bluuebunny/crossref_metadata_2025 huggingface dataset:
Acoustic correlates of prominence in Yawarana
Authors: Cáceres Arandia Natalia , Moore Alyssa , Post Zac , Gildea Spike , Baese-Berk Melissa M.
Published: April 2018

Yawarana (Cariban) is a critically endangered language of Venezuela, with 20–30 speakers and little published research beyond wordlists. In these wordlists, orthographic indications of stress and/or vowel length are inconsistent. As part of our language documentation project, we examine acoustic correlates of prominence in Yawarana. Many other languages in the Cariban family have a clear rhythmic stress system, with vowel lengthening and pitch excursion marking prominence; Yawarana does not mark prominence in the same way. Even so, in some situations, native speakers do appear to attend to stress (i.e., when correcting the pronunciation of language learners). Here, we ask what the acoustic correlates of prominence are, paying particular attention to intensity, pitch, and duration information. We are examining over 200 lexical items produced by four native speakers. These items are repeated in isolation, produced in carrier phrases, and produced in narratives and conversations. We compare measures of prominence in each of these situations. This investigation will pave the way for a more in-depth study of acoustic features of Yawarana and will inform future studies of prominence in other Cariban languages.
A characterization of the instantaneous wave front distortion characteristics in SW06 and ASIAEX 2001 data and strategies for exploiting lucky scintillations
Authors: Kirsteins Ivars P.
Published: April 2018

Long line arrays are highly susceptible to signal wave front distortions caused by random medium effects like internal waves. Effects include large localization errors, biases, and loss of array gain. In earlier work, we had showed evidence from real data [Kirsteins and Ge, IEEE UASP workshop, Oct. 2017] that lucky scintillations, i.e., moments when the instantaneous signal wave front is relatively undistorted, occur regularly at much shorter time scales even during periods of strong internal wave activity that could potentially be exploited to improve array processing in environments with apparently poor spatial coherence. To better understand the phenomenon of lucky scintillations and how they can be used in array processing, we characterize in this paper the instantaneous or short time signal wave front distortion behaviors of horizontal line array (HLA) data from the Shallow Water 2006 (SW06) and ASIAEX 2001 experiments provided by the Woods Hole Oceanographic Institute, examining the time scales and the rate at which these lucky scintillations occur. Our analysis suggests an alternative array processing strategy by collecting data snap shots over a time interval matched to the ocean random medium time scales and using only the best snap shots in the estimator.
Method for the measurement of the underwater transient sound characteristics in a reverberation tank
Authors: Yu Xinyue , Tang Rui , Li Qi , Zhang Junming
Published: April 2018

A method to evaluate the sound power of transient sound sources in reverberation tanks is proposed and tested. The method is based on the steady state sound field characteristics in closed space, which are analyzed by normal-wave theory. To eliminate the interference caused by the boundary of the sound field, the volume integral of the spatial mean-square pressure in local space is measured and the sound power density of the non-anechoic is then obtained. Using the relationship between the sound field in the enclosed space and that of the free field, the sound power of the sound source can be obtained using the measured spatial mean-square pressure. The sound power of an impulsive sound generated by a spherical sound source is measured in a reverberation tank and the results are compared with the sound power measured in anechoic pool to verify the accuracy of the proposed method. The proposed method can be used to measure the radiated sound power of different types of transient sound sources in reverberation tanks.
Machine learning–enabled identification of material phase transitions based on experimental data: Exploring collective dynamics in ferroelectric relaxors
Authors: Li Linglong , Yang Yaodong , Zhang Dawei , Ye Zuo-Guang , Jesse Stephen , Kalinin Sergei V. , Vasudevan Rama K.
Published: April 2018

Machine learning of dynamic responses allows determination of structural phase transitions in relaxor ferroelectrics.
Hydrophilic directional slippery rough surfaces for water harvesting
Authors: Dai Xianming , Sun Nan , Nielsen Steven O. , Stogin Birgitt Boschitsch , Wang Jing , Yang Shikuan , Wong Tak-Sing
Published: April 2018

A hydrophilic directional slippery rough surface outperforms conventional liquid-repellent surfaces in water harvesting.
Molecular engineered conjugated polymer with high thermal conductivity
Authors: Xu Yanfei , Wang Xiaoxue , Zhou Jiawei , Song Bai , Jiang Zhang , Lee Elizabeth M. Y. , Huberman Samuel , Gleason Karen K. , Chen Gang
Published: April 2018

Molecular engineering of intra- and interchain interactions transforms polymers into good heat conductors.
Shaken and stirred: Random organization reduces viscosity and dissipation in granular suspensions
Authors: Ness Christopher , Mari Romain , Cates Michael E.
Published: April 2018

Driven tuning dramatically enhances flowability in a broad class of suspended granular materials.
Giant perpendicular magnetic anisotropy in Fe/III-V nitride thin films
Authors: Yu Jie-Xiang , Zang Jiadong
Published: April 2018

Order-of-magnitude enhancement of PMA is induced by first-order correction of spin-orbit coupling.
Molecular Characterization of
qnrVC
Genes and Their Novel Alleles in Vibrio spp. Isolated from Food Products in China
Authors: Zhang Yanyan , Zheng Zhiwei , Chan Edward Wai-Chi , Dong Ning , Xia Xiaodong , Chen Sheng
Published: April 2018

