bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficiency and Market Power Gains in Bank Megamergers: Evidence from Value Line Forecasts
Authors: Devos Erik , Krishnamurthy Srinivasan , Narayanan Rajesh
Published: April 2016

This paper examines whether gains in bank megamergers occur due to efficiency improvements or the exercise of market power using financial statement line item forecasts from Value Line to infer the effect of the merger on prices and quantities. The average megamerger is associated with cost‐efficiency improvements. In the cross‐section, efficiency gains are limited to market expansion mergers while market overlap mergers and Too‐Big‐To‐Fail (TBTF) mergers exhibit monopoly gains. Efficiency gains dissipate when the resulting megabank size exceeds $150 billion in assets or 1.5% of gross domestic product indicating that banks thought to be TBTF are likely to be “Too‐Big‐To‐Be‐Efficient.”
Climate warming is predicted to reduce omega‐3, long‐chain, polyunsaturated fatty acid production in phytoplankton
Authors: Hixson Stefanie M. , Arts Michael T.
Published: April 2016

Phytoplankton are the main source of energy and omega‐3 (n‐3) long‐chain essential fatty acids (EFA) in aquatic ecosystems. Their growth and biochemical composition are affected by surrounding environmental conditions, including temperature, which continues to increase as a result of climate warming. Increasing water temperatures may negatively impact the production of EFA by phytoplankton through the process of homeoviscous adaptation. To investigate this, we conducted an exploratory data synthesis with 952 fatty acid (FA) profiles from six major groups of marine and freshwater phytoplankton. Temperature was strongly correlated with a decrease in the proportion of n‐3 long‐chain polyunsaturated FA (LC‐PUFA) and an increase in omega‐6 FA and saturated FA. Based on linear regression models, we predict that global n‐3 LC‐PUFA production will be reduced by 8.2% for eicosapentaenoic acid (EPA) and 27.8% for docosahexaenoic acid (DHA) with an increase in water temperature of 2.5 °C. Using a previously published estimate of the global production of EPA by diatoms, which contribute to most of the world's supply of EPA, we predict a loss of 14.2 Mt of EPA annually as a result of ocean warming. The n‐3 LC‐PUFA are vitally important for an array of key physiological functions in aquatic and terrestrial organisms, and these FA are mainly produced by phytoplankton. Therefore, reduced production of these EFA, as a consequence of climate warming, is predicted to negatively affect species that depend on these compounds for optimum physiological function. Such profound changes in the biochemical composition of phytoplankton cell membranes can lead to cascading effects throughout the world's ecosystems.
Skin image retrieval using Gabor wavelet texture feature
Authors: Ou X. , Pan W. , Zhang X. , Xiao P.
Published: April 2016

Objective

Skin imaging plays a key role in many clinical studies. We have used many skin imaging techniques, including the recently developed capacitive contact skin imaging based on fingerprint sensors. The aim of this study was to develop an effective skin image retrieval technique using Gabor wavelet transform, which can be used on different types of skin images, but with a special focus on skin capacitive contact images.

Methods

Content‐based image retrieval (CBIR) is a useful technology to retrieve stored images from database by supplying query images. In a typical CBIR, images are retrieved based on colour, shape, texture, etc. In this study, texture feature is used for retrieving skin images, and Gabor wavelet transform is used for texture feature description and extraction.

Results

The results show that the Gabor wavelet texture features can work efficiently on different types of skin images. Although Gabor wavelet transform is slower compared with other image retrieval techniques, such as principal component analysis (PCA) and grey‐level co‐occurrence matrix (GLCM), Gabor wavelet transform is the best for retrieving skin capacitive contact images and facial images with different orientations. Gabor wavelet transform can also work well on facial images with different expressions and skin cancer/disease images.

Conclusion

We have developed an effective skin image retrieval method based on Gabor wavelet transform, that it is useful for retrieving different types of images, namely digital colour face images, digital colour skin cancer and skin disease images, and particularly greyscale skin capacitive contact images. Gabor wavelet transform can also be potentially useful for face recognition (with different orientation and expressions) and skin cancer/disease diagnosis.
Potential mechanisms of coexistence in closely related forbs
Authors: Staples Timothy L. , Dwyer John M. , Loy Xingwen , Mayfield Margaret M.
Published: April 2016

The stable coexistence of very similar species has perplexed ecologists for decades and has been central to the development of coexistence theory. According to modern coexistence theory, species can coexist stably (i.e. persist indefinitely with no long‐term density trends) as long as species' niche differences exceed competitive ability differences, even if these differences are very small. Recent studies have directly quantified niche and competitive ability differences in experimental communities at small spatial scales, but provide limited information about stable coexistence across spatial scales in heterogeneous natural communities. In this study, we use experimental and observational approaches to explore evidence for niche and competitive ability differences between two closely related, ecologically similar and widely coexisting annual forbs: Trachymene cyanopetala and T. ornata. We experimentally tested for stabilizing niche differences and competitive ability differences between these species by manipulating species' frequencies, under both well‐watered and water‐stressed conditions. We considered these experimental results in light of extensive field observations to explore evidence of niche segregation at a range of spatial scales. We found little evidence of intra‐specific stabilization or competitive ability differences in laboratory experiments while observational studies suggested niche segregation across pollinator assemblages and small‐scale microclimate heterogeneity. Though we did not quantify long‐term stabilization of coexisting populations of these species, results are consistent with expectations for stable coexistence of similar species via a spatial storage effect allowing niche differences to overcome even small (to absent) competitive ability differences.
Conservative Protestantism and Anti‐Evolution Curricular Challenges Across States*
Authors: Johnson David R. , Scheitle Christopher P. , Ecklund Elaine Howard
Published: April 2016

Objective

Drawing on a symbolic politics perspective, we analyze state‐level “anti‐evolution” legislative attempts between 2000 and 2012 to alter science curricula in the United States.

