bluuebunny/crossref_metadata_2025 huggingface dataset:
Performing Reflexive Toxin A/B Enzyme Immunoassay in a Two-Step Algorithm for the Diagnosis of Clostridium difficile Infection Has Limited Clinical Utility
Authors: Mounajjed M , Pease R , Jung-Hynes B , Safdar N , Chen D
Published: August 2018

The differentiation of Clostridium difficile infection (CDI) from colonization is challenged by the suboptimal clinical specificity of nucleic acid amplification tests (NAAT). In this study, we examined the utility of testing for toxin via enzyme immunoassay (EIA) in specimens already tested by NAAT for the diagnosis of CDI in an attempt to differentiate colonization from infection. We tested 59 stool samples for the presence of C. difficile toxin B gene by NAAT followed by EIAs for glutamate dehydrogenase (GDH EIA) and toxins A and B (Toxin EIA). Two infectious disease physicians independently reviewed the patients’ electronic medical records retrospectively to categorize each patient as CDI-Likely, CDI-Unlikely, or CDI-Indeterminate. Clinical sensitivities and specificities were calculated using 3 definitions of “true” CDI status, being: (1) concordance between both reviewers, (2) concordance, and CDI-Indeterminate/discordant cases classified as CDI-Likely, and (3) concordance, and CDI-Indeterminate/discordant cases classified as CDI-Unlikely. Based on these definitions, clinical sensitivity and specificity for NAAT was 100% and 49-94%, GDH EIA was 83-85% and 43-89%, and Toxin EIA was 39-42% and 83-100%, respectively. 85% (22 of 26) of patients who were NAAT-positive but Toxin EIA-negative symptomatically benefited from treatment for CDI. The addition of EIA to NAAT for CDI diagnosis had limited utility for differentiating colonization from CDI and could have led to under treatment of patients with CDI.
Mathematical modeling supports fate restriction in neurogenic progenitors of the embryonic ventral spinal cord
Authors: Azaïs Manon , Agius Eric , Blanco Stéphane , Gautrais Jacques , Molina Angie , Pituello Fabienne , Tregan Jean-Marc
Published: August 2018

In the developing neural tube in chicken and mammals, neural stem cells proliferate and differentiate according to a stereotyped spatio-temporal pattern. Several actors have been identified in the control of this process, from tissue-scale morphogens patterning (Shh, BMP) to intrinsic determinants in neural progenitor cells. In a previous study (Bonnet et al. eLife 7, 2018), we have shown that the CDC25B phosphatase promotes the transition from proliferation to differentiation in a cell-cycle independent fashion. In this study, we set up a mathematical model linking progenitor modes of division to the dynamics of progenitors and differentiated populations. Here, we build on this previous model to propose a complete dynamical picture of this process. We start from the standard model in which progenitors are homogeneous and can perform any type of divisions (proliferative division yielding two progenitors, asymmetric neurogenic divisions yielding one progenitor and one neuron, and terminal symmetric divisions yielding two neurons). We constraint this model using published data about mode of divisions and population dynamics of progenitors/neurons at different developmental stages (Saade et al. Cell Reports 4, 2013), and check the effect of CDC25B gain of function in this context. Next, we explore the scenarios in which progenitors population is actually split into two different pools, one of which composed of cells that have lost the capacity to perform proliferative divisions (fate restriction). We show that one such scenario appears relevant and calls for further identification of the alternative role of CDC25B in such a fate restriction.
Orthogonal linear separation analysis: an approach to decompose the complex effects of a perturbagen
Authors: Mizuno Tadahaya , Kinoshita Setsuo , Maedera Shotaro , Ito Takuya , Kusuhara Hiroyuki
Published: August 2018

Drugs have multiple, not single, effects. Decomposition of drug effects into basic components helps us to understand the pharmacological properties of a drug and contributes to drug discovery. We have extended factor analysis and developed a novel profile data analysis method, orthogonal linear separation analysis (OLSA). OLSA contracted 11,911 genes to 118 factors from transcriptome data of MCF7 cells treated with 318 compounds in Connectivity Map. Ontology of the main genes constituting the factors detected significant enrichment of the ontology in 65 of 118 factors and similar results were obtained in two other data sets. One factor discriminated two Hsp90 inhibitors, geldanamycin and radicicol, while clustering analysis could not. Doxorubicin was estimated to inhibit Na+/K+ATPase, one of the suggested mechanisms of doxorubicin-induced cardiotoxicity. Based on the factor including PI3K/AKT/mTORC1 inhibition activity, 5 compounds were predicted to be novel autophagy inducers, and other analysis including western blotting revealed that 4 of the 5 actually induced autophagy. These findings indicate the potential of OLSA to decompose the effects of a drug and identify its basic components. (<175 words)
Processing of eukaryotic Okazaki fragments by redundant nucleases can be uncoupled from ongoing DNA replicationin vivo
Authors: Kahli Malik , Osmundson Joseph S. , Yeung Rani , Smith Duncan J.
Published: August 2018

