bluuebunny/crossref_metadata_2025 huggingface dataset:
How efficiently do corn‐ and soybean‐based cropping systems use water? A systems modeling analysis
Authors: Dietzel Ranae , Liebman Matt , Ewing Robert , Helmers Matt , Horton Robert , Jarchow Meghann , Archontoulis Sotirios
Published: September 2015

Agricultural systems are being challenged to decrease water use and increase production while climate becomes more variable and the world's population grows. Low water use efficiency is traditionally characterized by high water use relative to low grain production and usually occurs under dry conditions. However, when a cropping system fails to take advantage of available water during wet conditions, this is also an inefficiency and is often detrimental to the environment. Here, we provide a systems‐level definition of water use efficiency (sWUE) that addresses both production and environmental quality goals through incorporating all major system water losses (evapotranspiration, drainage, and runoff). We extensively calibrated and tested the Agricultural Production Systems sIMulator (APSIM) using 6 years of continuous crop and soil measurements in corn‐ and soybean‐based cropping systems in central Iowa, USA. We then used the model to determine water use, loss, and grain production in each system and calculated sWUE in years that experienced drought, flood, or historically average precipitation. Systems water use efficiency was found to be greatest during years with average precipitation. Simulation analysis using 28 years of historical precipitation data, plus the same dataset with ± 15% variation in daily precipitation, showed that in this region, 430 mm of seasonal (planting to harvesting) rainfall resulted in the optimum sWUE for corn, and 317 mm for soybean. Above these precipitation levels, the corn and soybean yields did not increase further, but the water loss from the system via runoff and drainage increased substantially, leading to a high likelihood of soil, nutrient, and pesticide movement from the field to waterways. As the Midwestern United States is predicted to experience more frequent drought and flood, inefficiency of cropping systems water use will also increase. This work provides a framework to concurrently evaluate production and environmental performance of cropping systems.
Impact of onabotulinumtoxinA on quality of life and practical aspects of daily living: A pooled analysis of two randomized controlled trials
Authors: Everaert Karel , Gruenenfelder Jennifer , Schulte‐Baukloh Heinrich , Egerdie Russell B , Khalaf Kristin , Joshi Manher , Ni Quanhong , Sussman David
Published: September 2015

Objective

To evaluate the impact of onabotulinumtoxinA on individual domains of the quality of life questionnaires in a pooled analysis of two phase 3 trials in overactive bladder patients with urinary incontinence who were inadequately managed by ≥1 anticholinergic.

Methods

Patients received intradetrusor injections of onabotulinumtoxinA 100U (n = 557) or placebo (n = 548). The proportions of patients with a positive response (condition “greatly improved” or “improved”) on the Treatment Benefit Scale, and changes in Incontinence Quality of Life scores and King's Health Questionnaire domain scores were analyzed in the overall population and subgroups with clean intermittent catheterization use and urinary tract infection status during the first 12 weeks of treatment. Responses to individual King's Health Questionnaire items were also assessed.

Results

Significantly greater proportions of onabotulinumtoxinA‐treated patients achieved positive Treatment Benefit Scale response versus placebo (61.8% vs 28.0%; P < 0.001). OnabotulinumtoxinA showed significantly greater improvements versus placebo in Incontinence Quality of Life total (22.5 vs 6.6), Incontinence Quality of Life subscale scores and all domains of the King's Health Questionnaire. Notably, a similar trend was observed regardless of clean intermittent catheterization/urinary tract infection status. Additionally, onabotulinumtoxinA resulted in significantly greater improvements than the placebo in practical aspects of patients daily lives, including pad use, need to change undergarments, sleep, relationship with partner and work life/daily activities.

Conclusion

In overactive bladder patients with urinary incontinence, onabotulinu‐mtoxinA 100U demonstrated significant improvements across the individual domains of the quality of life questionnaires, regardless of clean intermittent catheterization or urinary tract infection status, and provided a positive impact on practical aspects of patients' daily lives.
Failure of botulinum toxin injection for neurogenic detrusor overactivity: Switch of toxin versus second injection of the same toxin
Authors: Peyronnet Benoit , Castel‐Lacanal Evelyne , Manunta Andréa , Roumiguié Mathieu , Marque Philippe , Rischmann Pascal , Gamé Xavier
Published: September 2015

Objectives

To evaluate the efficacy of a second injection of the same toxin versus switching to a different botulinum toxin A after failure of a first detrusor injection in patients with neurogenic detrusor overactivity.

Methods

The charts of all patients who underwent detrusor injections of botulinum toxin A (either abobotulinumtoxinA or onabotulinumtoxinA) for the management of neurogenic detrusor overactivity at a single institution were retrospectively reviewed. Patients in whom a first detrusor injection had failed were included in the present study. They were managed by a second injection of the same toxin at the same dosage or by a new detrusor injection using a different botulinum toxin A. Success was defined as a resolution of urgency, urinary incontinence and detrusor overactivity in a patient self‐catheterizing seven times or less per 24 h.

Results

A total of 58 patients were included for analysis. A toxin switch was carried out in 29 patients, whereas the other 29 patients received a reinjection of the same toxin at the same dose. The success rate was higher in patients who received a toxin switch (51.7% vs 24.1%, P = 0.03). Patients treated with a switch from abobotulinumtoxinA to onabotulinumtoxinA and those treated with a switch from onabotulinumtoxinA to abobotulinumtoxinA had similar success rates (52.9% vs 50%, P = 0.88).

