bluuebunny/crossref_metadata_2025 huggingface dataset:
Post‐transplant monitoring of NK cell counts as a simple approach to predict the occurrence of opportunistic infection in liver transplant recipients
Authors: Fernández‐Ruiz M. , Silva J.T. , López‐Medrano F. , Allende L.M. , San Juan R. , Cambra F. , Justo I. , Paz‐Artal E. , Jiménez C. , Aguado J.M.
Published: June 2016

Background

Monitoring of peripheral blood lymphocyte subpopulation (PBLS) counts might be useful for estimating the risk of infection after liver transplantation (LT).

Methods

We prospectively measured total lymphocyte and PBLS counts at baseline and post‐transplant months 1 and 6 in 92 LT recipients. PBLS were enumerated by single‐platform 6‐color flow cytometry technology. Areas under receiver operating characteristic (ROC) curves were used to evaluate the accuracy of different PBLS for predicting cytomegalovirus (CMV) disease and overall opportunistic infection (OI). Adjusted hazard ratios (aHRs) for both outcomes were estimated by Cox regression.

Results

After a median follow‐up of 730.0 days, 29 patients (31.5%) developed 38 episodes of OI (including 22 episodes of CMV disease). The counts of CD3+, CD4+, and CD8+ T cells, and CD56+ CD16+ natural killer (NK) cells at month 1 were significantly lower in patients subsequently developing OI. The NK cell count was the best predictive parameter (area under ROC curve for predicting CMV disease: 0.78; P‐value = 0.001). Patients with an NK cell count <0.050 × 103 cells/μL had higher cumulative incidences of CMV disease (P‐value = 0.001) and overall OI (P‐value <0.001). In the multivariate models, an NK cell count <0.050 × 103 cells/μL at month 1 post transplantation remained as an independent risk factor for CMV disease (aHR: 5.54; P‐value = 0.003) and overall OI (aHR: 7.56; P‐value <0.001).

Conclusion

Post‐transplant kinetics of NK cell counts may be used as a simple and affordable proxy to the cell‐mediated immunity status in LT recipients and to their associated risk of OI.
Outcomes of spontaneous bacterial peritonitis in liver transplant recipients with allograft failure
Authors: Leong J. , Huprikar S. , Schiano T.
Published: June 2016

Background

Spontaneous bacterial peritonitis (SBP) carries appreciable morbidity and mortality in the pre‐liver transplant (LT) setting. However, the occurrence of SBP and its consequences in the post‐LT setting have not been well characterized.

Methods

This is a retrospective study of SBP occurring in post‐LT patients between January 2007 and December 2012. Outcomes were compared to a cohort of post‐LT patients with allograft failure and ascites without SBP.

Results

The most common indication for liver transplantation in this cohort was hepatitis C. A total of 29 episodes of SBP in 21 patients were identified. Escherichia coli (19%) and Klebsiella pneumoniae (10%) were the most frequent pathogens identified. Six patients died during their first episode of SBP. Ten patients were eventually listed for liver re‐transplantation (re‐LT) after their first episode of SBP; 5 of these patients were transplanted and the other 5 died. Of the 5 who were transplanted, 2 died shortly after re‐transplant, and 3 are still alive. The cause of death in the majority of patients was infection (83.3%). The median time from onset of ascites to death was 214 days (range: 10–1085 days) and from the first episode of SBP to death was 50.5 days (range: 4–549 days). In contrast, the median time from onset of ascites to death in patients with allograft failure and ascites without SBP was 331.5 days (45–2400 days).

Conclusions

Allograft failure with ascites is a poor prognostic factor and these patients should be considered high risk for re‐LT. SBP may accelerate the time to mortality.
The Good Clinical Practice guideline and its interpretation – perceptions of clinical trial teams in sub‐Saharan Africa
Authors: Vischer N. , Pfeiffer C. , Joller A. , Klingmann I. , Ka A. , Kpormegbe S. K. , Burri C.
Published: June 2016

Objectives

To explore the advantages and challenges of working with the Good Clinical Practice (GCP)‐International Conference of Harmonization (ICH) E6 guideline and its interpretation from the perspective of clinical trial teams based in sub‐Saharan Africa.

Methods

We conducted 60 key informant interviews with clinical trial staff at different levels in clinical research centres in Kenya, Ghana, Burkina Faso and Senegal and thematically analysed the responses.

Results

Clinical trial teams perceived working with ICH‐GCP as highly advantageous and regarded ICH‐GCP as applicable to their setting and efficiently applied. Only for informed consent did some clinical trial staff (one‐third) perceive the guideline as insufficiently applicable. Specific challenges included meeting the requirements for written and individual consent, conditions for impartial witnesses for illiterates or legally acceptable representatives for children, guaranteeing voluntary participation and ensuring full understanding of the consent given. It was deemed important to have ICH‐GCP compliance monitored by relevant ethics committees and regulatory authorities, without having guidelines applied overcautiously.

