bluuebunny/crossref_metadata_2025 huggingface dataset:
A common tag nucleotide variant inMMP7promoter increases risk for hypertension via enhanced interactions with CREB transcription factor
Authors: Subramanian Lakshmi , Maghajothi Sakthisree , Singh Mrityunjay , Kesh Kousik , Ananthamohan Kalyani , Sharma Saurabh , Khullar Madhu , Victor Suma M. , Swarnakar Snehasikta , Asthana Shailendra , Mullasari Ajit S. , Mahapatra Nitish R.
Published: March 2019

MMP7 (Matrilysin), a potent extracellular matrix degrading enzyme with wide substrate specificity, is emerging as a new regulator of cardiovascular diseases including coronary artery disease and atherosclerosis. However, potential contributions ofMMP7genetic variations to hypertension remain unknown. In this study, we first probed for the association of a tag single nucleotide polymorphism (SNP) in theMMP7gene promoter (-181A/G; rs11568818) with hypertension in an urban south Indian population (n=1517). The heterozygous A/G genotype showed a strong association with hypertension as compared to the A/A wild-type genotype (OR=1.641, 95% CI=1.276-2.109; p=1×10−4); AG genotype carriers also displayed significantly higher diastolic blood pressure and mean arterial pressure than AA genotype subjects. The study was replicated in a north Indian population (n=977) as well (OR=1.520, 95% CI =1.106-2.090; p=0.01). Transient transfection experiments usingMMP7promoter-luciferase reporter constructs revealed that the variant -181G allele conferred greater promoter activity than the -181A allele. Computational prediction and structure-based conformational and molecular dynamics simulation studies suggested higher binding affinity for the transcription factor CREB to the -181G promoter. In corroboration, over-expression/down-regulation of CREB and chromatin immunoprecipitation experiments provided convincing evidence for stronger binding of CREB with the -181G promoter. Further, the -181G promoter also displayed an enhanced response to hypoxia and epinephrine-treatment. The higher promoter activity of -181G allele also translated to increased MMP7 protein levels. Indeed,MMP7-181A/G heterozygous individuals displayed elevated plasma MMP7 levels which positively correlated with blood pressure. In conclusion, theMMP7A-181G promoter SNP increased expression of MMP7 under pathophysiological (such as hypoxic stress and catecholamine excess) conditions via increased interactions with the transcription factor CREB and enhanced the risk for hypertension in its carriers.
Is it reasonable to use of a kinship matrix for best linear unbiased prediction?
Authors: Kim Bongsong
Published: March 2019

The linear mixed model (LMM) is characterized to account for the variance-covariance among entities in a population toward calculating the best linear unbiased prediction (BLUP). Animal and plant breeders widely use the LMM because it is perceived that the a BLUP estimate informs an estimated breeding value (EBV), so to speak a combining ability as a parent, obtained by relating each entity to his/her relatives using the variance-covariance. The LMM practice routinely substitutes an external kinship matrix for the variance-covariance. The challenge relevant to the LMM practice is the fact that it is unrealistic to validate the EBVs because the real breeding values are not measurable but conceptual. This unreality actually means that the EBVs are vague. Although some previous studies measured correlations between the EBVs and empirical combining abilities, they are not sufficient to remove the vagueness of EBVs because uncontrollable environmental factors might interfere with phenotypic observations for measuring the combining abilities. To overcome the challenge, this study scrutinized the soundness of the routine LMM practice from the mathematical perspective. As a result, it was demonstrated that the BLUP estimates resulting from the routine LMM practice mislead the breeding values. The genuine BLUP represents the arithmetic means of multiple phenotypic observations per each entity, given all phenotypic observations adjusted to the mean of zero.
Molecular model of the nuclear pore complex reveals a thermoreversible FG-network with distinct territories occupied by different FG motifs
Authors: Huang Kai , Tagliazucchi Mario , Park Sung Hyun , Rabin Yitzhak , Szleifer Igal
Published: March 2019

Despite the intensive study of the nuclear pore complex (NPC), its functional core, the central transporter, remains poorly understood. Here, we investigate this unfolded and dynamic part of the NPC using a molecular theory that addresses both entropic and enthalpic effects of the intrinsically disordered phenylalanine-glycine-rich nucleoporins (FG-Nups). Our model shows that the cooperative effect of FG-pairing, specific spacer cohesion, and charge interaction leads to a remarkably elaborate gating structure inside the NPC. In particular, we find sequence-programmed “phase separation” between charge-rich and charge-poor regions, and a polarized electrostatic potential throughout the NPC. The model predicts a thermoreversible FG-network with inhomogeneous FG-pairing fraction in space, which features distinct territories of different types of FG motifs. Our theoretical anatomy of the central transporter reveals a clear sequence-structure-function relationship of the FG-Nups, and explains in a self-consistent way how nucleocytoplasmic transport can be efficient yet specific.
Urinary biomarker and histopathological evaluation of vancomycin and piperacillin-tazobactam nephrotoxicity in comparison with vancomycin in a rat model and a confirmatory cellular model
Authors: Pais Gwendolyn M. , Liu Jiajun , Avedissian Sean N. , Xanthos Theodoros , Chalkias Athanasios , d’Aloja Ernesto , Locci Emanuela , Gilchrist Annette , Prozialeck Walter C. , Rhodes Nathaniel J. , Lodise Thomas P. , Fitzgerald Julie C. , Downes Kevin , Zuppa Athena F. , Scheetz Marc H.
Published: March 2019