Conclusion

After failure of a first detrusor injection of botulinum toxin for neurogenic detrusor overactivity, a switch to a different toxin seems to be more effective than a second injection of the same toxin. The replacement of onabotulinumtoxin by abobotulinumtoxin or the reverse provides similar results.
Multiple Measures of Fixation on Social Content in Infancy: Evidence for a Single Social Cognitive Construct?
Authors: Gillespie‐Smith Karri , Boardman James P. , Murray Ian C. , Norman Jane E. , O'Hare Anne , Fletcher‐Watson Sue
Published: September 2015

The preference of infants to fixate on social information in a stimulus is well known. We examine how this preference manifests across a series of free‐viewing tasks using different stimulus types. Participants were thirty typically developing infants. We measured eye movements when viewing isolated faces, faces alongside objects in a grid, and faces naturally presented in photographed scenes. In each task, infants fixated social content for longer than nonsocial content. Social preference scores representing distribution of fixation to social versus general image content were highly correlated and thus combined into a single composite measure, which was independent of demographic and behavioral measures. We infer that multiple eye‐tracking tasks can be used to generate a composite measure of social preference in infancy. This approach may prove useful in the early characterization of developmental disabilities.
Three‐dimensional structure of seminiferous tubules in the adult mouse
Authors: Nakata Hiroki , Wakayama Tomohiko , Sonomura Takahiro , Honma Satoru , Hatta Toshihisa , Iseki Shoichi
Published: September 2015

Seminiferous tubules develop from sex cords, which are embryonic structures with simple C‐shaped arches. Histologically, the epithelium of adult mouse seminiferous tubules has been divided into 12 stages based on the associations of spermatogenic cells in four cycles of spermatogenesis. However, the gross characteristics of the seminiferous tubules themselves, including their number, length, run, and mutual relationships remain largely unknown. In the present study, we analyzed all seminiferous tubules in a single adult mouse testis with high resolution using serial paraffin sections and high‐perfomance three‐dimensional reconstruction software. There were 11 seminiferous tubules with an average length of 140 mm. Each tubule ran along circular paths within the testis while making convolutions with cranial and caudal hairpin turns. The cranial turns of all tubules were in contact with the tunica albuginea, whereas the caudal turns were not, resulting in funnel‐shaped networks of these tubules with tapered caudal portions. The caudally located networks surrounded the preceding cranially located networks from the bottom and outside, similar to stacked paper cups. Five out of the 11 seminiferous tubules were continuous from one end to the other both connected with the rete testis (10 connection points). Nine branching points, one blind end, and 18 more connection points with the rete testis were detected in the remaining six seminiferous tubules, making the paths of these tubules complicated to various degrees. The present study revealed that the 3D structures of seminiferous tubules were highly regular as a whole in the adult mouse testis.
Optimal preservation of porcine cardiac tissue prior to diffusion tensor magnetic resonance imaging
Authors: Agger Peter , Lass Thomas , Smerup Morten , Frandsen Jesper , Pedersen Michael
Published: September 2015

The effects of ex vivo preservation techniques on the quality of diffusion tensor magnetic resonance imaging in hearts are poorly understood, and the optimal handling procedure prior to investigation remains to be determined. Therefore, 24 porcine hearts were examined in six groups treated with different preservation techniques, including chemical fixation and freezing. Diffusion properties of each heart were assessed with diffusion tensor imaging in terms of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da) and radial diffusivity (Dr). Tractography was performed to visualize the course of the cardiomyocytes, assuming greater diffusivity in the longitudinal than the transverse axis of individual cardiomyocytes. Significant differences in MD, Da and Dr were found, as well as in FA between groups (P < 0.001). Freezing of specimens resulted in the lowest mean FA of 0.21 (0.06) and highest Dr of 8.92 (1.5) mm2 s−1. The highest mean FA was found to be 0.43 (0.11) in hearts perfusion‐fixed with formalin. Calculated tractographies were indistinguishable among groups except in frozen specimens, where no fibres could be tracked. Perfusion fixation with formalin provided the best tractography, but immersion fixation yielded diffusion data most similar to fresh hearts. These findings suggest that parameters derived from diffusion tensor imaging in ex vivo hearts are sensitive to fixation and storage methods. In particular, freezing of specimens should be avoided prior to diffusion tensor imaging investigation due to significant changes in diffusion parameters and subsequent image deteriorations.
Paradoxical Utopia: The Millennium Villages Project in Theory and Practice
Authors: Wilson Japhy
Published: September 2015

The Millennium Villages Project (MVP) aims to achieve the Millennium Development Goals in villages across sub‐Saharan Africa, through an integrated set of interventions designed to catalyse the transformation of ‘sub‐subsistence farmers’ into ‘small‐scale entrepreneurs’. I conceptualize the MVP as a paradoxical utopia, which is attempting to socially produce the supposedly natural order of a market society, through the staging of a fantasy of harmonious capitalist development that misrepresents the realities of rural African capitalism. Drawing on field research conducted in the Millennium Villages of Ruhiira, Uganda, and Bonsaaso, Ghana, I show how the conceptual failings of the MVP have led to the elite capture of project inputs, the absence of inclusive participation and a lack of long‐term sustainability. In Ruhiira, the MVP has contributed to the consolidation of existing relations of inequality, while in Bonsaaso it has been overwhelmed by an influx of foreign gold miners. Through its failure to stage its fantasy of capitalist development in these cases, the MVP has paradoxically succeeded in consolidating the actual social relations of capitalism.
The Effect of Three Times a Week Glatiramer Acetate on Cerebral T1 Hypointense Lesions in Relapsing‐Remitting Multiple Sclerosis
Authors: Zivadinov Robert , Dwyer Michael G. , Ramasamy Deepa P. , Davis Mat D. , Steinerman Joshua R. , Khan Omar
Published: September 2015

