bluuebunny/crossref_metadata_2025 huggingface dataset:
A pivotal role of serine 225 phosphorylation in the function of hepatitis C virus NS5A revealed with the application of a phosphopeptide antiserum and super-resolution microscopy
Authors: Goonawardane Niluka , Yin Chunhong , Harris Mark
Published: August 2018

NS5A is a multi-functional phosphoprotein that plays a key role in both viral replication and assembly. The identity of the kinases that phosphorylate NS5A, and the consequences for HCV biology, remain largely undefined. We previously identified serine 225 (S225) within low complexity sequence (LCS) I as a major phosphorylation site and used a phosphoablatant mutant (S225A) to define a role for S225 phosphorylation in the regulation of genome replication, interactions of NS5A with several host proteins and the sub-cellular localisation of NS5A. To investigate this further, we raised an antiserum to S225 phosphorylated NS5A (pS225). Western blot analysis revealed that pS225 was exclusively found in the hyper-phosphorylated NS5A species. Furthermore, using kinase inhibitors we demonstrated that S225 was phosphorylated by casein kinase 1α (CK1α) and polo-like kinase 1 (PLK1). Using a panel of phosphoablatant mutants of other phosphorylation sites in LCSI we obtained the first direct evidence of bidirectional hierarchical phosphorylation initiated by phosphorylation at S225.

Using super-resolution microscopy (Airyscan and Expansion), we revealed a unique architecture of NS5A-positive clusters in HCV-infected cells - pS225 was concentrated on the surface of these clusters, close to lipid droplets. Pharmacological inhibition of S225 phosphorylation resulted in the condensation of NS5A-positive clusters into larger structures, recapitulating the S225A phenotype. Although S225 phosphorylation was not specifically affected by daclatasvir treatment, the latter also resulted in a similar condensation. These data are consistent with a key role for S225 phosphorylation in the regulation of NS5A function.

Importance

NS5A has obligatory roles in the hepatitis C virus lifecycle, and is proposed to be regulated by phosphorylation. As NS5A is a target for highly effective direct-acting antivirals (DAAs) such as daclatasvir (DCV) it is vital to understand how phosphorylation occurs and regulates NS5A function. We previously identified serine 225 (S225) as a major phosphorylation site. Here we used an antiserum specific for NS5A phosphorylated at S225 (pS225-NS5A) to identify which kinases phosphorylate this residue. Using super-resolution microscopy we showed that pS225 was present in foci on the surface of larger NS5A-positive clusters likely representing genome replication complexes. This location would enable pS225-NS5A to interact with cellular proteins and regulate the function and distribution of these complexes. Both loss of pS225 and DCV treatment resulted in similar changes to the structure of these complexes, suggesting that DAA treatment might target a function of NS5A that is also regulated by phosphorylation.
Inferring macro-ecological patterns from local species' occurrences
Authors: Tovo Anna , Formentin Marco , Suweis Samir , Stivanello Samuele , Azaele Sandro , Maritan Amos
Published: August 2018

Biodiversity provides support for life, vital provisions, regulating services and has positive cultural impacts. It is therefore important to have accurate methods to measure biodiversity, in order to safeguard it when we discover it to be threatened. For practical reasons, biodiversity is usually measured at fine scales whereas diversity issues (e.g. conservation) interest regional or global scales. Moreover, biodiversity may change across spatial scales. It is therefore a key challenge to be able to translate local information on biodiversity into global patterns. Many databases give no information about the abundances of a species within an area, but only its occurrence in each of the surveyed plots. In this paper, we introduce an analytical framework to infer species richness and abundances at large spatial scales in biodiversity-rich ecosystems when species presence/absence information is available on various scattered samples (i.e. upscaling). This framework is based on the scale-invariance property of the negative binomial. Our approach allows to infer and link within a unique framework important and well-known biodiversity patterns of ecological theory, such as the Species Accumulation Curve (SAC) and the Relative Species Abundance (RSA) as well as a new emergent pattern, which is the Relative Species Occupancy (RSO). Our estimates are robust and accurate, as confirmed by tests performed on both in silico-generated and real forests. We demonstrate the accuracy of our predictions using data from two well-studied forest stands. Moreover, we compared our results with other popular methods proposed in the literature to infer species richness from presence-absence data and we showed that our framework gives better estimates. It has thus important applications to biodiversity research and conservation practice.
Tracking a Serial Killer: Integrating Phylogenetic Relationships, Epidemiology, and Geography for Two Invasive Meningococcal Disease Outbreaks
Authors: Ezeoke Ifeoma , Galac Madeline R. , Lin Ying , Liem Alvin T. , Roth Pierce A. , Kilianski Andrew , Gibbons Henry S. , Bloch Danielle , Kornblum John , Rosso Paula Del , Janies Daniel A. , Weiss Don
Published: August 2018

Background

While overall rates of meningococcal disease have been declining in the United States for the past several decades, New York City (NYC) has experienced two serogroup C meningococcal disease outbreaks in 2005-2006 and in 2010-2013. The outbreaks were centered within drug use and sexual networks, were difficult to control, and required vaccine campaigns.