Introduction

Vancomycin and piperacillin tazobactam (VAN+TZP) are two of the most commonly utilized antibiotics in the hospital setting and are reported in clinical studies to increase acute kidney injury (AKI). However, no clinical study has demonstrated that synergistic toxicity occurs, only that serum creatinine (SCr) increases with VAN+TZP. The purpose of this study was to assess biologic plausibility by quantifying kidney injury between VAN, TZP, and VAN+TZP treatments using a translational rat model of AKI and rat kidney epithelial cell studies.

Methods

(i) Male Sprague-Dawley rats (n=32) received either saline, VAN 150 mg/kg/day intravenously, TZP 1400 mg/kg/day via intraperitoneal injection, or VAN+TZP. Animals were placed in metabolic cages pre-study and on drug dosing days 1-3. Urinary biomarkers and histopathology were analyzed. (ii) Cellular injury of VAN+TZP was assessed in serum-deprived rat kidney cells (NRK-52E) using an alamarBlue® viability assay. Cells were incubated with antibiotics VAN, TZP, cefepime, and gentamicin alone or combined with the same drugs plus VAN 1 mg/mL.

Results

In the VAN-treated rats, urinary KIM-1 and clusterin were increased on days 1, 2, and 3 compared to controls (P<0.001). Elevations were seen only after 3 days of treatment with VAN+TZP (P<0.001 KIM-1, P<0.05 clusterin). Histopathology was only elevated in the VAN group when compared to TZP as a control (P=0.04). Results were consistent across biomarkers and histopathology suggesting that adding TZP did not worsen VAN induced AKI and may even be protective. In NRK-52E cells, VAN alone caused moderate cell death with high doses (IC5048.76 mg/mL). TZP alone did not cause cellular death under the same conditions. VAN+TZP was not different from VAN alone in NRK-52E cells (P>0.2).

Conclusions

VAN+TZP does not cause more kidney injury than VAN alone in a rat model of VIKI or in rat kidney epithelial cells.
CUT&Tag for efficient epigenomic profiling of small samples and single cells
Authors: Kaya-Okur Hatice S. , Wu Steven J. , Codomo Christine A. , Pledger Erica S. , Bryson Terri D. , Henikoff Jorja G. , Ahmad Kami , Henikoff Steven
Published: March 2019

Many chromatin features play critical roles in regulating gene expression. A complete understanding of gene regulation will require the mapping of specific chromatin features in small samples of cells at high resolution. Here we describe Cleavage Under Targets and Tagmentation (CUT&Tag), an enzyme-tethering strategy that provides efficient high-resolution sequencing libraries for profiling diverse chromatin components. In CUT&Tag, a chromatin protein is boundin situby a specific antibody, which then tethers a protein A-Tn5 transposase fusion protein. Activation of the transposase efficiently generates fragment libraries with high resolution and exceptionally low background. All steps from live cells to sequencing-ready libraries can be performed in a single tube on the benchtop or a microwell in a high-throughput pipeline, and the entire procedure can be performed in one day. We demonstrate the utility of CUT&Tag by profiling histone modifications, RNA Polymerase II and transcription factors on low cell numbers and single cells.
Base pairing interactions between substrate RNA and H/ACA guide RNA modulate the kinetics of pseudouridylation, but not the affinity of substrate binding by H/ACA small nucleolar Ribonucleoproteins
Authors: Kelly Erin Katelyn , Czekay Dominic Philip , Kothe Ute
Published: March 2019

H/ACA small nucleolar ribonucleoproteins (snoRNPs) pseudouridylate RNA in eukaryotes and archaea. They target many RNAs site-specifically through base-pairing interactions between H/ACA guide and substrate RNA. Besides ribosomal RNA (rRNA) and small nuclear RNA (snRNA), H/ACA snoRNPs are thought to also modify messenger RNA (mRNA) with potential impacts on gene expression. However, the base-pairing between known target RNAs and H/ACA guide RNAs varies widely in nature, and therefore the rules governing substrate RNA selection are still not fully understood. To provide quantitative insight into substrate RNA recognition, we systematically altered the sequence of a substrate RNA target by the Saccharomyces cerevisiae H/ACA guide RNA snR34. Time courses measuring pseudouridine formation revealed a gradual decrease in the initial velocity of pseudouridylation upon reducing the number of base pairs between substrate and guide RNA. Changing or inserting nucleotides close to the target uridine severely impairs pseudouridine formation. Interestingly, filter binding experiments show that all substrate RNA variants bind to H/ACA snoRNPs with nanomolar affinity. Next, we showed that binding of inactive, near-cognate RNAs to H/ACA snoRNPs does not inhibit their activity for cognate RNAs, presumably because near-cognate RNAs dissociate rapidly. We discuss that the modulation of initial velocities by the base pairing strength might affect the order and efficiency of pseudouridylation in rRNA during ribosome biogenesis. Moreover, the binding of H/ACA snoRNPs to near-cognate RNAs may be a mechanism to search for cognate target sites. Together, our data provide critical information to aid in the prediction of productive H/ACA guide – substrate RNA pairs.
The integration of Gaussian noise by long-range amygdala inputs in frontal circuit promotes fear learning
Authors: Aime Mattia , Augusto Elisabete , Kouskoff Vladimir , Martin Christelle , Humeau Yann , Chenouard Nicolas , Gambino Frédéric
Published: March 2019