BACKGROUND AND PURPOSE

Two definitions of T1 hypointense (T1H) lesions can be derived from pre‐contrast images: those that may or may not have a corresponding gadolinium‐enhancing correlate on post‐contrast images (T1H total), and those that are simultaneously non‐gadolinium‐enhancing on post‐contrast scans (T1H non‐enhancing). To determine the differences in lesion evolution between these two T1H definitions, we examined the effect of glatiramer acetate 40 mg/mL three times weekly subcutaneous injection (GA40) on the number of new or enlarging T1H total and T1H non‐enhancing lesions in patients with relapsing‐remitting multiple sclerosis (RRMS).

METHODS

The Phase III GALA study randomized 1404 RRMS subjects 2:1 to receive GA40 or placebo for 12 months. MRI scans were obtained at baseline and at months 6 and 12. Cumulative numbers of T1H total and of T1H non‐enhancing lesions were analyzed using an adjusted negative binomial regression model. A total of 1,357 patients had MRI data collected at either the month 6 or month 12 visit.

RESULTS

Among the 1,357 patients with MRI scans performed at either the month 6 or month 12 visit, 883 treated with GA40 developed an adjusted cumulative mean of 1.72 T1H total lesions versus 2.62 in 440 placebo controls (risk ratio, .66; 95% CI, .54‐.80; P < .0001). On T1H non‐enhanced scans, GA40‐treated patients developed an adjusted cumulative mean of 1.35 T1H non‐enhancing lesions versus 1.91 in placebo controls (risk ratio, .71; CI, .58‐.87; P = .0009).

CONCLUSIONS

GA40 significantly reduced the number of new or enlarging T1H total lesions and T1H non‐enhancing lesions compared with placebo. Although the treatment effect magnitude was comparable with both definitions, the use of T1H non‐enhancing lesions may be more relevant for more uniform standardization in future clinical trials.
Determination of the status of stakeholder participation in the management of the Lake Malawi basin through application of Integrated Lake Basin Management
Authors: Chidammodzi C. L. , Muhandiki V. S.
Published: September 2015

Lake Malawi is the southernmost of the Great Rift Valley Lakes of Africa and boasts the world's greatest freshwater fish biodiversity. Along with its basin, the lake provides many benefits to the country of Malawi. Settlements, agriculture and fishing are some of the major uses of the lake basin, making community involvement a necessary component of its management. With the use of key informant interviews, questionnaire survey, document review and site observations, this study demonstrates the applicability of the Integrated Lake Basin Management framework in the Lake Malawi Basin in regard to stakeholder participation. The main objective was to assess the participation of stakeholders, especially local communities, in the management of the lake basin. The framework applied in this study is discussed. The study findings indicate strong to very strong stakeholder participation, with notably high levels of awareness and women's involvement. Enhancing the understanding of the complex nature of lake basin issues, especially those related to the linkages between the water body and the basin, is a topic requiring further attention.
Self‐Healing Extranodal Cutaneous Rosai‐Dorfman in a Child
Authors: Toledo del Castillo Blanca , Mata‐Fernández Cristina , Rodríguez Soria Virna J. , Parra Blanco Verónica , Loughlin Gerard , Campos‐Domínguez Minia
Published: September 2015

Sinus histiocytosis with massive lymphadenopathy, or Rosai‐Dorfman disease (RDD), is commonly characterized by painless cervical lymphadenopathy. Exclusively cutaneous Rosai‐Dorfman disease is rare. In the absence of massive lymphadenopathy, the nonspecific skin lesions may complicate the diagnosis. To our knowledge, the case reported herein is the youngest case of extranodal cutaneous RDD.
Neonatal Hairy Ear Pinnae and Gestational Diabetes: Just a Coincidence?
Authors: Valerio Enrico , Riello Laura , Chirico Michela , Semenzato Rossella , Cutrone Mario
Published: September 2015

A newborn girl of 36 weeks gestation was noted to have several anomalies, including bilateral low ear attachment with ear pinnae hypertrichosis, left preauricular pit, micrognathia, short lingual frenulum, and short neck. Pregnancy history revealed poorly controlled maternal gestational diabetes (GD). Localized hypertrichosis of the ear pinnae may represent a potential marker of GD and thereby alert physicians to suspect other potentially GD‐associated conditions such as macrosomia, asphyxia, respiratory distress, hypoglycemia, hypocalcemia, hyperbilirubinemia, polycythemia, hypertrophic cardiomyopathy, and congenital anomalies, particularly those involving the central nervous system.
The U.S. Pediatric Dermatology Workforce: An Assessment of Productivity and Practice Patterns
Authors: Fogel Alexander L. , Teng Joyce M. C.
Published: September 2015

Background

Pediatric dermatology has always played an important role in children's healthcare, but there has been a shortage of pediatric dermatologists nationwide for more than a decade, and few metrics of productivity and practice patterns exist. This study sought to provide insight into these and other factors of the pediatric dermatology workforce.

Methods

Electronic surveys were distributed to all 226 U.S. board‐certified pediatric dermatologists.