Prior to ligation, each Okazaki fragment synthesized on the lagging strand in eukaryotes must be nucleolytically processed. Nuclease cleavage takes place in the context of 5’ flap structures generated via strand-displacement synthesis by DNA polymerase delta. At least three DNA nucleases: Rad27 (Fen1), Dna2, and Exo1, have been implicated in processing Okazaki fragment flaps. However, neither the contributions of individual nucleases to lagging-strand synthesis nor the structure of the DNA intermediates formed in their absence have been clearly definedin vivo.By conditionally depleting lagging-strand nucleases and directly analyzing Okazaki fragments synthesizedin vivoinS. cerevisiae, we conduct a systematic evaluation of the impact of Rad27, Dna2 and Exo1 on lagging-strand synthesis. We find that Rad27 processes the majority of lagging-strand flaps, with a significant additional contribution from Exo1 but not from Dna2. When nuclease cleavage is impaired, we observe a reduction in strand-displacement synthesis as opposed to the widespread generation of long Okazaki fragment 5’ flaps, as predicted by some models. Further, using cell cycle-restricted constructs, we demonstrate that both the nucleolytic processing and the ligation of Okazaki fragments can be uncoupled from DNA replication and delayed until after synthesis of the majority of the genome is complete.
A Transcriptome Wide Association Study implicates specific pre- and post-synaptic abnormalities in Schizophrenia
Authors: Hall Lynsey S , Medway Christopher W , Pardinas Antonio F , Rees Elliott G , Escott-Price Valentina , Pocklington Andrew , Holmans Peter A , Walters James TR , Owen Michael J , O’Donovan Michael C
Published: August 2018

Schizophrenia is a complex highly heritable disorder. Genome-wide association studies have identified multiple loci that influence the risk of developing schizophrenia, although the causal variants driving these associations and their impacts on specific genes are largely unknown. Here we link genetic findings to gene expression in the human brain by performing a transcriptome-wide association study (TWAS) in which we integrate the largest published genome-wide association dataset of schizophrenia, with publically available post mortem expression data from the dorsolateral prefrontal cortex (DLPFC). We identify a significant correlation between schizophrenia risk and expression at eighty-nine genes in DLPFC, including forty-two genes not identified in earlier TWAS of this transcriptomic resource. Genes whose expression correlate with schizophrenia were enriched for those involved in nervous system development, abnormal synaptic transmission, reduced long term potentiation, and calcium-dependent cell-cell adhesion. Previous genetic studies have implicated post-synaptic glutamatergic and gabaergic processes in schizophrenia; here we extend this to include molecules that regulate presynaptic transmitter release. We identify specific candidate genes to which we assign predicted directions of effect in terms of expression level, facilitating downstream experimental studies geared towards a better mechanistic understanding of schizophrenia pathogenesis.
Sfp1 regulates the SAGA component Tra1 in response to proteotoxic stress inSaccharomyces cerevisiae
Authors: Jiang Yuwei , Berg Matthew D. , Genereaux Julie , Ahmed Khadija , Duennwald Martin L. , Brandl Christopher J. , Lajoie Patrick
Published: August 2018

Proteotoxic stress triggers transcriptional responses that allow cells to compensate for the accumulation of toxic misfolded proteins. Chromatin remodeling regulates gene expression in response to the accumulation of misfolded polyQ proteins associated with Huntington’s disease (HD). Tra1 is an essential component of both the SAGA/SLIK and NuA4 transcription co-activator complexes and is linked to multiple cellular processes associated with misfolded protein stress, including the heat shock response. Cells with compromised Tra1 activity display phenotypes distinct from deletions encoding components of the SAGA and NuA4 complexes, indicating a potentially unique regulatory role of Tra1 in the cellular response to protein misfolding. Here, we employed a yeast model of HD to define how the expression of toxic polyQ expansion proteins affects Tra1 expression and function. Expression of expanded polyQ proteins, mimics deletion of SAGA/NuA4 components and results in growth defects under stress conditions. Moreover, deleting genes encoding SAGA and, to a lesser extent, NuA4 components exacerbates polyQ toxicity. Also, cells carrying a mutant Tra1 allele displayed increased sensitivity to polyQ toxicity. Interestingly, expression of polyQ proteins also upregulated the expression ofTRA1and other genes encoding SAGA components, revealing a feedback mechanism aimed at maintaining Tra1and SAGA functional integrity. Moreover, deleting the TORC1 (Target of Rapamycin) effectorSFP1specifically abolished upregulation ofTRA1upon expression of polyQ proteins. While Sfp1 is known to adjust ribosome biogenesis and cell size in response to stress, we identified a new role for Sfp1 in the control of Tra1, linking TORC1 and cell growth regulation to functions of the SAGA acetyltransferase complex during misfolded protein stress.
A pilot investigation of chemonucleolysis-induced intervertebral disc degeneration in the ovine lumbar spine
Authors: Borem Ryan , Walters Joshua , Madeline Allison , Madeline Lee , Easley Jeremiah , Gill Sanjitpal , Mercuri Jeremy
Published: August 2018