Conclusion

Clinical trial teams in sub‐Saharan Africa perceived GCP as a helpful guideline, despite having been developed by northern organisations and despite the high administrative burden of implementing it. To mitigate consent challenges, we suggest adapting GCP and making use of the flexibility it offers.
A Devonian predatory fish provides insights into the early evolution of modern sarcopterygians
Authors: Lu Jing , Zhu Min , Ahlberg Per Erik , Qiao Tuo , Zhu You’an , Zhao Wenjin , Jia Liantao
Published: June 2016

A 409-million-year-old predatory fish provides unique insights into the early evolution of modern lobe-finned fishes.
Noninvasive, near-field terahertz imaging of hidden objects using a single-pixel detector
Authors: Stantchev Rayko Ivanov , Sun Baoqing , Hornett Sam M. , Hobson Peter A. , Gibson Graham M. , Padgett Miles J. , Hendry Euan
Published: June 2016

Terahertz imaging for noninvasive measurements.
Tuning ice nucleation with counterions on polyelectrolyte brush surfaces
Authors: He Zhiyuan , Xie Wen Jun , Liu Zhenqi , Liu Guangming , Wang Zuowei , Gao Yi Qin , Wang Jianjun
Published: June 2016

This work is the first to show that the ion specificity in tuning HIN on ionic surfaces follows the Hofmeister series.
Quantifying Variability in Growth and Thermal Inactivation Kinetics of Lactobacillus plantarum
Authors: Aryani D. C. , den Besten H. M. W. , Zwietering M. H.
Published: June 2016

The presence and growth of spoilage organisms in food might affect the shelf life. In this study, the effects of experimental, reproduction, and strain variabilities were quantified with respect to growth and thermal inactivation using 20
Lactobacillus plantarum
strains. Also, the effect of growth history on thermal resistance was quantified. The strain variability in μ
max
was similar (
P
> 0.05) to reproduction variability as a function of pH, a
w
, and temperature, while being around half of the reproduction variability (
P
< 0.05) as a function of undissociated lactic acid concentration [HLa]. The cardinal growth parameters were estimated for the
L. plantarum
strains, and the pH
min
was between 3.2 and 3.5, the
a
w,min
was between 0.936 and 0.953, the [HLa
max
], at pH 4.5, was between 29 and 38 mM, and the
T
min
was between 3.4 and 8.3°C. The average
D
values ranged from 0.80 min to 19 min at 55°C, 0.22 to 3.9 min at 58°C, 3.1 to 45 s at 60°C, and 1.8 to 19 s at 63°C. In contrast to growth, the strain variability in thermal resistance was on average six times higher than the reproduction variability and more than ten times higher than the experimental variability. The strain variability was also 1.8 times higher (
P
< 0.05) than the effect of growth history. The combined effects of strain variability and growth history on
D
value explained all of the variability as found in the literature, although with bias. Based on an illustrative milk-processing chain, strain variability caused ∼2-log
10
differences in growth between the most and least robust strains and >10-log
10
differences after thermal treatment.

IMPORTANCE
Accurate control and realistic prediction of shelf life is complicated by the natural diversity among microbial strains, and limited information on microbiological variability is available for spoilage microorganisms. Therefore, the objectives of the present study were to quantify strain variability, reproduction (biological) variability, and experimental variability with respect to the growth and thermal inactivation kinetics of
Lactobacillus plantarum
and to quantify the variability in thermal resistance attributed to growth history. The quantitative knowledge obtained on experimental, reproduction, and strain variabilities can be used to improve experimental designs and to adequately select strains for challenge growth and inactivation tests. Moreover, the integration of strain variability in prediction of microbial growth and inactivation kinetics will result in more realistic predictions of
L. plantarum
dynamics along the food production chain.
Heterologous Production and Characterization of Two Glyoxal Oxidases from Pycnoporus cinnabarinus
Authors: Daou Marianne , Piumi François , Cullen Daniel , Record Eric , Faulds Craig B.
Published: June 2016

The genome of the white rot fungus
Pycnoporus cinnabarinus
includes a large number of genes encoding enzymes implicated in lignin degradation. Among these, three genes are predicted to encode glyoxal oxidase, an enzyme previously isolated from
Phanerochaete chrysosporium
. The glyoxal oxidase of
P. chrysosporium
is physiologically coupled to lignin-oxidizing peroxidases via generation of extracellular H
2
O
2
and utilizes an array of aldehydes and α-hydroxycarbonyls as the substrates. Two of the predicted glyoxal oxidases of
P. cinnabarinus
, GLOX1 (
Pci
GLOX1) and GLOX2 (
Pci
GLOX2), were heterologously produced in
Aspergillus niger
strain D15#26 (
pyrG
negative) and purified using immobilized metal ion affinity chromatography, yielding 59 and 5 mg of protein for
Pci
GLOX1 and
Pci
GLOX2, respectively. Both proteins were approximately 60 kDa in size and N-glycosylated. The optimum temperature for the activity of these enzymes was 50°C, and the optimum pH was 6. The enzymes retained most of their activity after incubation at 50°C for 4 h. The highest relative activity and the highest catalytic efficiency of both enzymes occurred with glyoxylic acid as the substrate. The two
P. cinnabarinus
enzymes generally exhibited similar substrate preferences, but
Pci
GLOX2 showed a broader substrate specificity and was significantly more active on 3-phenylpropionaldehyde.