Methods

Whole Genome Sequencing (WGS) was used to analyze preserved meningococcal isolates collected before and during the two outbreaks. We integrated and analyzed epidemiologic, geographic, and genomic data to better understand transmission networks among patients. Betweenness centrality was used as a metric to understand the most important geographic nodes in the transmission networks. Comparative genomics was used to identify genes associated with the outbreaks.

Results

Neisseria meningitidis serogroup C (ST11/ET-37) was responsible for both outbreaks with each outbreak having distinct phylogenetic clusters. WGS did identify some misclassifications of isolates that were more distant from the rest of the outbreak, as well as those that should have been included based on high genomic similarity. Genomes for the second outbreak were more similar than the first and no mutation was found to either be unique or specific to either outbreak lineage. Betweenness centrality as applied to transmission networks based on phylogenetic analysis demonstrated that the outbreaks were transmitted within focal communities in NYC with few transmission events to other locations.

Conclusions

Neisseria meningitidis is an ever changing pathogen and comparative genomic analyses can help elucidate how it spreads geographically to facilitate targeted interventions to interrupt transmission.
Mediating role of students’ engagement to their classes
Authors: Siddiqi Ahmed
Published: August 2018

Purpose

The purpose of this paper is to establish the mediating role of students’ engagement to their classes, for the conventional relationship between teachers’ efforts and students’ development, for a better understanding of the instruction-based classroom learning.

Design/methodology/approach

The investigation is made using a mult-istage-stratified-systematic sample of 500 students from business and engineering schools with an almost equal representation of both the genders and the type of schools’ ownership. A structural equation modeling is used for this mediation analysis.

Findings

The mediating role of students’ engagement is identically established both for business and engineering schools and for both genders. However, in public sector universities, this mediation is insignificant.

Research limitations/implications

The investigation is limited only to business and engineering schools, and this limitation may conceal some factor(s) more important for other schools. Further, the investigation is reading data from Lahore, a metropolitan, which may hide some factor(s) some appropriate for smaller cities.

Originality/value

The data are gathered, analyzed and discussed through the lens of the socio-cultural theory, allowing for a comprehensive understanding to emerge for students’ engagement to their classes.
Prevalence and potential virulence of Escherichia coli in ready-to-eat raw mixed vegetable salads in collective catering in Abidjan, Côte d’Ivoire
Authors: Toe Evelyne , Dadié Adjéhi , Dako Etienne , Loukou Guillaume , Dje Marcelin Koffi , Blé Y.C.
Published: August 2018

Purpose

Vegetable salads, despite their recognized health benefits, are an increasingly common cause of foodborne illness worldwide. The purpose of this paper is to determine the prevalence of E. coli with virulence genes in ready-to-eat raw mixed vegetable salads sold in collective catering in Abidjan.

Design/methodology/approach

A total of 436 strains of E. coli were isolated from 306 ready-to-eat raw mixed vegetables salads and then identified biochemically and molecularly based on the uidA gene responsible for beta-glucuronidase activity. The virulence genes were determined by polymerase chain reaction.

Findings

The prevalence in vegetable salads of E. coli with virulence genes was 35.3 percent. The distribution of pathovars was 21.2 percent enterotoxigenic (ETEC), 4.9 percent enteropathogenic (EPEC), 0.7 percent Shigatoxigenic (STEC), and 7.5 percent Enteroaggregative E. coli (EAEC). It appears from the study that vegetable salads sold in collective catering in Abidjan are at risk for contamination by E. coli pathovars.

Originality/value

Processing conditions for these salads during preparation appear to be hygienically insufficient, so measures to control the risk of contamination are necessary.
The art of tastings: enhancing the arts festival experience
Authors: Viljoen Armand , Kruger Martinette , Saayman Melville
Published: August 2018

Purpose

The role and importance of arts festivals are well documented within the festival and events literature. Art and culture, as well as the subsequent enhancement thereof, are especially significant in multicultural societies. However, little is known regarding the role of culinary experiences within an arts festival setting. The paper aims to discuss these issues.

Design/methodology/approach

The case study was a well-known and popular Afrikaans national arts festival held annually in Potchefstroom, South Africa. Visitors to three distinct tasting experiences (brandy, whisky and sparkling wine, including Méthode Cap Classique), offered as part of the festival programme, were surveyed.

Findings

In the analyses, 292 completed questionnaires were included, which revealed three managerial factors for a successful tasting experience, as well as six tasting experience dimensions. In all cases, the experiences exceeded the expectations. This research greatly contributes towards the body of knowledge regarding tasting experiences at national arts festivals, an aspect that has not been researched to date.

Practical implications

Based on the results, practical implications are provided to enhance the current tasting experiences as well as visitor loyalty. This research is a stepping stone towards understanding the needs and preferences of the visitors, as well as identifying how the festival can capitalise on delivering these experiences.

Originality/value

This research identified for the first time the factors that contribute to a memorable tasting experience, as well as evaluated the tasting experience dimensions.
Flexural behavior of fire-damaged reinforced concrete beams repaired with high-strength fiber reinforced mortar
Authors: Abdullah Muhd Afiq Hizami , Mohd Zahid Mohd Zulham Affandi , Ayob Afizah , Muhamad Khairunnisa
Published: August 2018

Purpose

The purpose of this study is to investigate the effect on flexural strength of fire-damaged concrete repaired with high-strength mortar (HSM).