Results

A total of 108/226 (48%) of the electronic surveys were returned. Sixty percent of respondents were employed full‐ or part‐time in academic environments and 81% were salaried. Respondents reported that children constituted 79.5% of their practice, and the average respondent spent 3.8 days/week treating 92.6 patients, considerably lower than the 136.3 patients/week that the average general dermatologist sees. The academic practice environment was associated with children constituting a larger proportion of the practice (p < 0.001), fewer patients seen per week (85.9, p < 0.001), and longer median new patient wait times (60 vs 15 days) than in other practice environments. Private practitioners saw significantly more patients per week than those in academic environments (112.7, p = 0.005). Male and female practitioners reported approximately equal patient care days per week, similar wait times, and similar proportions of children in their practices.

Conclusions

This assessment revealed productivity and practice pattern differences between the various pediatric dermatology practice environments and between pediatric and general dermatology. This study provides important information for workforce planning and care availability assessments and baseline information for future studies.
A first insight into the scanning behaviour of the presocial blow fly larvae
Authors: Boulay Julien , Betremieux Cécile , Hédouin Valéry , Charabidzé Damien
Published: September 2015

Aggregation of necrophagous larvae has several benefits: the sharing of salivary enzymes (exodigestion), temperature regulation, protection from predators and parasites, etc., and is well developed in blow flies (Diptera:Calliphoridae). The present study focuses on the aggregation mechanism used by the necrophagous larvae ofLucilia sericataMeigen, the common green bottle fly. The ability of single larva to detect and follow a signal (trail) created by conspecifics is investigated initially. A circular ring is drawn in aPetri dish where 20 starved larvae have crawled for a period of 30 min. A naïve (test) larva is then placed in the dish and video‐tracked. Naïve larvae are able to detect the boundaries of the larvae‐crawled area and stay preferentially within this conspecific‐marked zone. In a second step, the orientation of larvae by scanning, a dedicated, ground‐signal detection behaviour of dipteran larvae, is analyzed. Four experimental conditions are tested: control, presence of food, conspecifics, and food + conspecifics. When conspecifics have been previously present in a given area, the scanning behaviour by naïve larvae in this area decreases (both in number and frequency of scans). Accordingly, scanning by necrophagous larvae ofL. sericatashould be considered not only as locomotion behaviour, but also as a potential way to detect signals from conspecifics for the purpose of aggregation. The chemical composition of the attractant(s), the behavioural effects (attraction or retention) and the implication of larval signalling in the aggregation process are new fields to explore.
Gene Expression and Localization of NGF and Its Cognate Receptors NTRK1 and NGFR in the Sex Organs of Male Rabbits
Authors: Maranesi M , Zerani M , Leonardi L , Pistilli A , Arruda‐Alencar J , Stabile AM , Rende M , Castellini C , Petrucci L , Parillo F , Moura A , Boiti C
Published: September 2015

Contents

Experiments were devised to characterize the expression of nerve growth factor, beta polypeptide (NGF), and its cognate receptors neurotrophic tyrosine kinase receptor type 1 (NTRK1) and nerve growth factor receptor (NGFR) in rabbit male sex organs, as well as the concentrations of NGF in both seminal and blood plasma of sexually mature male rabbits. Immunoreactivity and gene expression for NGF and cognate receptors were detected in testis, prostate gland and seminal vesicle. The highest levels of NGF and NTRK1 transcripts were found in the prostate, while intermediate expressions were found in the testis. NGFR transcripts were expressed at the same levels in both testis and prostate and were more abundant than in seminal vesicles. The widespread distribution of NGF in all prostate glandular cells, together with its relative high mRNA abundance, confirms that the prostate of rabbits is the main source of this neurotrophin. In conclusion, the present data suggest that the NGF system is involved in the testicular development and spermatogenesis of rabbits and that NGF may act as a potential ovulation‐inducing factor being abundantly present in the seminal plasma.
Services Productivity, Trade Policy and Manufacturing Exports
Authors: Hoekman Bernard , Shepherd Ben
Published: September 2015

This paper analyses the linkage between services and manufacturing productivity performance, using firm‐level data for over 100 developing countries. We find strong evidence for such a linkage, although the effect is small: at the average rate of services input intensity, a 10 per cent improvement in services productivity is associated with an increase in manufacturing productivity of 0.3 per cent. Services trade restrictiveness indices are found to be a statistically significant determinant of manufactured exports performance, a finding that is robust to the inclusion of the overall level of trade restrictiveness that is applied against manufactured exports directly. The main channel through which services trade restrictions negatively affect manufactured exports is through FDI, a finding that is consistent with the stylised fact in the literature that FDI is a key channel for trade in services and an important vehicle through which services technology and know‐how is transferred across countries. At the sectoral level, restrictions on transport and retail distribution services have the largest negative impact on exports of manufactures.
The two-color Soergel calculus
Authors: Elias Ben
Published: September 2015

We give a diagrammatic presentation for the category of Soergel bimodules for the dihedral group$W$. The (two-colored) Temperley–Lieb category is embedded inside this category as the degree$0$morphisms between color-alternating objects. The indecomposable Soergel bimodules are the images of Jones–Wenzl projectors. When$W$is infinite, the parameter$q$of the Temperley–Lieb algebra may be generic, yielding a quantum version of the geometric Satake equivalence for$\mathfrak{sl}_{2}$. When$W$is finite,$q$must be specialized to an appropriate root of unity, and the negligible Jones–Wenzl projector yields the Soergel bimodule for the longest element of$W$.
Spatial fractionation of the dose using neon and heavier ions: A Monte Carlo study
Authors: Peucelle C. , Martínez‐Rovira I. , Prezado Y.
Published: September 2015

Purpose:

This work explores a new radiation therapy approach which might trigger a renewed use of neon and heavier ions to treat cancers. These ions were shown to be extremely efficient in radioresistant tumor killing. Unfortunately, the efficient region also extends into the normal tissue in front of the tumor. The strategy the authors propose is to profit from the well‐established sparing effect of thin spatially fractionated beams, so that the impact on normal tissues might be minimized while a high tumor control is achieved. The main goal of this work is to provide a proof of concept of this new approach. With that aim, a dosimetric study was carried out as a first step to evaluate the interest of further explorations of this avenue.

