bluuebunny/crossref_metadata_2025 huggingface dataset:
Neoliberal shareholder value and the re-privatization of corporations
Authors: Nwoke Uchechukwu , Ajibo Collins Chikodi , Umahi Timothy Okechukwu
Published: October 2018

Purpose

This paper aims to investigate the extent to which the ideology of shareholder value is compatible with that of transformative corporate social responsibility (CSR). It traces the transformation of corporations from quasi-public institutions at inception to purely private enterprises beginning from the middle of the nineteenth century and attempts to locate the ideology of CSR within the wider viewpoint of shareholder value.

Design/methodology/approach

This paper adopts a doctrinal approach through a critical evaluation of the nature and implications of the shareholder value ideology. Using existing literature in the area, it traces the evolution of the shareholder value ideology and how it is antithetical to any meaningful CSR regime.

Findings

The paper finds that there is a fundamental tension between ideas about the desirability of effective CSR and the belief that it is to the benefit of society as a whole for corporations to be run solely in the interest of their shareholders and for managers to seek to maximize shareholder value. This ideological tension renders contemporary CSR ineffective.

Originality/value

The paper offers a fresh insight or analysis into the transformation of corporations from quasi-social institutions to purely private enterprises in the middle of the nineteenth century. It does this by engaging in a historical narrative of the evolution of the corporate form and how contemporary ideas of shareholder value have resulted in the emergence of a contemporary CSR devoid of the radical spirit of CSR in the 1950s and 1960s.
The moderation effect of customer orientation variable on the influence of professional competence toward the quality of strategy implementation
Authors: Wahyono Wahyono
Published: October 2018

Purpose

This paper aims to investigate the moderation effect of customer orientation variable on the influence of professional competence toward the quality of strategy implementation.

Design/methodology/approach

This research is quantitative explanative associative, which is trying to explain the causality relationship between exogenous and endogenous variables. The research was conducted in the Shariah banking office in Central Java Province. The population of this research is all top and middle levels of Shariah Commercial Bank in Central Java region. The sampling technique used in this research is non-probability sampling, that is, purposive sampling, which is the method of determining the sample based on certain criteria and the research sample obtained is 113 respondents. The research approach used is quantitative with the analysis tool of Generalized Structure Component Analysis.

Findings

There is influence of professional competence variable and customer orientation on quality of implementation strategy. The higher the professional competence and customer orientation, the higher the quality of strategy implementation. It is also found that customer orientation moderates the influence of professional competence variables, which are quasi-moderating and reinforcing.

Originality/value

This research has two sources of problems, which are research gap and business phenomenon. Research on Drucker’s business purpose (1954) is realized when a firm identifies the relationship between strategic methods and its ability to generate profits. This research attempts to solve the problem or gap between market orientation and business performance, which has been widely researched by marketing experts, but still shows controversial results. In this research, the researcher takes the definition of Narver and Slater (1990) to examine market orientation because the mostly found empirical research on market orientation and innovation (Han, et.al. 1998; Subin and Workman, 2004; Ferrel and Luke, 2000) has used this conceptualization and its associated operations. Therefore, to compare and distinguish the results of this research with the results of previous research, this research uses the definition of Narver and Slater (1990). No previous study has comprehensively studied the moderating effects of customer orientation on the relation between profesional competence toward quality of strategy implementation, especially in a commercial bank in Central Java region.
Networking and new venture’s performance: mediating role of competitive advantage
Authors: Anwar Muhammad , Rehman Atiq Ur , Shah Syed Zulfiqar Ali
Published: October 2018

Purpose

The purpose of this paper is to investigate the effect of different types of networking, namely, business networking, financial networking and political networking, on the performance of new ventures and the extent to which competitive advantage influences the process.

Design/methodology/approach

Data were collected through a structured questionnaire using sample size of 319 newly established ventures in Pakistan – an emerging economy. The hypotheses were tested with structural equation modeling by using AMOS 21.

Findings

Results of the study indicate that business networking, financial networking and political networking significantly and positively contribute to new ventures performance and competitive advantage. Results also show that competitive advantage is a strong mediator between financial networking and new venture performance, as well as between business networking and new venture performance, respectively. However, in case of relationship between political networking and new venture performance, competitive advantage plays only a partial mediating role.

Practical implications

The study suggests that the owners and managers of new ventures should devote considerable efforts to developing all the three types of networks; in particular these networks are important for newly established ventures operating in emerging markets to access resources and to enhance performance.

Originality/value

Extensive review of available literature indicates that this is the first paper to assess the impact of networking on new ventures’ performance with a mediating role of competitive advantage. This study contributes to the existing literature through empirical evidence.
Sovereign entrepreneurship
Authors: Salter Alexander
Published: October 2018

Purpose

The purpose of this paper is to develop a theory of sovereign entrepreneurship, which is a special kind of political entrepreneurship.

Design/methodology/approach

This paper uses qualitative methods/historical survey.