Survival depends on the ability of animals to select the appropriate behavior in response to threat and safety sensory cues. However, the synaptic and circuit mechanisms by which the brain learns to encode accurate predictors of threat and safety remain largely unexplored. Here, we show that frontal association cortex (FrA) pyramidal neurons integrate auditory cues and basolateral amygdala (BLA) inputs non-linearly in a NMDAR-dependent manner. We found that the response of FrA pyramidal neurons was more pronounced to Gaussian noise than to pure 8 kHz tone, and that the activation of BLA-to-FrA axons was the strongest during safe periods in between conditioning pairings. Blocking BLA-to-FrA signaling specifically at the time of presentation of Gaussian noise (but not 8 kHz tone) as a safety signal impaired the formation of auditory fear memories. Taken together, our data reveal a circuit mechanism that facilitates the formation of fear traces in the FrA, thus providing a new framework for probing discriminative learning and related disorders.
Large-scale kinetic metabolic models ofPseudomonas putidafor a consistent design of metabolic engineering strategies
Authors: Tokic Milenko , Miskovic Ljubisa , Hatzimanikatis Vassily
Published: March 2019

A high tolerance ofPseudomonas putidato toxic compounds and its ability to grow on a wide variety of substrates makes it a promising candidate for the industrial production of biofuels and biochemicals. Engineering this organism for improved performances and predicting metabolic responses upon genetic perturbations requires reliable descriptions of its metabolism in the form of stoichiometric and kinetic models. In this work, we developed large-scale kinetic models ofP. putidato predict the metabolic phenotypes and design metabolic engineering interventions for the production of biochemicals. The developed kinetic models contain 775 reactions and 245 metabolites. We started by a gap-filling and thermodynamic curation of iJN1411, the genome-scale model ofP. putidaKT2440. We then applied the redGEM and lumpGEM algorithms to reduce the curated iJN1411 model systematically, and we created three core stoichiometric models of different complexity that describe the central carbon metabolism ofP. putida. Using the medium complexity core model as a scaffold, we employed the ORACLE framework to generate populations of large-scale kinetic models for two studies. In the first study, the developed kinetic models successfully captured the experimentally observed metabolic responses to several single-gene knockouts of a wild-type strain ofP. putidaKT2440 growing on glucose. In the second study, we used the developed models to propose metabolic engineering interventions for improved robustness of this organism to the stress condition of increased ATP demand. Overall, we demonstrated the potential and predictive capabilities of developed kinetic models that allow for rational design and optimization of recombinantP. putidastrains for improved production of biofuels and biochemicals.
Elucidation of the viral disassembly switch of tobacco mosaic virus
Authors: Weis Felix , Beckers Maximilian , von der Hocht Iris , Sachse Carsten
Published: March 2019

Stable capsid structures of viruses protect viral RNA while they also require controlled disassembly for releasing the viral genome in the host cell. A detailed understanding of viral disassembly processes and the involved structural switches is still lacking. Biochemically, this process has been extensively studied using the tobacco mosaic virus model system and carboxylate interactions have been proposed to play a critical part in this process. Here, we present two cryo-EM structures of the helical TMV assembly at 2.1 and 2.0 Å resolution in conditions of high Ca2+concentration at low pH and in water. Based on our atomic models, we identified the conformational details of the disassembly switch mechanism: in high Ca2+/acidic pH environment the virion is stabilized between neighboring subunits through carboxyl groups E95 and E97 in close proximity to a Ca2+binding site. Upon increase in pH and lower Ca2+levels, mutual repulsion of the E95/E97 pair and Ca2+removal destabilize the network of interactions at lower radius and release the switch of virus disassembly. Our TMV structures revealed the conformational details for one of the reference systems of viral assembly/disassembly and provide the mechanistic explanation of a plethora of experimental results that were acquired over decades.