Intervertebral disc (IVD) degeneration (IVDD) initiates in the nucleus pulposus (NP) and is marked by elevated levels of pro-inflammatory cytokines and matrix-degrading proteases, leading to structural and functional disruption. IVDD therapeutics are currently being investigated; however, such approaches require validation using large animal models that recapitulate clinical, biochemical, and biomechanical hallmarks of the human pathology. Others have previously utilized intradiscal administration of chondroitinase-ABC (C-ABC) to initiate IVDD in the NP of sheep lumbar IVDs. While these studies examined changes in IVD height, hydration, and tissue micro-architecture, changes in biochemical content and mechanical properties were not assessed. Thus, the objective herein was to comprehensively characterize this ovine model IVDD for salient features reported in human degenerate IVDs by evaluating biochemical, biomechanical, and histological changes. Briefly, C-ABC (1U) was administered via intradiscal injection into the L1/2, L2/3, and L3/4 IVDs, and degeneration was assessed at 6- and 10-weeks via longitudinal magnetic resonance (MR) imaging. After 6 weeks, degenerative samples showed significant reductions in IVD heights (p=0.048) and MR imaging index (p=0.048), which worsened at 10 weeks. Post-mortem degenerate and controls IVDs were evaluated for differences in interleukin-1β concentration, axial and torsional functional spinal unit kinematics, and histological microarchitecture. Degenerate IVDs demonstrated significantly elevated concentrations of interleukin-1β (p=0.002). Additionally, degenerative samples showed increased creep displacement (p=0.022) and compressive stiffness’s (p=0.007) concurrent with decreased long-term elastic (p=0.007) and viscous dampening coefficients (p=0.002). Histological analysis of degenerative IVDs showed changes in microarchitecture, including derangement of the nucleus pulposus and annulus fibrosus tissue as well as cartilaginous end-plate irregularities. This pilot study demonstrated that intradiscal injection of 1U C-ABC induces significant and progressive degeneration of sheep lumbar IVDs over the time course investigated. The changes observed in this pilot’s study small sample size resemble the hallmarks of moderate to severe IVD degeneration observed in humans. Further study is warranted on a larger sample size to further validate these findings.
Genome-wide CRISPR Screens in Primary Human T Cells Reveal Key Regulators of Immune Function
Authors: Shifrut Eric , Carnevale Julia , Tobin Victoria , Roth Theodore L. , Woo Jonathan M. , Bui Christina , Li P. Jonathan , Diolaiti Morgan , Ashworth Alan , Marson Alexander
Published: August 2018

Human T cells are central effectors of immunity and cancer immunotherapy. CRISPR-based functional studies in T cells could prioritize novel targets for drug development and improve the design of genetically reprogrammed cell-based therapies. However, large-scale CRISPR screens have been challenging in primary human cells. We developed a new method, sgRNA lentiviral infection with Cas9 protein electroporation (SLICE), to identify regulators of stimulation responses in primary human T cells. Genome-wide loss-of-function screens identified essential T cell receptor signaling components and genes that negatively tune proliferation following stimulation. Targeted ablation of individual candidate genes validated hits and identified perturbations that enhanced cancer cell killing. SLICE coupled with single-cell RNA-Seq revealed signature stimulation-response gene programs altered by key genetic perturbations. SLICE genome-wide screening was also adaptable to identify mediators of immunosuppression, revealing genes controlling response to adenosine signaling. The SLICE platform enables unbiased discovery and characterization of functional gene targets in primary cells.
Molecular recording of mammalian embryogenesis
Authors: Chan Michelle M. , Smith Zachary D. , Grosswendt Stefanie , Kretzmer Helene , Norman Thomas , Adamson Britt , Jost Marco , Quinn Jeffrey J. , Yang Dian , Meissner Alexander , Weissman Jonathan S.
Published: August 2018

Understanding the emergence of complex multicellular organisms from single totipotent cells, or ontogenesis, represents a foundational question in biology. The study of mammalian development is particularly challenging due to the difficulty of monitoring embryosin utero, the variability of progenitor field sizes, and the indeterminate relationship between the generation of uncommitted progenitors and their progression to subsequent stages. Here, we present a flexible, high information, multi-channel molecular recorder with a single cell (sc) readout and apply it as an evolving lineage tracer to define a mouse cell fate map from fertilization through gastrulation. By combining lineage information with scRNA-seq profiles, we recapitulate canonical developmental relationships between different tissue types and reveal an unexpected transcriptional convergence of endodermal cells from extra-embryonic and embryonic origins, illustrating how lineage information complements scRNA-seq to define cell types. Finally, we apply our cell fate map to estimate the number of embryonic progenitor cells and the degree of asymmetric partitioning within the pluripotent epiblast during specification. Our approach enables massively parallel, high-resolution recording of lineage and other information in mammalian systems to facilitate a quantitative framework for describing developmental processes.
Communication of information in the digital age among social sciences students
Authors: Pinto Maria , Fernandez-Pascual Rosaura , Sales Dora
Published: August 2018

Purpose

The purpose of this paper is to analyze the informational behavior of a group of future professionals in the field of social sciences (SS), in terms of their competence in the communication–dissemination of information.

Design/methodology/approach

The IL-HUMASS, EVALCI/KN and EVALCI/SK tests regarding the affective (attitudes, motivations) and cognitive (knowledge, skills) dimensions are distributed to a stratified sample of five universities and eight degree courses in Spain. Infographics and non-parametric methods allow to compare the disciplinary profiles with regard to gender, academic course and academic degrees. An Information Literacy Communication synthetic indicator based on structural equation modeling includes the subjective and effective dimensions to measure the holistic learning outcomes in communication–dissemination of information.