Method

We use structural equation modeling to examine whether interest groups, public opinion, government political climate, and science and engineering workforces mediate influence of the religious composition of a state on anti‐evolution legislation.

Results

State conservative Protestant adherence does influence anti‐evolution legislation efforts indirectly by increasing the influence of conservative Protestants in state GOP bodies. While a state's conservative Protestant adherence rate does increase anti‐evolution public opinion and the likelihood of anti‐evolution organizations being active in the state, these do not increase the likelihood of anti‐evolution legislation being considered by state governments.

Conclusion

The results suggest that anti‐evolution legislation activity is a ceremonial act on the part of politicians, which legitimates the values of conservative Protestants and generates political support.
Constructal Design of an Entropic Wall With Circulating Water Inside
Authors: Trancossi Michele , Stewart Jill , Dumas Antonio , Madonia Mauro , Marques Jose Pascoa
Published: April 2016

An entropic wall with circulating water inside could be a solution for acclimatizing a new building with high-energy efficiency and high levels of internal comfort. If circulating water is thermally stabilized by exchanging in the ground such has it happens in geothermal plants, a thermal shield could be realized keeping walls in comfort conditions and minimizing energy needs for further temperature regulations. This paper presents optimization guidelines of such a wall with the objective of maximizing the performances of the wall for reaching optimal internal wellness conditions. Optimization has been realized by a constructal law based method, which has been personalized by a step-by-step process and has been named constructal design for efficiency (CDE). The optimization of the system has been produced at different levels. It starts from a preliminary analysis at system levels, which allow defining the best objectives that could be reached. After this preliminary process, the system has been divided into modules, and the critical ones which have higher influence on the performances of the system have been evaluated. This analysis has been coupled also with an industrial analysis with the goal of defining an effective layout, which could be also manufactured with acceptable costs. The result has produced a final solution with a very good compromise between energetic performances and minimization of costs at industrial level. The results open interesting perspectives for the constructal law to become the core of an effective methodology of an industrial design which can couple perfectly with the modular approach which is currently the major part of industrial companies.
Effects of Operating Temperature on the Heat Transfer Characteristics of Photovoltaic Systems in the Upper Midwest
Authors: Choi Wongyu , Pate Michael B. , Warren Ryan D. , Nelson Ron M.
Published: April 2016

This paper presents the heat transfer characteristics of a stationary PV system and a dual-axis tracking PV system installed in the Upper Midwest, U.S. Because past solar research has focused on the warmer, sunnier Southwest, a need exists for solar research that focuses on this more-populated and colder Upper Midwest region. Meteorological and PV experimental data were collected and analyzed for the two systems over a one-year period. At solar irradiance levels larger than 120 W/m2, the array temperatures of the dual-axis tracking PV system were found to be lower than those of the stationary system by 1.8 °C, which is a strong evidence of the different heat transfer trends for both systems. The hourly averaged heat transfer coefficients for the experiment year were found to be 20.8 and 29.4 W/m2 °C for the stationary and tracking systems, respectively. The larger heat transfer coefficient of the dual-axis tracking system can be explained by the larger area per unit PV module exposed to the ambient compared to the stationary system. The experimental temperature coefficients for power at a solar irradiance level of 1000 W/m2 were −0.30% and −0.38%/ °C for the stationary and dual-axis tracking systems, respectively. These values are lower than the manufacturer's specified value −0.5/ °C. Simulations suggest that annual conversion efficiencies could potentially be increased by approximately 4.3% and 4.6%, respectively, if they were operated at lower temperatures.
A reduced-order integral formulation to account for the finite size effect of isotropic square panels using the transfer matrix method
Authors: Bonfiglio Paolo , Pompoli Francesco , Lionti Riccardo
Published: April 2016

The transfer matrix method is a well-established prediction tool for the simulation of sound transmission loss and the sound absorption coefficient of flat multilayer systems. Much research has been dedicated to enhancing the accuracy of the method by introducing a finite size effect of the structure to be simulated. The aim of this paper is to present a reduced-order integral formulation to predict radiation efficiency and radiation impedance for a panel with equal lateral dimensions. The results are presented and discussed for different materials in terms of radiation efficiency, sound transmission loss, and the sound absorption coefficient. Finally, the application of the proposed methodology for rectangular multilayer systems is also investigated and validated against experimental data.
Rotational speed invariant fault diagnosis in bearings using vibration signal
imaging and local binary patterns
Authors: Khan Sheraz Ali , Kim Jong-Myon
Published: April 2016

Structural vibrations of bearing housings are used for diagnosing fault conditions in bearings, primarily by searching for characteristic fault frequencies in the envelope power spectrum of the vibration signal. The fault frequencies depend on the non-stationary angular speed of the rotating shaft. This paper explores an imaging-based approach to achieve rotational speed independence. Cycle length segments of the rectified vibration signal are stacked to construct grayscale images which exhibit unique textures for each fault. These textures show insignificant variation with the rotational speed, which is confirmed by the classification results using their local binary pattern histograms.
Intersections of the Lamb mode dispersion curves of free isotropic plates
Authors: Every A. G.
Published: April 2016