Significance Statement

Tobacco mosaic virus presents the text-book example of virus structure and RNA release from a viral capsid through disassembly. Despite the wealth of structural and biochemical data on the assembly/disassembly properties generated from more than 80 years of research, the atomic-resolution structural details of the proposed conformational changes have not been resolved to date. The here determined high-resolution cryo-EM structures reveal the conformational details of the molecular disassembly switch. When the virus enters the cell, carboxylate repulsion and loss of calcium-ion coordination destabilize the switch region and can trigger RNA release through virus disassembly. The two determined structural states resolve a long-standing question on environment-driven virus disassembly switches.
Chemical screening pipeline for identification of specific plant autophagy modulators
Authors: Dauphinee Adrian N. , Cardoso Catarina , Dalman Kerstin , Ohlsson Jonas A. , Fick Stina Berglund , Robert Stephanie , Hicks Glenn R. , Bozhkov Peter V. , Minina Elena A.
Published: March 2019

Autophagy is a major catabolic process in eukaryotes with a key role in homeostasis, programmed cell death and aging. In plants, autophagy is also known to regulate agriculturally important traits such as stress resistance, longevity, vegetative biomass and seed yield. Despite its significance, there is still a shortage of reliable tools modulating plant autophagy. Here we describe the first robust pipeline for identification of specific plant autophagy-modulating compounds. Our screening protocol comprises four phases: (i) high-throughput screening of chemical compounds in cell cultures of Nicotiana tabacum; (ii) confirmation of the identified hits in planta using Arabidopsis thaliana; (iii) further characterization of the effect using conventional molecular biology methods; (iv) verification of chemical specificity on autophagy in planta. The methods detailed here streamline identification of specific plant autophagy modulators and aid in unravelling the molecular mechanisms of plant autophagy.
Driving new narratives: women-leader identities in the automotive industry
Authors: Bullock Christina L.
Published: March 2019

Purpose

The purpose of this paper is to examine the identity-related work experiences of women in leadership in the US automotive industry. Drawing upon the communication theory of identity’s four identity frames, this study analyzes women’s narratives to better understand their self-concepts, work relationships and activities within larger corporate automotive contexts.

Design/methodology/approach

A qualitative methodology consisting of 16 in-depth interviews with women in leadership in automotive organizations was adopted. Interviews examined women’s perceptions and identities at work, including their daily behaviors, relationships with others and their perceptions of the larger automotive community.

Findings

Findings demonstrate that women in leadership in the automotive industry experience contradictory feelings, messages and interactions that impact their identity perceptions and expectations for performance and achievement in their work settings.

Practical implications

The experiences of women in leadership in US automotive organizations could provide examples of identity-related topics valuable to practitioner fields where women seek relevant, gender-specific, guidance, resources and strategies to advance in their careers.

Social implications

The findings in this study raise awareness about some of the social issues women in leadership face in automotive corporations, including complex identity-related challenges present in their workplaces.

Originality/value

This paper is the first of its type to examine the narratives of women’s career life in leadership in automotive organizations through a communication theory of identity lens. It extends knowledge about female leaders as they navigate the dissonant worlds of achieving higher positions whilst holding membership in a marginalized group.
Determinants of banking consumers’ engagement in post service failure positive word-of-mouth
Authors: Harun Ahasan , Rokonuzzaman Md , Prybutok Gayle , Prybutok Victor R.
Published: March 2019

Purpose

The purpose of this paper is to develop and examine a theoretical framework that evaluates the effects of banking consumers’ justice perception on their post-complaint mindsets. It also aims to help business strategists to customize service failure management activities to achieve a competitive advantage.

Design/methodology/approach

To examine the proposed framework using partial least square structural equation modeling, the authors collected data through a survey. The authors also evaluated the proposed framework through multi-group analysis and importance-performance map analysis (IPMA).

Findings

Results show that recovery disconfirmation mediates the relationship between banking consumers’ perception of justice and recovery satisfaction. Moreover, after a service failure, brand equity and loyalty mediate the relationship between recovery satisfaction and positive word-of-mouth behavior. IPMA analysis at the construct level shows that fostering the perception of recovery satisfaction is crucial for creating a positive post-failure impression in the mind of the banking consumer.

Practical implications

For banking practitioners, the findings of this research provide a strategic blueprint for managing service failure by developing relationships with consumers, thus creating an opportunity to gain competitive advantage.

Originality/value

Anchored in the theoretical framework of justice theory (Adams, 1963), expectation disconfirmation theory (Oliver, 1977) and social exchange theory (Kelley and Thibaut, 1978), the research adds to the literature by providing a critical evaluation of how to influence banking consumers’ post-complaint behavior from a more systematic perspective.
Propensity of contracting loans services from FinTech’s in Brazil
Authors: Contreras Pinochet Luis Hernan , Diogo Guilherme Tongnole , Lopes Evandro Luiz , Herrero Eliane , Bueno Ricardo Luiz Pereira
Published: March 2019

Purpose

Given the large global investments made in FinTechs and the context of Brazilian credit (which has been suffering from the effects of the crisis in the last decade), the purpose of this paper is to study the propensity of consumption of credit services offered by FinTechs of loans. In order to discover the factors that influenced the propensity to apply for FinTech loans, a theoretical model was designed, which was tested by means of a survey given to individuals who might contract loans.

Design/methodology/approach

The final sample consisted of 507 individuals whose data were analyzed through structural equation modeling (SEM), with estimation of partial least squares.

Findings

From the results of the research, it was possible to draw a profile of the FinTechs of Brazilian loans and also to estimate the antecedents of the propensity to utilize this type of service.

Research limitations/implications

The model proposed in this work was developed to measure the propensity to consume in relation to the credit services offered by lending FinTechs.

