bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of hepatitis C virus recurrence after transplantation with sofosbuvir/ledipasvir: The role of ribavirin
Authors: Globke Brigitta , Raschzok Nathanael , Teegen Eva‐Maria , Pratschke Johann , Schott Eckart , Eurich Dennis
Published: December 2016

Background

Hepatitis C virus (HCV) recurrence after liver transplantation (LT) used to be a serious problem in the era of interferon‐based treatment. Since the introduction of modern directly acting antivirals, treatment has become easier and shorter. According to published data, in the natural course of hepatitis C infection the duration of antiviral treatment with sofosbuvir (SOF) and ledipasvir (LDV) may be shortened to 12 instead of 24 weeks, using ribavirin (RBV) in addition. Furthermore, the question of whether or not RBV is really necessary, in a 12‐week SOF/LDV treatment in the post‐transplant setting, is still unanswered.

Patients and methods

At our institution, 100 liver transplant patients with HCV recurrence underwent interferon‐free SOF‐based treatment. A total of 51 patients received SOF/LDV with or without RBV. Twenty‐nine HCV genotype 1 or 4 patients with histologically proven stage 0‐2 fibrosis were treated with SOF/LDV for 12 weeks; another 22 patients with advanced fibrosis (stage 3‐4) either received SOF/LDV plus weight‐adjusted RBV or prolonged treatment for 24 weeks.

Results

End of treatment response and sustained virological response (SVR) were achieved in 100% of the 51 patients, irrespective of the treatment group. Patients with prolonged treatment duration or with RBV developed significantly more adverse events (AEs) compared to the SOF/LDV group: 19 (86.4%) vs 8 (27.6%), P<.001. One of the predominant and most relevant AEs was the development of anemia in 43.1% of 10 patients receiving RBV, which was a significant result (P<.001). RBV co‐medication had to be reduced in 11 (55%) patients and then stopped in 8 (40%) patients because of AEs. No significant difference was observed among the groups regarding kidney function.

Conclusion

The SOF/LDV combination is a reliable therapy of recurrent HCV infection after LT. It is easy to administer and to achieve SVR in immunocompromised patients without interactions with immunosuppressive medications. Considering the high rate of AEs, frequent discontinuation of RBV treatment, and the 100% SVR, the use of RBV as co‐medication in a 12‐week SOF/LDV regimen does not seem to be justified after LT.
Association between diabetes mellitus and active tuberculosis in Africa and the effect of HIV
Authors: Bailey S. L. , Ayles H.
Published: December 2016

Objective

To determine current evidence for the association between diabetes and active tuberculosis in Africa, and how HIV modifies, or not, any association between diabetes and active tuberculosis.

Methods

We conducted a systematic review by searching the EMBASE, Global Health and MEDLINE databases. Studies were eligible for inclusion if they explored the association between diabetes mellitus prevalence and active tuberculosis incidence or prevalence, used a comparison group, were conducted in an African population and adjusted the analysis for at least age. Study characteristics were compared, and risk of bias was assessed. The range of effect estimates was determined for the primary association and for effect modification by HIV.

Results

Three eligible studies were identified: two investigated the primary association and two investigated HIV as a potential effect modifier. All studies were case–control studies, including a combined total of 1958 tuberculosis cases and 2111 non‐tuberculosis controls. Diabetes diagnostic methods and analysis strategies varied between studies. Individual study adjusted odds ratios of active tuberculosis for the effect of diabetes mellitus (unstratified) ranged from 0.88 (95% CI 0.17–4.58) to 10.7 (95% CI 4.5–26.0). Individual study P‐values for HIV interaction ranged from 0.01 to 0.83. Quantitative synthesis of individual study data was not performed due to heterogeneity between studies.

Conclusions

Few data currently exist on the association between diabetes and active tuberculosis in Africa, and on the effect of HIV on this association. Existing data are disparate. More regional research is needed to guide policy and practice on the care and control of tuberculosis and diabetes in Africa.
Tobacco pollen tubes – a fast and easy tool for studying lipid droplet association of plant proteins
Authors: Müller Anna Ophelia , Blersch Katharina Franziska , Gippert Anna Lena , Ischebeck Till
Published: December 2016

In recent years, lipid droplets have emerged as dynamic organelles rather than inactive storage sites for triacylglycerol. The number of proteins known to be associated with lipid droplets has increased, but remains small in comparison with those found with other organelles. Also the mechanisms of how lipid droplets are recognized and bound by proteins need deeper investigation. Here, we present a fast, simple and inexpensive approach to assay proteins for their association with lipid droplets in vivo that can help to screen protein candidates or mutated variants of proteins for their association in an efficient manner. For this, a system to transiently transform Nicotiana tabacum pollen grains was used because these naturally contain lipid droplets. We designed vectors for fast cloning of genes as fusions with either mVenus or mCherry. This allowed us to assay colocalization with lipid droplets stained with Nile Red and Bodipy 505/515, respectively. We successfully tested our system not only for proteins from Arabidopsis thaliana, but also for proteins from the moss Physcomitrella patens and the alga Chlamydomonas reinhardtii. The small size of the vector used allows easy exchange of codons by site‐directed mutagenesis. We used this to show that two proline residues in the proline knot of a caleosin are not essential for the binding of lipid droplets. We also demonstrated that peroxisomes are not associated with the lipid droplets in tobacco pollen tubes, which reduces the risk of false interpretation of microscopic data in our system.
Cytogenetic features of rRNA genes across land plants: analysis of the Plant rDNA database
Authors: Garcia Sònia , Kovařík Ales , Leitch Andrew R. , Garnatje Teresa
Published: December 2016