Findings

Significant differences regarding the informational behavior of future professionals in SS are discovered. The synthetic indicator allows academic degrees to be ranked in order to identify those in need of initiatives aimed at improving communication–dissemination competence.

Practical implications

Findings must be taken into account to design effective learning programs. This methodological approach can be expanded to scientific and academic environments.

Originality/value

The paper puts forward the first evidence-based study on communication–dissemination competence among future SS professionals, as no similar research has been found in the scientific literature. It is also the first time that the definition of a predictive performance indicator, based on a powerful statistical methodology, has been proposed.
Academic research in emerging knowledge-based economies
Authors: Hadiwattege Chandanie , Senaratne Sepani , Sandanayake Yasangika , Fernando Nirodha Gayani
Published: August 2018

Purpose

Knowledge-based economies are popular in the present world. Simultaneously, universities are becoming more responsible for leading economic development through research. As a key contributor to the national economy, it is vital for the construction industry to move beyond outdated practices, and hence, reviewing the role of academic research in empowering the construction industry with knowledge is essential. The purpose of this paper is to focus on how relevant theories conceptualise the expected role of academic research in the innovative development of an industry and the specific location in the Sri Lankan construction industry.

Design/methodology/approach

Following a comprehensive literature review, empirical data were collected from the Sri Lankan context with a mixed approach informed by a pragmatist philosophical stance. The perspective of academia and industry practitioners were deductively obtained through surveys and inductively explored through qualitative interviews.

Findings

This study provides evidence that academic research in Sri Lanka does not contribute effectively to innovative construction management. Due to the absence of industry-focussed knowledge dissemination strategies, the academic–industry relationships are mostly non-research based. The industry lacks in research-informed-decision making, leading to lesser innovations.

Research limitations/implications

The research conclusions are more applicable to the developing country construction industry contexts.

Practical implications

The research urges the need for improved academic–industry research collaborations and strategic knowledge dissemination movements.

Originality/value

The research confirms that academic research is a major integral part of the developing construction industry in a knowledge-based economy. In establishing the expected role of academic research, the research revealed the current practice to be under-located. Hence, the research prescribes the necessary actions; research collaborations in major and subsequent requirements.
“English is an unwritten rule here”
Authors: Sanden Guro R. , Kankaanranta Anne
Published: August 2018

Purpose

The purpose of this paper is to examine the implications of corporate language policies that are implemented without formal decision-making processes.

Design/methodology/approach

A qualitative case study based on three Scandinavian multinational corporations which use English as a common corporate language without formal language policy decisions.

Findings

Non-formalised language policies are found to be clearly distinct from formalised language policies in terms of language policy format, language policy focus, language policy formation, language planning agency and management style. Non-formalised language policies can represent a type of informal control, but the absence of a policy document leaves employees without a common reference point which may cause confusion and inter-collegial conflict.

Originality/value

The study offers a nuanced perspective on the role of language policies in corporate communication by demonstrating that language policies may come in a variety of different forms, also as implicit assumptions about language use. Findings reveal benefits and drawbacks of the different language policy approaches.
Diagnosing member-customer ostracism in co-operatives and counterpoising its relationship-poisoning effects
Authors: Benos Theo , Kalogeras Nikos , de Ruyter Ko , Wetzels Martin
Published: August 2018

Purpose

This paper aims to examine a core member-customer threat in co-operatives (co-ops) by drawing from ostracism research, assessing co-op ostracism’s impact on critical membership and relational exchange outcomes and discussing why relationship marketing research needs to pay more attention to the overlooked role of implicit mistreatment forms in customer harm-doing.

Design/methodology/approach

Three studies were conducted. In Study 1, ostracism in co-ops was explored, and a measurement scale for co-op ostracism was developed. In Study 2, the core conceptual model was empirically tested with data from members of three different co-ops. In Study 3, a coping strategy was integrated into an extended model and empirically tested with a new sample of co-op members.

Findings

Ostracism is present in co-ops and “poisons” crucial relational (and membership) outcomes, despite the presence of other relationship-building or relationship-destroying accounts. Coupling entitativity with cognitive capital attenuates ostracism’s impact.

Research limitations/implications

Inspired by co-ops’ membership model and inherent relational advantage, this research is the first to adopt a co-op member-customer perspective and shed light on an implicit relationship-destroying factor.

Practical implications

Co-op decision makers might use the diagnostic tool developed in the paper to detect ostracism and fight it. Moreover, a novel coping strategy for how co-ops (or other firms) might fend off ostracism threats is offered in the article.

Originality/value

The present study illuminates a dark side of a relationally profuse customer context, painting a more complete picture of relationship marketing determinants. Little attention has been given to ostracism as a distinct and important social behaviour in marketing research and to co-ops as a research context.
Managing group flow experiences in escape rooms
Authors: Kolar Tomaž , Čater Barbara
Published: August 2018

Purpose

This paper theoretically and empirically aims to explore customer group flow experiences with an urban adventure game called “escape rooms”.

Design/methodology/approach

A comprehensive model of group flow antecedents and consequences is proposed and empirically verified by means of survey research and SEM methodology.

Findings

The results indicate that key determinants of group flow experiences are the collective challenge/skills balance, and theming and storytelling. Group flow, in turn, significantly affects participants’ revisit intentions and word-of-mouth communications, as well as group cohesion and subjective quality of life.