Design/methodology/approach

Reinforced concrete beams with dimension of 100 mm × 100 mm × 500 mm were used in this study. Beams were then heated to 400°C and overlaid with either HSM or high-strength fiber reinforced mortar (HSFM) to measure the effectiveness of repair material. Repaired beams of different material were then tested for flexural strength. Another group of beams was also repaired and tested by the same procedure but was heated at higher temperature of 600°C.

Findings

Repair of 400°C fire-damaged samples using HSM regained 72 per cent of its original flexural strength, 100.8 per cent of its original toughness and 56.9 per cent of its original elastic stiffness. Repair of 400°C fire-damaged samples using HSFM regained 113.5 per cent of its original flexural strength, 113 per cent of its original toughness and 85.1 per cent of its original elastic stiffness. Repair of 600°C fire-damaged samples using HSM regained 18.7 per cent of its original flexural strength, 25.9 per cent of its original peak load capacity, 26.1 per cent of its original toughness and 22 per cent of its original elastic stiffness. Repair of 600°C fire-damaged samples using HSFM regained 68.4 per cent of its original flexural strength, 96.5 per cent of its original peak load capacity, 71.2 per cent of its original toughness and 52.2 per cent of its original elastic stiffness.

Research limitations/implications

This research is limited to the size of the furnace. The beam specimen is limited to 500 mm of length and overall dimensions. This dimension is not practical in actual structure, hence it may cause exaggeration of deteriorating effect of heating on reinforced concrete beam.

Practical implications

This study may promote more investigation of using HSM as repair material for fire-damaged concrete. This will lead to real-world application and practical solution for fire-damaged structure.

Social implications

The aim of this research in using HSM mostly due to the material’s high workability which will ease its application and promote quality in repair of damaged structure.

Originality/value

There is a dearth of research on using HSM as repair material for fire-damaged concrete. Some research has been carried out using mortar but at lower strength compared to this research.
The impact of switching costs on customer complaint behavior and service recovery evaluation
Authors: Bergel Maxi , Brock Christian
Published: August 2018

Purpose

The purpose of this paper is to examine the impact of three different dimensions of switching costs on customer dissatisfaction response styles as well as on the evaluation of service recovery.

Design/methodology/approach

Study 1 is a scenario-based experiment and Study 2 uses a critical incident technique combined with survey-based measures of switching costs, dissatisfaction responses and perceived complaint handling.

Findings

The results of these studies highlight the need to consider the different effects of switching costs. Not only do different switching costs lead to varying customer dissatisfaction responses, they also have differential moderator effects on the interrelationships between customer-perceived recovery justice and service recovery satisfaction.

Research limitations/implications

Service failure severity was an influential control variable. Future studies should investigate how the type, context and severity of service failure influence customers’ complaint behavior. Furthermore, participants had trouble differentiating between their relations toward their service provider in general and one particular employee. Hence, further research should explore the relationship between customers and frontline employees.

Practical implications

The authors encourage managers to take a closer look at the switching cost dimensions of their service industry. This may lead practitioners to promote differentiated strategies for complaint stimulation and complaint handling.

Originality/value

This is the first study to simultaneously explore all three dimensions of switching costs when examining their impact on customers’ dissatisfaction response styles as well as the moderating effects in the recovery process. In doing so, this study reveals some hitherto uncovered effects.
Go home and kick the dog
Authors: Moon Tae Won , Hur Won-Moo
Published: August 2018

Purpose

The purpose of this paper is to examine the spillover effects of coworker incivility on customer-directed counterproductive work behavior (CWB) and how emotional exhaustion mediates the relationship between them. The authors predicted that job calling and perceived organizational support (POS) would moderate the relationship between experienced coworker incivility and service employees’ emotional exhaustion, respectively.

Design/methodology/approach

Survey data from 252 frontline employees working at six full-service luxury hotels in South Korea were examined.

Findings

The results indicated that experienced coworker incivility was positively related to customer-directed CWB. In addition, the relationship between experienced coworker incivility and customer-directed CWB was mediated by emotional exhaustion. Finally, employees’ job calling attenuated the positive effects of experienced coworker incivility on customer-directed CWB. The theoretical and practical implications of this study are discussed, together with its limitations and future research directions.

Originality/value

The main contribution of the study is to provide an empirical framework for how instances of coworker incivility spillover, which lead to the target employee’s customer-directed CWB through emotional exhaustion, and how personal (e.g. job calling) may buffer against negative effects.
The fall and rise of intellectual capital accounting: new prospects from the Big Data revolution
Authors: La Torre Matteo , Botes Vida L. , Dumay John , Rea Michele Antonio , Odendaal Elza
Published: August 2018

Purpose

As Big Data is creating new underpinnings for organisations’ intellectual capital (IC) and knowledge management, this paper aims to analyse the implications of Big Data for IC accounting to provide new conceptual and practical insights about the future of IC accounting.

Design/methodology/approach

Based on a conceptual framework informed by decision science theory, the authors explain the factors supporting Big Data’s value and review the academic literature and practical evidence to analyse the implications of Big Data for IC accounting.