The online resource http://www.plantrdnadatabase.com/ stores information on the number, chromosomal locations and structure of the 5S and 18S‐5.8S‐26S (35S) ribosomal DNAs (rDNA) in plants. This resource was exploited to study relationships between rDNA locus number, distribution, the occurrence of linked (L‐type) and separated (S‐type) 5S and 35S rDNA units, chromosome number, genome size and ploidy level. The analyses presented summarise current knowledge on rDNA locus numbers and distribution in plants. We analysed 2949 karyotypes, from 1791 species and 86 plant families, and performed ancestral character state reconstructions. The ancestral karyotype (2n = 16) has two terminal 35S sites and two interstitial 5S sites, while the median (2n = 24) presents four terminal 35S sites and three interstitial 5S sites. Whilst 86.57% of karyotypes show S‐type organisation (ancestral condition), the L‐type arrangement has arisen independently several times during plant evolution. A non‐terminal position of 35S rDNA was found in about 25% of single‐locus karyotypes, suggesting that terminal locations are not essential for functionality and expression. Single‐locus karyotypes are very common, even in polyploids. In this regard, polyploidy is followed by subsequent locus loss. This results in a decrease in locus number per monoploid genome, forming part of the diploidisation process returning polyploids to a diploid‐like state over time.
The functions of plant small RNAs in development and in stress responses
Authors: Li Shengjun , Castillo‐González Claudia , Yu Bin , Zhang Xiuren
Published: December 2016

Like metazoans, plants use small regulatory RNAs (sRNAs) to direct gene expression. Several classes of sRNAs, which are distinguished by their origin and biogenesis, exist in plants. Among them, microRNAs (miRNAs) and trans‐acting small interfering RNAs (ta‐siRNAs) mainly inhibit gene expression at post‐transcriptional levels. In the past decades, plant miRNAs and ta‐siRNAs have been shown to be essential for numerous developmental processes, including growth and development of shoots, leaves, flowers, roots and seeds, among others. In addition, miRNAs and ta‐siRNAs are also involved in the plant responses to abiotic and biotic stresses, such as drought, temperature, salinity, nutrient deprivation, bacteria, virus and others. This review summarizes the roles of miRNAs and ta‐siRNAs in plant physiology and development.
High‐efficiency gene targeting in hexaploid wheat using DNA replicons and CRISPR/Cas9
Authors: Gil‐Humanes Javier , Wang Yanpeng , Liang Zhen , Shan Qiwei , Ozuna Carmen V. , Sánchez‐León Susana , Baltes Nicholas J. , Starker Colby , Barro Francisco , Gao Caixia , Voytas Daniel F.
Published: December 2016

The ability to edit plant genomes through gene targeting (GT) requires efficient methods to deliver both sequence‐specific nucleases (SSNs) and repair templates to plant cells. This is typically achieved using Agrobacterium T‐DNA, biolistics or by stably integrating nuclease‐encoding cassettes and repair templates into the plant genome. In dicotyledonous plants, such as Nicotinana tabacum (tobacco) and Solanum lycopersicum (tomato), greater than 10‐fold enhancements in GT frequencies have been achieved using DNA virus‐based replicons. These replicons transiently amplify to high copy numbers in plant cells to deliver abundant SSNs and repair templates to achieve targeted gene modification. In the present work, we developed a replicon‐based system for genome engineering of cereal crops using a deconstructed version of the wheat dwarf virus (WDV). In wheat cells, the replicons achieve a 110‐fold increase in expression of a reporter gene relative to non‐replicating controls. Furthermore, replicons carrying CRISPR/Cas9 nucleases and repair templates achieved GT at an endogenous ubiquitin locus at frequencies 12‐fold greater than non‐viral delivery methods. The use of a strong promoter to express Cas9 was critical to attain these high GT frequencies. We also demonstrate gene‐targeted integration by homologous recombination (HR) in all three of the homoeoalleles (A, B and D) of the hexaploid wheat genome, and we show that with the WDV replicons, multiplexed GT within the same wheat cell can be achieved at frequencies of ~1%. In conclusion, high frequencies of GT using WDV‐based DNA replicons will make it possible to edit complex cereal genomes without the need to integrate GT reagents into the genome.
The role of semiotics in connecting the spaces, words and embodied experiences of refugee politics
Authors: Cole Georgia
Published: December 2016