Practical implications

The supported research model provides an insight into how group flow experiences can be facilitated by means of gamification and yields important managerial implications. These are systematically discussed in regard to antecedent and consequence constructs.

Originality/value

This paper is one of the first papers to systematically examine the antecedents and consequences of group flow experiences at adventure game-based attractions. It contributes to the understanding and management of peak experiences in contemporary hospitality and tourism.
Doing good across organizational boundaries
Authors: Lam Hugo K.S.
Published: August 2018

Purpose

The purpose of this paper is to theoretically hypothesise and empirically test the impact of sustainable supply chain practices (SSCPs) on firms’ financial risk.

Design/methodology/approach

This research adopts signalling theory to explain the signalling role of SSCPs and the moderating role of the signalling environment in terms of supply chain characteristics. It collects and combines longitudinal secondary data from multiple sources to test the direct impact of SSCPs on firms’ financial risk and the moderating role of supply chain complexity and efficiency. It conducts various additional tests to check the robustness of the findings and to account for alternative explanations.

Findings

This research shows that SSCPs help firms reduce financial risk but do not affect their returns. Moreover, the risk reduction of SSCPs is greater for firms with more complex and efficient supply chains. The findings are robust to alternative variable measurements and analysing strategies.

Research limitations/implications

This research reveals the role of SSCPs in reducing financial risk, urging researchers to pay more attention to the financial risk implications of supply chain practices in general and SSCPs in particular.

Practical implications

This research encourages firms to engage in SSCPs to reduce financial risk and enables them to assess the urgency of their SSCPs investments in view of the complexity and efficiency of their supply chains.

Originality/value

This is the first research examining the impact of SSCPs on financial risk, based on longitudinal secondary data and signalling theory. The empirical evidence documented and the theoretical perspective adopted offer important implications for future practice and research on SSCPs.
Illness-related worries as a mediator among depression, anxiety and self-care in heart failure patients
Authors: Mansouriyeh Nastaran , Poursharifi Hamid , Taban Sadeghi Mohammad Reza , Seirafi Mohammad Raze
Published: August 2018

Purpose

The purpose of this paper is to investigate the role of illness-related worries as a mediator among depression, anxiety and self-care in heart failure (HF) patients was the aim of this study.

Design/methodology/approach

This study was descriptive and correlational study. In total, 149 patients with HF were selected for sampling in 2016. Patients completed self-care behavior scale, illness-related worries questionnaire and Depression Anxiety Stress Scale (DASS) questionnaires. The Pearson correlation coefficient and Sobel test were also done.

Findings

According to the analysis of the Sobel test, the role of illness-related worries as a mediator in the relationship between depression and self-care result was −5.37. Sobel test analysis was done to assess the role of illness-related worries as mediator between anxiety and self-care (6.66). The correlation between depression and self-care was 0.488 (p<0.01); correlation between anxiety and self-care was 0.4 (p<0.01); correlation between anxiety and depression was 0.79 (p<0.01); and the correlation between illness-related worries and self-care was 0.71 (p<0.01).

Originality/value

Illness-related worries can serve as a mediator in the relationship among depression, anxiety and self-care. There was a significant correlation among the research variables. Therefore, educational programs to reduce depression, anxiety and increase self-care should be given priority to for HF patients.
Spit guards, ethical policing and the need for an evidence-based approach
Authors: Joyce Peter , Laverick Wendy
Published: August 2018

Purpose

The purpose of this paper is to assess the advantages and disadvantages of the use of spit guards by police forces in the UK and to make recommendations regarding an evidence-based approach to decisions related to the use of such equipment.

Design/methodology/approach

The paper is based upon an examination of a range of primary source material, secondary sources and grey literature.

Findings

Although the use of spit guards can be justified by factors that include the need to protect police officers from contracting serious infectious diseases, there are a number of problems that concern ethical policing and human rights. Concerns arise when spit guards are deployed against vulnerable individuals, are used offensively rather than defensively and when such equipment is deployed disproportionately against persons from Black and Minority Ethnic (BME) communities. Additionally, the image of the police may suffer if spit guards are accompanied by the use of excessive force which may be perceived as an abuse of police power.

Practical implications

The paper makes recommendations that a comprehensive evidence base is required to assist practitioners to make informed decisions regarding the deployment of spit guards. This evidence base should include the extent to which officers are spat at, medical evidence relating to spitting and the transmission of serious diseases, the views of the public concerning the deployment of spit guards and estimations as to whether such equipment will deter spitting by suspects of crime.

Originality/value

This paper provides an original academic contribution to the ongoing debate on the use of spit guards within policing. In particular, it brings together a wide range of material that relates to this topic and presents it as a coherent set of arguments located in a single source.
Factors relevant to the prognosis of patients with esophageal cancer who received intensity‐modulated radiotherapy
Authors: Yin Hongmei , Li Duojie , Zhu Chaomang , Wang Mingxi , Wei Nannan
Published: August 2018

Background

The aim of this study was to evaluate the clinical factors relevant to the prognosis of patients with esophageal cancer who received intensity‐modulated radiotherapy (IMRT).