Findings

In reflecting on Big Data’s ability to supply a new value for IC and its implications for IC accounting, the authors conclude that Big Data represents a new IC asset, and this represents a rationale for a renewed wave of interest in IC accounting. IC accounting can contribute to understand the determinants of Big Data’s value, such as data quality, security and privacy issues, data visualisation and users’ interaction. In doing so, IC measurement, reporting and auditing need to keep focusing on how human capital and organisational and technical processes (structural capital) can unlock or even obstruct Big Data’s value for IC.

Research limitations/implications

The topic of Big Data in IC and accounting research is in its infancy; therefore, this paper acts at a normative level. While this represents a research limitation of the study, it is also a call for future empirical studies.

Practical implications

Once again, practitioners and researchers need to face the challenge of avoiding the trap of IC accountingisation to make IC accounting relevant for the Big Data revolution. Within the euphoric and utopian views of the Big Data revolution, this paper contributes to enriching awareness about the practical factors underpinning Big Data’s value for IC and foster the cognitive and behavioural dynamic between data, IC information and user interaction.

Social implications

The paper is relevant to prepares, users and auditors of financial statements.

Originality/value

This paper aims to instill a novel debate on Big Data into IC accounting research by providing new avenues for future research.
Aha! “take on Me’s”: bridging the North sea with relational autoethnography
Authors: Klevan Trude , Karlsson Bengt , Turner Lydia , Short Nigel , Grant Alec
Published: August 2018

Purpose

The purpose of this paper is to explore how sharing stories of being a mental health professional and academic, based more broadly on serendipity and searching in life, can serve as means for bridging and developing cross-cultural understandings and collaborative work.

Design/methodology/approach

This paper is a relational autoethnography based on face-to-face and written conversational dialogue between five mental health academics from the UK and Norway.

Findings

The very practice of writing this paper displays and serves the purpose of bridging people, cultures and understandings, at several levels, in the facilitation of new research and writing projects. Troubling traditional boundaries between “us” and “them, and the “knower” and the “known,” the writing is theoretically underpinned by Friendship as Method, situated in a New Materialist context.

Originality/value

Through its conversational descriptions and explorations the paper shows how doing relational autoethnography can be purposeful in developing cross-cultural understandings and work at both professional and personal levels. It also demonstrates how autoethnography as relational practice can be useful in the sharing of this methodology between people who are more and less familiar with it.
Do Medical Homes Improve Quality of Care for Persons with Multiple Chronic Conditions?
Authors: Swietek Karen E. , Domino Marisa Elena , Beadles Christopher , Ellis Alan R. , Farley Joel F. , Grove Lexie R. , Jackson Carlos , DuBard C. Annette
Published: August 2018

Objective

To examine the association between medical home enrollment and receipt of recommended care for Medicaid beneficiaries with multiple chronic conditions (MCC).

Data Sources/Study Setting

Secondary claims data from fiscal years 2008–2010. The sample included nonelderly Medicaid beneficiaries with at least two of eight target conditions (asthma, chronic obstructive pulmonary disease, diabetes, hypertension, hyperlipidemia, seizure disorder, major depressive disorder, and schizophrenia).

Study Design

We used linear probability models with person‐ and year‐level fixed effects to examine the association between patient‐centered medical home (PCMH) enrollment and nine disease‐specific quality‐of‐care metrics, controlling for selection bias and time‐invariant differences between enrollees.

Data Collection Methods

This study uses a dataset that links Medicaid claims with other administrative data sources.

Principal Findings

Patient‐centered medical home enrollment was associated with an increased likelihood of receiving eight recommended mental and physical health services, including A1C testing for persons with diabetes, lipid profiles for persons with diabetes and/or hyperlipidemia, and psychotherapy for persons with major depression and persons with schizophrenia. PCMH enrollment was associated with overuse of short‐acting β‐agonists among beneficiaries with asthma.

Conclusions

The PCMH model can improve quality of care for patients with multiple chronic conditions.
Linkage of VA and State Prescription Drug Monitoring Program Data to Examine Concurrent Opioid and Sedative‐Hypnotic Prescriptions among Veterans
Authors: Carlson Kathleen F. , Gilbert Tess A. , Morasco Benjamin J. , Wright Dagan , Otterloo Joshua Van , Herrndorf Aldona , Cook Lawrence J.
Published: August 2018

Objective

To examine the prevalence of concurrent Veterans Health Administration (VA) and non‐VA prescriptions for opioids and sedative‐hypnotic medications among post‐9/11 veterans in Oregon.

Data Sources

VA health care and prescription data were probabilistically linked with Oregon Prescription Drug Monitoring Program (PDMP) data.

Study Design

This retrospective cohort study examined concurrent prescriptions among n = 19,959 post‐9/11 veterans, by year (2014–2016) and by patient demographic and clinical characteristics. Veterans were included in the cohort for years in which they received VA outpatient care; those receiving hospice or palliative care were excluded. Concurrent prescriptions were defined as ≥1 days of overlap between outpatient prescriptions for opioids and/or sedative‐hypnotics (categorized as benzodiazepines vs. non‐benzodiazepines).