This study reports the prevalences of
qnrVC
genes in 74 ciprofloxacin-resistant
Vibrio
sp. isolates. Two novel functional
qnrVC
alleles,
qnrVC8
and
qnrVC9
, sharing 98% and 99% nucleotide similarity with
qnrVC6
and
qnrVC7
, respectively, were identified. Our findings suggested that carriage of
qnrVC
alleles, together with target mutations in
gyrA
and
parC
genes, may contribute to the development of fluoroquinolone resistance in
Vibrio
species, posing a serious threat to public health.
Adipocyte Model of Mycobacterium tuberculosis Infection Reveals Differential Availability of Iron to Bacilli in the Lipid-Rich Caseous Environment
Authors: Nandy Ananya , Mondal Anupam Kumar , Pandey Rajesh , Arumugam Prabhakar , Dawa Stanzin , Jaisinghani Neetika , Rao Vivek , Dash Debasis , Gandotra Sheetal
Published: April 2018

Mycobacterium tuberculosis
, a successful human pathogen, utilizes multiple carbon sources from the host but adapts to a fatty-acid-rich environment
in vivo
. We sought to delineate the physiologic response of
M. tuberculosis
to a lipid-rich environment by using differentiated adipocytes as a model system. Global transcriptome profiling based on RNA sequencing was performed for bacilli from infected adipocytes and preadipocytes. Genes involved in
de novo
fatty acid synthesis were downregulated, while those predicted to be involved in triglyceride biosynthesis were upregulated, in bacilli isolated from adipocytes, indicating reliance on host-derived fatty acids. Transcription factor network analysis indicated suppression of IdeR-regulated genes, suggesting decreased iron uptake by
M. tuberculosis
in the adipocyte model. This suppression of iron uptake coincided with higher ferritin and iron levels in adipocytes than in preadipocytes. In accord with the role of iron in mediating oxidative stress, we observed upregulation of genes involved in mitigating oxidative stress in
M. tuberculosis
isolated from adipocytes. We provide evidence that oleic acid, a major host-derived fatty acid, helps reduce the bacterial cytoplasm, thereby providing a safe haven for an
M. tuberculosis
mutant that is sensitive to iron-mediated oxidative stress. Via an independent mechanism, host ferritin is also able to rescue the growth of this mutant. Our work highlights the inherent synergy between macronutrients and micronutrients of the host environment that converge to provide resilience to the pathogen. This complex synergy afforded by the adipocyte model of infection will aid in the identification of genes required by
M. tuberculosis
in a caseous host environment.
Vibrio cholerae Outer Membrane Vesicles Inhibit Bacteriophage Infection
Authors: Reyes-Robles Tamara , Dillard Rebecca S. , Cairns Lynne S. , Silva-Valenzuela Cecilia A. , Housman Max , Ali Afsar , Wright Elizabeth R. , Camilli Andrew
Published: April 2018

Phages have been increasingly recognized for the significance of their interactions with bacterial cells in multiple environments. Bacteria use myriad strategies to defend against phage infection, including restriction modification, abortive infection, phase variation of cell surface receptors, phage-inducible chromosomal islands, and clustered regularly interspaced short palindromic repeat(s) (CRISPR)-Cas systems. The data presented here suggest that the apparently passive process of OMV release can also contribute to phage defense. By considering the effect of OMVs on
V. cholerae
infection by three unique virulent phages, ICP1, ICP2, and ICP3, we show that,
in vitro
, a reproducible reduction in bacterial killing is both dose and phage receptor dependent. This work supports a role for OMVs as natural decoys to defend bacteria from phage predation.
Comparative Analysis of
UL16
Mutants Derived from Multiple Strains of Herpes Simplex Virus 2 (HSV-2) and HSV-1 Reveals Species-Specific Requirements for the UL16 Protein
Authors: Gao Jie , Yan Xiaohu , Banfield Bruce W.
Published: April 2018

Orthologs of the herpes simplex virus (HSV)
UL16
gene are conserved throughout the
Herpesviridae
. Because of this conservation, one might expect that the proteins perform similar functions for all herpesviruses. Previous studies on a
UL16
-null mutant derived from HSV-2 strain 186 revealed a roughly 100-fold replication defect and a critical role for UL16 in the nuclear egress of capsids. These findings were in stark contrast to what has been observed with
UL16
mutants of HSV-1 and pseudorabies virus, where roughly 10-fold replication deficiencies that were accompanied by defects in the secondary envelopment of cytoplasmic capsids were reported. One possible explanation for this discrepancy is that HSV-2 strain 186 is not representative of the HSV-2 species. To address this possibility, multiple
UL16
-null mutants were constructed in multiple HSV-2 and HSV-1 strains by CRISPR/Cas9 mutagenesis, and their phenotypes were characterized side by side. This analysis showed that all the HSV-2
UL16
mutants had 50- to 100-fold replication deficiencies that were accompanied by defects in the nuclear egress of capsids, as well as defects in the secondary envelopment of cytoplasmic capsids. By contrast, most HSV-1
UL16
mutants had 10-fold replication deficiencies that were accompanied by defects in secondary envelopment of cytoplasmic capsids. These findings indicated that UL16 has HSV species-specific functions. Interestingly, HSV-1 UL16 could promote the nuclear egress of HSV-2
UL16
-null strains, suggesting that, unlike HSV-1, HSV-2 lacks an activity that can promote nuclear egress in the absence of UL16.