Methods

The data of 60 patients admitted to our hospital from January 2014 to December 2015 with pathologically confirmed esophageal cancer were retrospectively reviewed. All patients received IMRT. Patients were divided into groups according to two‐year survival: those who survived > 2 years after treatment, and those who died within 2 years of treatment. The potential clinical factors relevant to prognosis were evaluated by logistic regression analysis.

Results

Single factor analysis showed that lesion length (P < 0.05), tumor diameter (P < 0.05), T stage (P < 0.05), N stage (P < 0.05), and combined chemotherapy (P < 0.05) were associated with the prognosis of esophageal cancer patients who received IMRT. Logistic regression analysis demonstrated that T stage (odds ratio = 3.62; P < 0.05) and N stage (odds ratio = 2.98; P < 0.05) were independent factors relevant to prognosis.

Conclusion

T stage and N stage influence the long‐term curative effects of IMRT for esophageal cancer. The higher the stage, the lower the two‐year survival rate.
Comparison study of computed tomography‐guided radiofrequency and microwave ablation for pulmonary tumors: A retrospective, case‐controlled observational study
Authors: Chi Jiachang , Ding Min , Shi Yaoping , Wang Tao , Cui Dan , Tang Xiaoyin , Li Ping , Zhai Bo
Published: August 2018

Background

The aim of this study was to compare the safety, efficacy, and prognostic value of radiofrequency ablation (RFA) and microwave ablation (MWA) for lung tumors.

Methods

Between March 2012 and January 2018, 238 patients with lung cancer were treated with MWA (139, 58.4%) or RFA (99, 41.6%) in our center. Patient and tumor characteristics, complications, complete ablation (CA) rate, and prognosis were compared between the groups. Meta‐analysis was used to systematically compare the outcomes of RFA and MWA for the treatment of lung tumors.

Results

Ablation was successfully completed in all patients and no procedure‐related death occurred. The total complication rates in the RFA and MWA groups were 24.2% (24/99) and 16.5% (23/139), respectively, and there was no statistically significant difference (P = 0.142). The initial and total CA rates were similar at P > 0.05 (RFA vs. MWA: initial CA, 97.0% vs. 96.4%; total CA, 99.0% vs. 98.6%, respectively). During follow‐up, there was no significant difference in median progression‐free (RFA vs. MWA: 12.5 months, 95% confidence interval [CI] 5.002–19.998 vs. 9.5 months, 95% CI 6.623–12.377; P = 0.673) or overall survival (RFA vs. MWA: 33 months, 95% CI 27.070–38.930 vs. 30 months, 95% CI, 18.482–41.518; P = 0.410) between the groups. Combined with the results of published comparison studies, meta‐analysis further confirmed that the outcomes of these two treatments were similar.

Conclusion

Both RFA and MWA are safe and effective treatments with a survival benefit for selected patients with primary and metastatic lung tumors.
Deviations from the Mandatory Adoption of IFRS in the European Union: Implementation, Enforcement, Incentives, and Compliance
Authors: Pownall Grace , Wieczynska Maria
Published: August 2018

In this paper, we evaluate the common assumption that European Union (EU) firms began using international financial reporting standards (IFRS) in 2005 when the EU formally adopted IFRS. Although the incidence of firms using local (or some other) GAAP declined between 2005 and 2012, it is still non‐trivial. By 2012 the incidence of non‐IFRS financial statements was still in excess of 17 percent (87 percent of which were fully consolidated). We estimate a model of the non‐adoption of IFRS as a function of implementation features of the IFRS regulation, country‐specific enforcement, and firm‐specific reporting incentives. As expected, being specifically required by EU‐wide and country‐specific rules to adopt IFRS is positively associated with IFRS adoption but does not constitute a complete explanation. Proxies for enforcement are significantly associated with non‐adoption, but the marginal effects of the enforcement variables are weak. We find that larger firms, firms with foreign operations and more analyst following, and firms that issue new debt and equity were more likely to adopt IFRS, both when the regulation was initially imposed and in subsequent years. We conclude that many EU firms do not use IFRS; that some firms exploited definitions, exemptions, and deferrals to avoid adopting IFRS while some firms simply failed to comply with the regulation; and that firms responded to their incentives in deciding whether to adopt IFRS.
Do Clients Get What They Pay For? Evidence from Auditor and Engagement Fee Premiums
Authors: Moon James R. , Shipman Jonathan E. , Swanquist Quinn T. , Whited Robert L.
Published: August 2018

Despite the intuitive appeal, prior research finds mixed evidence on whether higher audit fees translate to superior audit quality. Under the assumption that product differentiation between auditors is based, in large part, on the level of financial statement assurance, we propose more refined measures of excess audit fees that separate auditor premiums from other fee premiums. Consistent with our conjecture, we identify significant variation in audit pricing across auditors (i.e., auditor premiums) that relates positively to audit quality. Conversely, we find no evidence that higher engagement‐specific fee premiums (i.e., fee model residuals) are positively related to proxies for audit quality. Additional tests indicate that our results do not simply reflect premiums attributable to auditor characteristics evaluated in prior research (e.g., Big 4 membership, office size, and industry expertise). In fact, our findings suggest that the positive association between auditor premiums and audit quality is better captured at the auditor level than it is at the auditor “tier,” office, auditor‐industry, or engagement levels. In sum, our results suggest that auditors charging higher fees, on average, deliver superior levels of financial statement assurance, but engagement‐specific fee premiums do not reflect quality‐enhancing audit effort. These contrasting results provide a possible explanation for the mixed findings in prior research.
Customers’ Risk Factor Disclosures and Suppliers’ Investment Efficiency
Authors: Chiu Tzu‐Ting , Kim Jeong‐Bon , Wang Zheng
Published: August 2018