Despite the every‐day prevalence of the term ‘refugee’, fundamental questions often remain unasked. What meanings do actors associate with the label? What intentions might be driving the word's use and/or manipulation? And what implications might the existence of multiple interpretations have for the persons under discussion and the processes within which they sit? Though this is evidently important in popular accounts, where the term's misuse fuels anti‐immigration sentiments and societal mistrust, the ramifications of these multiple interpretations for assisting refugees and negotiating durable solutions have lacked critical exploration. Existing approaches to understanding the politics of the refugee regime have tended to focus on physical sites of contestation, such as refugee camps. This article re‐introduces semiotics as a heuristic framework through which to understand how the word ‘refugee’ in itself constitutes a disputed arena, and to explore what impacts this has on negotiations over their future. This approach is used to explain the controversial negotiations surrounding the invocation of the Cessation Clause for Rwandan refugees in Uganda. Extensive resistance to the cancellation of Rwandan refugees’ statuses has not been met by commensurate attempts to explain when, why and how this process unfolded. Through conceptualising the word ‘refugee’ as a sign according to the Saussurean and Barthean models of semiotics, this piece charts the multiple meanings that this label signified alongside its established legal‐normative definition, and discusses what implications this had for how durable solutions were negotiated. Disaggregating the label provides a route through which to explore what enables the conceptual and spatial dissonance that plagues certain attempts to conclude protracted refugee situations. The piece concludes by discussing the analytical possibilities that emerge from re‐engaging with socio‐semiotic approaches, including through proposing greater engagement with the political geographies of words and their meanings.
A large national study of ferritin testing in Canadian blood donors
Authors: Goldman Mindy , Uzicanin Samra , Osmond Lori , Scalia Vito , O'Brien Sheila F.
Published: December 2016

BACKGROUND

We assessed risk groups for iron deficiency and the feasibility and efficacy of ferritin testing in a large blood center.

STUDY DESIGN AND METHODS

Donors were informed of possible testing in the predonation pamphlet. Plasma ferritin was measured on retention samples (n = 12,595) from representative clinics. Low‐ferritin donors (<25 µg/L) were sent a letter and information sheet and not called for 6 months. Ferritin testing was repeated on 25% of donors; donor return rate and frequency were monitored.

RESULTS

Low‐ferritin donors represented 2.9% of first‐time and reactivated (no donation in past 12 months) male donors, 32.2% of first‐time and reactivated female donors, 41.6% of repeat male donors, and 65.1% of repeat female donors. A mean of 11.7 months after index donation, the return rate was 76% for normal and 58% for low‐ferritin donors; returning low‐ferritin donors had made approximately one fewer donation. Ferritin increased by 16.3 and 12.1 µg/L in male and female low‐ferritin donors and decreased by 17 µg/L in male and female normal‐ferritin donors.

CONCLUSION

The minimum hemoglobin level will be increased to 130 g/L for male donors and the minimum interdonation interval changed to 84 days (four donations yearly) for female donors based on iron deficiency risk groups. Large‐scale ferritin testing was feasible. Donors informed of low‐ferritin results had a lower return rate, donated less often, and had an increase in ferritin on return, approximately 1 year after initial testing, compared to donors with normal ferritin results.
Rapid and durable response to intravenous immunoglobulin in delayed heparin‐induced thrombocytopenia: a case report
Authors: Lei Brandon Z. , Shatzel Joseph J. , Sendowski Merav
Published: December 2016

BACKGROUND

Heparin‐induced thrombocytopenia (HIT) results in platelet consumption and a virulent thrombotic state, which generally responds to cessation of heparin and initiation of anticoagulation. Rarely, delayed HIT can occur and/or persist after heparin is discontinued.

STUDY DESIGN AND METHODS

A 47‐year‐old male developed delayed HIT with severe thrombocytopenia and thrombosis after cardiac surgery. Thrombocytopenia developed and persisted after heparin cessation and did not improve despite sequential use of argatroban followed by bivalirudin. Treatment with intravenous immunoglobulin (IVIg) was well tolerated and resulted in rapid resolution of thrombocytopenia.

RESULTS

There are few case reports on the management of delayed HIT with severe and prolonged thrombocytopenia. The risk for thrombosis and bleeding in the setting of an undefined time course increases uncertainty in management.

CONCLUSION

This case, along with others accumulating in the literature, suggest that IVIg may be effective in treating delayed HIT with persistent thrombocytopenia.
Reducing blood volume requirements for clinical pathology testing in toxicologic studies—points to consider
Authors: Poitout‐Belissent Florence , Aulbach Adam , Tripathi Niraj , Ramaiah Lila
Published: December 2016

In preclinical safety assessment, blood volume requirements for various endpoints pose a major challenge. The goal of this working group was to review current practices for clinical pathology (CP) testing in preclinical toxicologic studies, and to discuss advantages and disadvantages of methods for reducing blood volume requirements. An industry‐wide survey was conducted to gather information on CP instrumentation and blood collection practices for hematology, clinical biochemistry, and coagulation evaluation in laboratory animals involved in preclinical studies. Based on the survey results and collective experience of the authors, the working group proposes the following “points to consider” for CP testing: (1) For most commercial analyzers, 0.5 mL and 0.8 mL of whole blood are sufficient for hematology and biochemistry evaluation, respectively. (2) Small analyzers with low volume requirements and low throughput have limited utility in preclinical studies. (3) Sample pooling or dilution is inappropriate for many CP methods. (4) Appropriate collection sites should be determined based on blood volume requirements and technical expertise. (5) Microsampling does not provide sufficient volume given current analyzer and quality assurance requirements. (6) Study design considerations include: the use of older/larger animals (rodents), collection of CP samples before toxicokinetic samples, use of separate subsets of mice for hematology and clinical biochemistry testing, use of a priority list for clinical biochemistry, and when possible, eliminating coagulation testing.
Spatial Probabilistic Modeling of Corrosion in Ship
Structures
Authors: Luque Jesus , Hamann Rainer , Straub Daniel
Published: December 2016