The intersections between Lamb mode dispersion curves of free isotropic plates at real values of frequency and wave number are examined for the full allowed range of Poisson's ratio σ. The generic intersections between the dispersion curves for symmetric and anti-symmetric branches are classified into three types. Type F intersections are conditioned by the two additional real solutions of Rayleigh's cubic equation that occur for σ<0.26308. Types I and II intersections occur for all values of σ, and are distinguished by the vanishing or divergence of the tangent functions in the defining equations for the Lamb modes. A brief discussion is provided of intersections between branches of like symmetry and additional intersections between unlike symmetry branches that occur for special values of σ.
Psychological Distress in Elite Adolescent Soccer Players Following Deselection
Authors: Blakelock David J. , Chen Mark A. , Prescott Tim
Published: April 2016

Elite adolescent soccer players may represent one athletic population that is vulnerable to developing psychological distress following deselection. This study examined the proportion of players experiencing clinical levels of psychological distress following selection procedures and whether player status (i.e., deselected vs. retained) had a significant effect on psychological distress. Data was collected from 91 players who completed the General Health Questionnaire -12 at three time points: 7–14 days before selection procedures, 7 days after and 21 days after. Although outcomes were heterogeneous, a sizable proportion of deselected players were found to experience clinical levels of psychological distress. A factorial ANOVA (p < .001) found that deselected players experienced higher levels of psychological distress than retained players at postselection time points. The research provides evidence that some deselected players are “at risk” of developing clinical levels of psychological distress. Clinical implications and recommendations for future research are discussed.
An Investigation of Body Image in Athletes With Physical Disabilities
Authors: Galli Nick , Reel Justine J. , Henderson Hester , Detling Nicole
Published: April 2016

The purpose of this study was twofold: (a) to explore the body image of athletes with physical disabilities, and (b) to understand how sport influences body image among these athletes. We interviewed 20 male and female athletes (Mage = 34.25, SD = 8.49) from a variety of sports regarding their body image and the role of sport in influencing body image. A thematic analysis (Braun & Clarke, 2006) was used to generate six themes: (a) personal significance of injury and disability, (b) noncentrality of the body and disability, (c) positive influence of sport on body esteem, (d) social factors influencing body-related emotions and perceptions, (e) body critiques and preferences, and (f) positive thoughts and emotions about the body. Sport seemed to be an important vehicle for experiencing body-related pride, and athletes expressed an intimate connection with the body parts that enabled them to physically compete.
Metalloprotease cleavage of the N terminus of the orphan G protein–coupled receptor GPR37L1 reduces its constitutive activity
Authors: Coleman James L. J. , Ngo Tony , Schmidt Johannes , Mrad Nadine , Liew Chu Kong , Jones Nicole M. , Graham Robert M. , Smith Nicola J.
Published: April 2016

The N terminus of the receptor GPR37L1 enables constitutive signaling to Gα
s
.
Gβ promotes pheromone receptor polarization and yeast chemotropism by inhibiting receptor phosphorylation
Authors: Ismael Amber , Tian Wei , Waszczak Nicholas , Wang Xin , Cao Youfang , Suchkov Dmitry , Bar Eli , Metodiev Metodi V. , Liang Jie , Arkowitz Robert A. , Stone David E.
Published: April 2016

The Gβ subunit promotes mating responses in yeast by keeping pheromone receptors at the cell surface.
Focus Issue: New insights in GPCR to G protein signaling
Authors: Gough Nancy R.
Published: April 2016

Complexity in how G proteins and their receptors signal continues to emerge.
Mutations Decreasing Intrinsic β-Lactam Resistance Are Linked to Cell Division in the Nosocomial Pathogen Acinetobacter baumannii
Authors: Knight Daniel , Dimitrova Daniela D. , Rudin Susan D. , Bonomo Robert A. , Rather Philip N.
Published: April 2016

Transposon mutagenesis was used to identify novel determinants of intrinsic β-lactam resistance in
Acinetobacter baumannii
. An EZ-Tn5 transposon insertion in a gene corresponding to the A1S_0225 sequence resulted in a 4-fold decrease in resistance to ampicillin, cefotaxime, imipenem, and ceftriaxone but did not alter resistance to other classes of antibiotics. Based on this phenotype, the gene was designated
blhA
(
β
-
l
actam
h
ypersusceptibility). The
blhA
::EZ-Tn5 mutation conferred a similar phenotype in
A. baumannii
strain ATCC 17978. The wild-type
blhA
gene complemented the
blhA
::EZTn5 insertion and restored β-lactam resistance levels back to wild-type levels. The
blhA
mutation also increased β-lactam susceptibility in an
adeB adeJ
double mutant, indicating that the
blhA
mutation acted independently of these efflux systems to mediate susceptibility. In addition, mRNA levels for the
bla
OXA
and
bla
ADC
β-lactamase genes were not altered by the
blhA
mutation. The
blhA
mutation resulted in a prominent cell division and morphological defect, with cells exhibiting a highly elongated phenotype, combined with large bulges in some cells. The
blhA
gene is unique to
Acinetobacter
and likely represents a novel gene involved in cell division. Three additional mutations, in
zipA
,
zapA
, and
ftsK
, each of which encode predicted cell division proteins, also conferred increased β-lactam susceptibility, indicating a common link between cell division and intrinsic β-lactam resistance in
A. baumannii
.
Combination Pod-Intravaginal Ring Delivers Antiretroviral Agents for HIV Prophylaxis: Pharmacokinetic Evaluation in an Ovine Model
Authors: Moss John A. , Butkyavichene Irina , Churchman Scott A. , Gunawardana Manjula , Fanter Rob , Miller Christine S. , Yang Flora , Easley Jeremiah T. , Marzinke Mark A. , Hendrix Craig W. , Smith Thomas J. , Baum Marc M.
Published: April 2016