Principal Findings

Among 5,882 veterans who filled opioid or sedative‐hypnotic prescriptions at VA pharmacies, 1,036 (17.6 percent) filled concurrent prescriptions from non‐VA pharmacies. Within drug class, 15.1, 8.8, and 4.6 percent received concurrent VA and non‐VA opioids, benzodiazepines, and non‐benzodiazepines, respectively. Veteran demographics and clinical diagnoses were associated with the likelihood of concurrent prescriptions, as was enrollment in the Veterans Choice Program.

Conclusions

A considerable proportion of post‐9/11 veterans receiving VA care in Oregon filled concurrent prescriptions for opioids and sedative‐hypnotics. Fragmentation of care may contribute to prescription drug overdose risk among veterans.
Programmable activation of Bombyx gene expression using CRISPR/dCas9 fusion systems
Authors: Wang Xiao‐Gang , Ma San‐Yuan , Chang Jia‐Song , Shi Run , Wang Ruo‐Lin , Zhao Ping , Xia Qing‐You
Published: August 2018

The recently developed clustered regularly interspaced short palindromic repeats (CRISPR)‐based techniques have made it possible to reprogram target gene expression without cloning complementary DNA or disturbing genomic sequence in mammalian cells and several multicellular organisms. We previously showed that CRISPR‐associated protein 9 (Cas9) and CRISPR from Prevotella and Francisella 1 (Cpf1) could induce target mutations, deletions, inversions, and duplications both singly and multiplex in silkworm, Bombyx mori. However, it remains unknown whether the CRISPR activation (CRISPRa) system can be used in B. mori. In this study, we investigated the CRISPRa system, in which a nuclease dead Streptococcus pyogenes Cas9 (SpCas9) is fused to two transcription activation domains, including VP64 (a tetramer of the herpes simplex VP16 transcriptional activator domain), and VPR (a tripartite activator, composed of VP64, p65, and Rta). The results showed that both dCas9‐VP64 and dCas9‐VPR systems could be used in B. mori cells, of which the latter showed significantly higher activity. The dCas9‐VPR system showed considerable activity on all five tested target genes, and further analysis revealed that the up‐regulation of genes was negatively correlated to their basal expression level. We also observed that this system could be used to upregulate a range of target genes. Taken together, our findings demonstrate that CRISPRa can be a powerful tool to study gene functions in B. mori and perhaps other non‐drosophila insects.
Fiberoptic intubation of severely obese patients through supraglottic airway: A prospective, randomized trial of the Ambu® AuraGain™ laryngeal mask vs the i‐gel™ airway
Authors: Moser Berthold , Keller Christian , Audigé Laurent , Dave Mital H. , Bruppacher Heinz R.
Published: August 2018

Introduction

Airway management in severely obese patients remains a challenging issue for anaesthetists and may lead to life‐threatening situations. Supraglottic airway devices, such as the i‐gel™ or the AuraGain™, were developed, with the possibility to ventilate the patient or use them as a conduit for endotracheal intubation.

Methods

In our randomized prospective trial, we hypothesized a 10 seconds faster fiberoptic trans‐device intubation time through the AuraGain™ laryngeal mask compared to the i‐gel™ laryngeal mask in severely obese patients. We randomly assigned 44 patients to the AuraGain or i‐gel group and measured trans‐device intubation time after 5 minutes of successful ventilation through the device. Secondary parameters relating to the trans‐device intubation success, oropharyngeal leak pressure, and parameters regarding insertion of the supraglottic airway devices were measured. Postoperative airway morbidity was determined 5 hours after surgery.

Results

Mean (SD) intubation time was 55.7 (5.8) seconds for the AuraGain™ vs 54.1 (8.5) for i‐gel™ mask (95% CI −2.7 to 5.9; P = 0.474), respectively, on a mean body mass index (BMI) of 39.4 kg/m2 in the AuraGain™ group vs 38.9 kg/m2 in i‐gel™ group. No difference could be found in the other studied parameters.

Conclusions

Time for intubation through both supraglottic airway devices was similar. Attributed to fast possibility of securing the airway with both supraglottic airway devices, we believe that both, AuraGain™ and i‐gel™, can be a good alternative in the airway management in obese patients.
A bidirectional path analysis model of smoking cessation self‐efficacy and concurrent smoking status: impact on abstinence outcomes
Authors: Clyde Matthew , Pipe Andrew , Reid Robert , Els Charl , Tulloch Heather
Published: August 2018

Self‐efficacy is routinely associated with abstinence in the addictions literature, and is a major component relapse‐prevention models. The magnitude of this relationship has been brought into question following equivocal results in studies controlling for concurrent smoking status. The aim of our study was to clarify the relationship between cessation self‐efficacy, smoking status, and cessation outcomes in a cohort of treatment‐seeking smokers. Smokers participating in the FLEX trial, a randomized trial investigating the efficacy of three pharmacologic treatments for smoking cessation, completed questionnaires assessing cessation self‐efficacy at baseline and at weeks 1, 3, 5 and 10 post‐target quit date; smoking status was verified using expired carbon monoxide. Structural models were fit in order to ascertain the relationship between cessation self‐efficacy and concurrent smoking at each time‐point, and to assess the association between cessation self‐efficacy, smoking and seven‐day point prevalence smoking status at week 10. A total of 737 treatment‐seeking smokers participated. In our path model, self‐efficacy and smoking status at all time points were associated with week 10 abstinence (except week 3 self‐efficacy), after controlling these values' previous time‐points. All direct pathways between cessation self‐efficacy and smoking were also significant, supporting a bidirectional relationship. Our results support a bidirectional and reciprocal relationship between cessation self‐efficacy and concurrent smoking behavior; participants with higher confidence were more likely to be smoke‐free, and concurrent smoking status predicted levels of confidence over the ensuing weeks. Both measures were associated with week 10 abstinence. Our results indicate that while correlated, both cessation self‐efficacy and current smoking behavior during a cessation attempt are important independent markers of ultimate cessation success.
Homeostatic impact of sulfite and hydrogen sulfide on cysteine catabolism
Authors: Kohl Joshua B , Mellis Anna‐Theresa , Schwarz Guenter
Published: August 2018