Corrosion in ship structures is influenced by a variety of factors that are varying in time and space. Existing corrosion models used in practice only partially address the spatial variability of the corrosion process. Typical estimations of corrosion model parameters are based on averaging measurements for one ship type over structural elements from different ships and operational conditions. Most models do not explicitly predict the variability and correlation of the corrosion process among multiple locations in the structure. This correlation is of relevance when determining the necessary inspection coverage, and it can influence the reliability of the ship structure. In this paper, we develop a probabilistic spatiotemporal corrosion model based on a hierarchical approach, which represents the spatial variability and correlation of the corrosion process. The model includes as hierarchical levels vessel–compartment–frame–structural element–plate element. At all levels, variables representing common influencing factors (e.g., coating life) are introduced. Moreover, at the lowest level, which is the one of the plate element, the corrosion process can be modeled as a spatial random field. For illustrative purposes, the model is trained through Bayesian analysis with measurement data from a group of tankers. In this application, the spatial dependence among corrosion processes in different parts of the ships is identified and quantified using the proposed hierarchical model. Finally, how this spatial dependence can be exploited when making inference on the future condition of the ships is demonstrated.
Stick–Slip Motion of the Chaplygin Sleigh With a Piecewise-Smooth Nonholonomic Constraint
Authors: Fedonyuk Vitaliy , Tallapragada Phanindra
Published: December 2016

The Chaplygin sleigh is a canonical problem of mechanical systems with nonholonomic constraints. Such constraints often arise due to the role of a no-slip requirement imposed by friction. In the case of the Chaplygin sleigh, it is well known that its asymptotic motion is that of pure translation along a straight line. Any perturbations in angular velocity decay and result in an increase in asymptotic speed of the sleigh. Such motion of the sleigh is under the assumption that the magnitude of friction is as high as necessary to prevent slipping. We relax this assumption by setting a maximum value to the friction. The Chaplygin sleigh is then under a piecewise-smooth nonholonomic constraint and transitions between “slip” and “stick” modes. We investigate these transitions and the resulting nonsmooth dynamics of the system. We show that the reduced state space of the system can be partitioned into sets of distinct dynamics and that the stick–slip transitions can be explained in terms of transitions of the state of the system between these sets.
Nonlinear Assembly Tolerance Design for Spatial Mechanisms Based on Reliability Methods
Authors: Yin Yin , Hong Nie , Fei Feng , Xiaohui Wei , Huajin Ni
Published: December 2016

Assembly tolerance design for spatial mechanisms is a complex engineering problem that involves a highly nonlinear dimension chain equation and challenges in simplifying the spatial mechanism matrix equation. To address the nonlinearity of the problem and the difficulty of simplifying the dimension chain equation, this paper investigates the use of the Rackwitz–Fiessler (R–F) reliability analysis method and several surrogate model methods, respectively. The tolerance analysis results obtained for a landing gear assembly problem using the R–F method and the surrogate model methods indicate that compared with the extremum method and the probability method, the R–F method allows more accurate and efficient computation of the successful assembly rate, a reasonable tolerance allocation design, and cost reductions of 37% and 16%, respectively. Moreover, the surrogate-model-based computation results show that the support vector machine (SVM) method offers the highest computational accuracy among the three investigated surrogate methods but is more time consuming, whereas the response surface method and the back propagation (BP) neural network method offer relatively low accuracy but higher calculation efficiency. Overall, all of the surrogate model methods provide good computational accuracy while requiring far less time for analysis and computation compared with the simplification of the dimension chain equation or the Monte Carlo method.
Robust Design Optimization for Crashworthiness of Vehicle Side
Impact
Authors: Chakraborty Souvik , Chatterjee Tanmoy , Chowdhury Rajib , Adhikari Sondipon
Published: December 2016

Optimization for crashworthiness is of vast importance in automobile industry. Recent advancement in computational prowess has enabled researchers and design engineers to address vehicle crashworthiness, resulting in reduction of cost and time for new product development. However, a deterministic optimum design often resides at the boundary of failure domain, leaving little or no room for modeling imperfections, parameter uncertainties, and/or human error. In this study, an operational model-based robust design optimization (RDO) scheme has been developed for designing crashworthiness of vehicle against side impact. Within this framework, differential evolution algorithm (DEA) has been coupled with polynomial correlated function expansion (PCFE). An adaptive framework for determining the optimum basis order in PCFE has also been presented. It is argued that the coupled DEA–PCFE is more efficient and accurate, as compared to conventional techniques. For RDO of vehicle against side impact, minimization of the weight and lower rib deflection of the vehicle are considered to be the primary design objectives. Case studies by providing various emphases on the two objectives have also been performed. For all the cases, DEA–PCFE is found to yield highly accurate results.
Implantable microcoils for intracortical magnetic stimulation
Authors: Lee Seung Woo , Fallegger Florian , Casse Bernard D. F. , Fried Shelley I.
Published: December 2016

