bluuebunny/crossref_metadata_2025 huggingface dataset:
FunSPU: a versatile and adaptive multiple functional annotation-based association test of whole-genome sequencing data
Authors: Ma Yiding , Wei Peng
Published: June 2018

Despite ongoing large-scale population-based whole-genome sequencing (WGS) projects such as the NIH NHLBI TOPMed program and the NHGRI Genome Sequencing Program, WGS-based association analysis of complex traits remains a tremendous challenge due to the large number of rare variants, many of which are non-trait-associated neutral variants. External biological knowledge, such as functional annotations based on ENCODE, may be helpful in distinguishing causal rare variants from neutral ones; however, each functional annotation can only provide certain aspects of the biological functions. Our knowledge for selecting informative annotations a priori is limited, and incorporating non-informative annotations will introduce noise and lose power. We propose FunSPU, a versatile and adaptive test that incorporates multiple biological annotations and is adaptive at both the annotation and variant levels and thus maintains high power even in the presence of noninformative annotations. In addition to extensive simulations, we illustrate our proposed test using the TWINSUK cohort (n=1,752) of UK10K WGS data based on six functional annotations: CADD, RegulomeDB, FunSeq, Funseq2, GERP++, and GenoSkyline. We identified genome-wide significant genetic loci on chromosome 19 near gene TOMM40 and APOC4-APOC2 associated with low-density lipoprotein (LDL), which are replicated in the UK10K ALSPAC cohort (n=1,497). These replicated LDL-associated loci were missed by existing rare variant association tests that either ignore external biological information or rely on a single source of biological knowledge. We have implemented the proposed test in an R package “FunSPU”.
Ultra-Rapid Serial Visual Presentation Reveals Dynamics of Feedforward and Feedback Processes in the Ventral Visual Pathway
Authors: Mohsenzadeh Yalda , Qin Sheng , Cichy Radoslaw M , Pantazis Dimitrios
Published: June 2018

Human visual recognition activates a dense network of overlapping feedforward and recurrent neuronal processes, making it hard to disentangle processing in the feedforward from the feedback direction. Here, we used ultra-rapid serial visual presentation to suppress sustained activity that blurs the boundaries of processing steps, enabling us to resolve two distinct stages of processing with MEG multivariate pattern classification. The first processing stage was the rapid activation cascade of the bottom-up sweep, which terminated early as visual stimuli were presented at progressively faster rates. The second stage was the emergence of categorical information with peak latency that shifted later in time with progressively faster stimulus presentations, indexing time-consuming recurrent processing. Using MEG-fMRI fusion with representational similarity, we localized recurrent signals in early visual cortex. Together, our findings segregated an initial bottom-up sweep from subsequent feedback processing, and revealed the neural signature of increased recurrent processing demands for challenging viewing conditions.
Ligand Modulates Cross-Coupling between Riboswitch Folding and Transcriptional Pausing
Authors: Widom Julia R , Nedialkov Yuri A , Rai Victoria , Hayes Ryan , Brooks Charles L , Artsimovitch Irina , Walter Nils G
Published: June 2018

Numerous classes of riboswitches have been found to regulate bacterial gene expression in response to physiological cues, offering new paths to anti-bacterial drugs. As common studies of isolated riboswitches lack the functional context of the transcription machinery, we here combine single-molecule, biochemical and simulation approaches to investigate the coupling between co-transcriptional folding of the pseudoknot-structured preQ1 riboswitch and RNA polymerase (RNAP) pausing. We show that pausing at a site immediately downstream of the riboswitch requires a ligand-free pseudoknot in the nascent RNA, a precisely spaced sequence resembling the pause consensus, and electrostatic and steric interactions with the RNAP exit channel. While interactions with RNAP stabilize the native fold of the riboswitch, binding of the ligand signals RNAP release from the pause. Our results demonstrate that the nascent riboswitch and its ligand actively modulate the function of RNAP and vice versa, a paradigm likely to apply to other cellular RNA transcripts.
MGDrivE: A modular simulation framework for the spread of gene drives through spatially-explicit mosquito populations
Authors: Sánchez C. Héctor M. , Wu Sean L. , Bennett Jared B. , Marshall John M.
Published: June 2018

Malaria, dengue, Zika, and other mosquito-borne diseases continue to pose a major global health burden through much of the world, despite the widespread distribution of insecticide-based tools and antimalarial drugs. The advent of CRISPR/Cas9-based gene editing and its demonstrated ability to streamline the development of gene drive systems has reignited interest in the application of this technology to the control of mosquitoes and the diseases they transmit. The versatility of this technology has also enabled a wide range of gene drive architectures to be realized, creating a need for their population-level and spatial dynamics to be explored. To this end, we present MGDrivE (Mosquito Gene Drive Explorer): a simulation framework designed to investigate the population dynamics of a variety of gene drive architectures and their spread through spatially-explicit mosquito populations. A key strength of the MGDrivE framework is its modularity: a) a genetic inheritance module accommodates the dynamics of gene drive systems displaying user-defined inheritance patterns, b) a population dynamic module accommodates the life history of a variety of mosquito disease vectors and insect agricultural pest species, and c) a landscape module accommodates the distribution of insect metapopulations connected by migration in space. Example MGDrivE simulations are presented to demonstrate the application of the framework to CRISPR/Cas9-based homing gene drive for: a) driving a disease-refractory gene into a population (i.e. population replacement), and b) disrupting a gene required for female fertility (i.e. population suppression), incorporating homing-resistant alleles in both cases. We compare MGDrivE with other genetic simulation packages, and conclude with a discussion of future directions in gene drive modeling.
Single cell RNAseq provides a molecular and cellular cartography of changes to the human endometrium through the menstrual cycle
Authors: Wang Wanxin , Vilella Felipe , Alama Pilar , Moreno Inmaculada , Mignardi Marco , Pan Wenying , Simon Carlos , Quake Stephen R.
Published: June 2018