Cysteine is one of the two key sulfur‐containing amino acids with important functions in redox homeostasis, protein functionality and metabolism. Cysteine is taken up by mammals via their diet and can also be derived from methionine via the transsulfuration pathway. The cellular concentration of cysteine is kept within a narrow range by controlling its synthesis and degradation. There are two pathways for the catabolism of cysteine leading to sulfate, taurine and thiosulfate as terminal products. The oxidative pathway produces taurine and sulfate, while the H2S pathway involves different enzymatic reactions leading to the formation and clearance of H2S, an important signalling molecule in mammals, resulting in thiosulfate and sulfate. Sulfite is a common intermediate in both catabolic pathways. Sulfite is considered as cytotoxic and produces neurotoxic S‐sulfonates. As a result, a deficiency in the terminal steps of cysteine or H2S catabolism leads to severe forms of encephalopathy with the accumulation of sulfite and H2S in the body. This review links the homeostatic regulation of both cysteine catabolic pathways to sulfite and H2S.

Linked Articles

This article is part of a themed section on Chemical Biology of Reactive Sulfur Species. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.4/issuetoc
Melanophore multinucleation pathways in zebrafish
Authors: Usui Yuu , Kondo Shigeru , Watanabe Masakatsu
Published: August 2018

In zebrafish, apart from mononuclear melanophores, bi‐ and trinuclear melanophores are frequently observed; however, the manner in which multinucleation of these cells occurs during fish development remains unknown. Here, we analyzed the processes underlying multinucleation of zebrafish melanophores. Transgenic zebrafish in which melanophore nuclei were labeled with a histone H2B‐red fluorescent reporter protein were used to evaluate the distribution of mono‐, bi‐, and trinuclear melanophores in both the trunk and fin. Half of the melanophores examined were binuclear and approximately 1% were trinuclear. We compared cell size, cell motility, and survival rate between mono‐ and binuclear melanophores grown in a culture dish, and we found that cell size and survival rate were significantly larger in binuclear melanophores. We then analyzed the behavior of melanoblasts and melanophores from transgenic zebrafish using in vivo and in vitro live‐cell imaging. We detected division and differentiation of melanoblasts, as well as melanoblast nuclear division without subsequent cellular division. In addition, we observed cellular and nuclear division in melanophores, although these events were very infrequent in vitro. On the basis of our findings, we present a scheme for melanophore multinucleation in zebrafish.
Decision tree for ward admissions of older patients at the emergency department after a fall
Authors: Trevisan Caterina , Di Gregorio Patrizia , Debiasi Eugenio , Pedrotti Martina , La Guardia Mario , Manzato Enzo , Sergi Giuseppe , March Albert
Published: August 2018

Aim

Falls are a prevalent issue for the older population, and for the healthcare system in terms of emergency department (ED) access and hospitalizations. There is still a lack of knowledge and guidelines, however, regarding the need to hospitalize older patients accessing the ED after a fall. In the present study, we aimed to analyze the factors and the decisional process that led to older patients accessing the ED after a fall being admitted to hospital or discharged.

Methods

The study sample included 2144 older people who accessed the ED after a fall. For each patient, we obtained information on the nature of the fall and the related injuries, previous falls, dementia and ongoing medical therapies. As the outcome variable, we considered the indication for ward admission after the ED visit.

Results

Of the 2144 individuals who accessed the ED after a fall, 38% had at least one fracture, and 40.1% were admitted to a ward. The decision tree obtained using the chi‐squared automatic interaction detection algorithm showed that the indication for ward admission could be accurately predicted (risk estimate 0.205) by just five factors, namely: presence and severity of fall‐related injuries, reportedly suspicious fall dynamics, use of anticoagulants, polypharmacy, and dementia.

Conclusions

The need for ward admission in older patients who access the ED after a fall seems to be determined not only by the severity of fall‐related injuries, but also by the fall dynamics and the individual's clinical complexity. Geriatr Gerontol Int 2018; 18: 1388–1392.
Abnormal coagulation and enhanced fibrinolysis due to lysinuric protein intolerance associates with bleeds and renal impairment
Authors: Pitkänen H. H. , Kärki M. , Niinikoski H. , Tanner L. , Näntö‐Salonen K. , Pikta M. , Kopatz W. F. , Zuurveld M. , Meijers J. C. M. , Brinkman H. J. M. , Lassila R.
Published: August 2018

Introduction

Lysinuric protein intolerance (LPI), a rare autosomal recessive transport disorder of cationic amino acids lysine, arginine and ornithine, affects intestines, lungs, liver and kidneys. LPI patients may display potentially life‐threatening bleeding events, which are poorly understood.