Magnetic stimulation from cortically implantable microcoils can activate neuronal circuits with high selectivity and reliability.
Timing of the formation and migration of giant planets as constrained by CB chondrites
Authors: Johnson Brandon C. , Walsh Kevin J. , Minton David A. , Krot Alexander N. , Levison Harold F.
Published: December 2016

Early dynamical excitement by giant planets leads to the formation of the unique CB chondrite meteorites.
Suppressing relaxation in superconducting qubits by quasiparticle pumping
Authors: Gustavsson Simon , Yan Fei , Catelani Gianluigi , Bylander Jonas , Kamal Archana , Birenbaum Jeffrey , Hover David , Rosenberg Danna , Samach Gabriel , Sears Adam P. , Weber Steven J. , Yoder Jonilyn L. , Clarke John , Kerman Andrew J. , Yoshihara Fumiki , Nakamura Yasunobu , Orlando Terry P. , Oliver William D.
Published: December 2016

Extending qubit lifetime through a shaped environment

Qubits are the quantum two-level systems that encode and process information in quantum computing. Kept in isolation, qubits can be stable. In a practical setting, however, qubits must be addressed and interact with each other. Such an environment is typically viewed as a source of decoherence and has a detrimental effect on a qubit's ability to retain encoded information. Gustavsson
et al.
used a sequence of pulses as a source of “environment shaping” that could substantially increase the coherence time of a superconducting qubit.

Science
, this issue p.
1573
Discovery of Polyesterases from Moss-Associated Microorganisms
Authors: Müller Christina Andrea , Perz Veronika , Provasnek Christoph , Quartinello Felice , Guebitz Georg M. , Berg Gabriele
Published: December 2016

The growing pollution of the environment with plastic debris is a global threat which urgently requires biotechnological solutions. Enzymatic recycling not only prevents pollution but also would allow recovery of valuable building blocks. Therefore, we explored the existence of microbial polyesterases in microbial communities associated with the
Sphagnum magellanicum
moss, a key species within unexploited bog ecosystems. This resulted in the identification of six novel esterases, which were isolated, cloned, and heterologously expressed in
Escherichia coli
. The esterases were found to hydrolyze the copolyester poly(butylene adipate-
co
-butylene terephthalate) (PBAT) and the oligomeric model substrate bis[4-(benzoyloxy)butyl] terephthalate (BaBTaBBa). Two promising polyesterase candidates, EstB3 and EstC7, which clustered in family VIII of bacterial lipolytic enzymes, were purified and characterized using the soluble esterase substrate
p
-nitrophenyl butyrate (

K
m

values of 46.5 and 3.4 μM, temperature optima of 48°C and 50°C, and pH optima of 7.0 and 8.5, respectively). In particular, EstC7 showed outstanding activity and a strong preference for hydrolysis of the aromatic ester bond in PBAT. Our study highlights the potential of plant-associated microbiomes from extreme natural ecosystems as a source for novel hydrolytic enzymes hydrolyzing polymeric compounds.

IMPORTANCE
In this study, we describe the discovery and analysis of new enzymes from microbial communities associated with plants (moss). The recovered enzymes show the ability to hydrolyze not only common esterase substrates but also the synthetic polyester poly(butylene adipate-
co
-butylene terephthalate), which is a common material employed in biodegradable plastics. The widespread use of such synthetic polyesters in industry and society requires the development of new sustainable technological solutions for their recycling. The discovered enzymes have the potential to be used as catalysts for selective recovery of valuable building blocks from this material.
Distribution and Differential Survival of Traditional and Alternative Indicators of Fecal Pollution at Freshwater Beaches
Authors: Cloutier Danielle D. , McLellan Sandra L.
Published: December 2016

Alternative indicators have been developed that can be used to identify host sources of fecal pollution, yet little is known about how their distribution and fate compare to traditional indicators.
Escherichia coli
and enterococci were widely distributed at the six beaches studied and were detected in almost 95% of water samples (
n
= 422) and 100% of sand samples (
n
= 400). Berm sand contained the largest amount of
E. coli
(
P
< 0.01), whereas levels of enterococci were highest in the backshore (
P
< 0.01).
E. coli
and enterococci were the lowest in water, using a weight-to-volume comparison. The gull-associated
Catellicoccus marimammalium
(Gull2) marker was found in over 80% of water samples, regardless of
E. coli
levels, and in 25% of sand samples. Human-associated
Bacteroides
(HB) and
Lachnospiraceae
(Lachno2) were detected in only 2.4% of water samples collected under baseflow and post-rain conditions but produced a robust signal after a combined sewage overflow, despite low
E. coli
concentrations. Burdens of
E. coli
and enterococci in water and sand were disproportionately high in relation to alternative indicators when comparing environmental samples to source material. In microcosm studies, Gull2, HB, and Lachno2 quantitative PCR (qPCR) signals were reduced twice as quickly as those from
E. coli
and enterococci and approximately 20% faster than signals from culturable
E. coli
. High concentrations of alternative indicators in source material illustrated their high sensitivity for the identification of fecal sources; however, differential survival and the potential for long-term persistence of traditional fecal indicators complicate the use of alternative indicator data to account for the levels of
E. coli
and enterococci in environmental samples.