Preexposure prophylaxis (PrEP) against HIV using oral regimens based on the nucleoside reverse transcriptase inhibitor tenofovir disoproxil fumarate (TDF) has been effective to various degrees in multiple clinical trials, and the CCR5 receptor antagonist maraviroc (MVC) holds potential for complementary efficacy. The effectiveness of HIV PrEP is highly dependent on adherence. Incorporation of the TDF-MVC combination into intravaginal rings (IVRs) for sustained mucosal delivery could increase product adherence and efficacy compared with oral and vaginal gel formulations. A novel pod-IVR technology capable of delivering multiple drugs is described. The pharmacokinetics and preliminary local safety characteristics of a novel pod-IVR delivering a combination of TDF and MVC were evaluated in the ovine model. The device exhibited sustained release at controlled rates over the 28-day study and maintained steady-state drug levels in cervicovaginal fluids (CVFs). Dilution of CVFs during lavage sample collection was measured by ion chromatography using an inert tracer, allowing corrected drug concentrations to be measured for the first time. Median, steady-state drug levels in vaginal tissue homogenate were as follows: for tenofovir (TFV;
in vivo
hydrolysis product of TDF), 7.3 × 10
2
ng g
−1
(interquartile range [IQR], 3.0 × 10
2
, 4.0 × 10
3
); for TFV diphosphate (TFV-DP; active metabolite of TFV), 1.8 × 10
4
fmol g
−1
(IQR, 1.5 × 10
4
, 4.8 × 10
4
); and for MVC, 8.2 × 10
2
ng g
−1
(IQR, 4.7 × 10
2
, 2.0 × 10
3
). No adverse events were observed. These findings, together with previous pod-IVR studies, have allowed several lead candidates to advance into clinical evaluation.
New Ceftriaxone- and Multidrug-Resistant Neisseria gonorrhoeae Strain with a Novel Mosaic
penA
Gene Isolated in Japan
Authors: Nakayama Shu-ichi , Shimuta Ken , Furubayashi Kei-ichi , Kawahata Takuya , Unemo Magnus , Ohnishi Makoto
Published: April 2016

We have characterized in detail a new ceftriaxone- and multidrug-resistant
Neisseria gonorrhoeae
strain (FC428) isolated in Japan in 2015. FC428 differed from previous ceftriaxone-resistant strains and contained a novel mosaic
penA
allele encoding a new mosaic penicillin-binding protein 2 (PBP 2). However, the resistance-determining 3′-terminal region of
penA
was almost identical to the regions of two previously reported ceftriaxone-resistant strains from Australia and Japan, indicating that both ceftriaxone-resistant strains and conserved ceftriaxone resistance-determining PBP 2 regions might spread.
Pharmacokinetic Evaluation of Sulfamethoxazole at 800 Milligrams Once Daily in the Treatment of Tuberculosis
Authors: Alsaad N. , Dijkstra J. A. , Akkerman O. W. , de Lange W. C. M. , van Soolingen D. , Kosterink J. G. W. , van der Werf T. S. , Alffenaar J. W. C.
Published: April 2016

For treatment of multidrug-resistant tuberculosis (MDR-TB), there is a scarcity of antituberculosis drugs. Co-trimoxazole is one of the available drug candidates, and it is already frequently coprescribed for TB-HIV-coinfected patients. However, only limited data are available on the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of co-trimoxazole in TB patients. The objective of this study was to evaluate the PK parameters and
in vitro
PD data on the effective part of co-trimoxazole: sulfamethoxazole. In a prospective PK study in patients infected with drug-susceptible
Mycobacterium tuberculosis
(drug-susceptible TB patients) (age, >18), sulfamethoxazole-trimethoprim (SXT) was administered orally at a dose of 960 mg once daily. One-compartment population pharmacokinetic modeling was performed using MW\Pharm 3.81 (Mediware, Groningen, The Netherlands). The area under the concentration-time curve for the free, unbound fraction of a drug (ƒAUC)/MIC ratio and the period in which the free concentration exceeded the MIC (f
T
> MIC) were calculated. Twelve patients received 960 mg co-trimoxazole in addition to first-line drugs. The pharmacokinetic parameters of the population model were as follows (geometric mean ± standard deviation [SD]): metabolic clearance (CL

m

), 1.57 ± 3.71 liters/h; volume of distribution (
V
), 0.30 ± 0.05 liters · kg lean body mass
−1
; drug clearance/creatinine clearance ratio (

f
r

), 0.02 ± 0.13; gamma distribution rate constant (ktr_po), 2.18 ± 1.14; gamma distribution shape factor (n_po), 2.15 ± 0.39. The free fraction of sulfamethoxazole was 0.3, but ranged between 0.2 and 0.4. The median value of the MICs was 9.5 mg/liter (interquartile range [IQR], 4.75 to 9.5), and that of theƒAUC/MIC ratio was 14.3 (IQR, 13.0 to 17.5). The percentage of ƒ
T
> MIC ranged between 43 and 100% of the dosing interval. The PK and PD data from this study are useful to explore a future dosing regimen of co-trimoxazole for MDR-TB treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT01832987.)
Colistin and Polymyxin B Dosage Regimens against Acinetobacter baumannii: Differences in Activity and the Emergence of Resistance
Authors: Cheah Soon-Ee , Li Jian , Tsuji Brian T. , Forrest Alan , Bulitta Jürgen B. , Nation Roger L.
Published: April 2016