This study examines the effect of downstream firms’ (i.e., customers’) risk factor disclosures contained in annual reports on the investment efficiency of upstream firms (i.e., suppliers). We find that more informative disclosures of customers’ risk factors are associated with less under‐ or overinvestment by suppliers. In addition, this inverse association is stronger when the suppliers are at a bargaining disadvantage, when they operate in the durable goods industries, and when they are more concerned about the volatility of future demand. Overall, our results suggest that risk factor disclosures provided by firms in their annual reports contain useful information that could potentially help their suppliers achieve better investment efficiency.

Divulgation d'information sur les facteurs de risque des clients et efficience de l'investissement des fournisseurs
‘Millennials’: Perceived generational opportunities and intergenerational conflict in Australia
Authors: Cannon Lisa , Kendig Hal
Published: August 2018

Objective

To investigate the perceptions of intergenerational conflict and lifelong opportunities of the Millennial cohort.

Methods

Data were collected in the Attitudes to Ageing in Australia Study as part of the 2015–2017 national Australian Survey of Social Attitudes (n = 2049, aged 18 and older). Variations by age cohorts and individual characteristics were examined in descriptive analyses and binary logistic regressions.

Results

Overall, the majority of people at all ages thought opportunities were worse for younger people than for baby boomers, but few perceived strong conflict between younger and older people. Millennials were the most likely to perceive strong conflict. People rendered ‘disadvantaged’ by their socio‐economic positions were more likely to perceive better opportunities for younger people and strong intergenerational conflict.

Conclusion

Policymakers should address the barriers that Millennials and other socio‐economically disadvantaged people face to improve their lifelong opportunities and address increasing social inequalities in Australia.
The safety and sensitivity of a telemetric capsule to monitor gastrointestinal hydrogen production in vivo in healthy subjects: a pilot trial comparison to concurrent breath analysis
Authors: Berean Kyle J. , Ha Nam , Ou Jian Zhen , Chrimes Adam F. , Grando Danilla , Yao Chu K. , Muir Jane G. , Ward Stephanie A. , Burgell Rebecca E. , Gibson Peter R. , Kalantar‐Zadeh Kourosh
Published: August 2018

Background

Intestinal gases are currently used for the diagnosis of disorders including small intestinal bacterial overgrowth and carbohydrate malabsorption.

Aim

To compare the performance of measuring hydrogen production within the gut directly with the telemetric gas‐sensing capsule with that of indirect measurement through breath testing.

Methods

Using standard breath testing protocols, the capsules and breath tests were simultaneously evaluated in a single‐blinded trial in 12 healthy subjects. Eight received a single dose of 1.25‐40 g inulin and four 20 or 40 g glucose. Safety and reliability of the capsules were also assessed.

Results

There were no reported adverse events. All capsules were retrieved and operated without failure. Capsule measurements were in agreement with breath test measurements in magnitude but not in timing; minimal hydrogen production was observed after glucose ingestion and capsule measurements correlated with breath hydrogen after ingestion of 40 g inulin. A dose‐dependent increase in concentration of hydrogen was observed from the capsule following ingestion of inulin as low as 1.25 g compared with >10 g for breath measurements. Specifically, the capsule measured >3000 times higher concentrations of hydrogen compared to breath tests, resulting in a signal‐to‐noise ratio of 23.4 for the capsule compared to 4.2 for the breath test.

Conclusions

The capsule showed high sensitivity and signal‐to‐noise ratio in measuring luminal hydrogen concentrations, provided information on the site of intestinal gas production, and demonstrated safety and reliability. The capsule has potential for improving diagnostic precision for disorders such as small intestinal bacterial overgrowth.
Risk of serious infection in healthcare workers with inflammatory bowel disease: a case‐control study of the Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif (GETAID)
Authors: Gagnière Charlotte , Bourrier Anne , Seksik Philippe , Gornet Jean‐Marc , DeWit Olivier , Nancey Stephane , Altwegg Romain , Abitbol Vered , Laharie David , Reenaers Catherine , Buisson Anthony , Pariente Benjamin , Viennot Stephanie , Vuitton Lucine , Stefanescu Carmen , Marteau Philippe , Bouguen Guillaume , Cosnes Jacques , Amiot Aurelien ,   the GETAID INFOPRO study group
Published: August 2018

Background

Whether healthcare workers with inflammatory bowel disease (IBD) are at increased risk of severe infection due to daily pathogen exposure is controversial.

Aim

To assess the risk of severe infection in healthcare workers with IBD in a large multicentre case‐control study.

Methods

The study population comprised 482 healthcare workers with IBD from 17 centres who were matched for gender, age, disease subtype and year of diagnosis to 482 controls (non‐healthcare workers with IBD). The study period was between the date of diagnosis of IBD and June 2016. Severe infection was defined as any community‐acquired infection that required hospitalisation.