Methods:

The gate/geant4 v.6.1 Monte Carlo simulation platform was employed to simulate arrays of rectangular minibeams (700 μm × 2 cm) of four ions (Ne, Si, Ar, and Fe). The irradiations were performed with a 2 cm‐long spread‐out Bragg peak centered at 7 cm‐depth. Dose distributions in a water phantom were scored considering two minibeams center‐to‐center distances: 1400 and 3500 μm. Peak and valley doses, peak‐to‐valley dose ratios (PVDRs), beam penumbras, and relative contribution of nuclear fragments and electromagnetic processes were assessed as figures of merit. In addition, the type and proportion of the secondary nuclear fragments were evaluated in both peak and valley regions.

Results:

Extremely high PVDR values (>100) and low valley doses were obtained. The higher the atomic number (Z) of the primary ion is, the lower the valleys and the narrower the penumbras. Although the yield of secondary nuclear products increases with Z, the actual dose being deposited by the secondary nuclear fragments in the valleys starts to be the dominant contribution at deeper points, helping in the sparing of proximal normal tissues. Additionally, a wider center‐to‐center distance leads to a minimized contribution of heavier secondary fragments in valleys.

Conclusions:

The computed dose distributions suggest that a spatial fractionation of the dose combined to the use of submillimetric field sizes might allow profiting from the high efficiency of neon and heavier ions for the treatment of radioresistant tumors, while preserving normal tissues. The authors’ results support the further exploration of this avenue. Next steps include the realization of biological experiment to confirm the shifting of normal tissue complication probability curves.
Your daily drug resets your clock
Authors: Kelner Katrina L.
Published: September 2015

Caffeine delays the human circadian clock and affects cellular timekeeping through an adenosine receptor–dependent mechanism.
Microbiological Assessment of Polymyxin B Components Tested Alone and in Combination
Authors: Kassamali Zahra , Prince Randall A. , Danziger Larry H. , Rotschafer John C. , Rhomberg Paul R. , Jones Ronald N.
Published: September 2015

We investigated the antimicrobial activity of four polymyxin B components, B1, B2, B3, and isoleucine (Ile)-B1, individually and in combination. B3 was the most active agent against all organisms tested except
Acinetobacter baumannii
, for which Ile-B1 was most active. One combination met the criteria for synergy, B3 plus Ile-B1. No combinations exhibited antagonism. The dominant components of polymyxin B products (B1 and B2) were associated with the lowest probability of improved antibacterial activity when combined.
Role of Semen on Vaginal HIV-1 Transmission and Maraviroc Protection
Authors: Council Olivia D. , Swanson Michael D. , Spagnuolo Rae Ann , Wahl Angela , Garcia J. Victor
Published: September 2015

We used bone marrow/liver/thymus (BLT) humanized mice to establish the effect of semen on vaginal HIV infection and on the efficacy of topically applied maraviroc. Our results demonstrate that vaginal transmission of cell-free HIV occurs efficiently in the presence of semen and that topically applied maraviroc efficiently prevents HIV transmission in the presence of semen. We also show that semen has no significant effect on the transmission of transmitted/founder viruses or cell-associated viruses.
Bactericidal Effect of Tomatidine-Tobramycin Combination against Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa Is Enhanced by Interspecific Small-Molecule Interactions
Authors: Boulanger Simon , Mitchell Gabriel , Bouarab Kamal , Marsault Éric , Cantin André , Frost Eric H. , Déziel Eric , Malouin François
Published: September 2015

This study investigated the antibacterial activity of the plant alkaloid tomatidine (TO) against
Staphylococcus aureus
grown in the presence of
Pseudomonas aeruginosa
. Since the
P. aeruginosa
exoproduct 4-hydroxy-2-heptylquinoline-
N
-oxide (HQNO) is known to cause a respiratory deficiency in
S. aureus
and respiratory-deficient
S. aureus
are known to be hypersensitive to TO, we assessed kill kinetics of TO (8 μg/ml) against
S. aureus
in coculture with
P. aeruginosa
. Kill kinetics were also assessed using
P. aeruginosa
mutants deficient in the production of different exoproducts and quorum sensing-related compounds. After 24 h in coculture, TO increased the killing of
S. aureus
by 3.4 log
10
CFU/ml in comparison to that observed in a coculture without TO. The effect of TO was abolished when
S. aureus
was in coculture with the
lasR
rhlR
,
pqsA
,
pqsL
, or
lasA
mutant of
P. aeruginosa
. The bactericidal effect of TO against
S. aureus
in coculture with the
pqsL
mutant was restored by supplemental HQNO. In an
S. aureus
monoculture, the combination of HQNO and TO was bacteriostatic, indicating that the
pqsL
mutant produced an additional factor required for the bactericidal effect. The bactericidal activity of TO was also observed against a tobramycin-resistant methicillin-resistant
S. aureus
(MRSA) in coculture with
P. aeruginosa
, and the addition of tobramycin significantly suppressed the growth of both microorganisms. TO shows a strong bactericidal effect against
S. aureus
when cocultured with
P. aeruginosa
. The combination of TO and tobramycin may represent a new treatment approach for cystic fibrosis patients frequently cocolonized by MRSA and
P. aeruginosa
.
In Vivo
Evolution of CMY-2 to CMY-33 β-Lactamase in Escherichia coli Sequence Type 131: Characterization of an Acquired Extended-Spectrum AmpC Conferring Resistance to Cefepime
Authors: Pires João , Taracila Magdalena , Bethel Christopher R. , Doi Yohei , Kasraian Sara , Tinguely Regula , Sendi Parham , Bonomo Robert A. , Endimiani Andrea
Published: September 2015