Infections caused by multidrug-resistant
Acinetobacter baumannii
are a major public health problem, and polymyxins are often the last line of therapy for recalcitrant infections by such isolates. The pharmacokinetics of the two clinically used polymyxins, polymyxin B and colistin, differ considerably, since colistin is administered as an inactive prodrug that undergoes slow conversion to colistin. However, the impact of these substantial pharmacokinetic differences on bacterial killing and resistance emergence is poorly understood. We assessed clinically relevant polymyxin B and colistin dosage regimens against one reference and three clinical
A. baumannii
strains in a dynamic one-compartment
in vitro
model. A new mechanism-based pharmacodynamic model was developed to describe and predict the drug concentrations and viable counts of the total and resistant populations. Rapid attainment of target concentrations was shown to be critical for polymyxin-induced bacterial killing. All polymyxin B regimens achieved peak concentrations of at least 1 mg/liter within 1 h and caused ≥4 log
10
killing at 1 h. In contrast, the slow rise of colistin concentrations to 3 mg/liter over 48 h resulted in markedly reduced bacterial killing. A significant (4 to 6 log
10
CFU/ml) amplification of resistant bacterial populations was common to all dosage regimens. The developed mechanism-based model explained the observed bacterial killing, regrowth, and resistance. The model also implicated adaptive polymyxin resistance as a key driver of bacterial regrowth and predicted the amplification of preexisting, highly polymyxin-resistant bacterial populations following polymyxin treatment. Antibiotic combination therapies seem the most promising option for minimizing the emergence of polymyxin resistance.
ICE
Spy
009, a Conjugative Genetic Element Carrying
mef
(E) in Streptococcus pyogenes
Authors: Del Grosso Maria , Camilli Romina , Rizzi Ermanno , Pietrelli Alessandro , De Bellis Gianluca , Pantosti Annalisa
Published: April 2016

Efflux-mediated macrolide resistance due to
mef
(E) and
mel
, carried by the mega element, is common in
Streptococcus pneumoniae
, for which it was originally characterized, but it is rare in
Streptococcus pyogenes
. In
S. pyogenes
, mega was previously found to be enclosed in Tn
2009
, a composite genetic element of the Tn
916
family containing
tet
(M) and conferring erythromycin and tetracycline resistance. In this study,
S. pyogenes
isolates containing
mef
(E), apparently not associated with other resistance determinants, were examined to characterize the genetic context of mega. By whole-genome sequencing of one isolate, MB56Spyo009, we identified a novel composite integrative and conjugative element (ICE) carrying mega, designated ICE
Spy
009, belonging to the ICE
Sa
2603 family. ICE
Spy
009 was 55 kb long, contained 61 putative open reading frames (ORFs), and was found to be integrated into
hylA
, a novel integration site for the ICE
Sa
2603 family. The modular organization of the ICE was similar to that of members of the ICE
Sa
2603 family carried by different streptococcal species. In addition, a novel cluster of accessory resistance genes was found inside a region that encloses mega. PCR mapping targeting ICE
Spy
009 revealed the presence of a similar ICE in five other isolates under study. While in three isolates the integration site was the same as that of ICE
Spy
009, in two isolates the ICE was integrated into
rplL
, the typical integration site of the ICE
Sa
2603 family. ICE
Spy
009 was able to transfer macrolide resistance by conjugation to both
S. pyogenes
and
S. pneumoniae
, showing the first evidence of the transferability of mega from
S. pyogenes
.
Elucidation of Mechanisms of Ceftazidime Resistance among Clinical Isolates of Pseudomonas aeruginosa by Using Genomic Data
Authors: Kos Veronica N. , McLaughlin Robert E. , Gardner Humphrey A.
Published: April 2016

Ceftazidime is one of the few cephalosporins with activity against
Pseudomonas aeruginosa
. Using whole-genome comparative analysis, we set out to determine the prevalent mechanism(s) of resistance to ceftazidime (CAZ) using a set of 181 clinical isolates. These isolates represented various multilocus sequence types that consisted of both ceftazidime-susceptible and -resistant populations. A presumptive resistance mechanism against ceftazidime was identified in 88% of the nonsusceptible isolates using this approach.
The Metalloprotease Mpl Supports Listeria monocytogenes Dissemination through Resolution of Membrane Protrusions into Vacuoles
Authors: Alvarez Diego E. , Agaisse Hervé
Published: April 2016