IMPORTANCE
This study addresses the poorly understood role of how fungal peroxidases obtain an
in situ
supply of hydrogen peroxide to enable them to oxidize a variety of organic and inorganic compounds. This cooperative activity is intrinsic in the living organism to control the amount of toxic H
2
O
2
in its environment, thus providing a feed-on-demand scenario, and can be used biotechnologically to supply a cheap source of peroxide for the peroxidase reaction. The secretion of multiple glyoxal oxidases by filamentous fungi as part of a lignocellulolytic mechanism suggests a controlled system, especially as these enzymes utilize fungal metabolites as the substrates. Two glyoxal oxidases have been isolated and characterized to date, and the differentiation of the substrate specificity of the two enzymes produced by
Pycnoporus cinnabarinus
illustrates the alternative mechanisms existing in a single fungus, together with the utilization of these enzymes to prepare platform chemicals for industry.
Biochemical Characteristics and Substrate Degradation Pattern of a Novel Exo-Type β-Agarase from the Polysaccharide-Degrading Marine Bacterium Flammeovirga sp. Strain MY04
Authors: Han Wenjun , Cheng Yuanyuan , Wang Dandan , Wang Shumin , Liu Huihui , Gu Jingyan , Wu Zhihong , Li Fuchuan
Published: June 2016

Exo-type agarases release disaccharide units (3,6-anhydro-
l
-galactopyranose-α-1,3-
d
-galactose) from the agarose chain and, in combination with endo-type agarases, play important roles in the processive degradation of agarose. Several exo-agarases have been identified. However, their substrate-degrading patterns and corresponding mechanisms are still unclear because of a lack of proper technologies for sugar chain analysis. Herein, we report the novel properties of AgaO, a disaccharide-producing agarase identified from the genus
Flammeovirga
. AgaO is a 705-amino-acid protein that is unique to strain MY04. It shares sequence identities of less than 40% with reported GH50 β-agarases. Recombinant AgaO (rAgaO) yields disaccharides as the sole final product when degrading agarose and associated oligosaccharides. Its smallest substrate is a neoagarotetraose, and its disaccharide/agarose conversion ratio is 0.5. Using fluorescence labeling and two-stage mass spectrometry analysis, we demonstrate that the disaccharide products are neoagarobiose products instead of agarobiose products, as verified by
13
C nuclear magnetic resonance spectrum analysis. Therefore, we provide a useful oligosaccharide sequencing method to determine the patterns of enzyme cleavage of glycosidic bonds. Moreover, AgaO produces neoagarobiose products by gradually cleaving the units from the nonreducing end of fluorescently labeled sugar chains, and so our method represents a novel biochemical visualization of the exolytic pattern of an agarase. Various truncated AgaO proteins lost their disaccharide-producing capabilities, indicating a strict structure-function relationship for the whole enzyme. This study provides insights into the novel catalytic mechanism and enzymatic properties of an exo-type β-agarase for the benefit of potential future applications.

IMPORTANCE
Exo-type agarases can degrade agarose to yield disaccharides almost exclusively, and therefore, they are important tools for disaccharide preparation. However, their enzymatic mechanisms and agarose degradation patterns are still unclear due to the lack of proper technologies for sugar chain analysis. In this study, AgaO was identified as an exo-type agarase of agarose-degrading
Flammeovirga
bacteria, representing a novel branch of glycoside hydrolase family 50. Using fluorescence labeling, high-performance liquid chromatography, and mass spectrum analysis technologies, we provide a useful oligosaccharide sequencing method to determine the patterns of enzyme cleavage of glycosidic bonds. We also demonstrate that AgaO produces neoagarobiose by gradually cleaving disaccharides from the nonreducing end of fluorescently labeled sugars. This study will benefit future enzyme applications and oligosaccharide studies.
Phylogenetically Structured Differences in rRNA Gene Sequence Variation among Species of Arbuscular Mycorrhizal Fungi and Their Implications for Sequence Clustering
Authors: House Geoffrey L. , Ekanayake Saliya , Ruan Yang , Schütte Ursel M. E. , Kaonongbua Wittaya , Fox Geoffrey , Ye Yuzhen , Bever James D.
Published: June 2016

Arbuscular mycorrhizal (AM) fungi form mutualisms with plant roots that increase plant growth and shape plant communities. Each AM fungal cell contains a large amount of genetic diversity, but it is unclear if this diversity varies across evolutionary lineages. We found that sequence variation in the nuclear large-subunit (LSU) rRNA gene from 29 isolates representing 21 AM fungal species generally assorted into genus- and species-level clades, with the exception of species of the genera
Claroideoglomus
and
Entrophospora
. However, there were significant differences in the levels of sequence variation across the phylogeny and between genera, indicating that it is an evolutionarily constrained trait in AM fungi. These consistent patterns of sequence variation across both phylogenetic and taxonomic groups pose challenges to interpreting operational taxonomic units (OTUs) as approximations of species-level groups of AM fungi. We demonstrate that the OTUs produced by five sequence clustering methods using 97% or equivalent sequence similarity thresholds failed to match the expected species of AM fungi, although OTUs from AbundantOTU, CD-HIT-OTU, and CROP corresponded better to species than did OTUs from mothur or UPARSE. This lack of OTU-to-species correspondence resulted both from sequences of one species being split into multiple OTUs and from sequences of multiple species being lumped into the same OTU. The OTU richness therefore will not reliably correspond to the AM fungal species richness in environmental samples. Conservatively, this error can overestimate species richness by 4-fold or underestimate richness by one-half, and the direction of this error will depend on the genera represented in the sample.