IMPORTANCE
HSV-2 and HSV-1 are important human pathogens that cause distinct diseases in their hosts. A complete understanding of the morphogenesis of these viruses is expected to reveal vulnerabilities that can be exploited in the treatment of HSV disease. UL16 is a virion structural component that is conserved throughout the
Herpesviridae
and functions in virus morphogenesis; however, previous studies have suggested different roles for UL16 in the morphogenesis of HSV-2 and HSV-1. This study sought to resolve this apparent discrepancy by analyzing multiple UL16 mutant viruses derived from multiple strains of HSV-2 and HSV-1. The data indicate that UL16 has HSV species-specific functions, as HSV-2 has a requirement for UL16 in the escape of capsids from the nucleus whereas both HSV-2 and HSV-1 require UL16 for final envelopment of capsids at cytoplasmic membranes.
Microbiota and Metatranscriptome Changes Accompanying the Onset of Gingivitis
Authors: Nowicki Emily M. , Shroff Raghav , Singleton Jacqueline A. , Renaud Diane E. , Wallace Debra , Drury Julie , Zirnheld Jolene , Colleti Brock , Ellington Andrew D. , Lamont Richard J. , Scott David A. , Whiteley Marvin
Published: April 2018

Over half of adults experience gingivitis, a mild yet treatable form of periodontal disease caused by the overgrowth of oral microbes. Left untreated, gingivitis can progress to a more severe and irreversible disease, most commonly chronic periodontitis. While periodontal diseases are associated with a shift in the oral microbiota composition, it remains unclear how this shift impacts microbiota function early in disease progression. Here, we analyzed the transition from health to gingivitis through both 16S v4-v5 rRNA amplicon and metatranscriptome sequencing of subgingival plaque samples from individuals undergoing an experimental gingivitis treatment. Beta-diversity analysis of 16S rRNA reveals that samples cluster based on disease severity and patient but not by oral hygiene status. Significant shifts in the abundance of several genera occurred during disease transition, suggesting a dysbiosis due to development of gingivitis. Comparing taxonomic abundance with transcriptomic activity revealed concordance of bacterial diversity composition between the two quantification assays in samples originating from both healthy and diseased teeth. Metatranscriptome sequencing analysis indicates that during the early stages of transition to gingivitis, a number of virulence-related transcripts were significantly differentially expressed in individual and across pooled patient samples. Upregulated genes include those involved in proteolytic and nucleolytic processes, while expression levels of those involved in surface structure assembly and other general virulence functions leading to colonization or adaptation within the host are more dynamic. These findings help characterize the transition from health to periodontal disease and identify genes associated with early disease.

IMPORTANCE
Although more than 50% of adults have some form of periodontal disease, there remains a significant gap in our understanding of its underlying cause. We initiated this study in order to better characterize the progression from oral health to disease. We first analyzed changes in the abundances of specific microorganisms in dental plaque collected from teeth during health and gingivitis, the mildest form of periodontal disease. We found that the clinical score of disease and patient from whom the sample originated but not tooth brushing are significantly correlated with microbial community composition. While a number of virulence-related gene transcripts are differentially expressed in gingivitis samples relative to health, not all are increased, suggesting that the overall activity of the microbiota is dynamic during disease transition. Better understanding of which microbes are present and their function during early periodontal disease can potentially lead to more targeted prophylactic approaches to prevent disease progression.
Viral Diversity of House Mice in New York City
Authors: Williams Simon H. , Che Xiaoyu , Garcia Joel A. , Klena John D. , Lee Bohyun , Muller Dorothy , Ulrich Werner , Corrigan Robert M. , Nichol Stuart , Jain Komal , Lipkin W. Ian
Published: April 2018

The microbiome of wild
Mus musculus
(house mouse), a globally distributed invasive pest that resides in close contact with humans in urban centers, is largely unexplored. Here, we report analysis of the fecal virome of house mice in residential buildings in New York City, NY. Mice were collected at seven sites in Manhattan, Queens, Brooklyn, and the Bronx over a period of 1 year. Unbiased high-throughput sequencing of feces revealed 36 viruses from 18 families and 21 genera, including at least 6 novel viruses and 3 novel genera. A representative screen of 15 viruses by PCR confirmed the presence of 13 of these viruses in liver. We identified an uneven distribution of diversity, with several viruses being associated with specific locations. Higher mouse weight was associated with an increase in the number of viruses detected per mouse, after adjusting for site, sex, and length. We found neither genetic footprints to known human viral pathogens nor antibodies to lymphocytic choriomeningitis virus.