IMPORTANCE
E. coli
and enterococci are general indicators of fecal pollution and may persist in beach sand, making their use problematic for many applications. This study demonstrates that gull fecal pollution is widespread at Great Lakes beaches, whereas human and ruminant contamination is evident only after major rain events. An exploration of sand as a reservoir for indicators found that
E. coli
was ubiquitous, while gull host markers were detected in only 25% of samples.
In situ
sand beach microcosms provided decay rate constants for
E. coli
and enterococci relative to alternative indicators, which establish comparative benchmarks that would be helpful to distinguish recent from past pollution. Overall, alternative indicators are useful for identifying sources and assessing potentially high health risk contamination events; however, beach managers should be cautious in attempting to directly link their detection to the levels of
E. coli
or enterococci.
Relationships and Evolution of Double-Stranded RNA Totiviruses of Yeasts Inferred from Analysis of L-A-2 and L-BC Variants in Wine Yeast Strain Populations
Authors: Rodríguez-Cousiño Nieves , Esteban Rosa
Published: December 2016

Saccharomyces cerevisiae
killer strains secrete a protein toxin active on nonkiller strains of the same (or other) yeast species. Different killer toxins, K1, K2, K28, and Klus, have been described. Each toxin is encoded by a medium-size (1.5- to 2.3-kb) M double-stranded RNA (dsRNA) located in the cytoplasm. M dsRNAs require L-A helper virus for maintenance. L-A belongs to the
Totiviridae
family, and its dsRNA genome of 4.6 kb codes for the major capsid protein Gag and a minor Gag-Pol protein, which form the virions that separately encapsidate L-A or the M satellites. Different L-A variants exist in nature; on average, 24% of their nucleotides are different. Previously, we reported that L-A-lus was specifically associated with Mlus, suggesting coevolution, and proposed a role of the toxin-encoding M dsRNAs in the appearance of new L-A variants. Here we confirm this by analyzing the helper virus in K2 killer wine strains, which we named L-A-2. L-A-2 is required for M2 maintenance, and neither L-A nor L-A-lus shows helper activity for M2 in the same genetic background. This requirement is overcome when coat proteins are provided in large amounts by a vector or in
ski
mutants. The genome of another totivirus, L-BC, frequently accompanying L-A in the same cells shows a lower degree of variation than does L-A (about 10% of nucleotides are different). Although L-BC has no helper activity for M dsRNAs, distinct L-BC variants are associated with a particular killer strain. The so-called L-BC-lus (in Klus strains) and L-BC-2 (in K2 strains) are analyzed.

IMPORTANCE
Killer strains of
S. cerevisiae
secrete protein toxins that kill nonkiller yeasts. The “killer phenomenon” depends on two dsRNA viruses: L-A and M. M encodes the toxin, and L-A, the helper virus, provides the capsids for both viruses. Different killer toxins exist: K1, K2, K28, and Klus, encoded on different M viruses. Our data indicate that each M dsRNA depends on a specific helper virus; these helper viruses have nucleotide sequences that may be as much as 26% different, suggesting coevolution. In wine environments, K2 and Klus strains frequently coexist. We have previously characterized the association of Mlus and L-A-lus. Here we sequence and characterize L-A-2, the helper virus of M2, establishing the helper virus requirements of M2, which had not been completely elucidated. We also report the existence of two specific L-BC totiviruses in Klus and K2 strains with about 10% of their nucleotides different, suggesting different evolutionary histories from those of L-A viruses.
Draft Genome Sequences of Two
Fabibacter
sp. Strains Isolated from Coastal Surface Water of Aburatsubo Inlet, Japan
Authors: Kaneko Ryo , Wong Shu-Kuan , Ogura Yoshitoshi , Hayashi Tetsuya , Yoshizawa Susumu , Hamasaki Koji
Published: December 2016

Here, we report the draft genome sequences of
Fabibacter
sp. strain 4D4 and
F. misakiensis
strain SK-8
T
, isolated from surface seawater of a semienclosed inlet.
Draft Genome Sequences of Two Historical Listeria monocytogenes Strains from Human Listeriosis Cases in 1933
Authors: Dutta Vikrant , Lee Sangmi , Ward Todd J. , Orwig Nathane , Altermann Eric , Jima Dereje , Parsons Cameron , Kathariou Sophia
Published: December 2016

We report here the draft genome sequences of two
Listeria monocytogenes
strains from some of the earliest reported cases of human listeriosis in North America. The strains were isolated in 1933 from patients in Massachusetts and Connecticut, USA, and belong to the widely disseminated hypervirulent clonal complex 1 (CC1) and CC2.
Tidal rhythmites in the southern Bouse Formation as evidence for post-Miocene uplift of the lower Colorado River corridor
Authors: O’Connell Brennan , Dorsey Rebecca J. , Humphreys Eugene D.
Published: December 2016