IMPORTANCE
Arbuscular mycorrhizal (AM) fungi form important mutualisms with the roots of most plant species. Individual AM fungi are genetically diverse, but it is unclear whether the level of this diversity differs among evolutionary lineages. We found that the amount of sequence variation in an rRNA gene that is commonly used to identify AM fungal species varied significantly between evolutionary groups that correspond to different genera, with the exception of two genera that are genetically indistinguishable from each other. When we clustered groups of similar sequences into operational taxonomic units (OTUs) using five different clustering methods, these patterns of sequence variation caused the number of OTUs to either over- or underestimate the actual number of AM fungal species, depending on the genus. Our results indicate that OTU-based inferences about AM fungal species composition from environmental sequences can be improved if they take these taxonomically structured patterns of sequence variation into account.
Microbial Transformations of Selenium Species of Relevance to Bioremediation
Authors: Eswayah Abdurrahman S. , Smith Thomas J. , Gardiner Philip H. E.
Published: June 2016

Selenium species, particularly the oxyanions selenite (SeO32−) and selenate (SeO42−), are significant pollutants in the environment that leach from rocks and are released by anthropogenic activities. Selenium is also an essential micronutrient for organisms across the tree of life, including microorganisms and human beings, particularly because of its presence in the 21st genetically encoded amino acid, selenocysteine. Environmental microorganisms are known to be capable of a range of transformations of selenium species, including reduction, methylation, oxidation, and demethylation. Assimilatory reduction of selenium species is necessary for the synthesis of selenoproteins. Dissimilatory reduction of selenate is known to support the anaerobic respiration of a number of microorganisms, and the dissimilatory reduction of soluble selenate and selenite to nanoparticulate elemental selenium greatly reduces the toxicity and bioavailability of selenium and has a major role in bioremediation and potentially in the production of selenium nanospheres for technological applications. Also, microbial methylation after reduction of Se oxyanions is another potentially effective detoxification process if limitations with low reaction rates and capture of the volatile methylated selenium species can be overcome. This review discusses microbial transformations of different forms of Se in an environmental context, with special emphasis on bioremediation of Se pollution.
Development of a CRISPR-Cas9 Tool Kit for Comprehensive Engineering of Bacillus subtilis
Authors: Westbrook Adam W. , Moo-Young Murray , Chou C. Perry
Published: June 2016

The establishment of a clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 system for strain construction in
Bacillus subtilis
is essential for its progression toward industrial utility. Here we outline the development of a CRISPR-Cas9 tool kit for comprehensive genetic engineering in
B. subtilis
. In addition to site-specific mutation and gene insertion, our approach enables continuous genome editing and multiplexing and is extended to CRISPR interference (CRISPRi) for transcriptional modulation. Our tool kit employs chromosomal expression of Cas9 and chromosomal transcription of guide RNAs (gRNAs) using a gRNA transcription cassette and counterselectable gRNA delivery vectors. Our design obviates the need for multicopy plasmids, which can be unstable and impede cell viability. Efficiencies of up to 100% and 85% were obtained for single and double gene mutations, respectively. Also, a 2.9-kb hyaluronic acid (HA) biosynthetic operon was chromosomally inserted with an efficiency of 69%. Furthermore, repression of a heterologous reporter gene was achieved, demonstrating the versatility of the tool kit. The performance of our tool kit is comparable with those of systems developed for
Escherichia coli
and
Saccharomyces cerevisiae
, which rely on replicating vectors to implement CRISPR-Cas9 machinery.

IMPORTANCE
In this paper, as the first approach, we report implementation of the CRISPR-Cas9 system in
Bacillus subtilis
, which is recognized as a valuable host system for biomanufacturing. The study enables comprehensive engineering of
B. subtilis
strains with virtually any desired genotypes/phenotypes and biochemical properties for extensive industrial application.
Effects of Carbohydrate Source on Genetic Competence in Streptococcus mutans
Authors: Moye Zachary D. , Son Minjun , Rosa-Alberty Ariana E. , Zeng Lin , Ahn Sang-Joon , Hagen Stephen J. , Burne Robert A.
Published: June 2016

The capacity to internalize and catabolize carbohydrates is essential for dental caries pathogens to persist and cause disease. The expression of many virulence-related attributes by
Streptococcus mutans
, an organism strongly associated with human dental caries, is influenced by the peptide signaling pathways that control genetic competence. Here, we demonstrate a relationship between the efficiency of competence signaling and carbohydrate source. A significant increase in the activity of the promoters for
comX
,
comS
, and
comYA
after exposure to competence-stimulating peptide (CSP) was observed in cells growing on fructose, maltose, sucrose, or trehalose as the primary carbohydrate source, compared to cells growing on glucose. However, only cells grown in the presence of trehalose or sucrose displayed a significant increase in transformation frequency. Notably, even low concentrations of these carbohydrates in the presence of excess glucose could enhance the expression of
comX
, encoding a sigma factor needed for competence, and the effects on competence were dependent on the cognate sugar:phosphotransferase permease for each carbohydrate. Using green fluorescent protein (GFP) reporter fusions, we observed that growth in fructose or trehalose resulted in a greater proportion of the population activating expression of
comX
and
comS
, encoding the precursor of
comX
-inducing peptide (XIP), after addition of CSP, than growth in glucose. Thus, the source of carbohydrate significantly impacts the stochastic behaviors that regulate subpopulation responses to CSP, which can induce competence in
S. mutans
.