Cefepime is frequently prescribed to treat infections caused by AmpC-producing Gram-negative bacteria. CMY-2 is the most common plasmid-mediated AmpC (pAmpC) β-lactamase. Unfortunately, CMY variants conferring enhanced cefepime resistance have been reported. Here, we describe the evolution of CMY-2 to an extended-spectrum AmpC (ESAC) in clonally identical
Escherichia coli
isolates obtained from a patient. The CMY-2-producing
E. coli
isolate (CMY-2-
Ec
) was isolated from a wound. Thirty days later, one CMY-33-producing
E. coli
isolate (CMY-33-
Ec
) was detected in a bronchoalveolar lavage fluid sample. Two weeks before the isolation of CMY-33-
Ec
, the patient received cefepime. CMY-33-
Ec
and CMY-2-
Ec
were identical by repetitive extragenic palindromic-PCR (rep-PCR), being of hyperepidemic sequence type 131 (ST131) but showing different β-lactam MICs (e.g., cefepime MIC, 16 and ≤0.5 μg/ml for CMY-33-
Ec
and CMY-2-
Ec
, respectively). Identical CMY-2-
Ec
isolates were also found in a rectal swab. CMY-33 differs from CMY-2 by a Leu293-Ala294 deletion. Expressed in
E. coli
strain DH10B, both CMYs conferred resistance to ceftazidime (≥256 μg/ml), but the cefepime MICs were higher for CMY-33 than CMY-2 (8 versus 0.25 μg/ml, respectively). The
k
cat
/

K
m

or inhibitor complex inactivation (
k
inact
)/

K
i

app
(μM
−1
s
−1
) indicated that CMY-33 possesses an extended-spectrum β-lactamase (ESBL)-like spectrum compared to that of CMY-2 (e.g., cefoxitin, 0.2 versus 0.4; ceftazidime, 0.2 versus not measurable; cefepime, 0.2 versus not measurable; and tazobactam, 0.0018 versus 0.0009, respectively). Using molecular modeling, we show that a widened active site (∼4-Å shift) may play a significant role in enhancing cefepime hydrolysis. This is the first
in vivo
demonstration of a pAmpC that under cephalosporin treatment expands its substrate spectrum, resembling an ESBL. The prevalence of CMY-2-
Ec
isolates is rapidly increasing worldwide; therefore, awareness that cefepime treatment may select for resistant isolates is critical.
In Vitro
and
In Vivo
Investigation of the Inhibition of Trypanosoma brucei Cell Growth by Lipophilic Bisphosphonates
Authors: Yang Gyongseon , Zhu Wei , Kim Kuglae , Byun Soo Young , Choi Gahee , Wang Ke , Cha Jeong Seok , Cho Hyun-Soo , Oldfield Eric , No Joo Hwan
Published: September 2015

We report the results of a screen of a library of 925 potential prenyl synthase inhibitors against
Trypanosoma brucei
farnesyl diphosphate synthase (TbFPPS) and against
T. brucei
, the causative agent of human African trypanosomiasis. The most potent compounds were lipophilic analogs of the bone resorption drug zoledronate, some of which had submicromolar to low micromolar activity against bloodstream form
T. brucei
and selectivity indices of up to ∼300. We evaluated the effects of two such inhibitors on survival and parasitemia in a
T. brucei
mouse model of infection and found that survival increased by up to 16 days. We also investigated the binding of three lipophilic bisphosphonates to an expressed TbFPPS using crystallography and investigated the thermodynamics of binding using isothermal titration calorimetry.
Rate ofFKSMutations among Consecutive Candida Isolates Causing Bloodstream Infection
Authors: Shields Ryan K. , Nguyen M. Hong , Press Ellen G. , Cumbie Richard , Driscoll Eileen , Pasculle A. William , Clancy Cornelius J.
Published: September 2015

PreciseFKSmutation rates amongCandidaspecies are undefined because studies have not systematically screened consecutive, disease-causing isolates. The Sensititre YeastOne (SYO) assay measures echinocandin MICs againstCandidawith less variability than reference broth microdilution methods. However, clinical breakpoint MICs may overstate caspofungin nonsusceptibility compared to other agents. Our objectives were to determineCandidaFKSmutation rates by studying consecutive bloodstream isolates and to determine if discrepant susceptibility results were associated withFKSmutations.FKShot spots were sequenced in echinocandin-intermediate and -resistant isolates and those from patients with breakthrough candidemia or ≥3 days of prior echinocandin exposure. Overall, 453 isolates from 384 patients underwent susceptibility testing; 16% were echinocandin intermediate or resistant. Intermediate susceptibility rates were higher forCandida glabratathan for other species (P< 0.0001) and higher for caspofungin than for other agents (P< 0.0001). Resistance rates were similar between agents.FKSmutations were detected in 5% of sequenced isolates and 2% of isolates overall. Corresponding rates amongC. glabrataisolates were 8% and 4%, respectively. AmongCandida albicansisolates, rates were 5% and <1%, respectively. Mutations occurred exclusively with prior echinocandin exposure and were not detected in other species. Isolates with discrepant susceptibility results did not harborFKSmutations. Mutation rates among isolates resistant to ≥2, 1, and 0 agents were 75%, 13%, and 0%, respectively. In conclusion,FKSmutations were uncommon among non-C. glabrataspecies, even with prior echinocandin exposure. Discrepancies in echinocandin susceptibility by SYO testing were not driven by mutations and likely reflect imprecise caspofungin clinical breakpoints.
The FasX Small Regulatory RNA Negatively Regulates the Expression of Two Fibronectin-Binding Proteins in Group A Streptococcus
Authors: Danger Jessica L. , Makthal Nishanth , Kumaraswami Muthiah , Sumby Paul
Published: September 2015

