bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Scavenging Tool for Cancer Biomarker Discovery based on the Blood-Circulating Nanoparticle Protein Corona
Authors: Hadjidemetriou Marilena , Al-ahmady Zahraa , Buggio Maurizio , Swift Joe , Kostarelos Kostas
Published: August 2018

The prominent discrepancy between the significant investment towards plasma biomarker discovery and the very low number of biomarkers currently in clinical use stresses the need for novel discovery technologies. The discovery of protein biomarkers present in human blood by proteomics is tremendously challenging, owing to the large dynamic concentration range of blood proteins. Here, we describe the use of blood-circulating lipid-based nanoparticles (NPs) as a scavenging tool to comprehensively analyse the blood circulation proteome. We aimed to exploit the spontaneous interaction of NPs with plasma proteins once injected in the bloodstream, known as ‘protein corona’ and to facilitate the discovery of previously unreported biomarker molecules for cancer diagnostics. We employed two different tumor models, a subcutaneous melanoma model (B16-F10) and human lung carcinoma xenograft model (A549) and comprehensively compared by mass spectrometry the in vivo protein coronas formed onto clinically used liposomes, intravenously administered in healthy and tumor-bearing mice. The results obtained demonstrated the ability of blood-circulating liposomes to surface-capture and amplify low molecular weight (MW) and low abundant tumor specific proteins (intracellular products of tissue leakage) that could not be detected by plasma analysis, performed in comparison. Most strikingly, the NP (liposomal) corona formed in the xenograft model was found to consist of murine host response proteins, as well as human proteins released from the inoculated and growing human cancer cells. This study offers direct evidence that the in vivo NP protein corona could be deemed as a valuable tool of the blood proteome in experimental disease models to allow the discovery of potential biomarkers.

ToC Graphic
Tuberculosis in the military: Trends in notification and treatment outcomes within the Zimbabwe Defence Forces, Dependants and Communities 2010-2015
Authors: Muringazuva Caroline , Owiti Philip , Edwards Jeffrey , Mutetse Godfrey N , Dobbie Munyaradzi , Chimedza Jasper
Published: August 2018

Background

Historically, tuberculosis (TB) has been responsible for significant disease burden among the military both during peace and conflict. A routine review of Zimbabwe Defence Force (ZDF) data showed 36% of reported deaths could be attributed to TB. We conducted a study to determine the TB trends and outcomes among patients managed in ZDF health facilities between 2010-2015.

Methods

Retrospective cohort study of TB patients (military and dependents). Data were extracted from ZDF TB registers and analyzed for trends in notification and outcomes. Independent factors associated with unfavourable TB treatment outcomes were modeled using multivariable regression.

Results

Of the total 1298 TB patients, 84% were males, median age 37 years and 92% from Army facilities. Ninety three percentage had pulmonary TB, 87% were new patients and 68% HIV co-infected (97% on antiretroviral therapy[ART]). Number of TB cases reduced two-fold between 2010-2015 (317 vs 115). Treatment outcomes remained relatively stable with overall treatment success of 81%, 9.9% deaths, 0.2% loss to follow up, 2.2% treatment failure, 6.6% not evaluated. Clients who were HIV-positive and not on ART were 3.81 times likely to have unfavourable outcome.

Conclusion

This is the first study of TB in an African defence force showed decreasing trends in notified TB cases. Though treatment success was comparable over time, it still fell below international targets. Being HIV-positive (even with ART) was associated with increased unfavourable outcomes. Continued monitoring, evaluation and increased support of the TB programme within this high risk population is recommended.
Non-invasive spinal electro-magnetic stimulation (SEMS): a tool for evaluation and modulation of lower limb spinal-muscular transmission in healthy adults
Authors: Arvanian Victor L. , Petrosyan Hayk , Zou Chuancai , Leone Cynthia , Zaidi Mohammad , Hou Wei , Tesfa Asrat , Fahmy Magda , Kaufman Mark , Sisto Sue A.
Published: August 2018

Objective

Our earlier electrophysiological recordings using animal models revealed diminished transmission through spared fibers to motoneurons and leg muscles after incomplete spinal cord injury (SCI). Administration of spinal electro-magnetic stimulation (SEMS) at specific parameters induced transient improvement of transmission at neuro-muscular circuitry in SCI animals. In the current human study, we sought translate this knowledge to establish optimal parameters of SEMS for (i) neurophysiological evaluation via Compound Motor Action Potential (CMAP); and (ii) modulation at neuro-muscular circuitry via H-reflex and M-wave response in 12 healthy adults.

Methods

SEMS application was with a coil positioned over T12-S1 spinal levels. SEMS-evoked CMAP-responses were wirelessly measured simultaneously from biceps femoris (BF), semitendinosus (ST), vastus lateralis (VL), soleus (SOL), medial gastrocnemius (MG) and lateral gastrocnemius (LG) muscles. We also examined effects of SEMS trains on H-reflex and M-wave responses. H-reflexes and M-waves were measured simultaneously from SOL, MG and LG muscles and evoked by peripheral electrical stimulation of tibial nerves before and after each SEMS session.