IMPORTANCE
The signaling pathways that regulate development of genetic competence in
Streptococcus mutans
are intimately intertwined with the pathogenic potential of the organism, impacting biofilm formation, stress tolerance, and expression of known virulence determinants. Induction of the gene for the master regulator of competence, ComX, by competence-stimulating peptide (CSP) occurs in a subpopulation of cells. Here, we show that certain carbohydrates that are common in the human diet enhance the ability of CSP to activate transcription of
comX
and that a subset of these carbohydrates stimulates progression to the competent state. The cognate sugar:phosphotransferase permeases for each sugar are needed for these effects. Interestingly, single-cell analysis shows that the carbohydrates that increase
com
gene expression do so by enhancing the proportion of cells that respond to CSP. A mathematical model is developed to explain how carbohydrates modulate bistable behavior in the system via the ComRS pathway and ComX stability.
Periplasmic Cytophaga hutchinsonii Endoglucanases Are Required for Use of Crystalline Cellulose as the Sole Source of Carbon and Energy
Authors: Zhu Yongtao , Han Lanlan , Hefferon Kathleen L. , Silvaggi Nicholas R. , Wilson David B. , McBride Mark J.
Published: June 2016

The soil bacteriumCytophaga hutchinsoniiactively digests crystalline cellulose by a poorly understood mechanism. Genome analyses identified nine genes predicted to encode endoglucanases with roles in this process. No predicted cellobiohydrolases, which are usually involved in the utilization of crystalline cellulose, were identified. Chromosomal deletions were performed in eight of the endoglucanase-encoding genes:cel5A,cel5B,cel5C,cel9A,cel9B,cel9C,cel9E, andcel9F. Each mutant retained the ability to digest crystalline cellulose, although the deletion ofcel9Ccaused a modest decrease in cellulose utilization. Strains with multiple deletions were constructed to identify the critical cellulases. Cells of a mutant lacking bothcel5Bandcel9Cwere completely deficient in growth on cellulose. Cell fractionation and biochemical analyses indicate that Cel5B and Cel9C are periplasmic nonprocessive endoglucanases. The requirement of periplasmic endoglucanases for cellulose utilization suggests that cellodextrins are transported across the outer membrane during this process. Bioinformatic analyses predict that Cel5A, Cel9A, Cel9B, Cel9D, and Cel9E are secreted across the outer membrane by the type IX secretion system, which has been linked to cellulose utilization. These secreted endoglucanases may perform the initial digestion within amorphous regions on the cellulose fibers, releasing oligomers that are transported into the periplasm for further digestion by Cel5B and Cel9C. The results suggest that both cell surface and periplasmic endoglucanases are required for the growth ofC. hutchinsoniion cellulose and that novel cell surface proteins may solubilize and transport cellodextrins across the outer membrane.

IMPORTANCEThe bacteriumCytophaga hutchinsoniidigests crystalline cellulose by an unknown mechanism. It lacks processive cellobiohydrolases that are often involved in cellulose digestion. Critical cellulolytic enzymes were identified by genetic analyses. Intracellular (periplasmic) nonprocessive endoglucanases performed an important role in cellulose utilization. The results suggest a model involving partial digestion at the cell surface, solubilization and uptake of cellodextrins across the outer membrane by an unknown mechanism, and further digestion within the periplasm. The ability to sequester cellodextrins and digest them intracellularly may limit losses of soluble cellobiose to other organisms.C. hutchinsoniiuses an unusual approach to digest cellulose and is a potential source of novel proteins to increase the efficiency of conversion of cellulose into soluble sugars and biofuels.
Influence of Host Ecology and Behavior on Campylobacter jejuni Prevalence and Environmental Contamination Risk in a Synanthropic Wild Bird Species
Authors: Taff Conor C. , Weis Allison M. , Wheeler Sarah , Hinton Mitchell G. , Weimer Bart C. , Barker Christopher M. , Jones Melissa , Logsdon Ryane , Smith Woutrina A. , Boyce Walter M. , Townsend Andrea K.
Published: June 2016

Campylobacter jejuni
is a foodborne pathogen that often leads to human infections through the consumption of contaminated poultry. Wild birds may play a role in the transmission of
C. jejuni
by acting as reservoir hosts. Despite ample evidence that wild birds harbor
C. jejuni
, few studies have addressed the role of host ecology in transmission to domestic animals or humans. We tested the hypothesis that host social behavior and habitat play a major role in driving transmission risk.
C. jejuni
infection and host ecology were studied simultaneously in wild American crows (
Corvus brachyrhynchos
) in Davis, CA, over 3 years. We found that 178 of 337 samples tested were culture positive (53%), with infection varying by season and host age. Among adult crows, infection rates were highest during the winter, when migrants return and crows form large communal roosts. Nestlings had the highest risk of infection, and whole-genome sequencing supports the observation of direct transmission between nestlings. We deployed global positioning system (GPS) receivers to quantify habitat use by crows; space use was nonrandom, with crows preferentially occupying some habitats while avoiding others. This behavior drastically amplified the risk of environmental contamination from feces in specific locations. This study demonstrates that social behavior contributes to infection within species and that habitat use leads to a heterogeneous risk of cross-species transmission.

