitted to mechanical stimuli promote remineralization of the partially mineral-depleted subjacent substrate at the caries-affected dentin.
Multihelix rotating shield brachytherapy for cervical cancer
Authors: Dadkhah Hossein , Kim Yusung , Wu Xiaodong , Flynn Ryan T.
Published: October 2015

Purpose:

To present a novel brachytherapy technique, called multihelix rotating shield brachytherapy (H‐RSBT), for the precise angular and linear positioning of a partial shield in a curved applicator. H‐RSBT mechanically enables the dose delivery using only linear translational motion of the radiation source/shield combination. The previously proposed approach of serial rotating shield brachytherapy (S‐RSBT), in which the partial shield is rotated to several angular positions at each source dwell position [W. Yang et al., “Rotating‐shield brachytherapy for cervical cancer,” Phys. Med. Biol. 58, 3931–3941 (2013)], is mechanically challenging to implement in a curved applicator, and H‐RSBT is proposed as a feasible solution.

Methods:

A Henschke‐type applicator, designed for an electronic brachytherapy source (Xoft Axxent™) and a 0.5 mm thick tungsten partial shield with 180° or 45° azimuthal emission angles and 116° asymmetric zenith angle, is proposed. The interior wall of the applicator contains six evenly spaced helical keyways that rigidly define the emission direction of the partial radiation shield as a function of depth in the applicator. The shield contains three uniformly distributed protruding keys on its exterior wall and is attached to the source such that it rotates freely, thus longitudinal translational motion of the source is transferred to rotational motion of the shield. S‐RSBT and H‐RSBT treatment plans with 180° and 45° azimuthal emission angles were generated for five cervical cancer patients with a diverse range of high‐risk target volume (HR‐CTV) shapes and applicator positions. For each patient, the total number of emission angles was held nearly constant for S‐RSBT and H‐RSBT by using dwell positions separated by 5 and 1.7 mm, respectively, and emission directions separated by 22.5° and 60°, respectively. Treatment delivery time and tumor coverage (D90 of HR‐CTV) were the two metrics used as the basis for evaluation and comparison. For all the generated treatment plans, the D90 of the HR‐CTV in units of equivalent dose in 2 Gy fractions (EQD2) was escalated until the D2cc (minimum dose to hottest 2 cm3) tolerance of either the bladder (90 Gy3), rectum (75 Gy3), or sigmoid colon (75 Gy3) was reached.

Results:

Treatment time changed for H‐RSBT versus S‐RSBT by −7.62% to 1.17% with an average change of −2.8%, thus H‐RSBT treatments times tended to be shorter than for S‐RSBT. The HR‐CTV D90 also changed by −2.7% to 2.38% with an average of −0.65%.

Conclusions:

H‐RSBT is a mechanically feasible delivery technique for use in the curved applicators needed for cervical cancer brachytherapy. S‐RSBT and H‐RSBT were clinically equivalent for all patients considered, with the H‐RSBT technique tending to require less time for delivery.
Improved quality of intrafraction kilovoltage images by triggered readout of unexposed frames
Authors: Poulsen Per Rugaard , Jonassen Johnny , Schmidt Mai Lykkegaard , Jensen Carsten
Published: October 2015

Purpose:

The gantry‐mounted kilovoltage (kV) imager of modern linear accelerators can be used for real‐time tumor localization during radiation treatment delivery. However, the kV image quality often suffers from cross‐scatter from the megavoltage (MV) treatment beam. This study investigates readout of unexposed kV frames as a means to improve the kV image quality in a series of experiments and a theoretical model of the observed image quality improvements.

Methods:

A series of fluoroscopic images were acquired of a solid water phantom with an embedded gold marker and an air cavity with and without simultaneous radiation of the phantom with a 6 MV beam delivered perpendicular to the kV beam with 300 and 600 monitor units per minute (MU/min). An in‐house built device triggered readout of zero, one, or multiple unexposed frames between the kV exposures. The unexposed frames contained part of the MV scatter, consequently reducing the amount of MV scatter accumulated in the exposed frames. The image quality with and without unexposed frame readout was quantified as the contrast‐to‐noise ratio (CNR) of the gold marker and air cavity for a range of imaging frequencies from 1 to 15 Hz. To gain more insight into the observed CNR changes, the image lag of the kV imager was measured and used as input in a simple model that describes the CNR with unexposed frame readout in terms of the contrast, kV noise, and MV noise measured without readout of unexposed frames.