Practical implications

The consumer should intensify the use of these channels to shape financial products and services to their needs, thereby democratizing access to credit, which is often restricted in quantity and quality by policies of institutions that dominate the Brazilian lending market.

Originality/value

Aspects such as trust, personal innovation, perceived utility, ease of use and social influence, as well as the constructs that precede them like privacy, stigma and transactional distance, explain 41.5 percent of the propensity to use services from lending FinTechs in Brazil.
Analysing the 3PL service provider’s evaluation criteria through a sustainable approach
Authors: Gardas Bhaskar B. , D. Raut Rakesh , Narkhede Balkrishna E.
Published: March 2019

Purpose

The purpose of this paper is to identify and model the evaluation criteria for the selection of third-party logistics service provider (3PLSP) by an interpretive structural modelling (ISM) approach in the pharmaceutical sector.

Design/methodology/approach

Delphi technique was used for identifying the most significant criteria, and the ISM method was employed for developing the interrelationship among the criteria. Also, the critical criteria for having high influential power were identified by using the Matrice d’Impacts Croisés Multiplication Appliqués à un Classement analysis.

Findings

The most significant factors, namely, capability of robust supply network/distribution network, quality certification and health safety, service quality and environmental quality certifications, were found to have a high driving power, and these factors demand the maximum attention of the decision makers.

Research limitations/implications

As the ISM approach is a qualitative tool, the expert opinions were used for developing the structural model, and the judgments of the experts could be biased influencing the reliability of the model. The developed hierarchical concept is proposed to help the executives, decision and policy makers in formulating the strategies and the evaluation of sustainable 3PLSP.

Originality/value

It is an original research highlighting the association between the sustainable 3PLSP evaluation criteria by employing ISM tool in the pharmaceutical industry. This paper will guide the managers in understanding the importance of the evaluation criteria for the efficient selection of 3PLSP.
A two-way causal chain between lean management practices and lean values
Authors: Salhieh Loay , Abdallah Abdallah A.
Published: March 2019

Purpose

Organizations have varied levels of success with Lean implementation and many did not see tangible results. Some scholars believe the reason has to do with weak Lean culture or Lean values (LVs). The purpose of this paper is to study the relationship between Lean implementation practices and LVs. The research goes further to study the nature of this relationship; does LVs affect Lean practices only or do they affect each other in a reciprocal manner?

Design/methodology/approach

Literature regarding Lean implementation in various sectors was reviewed. Representatives from several organizations were surveyed. Results from both approaches are compared and presented to highlight the key challenges and drivers facing Lean implementation.

Findings

Lean works well on enhancing organization performance (OP) but the implementation has to be preceded by careful nourishment of the proper Lean culture and LVs. The relationship between Lean implementation and LVs is of a complex nature and driven by OP.

Practical implications

The study has important managerial implications that is if Lean is going to be sustained, continuous efforts has to be exerted by Lean professionals to engage leaders and decision makers in the organization and ensure proper values are nurtured.

Originality/value

This is the first study to examine the reciprocal relationship between Lean implementation practices and LVs while focusing on OP by employing a structural statistical model.
Mentoring characteristics and functions: mentoring’s influence on salespeople
Authors: Brashear-Alejandro Tom , Barksdale Hiram , Bellenger Danny Norton , Boles James S. , James Channelle
Published: March 2019

Purpose

This paper aims to examine a longitudinal study of mentoring functions and their effect on salesperson attitudes and intentions.

Design/methodology/approach

The research is based on a multi-year study of salespeople beginning when the salesperson entered the industry being examined.

Findings

The level of interaction between the mentor and protégé was found to be the only antecedent examined that related to the perceived quality of mentoring functions. Age, education and length of employment for both parties; the degree of age and education difference; and the length of the mentoring relationship were not significant. Successful mentoring appeared to be based heavily on a mentor’s willingness and ability to interact frequently with the protégé.

Originality/value

This study adds to the literature on mentoring, looking at mentoring in a sales context. Research examining mentoring in a sales setting is much more limited than in many other professions, so the findings represent a valuable addition to the sales mentoring literature. Its influence on sales socialization may be very important.
Applying social impact assessment (SIA) principles in assessing contribution of cultural heritage to social sustainability in rural landscapes
Authors: Gallou Eirini , Fouseki Kalliopi
Published: March 2019

Purpose

The purpose of this paper is to propose the use of social impact assessment (SIA) principles to evaluate the contribution of cultural heritage to social sustainability, supporting both a people-centered and socially responsible approach to heritage management.

Design/methodology/approach

Specifically, the paper explores SIA as a methodological tool for post-project evaluation, used to define projects’ contributions to aspects of social sustainability through analyzing impacts of participation in a rural context case study, that of the Scapa Flow landscape heritage scheme in Orkney Islands, Scotland, UK.

Findings

Based on research findings from the thematic analysis of 40 semi-structured interviews on impacts (with heritage managers, planners and participants in the scheme), the paper proposes a combination of heritage value assessment process with social impact identification to achieve a context-relevant assessment of social sustainability. Existing research around social capital and sense of place supports the analysis of relevant impacts and heritage values. Findings support overlaps between socio-environmental impacts, when looking at the role of heritage for community well-being in rural contexts.