Uncertainty over depositional paleoenvironments of the upper Miocene to lower Pliocene Bouse Formation obscures our understanding of the timing and magnitude of regional uplift as well as the conditions and processes that were active during integration and early evolution of the Colorado River (western United States). This paper presents new sedimentologic and quantitative evidence for a strong tidal influence on deposition of the basal carbonate member of the southern Bouse Formation. Lithofacies with tidal sedimentary structures include lime mudstone with reed and grass imprints; heterolithic facies with horizontal, flaser, wavy, and lenticular bedding; and cross-bedded grainstone with sigmoidal bundles, reactivation surfaces, and complex bedding. Systematic alternation of relatively thick and thin layers records a predominantly semidiurnal mixed-tidal depositional environment, and Fourier analysis highlights the cyclic, non-random nature of layer-thickness trends. These observations provide evidence that the southern Bouse Formation accumulated in a pre–Colorado River tide-dominated marine setting at the north end of the Gulf of California. Deposition at sea level requires ∼330 m of uplift in the lower Colorado River and western Colorado Plateau region during the past ∼5.0 m.y.
Mixed ethnicity and behavioural problems in the Millennium Cohort Study
Authors: Zilanawala Afshin , Sacker Amanda , Kelly Yvonne
Published: December 2016

Background

The population of mixed ethnicity individuals in the UK is growing. Despite this demographic trend, little is known about mixed ethnicity children and their problem behaviours. We examine trajectories of behavioural problems among non-mixed and mixed ethnicity children from early to middle childhood using nationally representative cohort data in the UK.

Methods

Data from 16 330 children from the Millennium Cohort Study with total difficulties scores were analysed. We estimated trajectories of behavioural problems by mixed ethnicity using growth curve models.

Results

White mixed (mean total difficulties score: 8.3), Indian mixed (7.7), Pakistani mixed (8.9) and Bangladeshi mixed (7.2) children had fewer problem behaviours than their non-mixed counterparts at age 3 (9.4, 10.1, 13.1 and 11.9, respectively). White mixed, Pakistani mixed and Bangladeshi mixed children had growth trajectories in problem behaviours significantly different from that of their non-mixed counterparts.

Conclusions

Using a detailed mixed ethnic classification revealed diverging trajectories between some non-mixed and mixed children across the early life course. Future studies should investigate the mechanisms, which may influence increasing behavioural problems in mixed ethnicity children.
Training paediatric healthcare staff in recognising, understanding and managing conflict with patients and families: findings from a survey on immediate and 6-month impact
Authors: Forbat Liz , Simons Jean , Sayer Charlotte , Davies Megan , Barclay Sarah
Published: December 2016

Background

Conflict is a recognised component of healthcare. Disagreements about treatment protocols, treatment aims and poor communication are recognised warning signs. Conflict management strategies can be used to prevent escalation, but are not a routine component of clinical training.

Objective

To report the findings from a novel training intervention, aimed at enabling paediatric staff to identify and understand the warning signs of conflict, and to implement conflict resolution strategies.

Design and setting

Self-report measures were taken at baseline, immediately after the training and at 6 months. Questionnaires recorded quantitative and qualitative feedback on the experience of training, and the ability to recognise and de-escalate conflict. The training was provided in a tertiary teaching paediatric hospital in England over 18 months, commencing in June 2013.

Intervention

A 4-h training course on identifying, understanding and managing conflict was provided to staff.

Results

Baseline data were collected from all 711 staff trained, and 6-month follow-up data were collected for 313 of those staff (44%). The training was successful in equipping staff to recognise and de-escalate conflict. Six months after the training, 57% of respondents had experienced conflict, of whom 91% reported that the training had enabled them to de-escalate the conflict. Learning was retained at 6 months with staff more able than at baseline recognising conflict triggers (Fischer's exact test, p=0.001) and managing conflict situations (Pearson's χ2test, p=0.001).

Conclusions

This training has the potential to reduce substantially the human and economic costs of conflicts for healthcare providers, healthcare staff, patients and relatives.
Epidemiology of 3825 injuries sustained in six seasons of National Collegiate Athletic Association men's and women's soccer (2009/2010–2014/2015)
Authors: Roos Karen G , Wasserman Erin B , Dalton Sara L , Gray Aaron , Djoko Aristarque , Dompier Thomas P , Kerr Zachary Y
Published: December 2016

Aim

To describe the epidemiology of National Collegiate Athletic Association (NCAA) men's and women's soccer injuries during the 2009/2010–2014/2015 academic years.

Methods

This descriptive epidemiology study used NCAA Injury Surveillance Program (NCAA-ISP) data during the 2009/2010–2014/2015 academic years, from 44 men's and 64 women's soccer programmes (104 and 167 team seasons of data, respectively). Non-time-loss injuries were defined as resulting in <24 h lost from sport. Injury counts, percentages and rates were calculated. Injury rate ratios (RRs) and injury proportion ratios (IPRs) with 95% CIs compared rates and distributions by sex.