Results:

Without readout of unexposed kV frames, the quality of intratreatment kV images decreased dramatically with reduced kV frequencies due to MV scatter. The gold marker was only visible for imaging frequencies ≥3 Hz at 300 MU/min and ≥5 Hz for 600 MU/min. Visibility of the air cavity required even higher imaging frequencies. Readout of multiple unexposed frames ensured visibility of both structures at all imaging frequencies and a CNR that was independent of the kV frame rate. The image lag was 12.2%, 2.2%, and 0.9% in the first, second, and third frame after an exposure. The CNR model predicted the CNR with triggered image readout with a mean absolute error of 2.0% for the gold marker.

Conclusions:

A device that triggers readout of unexposed frames during kV fluoroscopy was built and shown to greatly improve the quality of intratreatment kV images. A simple theoretical model successfully described the CNR improvements with the device.
Linearized two-hydrophone localization of a pulsed acoustic source in the presence of refraction: Theory and simulations
Authors: Skarsoulis E. K. , Dosso Stan E.
Published: October 2015

This paper develops an efficient three-dimensional localization method for transient acoustic sources, with uncertainty estimation, based on time differences between direct and surface-reflected arrivals at two hydrophones. The localization method accounts for refraction caused by a depth-dependent sound-speed profile using a ray-theoretic approach for calculating eigenray travel times and partial derivatives. Further, the method provides localization error estimates accounting for uncertainties of the arrival times and hydrophone locations, as well as for depth-dependent uncertainties in the sound-speed profile. In the first of two steps, source depth and range to each hydrophone are estimated using an iterative, linearized Gauss-Markov inversion scheme. In the second step, the estimated source ranges are combined with the hydrophone locations to obtain the source location in the horizontal. Localization performance is analyzed in a simulation study, and the linearized localization estimates and uncertainties are validated by comparison with a fully nonlinear (but numerically intensive) Markov-chain Monte Carlo inversion.
Modeling the effects of linear shallow-water internal waves on horizontal array coherence
Authors: Rouseff Daniel , Lunkov Andrey A.
Published: October 2015

The coherence length of a horizontal array is the maximum separation between two points where coherent processing gives useful gain when a distant source is at broadside. In shallow water, the coherence length is limited by the environmental variability caused by several relevant oceanographic processes. In the present study, a statistical model is developed that quantifies how one oceanographic process, linear internal waves, affects the coherence length. A key input to the ocean sub-model is the vertically integrated energy density of the internal wave field. The acoustic sub-model is based on the adiabatic normal mode approximation and so should be reasonable for frequencies under 1 kHz. Numerical calculations using environmental data from the Shallow Water 2006 Experiment (SW06) show how the coherence length of individual modes varies with consequent effects on array coherence. The coherence length is shown to be a strong function of where the source and array are positioned in the water column. For a bottom-mounted array above a moderately lossy seabed, the model predicts a coherence length that depends only weakly on range, an effect observed in field experiments.
Enjoyment, Barriers, and Beliefs About Physical Activity in Adolescents With and Without Autism Spectrum Disorder
Authors: Stanish Heidi , Curtin Carol , Must Aviva , Phillips Sarah , Maslin Melissa , Bandini Linda
Published: October 2015

The authors compared physical activity enjoyment, perceived barriers, beliefs, and self-efficacy between adolescents with autism spectrum disorder (ASD) and typically developing (TD) adolescents. A questionnaire was verbally administered to 35 adolescents with ASD and 60 TD adolescents. Compared with TD adolescents, fewer adolescents with ASD enjoyed team sports (65% vs. 95%, p < .001) and physical education (84% vs. 98%, p = .02). A greater proportion of adolescents with ASD perceived that physical activities were too hard to learn (16% vs. 0%, p < .01), and fewer believed that physical activity was a way to make friends (68% vs. 97%, p < .001). Fewer adolescents with ASD preferred to do physical activity in their free time (25% vs. 58%, p < .01). Most adolescents with ASD felt that physical activity is fun (84%), but the proportion was lower than in TD adolescents (98%, p = .03). Some perceptions about physical activity were similar between the 2 groups, but differences identified may inform program development.
The Impact of Paralympic School Day on Student Attitudes Toward Inclusion in Physical Education
Authors: McKay Cathy , Block Martin , Park Jung Yeon
Published: October 2015