Research limitations/implications

The qualitative approach allows for a context-relevant, bottom up impact assessment and allows for multiple stakeholders perceptions to be included.

Practical implications

The proposed methodological approach has greater implications for the work of institutions and professionals involved in project evaluations that can inform participatory heritage project planning, ensuring high social relevance.

Social implications

Application of SIA principles in heritage sector can increase social benefits of heritage projects and enable wider community participation in processes of heritage management.

Originality/value

Through this case study, the effectiveness of SIA principles when applied in cultural heritage project evaluation is discussed, reflecting on a novel methodology for impact assessment in heritage.
Compensation clawback policies and corporate lawsuits
Authors: Arena Matteo P. , Nguyen Nga Q.
Published: March 2019

Purpose

The purpose of this paper is to study the relation between compensation clawbacks and lawsuits and analyze how these two corporate disciplinary forces interact. This paper hypothesizes that by allowing firms to recoup compensation from managers who breach their fiduciary duty, clawbacks provide a form of discipline that potentially reduces the likelihood of managerial wrongdoing, which, in turn, lowers the risk of corporate lawsuits.

Design/methodology/approach

This paper identifies whether or not a company in the S&P 1500 had a clawback policy between 2007 and 2014 by searching the company filings and press releases. The authors also construct different proxies for litigation risk and lawsuit outcomes using the Audit Analytics Database. They then perform a variety of empirical tests to examine the association between clawbacks and litigation risk and the association between clawbacks and litigation outcomes.

Findings

This paper finds that firms with higher litigation risk are more likely to adopt a clawback policy. In addition, after the adoption of clawback provisions, litigation risk significantly declines, suggesting that clawback policies are effective in reducing the likelihood of corporate lawsuits. Furthermore, firms with clawback policies are approximately 50 per cent more likely to have lawsuits against them dismissed or settled for lower amounts (approximately 12 per cent lower).

Practical implications

The findings of this paper provide insights to the efficacy of a current change in compensation regulation, the mandatory clawback adoption requirement by the Dodd–Frank Act of 2010.

Originality/value

This paper contributes to the literature on both clawbacks and litigation, as it is the first to analyze the relation between the two.
Global financial regulation in the “New International Economic Order”
Authors: Belay Habtamu Simachew
Published: March 2019

Purpose

In 1974, the UN General Assembly adopted a landmark resolution proclaiming the establishment of a New International Economic Order. One of the basic aims of this declaration was to enhance the voice and participation of developing countries in the international economic decision-making process based on norms of equitable governance. More than four decades have passed since its adoption. This paper aims to reflect on the past 43 years of the global financial regulatory system in light of the notion of equitable governance as envisioned by the “New International Economic Order”.

Design/methodology/approach

This paper surveys the global financial regulatory system from the vantage point of equitable economic governance. This discussion covers the period that comes after the 1974 UN landmark resolutions that declare the establishment of a “New International Economic Order”. The authors use qualitative and quantitative approach in this study. They use descriptive statistics and intuitive discussions of certain cases to carry the objective of the paper forward.

Findings

First, part of the development in global financial regulation manifests the establishment of informal networks that embark on global regulatory issues, while being very exclusive in their membership policies. Second, the lack of full and effective participation of developing countries in the decision-making and norm setting remains unsolved in the global financial regulatory system. Third, the shadow role of the World Bank and International Monetary Fund was of great significance in assisting the implementation of non-binding regulatory rules of international finance in developing countries despite the concerns of legitimacy and equity in the making of international standards. In sum, the global financial regulatory system that emerged in the past four decades is quite different from that aspired by the NIEO.

Originality/value

The declaration of NIEO coincides with the collapse of the Bretton Wood’s fixed exchange rate which in turn leads to the emergence of a new financial system and regulatory development. This period marked the proliferation of informal networks that make policy recommendations or non-binding rules with global implications. As far as the literature review goes far, this paper is the first to survey the post Bretton Wood’s period of the global financial regulatory architecture based on the tenets of the “New International Economic Order”.
Weak spatiotemporal response of prey to predation risk in a freely interacting system
Authors: Cusack Jeremy J. , Kohl Michel T. , Metz Matthew C. , Coulson Tim , Stahler Daniel R. , Smith Douglas W. , MacNulty Daniel R.
Published: March 2019

The extent to which prey space use actively minimizes predation risk continues to ignite controversy. Methodological reasons that have hindered consensus include inconsistent measurements of predation risk, biased spatiotemporal scales at which responses are measured and lack of robust null expectations.

We addressed all three challenges in a comprehensive analysis of the spatiotemporal responses of adult female elk (Cervus elaphus) to the risk of predation by wolves (Canis lupus) during winter in northern Yellowstone,USA.

We quantified spatial overlap between the winter home ranges ofGPS‐collared elk and three measures of predation risk: the intensity of wolf space use, the distribution of wolf‐killed elk and vegetation openness. We also assessed whether elk varied their use of areas characterized by more or less predation risk across hours of the day, and estimated encounter rates between simultaneous elk and wolf pack trajectories. We determined whether observed values were significantly lower than expected if elk movements were random with reference to predation risk using a null model approach.