Aims

To characterize alterations in haemostatic and fibrinolytic variables associated with LPI.

Methods

We enrolled 15 adult patients (8 female) and assessed the clinical ISTH/SSC‐BAT bleeding score (BS). A variety of metabolic and coagulation assays, including fibrin generation test derivatives, clotting time (CT) and clot lysis time (CLT), thromboelastometry (ROTEM), and PFA‐100 and Calibrated Automated Thrombogram (CAT), were used.

Results

All patients had mild‐to‐moderate renal insufficiency, and moderate bleeding tendency (BS 4) without spontaneous bleeds. Mild anaemia and thrombocytopenia occurred. Traditional clotting times were normal, but in contrast, CT in fibrin generation test, and especially ROTEM FIBTEM was abnormal. The patients showed impaired primary haemostasis in PFA, irrespective of normal von Willebrand factor activity, but together with lowered fibrinogen and FXIII. Thrombin generation (TG) was reduced in vitro, according to CAT‐derived endogenous thrombin potential, but in vivo TG was enhanced in the form of circulating prothrombin fragment 1 and 2 values. Very high D‐dimer and plasmin‐α2‐antiplasmin (PAP) complex levels coincided with shortened CLT in vitro.

Conclusions

Defective primary haemostasis, coagulopathy, fibrin abnormality (FIBTEM, CT and CLT), low TG in vitro and clearly augmented fibrinolysis (PAP and D‐dimer) in vivo were all detected in LPI. Altered fibrin generation and hyperfibrinolysis were associated with the metabolic and renal defect, suggesting a pathogenetic link in LPI.
The Foundation Pharmacist Project: exploring new models of dual-sector postgraduate pharmacy training
Authors: Rathbone Adam P , Rokib Tahmina , Baqir Wasim , Campbell David
Published: August 2018

Objectives

To explore the experiences of primary care-based professional stakeholders in a dual-sector training programme for foundation pharmacists.

Methods

Professional stakeholders were defined as foundation pharmacists or members of staff working with foundation pharmacists such as general medical or nurse practitioners and administrative staff. Stakeholders were invited to participate via email and through gatekeepers. Participants were asked how they were involved in the training pathway, what their experiences had been and what they hoped for the future. Interviews were audio-recorded, transcribed and thematically analysed using computer software.

Key findings

Twenty-eight face-to-face semi-structured interviews were conducted. Five major themes were identified (1) benefits of integration (2) appropriateness of the work (3) perceived impact (4) identity development and (5) training and peer support. These findings outline participants’ experiences of establishing a scope of practice in primary and secondary care settings and developing mechanisms to negotiate non-prescriber status to save general practitioners, practice nurse, community pharmacy and administrator time. Foundation pharmacists were able to develop a professional identity whilst working in each care setting, highlighting the dominance of hospital pharmacy exposure in clinical knowledge acquisition and establishing a community of practice across organisational and geographical boundaries using WhatsApp as a peer support tool.

Conclusions

Foundation pharmacists are able to work within their own competencies in two different care settings, developing scopes of practice and contributing clinically to service provision. This work provides evidence that this type of training pathway can offer an appropriate landscape for pharmacy practitioner development. Further work is needed to explore the longitudinal outcomes of the programme.
When should the driver with a history of substance misuse be allowed to return to the wheel? A review of the substance misuse section of the Australian national guidelines
Authors: Ogden Edward J. D , Verster Joris C. , Hayley Amie C. , Downey Luke A. , Hocking Bruce , Stough Con K. , Scholey Andrew B. , Bonomo Yvonne
Published: August 2018

Assessing fitness to drive in applicants with a historical or current substance use disorder presents a specific clinical challenge. The Australian guidelines require evidence of remission and absence of cognitive change when considering applications for re‐licensing driver or individuals applying to reengage in safety‐sensitive work. This paper reviews some of the clinical and biochemical indicators that determine whether a particular person is in ‘remission’ and meets the criteria for return to driving or other safety‐sensitive occupation. It provides an overview of the challenges in establishing an evidence‐based approach to determining fitness for safety critical activities. There is no internationally accepted definition of ‘remission’. Review of the literature and examination of assessment protocols from other national jurisdictions are available for alcohol and the more important drugs of interest in road safety. Assessing fitness to drive when there is a history of substance misuse and/or substance use disorders is a complex issue that requires assessment of biomarkers, clinical findings and clinical assessment before the person returns to driving. We propose that hair testing provides a reliable and reproducible way to demonstrate remission and provide cost‐effective monitoring. Standardised psychological tests could provide a reproducible assessment of the cognitive effects of drug use and suitability to resume driving. We recommend that AustRoads amend the national guidelines to reflect an evidence‐based approach to assessing fitness to drive after conviction for offences related to alcohol and drug use.
The vitamin epidemic: what is the evidence for harm or value?
Authors: Kennedy Michael
Published: August 2018