The group A
Streptococcus
(GAS;
Streptococcus pyogenes
) causes more than 700 million human infections each year. The success of this pathogen can be traced in part to the extensive arsenal of virulence factors that are available for expression in temporally and spatially specific manners. To modify the expression of these virulence factors, GAS use both protein- and RNA-based regulators, with the best-characterized RNA-based regulator being the small regulatory RNA (sRNA) FasX. FasX is a 205-nucleotide sRNA that contributes to GAS virulence by enhancing the expression of the thrombolytic secreted virulence factor streptokinase and by repressing the expression of the collagen-binding cell surface pili. Here, we have expanded the FasX regulon, showing that this sRNA also negatively regulates the expression of the adhesion- and internalization-promoting, fibronectin-binding proteins PrtF1 and PrtF2. FasX posttranscriptionally regulates the expression of PrtF1/2 through a mechanism that involves base pairing to the
prtF1
and
prtF2
mRNAs within their 5′ untranslated regions, overlapping the mRNA ribosome-binding sites. Thus, duplex formation between FasX and the
prtF1
and
prtF2
mRNAs blocks ribosome access, leading to an inhibition of mRNA translation. Given that FasX positively regulates the expression of the spreading factor streptokinase and negatively regulates the expression of the collagen-binding pili and of the fibronectin-binding PrtF1/2, our data are consistent with FasX functioning as a molecular switch that governs the transition of GAS between the colonization and dissemination stages of infection.

IMPORTANCE
More than half a million deaths each year are a consequence of infections caused by GAS. Insights into how this pathogen regulates the production of proteins during infection may facilitate the development of novel therapeutic or preventative regimens aimed at inhibiting this activity. Here, we have expanded insight into the regulatory activity of the GAS small RNA FasX. In addition to identifying that FasX reduces the abundance of the cell surface-located fibronectin-binding proteins PrtF1/2, fibronectin is present in high abundance in human tissues, and we have determined the mechanism behind this regulation. Importantly, as FasX is the only mechanistically characterized regulatory RNA in GAS, it serves as a model RNA in this and related pathogens.
Bacillus anthracis lcp
Genes Support Vegetative Growth, Envelope Assembly, and Spore Formation
Authors: Liszewski Zilla Megan , Lunderberg J. Mark , Schneewind Olaf , Missiakas Dominique
Published: September 2015

Bacillus anthracis
, a spore-forming pathogen, replicates as chains of vegetative cells by regulating the separation of septal peptidoglycan. Surface (S)-layer proteins and
B. anthracis
S-layer-associated proteins (BSLs) function as chain length determinants and are assembled in the envelope by binding to the secondary cell wall polysaccharide (SCWP).
B. anthracis
expresses six different genes encoding LytR-CpsA-Psr (LCP) enzymes (
lcpB1
to -
4
,
lcpC
, and
lcpD
), which when expressed in
Staphylococcus aureus
promote attachment of wall teichoic acid to peptidoglycan. Mutations in
B. anthracis
lcpB3
and
lcpD
cause aberrations in cell size and chain length that can be explained as discrete defects in SCWP assembly; however, the function of the other
lcp
genes is not known. By deleting combinations of
lcp
genes from the
B. anthracis
genome, we generated variants with single
lcp
genes.
B. anthracis
expressing
lcpB3
alone displayed physiological cell size, vegetative growth, spore formation, and S-layer assembly. Strains expressing
lcpB1
or
lcpB4
displayed defects in cell size and shape, S-layer assembly, and spore formation yet sustained vegetative growth. In contrast, the
lcpB2
strain was unable to grow unless the gene was expressed from a multicopy plasmid (
lcpB2

++

), and variants expressing
lcpC
or
lcpD
displayed severe defects in growth and cell shape. The
lcpB2

++

,
lcpC
, or
lcpD
strains supported neither S-layer assembly nor spore formation. We propose a model whereby LCP enzymes fulfill partially overlapping functions in transferring SCWP molecules to discrete sites within the bacterial envelope.