In a human menstrual cycle, the endometrium undergoes remodeling, shedding, and regeneration, all of which are driven by substantial gene expression changes in the underlying cellular hierarchy. Despite its importance in human fertility and regenerative biology, mechanistic understanding of this unique type of tissue homeostasis remains rudimentary. We characterized the transcriptomic transformation of human endometrium at single cell resolution, dissecting the multidimensional cellular heterogeneity of this tissue across the entire natural menstrual cycle. We profiled the behavior of 6 endometrial cell types, including a previously uncharacterized ciliated epithelial cell type, during four major phases of endometrial transformation, and found characteristic signatures for each cell type and phase. We discovered that human window of implantation opens with an abrupt and discontinuous transcriptomic activation in the epithelia, accompanied with widespread decidualized feature in the stromal fibroblasts. These data reveal signatures in the luminal and glandular epithelia during epithelial gland reconstruction, and suggest a mechanism for adult gland formation.
Identification of Klebsiella pneumoniae complex members using MALDI-TOF mass spectrometry
Authors: Rodrigues Carla , Passet Virginie , Brisse Sylvain
Published: June 2018

Klebsiella pneumoniae (phylogroup Kp1), one of the most problematic pathogens associated with antibiotic resistance worldwide, is phylogenetically closely related to K. quasipneumoniae [subsp. quasipneumoniae (Kp2) and subsp. similipneumoniae (Kp4)], K. variicola (Kp3) and two unnamed phylogroups (Kp5 and Kp6). Together, Kp1 to Kp6 make-up the K. pneumoniae complex. Currently, the phylogroups can be reliably identified only by gene sequencing. Misidentification using standard methods is common and the clinical significance of K. pneumoniae complex members is therefore imprecisely defined. Here, we evaluated the potential of MALDI-TOF mass spectrometry to discriminate K. pneumoniae complex members. We report for the first time the existence of mass spectrometry biomarkers associated with the phylogroups, with a sensitivity and specificity ranging between 80-100% and 97-100%, respectively. Strains within phylogroups Kp1, Kp2, Kp4 and Kp5 each shared two specific peaks not observed in other phylogroups. Kp3 strains shared a peak that was only observed otherwise in Kp5. Finally, Kp6 had a diagnostic peak shared only with Kp1. Kp3 and Kp6 could therefore be identified by exclusion criteria (lacking Kp5 and Kp1-specific peaks, respectively). Further, ranked Pearson correlation clustering of spectra grouped strains according to their phylogroup. These results call for incorporation of spectra of all K. pneumoniae complex members into reference MALDI-TOF spectra databases, in which they are currently lacking. This advance may allow for simple and precise identification of K. pneumoniae and closely related species, opening the way to a better understanding of their epidemiology, ecology and pathogenesis.
The Histone H3-H4 Tetramer is a Copper Reductase Enzyme
Authors: Attar Narsis , Campos Oscar A. , Vogelauer Maria , Cheng Chen , Xue Yong , Schmollinger Stefan , Mallipeddi Nathan V. , Boone Brandon A. , Yen Linda , Yang Sichen , Zikovich Shannon , Dardine Jade , Carey Michael F. , Merchant Sabeeha S. , Kurdistani Siavash K.
Published: June 2018

Ancestral histones were present in organisms with small genomes, no nucleus, and little evidence for epigenetic regulation, suggesting histones may have additional older functions. We report that the histone H3-H4 tetramer is an enzyme that catalyzes the reduction of Cu2+to Cu1+when assembledin vitrofrom recombinant histones. Mutations of residues in the putative active site at the interface of the apposing H3 proteins alter the enzymatic activity and cellular processes such as Sod1 function or mitochondrial respiration that depend on availability of reduced copper. These effects are not due to altered gene expression or copper abundance but are consistent with decreased levels of cuprous ions. We propose that the H3-H4 tetramer is an oxidoreductase that provides biousable copper for cellular and mitochondrial chemistry. As the emergence of eukaryotes coincided with the Great Oxidation Event and decreased biousability of metals, the histone enzymatic function may have facilitated eukaryogenesis.
Targeting integrin alpha5 receptor in pancreatic stellate cells to diminish tumor-promoting effects in pancreatic cancer
Authors: Kuninty Praneeth R. , Bansal Ruchi , De Geus Sanne W.L. , Schnittert Jonas , van Baarlen Joop , Storm Gert , Bijlsma Maarten F. , van Laarhoven Hanneke W. , Kuppen Peter J.K. , Vahrmeijer Alexander L. , Östman Arne , Sier Cornelis F.M. , Prakash Jai
Published: June 2018