Although a small proportion of elk did show a tendency to minimize use of open vegetation at specific times of the day, overall we highlight a notable absence of spatiotemporal response by female elk to the risk of predation posed by wolves in northern Yellowstone.

Our results suggest that predator–prey interactions may not always result in strong spatiotemporal patterns of avoidance.
Impact of grazing, resource availability and light on prokaryotic growth and diversity in the oligotrophic surface global ocean
Authors: Teira Eva , Logares Ramiro , Gutiérrez‐Barral Alberto , Ferrera Isabel , Varela Marta M. , Morán Xosé Anxelu G. , Gasol Josep M.
Published: March 2019

The impact of grazing, resource competition and light on prokaryotic growth and taxonomic composition in subtropical and tropical surface waters were studied through 10 microcosm experiments conducted between 30°N and 30°S in the Atlantic, Pacific and Indian oceans. Under natural sunlight conditions, significant changes in taxonomic composition were only observed after the reduction of grazing by sample filtration in combination with a decrease in resource competition by sample dilution. Sunlight exposure significantly reduced prokaryote growth (11 ± 6%) and community richness (14 ± 4%) compared to continuous darkness but did not significantly change community composition. The largest growth inhibition after sunlight exposure occurred at locations showing deep mixed layers. The reduction of grazing had an expected and significant positive effect on growth, but caused a significant decrease in community richness (16 ± 6%), suggesting that the coexistence of many different OTUs is partly promoted by the presence of predators. Dilution of the grazer‐free prokaryotic community significantly enhanced growth at the level of community, but consistently and sharply reduced the abundance of Prochlorococcus and SAR11 populations. The decline of these oligotrophic bacterial taxa following an increase in resource availability is consistent with their high specialization for exploiting the limited resources available in the oligotrophic warm ocean.
Cone beam computed tomography devices in the evaluation of buccal bone in anterior teeth
Authors: Dantas LL , Ferreira PP , Oliveira LSAF , Neves FS , Campos PSF , Scarfe WC , Crusoe‐Rebello I
Published: March 2019

Objective

To determine the accuracy of various cone beam computed tomography (CBCT) devices in assessing the buccal bone in anterior teeth.

Material and Methods

A skull encased in tissue equivalent material was imaged with six CBCT devices: 3D Accuitomo 170 (J. Morita, Japan), CS 9000 3D (Carestream Dental, France), CS 9300 (Carestream Dental, France), Eagle 3D (Dabi Atlante, Brazil), i‐CAT Classic (Imaging Sciences International, USA) and Orthophos XG 3D (Sirona Dental System, USA). The exposure and acquisition protocols were determined using the manufacturer's guidelines, the voxel size adjusted as close as possible to 0.2 mm. Cross‐sectional images were evaluated randomly, and the buccal bone was assessed.

Results

The statistics were calculated based on a logistic regression model with the significance level set at 5%. All CBCT devices showed high accuracy; however, observers noted that the accuracy and sensitivity of CS 9300 device were slightly superior.

Conclusion

The diagnostic performance of all CBCT devices was high for the evaluation of buccal bone in anterior teeth. When the clinical usefulness of an imaging modality is equivalent, the choice of appropriate imaging should be directed towards the modality that delivers the least radiation dose to the patient for a specific diagnostic task.
A biodiversity hypothesis
Authors: Haahtela Tari
Published: March 2019

Biodiversity hypothesis states that contact with natural environments enriches the human microbiome, promotes immune balance and protects from allergy and inflammatory disorders. We are protected by two nested layers of biodiversity, microbiota of the outer layer (soil, natural waters, plants, animals) and inner layer (gut, skin, airways). The latter inhabits our body and is colonized from the outer layer. Explosion of human populations along with cultural evolution is profoundly changing our environment and lifestyle. Adaptive immunoregulatory circuits and dynamic homeostasis are at stake in the newly emerged urban surroundings. In allergy, and chronic inflammatory disorders in general, exploring the determinants of immunotolerance is the key for prevention and more effective treatment. Loss of immunoprotective factors, derived from nature, is a new kind of health risk poorly acknowledged until recently. The paradigm change has been implemented in the Finnish allergy programme (2008‐2018), which emphasized tolerance instead of avoidance. The first results are promising, as allergy burden has started to reduce. The rapidly urbanizing world is facing serious biodiversity loss with global warming, which are interconnected. Biodiversity hypothesis of health and disease has societal impact, for example, on city planning, food and energy production and nature conservation. It has also a message for individuals for health and well‐being: take nature close, to touch, eat, breathe, experience and enjoy. Biodiverse natural environments are dependent on planetary health, which should be a priority also among health professionals.
Association of preoperative total lymphocyte count with prognosis in resected left‐sided pancreatic cancer
Authors: Rho Seoung Yoon , Hwang Ho Kyoung , Chong Jae Uk , Yoon Dong Sup , Lee Woo Jung , Kang Chang Moo
Published: March 2019

Background

Immunologic factors such as neutrophil‐lymphocyte ratio and platelet‐lymphocyte ratio play an important role in predicting the oncologic outcome of patients in pancreatic ductal adenocarcinoma (PDAC). It is hypothesized that host immunity represented by total lymphocyte count at diagnostic stage would influence oncologic outcome in left‐sided PDAC.