IMPORTANCE
Campylobacter jejuni
is the most common cause of gastroenteritis in industrialized countries. Despite efforts to reduce the colonization of poultry flocks and eventual infection of humans, the incidence of human
C. jejuni
infection has remained high. Because wild birds can harbor strains of
C. jejuni
that eventually infect humans, there has long been speculation that wild birds might act as an important reservoir in the
C. jejuni
infection cycle. We simultaneously studied infection prevalence, social behavior, and movement ecology in wild American crows (
Corvus brachyrhynchos
). We found that social behavior contributed to patterns of infection and that movement behavior resulted in some areas having a high risk of transmission while others had a low risk. The incorporation of ecological data into studies of
C. jejuni
in wild birds has the potential to resolve when and how wild birds contribute to domestic animal and human
C. jejuni
infection, leading to better control of initial poultry contamination.
Return to play post-Achilles tendon rupture: a systematic review and meta-analysis of rate and measures of return to play
Authors: Zellers Jennifer A , Carmont Michael R , Grävare Silbernagel Karin
Published: June 2016

Aim

This systematic review and meta-analysis sought to identify return to play (RTP) rates following Achilles tendon rupture and evaluate what measures are used to determine RTP.

Design

A systematic review and meta-analysis were performed. Studies were assessed for risk of bias and grouped based on repeatability of their measure of RTP determination.

Data sources

PubMed, CINAHL, Web of Science and Scopus databases were searched to identify potentially relevant articles.

Eligibility criteria for selecting studies

Studies reporting RTP/sport/sport activity in acute, closed Achilles tendon rupture were included.

Results

108 studies encompassing 6506 patients were included for review. 85 studies included a measure for determining RTP. The rate of RTP in all studies was 80% (95% CI 75% to 85%). Studies with measures describing determination of RTP reported lower rates than studies without metrics described, with rates being significantly different between groups (p<0.001).

Conclusions

80 per cent of patients returned to play following Achilles tendon rupture; however, the RTP rates are dependent on the quality of the method used to measure RTP. To further understand RTP after Achilles tendon rupture, a standardised, reliable and valid method is required.
2016 consensus statement of the International Ankle Consortium: prevalence, impact and long-term consequences of lateral ankle sprains
Authors: Gribble Phillip A , Bleakley Chris M , Caulfield Brian M , Docherty Carrie L , Fourchet François , Fong Daniel Tik-Pui , Hertel Jay , Hiller Claire E , Kaminski Thomas W , McKeon Patrick O , Refshauge Kathryn M , Verhagen Evert A , Vicenzino Bill T , Wikstrom Erik A , Delahunt Eamonn
Published: June 2016

The Executive Committee of the International Ankle Consortium presents this 2016 position paper with recommendations for information implementation and continued research based on the paradigm that lateral ankle sprain (LAS), and the development of chronic ankle instability (CAI), serve as a conduit to a significant global healthcare burden. We intend our recommendations to serve as a mechanism to promote efforts to improve prevention and early management of LAS. We believe this will reduce the prevalence of CAI and associated sequelae that have led to the broader public health burdens of decreased physical activity and early onset ankle joint post-traumatic osteoarthritis. Ultimately, this can contribute to healthier lifestyles and promotion of physical activity.
Evidence review for the 2016 International Ankle Consortium consensus statement on the prevalence, impact and long-term consequences of lateral ankle sprains
Authors: Gribble Phillip A , Bleakley Chris M , Caulfield Brian M , Docherty Carrie L , Fourchet François , Fong Daniel Tik-Pui , Hertel Jay , Hiller Claire E , Kaminski Thomas W , McKeon Patrick O , Refshauge Kathryn M , Verhagen Evert A , Vicenzino Bill T , Wikstrom Erik A , Delahunt Eamonn
Published: June 2016

Lateral ankle sprains (LASs) are the most prevalent musculoskeletal injury in physically active populations. They also have a high prevalence in the general population and pose a substantial healthcare burden. The recurrence rates of LASs are high, leading to a large percentage of patients with LAS developing chronic ankle instability. This chronicity is associated with decreased physical activity levels and quality of life and associates with increasing rates of post-traumatic ankle osteoarthritis, all of which generate financial costs that are larger than many have realised. The literature review that follows expands this paradigm and introduces emerging areas that should be prioritised for continued research, supporting a companion position statement paper that proposes recommendations for using this summary of information, and needs for specific future research.
Diabetes case finding in the emergency department, using HbA1c: an opportunity to improve diabetes detection, prevention, and care
Authors: Hng Tien-Ming , Hor Amanda , Ravi Sumathy , Feng Xiaoqi , Lin Jaime , Astell-Burt Thomas , Chipps David , McLean Mark , Maberly Glen
Published: June 2016

Objective

We assessed the efficacy of routine glycated hemoglobin (HbA1c) testing to detect undiagnosed diabetes and prediabetes in an urban Australian public hospital emergency department (ED) located in an area of high diabetes prevalence.

Methods

Over 6 weeks, all patients undergoing blood sampling in the ED had their random blood glucose measured. If ≥5.5 mmol/L (99 mg/dL), HbA1c was measured on the same sample. HbA1c levels ≥6.5% (48 mmol/mol) and 5.7–6.4% (39–46 mmol/mol) were diagnostic of diabetes and prediabetes, respectively. Hospital records were reviewed to identify patients with previously diagnosed diabetes.

Results

Among 4580 presentations, 2652 had blood sampled of which 1267 samples had HbA1c measured. Of these, 487 (38.4%) had diabetes (either HbA1c≥6.5% or a prior diagnosis), and a further 347 (27.4%) had prediabetes. Among those with diabetes, 32.2% were previously undiagnosed.