Pancreatic stellate cells (PSCs) are the main precursors of cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma (PDAC), known to induce cancer aggressiveness. Integrin alpha5 (ITGA5), a fibronectin receptor, was found to be overexpressed by CAFs in stroma and linked to poor overall survival (log-rank p=0.022, n=137) of patients with PDAC. In vitro, knockdown of ITGA5 in human PSCs (hPSCs) inhibited their adhesion, migration, and proliferation and also inhibited TGF-β-mediated differentiation. In vivo, co-injection of PANC-1 tumor cells and hPSCs (sh-ITGA5) developed tumors with reduced fibrosis and slower growth rate compared to those composed of PANC-1 and hPSC (sh-Ctrl). Furthermore, we developed a ITGA5-antagonizing peptidomimetic (AV3) which inhibited TGFβ-mediated hPSC differentiation by blocking ITGA5/FAK pathway. In vivo, treatment with AV3 intraperitoneally attenuated tumor fibrosis and thereby enhanced the efficacy of gemcitabine in patient-derived xenografts in mice. Altogether, this study reports the therapeutic importance of ITGA5 in PDAC and provides novel therapeutic peptidomimetic to enhance the effect of chemotherapy.
17-(Allylamino)-17demethoxygeldanamycin reduces Endoplasmic Reticulum (ER) stress-induced mitochondrial dysfunction in C2C12 myotubes
Authors: Lightfoot Adam P. , Morgan Rhiannon S. , Parkes Joanna E. , Thoma Anastasia , Iwanejko Lesley A. , Cooper Robert G.
Published: June 2018

In patients with myositis, persistent skeletal muscle weakness in the absence of significant inflammatory cell infiltrates is a well-recognised, but poorly understood, cause of morbidity. This has led researchers to investigate cellular mechanisms independent of immune cells, which may contribute to this underlying muscle weakness. Chronic ER stress pathway activation is evident in the muscle of myositis patients, and is now a potential mediator of muscle weakness in the absence of inflammation. Abnormal ER stress pathway activation is associated with mitochondrial dysfunction, resulting in bioenergetic deficits and reactive oxygen species (ROS) generation, which in this context may potentially damage muscle proteins and thus impair contractile performance. This study examined whether treatment with the HSP90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17AAG) could mitigate these ER stress-induced changes. C2C12 myotubes were treated with the ER stress-inducing compound Tunicamycin, in the presence or absence of 17AAG. Myotubes were examined for changes relating to ER stress pathway activation, mitochondrial function, markers of oxidative damage and in myotubular dimensions. ER stress pathway activation caused mitochondrial dysfunction, as evidenced by reduced oxygen consumption and ATP generation and by increased gene expression levels of the bio-energetic regulator, uncoupling protein 3 (UCP-3), the latter indicative of electron transport chain uncoupling. ER stress pathway activation also caused increased gene expression of superoxide dismutase (SOD) 2 and peroxiredoxin (PRDX) 3, elevated H2O2 levels, and reduced total thiol pool levels and a significant diminution of myotubular dimensions. Exposure to 17AAG ameliorated these ER stress-induced changes. These findings, which suggest that 17AAG can reduce ER stress-induced mitochondrial dysfunction, oxidative damage and myotubular atrophy, have potential implications in the context of human myositis.
A new cancer-testis long noncoding RNA, the OTP-AS1 RNA
Authors: Karnaukhova Iuliia K. , Polev Dmitrii E. , Krukovskaya Larisa L. , Masharsky Alexey E. , Nazarenko Olga V. , Makashov Andrei A. , Kozlov Andrei P.
Published: June 2018

Orthopedia homeobox (OTP) gene encodes a homeodomain-containing transcription factor involved in brain development.OTPis mapped to human chromosome 5q14.1. Earlier we described transcription in the second intron of this gene in wide variety of tumors, but among normal tissues only in testis. In GeneBank these transcripts are presented by several 300-400 nucleotides long AI267901-like ESTs.

We assumed that AI267901-like ESTs belong to longer transcript(s). We used the Rapid Amplification of cDNA Ends (RACE) approach and other methods to find the full-length transcript. The found transcript was 2436 nucleotides long polyadenylated sequence in antisense toOTPgene. The corresponding gene consisted of two exons separated by an intron of 2961 bp long. The first exon was found to be 91 bp long and located in the third exon ofOTPgene. The second exon was 2345bp long and located in the second intron ofOTPgene.

The search of possible open reading frames (ORFs) showed the lack of significant ORFs. We have shown the expression of new gene in many human tumors and only in one sampled normal testis. The data suggest that we discovered a new antisense cancer-testis sequenceOTP-AS1(OTP- antisense RNA 1), which belongs to long noncoding RNAs (lncRNAs). According to our findings we assume thatOTP-AS1andOTPgenes may be the CT-coding gene/CT-ncRNA pair involved in regulatory interactions.