Results

Spinal levels for SEMS application to evoke CMAP-responses in corresponding muscles and amplitude/latency of these responses have been established. SEMS applied over L4-S1 spinal levels at 0.2 Hz rate for 30 min induced facilitation of H-reflexes and M-responses. Facilitation lasted for at least 1 hour after stopping SEMS and was associated with a decrease in threshold intensity and leftward shift of recruitment curve for H-reflex and M-wave. SEMS did not alter TMS-evoked responses in hand muscles.

Conclusion

SEMS is a novel, non-invasive approach for sustained neuromodulation of H-reflex and M-wave responses in triceps surae muscle group. The parameters of SEMS application established in this study for evaluation and neuromodulation of neural pathways innervating leg muscles in healthy individuals may be used as a reference for neurophysiological evaluation and long-lasting plasticity of the lower limb spino-neuromuscular circuitry in individuals with SCI.
Nanopore-based DNA sequencing in clinical microbiology: preliminary assessment of basic requirements
Authors: Harstad Håvard , Ahmad Rafi , Bredberg Anders
Published: August 2018

Aim

Identify basic requirements for a metagenomic nanopore sequencing protocol permitting frequent application in a clinical microbiology daily routine diagnostic setting.

Background

Nanopore sequencing with the Oxford Nanopore Technologies MinION device has a potential to markedly improve clinical diagnosis of infections. Reports have emerged recently that it may provide direct-from-clinical-sample information; for example, with urine samples, bronchial tuberculosis samples and orthopedic prostheses. However, the ideal protocol for clinical use remains to be determined, especially relating to detection of relevant pathogen quantities and to finding a reasonable level of economic costs.

Results

MinION can provide qualitatively and quantitatively correct identification of multiple species in metagenomics samples. For detection of clinically relevant quantities of bacteria (on a nanogram DNA level) there is a need for carrier DNA. Importantly, high-purity DNA and a naïve MinION flow cell seem to be critical parameters.

Conclusions

Our results suggest that high-purity clinical sample DNA, addition of carrier DNA and a naïve flow cell are critical factors for clinical use of MinION. A relatively high error rate may limit detection of antimicrobial resistance genes, and a realistic level of costs will require availability of a price-reduced and single-use flowcell.
Triggering MSR1 promotes JNK-mediated inflammation in IL-4 activated macrophages
Authors: Guo Manman , Härtlova Anetta , Gierliński Marek , Prescott Alan , Castellvi Josep , Losa Javier Hernandez , Petersen Sine K. , Wenzel Ulf A. , Dill Brian D. , Emmerich Christoph H. , Cajal Santiago Ramon Y , Russell David G. , Trost Matthias
Published: August 2018

Alternatively activated M2 macrophages play an important role in maintenance of tissue homeostasis by scavenging dead cells, cell debris and lipoprotein aggregates via phagocytosis. Using proteomics, we investigated how alternative activation, driven by IL-4, modulated the phagosomal proteome to control macrophage function. Our data indicate that alternative activation enhances homeostatic functions such as proteolysis, lipolysis and nutrient transport. Intriguingly, we identified the enhanced recruitment of the TAK1/MKK7/JNK signalling complex to phagosomes of IL-4 activated macrophages. The recruitment of this signalling complex was mediated through K63-polyubiquitylation of the macrophage scavenger receptor 1 (MSR1). Triggering of MSR1 in IL-4 activated macrophages leads to enhanced JNK activation, thereby promoting a phenotypic switch from an anti-inflammatory to a pro-inflammatory state, which was abolished upon MSR1 deletion or JNK inhibition. Moreover, MSR1 K63-polyubiquitylation correlated with the activation of JNK signalling in ovarian cancer tissue from human patients, suggesting that it may be relevant for macrophage phenotypic shift in vivo. Altogether, we identified that MSR1 signals through JNK via K63-polyubiquitylation and provide evidence for the receptor’s involvement in macrophage polarization.
Chromatin Immunoprecipitation for Chromatin Interaction Analysis Using Paired-End-Tag (ChIA-PET) Sequencing in Tadpole Tissues
Authors: Buisine Nicolas , Ruan Xiaoan , Ruan Yijun , Sachs Laurent M.
Published: August 2018

Proper gene expression involves communication between the regulatory elements and promoters of genes. Because regulatory elements can be located over a large range of genomic distances (from as close as a few hundred bp to as much as several Mb away), contact and communication between regulators and the core transcriptional machinery at promoters are mediated through DNA looping. Today, chromosome conformation capture (3C)-based methods efficiently probe chromosome folding in the nucleus and thus provide a molecular description of physical proximity between enhancer(s) and their target promoter(s). One such method, chromatin interaction analysis using paired-end-tag (ChIA-PET) sequencing, is a leading high-throughput method for detection of genome wide chromatin interactions. Briefly, the method involves cross-linkage of chromatin (-DNA) fibers in cells in situ, fragmentation of the fixed chromatin-DNA complexes by sonication, followed by enrichment of the chromatin complexes with a dedicated antibody through the process of immunoprecipitation (IP). Next, application of the ChIA-PET protocol followed by deep sequencing and mapping of reads to the reference genome reveals both binding sites and remote chromatin interactions mediated by the protein factors of interest. The method detailed here focuses on ChIP sample preparation and can be completed in ∼5 d. The ChIA-PET method is detailed in an associated protocol. Because not all chromatin immunoprecipitation protocols are suitable for ChIA-PET, it is important to strictly follow this procedure before performing the ChIA-PET protocol.
Altered β-Lactamase Selection Approach for Site-Directed Mutagenesis
Authors: Forloni Matteo , Liu Alex Y. , Wajapeyee Narendra
Published: August 2018