Methods

Between January 1992 and August 2017, total of 112 patients who underwent distal pancreatectomy for left‐sided PDAC were included and analysed.

Results

At the time of the diagnosis, total lymphocyte count at diagnosis of left‐sided PDAC was 1.8 ± 0.7 103/μL (mean value ± standard deviation). Among different cut‐off values, 1.7 showed most powerful significant differences in long‐term oncologic outcomes. The patients with preoperative lymphocyte count (≤1.7) was associated with early recurrence (median 8.4 months versus 18.1 months, P = 0.011) and shorter survival (median 18.6 months versus 35.9 months, P = 0.028). Patients with preoperative total lymphocyte count over 1.7 showed higher white blood cell count (P < 0.001), platelet count (P = 0.039), neutrophil count (P = 0.004) and monocyte count (P = 0.001). However, more interestingly, neutrophil‐lymphocyte ratio (P < 0.001) and platelet‐lymphocyte ratio (P < 0.001) were found to be significantly higher in those with total lymphocyte count less than 1.7. Lymphocyte to monocyte ratio was inversely related to preoperative total lymphocyte count (P < 0.001). Only age was identified to be significantly different (P = 0.007). However, other clinicopathological parameters generally known to be related to tumour aggressiveness, were not different between two groups.

Conclusion

In conclusion, preoperative total lymphocyte at diagnostic stage is simple, and good prognostic factor in left‐sided pancreatic cancer.
Retinal vasodilatation in the affected eye but reduced pressure autoregulation of both eyes in unilateral Coats’ disease
Authors: Petersen Line , Bek Toke
Published: March 2019

Background

Coats’ disease is characterized by vascular hyperpermeability, oedema and accumulation of exudates related to impairment of retinal vascular function. The background for the development of the disease is unknown, but it is likely that the study of diameter changes of retinal vessels may contribute to understanding the pathophysiology of the disease.

Methods

In seven patients with unilateral Coats’ disease (mean age = 34.7 years, range: 11–69 years), the baseline diameter and reactivity of retinal vessels during an increase in the arterial blood pressure by isometric exercise and in the metabolism by flicker stimulation were measured on video recordings of the retina obtained with the Dynamic Vessel Analyzer.

Results

The baseline diameter of retinal vessels was larger in the affected than in the unaffected eyes which was significant for the arterioles (p = 0.02), but not for the venules (p = 0.15). During an increase in the arterial blood pressure induced by isometric exercise, the normal contraction of arterioles was absent in both eyes (p > 0.7), whereas there was a significant dilatation of the venules in the unaffected eyes (p = 0.04). Stimulation with flickering light induced normal dilatation of retinal vessels in both affected and unaffected eyes.

Conclusion

Unilateral Coats’ disease is accompanied by vasodilatation in the affected eye but impaired pressure autoregulation in both eyes. A further investigation of the disease should include an elucidation of the background for dilatation of retinal vessels in affected eyes and whether impaired pressure autoregulation can be found in vessels elsewhere in the body.
Associations of statin use with glycaemic traits and incident type 2 diabetes
Authors: Ahmadizar Fariba , Ochoa‐Rosales Carolina , Glisic Marija , Franco Oscar H. , Muka Taulant , Stricker Bruno H.
Published: March 2019

Aims

There are several epidemiological studies on the association between statins and incident diabetes, but most of them lack details. In this study, we aimed to investigate the association of statin use with glycaemic traits and incident type 2 diabetes.

Methods

Using the prospective population‐based Rotterdam Study, we included 9535 individuals free from diabetes at baseline (>45 years) during the study period between 1997 and 2012. Linear regression analysis was applied to examine the cross‐sectional associations between statin use and glycaemic traits including fasting blood serum of glucose and insulin concentrations, and insulin resistance. In a longitudinal follow‐up study, we applied a Cox regression analysis to determine adjusted hazard ratios (HR) for incident type 2 diabetes in new users of statins.

Results

The mean age at baseline was 64.3 ± 10.1 years and 41.7% were men. In the fully adjusted model, compared to never users of statins, baseline use of statins was associated with higher concentrations of serum fasting insulin (β = 0.07; 95% CI: 0.02–0.13) and insulin resistance (β = 0.09; 95% CI: 0.03–0.14). Ever use of statins was associated with a 38% higher risk of incident type 2 diabetes (HR = 1.38; 95% CI: 1.09–1.74). This risk was more prominent in subjects with impaired glucose homeostasis and in overweight/obese individuals.

Conclusions

Individuals using statins may be at higher risk for hyperglycaemia, insulin resistance and eventually type 2 diabetes. Rigorous preventive strategies such as glucose control and weight reduction in patients when initiating statin therapy might help minimize the risk of diabetes.