Author summary

Previously, long non-coding RNAs (lncRNAs) were considered as genetic “noise”. However, it was later shown that only 2% of genomic transcripts have a protein-coding ability. Non-coding RNA is divided into short non-coding RNAs (20-200 nucleotides) and long noncoding RNAs (200-100,000 nucleotides). Genes encoding lncRNA often overlap or are adjacent to protein-coding genes, and localization of this kind is beneficial in order to regulate the transcription of neighboring genes. Studies have shown that of lncRNAs play many roles in the regulation of gene expression. New evidence indicates that dysfunctions of lncRNAs are associated with human diseases and cancer.

In our study we found a new cancer-testis long noncoding RNA (OTP-AS1), which is an antisense of protein-coding cancer-testis gene (OTP). Thus,OTP-AS1andOTPgenes may be the CT-coding gene/CT-ncRNA pair involved in regulatory interactions. This is supported by the similar profile of their expression.OTP-AS1may be of interest as a potential diagnostic marker of cancer or a potential target for cancer therapy.

Part ofOTP-AS1gene (5’-end of the second exon) is evolutionary younger than the rest of gene sequence and is less conservative. This linksOTP-AS1gene with so-called TSEEN (tumor-specifically expressed, evolutionary novel) genes described by the authors in previous papers.
SpoT and GppA hydrolases prevent the gratuitous activation of RelA by pppGpp inEscherichia coli
Authors: Sanyal Rajeshree , Harinarayanan Rajendran
Published: June 2018

Stringent response, a conserved regulation seen in bacteria, is effected through the modified nucleotides (p)ppGpp. The metabolic cycle of these molecules is driven by the synthase activity of RelA and SpoT and the hydrolase activity of SpoT and GppA which together sets the basal (p)ppGpp pool. Growth arrest due to (p)ppGpp accumulation from basal RelA activity apparently explained the essentiality of SpoT hydrolase function. We found, pppGpp degradation was enhanced when the SpoT hydrolase activity was lowered or eliminated and when this was alleviated by inactivation of the GppA hydrolase, gratuitous synthesis of (p)ppGpp by RelA was activated, leading to growth arrest. The RelA-ribosome interaction was not mandatory for these phenotypes. Our results show, for the first time, elevated pppGpp promoted the amplification of RelA-mediated stringent response in the absence of established RelA activating signals in the cell and the SpoT and GppA hydrolases prevented this. The accumulation of pppGpp inhibited the SpoT hydrolase activity. We propose this autocatalytic activation of RelA by pppGpp is likely to be an allosteric regulation and can result in a bistable switch.
Single-cell ID-seq identifies BMP signaling as a driver of a late stage epidermal differentiation program
Authors: van Eijl Roderick E. , van Buggenum Jessie A.G. , Tanis Sabine E.J. , Hendriks Joost , Mulder Klaas W.
Published: June 2018

Abstract

Epidermal homeostasis requires balanced and coordinated adult stem cell renewal and differentiation. These processes are controlled by both extracellular signaling and by cell intrinsic transcription regulatory networks, yet how these control mechanisms are integrated to achieve this unclear. Here, we developed single-cell ID-seq and measured 69 antibody-DNA conjugates (including 34 phospho-specific epitopes) to study the activation state of signaling pathways during epidermal differentiation at the single-cell level. Computational pseudo-timing inference revealed activation of the JAK-STAT, WNT and BMP pathways along the epidermal differentiation trajectory. During differentiation, cells start producing BMP2 ligands and activate the canonical intracellular effectors SMAD1/5/9. Mechanistically, the BMP pathway is responsible for directly activating a specific transcription program that includes the key differentiation transcription factors MAF and MAFB to allow terminal differentiation. We propose that incorporating autocrine signaling pathway activation into a transcription regulatory network enables regional coordination of transcription programs during epidermal differentiation.
Biophysical insights into a highly selective L-arginine-binding lipoprotein of a pathogenic treponeme
Authors: Deka Ranjit K. , Liu Wei Z. , Tso Shih-Chia , Norgard Michael V. , Brautigam Chad A.
Published: June 2018

Biophysical and biochemical studies on the lipoproteins and other periplasmic proteins from the spirochetal speciesTreponema pallidumhave yielded numerous insights into the functioning of the organism’s peculiar membrane organization, its nutritional requirements, and intermediary metabolism. However, not allT. pallidumproteins have proven to be amenable to biophysical studies. One such recalcitrant protein is Tp0309, a putative polar-amino-acid-binding protein of an ABC transporter system. To gain further information on its possible function, a homolog of the protein from the related speciesT. vincentiiwas used as a surrogate. This protein, Tv2483, was crystallized, resulting in the determination of its crystal structure at a resolution of 1.75 Å. The protein has a typical fold for a ligand-binding protein, and a single molecule of L-arginine was bound between its two lobes. Differential scanning fluorimetry and isothermal titration calorimetry experiments confirmed that L-arginine bound to the protein with unusually high selectivity. However, further comparison to Tp0309 showed differences in key amino-acid-binding residues may impart an alternate specificity for theT. pallidumprotein.
Polycystic kidney disease: a Hippo connection
Authors: Ma Shenghong , Guan Kun-Liang
Published: June 2018