Complementary medicines are a multibillion‐dollar industry of which vitamin supplements are an important component. Most of the claims of benefit are not evidenced‐based, and vitamin supplements may be associated with severe adverse reactions that are uncommon but can occur with high doses of some vitamins. There is no case for vitamin supplementation in normal, healthy, non‐pregnant or lactating adults who are receiving the recommended daily intake of nutrients.
Enhancing self‐care strategies in heart failure through patient‐reported outcome measures
Authors: Segan Louise , Nanayakkara Shane , Mak Vivian , Kaye David
Published: August 2018

Heart failure (HF) is a major cause of morbidity and mortality, requiring collaborative patient‐centred care. Patient engagement is fundamental to long‐term management; patient‐reported outcome measures are an increasingly recognised method of assessing medical interventions. A qualitative study of 31 patients with HF found they were twice as likely to use their own management strategies including electronic platforms rather than existing resources. Barriers to self‐care included patient education, timely recognition of signs and symptoms of HF with an appropriate escalation plan, non‐adherence and polypharmacy.
Qualitative study on the experiences of hepatitis B carriers in coping with the disease
Authors: Valizadeh Leila , Zamanzadeh Vahid , Zabihi Ali , Negarandeh Reza , Jafarian Amiri Seyedeh Roghayeh
Published: August 2018

Aim: Hepatitis is a systemic infection that causes restrictions in the life of many patients due to its chronic nature and it necessitates the use of coping strategies to improve the quality of life. This study aims to demonstrate the experiences of hepatitis B carriers in coping with the disease.

Methods: The present study was conducted by using a qualitative content analysis. The data were collected through 18 unstructured and in‐depth interviews from 2014 to 2016 at medical centers, a gastrointestinal and liver diseases research center in the cities of Babol and Amol (northern Iran) and Tabriz (north‐western Iran) with patients infected with hepatitis B. The study was carried out by using purposive sampling.

Results: The data analysis led to the extraction of the main theme, “attempting an active expansion of interactions,” and its three subthemes, including: “denial of the disease,” “protecting oneself or others,” and “coping with the disease.”

Conclusion: Patients with hepatitis B use different strategies to cope with this disease. In order for patients to properly face the disease and to live with minimum challenges and limitations, they need to be suitably understood and supported. Therefore, consideration of education and consultation programs regarding the different aspects of this disease is urgent.
Human dynamics in space and time: A brief history and a view forward
Authors: Yuan May
Published: August 2018

This article highlights the key intellectual development in human dynamics research, examines the modeling emphases in publications, and argues for research directions in need. Human dynamics research is discussed in two broad directions: spacing time and timing space, to model human activities and interactions. Time is essential to human dynamics research. Space, while often being overlooked, in complement with time is critical to understanding human dynamics because knowing where activities take place is essential to knowing how and why people act and interact. Some interactions allow remote or asynchronized participations, and others require movement to collocate individuals for participating in synchronized activities. A spacing time approach examines the temporal gaps between interactions. A timing space approach investigates the spatial pulses between interactions. Primary research in the spacing time of human dynamics established queueing theories to explain the bursts and heavy‐tailed distribution of human interactions. Although research on the timing space of human dynamics enjoys growing popularity with data from geo‐tagged social media and location‐aware social internet of things (SIoT), its publications remain mostly exploratory. This article suggests a hierarchical framework to systematically study human dynamics and relate findings to build the body of knowledge about human dynamics.
MicroRNA-30c-5p modulates neuropathic pain in rodents
Authors: Tramullas Mónica , Francés Raquel , de la Fuente Roberto , Velategui Sara , Carcelén María , García Raquel , Llorca Javier , Hurlé María A.
Published: August 2018

miR-30c-5p expression modulates pain in rodent models of nerve injury and is overexpressed in patients with neuropathic pain due to leg ischemia.
Genome Sequence of Oenococcus oeni UNQOe19, the First Fully Assembled Genome Sequence of a Patagonian Psychrotrophic Oenological Strain
Authors: Iglesias Néstor G. , Valdés La Hens Danay , Olguin Nair T. , Bravo-Ferrada Bárbara M. , Brizuela Natalia S. , Tymczyszyn E. Elizabeth , Bibiloni Horacio , Caballero Adriana C. , Delfederico Lucrecia , Semorile Liliana
Published: August 2018

Oenococcus oeni
UNQOe19 is a native strain isolated from a Patagonian pinot noir wine undergoing spontaneous malolactic fermentation. Here, we present the 1.83-Mb genome sequence of
O. oeni
UNQOe19, the first fully assembled genome sequence of a psychrotrophic strain from an Argentinean wine.
Fifteen-minute consultation: Chickenpox vaccine—should parents immunise their children privately?
Authors: Gray Sebastian J , Cathie Katrina
Published: August 2018

Varicella zoster virus primarily causes chickenpox, usually a mild self-limiting illness of childhood. However, complications occur in 1% with 4200 annual deaths. Since the first vaccination was developed in the 1970s, many countries have introduced universal mass immunisation, but the UK currently only routinely immunises ‘at-risk’ populations. With increasing availability of private varicella vaccination, this article reviews the pros and cons of whether parents should be immunising their children with the chickenpox vaccine privately.