Many protocols exist to perform site-directed mutagenesis, and here we present one of the more commonly used ones—site-directed mutagenesis by altered β-lactamase selection. β-Lactamase is an enzyme that cleaves ampicillin, rendering it impotent to bacteria. Certain mutations in the active site of β-lactamase can alter the substrate specificity of the enzyme and allow it to have increased hydrolytic activity for the cephalosporin family of antibiotics, a property not shared by wild-type lactamases. E. coli cells carrying the β-lactamase triple mutant G238S:E240:R241G show increased resistance to cefotaxime and ceftriaxone, two cephalosporins, compared with wild-type cells. This protocol takes advantage of this property to select for plasmids that have undergone site-directed mutagenesis.
High-involvement human resource practices, employee learning and employability
Authors: Liu Wei
Published: August 2018

Purpose

Although environmental factors at the organizational level are of importance for individual employability, very few studies have investigated how the practices an organization implements can facilitate employability. The purpose of this paper is to analyze how high-involvement human resources (HIHR) practices (i.e. recognition, competence development, empowerment, information sharing and fair rewards) influence employee learning, which contributes to employability.

Design/methodology/approach

The data were collected from 288 pairs of employees and their direct supervisors in Chinese companies. In this study, we measure perceived employability from both employees and their direct supervisors. Structural equation modeling (SEM) analysis is conducted to test the hypotheses.

Findings

The results indicate that employees’ perceptions of the HIHR practices of recognition, competence development, empowerment and information sharing are positively related to employee learning, and then facilitate self- and supervisor-ratings of employees’ employability. Practices of fair rewards have a negative effect on employee learning and employability.

Originality/value

This study contributes to employability and human resource management literature in several ways. First, the study raises the association between different HIHR practices and perceived employability through employee learning. Second, the study considers both self-rating and supervisor-rating of employability to improve the effectiveness of the results.
Institutional barriers to women’s employment in Saudi Arabia
Authors: Alfarran Abeer , Pyke Joanne , Stanton Pauline
Published: August 2018

Purpose

The purpose of this paper is to explore the effectiveness of the Saudi employment programme “Nitaqat” in addressing institutional barriers to women’s employment in the Saudi private sector. The paper has a particular focus on the perspectives of unemployed women as the intended recipients of increased employment opportunities.

Design/methodology/approach

This paper adopts a qualitative approach, drawing on findings from face-to-face interviews conducted with two groups of stakeholders, government officials and unemployed Saudi women.

Findings

Four key findings are identified. First, the considerable cultural and regulatory barriers of a conservative society are resilient impediments to the success of Saudi employment policy. Second, discrimination against women is endemic in the Saudi society; however, it is largely unrecognised within the Saudi culture and often accepted by women themselves. Third, due to government regulations, cultural constraints and the gendered educational system, the private sector contributes to sustaining labour market segmentation through discriminatory practices. Finally, while a positive change is taking place in Saudi Arabia regarding women’s employment, it is incremental and uneven.

Originality/value

This paper provides new insights into the institutional barriers related to the labour force participation of Saudi women from the perspective of Saudi women themselves.
Validity of self-reported conflict handling preferences and the role of self-enhancement
Authors: Johnson Kirsten E. , Hall Judith A.
Published: August 2018

Purpose

This paper aims to assess predictive and convergent validity of a trait measure of conflict handling styles (DUTCH) with two alternative methods of measuring such styles: a vignette measure of behavioral choices (CB-Pref) and behavior in a role-played conflict. In addition, this paper investigates self-enhancement in responses to the two self-report measures.

Design/methodology/approach

In Studies 1 (N= 117), 2 (N= 116) and 4 (N= 68), participants completed the DUTCH and CB-Pref. In Study 3 (N= 56 dyads), participants completed the DUTCH and a role-played conflict. In Study 4, participants also responded to the measures as either a typical person or an ideal person would.

Findings

The DUTCH predicted four of five styles individuals chose across nine vignettes of the CB-Pref. In Study 4, the DUTCH predicted three of the five. In Study 3, only the DUTCH’s forcing style predicted actual behavior. In Study 4, participants rated themselves as more constructive and less destructive than typical, but less constructive than ideal. Participants in general were somewhat self-enhancing on both self-report measures, but individual differences in social desirability were generally unrelated to self-report responses.

Originality/value

This work takes a multi-method approach to assessing the validity of a self-report conflict style measure, allowing for the assessment of the measure’s predictive and convergent validity when predicting self-reported style tendencies to style selected in vignettes and behavior in a role-played conflict.
Informing quality in emergency care: understanding patient experiences
Authors: Swallmeh Esmat , Byers Vivienne , Arisha Amr
Published: August 2018

Purpose

Assessing performance and quality in healthcare organisations is moving from focussing solely on clinical care measurement to considering the patient experience as critical. Much patient experience research is quantitative and survey based. The purpose of this paper is to report a qualitative study gathering in-depth data in an emergency department (ED).