The purpose of this study was to determine if Paralympic School Day (PSD), a published disability awareness program, would have a positive impact on the attitudes of students without disabilities toward the inclusion of students with disabilities in physical education classes. Participants were 143 sixth-grade students who were divided into 2 groups (experimental n = 71, control n = 72), with the experimental group receiving the PSD treatment. Participants responded 2 times to Siperstein’s Adjective Checklist and Block’s Children’s Attitudes Toward Integrated Physical Education–Revised (CAIPE-R) questionnaire. Four ANCOVA tests were conducted. Results indicated a significant PSD treatment effect across all 4 measures: Adjective Checklist (p = .046, η2 = .03), CAIPE-R (p = .002, η2 = .04), inclusion subscale (p = .001, η2 = .05), and sport-modification subscale (p = .027, η2 = .02).
Similarities and Differences in the Determinants of Trips Outdoors Performed by UK Urban- and Rural-Living Older Adults
Authors: de Koning Jolanthe L. , Stathi Afroditi , Fox Kenneth R.
Published: October 2015

The frequency of trips outdoors is a strong indicator of older adults’ physical activity levels. This qualitative study compared and contrasted determinants of trips outdoors between rural- (n = 13) and urban-living (n = 15) people aged 65 and older living in England. Interview transcripts were analyzed through directed and summative content analysis employing the Ecological Model framework. Some personal-level determinants (age-related barriers) and environment-level factors (car dependence, bus services) were shared across samples. The main differences were seen in how a community-based social network instigated trips outdoors for rural participants while family ties mostly led to trips outdoors for urban-living participants. Urban participants used and valued recreational facilities, but rural participants did not report them as important in determining trips outdoors. Strategies to improve public transport and minimize age-related barriers may translate from urban to rural contexts. However, social and/or physical environment interventions could be more effective if they were rural-grounded, not urban-translated.
CD4
+
T cell–dependent and CD4
+
T cell–independent cytokine-chemokine network changes in the immune responses of HIV-infected individuals
Authors: Arnold Kelly B. , Szeto Gregory L. , Alter Galit , Irvine Darrell J. , Lauffenburger Douglas A.
Published: October 2015

Mathematical analysis of the cytokine secretion profiles of collections of patient immune cells uncovers network-level effects of HIV infection.
Essential roles for Ca
v
β2 and Ca
v
1 channels in thymocyte development and T cell homeostasis
Authors: Jha Archana , Singh Ashish K. , Weissgerber Petra , Freichel Marc , Flockerzi Veit , Flavell Richard A. , Jha Mithilesh K.
Published: October 2015

Disruption of voltage-gated calcium channels in thymocytes inhibits T cell development in mice.
Matters of context guide future research in TGFβ superfamily signaling
Authors: Akhurst Rosemary J. , Padgett Richard W.
Published: October 2015

The rich contextual nature of TGFβ signaling output offers clues for future therapeutic strategies.
A new peptide for treating retinal disease
Authors: Smith Orla
Published: October 2015

A stable small peptide that binds to two retinal VEGF receptors blocks angiogenesis in animal models of human retinal diseases.
Changes over time build neuronal diversity
Authors: Hines Pamela J.
Published: October 2015

Neuronal progenitors themselves change during development, even while continuing to generate new neurons.
Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit
Authors: Abdul-Aziz Mohd H. , Abd Rahman Azrin N. , Mat-Nor Mohd-Basri , Sulaiman Helmi , Wallis Steven C. , Lipman Jeffrey , Roberts Jason A. , Staatz Christine E.
Published: October 2015

Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a 1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CL
CR
), such that a 30-ml/min increase in the estimated CL
CR
would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every 8 h as a 4-h infusion is optimal for patients with a CL
CR
of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CL
CR
of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved.
Molecular Characterization of Carbapenem-Nonsusceptible Enterobacterial Isolates Collected during a Prospective Interregional Survey in France and Susceptibility to the Novel Ceftazidime-Avibactam and Aztreonam-Avibactam Combinations
Authors: Dupont Hervé , Gaillot Olivier , Goetgheluck Anne-Sophie , Plassart Claire , Emond Jean-Philippe , Lecuru Marion , Gaillard Nicolas , Derdouri Sarah , Lemaire Baptiste , Girard de Courtilles Marion , Cattoir Vincent , Mammeri Hedi
Published: October 2015

An interregional surveillance program was conducted in the northwestern part of France to determine the prevalence of carbapenem-nonsusceptible
Enterobacteriaceae
(CNSE) isolates and their susceptibility to ceftazidime-avibactam and aztreonam-avibactam combinations. Nonduplicate CNSE clinical isolates were prospectively collected from six hospitals between June 2012 and November 2013. MICs of ceftazidime and aztreonam, alone or combined with a fixed concentration of avibactam (4 μg/ml), and those of carbapenems (comparator agents) were determined. MICs of ertapenem in combination with phenylalanine arginine-naphthylamide dihydrochloride (PAβN) were also determined to assess active efflux. Genes encoding carbapenemases, plasmid-mediated AmpC enzymes, extended-spectrum β-lactamases (ESBLs), and major outer membrane proteins (OMPs) were amplified and sequenced. OMPs were also extracted for SDS-PAGE analysis. Among the 139 CNSE isolates, mainly
Enterobacter
spp. and
Klebsiella pneumoniae
, 123 (88.4%) were ertapenem nonsusceptible, 12 (8.6%) exhibited reduced susceptibility to all carbapenems, and 4
Proteeae
isolates (2.9%) were resistant to imipenem. Carbapenemase production was detected in only two isolates (producing OXA-48 and IMI-3). In contrast, OMP deficiency, in association with AmpCs and/or ESBLs (mainly CTX-M-9, SHV-12, and CTX-M-15), was largely identified among CNSE isolates. The ceftazidime-avibactam and aztreonam-avibactam combinations exhibited potent activity against CNSE isolates (MIC
50
/MIC
90
, 1/1 μg/ml and 0.5/0.5 μg/ml, respectively) compared to that of ceftazidime and aztreonam alone (MIC
50
/MIC
90
, 512/512 μg/ml and 128/512 μg/ml, respectively). This study reveals the
in vitro
activity of ceftazidime-avibactam and aztreonam-avibactam combinations against a large collection of porin-deficient enterobacterial isolates that are representative of the CNSE recovered in the northern part of France.
Risk Factors and Outcomes for Bloodstream Infections Secondary to Clostridium difficile Infection
Authors: Falcone Marco , Russo Alessandro , Iraci Federica , Carfagna Paolo , Goldoni Paola , Vullo Vincenzo , Venditti Mario
Published: October 2015

We determined the incidence, risk factors, and outcomes of bloodstream infections (BSI) subsequent to
Clostridium difficile
infection (CDI). We performed a retrospective study of all patients with definite diagnosis of CDI admitted from January 2014 to December 2014 in two large hospitals in Rome. Two groups of patients were analyzed: those with CDI and subsequent BSI (CDI/BSI
+
) and those with CDI and no evidence of primary BSI (CDI/BSI
−
). Data about clinical features, microbiology, treatments, and mortality were obtained. Overall, 393 cases of CDI were included in the final analysis: 72 developed a primary nosocomial BSI, while 321 had CDI without microbiological and clinical evidence of BSI. Etiologic agents of BSI were
Candida
species (47.3%),
Enterobacteriaceae
(19.4%), enterococci (13.9%), and mixed infections (19.4%). In multivariate analysis, ribotype 027 status (odds ratio [OR], 6.5), CDI recurrence (OR, 5.5), severe CDI infection (OR, 8.3), and oral vancomycin at >500 mg/day (OR, 3.1) were recognized as factors independently associated with the development of nosocomial BSI. Thirty-day mortality from CDI diagnosis was higher for patients of the CDI/BSI
+
group than for the controls (38.9 versus 13.1%;
P
< 0.001). Among patients of the CDI/BSI
+
group, mortality attributable to primary BSI was as high as 57%. Our findings suggest that severe CDI is complicated by the development of nosocomial BSI.
Candida
species and enteric bacteria appear to be the leading causative pathogens and are associated with poor outcomes.
Surface Polysaccharide Mutants Reveal that Absence of O Antigen Reduces Biofilm Formation of Actinobacillus pleuropneumoniae
Authors: Hathroubi S. , Hancock M. A. , Bossé J. T. , Langford P. R. , Tremblay Y. D. N. , Labrie J. , Jacques M.
Published: October 2015