IMPORTANCE
Products of genes essential for bacterial envelope assembly represent targets for antibiotic development. The LytR-CpsA-Psr (LCP) enzymes tether bactoprenol-linked intermediates of secondary cell wall polymers to the C6 hydroxyl of
N
-acetylmuramic acid in peptidoglycan; however, the role of LCPs as a target for antibiotic therapy is not defined. We show here that LCP enzymes are essential for the cell cycle, vegetative growth, and spore formation of
Bacillus anthracis
, the causative agent of anthrax disease. Furthermore, we assign functions for each of the six LCP enzymes, including cell size and shape, vegetative growth and sporulation, and S-layer and S-layer-associated protein assembly.
Involving migrants in the development of guidelines for communication in cross-cultural general practice consultations: a participatory learning and action research project
Authors: O'Reilly-de Brún Mary , MacFarlane Anne , de Brún Tomas , Okonkwo Ekaterina , Bonsenge Bokanga Jean Samuel , Manuela De Almeida Silva Maria , Ogbebor Florence , Mierzejewska Aga , Nnadi Lovina , van den Muijsenbergh Maria , van Weel-Baumgarten Evelyn , van Weel Chris
Published: September 2015

Objective

The aim of this research was to involve migrants and other key stakeholders in a participatory dialogue to develop a guideline for enhancing communication in cross-cultural general practice consultations. In this paper, we focus on findings about the use of formal versus informal interpreters because dialogues about these issues emerged as central to the identification of recommendations for best practice.

Design

This qualitative case study involved a Participatory Learning and Action (PLA) research methodology.

Participants

The sample comprised 80 stakeholders: 51 from migrant communities; 15 general practitioners (GPs) and general practice staff; 7 established migrants as peer researchers; 5 formal, trained interpreters; and 2 service planners from the national health authority.

Setting

Galway, Ireland.

Results

There was 100% consensus across stakeholder groups that while informal interpreters haveusesfor migrants and general practice staff, they are not consideredacceptableas best practice. There was also 100% consensus that formal interpreters who are trained and working as per a professional code of practice are acceptable as best practice.

Conclusions

Policymakers and service planners need to work in partnership with service providers and migrants to progress the implementation of professional, trained interpreters as a routine way of working in general practice.
Australia's 1996 gun law reforms: faster falls in firearm deaths, firearm suicides, and a decade without mass shootings
Authors: Chapman S , Alpers P , Agho K , Jones M
Published: September 2015

Background

After a 1996 firearm massacre in Tasmania in which 35 people died, Australian governments united to remove semi-automatic and pump-action shotguns and rifles from civilian possession, as a key component of gun law reforms.

Objective

To determine whether Australia's 1996 major gun law reforms were associated with changes in rates of mass firearm homicides, total firearm deaths, firearm homicides and firearm suicides, and whether there were any apparent method substitution effects for total homicides and suicides.

Design

Observational study using official statistics. Negative binomial regression analysis of changes in firearm death rates and comparison of trends in pre-post gun law reform firearm-related mass killings.

Setting

Australia, 1979–2003.

Main outcome measures

Changes in trends of total firearm death rates, mass fatal shooting incidents, rates of firearm homicide, suicide and unintentional firearm deaths, and of total homicides and suicides per 100 000 population.

Results

In the 18 years before the gun law reforms, there were 13 mass shootings in Australia, and none in the 10.5 years afterwards. Declines in firearm-related deaths before the law reforms accelerated after the reforms for total firearm deaths (p=0.04), firearm suicides (p=0.007) and firearm homicides (p=0.15), but not for the smallest category of unintentional firearm deaths, which increased. No evidence of substitution effect for suicides or homicides was observed. The rates per 100 000 of total firearm deaths, firearm homicides and firearm suicides all at least doubled their existing rates of decline after the revised gun laws.

Conclusions

Australia's 1996 gun law reforms were followed by more than a decade free of fatal mass shootings, and accelerated declines in firearm deaths, particularly suicides. Total homicide rates followed the same pattern. Removing large numbers of rapid-firing firearms from civilians may be an effective way of reducing mass shootings, firearm homicides and firearm suicides.
Acute effects of protein composition and fibre enrichment of yogurt consumed as snacks on appetite sensations and subsequent ad libitum energy intake in healthy men
Authors: Doyon Caroline Y. , Tremblay Angelo , Rioux Laurie-Eve , Rhéaume Caroline , Cianflone Katherine , Poursharifi Pegah , Turgeon Sylvie L.
Published: September 2015

The objective of the study was to assess the impact of protein composition and/or fibre enrichment of yogurt on appetite sensations and subsequent energy intake. In this double-blind crossover study, 20 healthy men (aged 32.4 ± 9.1 years) were submitted to 5 randomized testing sessions, during which they had to consume 5 isocaloric and isonproteinemic yogurt snacks (120-g servings, ∼230 kJ, ∼4.5 g protein) differing by their casein-to-whey protein ratio (C:W) or dietary fibre content: (i) control C:W = 2.8:1; (ii) high whey (HW) C:W = 1.5:1, and fibre-enriched formulations using control; (iii) 2.4 g of inulin; (iv) 1.9 g of inulin and 0.5 g of β-glucan (+IN-βG); and (v) 0.5 g of β-glucan. Appetite sensations were assessed using 150-mm visual analog scales. Plasma variables (glucose, insulin, ghrelin) were measured at 30-min intervals post-yogurt consumption for 2 h. Finally, energy intakes during ad libitum lunches offered 2 h after yogurt snacks were recorded. None of the yogurts impacted appetite sensations. Ad libitum energy intake was significantly different only between HW and control yogurts (–812 kJ; p = 0.03). Regarding post-yogurt plasma variables, a significant difference was found only between ghrelin area under the curve of the +IN-βG and the HW yogurts (–15 510 pmol/L per 120 min, p = 0.04). In conclusion, although appetite sensations were not influenced by variations in yogurts’ protein compositions, a reduced energy intake was observed during the ad libitum lunch after the HW yogurt that may be attributable to its lower C:W. Surprisingly, the fibre enrichments studied did not exert effect on appetite sensations and energy intake.