Findings

Sovereignty is rooted in self-enforced exchange of political property rights. Sovereign entrepreneurship is the creative employment of political property rights to advance a plan.

Research limitations/implications

Because a polity’s constitution is determined by its distribution of political property rights, sovereign entrepreneurship and constitutional change are necessarily linked. The author illustrated how sovereign entrepreneurship can be applied by using it to explain the rise of modern states.

Practical implications

In addition to studying instances of sovereign entrepreneurship in distant history, scholars can apply it to recent history. Sovereign entrepreneurship can be especially helpful as a tool for doing analytic narratives of low-n cases of political-economic development, especially when those polities attract interests for being “development miracles.”

Originality/value

This paper uses treats sovereignty as a political property right.
Bat overpasses: An insufficient solution to restore habitat connectivity across roads
Authors: Claireau Fabien , Bas Yves , Puechmaille Sébastien J. , Julien Jean‐François , Allegrini Benjamin , Kerbiriou Christian
Published: October 2018

Roads have many negative effects on wildlife, including their role in habitat fragmentation. Habitat fragmentation affects bats during their daily movements between roosts and foraging areas. As bats are protected in Europe, developers must implement specific mitigation measures that are hierarchically structured to achieve a null net impact. However, very few specific mitigation measures have been undertaken specifically for bats. Bat overpasses (e.g. gantries) are among proposed improvements intended to reduce the impact of roads, but they have rarely been tested. The effectiveness of overpasses in facilitating safe road crossing of bats is critical for justifying the implementation of this mitigation measure. We therefore assessed whether bat overpasses are effectively used by bats.

We studied three bat overpasses with different designs in France. We developed an innovative method to characterize bat crossings using acoustic flight path reconstruction (AFPR). We used six pairs of stereo acoustic recorders in different habitat types that were located on both sides of the road, and operated simultaneously throughout the night.

Recording data contained 57,941 bat passes and 284 bat crossings from six species of bats at the three study sites. Our results suggest that crossings are more numerous if an overpass is located where bat commuting routes have been identified by environmental impact assessment. However, we found that the proportion of bat crossings along the commuting route was the same with or without an overpass; thus highlighting that bat overpasses do not fully restore habitat connectivity.

Synthesis and applications. Our study demonstrates that acoustic flight path reconstruction (AFPR) is a useful approach to obtain information on bat flight behaviour. We also emphasize the importance of field testing the effectiveness of mitigation measures, such as those intended to offset the impact of roads on biodiversity, and highlight that such measures should not be implemented based on their theoretical effectiveness alone.
Missing the people for the trees: Identifying coupled natural–human system feedbacks driving the ecology of Lyme disease
Authors: MacDonald Andrew J. , Larsen Ashley E. , Plantinga Andrew J.
Published: October 2018

Infectious diseases are rapidly emerging and many are increasing in incidence across the globe. Processes of land‐use change, notably habitat loss and fragmentation, have been widely implicated in the emergence and spread of zoonoses such as Lyme disease, yet evidence remains equivocal.

Here, we discuss and apply an innovative approach from the social sciences; instrumental variables, which seeks to tease out causality from observational data. Using this approach, we revisit the effect of forest fragmentation on Lyme disease incidence, focusing on human interaction with fragmented landscapes. Although human interaction with infected ticks is of clear and fundamental importance to human disease incidence, human activities that influence exposure have been largely overlooked in ecology literature.

Using county‐level land‐use and Lyme disease incidence data for ~800 counties from the northeastern United States over the span of a decade, we illustrate (a) that human interaction with fragmented forest landscapes reliably predicts Lyme disease incidence, while ecological measures of forest fragmentation alone are unreliable predictors and (b) that identifying the effect of forest fragmentation on human disease entails addressing the feedback between Lyme disease risk and human decisions to avoid interaction with high‐risk landscapes.

Synthesis and applications. Our innovative approach and novel results help to clarify the equivocal literature on the effects of forest fragmentation on Lyme disease and illustrate the key role that human behaviour may be playing in the ecology of Lyme disease in North America. Accounting for human activity and behaviour in the ecology of disease more broadly may result in improved understanding of both the ecological drivers of disease, as well as actionable intervention strategies to reduce disease burden in a changing world. For example, our model results indicate that forest fragmentation by human settlement increases Lyme disease incidence, which has practical implications for land‐use policy aimed at disease reduction. Specifically, our model suggests land‐use regulations that reduce parcel size would be an actionable approach to reduce Lyme disease transmission for policymakers concerned about increasing Lyme disease incidence in the northeastern United States.
Banks as Tax Planning Intermediaries
Authors: GALLEMORE JOHN , GIPPER BRANDON , MAYDEW EDWARD
Published: October 2018