IMPORTANCE
Mice carry a wide range of infectious agents with zoonotic potential. Their proximity to humans in the built environment is therefore a concern for public health. Laboratory mice are also the most common experimental model for investigating the pathobiology of infectious diseases. In this survey of mice trapped in multiple locations within New York City over a period of 1 year, we found a diverse collection of viruses that includes some previously not associated with house mice and others that appear to be novel. Although we found no known human pathogens, our findings provide insights into viral ecology and may yield models that have utility for clinical microbiology.
Impact of Long-Term Erythromycin Therapy on the Oropharyngeal Microbiome and Resistance Gene Reservoir in Non-Cystic Fibrosis Bronchiectasis
Authors: Choo Jocelyn M. , Abell Guy C. J. , Thomson Rachel , Morgan Lucy , Waterer Grant , Gordon David L. , Taylor Steven L. , Leong Lex E. X. , Wesselingh Steve L. , Burr Lucy D. , Rogers Geraint B.
Published: April 2018

Recent demonstrations that long-term macrolide therapy can prevent exacerbations in chronic airways diseases have led to a dramatic increase in their use. However, little is known about the wider, potentially adverse impacts of these treatments. Substantial disruption of the upper airway commensal microbiota might reduce its contribution to host defense and local immune regulation, while increases in macrolide resistance carriage would represent a serious public health concern. Using samples from a randomized controlled trial, we show that low-dose erythromycin given over 48 weeks influences the composition of the oropharyngeal commensal microbiota. We report that macrolide therapy is associated with significant changes in the relative abundances of members of the
Actinomyces
genus and with significant increases in the carriage of transmissible macrolide resistance. Determining the clinical significance of these changes, relative to treatment benefit, now represents a research priority.
Iron Acquisition and Siderophore Release by Carbapenem-Resistant Sequence Type 258 Klebsiella pneumoniae
Authors: Holden Victoria I. , Wright Meredith S. , Houle Sébastien , Collingwood Abigail , Dozois Charles M. , Adams Mark D. , Bachman Michael A.
Published: April 2018

Carbapenem-resistant
Enterobacteriaceae
, including
K. pneumoniae
, are a major health care concern worldwide because they cause a wide range of infection and are resistant to all or nearly all antibiotics. To cause infection, these bacteria must acquire iron, and a major mechanism of acquiring iron is by secreting a molecule called enterobactin that strips iron from host proteins. However, a subset of carbapenem-resistant
K. pneumoniae
strains that lack a portion of the
entS
gene that is required for enterobactin secretion was recently discovered. To understand how these mutant strains obtain iron, we studied their transcriptional responses, bacterial growth, and enterobactin secretion under iron-limited conditions. We found that strains both with mutated and intact
entS
genes grow under iron-limiting conditions, secrete enterobactin, and utilize an alternate iron source, hemin, for growth. Our data indicate that carbapenem-resistant
K. pneumoniae
can use varied methods for iron uptake during infection.
Pseudomonas aeruginosa
gshA
Mutant Is Defective in Biofilm Formation, Swarming, and Pyocyanin Production
Authors: Van Laar Tricia A. , Esani Saika , Birges Tyler J. , Hazen Bethany , Thomas Jason M. , Rawat Mamta
Published: April 2018

Pseudomonas aeruginosa
is a ubiquitous bacterium that can cause severe opportunistic infections, including many hospital-acquired infections. It is also a major cause of infections in patients with cystic fibrosis.
P. aeruginosa
is intrinsically resistant to a number of drugs and is capable of forming biofilms that are difficult to eradicate with antibiotics. The number of drug-resistant strains is also increasing, making treatment of
P. aeruginosa
infections very difficult. Thus, there is an urgent need to understand how
P. aeruginosa
causes disease in order to find novel ways to treat infections. We show that the principal redox buffer, glutathione (GSH), is involved in intrinsic resistance to the fosfomycin and rifampin antibiotics. We further demonstrate that GSH plays a role in
P. aeruginosa
disease and infection, since a mutant lacking GSH has less biofilm formation, is less able to swarm, and produces less pyocyanin, a pigment associated with infection.
Role of kinesiophobia on pain, disability and quality of life in people suffering from chronic musculoskeletal pain: a systematic review
Authors: Luque-Suarez Alejandro , Martinez-Calderon Javier , Falla Deborah
Published: April 2018

Objective

(1) To explore the level of association between kinesiophobia and pain, disability and quality of life in people with chronic musculoskeletal pain (CMP) detected via cross-sectional analysis and (2) to analyse the prognostic value of kinesiophobia on pain, disability and quality of life in this population detected via longitudinal analyses.

Design

A systematic review of the literature including an appraisal of the risk of bias using the adapted Newcastle Ottawa Scale. A synthesis of the evidence was carried out.

Data sources

An electronic search of PubMed, AMED, CINAHL, PsycINFO, PubPsych and grey literature was undertaken from inception to July 2017.

Eligibility criteria for selecting studies

Observational studies exploring the role of kinesiophobia (measured with the Tampa Scale for Kinesiophobia) on pain, disability and quality of life in people with CMP.

Results

Sixty-three articles (mostly cross-sectional) (total sample=10 726) were included. We found strong evidence for an association between a greater degree of kinesiophobia and greater levels of pain intensity and disability and moderate evidence between a greater degree of kinesiophobia and higher levels of pain severity and low quality of life. A greater degree of kinesiophobia predicts the progression of disability overtime, with moderate evidence. A greater degree of kinesiophobia also predicts greater levels of pain severity and low levels of quality of life at 6 months, but with limited evidence. Kinesiophobia does not predict changes in pain intensity.