Conclusions

Routine HbA1c testing in the ED identifies a large number of people with undiagnosed diabetes and prediabetes, and provides an opportunity to improve their care.
Association between neighbourhood air pollution concentrations and dispensed medication for psychiatric disorders in a large longitudinal cohort of Swedish children and adolescents
Authors: Oudin Anna , Bråbäck Lennart , Åström Daniel Oudin , Strömgren Magnus , Forsberg Bertil
Published: June 2016

Objective

To investigate associations between exposure to air pollution and child and adolescent mental health.

Design

Observational study.

Setting

Swedish National Register data on dispensed medications for a broad range of psychiatric disorders, including sedative medications, sleeping pills and antipsychotic medications, together with socioeconomic and demographic data and a national land use regression model for air pollution concentrations for NO2, PM10and PM2.5.

Participants

The entire population under 18 years of age in 4 major counties. We excluded cohort members whose parents had dispensed a medication in the same medication group since the start date of the register. The cohort size was 552 221.

Main outcome measures

Cox proportional hazards models to estimate HRs and their 95% CIs for the outcomes, adjusted for individual-level and group-level characteristics.

Results

The average length of follow-up was 3.5 years, with an average number of events per 1000 cohort members of ∼21. The mean annual level of NO2was 9.8 µg/m3. Children and adolescents living in areas with higher air pollution concentrations were more likely to have a dispensed medication for a psychiatric disorder during follow-up (HR=1.09, 95% CI 1.06 to 1.12, associated with a 10 µg/m3increase in NO2). The association with NO2was clearly present in 3 out of 4 counties in the study area; however, no statistically significant heterogeneity was detected.

Conclusion

There may be a link between exposure to air pollution and dispensed medications for certain psychiatric disorders in children and adolescents even at the relatively low levels of air pollution in the study regions. The findings should be corroborated by others.
Effectiveness of interventions to reduce ordering of thyroid function tests: a systematic review
Authors: Zhelev Zhivko , Abbott Rebecca , Rogers Morwenna , Fleming Simon , Patterson Anthea , Hamilton William Trevor , Heaton Janet , Thompson Coon Jo , Vaidya Bijay , Hyde Christopher
Published: June 2016

Objectives

To evaluate the effectiveness of behaviour changing interventions targeting ordering of thyroid function tests.

Design

Systematic review.

Data sources

MEDLINE, EMBASE and the Cochrane Database up to May 2015.

Eligibility criteria for selecting studies

We included studies evaluating the effectiveness of behaviour change interventions aiming to reduce ordering of thyroid function tests. Randomised controlled trials (RCTs), non-randomised controlled studies and before and after studies were included. There were no language restrictions.

Study appraisal and synthesis methods

2 reviewers independently screened all records identified by the electronic searches and reviewed the full text of any deemed potentially relevant. Study details were extracted from the included papers and their methodological quality assessed independently using a validated tool. Disagreements were resolved through discussion and arbitration by a third reviewer. Meta-analysis was not used.

Results

27 studies (28 papers) were included. They evaluated a range of interventions including guidelines/protocols, changes to funding policy, education, decision aids, reminders and audit/feedback; often intervention types were combined. The most common outcome measured was the rate of test ordering, but the effect on appropriateness, test ordering patterns and cost were also measured. 4 studies were RCTs. The majority of the studies were of poor or moderate methodological quality. The interventions were variable and poorly reported. Only 4 studies reported unsuccessful interventions but there was no clear pattern to link effect and intervention type or other characteristics.

Conclusions

The results suggest that behaviour change interventions are effective particularly in reducing the volume of thyroid function tests. However, due to the poor methodological quality and reporting of the studies, the likely presence of publication bias and the questionable relevance of some interventions to current day practice, we are unable to draw strong conclusions or recommend the implementation of specific intervention types. Further research is thus justified.

Trial registration number

CRD42014006192.
Prevalence of tinnitus and hyperacusis in children and adolescents: a systematic review
Authors: Rosing Susanne Nemholt , Schmidt Jesper Hvass , Wedderkopp Niels , Baguley David M
Published: June 2016

Objectives

To systematically review studies of the epidemiology of tinnitus and hyperacusis in children and young people, in order to determine the methodological differences implicated in the variability of prevalence estimates and the influence of population characteristics on childhood tinnitus and hyperacusis.

Data sources

Articles were retrieved from PubMed, EMBASE and Scopus databases and from the relevant reference lists using the methods described in the study protocol, which has previously been published. Reporting Items for Systematic Review (PRISMA) guidelines were followed.

Eligibility criteria

Studies addressing childhood prevalence, for example, children and young people aged 5–19 years.

Data selection

2 reviewers independently assessed the studies for eligibility, extracted data and assessed study consistency. Owing to the heterogeneity in the methodologies among the reported studies, only narrative synthesis of the results was carried out.

Results

Having identified 1032 publications, 131 articles were selected and 25 articles met the inclusion criteria and had sufficient methodological consistency to be included. Prevalence estimates of tinnitus range from 4.7% to 46% in the general paediatric population and among children with normal hearing, and from 23.5% to 62.2% of population of children with hearing loss. Reported prevalence ranged from 6% to 41.9% when children with hearing loss and normal hearing were both included. The prevalence of hyperacusis varied from 3.2% to 17.1%.

Conclusions

Data on prevalence vary considerably according to the study design, study population and the research question posed. The age range of children studied was varied and a marked degree of variation between definitions (tinnitus, hyperacusis) and measures (severity, perception, annoyance) was observed. The lack of consistency among studies indicates the necessity of examining the epidemiology of tinnitus and hyperacusis in children and adolescents with a set of standardised criteria.