Design/methodology/approach

The authors used empirical data from seven focus groups to understand patient experience as participants progressed through a major teaching hospital in an Ireland ED. A convenience sampling technique was used, and 42 participants were invited to share their perceptions and outline key factors affecting their journey. A role-playing exercise was used to develop improvement themes. Data were analysed using thematic analysis and data analysis software (NVivo 10).

Findings

Capturing ED patient experience increases our understanding and process impact on the patient journey. Factors identified include information, access, assurance, responsiveness and empathy, reliability and tangibles such as surroundings, food and seating.

Research limitations/implications

Owing to the ED patient’s emergency nature, participants were recruited if triaged at levels 3–5 (Manchester Triage System). The study explored patients’ immediate rather thanpost hocexperiences where recollections may change over time.

Originality/value

To the authors’ knowledge, no study has examined in-depth, ED patient experience in Ireland using qualitative interviewing, obtaining critical process insights as it occurs. The potential to inform patient process improvements in Irish EDs is significant.
Infant mortality rate in India: mediating causes
Authors: Arockiasamy Arulraj , Anburose Antonyraj
Published: August 2018

Purpose

The purpose of this paper is to develop a new approach to health service quality assurance.

Design/methodology/approach

Data were collected using a structured, eight-section questionnaire. Stratified random samples were drawn from four villages based in four Indian regions.

Findings

Psychological discomfort is an infant mortality rate (IMR) mediating factor. The root mean square error of approximation fit statistic for the model was 0.08, which was considered the best fit.

Practical implications

Addressing mediating causes can reduce IMR in developing countries.

Originality/value

The model that the authors described helps health institution managers to map quality assurance health management and economics.
An integrative approach to improving patient care pathways
Authors: Williams Sharon , Radnor Zoe
Published: August 2018

Purpose

Globally, healthcare managers continue to struggle with increasing demands for their services being delivered with limited or shrinking resources. It is, therefore, clear that systems, processes and practices need to change to meet these challenges. The purpose of this paper is to assess how integrating two improvement technologies, Lean and integrated care pathways (ICP) might help.

Design/methodology/approach

Lean and ICP in healthcare provide a platform to develop conceptual frameworks for integrating two approaches.

Findings

A conceptual integrated framework is provided to assist care pathway designers and implementers to consider the synergistic benefits of combining approaches to improvement.

Research limitations/implications

The authors provide a conceptual framework that requires empirically testing.

Practical implications

This research provides a conceptual framework to aid practitioners to improve healthcare design and delivery.

Originality/value

For the first time, the authors bring together two approaches to improving patient care pathway design and consider how these are linked in relation to improving healthcare delivery.
Levelling bed occupancy: reconfiguring surgery schedules via simulation
Authors: Yip Kenneth , Leung Louisa , Yeung Deacons
Published: August 2018

Purpose

The purpose of this paper is to present simulation modelling to reconfigure a 700-bed Hong Kong hospital’s master surgery schedule (MSS), aiming to improve patient flow, capacity management and resource allocation through levelling bed occupancy within the hospital.

Design/methodology/approach

A discrete-event simulation model was developed to understand how changes to the MSS would affect bed occupancy, thereby providing business intelligence for short- and long-term hospital planning. A decision tool was subsequently developed for hospital managers to test different scenarios.

Findings

Simulation modelling showed that significant bed occupancy levelling could be achieved through small and practicable changes to the MSS. Optimisation routines conducted using the simulation model then gave additional insights into how the schedule should be revamped for the long term.

Practical implications

The authors show how operations research methods are useful for guiding hospital operational planning. The authors show that a data-driven and evidence-based model enables hospital managers to critically explore various scheduling changes, while also providing a scientific common ground for discussion among important stakeholders. It is a crucial step forward when adopting advanced analytics for Hong Kong hospital operational planning.

Originality/value

The authors provide a robust method for evaluating the relationship between Hong Kong hospital’s MSS and its bed occupancy. Through simulating various changes to the surgical schedule, valuable and practicable insights were made available for hospital managers to make short- and longer-term changes that enhance the system’s overall efficiency and service quality.
Estimating facilities maintenance cost using post-occupancy evaluation and fuzzy set theory
Authors: Alshibani Adel , Hassanain Mohammad A.
Published: August 2018

Purpose

The purpose of this paper is to introduce a new general approach for estimating the maintenance cost of constructed facilities. The proposed approach consists of four components, including: facility work breakdown structure; historical maintenance cost and cost contingency data of actual completed projects; feedback obtained from the post-occupancy evaluation (POE); and fuzzy set theory (FST) to define the uncertainty associated with the maintenance cost and cost contingency as an alternative approach to simulation.

Design/methodology/approach

Literature review of the existing methods used for estimating maintenance cost of constructed facilities was conducted to highlight the limitations of the existing methods and models. The paper then introduced a new approach in which the results obtained from POE are integrated with the estimator’s judgment in estimating maintenance cost of constructed facility. As a proof of concept, the developed approach is tested on a private school facility in the city of Khobar, Saudi Arabia. The application of the proposed approach in this case project demonstrates its applicability and features in comparison with the existing practice.