Summary/conclusions

The results of this review encourage clinicians to consider kinesiophobia in their preliminary assessment. More longitudinal studies are needed, as most of the included studies were cross-sectional in nature.

Trial registration number

CRD42016042641.
Associations of smoking and alcohol consumption with healthy ageing: a systematic review and meta-analysis of longitudinal studies
Authors: Daskalopoulou Christina , Stubbs Brendon , Kralj Carolina , Koukounari Artemis , Prince Martin , Prina A. Matthew
Published: April 2018

Objectives

The number of older people is growing across the world; however, quantitative synthesis of studies examining the impact of lifestyle factors on the ageing process is rare. We conducted a systematic review and meta-analysis of longitudinal studies to synthesise the associations of smoking and alcohol consumption with healthy ageing (HA).

Methods

Major electronic databases were searched from inception to March 2017 (prospectively registered systematic reviews registration number CRD42016038130). Studies were assessed for methodological quality. Random-effect meta-analysis was performed to calculate pooled ORs and 95% CI.

Results

In total, we identified 28 studies (n=184 543); 27 studies reported results on smoking, 22 on alcohol consumption. 23 studies reported a significant positive association of never or former smoking with HA and 4 non-significant. 12 studies reported a significant positive association of alcohol consumption with HA, 9 no association and 1 negative. Meta-analysis revealed increased pooled OR of HA for never smokers compared with current smokers (2.36, 95% CI 2.03 to 2.75), never smokers compared with former smokers (1.32, 95% CI 1.23 to 1.41), former or never smokers compared with current smokers (1.72, 95% CI 1.20 to 2.47), never smokers compared with past or current smokers (1.29, 95% CI 1.16 to 1.43); drinkers compared with non-drinkers (1.28, 95% CI 1.08 to 1.52), light drinkers compared with non-drinkers (1.12, 95% CI 1.03 to 1.22), moderate drinkers compared with non-drinkers (1.35, 95% CI 0.93 to 1.97) and high drinkers compared with non-drinkers (1.25, 95% CI 1.09 to 1.44). There was considerable heterogeneity in the definition and measurement of HA and alcohol consumption.

Conclusions

There is consistent evidence from longitudinal studies that smoking is negatively associated with HA. The associations of alcohol consumption with HA are equivocal. Future research should focus on the implementation of a single metric of HA, on the use of consistent drinking assessment among studies and on a full-range of confounding adjustment. Our research also highlighted the limited research on ageing in low-and-middle-income countries.
Prognostic value of ki67 in BCG-treated non-muscle invasive bladder cancer: a meta-analysis and systematic review
Authors: He Yuhui , Wang Ning , Zhou Xiaofeng , Wang Jianfeng , Ding Zhenshan , Chen Xing , Deng Yisen
Published: April 2018

Objectives

The aim of this study was to explore the prognostic value of ki67 as a marker in patients with non-muscle invasive bladder cancer (NMIBC) treated with BCG.

Methods

Studies were systematically retrieved from the relevant databases (Web of Science, PubMed, Cochrane Library and Embase), and the expiry date was May 2017. The research steps referred to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement.

Results

A total of 11 studies that complied with the inclusion criteria were included. The expression of ki67 was not statistically significantly associated with recurrence-free survival (RFS) (HR 1.331; 95% CI 0.980 to 1.809). No significant heterogeneity was found among all included studies (I2=36.7%, p=0.148). The expression of ki67 was statistically significantly associated with progression-free survival (PFS) (HR 2.567; 95% CI 1.562 to 4.219), and the overexpression of ki67 was the risk factor for PFS. Significant heterogeneity was noted among all the included studies (I2=55.6%, p=0.021). The studies that might cause heterogeneity were excluded using the Galbraith plot, and then the meta-analysis was performed again. The results showed that the expression of ki67 was still associated with PFS (HR 2.922; 95% CI 2.002 to 4.266).

Conclusions

The overexpression of ki67 was the risk factor for PFS, and the relationship between the expression of ki67 and RFS was not statistically significant in patients with NMIBC treated with BCG intravesical immunotherapy. Well-designed, prospective, with a large sample size are still needed to validate the findings.
Preventing emergency department (ED) visits and hospitalisations of older adults with cognitive impairment compared with the general senior population: what do we know about avoidable incidents? Results from a scoping review
Authors: Gagnon-Roy Mireille , Hami Benyahia , Généreux Mélissa , Veillette Nathalie , Sirois Marie-Josée , Egan Mary , Provencher Véronique
Published: April 2018

Objectives

Older cognitively impaired adults present a higher risk of hospitalisation and mortality following a visit to the emergency department (ED). Better understanding of avoidable incidents is needed to prevent them and the associated ED presentations in community-dwelling adults. This study aimed to synthetise the actual knowledge concerning these incidents leading this population to ED presentation, as well as possible preventive measures to reduce them.

Design

A scoping review was performed according to the Arksey and O’Malley framework.

Methods

Scientific and grey literature published between 1996 and 2017 were examined in databases (Medline, Cumulative Index of Nursing and Allied Health, Ageline, Scopus, ProQuest Dissertations/theses, Evidence-based medecine (EBM) Reviews, Healthstar), online library catalogues, governmental websites and published statistics. Sources discussing avoidable incidents leading to ED presentations were included and then extended to those discussing hospitalisation and mortality due to a lack of sources. Data (type, frequency, severity and circumstances of incidents, preventive measures) was extracted using a thematic chart, then analysed with content analysis.