Mutations in PKD1 and PKD2 are the leading cause of autosomal dominant polycystic kidney disease (ADPKD). In this issue of Genes & Development, a report by Cai and colleagues (pp. 781–793) reveals new insight into the molecular basis by which PKD1 deficiency leads to cystic kidney pathogenesis. By using extensive mouse genetic analyses coupled with in vitro cystic assays, the investigators delineate a RhoA–YAP–c-Myc signaling axis as a key downstream from PKD1 deficiency in ADPKD pathogenesis. Their findings provide evidence that the Hippo pathway could be a potential target for treating ADPKD.
M4Au12Ag32(p-MBA)30(M= Na, Cs) bimetallic monolayer-protected clusters: synthesis and structure
Authors: Conn Brian E. , Bhattarai Badri , Atnagulov Aydar , Yoon Bokwon , Landman Uzi , Bigioni Terry P.
Published: June 2018

Crystals ofM4Au12Ag32(p-MBA)30bimetallic monolayer-protected clusters (MPCs), wherep-MBA isp-mercaptobenzoic acid andM+is a counter-cation (M = Na, Cs) have been grown and their structure determined. The molecular structure of triacontakis[(4-carboxylatophenyl)sulfanido]dodecagolddotriacontasilver, Au12Ag32(C7H5O2S)30or C210H150Ag32Au12O60S30, exhibits point group symmetry 3 at 100 K. The overall diameter of the MPC is approximately 28 Å, while the diameter of the Au12Ag20metallic core is 9 Å. The structure displays ligand bundling and intermolecular hydrogen bonding, which gives rise to a framework structure with 52% solvent-filled void space. The positions of theM+cations and the DMF solvent molecules within the void space of the crystal could not be determined. Three out of the five crystallographically independent ligands in the asymmetric unit cell are disordered over two sets of sites. Comparisons are made to the all-silverM4Ag44(p-MBA)30MPCs and to expectations based on density functional theory.
Thirty years of Accounting, Auditing and Accountability Journal
Authors: Dumay John , de Villiers Charl , Guthrie James , Hsiao Pei-Chi
Published: June 2018

Purpose

The purpose of this paper is to analyse the highly cited articles published in Accounting, Auditing and Accountability Journal (AAAJ), since its inception, to answer three research questions: first, how have scholarly articles published in AAAJ developed? second, what are the focus areas and characteristics of articles in AAAJ, and who are the influential authors? third, who are the emerging next generation scholars and what are the emerging research themes in AAAJ?

Design/methodology/approach

A structured literature review (SLR) was used to analyse 126 most cited classic AAAJ articles and 21 additional emerging articles published between 1988 and 2016. Traditional literature reviews can have varied results because of a lack of rigour. The SLR method allows for an examination in detail of the articles, authors, focus areas and pattern of AAAJ publishing over three decades.

Findings

The findings show increased diversity in more recent years in theories, methods, origins, focus areas, and where AAAJ articles are cited, which highlights that the interdisciplinary accounting research project is maturing and remaining true to the ideal of being inclusive.

Research limitations/implications

Within this diversity, the analyses show that AAAJ remains focussed on and presents opportunities for impactful accounting research related to social issues, including non-financial corporate reporting/disclosure, public sector accounting, corporate governance and alternative forms of accounting, audit and accountability. Additionally, there is a need for more practice-based research to address the “wicked” problems at the intersection between accounting and society.

Originality/value

This paper presents accounting researchers with an opportunity to develop insightful and publishable studies. Also, it serves as a basis for developing future research agendas in the interdisciplinary accounting field.
Fiscal decentralization in Korea
Authors: Cho Im Gon
Published: June 2018

Purpose

The purpose of this paper is to make policy recommendations for the current fiscal decentralization discussion by examining the operating mechanisms of local taxes, unconditional grants, and conditional grants within the fiscal relationships between the national government and local governments in Korea.

Design/methodology/approach

After examining the current fiscal relationships between the national government and the local governments, this paper analyzes trends of local taxes, unconditional grants from both national and high-level local governments, and conditional grants from both national and high-level (or provincial level) local governments between 2002 and 2015. Local governments are classified into high-level local governments, and three types of low-level local governments are: si, kun, and ku.

Findings

Since the structure of local government finances in Korea is very complicatedly intertwined, the present decentralization discussion regarding increasing the share of local tax revenues may not achieve its purpose of fiscal decentralization. The authorities in charge of revenue allocation should be first decentralized at high-level local governments; high-level local governments should then arrange unconditional and conditional grants from high-level local governments to low-level local governments while taking into consideration unconditional and conditional grants from the national government to low-level governments.

Originality/value

The dichotomy between the central government and local municipalities has been utilized in the existing discussion regarding fiscal decentralization in Korea, but this study highlights the important resource allocation roles of high-level local governments.
Agile manufacturing and business performance
Authors: Nabass Esraa Hussein , Abdallah Ayman Bahjat
Published: June 2018

Purpose

The purpose of this paper is to examine the effect of agile manufacturing (AM) on business performance and operational performance (OP) dimensions in manufacturing companies in Jordan. It also explores the indirect effect of AM on business performance through OP dimensions of cost, quality, delivery and flexibility.

Design/methodology/approach

The study analyzes survey data collected from 282 manufacturing companies from different industries in Jordan. Validity and reliability analyses were performed using SPSS and Amos, and the research hypotheses were tested using structural equation modeling.