Findings

The application of the developed approach on a school case project demonstrated that the developed approach can provide a reliable facility maintenance cost estimate, narrow the uncertainties and vagueness associated with the estimated cost, and provide the estimator with the necessary information to conduct risk analysis with less effort, less computations and less complexity comparing with that provided by complex simulation. The results also showed that integrating POE in the estimating process can provide more accurate cost estimate with high level of confidence.

Originality/value

The paper presents a new approach for estimating facility maintenance cost. The developed approach introduced a new concept that assists maintenance contractors in preparing facility maintenance estimate with improved accuracy while satisfying the facility user’s needs. The proposed approach integrates the estimator’s judgment with POE to model the uncertainties associated with cost using FST as an alternative approach for complex simulation.
Linkages between empowering leadership and subjective well-being and work performance via perceived organizational and co-worker support
Authors: Kim Daeho , Moon Chul Woo , Shin Jiseon
Published: August 2018

Purpose

The purpose of this paper is to examine the effects of empowering leadership at the team level on employees’ subjective well-being (SWB) and work performance through perceived social support. Based on social exchange theory (Blau, 1964), the study identifies the mediating effects of perceived social support in the relationship between empowering leadership and both employees’ well-being and work performance.

Design/methodology/approach

The study utilized a survey of 1,225 employees working for an organization in South Korea and archival data of the organization. It employed hierarchical linear modeling analyses and the CWC(M) procedure for the tests of multilevel mediation.

Findings

It was observed that perceived organizational support (POS) and co-worker support (PCS) mediated the relationship between empowering leadership and SWB, but not the relationship between empowering leadership and performance. There was a significant direct effect of empowering leadership on both POS and PCS, which subsequently led to improved work performance.

Originality/value

Taking a multilevel approach to leadership and relying on both self-reported and organizational archival data, this study contributes to the literature on leadership and well-being by examining the relationships between empowering leadership toward a team and team members’ well-being and performance, and by revealing the crucial mechanisms that underlie them. The study helps to elucidate the impact of empowering leadership on employee SWB, which has largely been neglected in prior management research.
Key mechanisms underlying netrin‐1 prevention of impaired spatial and object memory in Aβ1‐42 CA1‐injected rats
Authors: Zamani Elham , Parviz Mohsen , Roghani Mehrdad , Mohseni‐moghaddam Parvaneh
Published: August 2018

Alzheimer's disease (AD) is a neurodegenerative disorder with an incompletely defined aetiology that is associated with memory and cognitive impairment. Currently available therapeutics only provide temporary assistance with symptoms. In spite of plentiful research in the field and the generation of thousands of studies, much is still to be clarified on precise mechanisms of pathobiology, prevention modalities, disease course and cure. Netrin‐1, a laminin family protein, is said to have anti‐inflammatory and anti‐apoptotic effects and has a key role in neurogenesis and morphogenesis of neural structures. Accordingly, this study was designed to investigate protective effects of bilateral intrahippocampal fissure microinjections of netrin‐1 on memory impairment in rat model of AD. Concomitant administration of netrin‐1 with amyloid beta 1‐42 (Aβ1‐42) improved cognitive dysfunction in novel object recognition task (NOR), ameliorated impaired spatial memory in Morris water maze (MWM) setting, increased neuronal density and reduced amyloid aggregation in rat AD model. Netrin‐1 was also seen to prevent Aβ1‐42‐induced caspase‐3, caspase‐7 and NF‐κB (nuclear factor kappa‐light‐chain‐enhancer of activated B cells) activation. Therefore, based on the data reported here, netrin‐1 may be a promising biologic therapeutic that addresses the memory and neuronal loss associated with AD.
FAS A‐670G and Fas ligand IVS2nt A 124G polymorphisms are significantly increased in women with pre‐eclampsia and may contribute to HELLP syndrome: a case‐controlled study
Authors: Raguema N , Zitouni H , Ben Ali Gannoun M , Benletaifa D , Almawi WY , Mahjoub T , Lavoie JL
Published: August 2018

Objective

We evaluated the association between the Fas‐670A/G and the Fas ligand FasL IVS2nt 124 A/G polymorphisms and the risk of pre‐eclampsia and its complications.

Design

A case‐controlled study.

Setting

University Hospitals in most areas of Tunisia.

Population

We recruited 300 pregnant women who developed pre‐eclampsia and 300 age‐matched healthy pregnant women from the same hospital.

Methods

Genotyping of Fas‐670A/G and the FasL IVS2nt 124A/G gene polymorphisms were conducted using polymerase chain reaction‐restriction fragment length polymorphism among our cohort.

Main outcome measures

Fisher's exact test was used to compare the statistical differences between groups for categorical variables and Student t tests were used for continuous variables.

Results

The frequency of the Fas‐670G gene variant was significantly increased in women with pre‐eclampsia (42%) compared with control women (30%; P < 0.001). Also, a statistically significant difference was obtained in the distribution of the FasL IVS2nt 124G gene variant when comparing women with pre‐eclampsia (43%) with controls (30%; P < 0.001). Interestingly, we found that the carriage of Fas‐670G was associated with increased liver enzymes, suggesting an increased prevalence of the haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, a pre‐eclampsia complication.