Results

67 sources were included in this scoping review. Five types of avoidable incidents (falls, burns, transport accidents, harm due to self-negligence and due to wandering) emerged, and all but transport accidents were more frequent in cognitively impaired seniors. Differences regarding circumstances were only reported for burns, as scalding was the most prevalent mechanism of injury for this population compared with flames for the general senior population. Multifactorial interventions and implications of other professionals (eg, pharmacist, firefighters) were reported as potential interventions to reduce avoidable incidents. However, few preventive measures were specifically tested in this population.

Conclusions

Primary research that screens for cognitive impairment and involves actors (eg, paramedics) to improve our understanding of avoidable incidents leading to ED visits is greatly needed. This knowledge is essential to develop preventive measures tailored to the needs of older cognitively impaired adults.
Competencies necessary for becoming a leader in the field of community medicine: a Japanese qualitative interview study
Authors: Kainuma Mosaburo , Kikukawa Makoto , Nagata Masaharu , Yoshida Motofumi
Published: April 2018

Objectives

To clarify competencies for inclusion in our curriculum that focuses on developing leaders in community medicine.

Design

Qualitative interview study.

Setting

All six regions of Japan, including urban and rural areas.

Participants

Nineteen doctors (male: 18, female: 1) who play an important leadership role in their communities participated in semistructured interviews (mean age 48.3 years, range 34–59; mean years of clinical experience 23.1 years, range 9–31).

Method

Semistructured interviews were held and transcripts were independently analysed and coded by the first two authors. The third and fourth authors discussed and agreed or disagreed with the results to give a consensus agreement. Doctors were recruited by maximum variation sampling until thematic saturation was achieved.

Results

Six themes emerged: (1)‘Medical ability’: includes psychological issues and difficult cases in addition to basic medical problems. High medical ability gives confidence to other medical professionals. (2)‘Long term perspective’: the ability to develop a long-term, comprehensive vision and to continuously work to achieve the vision. Cultivation of future generations of doctors is included. (3) ‘Team building’:the ability to drive forward programmes that include residents and local government workers, to elucidate a vision, to communicate and to accept other medical professionals. (4)‘Ability to negotiate’: the ability to negotiate with others to ensure that programmes and visions progress smoothly (5) ‘Management ability’: the ability to run a clinic, medical unit or medical association. (6) ‘Enjoying oneself’: doctors need to feel an attraction to community medicine, that it be fun and challenging for them.

Conclusions

We found six competencies that are needed by leaders in the field of community medicine. The results of this study will contribute to designing a curriculum that develops such leaders.
The French prospective multisite registry on sudden unexpected infant death (OMIN): rationale and study protocol
Authors: Levieux Karine , Patural Hugues , Harrewijn Inge , Briand Huchet Elisabeth , de Visme Sophie , Gallot Géraldine , Chalumeau Martin , Gras Le Guen Christèle , Hanf Matthieu
Published: April 2018

Introduction

Even after ‘back-to-sleep’ campaigns, sudden unexpected infant death (SUID) continues to be the leading cause of death for infants 1 month to 1 year old in developed countries, with devastating social, psychological and legal implications for families. To sustainably tackle this problem and decrease the number of SUIDs, a French SUID registry was initiated in 2015 to (1) inform prevention with standardised data, (2) understand the mechanisms leading to SUID and the contribution of the already known or newly suggested risk factors and (3) gather a multidisciplinary group of experts to coordinate and develop innovative and urgent research in the SUID area.

Methods and analysis

This observational multisite prospective observatory includes all cases of sudden unexpected deaths in children younger than 2 years occurring in the French territory covered by the 35 participating French referral centres. From these cases, various data concerning sociodemographic conditions, death scene, personal and family medical history, parental behaviours, sleep environment, clinical examinations, biological and imagery investigations and autopsy are systematically collected. These data will be complemented as of 2018 with a biobank of diverse biological samples (blood, hair, urine, faeces and cerebrospinal fluid), with other administrative health-related data (health claim reimbursements and hospital admissions) and socioenvironmental data. Insights from exploratory descriptive statistics and thematic analysis will be combined for the design of targeted strategies to effectively reduce preventable infant deaths.

Ethics and dissemination

The French sudden unexpected infant death registry (Observatoire National des Morts Inattendues du Nourrisson registry;OMIN) was approved in 2015 by the French Data Protection Authority in clinical research (Commission Nationale de l’Informatique et des Libertés: number 915273) and by an independent ethics committee (Groupe Nantais d’Ethique dans le Domaine de la Santé: number 2015-01-27). Results will be discussed with associations of families affected by SUID, caregivers, funders of the registry, medical societies and researchers and will be submitted to international peer-reviewed journals and presented at international conferences.
Last Year of Life Study Cologne (LYOL-C): protocol for a cross-sectional mixed methods study to examine care trajectories and transitions in the last year of life until death
Authors: Strupp Julia , Hanke Gloria , Schippel Nicolas , Pfaff Holger , Karbach Ute , Rietz Christian , Voltz Raymond
Published: April 2018

Introduction

The last year of life constitutes a particularly vulnerable phase for patients, involving nearly all health and social care structures. Yet, little scientific evidence is available that provides insight into the trajectories including the number and types of care setting transitions, transitions into palliative care and the dying phase. Only few studies have focused on difficulties associated with having to move between health and social care settings in the last year of life, although patients face a significant risk of adverse events. The Last Year of Life Study Cologne (LYOL-C) aims to fill this gap.