Actinobacillus pleuropneumoniae
is a Gram-negative bacterium belonging to the
Pasteurellaceae
family and the causative agent of porcine pleuropneumonia, a highly contagious lung disease causing important economic losses. Surface polysaccharides, including lipopolysaccharides (LPS) and capsular polysaccharides (CPS), are implicated in the adhesion and virulence of
A. pleuropneumoniae
, but their role in biofilm formation is still unclear. In this study, we investigated the requirement for these surface polysaccharides in biofilm formation by
A. pleuropneumoniae
serotype 1. Well-characterized mutants were used: an O-antigen LPS mutant, a truncated core LPS mutant with an intact O antigen, a capsule mutant, and a poly-
N
-acetylglucosamine (PGA) mutant. We compared the amount of biofilm produced by the parental strain and the isogenic mutants using static and dynamic systems. Compared to the findings for the biofilm of the parental or other strains, the biofilm of the O antigen and the PGA mutants was dramatically reduced, and it had less cell-associated PGA. Real-time PCR analyses revealed a significant reduction in the level of
pgaA
,
cpxR
, and
cpxA
mRNA in the biofilm cells of the O-antigen mutant compared to that in the biofilm cells of the parental strain. Specific binding between PGA and LPS was consistently detected by surface plasmon resonance, but the lack of O antigen did not abolish these interactions. In conclusion, the absence of the O antigen reduces the ability of
A. pleuropneumoniae
to form a biofilm, and this is associated with the reduced expression and production of PGA.
Morphology-Independent Virulence of Candida Species during Polymicrobial Intra-abdominal Infections with Staphylococcus aureus
Authors: Nash Evelyn E. , Peters Brian M. , Fidel Paul L. , Noverr Mairi C.
Published: October 2015

Intra-abdominal polymicrobial infections cause significant morbidity and mortality. An experimental mouse model ofCandida albicans-Staphylococcus aureusintra-abdominal infection (IAI) results in 100% mortality by 48 to 72 h postinoculation, while monomicrobial infections are avirulent. Mortality is associated with robust local and systemic inflammation without a requirement forC. albicansmorphogenesis. However, the contribution of virulence factors coregulated during the yeast-to-hypha transition is unknown. This also raised the question of whether otherCandidaspecies that are unable to form hyphae are as virulent asC. albicansduring polymicrobial IAI. Therefore, the purpose of this study was to evaluate the ability of non-albicans Candida(NAC) species with various morphologies andC. albicanstranscription factor mutants (efg1/efg1andcph1/cph1) to induce synergistic mortality and the accompanying inflammation. Results showed thatS. aureuscoinoculated withC. kruseiorC. tropicaliswas highly lethal, similar toC. albicans, whileS. aureus-C. dubliniensis,S. aureus-C. parapsilosis, andS. aureus-C. glabratacoinoculations resulted in little to no mortality. Local and systemic interleukin-6 (IL-6) and prostaglandin E2(PGE2) levels were significantly elevated during symptomatic and/or lethal coinfections, and hypothermia strongly correlated with mortality. Coinoculation withC. albicansstrains deficient in the transcription factor Efg1 but not Cph1 reversed the lethal outcome. These results support previous findings and demonstrate that selectCandidaspecies, without reference to any morphological requirement, induce synergistic mortality, with IL-6 and PGE2acting as key inflammatory factors. Mechanistically, signaling pathways controlled by Efg1 are critical for the ability ofC. albicansto induce mortality from an intra-abdominal polymicrobial infection.
Global and Targeted Lipid Analysis of
Gemmata obscuriglobus
Reveals the Presence of Lipopolysaccharide, a Signature of the Classical Gram-Negative Outer Membrane
Authors: Mahat Rajendra , Seebart Corrine , Basile Franco , Ward Naomi L.
Published: October 2015