Conclusion

The Fas‐670G and FasL IVS2nt 124G polymorphisms are associated with a higher risk of pre‐eclampsia and its complications.

Tweetable abstract

Polymorphisms in the Fas and FasL genes are associated with increased risk of pre‐eclampsia and HELLP syndrome.
Performance of SAPS II according to ICU length of stay: Protocol for an observational study
Authors: Granholm Anders , Christiansen Christian Fynbo , Christensen Steffen , Perner Anders , Møller Morten Hylander
Published: August 2018

Background

Severity scores, including the Simplified Acute Physiology Score (SAPS) II, are widely used in the intensive care unit (ICU) to predict mortality outcomes using data from ICU admission or shortly hereafter. For patients with longer ICU length of stay (LOS), the predictive performance of admission‐based severity scores may deteriorate compared to patients with shorter ICU LOS. This protocol and statistical analysis plan outlines a study that will assess the influence of ICU LOS on the performance of SAPS II for predicting 90‐day post‐ICU mortality.

Methods

A Danish nationwide cohort study including adult (≥18 years) ICU patients admitted to a Danish ICU between 1 January 2012 and 30 June 2016. The study will be conducted using the Danish Intensive Care Database (DID), which contains data routinely, prospectively, and consecutively reported for all Danish ICU admissions. Discrimination of SAPS II for predicting 90‐day post‐ICU mortality will be assessed for the entire cohort and stratified according to ICU LOS. A first‐level recalibration of SAPS II will be performed, and if adequate, standardised mortality ratios and calibration stratified according to ICU LOS will be reported.

Conclusions

The outlined large, nationwide cohort study will provide important, contemporary information about the influence of ICU LOS on severity score performance relevant for ICU clinicians, researchers, and administrators. Publication of the protocol and statistical analysis plan prior to study conduct ensures transparency, and limits the risk of publication bias, post hoc changes in analyses, and challenges with multiple comparisons.
Explicit Attitudes, Working Memory Capacity, and Driving After Drinking
Authors: Hatz Laura E. , McCarty Kayleigh N. , Bartholow Bruce D. , McCarthy Denis M.
Published: August 2018

Background

Attitudes toward driving after drinking are strongly predictive of drinking and driving behavior. This study tested working memory capacity (WMC) as a moderator of the association between attitudes and drinking and driving behavior. Consistent with dual process models of cognition, we hypothesized that the association between perceived danger and drinking and driving would be stronger for individuals with higher WMC.

Methods

Participants (N = 161) enrolled in larger alcohol administration study were randomly assigned to an alcohol (n = 57), placebol (n = 52), or control (n = 52, not included) beverage condition. Past‐year frequency of driving after drinking and WMC were assessed at baseline. Attitudes were assessed by asking participants to rate the perceived danger of driving at their current level of intoxication twice on the ascending limb (AL1, AL2), at peak breath alcohol concentration (BrAC), and twice on the descending limb (DL1, DL2).

Results

Analyses across the BrAC curve indicated that the hypothesized interaction was observed for the alcohol but not placebo condition. Analyses for each assessment point indicated that the interaction was significant for the ascending limb and peak BrAC. In the alcohol condition, for those higher in WMC, lower perceived dangerousness was strongly associated with increased driving after drinking (AL1: incident rate ratios [IRR] = 5.87, Wald's χ2 = 12.39, p = 0.006, 95% CI [2.19, 15.75]; AL2: IRR = 8.17, Wald's χ2 = 11.39, p = 0.001, 95% CI [2.41, 27.66]; Peak: IRR = 5.11, Wald's χ2 = 9.84, p = 0.002, 95% CI [1.84, 14.16]). Associations were not significant at low WMC.

Conclusions

Results suggest that individuals higher in WMC are more likely to act consistently with their explicit attitudes toward drinking and driving. Findings may have implications for existing drinking and driving interventions and suggest the potential for novel interventions targeting implicit associations or WMC.
Comprehensive causal models and harm minimization principles should guide regulations on vapourizers
Authors: Etter Jean‐François
Published: August 2018

Commentary to: Gateway effects and electronic cigarettes
Parental alcohol use disorder and offspring marital outcomes
Authors: Salvatore Jessica E. , Larsson Lönn Sara , Long Elizabeth C. , Sundquist Jan , Kendler Kenneth S. , Sundquist Kristina , Edwards Alexis C.
Published: August 2018

Aims

We tested whether parental alcohol use disorder (AUD) predicted adult offspring's likelihood of marriage and marriage to an AUD‐affected spouse; whether effects differed as a function of the sex or number of affected parents; and whether they were robust to confounders.

Design

Sex‐stratified Cox and logistic regression models.

Setting

Sweden.

Participants

A total of 1 171 070 individuals (51.40% male) born 1965–75.

Measurements

Obtained from legal, medical and pharmacy registries. Predictor was parent AUD. Outcomes were marriage and spouse AUD. Adjustments included offspring birth year and AUD; and parental education, marriage, divorce, criminal behavior and drug abuse.