Methods and analysis

LYOL-C is a mixed-methods study composed of four steps: (1) Claims data collected by the statutory health insurance funds of deceased persons will be analysed with regard to patient care trajectories, health service transitions and costs in the last year of life. (2) Patient trajectories and transitions in healthcare will additionally be reconstructed by analysing the retrospective accounts of bereaved relatives (n=400) using a culturally adapted version of the Views of Informal Carers—Evaluation of Services Short Form questionnaire and the Patient Assessment of Care for Chronic Conditions Short Form questionnaire adapted for relatives. (3) Qualitative interviews with bereaved relatives (n=40–60) will provide in-depth insight into reasons for transitions and effects on patients’ quality of life. (4) Focus groups (n=3–5) with Healthcare Professionals will be conducted to discuss challenges associated with transitions in the last year of life.

Ethics and dissemination

Ethical approval has been obtained from the Ethics Commission of the Faculty of Medicine of Cologne University (#17–188). Results will be submitted for publication in peer-reviewed journals and presented at national and international conferences.

Trial registration number

The study is registered in the German Clinical Trials Register (DRKS00011925) and in the Health Services Research Database (VfD_CoRe-Net_17_003806).
Understanding students’ and clinicians’ experiences of informal interprofessional workplace learning: an Australian qualitative study
Authors: Rees Charlotte E , Crampton Paul , Kent Fiona , Brown Ted , Hood Kerry , Leech Michelle , Newton Jennifer , Storr Michael , Williams Brett
Published: April 2018

Objectives

While postgraduate studies have begun to shed light on informal interprofessional workplace learning, studies with preregistration learners have typically focused on formal and structured work-based learning. The current study investigated preregistration students’ informal interprofessional workplace learning by exploring students’ and clinicians’ experiences of interprofessional student-clinician (IPSC) interactions.

Design

A qualitative interview study using narrative techniques was conducted.

Setting

Student placements across multiple clinical sites in Victoria, Australia.

Participants

Through maximum variation sampling, 61 participants (38 students and 23 clinicians) were recruited from six professions (medicine, midwifery, nursing, occupational therapy, paramedicine and physiotherapy).

Methods

We conducted 12 group and 10 individual semistructured interviews. Themes were identified through framework analysis, and the similarities and differences in subthemes by participant group were interrogated.

Results

Six themes relating to four research questions were identified: (1) conceptualisations of IPSC interactions; (2) context for interaction experiences; (3) the nature of interaction experiences; (4) factors contributing to positive or negative interactions; (5) positive or negative consequences of interactions and (6) suggested improvements for IPSC interactions. Seven noteworthy differences in subthemes between students and clinicians and across the professions were identified.

Conclusions

Despite the results largely supporting previous postgraduate research, the findings illustrate greater breadth and depth of understandings, experiences and suggestions for preregistration education. Educators and students are encouraged to seek opportunities for informal interprofessional learning afforded by the workplace.
Role of patient and public involvement in implementation research: a consensus study
Authors: Gray-Burrows Kara A , Willis Thomas A , Foy Robbie , Rathfelder Martin , Bland Pauline , Chin Allison , Hodgson Susan , Ibegbuna Gus , Prestwich Graham , Samuel Kirsty , Wood Laurence , Yaqoob Farhat , McEachan Rosemary R C
Published: April 2018

Background

Patient and public involvement (PPI) is often an essential requirement for research funding. Distinctions can be drawn between clinical research, which generally focuses on patients, and implementation research, which generally focuses on health professional behaviour. There is uncertainty about the role of PPI in this latter field. We explored and defined the roles of PPI in implementation research to inform relevant good practice guidance.

Methods

We used a structured consensus process using a convenience sample panel of nine experienced PPI and two researcher members. We drew on available literature to identify 21 PPI research roles. The panel rated their agreement with roles independently online in relation to both implementation and clinical research. Disagreements were discussed at a face-to-face meeting prior to a second online rating of all roles. Median scores were calculated and a final meeting held to review findings and consider recommendations.

Results

Ten panellists completed the consensus process. For clinical research, there was strong support and consensus for the role of PPI throughout most of the research process. For implementation research, there were eight roles with consensus and strong support, seven roles with consensus but weaker support and six roles with no consensus. There were more disagreements relating to PPI roles in implementation research compared with clinical research. PPI was rated as contributing less to the design and management of implementation research than for clinical research.