Listeria monocytogenesis an intracellular pathogen that disseminates within the intestinal epithelium through acquisition of actin-based motility and formation of plasma membrane protrusions that project into adjacent cells. The resolution of membrane protrusions into vacuoles from which the pathogen escapes results in bacterial spread from cell to cell. This dissemination process relies on themlp-actA-plcBoperon, which encodes ActA, a bacterial nucleation-promoting factor that mediates actin-based motility, and PlcB, a phospholipase that mediates vacuole escape. Here we investigated the role of the metalloprotease Mpl in the dissemination process. In agreement with previous findings showing that Mpl is required for PlcB activation, infection of epithelial cells with the ΔplcBor Δmplstrains resulted in the formation of small infection foci. As expected, the ΔplcBstrain displayed a strong defect in vacuole escape. However, the Δmplstrain showed an unexpected defect in the resolution of protrusions into vacuoles, in addition to the expected but mild defect in vacuole escape. The Δmplstrain displayed increased levels of ActA on the bacterial surface in protrusions. We mapped an Mpl-dependent processing site in ActA between amino acid residues 207 to 238. Similar to the Δmplstrain, the ΔactA207–238strain displayed increased levels of ActA on the bacterial surface in protrusions. Although the ΔactA207–238strain displayed wild-type actin-based motility, it formed small infection foci and failed to resolve protrusions into vacuoles. We propose that, in addition to its role in PlcB processing and vacuole escape, the metalloprotease Mpl is required for ActA processing and protrusion resolution.
Macrophage Apoptosis Triggered by IpaD from Shigella flexneri
Authors: Arizmendi Olivia , Picking William D. , Picking Wendy L.
Published: April 2016

Shigellosis, a potentially severe bacillary dysentery, is an infectious gastrointestinal disease caused by
Shigella
spp.
Shigella
invades the human colonic epithelium and avoids clearance by promoting apoptosis of resident immune cells in the gut. This process is dependent on the
Shigella
type III secretion system (T3SS), which injects effector proteins into target cells to alter their normal cellular functions. Invasion plasmid antigen D (IpaD) is a structural component that forms a complex at the tip of the T3SS apparatus needle. Recently, IpaD has also been shown to indirectly induce apoptosis in B lymphocytes. In this study, we explored the cytotoxicity profile during macrophage infection by
Shigella
and discovered that the pathogen induces macrophage cell death independent of caspase-1. Our results demonstrate that IpaD triggers apoptosis in macrophages through activation of host caspases accompanied by mitochondrial disruption. Additionally, we found that the IpaD N-terminal domain is necessary for macrophage killing and SipD, a structural homologue from
Salmonella
, was found to promote similar cytotoxicity. Together, these findings indicate that IpaD is a contributing factor to macrophage cell death during
Shigella
infection.
Population Dynamics of Phage and Bacteria in Spatially Structured Habitats Using Phage λ and Escherichia coli
Authors: Mitarai Namiko , Brown Stanley , Sneppen Kim
Published: April 2016

Bacteria living in physically structured habitats are exposed heterogeneously to both resources and different types of phages. While there have been numerous experimental approaches to examine spatially distributed bacteria exposed to phages, there is little theory to guide the design of these experiments, interpret their results, or expand the inferences drawn to a broader ecological and evolutionary context. Plaque formation provides a window into understanding phage-bacterium interactions in physically structured populations, including surfaces, semisolids, and biofilms. We develop models to address the plaque dynamics for a temperate phage and its virulent mutants. The models are compared with phage λ-
Escherichia coli
system to quantify their applicability. We found that temperate phages gave an increasing number of gradually smaller colonies as the distance increased from the plaque center. For low-lysogen frequency this resulted in plaques with most of the visible colonies at an intermediate distance between the center and periphery. Using spot inoculation, where phages in excess of bacteria were inoculated in a circular area, we measured the frequency and spatial distribution of lysogens. The spot morphology of
c
II-negative (
c
II
−
) and
c
III
−
mutants of phage λ displays concentric rings of high-density lysogenic colonies. The simplest of these ring morphologies was reproduced by including multiplicity of infection (MOI) sensitivity in lysis-lysogeny decisions, but its failure to explain the occasional observation of multiple rings in
c
III
−
mutant phages highlights unknown features of this phage. Our findings demonstrated advantages of temperate phages over virulent phages in exploiting limited resources in spatially distributed microbial populations.

IMPORTANCE
Phages are the most abundant organisms on earth, and yet little is known about how phages and bacterial hosts are influencing each other in density and evolution. Phages can be either virulent or temperate, a difference that is highlighted when a spatially structured bacterial population is infected. Phage λ is a temperate phage, with a capacity for dormancy that can be modified by single gene knockouts. The stochastic bias in the lysis-lysogeny decision's probability is reflected in plaque morphologies on bacterial lawns. We present a model for plaque morphology of both virulent and temperate phages, taking into account the underlying survival of bacterial microcolonies. It reproduces known plaque morphologies and speaks to advantages of temperate phages in a spatially structured environment.
A rare case of gallbladder fistulation with a 60-year-old appendicectomy scar
Authors: Thiruchandran Gajendiran , Joyce Megan , Baggott Paul James
Published: April 2016