Findings

Male and female offspring of AUD‐affected parents were more likely to marry at younger ages (< 25), illustrative unadjusted hazard ratio (HR)age 20 = 1.22 (1.17, 1.28) and 1.34 (1.20, 1.39) and were less likely to marry at older ages (> 25), HRage 30 = 0.79 (0.78, 0.81) and 0.82 (0.81, 0.84). Parental AUD was associated with higher odds of having an affected spouse for males and females, odds ratio (OR) = 1.47 (1.38, 1.57) and 1.63 (1.56, 1.70). Effects were more pronounced for those with two versus one AUD‐affected parent and adjustments attenuated effects negligibly. Daughters of affected mothers (versus fathers) were more likely to have AUD‐affected husbands, OR = 1.68 (1.54, 1.84) versus 1.56 (1.48, 1.64), while there was no difference in sons.

Conclusions

In Sweden, parental alcohol use disorder (AUD) is associated with a higher probability of marriage at younger ages, a lower probability of marriage at older ages and a higher likelihood of marriage to an affected spouse compared with no parental AUD. Most of these effects become stronger when the number of AUD‐affected parents increases from one to two, and most effects hold after controlling for parents’ socio‐economic status, marital history, other externalizing disorders and offspring's own AUD status. Daughters of affected mothers are more likely to have an affected spouse.
Nonparametric kernel estimation of the impact of tax policy on the demand for private health insurance in Australia
Authors: Gong Xiaodong , Gao Jiti
Published: August 2018

This paper is motivated by our attempt to answer a policy question: how is private health insurance take‐up in Australia affected by the income threshold at which the Medicare Levy Surcharge (MLS) kicks in? We propose a new difference deconvolution kernel estimator for the location and size of regression discontinuities. We also propose a bootstrapping procedure for estimating the confidence interval for the estimated discontinuity. Performance of the estimator is evaluated by Monte Carlo simulations before it is applied to estimating the effect of the income threshold of MLS on the take‐up of private health insurance in Australia, using contaminated data.
Precious reptiles: Social engagement and placemaking with saltwater crocodiles
Authors: Baynes‐Rock Marcus
Published: August 2018

In this paper I take up the call to expand the boundaries of social and physical landscapes in order to recognise the creative agencies of human and non‐human actors. In doing so, I wish to draw attention to the ways in which relations between both individuals and collectives combine to shape multi‐dimensional sociality in particular places. The place in question is a crocodile farm in tropical Australia. It is a curious place in that it was fostered by modes of objectification which serve to commoditise and conserve crocodiles at a species level with little attention to individuality. However, the particularity of crocodiles at the farming level compels their human handlers to make concessions to their demands. Crocodiles, by their refusals, attachments and individualities, elicit attention to their needs, which translates into practices and structures that are often at odds with profitability. In this way it is as much social processes as it is practicalities of producing skins which affect the farmed landscape and the beings it produces, creating a nexus of multispecies place‐making where individuals matter.
Cost‐effectiveness of surveillance schedules in older adults with non‐muscle‐invasive bladder cancer
Authors: Heijnsdijk Eveline A.M. , Nieboer Daan , Garg Tullika , Lansdorp‐Vogelaar Iris , de Koning Harry J. , Nielsen Matthew E.
Published: August 2018

Objective

To estimate the cost‐effectiveness of surveillance schedules for non‐muscle‐invasive bladder cancer (NMIBC) amongst older adults.

Patients and Methods

We developed a MIcrosimulation SCreening ANalysis (MISCAN) microsimulation model to compare the cost‐effectiveness of various surveillance schedules (every 3 months to every 24 months, for 2, 5 or 10 years or lifetime) for older adults (aged 65–85 years) with NMIBC. For each surveillance schedule we calculated total costs per patient and the number of quality adjusted life‐years (QALYs) gained. Incremental cost‐effectiveness ratios (ICERs), as incremental costs per QALY gained, were calculated using a 3% discount.

Results

As age increased, the number of QALYs gained per patient decreased substantially. Surveillance of patients aged 65 years resulted in 2–7 QALYs gained, whereas surveillance at age 85 years led to <1 QALY gained. The total costs of the surveillance schedules also decreased as age increased. The ICER of 6‐monthly surveillance at age 65 years for lifetime was $4999 (American dollars)/QALY gained. Amongst patients aged >75 years, the incremental yield of QALY gains for any increase in surveillance frequency and/or duration was quite modest (<2 QALYs gained).