Findings

The results demonstrated that AM positively and directly affected business performance. It also positively affected OP dimensions of quality, delivery and flexibility. However, cost performance was not significantly affected by AM. In addition, quality performance and flexibility performance fully mediated the relationship between AM and business performance, whereas cost performance and delivery performance did not show mediating effects.

Originality/value

To the best of the knowledge, this is the first study that investigates the mediating effects of OP dimensions on the relationship between AM and business performance. In addition, a limited number of previous studies investigated the performance outcomes of AM. Furthermore, this area is under-investigated in the Middle East in general and in Jordan in particular.
Open innovation platforms in tourism: how do stakeholders engage and reach consensus?
Authors: Lalicic Lidija
Published: June 2018

Purpose

This paper aims to visualize the communication processes between stakeholders who discuss, reach consensus and engage with user-generated ideas through an open innovation platform facilitated by Destination Management Organization (DMO).

Design/methodology/approach

Various discussion and interaction styles between the different types of stakeholders on the innovation platform are analyzed using quantitative content analysis. Likewise, perceived issues among the stakeholders that motivate collaboration and consensus are identified.

Findings

This paper identifies that stakeholders interact with each other, reach agreements and solve joint problems on the platform by using predominantly constructive interaction styles. Meanwhile, feasibility and strategic issues appear to be the most dominant topics when discussing the fruition of ideas; however, this depends significantly on the category of the idea.

Practical implications

DMOs are given an understanding of why and how stakeholders engage with a certain idea and the kind of challenges they perceive when pursuing the execution of an idea. DMOs are advised to carefully design an open innovation platform to facilitate effective online discussions that may lead to working groups.

Originality/value

There is a scarcity of approaches in the field of tourism that invite stakeholders to innovate. This study aims to close this gap in tourism research by identifying how and which stakeholders respond to an invitation from a DMO to engage in an open innovation platform and, subsequently, how they interact with other partners to foster collaborative innovation projects in their destination.
HR outsourcing in small and medium-sized enterprises
Authors: Wallo Andreas , Kock Henrik
Published: June 2018

Purpose

Small and medium-sized enterprises (SMEs) are increasingly outsourcing human resource (HR) activities to outside labour market intermediaries. In this paper, the focus is on a specific type of labour market intermediary, the HR intermediary (HRI). The purpose of this paper is to describe and discuss SME outsourcing of HR services to membership-based HRIs, and potential problems and benefits that may arise in this process.

Design/methodology/approach

The empirical foundation comprises case studies of three Swedish HRIs and 12 of their SME clients. The data were collected through semi-structured interviews and a document study.

Findings

The findings show that social aspects such as trust, shared values, communication and commitment are crucial characteristics of the cooperation between HRIs and SMEs. These social aspects are a result of the owner/membership structure, and a distinguishing feature of the studied HRIs in comparison to other types of labour market intermediaries.

Research limitations/implications

The results of the study underline the need for increased research related to the intermediary concept and its meanings in different contexts. There is also a need for more empirical research on HRIs, e.g. comparisons between different types of HRIs, and studies of the emergence of virtual intermediaries. Future studies should focus on the role of LMIs and HRIs in regional development processes.

Practical implications

Companies that interact with HRIs should reflect on the different pros and cons that this cooperation may result in, both in the short term and in the longer term.

Originality/value

The study provides an enhanced understanding regarding the relations between SMEs and HRIs, based on the two broad types of SMEs (with low/high internal HR skills) and two types of HRIs (with short/long-term orientation).
Measuring the sustainability of Latin American capital cities
Authors: Coronado Francisco
Published: June 2018

Purpose

The purpose of this paper is to study the living conditions in ten capital cities in Latin America to propose indicators that could help to quantify the sustainability of those capital cities, and its impact over the competitiveness of a country.

Design/methodology/approach

It is proposed a linear model summing the score of ten quantifiable indicators and according with the result categorize the capitals as “sustainable city,” “weak sustainability” and “threatened sustainability.”

Findings

There is a good relationship between the sustainability of the city and the competitiveness of the country. This is the case of Mexico City, Buenos Aires, Santiago, followed by Lima, La Paz and Bogotá a similar result to the rank obtained by Mckinsey Global Institute (2011a, b). It is found that the four capitals categorized as “sustainable” have the highest potable water production, but it was not define a direct correlation between a country’s competitiveness and the development of important medium-sized cities.

Research limitations/implications

Limited availability of comparable information for the capital cities.

Practical implications

The results identified the need to improve specific services and conditions of the inhabitants.

Social implications

The capital cities concentrate the majority of the population of the countries reaching one-third of the total in four out of the ten cities evaluated.

Originality/value

The study presents selected indicators not in use to classify the cities sustainability.
The impact of carer status on participation in healthy activity and self‐reported health among Australian women over 50 years
Authors: Farrugia Teagan , Hewitt Alana , Bourke‐Taylor Helen , Joosten Annette V.
Published: June 2018

Background/aim

Occupational therapists frequently work with carers and their family member who requires direct services. In Australia, women provide the majority of informal care. Carer status is determined by the provision of informal help or supervision to an older person, or a person with a disability or long‐term health condition. Caregiving responsibilities can impact mental and physical health and reduce women's participation in leisure activities and the labour force. The aim of the study was to examine differences in the participation of Australian women, aged 50 years and over, with and without caregiving responsibilities, in self‐selected health promoting activities, self‐reported mental health and participation in physical activity.