Planctomycete bacteria possess many unusual cellular properties, contributing to a cell plan long considered to be unique among the bacteria. However, data from recent studies are more consistent with a modified Gram-negative cell plan. A key feature of the Gram-negative plan is the presence of an outer membrane (OM), for which lipopolysaccharide (LPS) is a signature molecule. Despite genomic evidence for an OM in planctomycetes, no biochemical verification has been reported. We attempted to detect and characterize LPS in the planctomycete
Gemmata obscuriglobus
. We obtained direct evidence for LPS and lipid A using electrophoresis and differential staining. Gas chromatography-mass spectrometry (GC-MS) compositional analysis of LPS extracts identified eight different 3-hydroxy fatty acids (3-HOFAs), 2-keto 3-deoxy-
d
-manno-octulosonic acid (Kdo), glucosamine, and hexose and heptose sugars, a chemical profile unique to Gram-negative LPS. Combined with molecular/structural information collected from matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) MS analysis of putative intact lipid A, these data led us to propose a heterogeneous hexa-acylated lipid A structure (multiple-lipid A species). We also confirmed previous reports of
G. obscuriglobus
whole-cell fatty acid (FA) and sterol compositions and detected a novel polyunsaturated FA (PUFA). Our confirmation of LPS, and by implication an OM, in
G. obscuriglobus
raises the possibility that other planctomycetes possess an OM. The pursuit of this question, together with studies of the structural connections between planctomycete LPS and peptidoglycans, will shed more light on what appears to be a planctomycete variation on the Gram-negative cell plan.

IMPORTANCE
Bacterial species are classified as Gram positive or negative based on their cell envelope structure. For 25 years, the envelope of planctomycete bacteria has been considered a unique exception, as it lacks peptidoglycan and an outer membrane (OM). However, the very recent detection of peptidoglycan in planctomycete species has provided evidence for a more conventional cell wall and raised questions about other elements of the cell envelope. Here, we report direct evidence of lipopolysaccharide in the planctomycete
G. obscuriglobus
, suggesting the presence of an OM and supporting the proposal that the planctomycete cell envelope is an extension of the canonical Gram-negative plan. This interpretation features a convoluted cytoplasmic membrane and expanded periplasmic space, the functions of which provide an intriguing avenue for future investigation.
Unplanned admissions and the organisational management of heart failure: a multicentre ethnographic, qualitative study
Authors: Simmonds Rosemary , Glogowska Margaret , McLachlan Sarah , Cramer Helen , Sanders Tom , Johnson Rachel , Kadam Umesh , Lasserson Daniel , Purdy Sarah
Published: October 2015

Objectives

Heart failure is a common cause of unplanned hospital admissions but there is little evidence on why, despite evidence-based interventions, admissions occur. This study aimed to identify critical points on patient pathways where risk of admission is increased and identify barriers to the implementation of evidence-based interventions.

Design

Multicentre, longitudinal, patient-led ethnography.

Setting

National Health Service settings across primary, community and secondary care in three geographical locations in England, UK.

Participants

31 patients with severe or difficult to manage heart failure followed for up to 11 months; 9 carers; 55 healthcare professionals.

Results

Fragmentation of healthcare, inequitable provision of services and poor continuity of care presented barriers to interventions for heart failure. Critical points where a reduction in the risk of current or future admission occurred throughout the pathway. At the beginning some patients did not receive a formal clinical diagnosis, in addition patients lacked information about heart failure, self-care and knowing when to seek help. Some clinicians lacked knowledge about diagnosis and management. Misdiagnoses of symptoms and discontinuity of care resulted in unplanned admissions. Approaching end of life, patients were admitted to hospital when other options including palliative care could have been appropriate.

Conclusions

Findings illustrate the complexity involved in caring for people with heart failure. Fragmented healthcare and discontinuity of care added complexity and increased the likelihood of suboptimal management and unplanned admissions. Diagnosis and disclosure is a vital first step for the patient in a journey of acceptance and learning to self-care/monitor. The need for clinician education about heart failure and specialist services was acknowledged. Patient education should be seen as an ongoing ‘conversation’ with trusted clinicians and end-of-life planning should be broached within this context.