Conclusion

With increasing age, surveillance for recurrences leads to substantially fewer QALYs gained. These data support age‐specific surveillance recommendations for patients treated for NMIBC.
A modern analogue of the Pleistocene steppe‐tundra ecosystem in southern Siberia
Authors: Chytrý Milan , Horsák Michal , Danihelka Jiří , Ermakov Nikolai , German Dmitry A. , Hájek Michal , Hájková Petra , Kočí Martin , Kubešová Svatava , Lustyk Pavel , Nekola Jeffrey C. , Pavelková Řičánková Věra , Preislerová Zdenka , Resl Philipp , Valachovič Milan
Published: August 2018

Steppe‐tundra is considered to have been a dominant ecosystem across northern Eurasia during the Last Glacial Maximum. As the fossil record is insufficient for understanding the ecology of this vanished ecosystem, modern analogues have been sought, especially in Beringia. However, Beringian ecosystems are probably not the best analogues for more southern variants of the full‐glacial steppe‐tundra because they lack many plant and animal species of temperate steppes found in the full‐glacial fossil record from various areas of Europe and Siberia. We present new data on flora, land snails and mammals and characterize the ecology of a close modern analogue of the full‐glacial steppe‐tundra ecosystem in the southeastern Russian Altai Mountains, southern Siberia. The Altaian steppe‐tundra is a landscape mosaic of different habitat types including steppe, mesic and wet grasslands, shrubby tundra, riparian scrub, and patches of open woodland at moister sites. Habitat distribution, species diversity, primary productivity and nutrient content in plant biomass reflect precipitation patterns across a broader area and the topography‐dependent distribution of soil moisture across smaller landscape sections. Plant and snail species considered as glacial relicts occur in most habitats of the Altaian steppe‐tundra, but snails avoid the driest types of steppe. A diverse community of mammals, including many species typical of the full‐glacial ecosystems, also occurs there. Insights from the Altaian steppe‐tundra suggest that the full‐glacial steppe‐tundra was a heterogeneous mosaic of different habitats depending on landscape‐scale moisture gradients. Primary productivity of this habitat mosaic combined with shallow snow cover that facilitated winter grazing was sufficient to sustain rich communities of large herbivores.
Nitric oxide and its role as a non‐adrenergic, non‐cholinergic inhibitory neurotransmitter in the gastrointestinal tract
Authors: Sanders Kenton M , Ward Sean M
Published: August 2018

NO is a neurotransmitter released from enteric inhibitory neurons and responsible for modulating gastrointestinal (GI) motor behaviour. Enteric neurons express nNOS (NOS1) that associates with membranes of nerve varicosities. NO released from neurons binds to soluble guanylate cyclase in post‐junctional cells to generate cGMP. cGMP‐dependent protein kinase type 1 (PKG1) is a major mediator but perhaps not the only pathway involved in cGMP‐mediated effects in GI muscles based on gene deletion studies. NOS1+ neurons form close contacts with smooth muscle cells (SMCs), interstitial cells of Cajal (ICC) and PDGFRα+ cells, and these cells are electrically coupled (SIP syncytium). Cell‐specific gene deletion studies have shown that nitrergic responses are due to mechanisms in SMCs and ICC. Controversy exists about the ion channels and other post‐junctional mechanisms that mediate nitrergic responses in GI muscles. Reduced nNOS expression in enteric inhibitory motor neurons and/or reduced connectivity between nNOS+ neurons and the SIP syncytium appear to be responsible for motor defects that develop in diabetes. An overproduction of NO in some inflammatory conditions also impairs normal GI motor activity. This review summarizes recent findings regarding the role of NO as an enteric inhibitory neurotransmitter.

Linked Articles

This article is part of a themed section on Nitric Oxide 20 Years from the 1998 Nobel Prize. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.2/issuetoc
Monetary policy tradeoffs between financial stability and price stability
Authors: Shukayev Malik , Ueberfeldt Alexander
Published: August 2018

We analyze the impact of interest rate policy on financial stability in an environment where banks can experience runs on their short‐term liabilities forcing them to sell assets at fire‐sale prices. Price adjustment frictions and a state‐dependent risk of financial crisis create the possibility of a policy tradeoff between price stability and financial stability. Focusing on Taylor rules with monetary policy possibly reacting to banks’ short‐term liabilities, we find that the optimized policy uses the extra tool to support investment at the expense of higher inflation and output volatility.
Could a higher inflation target enhance macroeconomic stability?
Authors: Dorich José , St‐Pierre Nicholas Labelle , Lepetyuk Vadym , Mendes Rhys R.
Published: August 2018

Recent international experience with the effective lower bound on nominal interest rates has rekindled interest in the benefits of inflation targets above 2%. We evaluate whether an increase in the inflation target to 3% or 4% could improve macroeconomic stability in the Canadian economy. We find that the magnitude of the benefits hinges critically on two elements: (i) the availability and effectiveness of unconventional monetary policy (UMP) tools at the effective lower bound and (ii) the level of the real neutral interest rate. In particular, we show that when the real neutral rate is in line with the central tendency of estimates, raising the inflation target yields some improvement in macroeconomic outcomes. There are only modest gains if effective UMP tools are available. In contrast, with a deeply negative real neutral rate, a higher inflation target substantially improves macroeconomic stability regardless of UMP.
Monetary policy and macroprudential policy: Different and separate?
Authors: Svensson Lars E. O.
Published: August 2018

The paper discusses how monetary and macroprudential policies can be distinguished, how appropriate goals for the two policies can be determined, whether the policies are best conducted separately or coordinately and by the same or different authorities and how they can be coordinated when desired. The institutional frameworks in Canada, Sweden and the UK are briefly compared. The Swedish example of monetary policy strongly “leaning against the wind” and the subsequent policy turnaround is summarized, as well as what estimates have been found of the costs and benefits of leaning against the wind.