We present an extremely unusual case of an external biliary fistula in an 87-year-old woman who presented with a 1-day history of spontaneous green discharge from a 60-year-old appendicectomy scar. Examination revealed a sinus in the right iliac fossa overlying her appendicectomy scar, with a raised white cell count and C reactive protein. A CT scan revealed a complex fistula connecting the gallbladder to the subcutaneous tissue in the right flank, which further connected inferiorly with a fistula to the previous appendicectomy scar and a small iliopsoas collection. Endoscopic retrograde cholangiopancreatography revealed several stones in the common bile duct, which were removed using a balloon catheter. The patient was further managed with a long course of antibiotics and discharged with a long-term drainage bag. A literature search revealed no previously reported cases of an external biliary fistula communicating with an appendicectomy scar.
Cluster randomised controlled trial of a financial incentive for mothers to improve breast feeding in areas with low breastfeeding rates: the NOSH study protocol
Authors: Relton Clare , Strong Mark , Renfrew Mary J , Thomas Kate , Burrows Julia , Whelan Barbara , Whitford Heather M , Scott Elaine , Fox-Rushby Julia , Anoyke Nana , Sanghera Sabina , Johnson Maxine , Sue Easton , Walters Stephen
Published: April 2016

Introduction

Breast feeding can promote positive long-term and short-term health outcomes in infant and mother. The UK has one of the lowest breastfeeding rates (duration and exclusivity) in the world, resulting in preventable morbidities and associated healthcare costs. Breastfeeding rates are also socially patterned, thereby potentially contributing to health inequalities. Financial incentives have been shown to have a positive effect on health behaviours in previously published studies.

Methods and analysis

Based on data from earlier development and feasibility stages, a cluster (electoral ward) randomised trial with mixed-method process and content evaluation was designed. The ‘Nourishing Start for Health’ (NOSH) intervention comprises a financial incentive programme of up to 6 months duration, delivered by front-line healthcare professionals, in addition to existing breastfeeding support. The intervention aims to increase the prevalence and duration of breast feeding in wards with low breastfeeding rates. The comparator is usual care (no offer of NOSH intervention). Routine data on breastfeeding rates at 6–8 weeks will be collected for 92 clusters (electoral wards) on an estimated 10 833 births. This sample is calculated to provide 80% power in determining a 4% point difference in breastfeeding rates between groups. Content and process evaluation will include interviews with mothers, healthcare providers, funders and commissioners of infant feeding services. The economic analyses, using a healthcare provider's perspective, will be twofold, including a within-trial cost-effectiveness analysis and beyond-trial modelling of longer term expectations for cost-effectiveness. Results of economic analyses will be expressed as cost per percentage point change in cluster level in breastfeeding rates between trial arms. In addition, we will present difference in resource use impacts for a range of acute conditions in babies aged 0–6 months.

Ethics and dissemination

Participating organisations Research and Governance departments approved the study. Results will be published in peer-reviewed journals and at conference presentations.

Trial registration number

ISRCTN44898617; Pre-results.
How does audit and feedback influence intentions of health professionals to improve practice? A laboratory experiment and field study in cardiac rehabilitation
Authors: Gude Wouter T , van Engen-Verheul Mariëtte M , van der Veer Sabine N , de Keizer Nicolette F , Peek Niels
Published: April 2016

Objective

To identify factors that influence the intentions of health professionals to improve their practice when confronted with clinical performance feedback, which is an essential first step in the audit and feedback mechanism.

Methods

We conducted a theory-driven laboratory experiment with 41 individual professionals, and a field study in 18 centres in the context of a cluster-randomised trial of electronic audit and feedback in cardiac rehabilitation. Feedback reports were provided through a web-based application, and included performance scores and benchmark comparisons (high, intermediate or low performance) for a set of process and outcome indicators. From each report participants selected indicators for improvement into their action plan. Our unit of observation was an indicator presented in a feedback report (selected yes/no); we considered selecting an indicator to reflect an intention to improve.

Results

We analysed 767 observations in the laboratory experiment and 614 in the field study, respectively. Each 10% decrease in performance score increased the probability of an indicator being selected by 54% (OR, 1.54; 95% CI 1.29% to 1.83%) in the laboratory experiment, and 25% (OR, 1.25; 95% CI 1.13% to 1.39%) in the field study. Also, performance being benchmarked as low and intermediate increased this probability in laboratory settings. Still, participants ignored the benchmarks in 34% (laboratory experiment) and 48% (field study) of their selections.

Conclusions

When confronted with clinical performance feedback, performance scores and benchmark comparisons influenced health professionals' intentions to improve practice. However, there was substantial variation in these intentions, because professionals disagreed with benchmarks, deemed improvement unfeasible or did not consider the indicator an essential aspect of care quality. These phenomena impede intentions to improve practice, and are thus likely to dilute the effects of audit and feedback interventions.

Trial registration number

NTR3251, pre-results.
Exploring the acceptability of a clinical decision rule to identify paediatric burns due to child abuse or neglect
Authors: Johnson Emma Louise , Hollén Linda Irene , Kemp Alison Mary , Maguire Sabine
Published: April 2016

Objective

An evidence based clinical decision rule (CDR) was developed from a systematic review and epidemiological study to identify burns due to child maltreatment (abuse or neglect). Prior to an implementation evaluation, we aim to explore clinicians' views of the CDR, the likelihood that it would influence their management and factors regarding its acceptability.

Methods

A semistructured questionnaire exploring demographics, views of the CDR and data collection pro forma, ability to recognise maltreatment and likelihood of following CDR recommended child protection (CP) action, was administered to 55 doctors and nurses in eight emergency departments and two burns units. Recognition of maltreatment was assessed via four fictitious case vignettes.