Trial registration number

CRD42014013456.
Socioeconomic status and health-related quality of life among patients with prostate cancer 6 months after radical prostatectomy: a longitudinal analysis
Authors: Klein Jens , Hofreuter-Gätgens Kerstin , Lüdecke Daniel , Fisch Margit , Graefen Markus , von dem Knesebeck Olaf
Published: June 2016

Objectives

To identify the associations between socioeconomic status (SES) and health-related quality of life (HRQOL) and the explanatory contribution of disease, patient and healthcare factors among patients with prostate cancer.

Design

Prospective cohort study.

Setting and participants

In all, 246 patients from 2 hospitals in Hamburg/Germany who underwent radical prostatectomy completed a questionnaire shortly before discharge from hospital and again 6 months later.

Outcome measures

HRQOL as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C-30 including global quality of life, 5 functional scales and 9 symptom scales/items. Generalised estimating equations were calculated to analyse longitudinal data.

Results

Lower SES measured by income, education and occupational status is significantly associated with lower HRQOL 6 months after treatment. This especially holds true for the functional scales. After introducing disease, patient and healthcare factors, associations remain significant in the majority of cases. The explanatory contribution of patient factors such as comorbidity or psychosocial characteristics and of healthcare factors is slightly stronger than that of disease factors.

Conclusions

We identified strong social inequalities in HRQOL among patients with prostate cancer 6 months after surgery, in Germany. The underlying causes could not be sufficiently identified, and further research regarding these associations and their explanatory factors is needed.
Central venous Access device SeCurement And Dressing Effectiveness (CASCADE) in paediatrics: protocol for pilot randomised controlled trials
Authors: Ullman Amanda J , Kleidon Tricia , Gibson Victoria , Long Debbie A , Williams Tara , McBride Craig A , Hallahan Andrew , Mihala Gabor , Cooke Marie , Rickard Claire M
Published: June 2016

Introduction

Paediatric central venous access devices (CVADs) are associated with a 25% incidence of failure. Securement and dressing are strategies used to reduce failure and complication; however, innovative technologies have not been evaluated for their effectiveness across device types. The primary aim of this research is to evaluate the feasibility of launching a full-scale randomised controlled efficacy trial across three CVAD types regarding CVAD securement and dressing, using predefined feasibility criteria.

Methods and analysis

Three feasibility randomised, controlled trials are to be undertaken at the Royal Children's Hospital and the Lady Cilento Children's Hospital, Brisbane, Australia. CVAD securement and dressing interventions under examination compare current practice with sutureless securement devices, integrated securement dressings and tissue adhesive. In total, 328 paediatric patients requiring a peripherally inserted central catheter (n=100); non-tunnelled CVAD (n=180) and tunnelled CVAD (n=48) to be inserted will be recruited and randomly allocated to CVAD securement and dressing products. Primary outcomes will be study feasibility measured by eligibility, recruitment, retention, attrition, missing data, parent/staff satisfaction and effect size. CVAD failure and complication (catheter-associated bloodstream infection, local infection, venous thrombosis, occlusion, dislodgement and breakage) will be compared between groups.

Ethics and dissemination

Ethical approval to conduct the research has been obtained. All dissemination will be undertaken using the CONSORT Statement recommendations. Additionally, the results will be sent to the relevant organisations which lead CVAD focused clinical practice guidelines development.

Trial registration numbers

ACTRN12614001327673; ACTRN12615000977572; ACTRN12614000280606.
Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence
Authors: Lavikainen Piia , Helin-Salmivaara Arja , Eerola Mervi , Fang Gang , Hartikainen Juha , Huupponen Risto , Korhonen Maarit Jaana
Published: June 2016

Objectives

Previous studies on the effect of statin adherence on cardiovascular events in the primary prevention of cardiovascular disease have adjusted for time-dependent confounding, but potentially introduced bias into their estimates as adherence and confounders were measured simultaneously. We aimed to evaluate the effect when accounting for time-dependent confounding affected by previous adherence as well as time sequence between factors.

Design

Retrospective cohort study.

Setting

Finnish healthcare registers.

Participants

Women aged 45–64 years initiating statin use for primary prevention of cardiovascular disease in 2001–2004 (n=42 807).

Outcomes

Acute cardiovascular event defined as a composite of acute coronary syndrome and acute ischaemic stroke was our primary outcome. Low-energy fractures were used as a negative control outcome to evaluate the healthy-adherer effect.

Results

During the 3-year follow-up, 474 women experienced the primary outcome event and 557 suffered a low-energy fracture. The causal HR estimated with marginal structural model for acute cardiovascular events for all the women who remained adherent (proportion of days covered ≥80%) to statin therapy during the previous adherence assessment year was 0.78 (95% CI: 0.65 to 0.94) when compared with everybody remaining non-adherent (proportion of days covered <80%). The result was robust against alternative model specifications. Statin adherers had a potentially reduced risk of experiencing low-energy fractures compared with non-adherers (HR 0.90, 95% CI 0.76 to 1.07).

Conclusions

Our study, which took into account the time dependence of adherence and confounders, as well as temporal order between these factors, is support for the concept that adherence to statins in women in primary prevention decreases the risk of acute cardiovascular events by about one-fifth in comparison to non-adherence. However, part of the observed effect of statin adherence on acute cardiovascular events may be due to the healthy-adherer effect.