Conclusions

The roles of PPI need to be tailored according to the nature of research to ensure authentic and appropriate involvement. We provide a framework to guide the planning, conduct and reporting of PPI in implementation research, and encourage further research to evaluate its use.
Ledipasvir/sofosbuvir with or without ribavirin for 8 or 12 weeks for the treatment of HCV genotype 4 infection: results from a randomised phase III study in Egypt
Authors: Shiha Gamal , Esmat Gamal , Hassany Mohamed , Soliman Reham , Elbasiony Mohamed , Fouad Rabab , Elsharkawy Aisha , Hammad Radi , Abdel-Razek Wael , Zakareya Talaat , Kersey Kathryn , Massetto Benedetta , Osinusi Anu , Lu Sophia , Brainard Diana M , McHutchison John G , Waked Imam , Doss Wahid
Published: April 2018

Objective

We evaluated the efficacy and safety of ledipasvir/sofosbuvir alone and with ribavirin for 8 and 12 weeks in Egyptian patients with and without cirrhosis, who were infected with hepatitis C virus (HCV) genotype 4, including those who had failed previous treatment with sofosbuvir regimens.

Design

In this open-label, multicentre, phase III study, treatment-naive patients were randomised to receive 8 or 12 weeks of ledipasvir/sofosbuvir±ribavirin. Interferon treatment-experienced patients were randomised to receive 12 weeks of ledipasvir/sofosbuvir±ribavirin, while sofosbuvir-experienced or ledipasvir/sofosbuvir-experienced patients received 12 weeks of ledipasvir/sofosbuvir+ribavirin. Randomisation was stratified by cirrhosis status. The primary endpoint was sustained virological response 12 weeks post-treatment (SVR12).

Results

We enrolled 255 patients from four centres in Egypt. Among treatment-naive patients, SVR12 rates were 95% and 90% for those receiving 8 weeks of ledipasvir/sofosbuvir alone and with ribavirin, respectively, and 98% for those receiving 12 weeks of ledipasvir/sofosbuvir both alone and with ribavirin. Among interferon-experienced patients, SVR rates were 94% for those receiving 12 weeks of ledipasvir/sofosbuvir and 100% for those receiving 12 weeks of ledipasvir/sofosbuvir plus ribavirin. All patients previously treated with sofosbuvir regimens who received ledipasvir/sofosbuvir plus ribavirin achieved SVR12. The most common adverse events, headache and fatigue, were more common among patients receiving ribavirin.

Conclusion

Among non-cirrhotic treatment-naive patients with HCV genotype 4, 8 weeks of ledipasvir/sofosbuvir±ribavirin was highly effective. Twelve weeks of ledipasvir/sofosbuvir±ribavirin was highly effective regardless of presence of cirrhosis or prior treatment experience, including previous treatment with sofosbuvir or ledipasvir/sofosbuvir.

Trial registration number

NCT02487030.
CD30 expression and its correlation with MYC and BCL2 in de novo diffuse large B-cell lymphoma
Authors: Gong Qi-Xing , Wang Zhen , Liu Chong , Li Xiao , Lu Ting-Xun , Liang Jin-Hua , Xu Wei , Li Jian-Yong , Zhang Zhi-Hong
Published: April 2018

Aim

CD30+ diffuse large B-cell lymphoma (DLBCL) has emerged as a new immunophenotypic variant ofde novoDLBCLs. However, the prevalence of CD30 positivity is variable according to different studies, and the prognostic significance of CD30 is also controversial. This study aimed to investigate the positive expression rate and prognostic impact of CD30 inde novoDLBCLs and try to find the correlated influences.

Methods

A total of 241 patients withde novoDLBCL in east China from 2008 to 2015 were included to investigate the prevalence, clinicopathological features and outcomes of CD30+de novoDLBCLs. Immunohistochemical evaluation for CD10, CD30, BCL2, BCL6, MUM1/IRF4, MYC and Ki67, and fluorescence in situ hybridisation for MYC and BCL2 gene alterations were performed.

Results

Using a >0% threshold, CD30 expression was detected in approximately 10% patient withde novoDLBCL. These predominately presented with centroblastic or anaplastic morphological patterns, less frequently showing immunoblastic morphology or ‘starry sky’ pattern, mutually exclusive with MYC gene rearrangement, and negatively associated with BCL2 protein expression. CD30 expression was associated with a favourable prognosis of patients’ outcomes. However, the multivariate analysis revealed that it was not an independent prognostic factor inde novoDLBCLs. The impact of CD30 might be influenced by the international prognostic index and the expression of MYC and BCL2 proteins.

Conclusion

CD30+ DLBCL may be a subset ofde novoDLBCLs with characteristic clinicopathological features, but the prognostic role of CD30 is limited.
Insights into Parkinson’s disease from computational models of the basal ganglia
Authors: Humphries Mark D , Obeso Jose Angel , Dreyer Jakob Kisbye
Published: April 2018

Movement disorders arise from the complex interplay of multiple changes to neural circuits. Successful treatments for these disorders could interact with these complex changes in myriad ways, and as a consequence their mechanisms of action and their amelioration of symptoms are incompletely understood. Using Parkinson’s disease as a case study, we review here how computational models are a crucial tool for taming this complexity, across causative mechanisms, consequent neural dynamics and treatments. For mechanisms, we review models that capture the effects of losing dopamine on basal ganglia function; for dynamics, we discuss models that have transformed our understanding of how beta-band (15–30 Hz) oscillations arise in the parkinsonian basal ganglia. For treatments, we touch on the breadth of computational modelling work trying to understand the therapeutic actions of deep brain stimulation. Collectively, models from across all levels of description are providing a compelling account of the causes, symptoms and treatments for Parkinson’s disease.