Methods

This cross‐sectional study investigated Australian women (N = 157) who completed a survey comprising demographic questions, the Depression Anxiety Stress Scales‐21 (DASS‐21), International Physical Activity Questionnaire‐Short Form (IPAQ‐SF) and the Health Promoting Activities Scale (HPAS). Differences between carers and non‐carers in participation in health promoting activities, mental health, physical activity and labour force participation were investigated using Mann–Whitney U and Kruskal–Wallis tests.

Results

Carers reported significantly lower participation in health promoting activities (P < 0.001), vigorous physical activity (P = 0.001) and moderate physical activity (P = 0.009). Carers also reported significantly higher responses than non‐carers, in symptoms of depression, anxiety and stress (P < 0.001). Carers were significantly more likely than non‐carers to be engaged in part‐time employment, with 37% of carers employed part‐time and 44% of carers not working.

Conclusion

These findings indicate significant differences between women with and without caregiving responsibilities and their participation in health promoting activities, self‐reported mental health, participation in physical activity and the labour force. Carers may benefit from occupational therapy that recognises the important role of carers in the life of their family member and supports carer's health and participation in health promoting activities.
Barriers and enablers to aligning rehabilitation goals to patient life roles following acquired brain injury
Authors: Sansonetti Danielle , Nicks Rebecca J. , Unsworth Carolyn
Published: June 2018

Background/aim

Life roles are integral to occupational therapy practice. Goal setting is a method of establishing priorities to measure outcomes. While acquired brain injury can impact a person's ability to fulfil meaningful life roles, the alignment of goals set in rehabilitation to life roles, is unclear. This study aimed to (i) explore the alignment of goals with life roles for people with an acquired brain injury participating in inpatient rehabilitation; and (ii) identify barriers and enablers to life role discussions within a patient‐directed goal setting framework.

Method

A mixed‐methods study was conducted on an inpatient rehabilitation unit in Victoria, Australia. Quantitative data were obtained from a retrospective file audit of randomly selected medical records. Qualitative data were collected through: a) interviews with patients and their families; and b) A focus group with occupational therapists. Thematic analysis of both audit data and narrative data was undertaken.

Results

Thirty files were examined and demonstrated 33% alignment between goals and life roles. Four interviews were completed with patients, with a family member participating in two of these. Themes identified were: readiness, role concept, recovery concept and goal review. Five therapists attended the focus group. Themes identified were: Patient factors, goal review, expectations, role change and environment. Interview and focus group data identified that barriers to life role discussions included: lack of patient and family readiness, patients’ difficulty understanding role concept, focus on impairments and lack of family/ significant others support. Enablers included: having early conversations involving family, regular goal review and use of standardised tools.

Conclusion

Goal setting in alignment with life roles is important in acquired brain injury rehabilitation, but may be limited. This process can be enhanced by including patients and their significant others in early goal setting conversations, along with regular goal review across the rehabilitation process.
Extensive nitrification and active ammonia oxidizers in two contrasting coastal systems of the Baltic Sea
Authors: Happel Elisabeth , Bartl Ines , Voss Maren , Riemann Lasse
Published: June 2018

Nitrification is important in nitrogen (N) cycling of aquatic environments, but knowledge about its regulation and importance is sparse. Here we examined nitrification and ammonia oxidizers in the Baltic Sea. We investigated two sites with different catchment characteristics (agricultural and forest), the Bay of Gdánsk (south) and the Öre Estuary (north), and measured pelagic nitrification rates and abundance, composition and expression of ammonia monooxygenase (amoA) genes. Highest nitrification rates were found in the nutrient rich Bay of Gdańsk. Interestingly, abundances of ammonia‐oxidizing archaea (AOA) and bacteria (AOB) were orders of magnitude lower than reported from other sites. Although AOA were most abundant at both sites, the highest expression levels were from AOB. Interestingly, few AOA and AOB taxa dominated amoA gene expression, with a Nitrosomarinus related phylotype showing widespread expression. AOA and AOB communities differed between sites and depths, respectively, with the composition in rivers being distinct. A storm event, causing an even depth distribution of nitrification and particles in the Bay of Gdańsk, indicated that the presence of particles stimulate nitrification. The study highlights coastal regions as dynamic sites of extensive pelagic nitrification, which may affect local food web dynamics and loss of N mediated by denitrification.
Low‐Carbon Gentrification: When Climate Change Encounters Residential Displacement
Authors: Bouzarovski Stefan , Frankowski Jan , Tirado Herrero Sergio
Published: June 2018

This article focuses on the emergence of ‘low‐carbon’ gentrification as a distinct urban phenomenon, a process that we see as the outcome of efforts to change the social and spatial composition of urban districts under the pretext of responding to climate change and energy efficiency imperatives. The article develops a conceptual framework for scrutinizing low‐carbon gentrification, predicated upon insights from literatures on ecological gentrification and displacement. It documents the existence of an ‘eco‐social paradox’ associated with new patterns of socio‐spatial segregation and energy efficiency retrofits. We interrogate the discursive and policy frameworks, socio‐spatial implications and political contestations of low‐carbon gentrification. Evidence is drawn from case study research in an inner‐city district of the Polish city of Gdańsk, where such processes have been unfolding since 2006 due to the implementation of a targeted urban regeneration programme. This investigation is positioned within a wider analysis of secondary written sources about similar developments in other geographical contexts across Europe and North America, where anecdotal evidence suggests that low‐carbon gentrification may be widespread and common.
Essential skills: BJOG launches the Research Methods Guides
Authors: Marsh Michael S
Published: June 2018