Analysis

Fisher's exact test and variability measured by coefficient of unalikeability.

Results

The majority of participants found the CDR and data collection pro forma useful (45/55, 81.8%). Only five clinicians said that they would not take the action recommended by the CDR (5/54, 9.3%). Lower grade doctors were more likely to follow the CDR recommendations (p=0.04) than any other grade, while senior doctors would consider it within their decision making. Factors influencing uptake include: brief training, background to CDR development and details of appropriate actions.

Conclusions

It is apparent that clinicians are willing to use a CDR to assist in identifying burns due to child maltreatment. However, it is clear that an implementation evaluation must encompass the influential variables identified to maximise uptake.
Primary care services located with EDs: a review of effectiveness
Authors: Ramlakhan Shammi , Mason Suzanne , O'Keeffe Colin , Ramtahal Alicia , Ablard Suzanne
Published: April 2016

Background

Primary care focused unscheduled care centres (UCC) co-located with major EDs have been proposed as a solution to the rise in ED attendances. They aim to reduce the burden of primary care patients attending the ED, hence reducing crowding, waits and cost.

This review analysed available literature in the context of the impact of general practitioner (GP) delivered, hospital-based (adjacent or within the ED) unscheduled care services on process outcomes, cost-effectiveness and patient satisfaction.

Methods

A narrative literature review of studies published between 1980 and 2015 was undertaken. All study types were reviewed and included if they reported a service model using hospital-based primary care clinicians with a control consisting of standard ED clinician-delivered care.

Results

The electronic searches yielded 7544 citations, with 20 records used in the review. These were grouped into three main themes: process outcomes, cost-effectiveness and satisfaction. A paradoxical increase in attendances has been described, which is likely to be attributable to provider-induced demand, and the evidence for improved throughput is poor. Marginal savings may be realised per patient, but this is likely to be overshadowed by the overall cost of introducing a new service.

Conclusions

There is little evidence to support the implementation of co-located UCC models. A robust evaluation of proposed models is needed to inform future policy.
Primary acute stroke thrombectomy within 3 h for large artery occlusion (PAST3-LAO): a pilot study
Authors: Lodi Yahia , Reddy Varun , Petro Gorge , Devasenapathy Ashok , Hourani Anas , Chou Chun-An
Published: April 2016

Background and purpose

In recent trials, acute ischemic stroke (AIS) from large artery occlusion (LAO) was resistant to intravenous thrombolysis and adjunctive stent retriever thrombectomy (SRT) was associated with better perfusion and outcomes. Despite benefit, 39–68% of patients had poor outcomes. Thrombectomy in AIS with LAO within 3 h is performed secondary to intravenous thrombolysis, which may be associated with delay. The purpose of our study is to evaluate the safety, feasibility, recanalization rate, and outcome of primary SRT within 3 h without intravenous thrombolysis in AIS from LAO.

Methods

Based on an institutionally approved protocol, stroke patients with LAO within 3 h were offered primary SRT as an alternative to intravenous recombinant tissue plasminogen activator. Consecutive patients who underwent primary SRT for LAO within 3 h from 2012 to 2014 were enrolled. Outcomes were measured using the modified Rankin Scale (mRS).

Results

18 patients with LAO of mean age 62.83±15.32 years and median NIH Stroke Scale (NIHSS) score 16 (10–23) chose primary SRT after giving informed consent. Near complete (TICI 2b in 1 patient) or complete (TICI 3 in 17 patients) recanalization was observed in all patients. Time to recanalization from symptom onset and groin puncture was 188.5±82.7 and 64.61±40.14 min, respectively. NIHSS scores immediately after thrombectomy, at 24 h and 30 days were 4 (0–12), 1 (0–12), and 0 (0–4), respectively. Asymptomatic perfusion-related hemorrhage developed in four patients (22%). 90-day outcomes were mRS 0 in 50%, mRS 1 in 44.4%, and mRS 2 in 5.6%.

Conclusions

Our study demonstrates that primary SRT in AIS from LAO is safe and feasible and is associated with complete recanalization and good outcome. Further study is required.
Synthesis of building blocks for an iterative approach towards oligomers of theStreptococcus pneumoniaetype 1 zwitterionic capsular polysaccharide repeating unit
Authors: Ní Cheallaigh Aisling , Oscarson Stefan
Published: April 2016

Zwitterionic capsular polysaccharide extracts, ∼8 kDa in mass, from Streptococcus pneumoniae type 1 (Spt1) have shown unique T-cell activating properties. Oligomers of the trisaccharide repeating unit of the Spt1 capsular polysaccharide [→3)-4-NH2-α-d-QuipNAc-(1→4)-α-d-GalpA-(1→3)-α-d-GalpA-(1-]nof defined length are needed to further investigate this response. An approach towards iteratively extendable trisaccharide building blocks of the zwitterionic capsular polysaccharides of Spt1 is described. Key elements include the comparison of pre-glycosylation oxidation and post-glycosylation oxidation approaches using thioglycoside donors to the target trisaccharide, the optimisation of the post-glycosylation oxidation approach, and the conversion of the trisaccharide to building blocks tailored for iterative glycosylation. The construction and evaluation of stereotunable 2-N-3-O-oxazolidinone donors for the common bacterial 2-acetamido-4-amino-2,4,6-trideoxy-α-d-galactopyranoside motif is also described, as is a key intermediate for their efficient synthesis.