Results

With a median follow‐up of 9.3 years, 139 severe infections were recorded among cases and controls, including 30 Clostridium difficile infections, 33 severe viral infections, nine tuberculosis infections, 21 community‐acquired pneumonia and 46 others. No difference was observed between healthcare workers and controls regarding the overall incidence rates of severe infection. An increased risk of tuberculosis was noted in healthcare workers. In multivariate analysis in the entire study population, severe infection was associated with current exposure to corticosteroids (OR = 3.05, 95% CI [2.06‐4.52], P < 0.001), immunosuppressants (OR = 1.98, 95% CI [1.38‐2.84], P < 0.001) and anti‐TNF agents (OR = 2.93, 95% CI [2.02‐4.27], P < 0.001) and reduced with Crohn's disease (OR = 0.63, 95% CI [0.43‐0.91], P = 0.01).

Conclusions

Healthcare workers with IBD do not have an increased risk of severe infection compared with other patients with IBD, except for tuberculosis. Screening for tuberculosis exposure should be assessed in this high‐risk population when treated with anti‐TNF agents.
Nucleotide receptor P2RY4 is required for head formation via induction and maintenance of head organizer in Xenopus laevis
Authors: Harata Ayano , Hirakawa Mika , Sakuma Tetsushi , Yamamoto Takashi , Hashimoto Chikara
Published: August 2018

Vertebrates have unique head structures that are mainly composed of the central nervous system, the neural crest, and placode cells. These head structures are brought about initially by the neural induction between the organizer and the prospective neuroectoderm at early gastrula stage. Purinergic receptors are activated by nucleotides released from cells and influence intracellular signaling pathways, such as phospholipase C and adenylate cyclase signaling pathways. As P2Y receptor is vertebrate‐specific and involved in head formation, we expect that its emergence may be related to the acquisition of vertebrate head during evolution. Here, we focused on the role of p2ry4 in early development in Xenopus laevis and found that p2ry4 was required for the establishment of the head organizer during neural induction and contributed to head formation. We showed that p2ry4 was expressed in the head organizer region and the prospective neuroectoderm at early gastrula stage, and was enriched in the head components. Disruption of p2ry4 function resulted in the small head phenotype and the reduced expression of marker genes specific for neuroectoderm and neural border at an early neurula stage. Furthermore, we examined the effect of p2ry4 disruption on the establishment of the head organizer and found that a reduction in the expression of head organizer genes, such as dkk1 and cerberus, and p2ry4 could also induce the ectopic expression of these marker genes. These results suggested that p2ry4 plays a key role in head organizer formation. Our study demonstrated a novel role of p2ry4 in early head development.
Open Design: Design in a Social Era
Authors: Laituri David
Published: August 2018

Open design—which continuously involves users—is one of the best and most efficient ways to make the most of social networks. It's also a terrific way to build new advocates for your startup brand.

Crowdfunding can help you launch a more desirable second‐generation product—first.
Building Alignment and Sparking Momentum with Tangible Future Scenarios
Authors: Lawrence Jill , Clark Brendon
Published: August 2018

Tangible Future Scenarios use props, improvisation, and a cooperative approach to invite discussion and drive further iterations with stakeholders.

This storytelling approach aims to align people and ideas more quickly.
The extended cytoplasmic tail of the human B4GALNT2 is critical for its Golgi targeting and post‐Golgi sorting
Authors: Groux‐Degroote Sophie , Schulz Céline , Cogez Virginie , Noël Maxence , Portier Lucie , Vicogne Dorothée , Solorzano Carlos , Dall'Olio Fabio , Steenackers Agata , Mortuaire Marlène , Gonzalez‐Pisfil Mariano , Henry Mélanie , Foulquier François , Héliot Laurent , Harduin‐Lepers Anne
Published: August 2018

The Sda/Cad antigen reported on glycoconjugates of human tissues has an increasingly recognized wide impact on the physio‐pathology of different biological systems. The last step of its biosynthesis relies on the enzymatic activity of the β1,4‐N‐acetylgalactosaminyltransferase‐II (B4GALNT2), which shows the highest expression level in healthy colon. Previous studies reported the occurrence in human colonic cells of two B4GALNT2 protein isoforms that differ in the length of their cytoplasmic tail, the long isoform showing an extended 66‐amino acid tail. We examined here, the subcellular distribution of the two B4GALNT2 protein isoforms in stably transfected colonic LS174T cells and in transiently transfected HeLa cells using fluorescence microscopy. While a similar subcellular distribution at the trans‐Golgi cisternae level was observed for the two isoforms, our study pointed to an atypical subcellular localization of the long B4GALNT2 isoform into dynamic vesicles. We demonstrated a critical role of its extended cytoplasmic tail for its Golgi targeting and post‐Golgi sorting and highlighted the existence of a newly described post‐Golgi sorting signal as well as a previously undescribed fate of a Golgi glycosyltransferase.

Database

The proteins β1,4GalNAcT II, β1,4‐GalT1, FucT I, FucT VI and ST3Gal IV are noted B4GALNT2, B4GALT1, FUT1, FUT6 and ST3GAL4, whereas the corresponding human genes are noted B4GALNT2, B4GALT1, FUT1, FUT6 and ST3GAL4 according to the HUGO nomenclature.