Results

There were 1554 men's soccer and 2271 women's soccer injuries with injury rates of 8.07/1000 athlete exposures (AE) and 8.44/1000AE, respectively. Injury rates for men and women did not differ in competitions (17.53 vs 17.04/1000AE; RR=1.03; 95% CI 0.94 to 1.13) or practices (5.47 vs 5.69/1000AE; RR=0.96; 95% CI 0.88 to 1.05). In total, 47.2% (n=733) of men's soccer injuries and 47.5% (n=1079) of women's were non-time loss. Most injuries occurred to the lower extremity and were diagnosed as sprains. Women had higher concussion rates (0.59 vs 0.34/1000AE; RR=1.76; 95% CI 1.32 to 2.35) than men.

Conclusions

Non-time-loss injuries accounted for nearly half of the injuries in men's and women's soccer. Sex differences were found in competition injuries, specifically for concussion. Further study into the incidence, treatment and outcome of non-time-loss injuries may identify a more accurate burden of these injuries.
Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol
Authors: Calderone Alicia , Stevens Wendy , Prior David , Nandurkar Harshal , Gabbay Eli , Proudman Susanna M , Williams Trevor , Celermajer David , Sahhar Joanne , Wong Peter K K , Thakkar Vivek , Dwyer Nathan , Wrobel Jeremy , Chin Weng , Liew Danny , Staples Margaret , Buchbinder Rachelle , Nikpour Mandana
Published: December 2016

Introduction

Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12–15% of patients with SSc and accounts for 30–40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH.

Methods and analysis

This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken.

Ethics and dissemination

Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals.

Trial registration number

ACTRN12614000418673, Pre-results.
Effect of the number of request calls on the time from call to hospital arrival: a cross-sectional study of an ambulance record database in Nara prefecture, Japan
Authors: Hanaki Nao , Yamashita Kazuto , Kunisawa Susumu , Imanaka Yuichi
Published: December 2016

Objectives

In Japan, ambulance staff sometimes must make request calls to find hospitals that can accept patients because of an inadequate information sharing system. This study aimed to quantify effects of the number of request calls on the time interval between an emergency call and hospital arrival.

Design and setting

A cross-sectional study of an ambulance records database in Nara prefecture, Japan.

Cases

A total of 43 663 patients (50% women; 31.2% aged 80 years and over): (1) transported by ambulance from April 2013 to March 2014, (2) aged 15 years and over, and (3) with suspected major illness.

Primary outcome measures

The time from call to hospital arrival, defined as the time interval from receipt of an emergency call to ambulance arrival at a hospital.

Results

The mean time interval from emergency call to hospital arrival was 44.5 min, and the mean number of requests was 1.8. Multilevel linear regression analysis showed that ∼43.8% of variations in transportation times were explained by patient age, sex, season, day of the week, time, category of suspected illness, person calling for the ambulance, emergency status at request call, area and number of request calls. A higher number of request calls was associated with longer time intervals to hospital arrival (addition of 6.3 min per request call; p<0.001). In an analysis dividing areas into three groups, there were differences in transportation time for diseases needing cardiologists, neurologists, neurosurgeons and orthopaedists.

Conclusions

The study revealed 6.3 additional minutes needed in transportation time for every refusal of a request call, and also revealed disease-specific delays among specific areas. An effective system should be collaboratively established by policymakers and physicians to ensure the rapid identification of an available hospital for patient transportation in order to reduce the time from the initial emergency call to hospital arrival.
Pay More Attention: a national mixed methods study to identify the barriers and facilitators to ensuring equal access to high-quality hospital care and services for children and young people with and without learning disabilities and their families
Authors: Oulton Kate , Wray Jo , Carr Lucinda , Hassiotis Angela , Jewitt Carey , Kerry Sam , Tuffrey-Wijne Irene , Gibson Faith
Published: December 2016

Introduction

Despite evidence of health inequalities for adults with intellectual disability (ID) there has yet to be a comprehensive review of how well hospital services are meeting the needs of children and young people (CYP) with ID and their families. We do not know how relevant existing recommendations and guidelines are to CYP, whether these are being applied in the paediatric setting or what difference they are making. Evidence of parental dissatisfaction with the quality, safety and accessibility of hospital care for CYP with ID exists. However, the extent to which their experience differs from parents of CYP without ID is not known and the views and experiences of CYP with ID have not been investigated. We will compare how services are delivered to, and experienced by CYP aged 5–15 years with and without ID and their families to see what inequalities exist, for whom, why and under what circumstances.

Methods and analysis

We will use a transformative, mixed methods case study design to collect data over four consecutive phases. We will involve CYP, parents and hospital staff using a range of methods; interviews, parental electronic diary, hospital and community staff questionnaire, patient and parent satisfaction questionnaire, content analysis of hospital documents and a retrospective mapping of patient hospital activity. Qualitative data will be managed and analysed using NVivo and quantitative data will be analysed using parametric and non-parametric descriptive statistics.

Ethics and dissemination

The study will run from December 2015 to November 2018. We have Health Authority Approval (IRAS project ID: 193932) for phase 1 involving staff only and ethical and Health Authority Approval for phases 2–4 (IRAS project ID: 178525). We will disseminate widely to relevant stakeholders, using a range of accessible formats, including social media. We will publish in international peer-reviewed journals and present to professional, academic and lay audiences through national and international conferences.