This series includes an interview with series Editor Dr Natalie AM Cooper in an audio podcast available at
https://soundcloud.com/bjog/rmg-interview
The new EU Conflict Minerals Regulation: Normative Power in International Relations?
Authors: Partzsch Lena
Published: June 2018

Over the last few years, European NGOs were very successful in raising awareness about international trade in minerals funding armed conflicts around the world. In May 2017, after more than three years of negotiation, the European Union signed the new Conflict Minerals Regulation. At first glance, this Regulation demonstrates ‘ethical’ or ‘normative’ power: The EU uses its commercial power to promote norms of international peace and security, accepting prospectively higher prices for imports of minerals. The Regulation also supports a re‐centring of the state after two and a half decades of economic liberalization. However, the EU only follows and lags behind the 2010 US Dodd‐Frank Act section 1502. The article shows that the EU does not reject collective norms, but is incapable or unwilling to put a tight rein on domestic businesses. The new EU Conflict Minerals Regulation stands only for symbolic normative power.
Intrapleural combination therapy with lobaplatin and erythromycin for non‐small cell lung cancer‐mediated malignant pleural effusion
Authors: Xu Lisheng , Wang Benjie , Gao Meimei , Zhang Yan , Qi Qian , Li Tao , Li Caiyu , Wang Aihua , Li Yu
Published: June 2018

Background

Malignant pleural effusion is a common complication of non‐small cell lung cancer (NSCLC); however, treatment options remain limited. This study evaluated the safety and efficacy of sequential intrapleural therapy with lobaplatin and erythromycin for NSCLC‐mediated malignant pleural effusion.

Methods

Fifty‐six patients with NSCLC complicated with malignant pleural effusion were recruited for a prospective single‐arm study from December 2014 to 2016; one patient dropped out. In addition to conventional systemic chemotherapy, lobaplatin and erythromycin were intrapleurally injected into subjects. Short and long‐term responses were analyzed. The concentration of ultrafilterable platinum in the pleural effusion and plasma were detected at different time points. Incidences of severe adverse reactions were observed.

Results

In the 55 evaluable patients, the effective rate of pleural effusion was 81.8% after six weeks of treatment. Six and twelve months after treatment, the effective rates were 60% and 21.8%, respectively, and the one‐year survival rate was 83.6%. The concentrations of lobaplatin in pleural effusion and plasma two hours after injecting 50 mg lobaplatin into the thoracic cavity were 13.763 ± 1.523 μg/mL and 1.120 ± 0.164 μg/mL, and 17 hours later were 1.961 ± 0.351 μg/mL and 0.578 ± 0.095 μg/mL, respectively. The rate of severe adverse reactions of the first cycle of systemic chemotherapy combined with lobaplatin and erythromycin did not significantly differ from the rate in the second cycle.

Conclusion

Intrapleural combination therapy with lobaplatin and erythromycin is a safe and efficient treatment for patients with NSCLC‐mediated malignant pleural effusion.
Nimotuzumab combined with chemotherapy as first‐line treatment for advanced lung squamous cell carcinoma
Authors: Si Xiaoyan , Wu Shafei , Wang Hanping , Zhang Xiaotong , Wang Mengzhao , Zeng Xuan , Zhang Li
Published: June 2018

Background

This study was conducted to evaluate the efficacy and safety of nimotuzumab combined with chemotherapy as first‐line therapy in advanced lung squamous cell carcinoma (LSCC), and to explore predictive biomarkers of the efficacy of nimotuzumab.

Methods

A retrospective study was conducted of patients with advanced LSCC administered nimotuzumab combined with chemotherapy as first‐line therapy from June 2012 to December 2016 at the Department of Respiratory Medicine, Peking Union Medical College Hospital. The associations between EGFR expression, EGFR gene copy numbers, and clinical efficacy were detected by immunohistochemistry and fluorescence in situ hybridization (FISH).

Results

Twenty‐six patients were enrolled, including 22 men and 4 women. The objective response rate was 50% and the disease control rate was 100%. The median progression‐free survival (PFS) and overall survival were 6.7 and 16.3 months, respectively. Patients whose samples were tested via FISH and showed positive EGFR expression had a trend of longer median PFS (10.0 months; P = 0.10). Adverse effects included 15 cases (57.7%) of bone marrow suppression, 15 (57.7%) of sensory neuropathy, 14 (53.8%) of alopecia, nine (34.6%) of nausea/vomiting and one case (3.8%) of elevated creatinine level. All adverse effects were attributed to chemotherapy.

Conclusion

Nimotuzumab combined with chemotherapy might be a possible option as first‐line therapy in patients with advanced LSCC. EGFR gene copy number examined by FISH might be a possible predictive biomarker.