We provide the first large‐scale empirical evidence of banks functioning as tax planning intermediaries. We posit that some banks specialize in assisting corporate clients with tax planning. In this role, banks make use of their centrality in financial relationships; access to private information; and ability to structure, execute, and participate in tax planning transactions for clients. We measure bank‐client relationships using loan contracts and measure client tax planning using either the cash effective tax rate or the unrecognized tax benefit balance. Using a difference‐in‐differences design, we find that firms experience meaningful tax reductions when they begin a relationship with a bank whose existing clients engage in above‐median tax planning. The effects of pairing with such tax intermediary banks are concentrated in relationships with larger or longer maturity loans, clients with foreign income or greater credit risk, and when the bank is an industry specialist or has above‐median investment banking activities. Finally, we find that potential clients are more likely to choose tax intermediary banks than nontax intermediary banks, suggesting that tax intermediary banks benefit by attracting new business. Collectively, our results suggest that some banks act as tax planning intermediaries, a role beyond the traditional one of financial intermediary.
Comparative proteomic analysis of four biotechnological strains Lactococcus lactis through label‐free quantitative proteomics
Authors: Silva Wanderson M. , Sousa Cassiana S. , Oliveira Leticia C. , Soares Siomar C. , Souza Gustavo F.M.H. , Tavares Guilherme C. , Resende Cristiana P. , Folador Edson L. , Pereira Felipe L. , Figueiredo Henrique , Azevedo Vasco
Published: October 2018

Lactococcus lactis is a bacteria with high biotechnological potential, where is frequently used in the amino acid production and production of fermented dairy products, as well as drug delivery systems and mucosal vaccine vector. The knowledge of a functional core proteome is important extremely for both fundamental understanding of cell functions and for synthetic biology applications. In this study, we characterized the L. lacits proteome from proteomic analysis of four biotechnological strains L. lactis: L. lactis subsp. lactis NCDO2118, L. lactis subsp. lactis IL1403, L. lactis subsp. cremoris NZ9000 and L. lactis subsp. cremoris MG1363. Our label‐free quantitative proteomic analysis of the whole bacterial lysates from each strains resulted in the characterization of the L. lactis core proteome that was composed by 586 proteins, which might contribute to resistance of this bacterium to different stress conditions as well as involved in the probiotic characteristic of L. lactis. Kegg enrichment analysis shows that ribosome, metabolic pathways, pyruvate metabolism and microbial metabolism in diverse environments were the most enriched. According to our quantitative proteomic analysis, proteins related to translation process were the more abundant in the core proteome, which represent an important step in the synthetic biology. In addition, we identified a subset of conserved proteins that are exclusive of the L. lactis subsp. cremoris or L. lactis subsp. lactis, which some are related to metabolic pathway exclusive. Regarding specific proteome of NCDO2118, we detected ‘strain‐specific proteins’. Finally, proteogenomics analysis allows the identification of proteins, which were not previously annotated in IL1403 and MG1363. The results obtained in this study allowed to increase our knowledge about the biology of L. lactis, which contributes to the implementation of strategies that make it possible to increase the biotechnological potential of this bacterium.
Deep‐Seated Landslides Drive Variability in Valley Width and Increase Connectivity of Salmon Habitat in the Oregon Coast Range
Authors: Beeson Helen W. , Flitcroft Rebecca L. , Fonstad Mark A. , Roering Joshua J.
Published: October 2018

Declines in populations of Pacific salmon have prompted extensive and costly restoration efforts, yet many populations are still in peril. An improved understanding of landscape‐scale controls on salmon habitat should help focus restoration resources on areas with the greatest potential to host productive habitat. We investigate the contribution of deep‐seated landslides (DSLs) to Coho Salmon habitat by comparing the quantity and connectivity of potential seasonal habitat observed in five streams with extensive DSLs to five lacking significant landsliding. Further, we measure valley width in these streams and relate it to connectivity. We show that median fractions of stream length identified as spawning, summer‐rearing, winter‐refuge habitat, and as having high connectivity among seasonal habitat types are greater in streams with DSLs and that distances between units of each seasonal habitat type are significantly lower in DSL terrain. The median R2 value for the relationship between drainage area and valley width is lower in landslide terrain and we observed that high connectivity among seasonal habitat types tends to occur where valley width is variable. Our results suggest that DSLs promote connectivity among seasonal habitat types for Coho Salmon and that prioritizing restoration projects in streams in DSL terrain could improve the effectiveness of salmonid recovery programs.
Heme oxygenase‐1 induction attenuates senescence in chronic obstructive pulmonary disease lung fibroblasts by protecting against mitochondria dysfunction
Authors: Even Benjamin , Fayad‐Kobeissi Sarah , Gagliolo Jean‐Marie , Motterlini Roberto , Boczkowski Jorge , Foresti Roberta , Dagouassat Maylis
Published: October 2018

Chronic obstructive pulmonary disease (COPD) is associated with lung fibroblast senescence, a process characterized by an irreversible proliferation arrest associated with secretion of inflammatory mediators. ROS production, known to induce senescence, is increased in COPD fibroblasts and mitochondria dysfunction participates in this process. Among the battery of cellular responses against oxidative stress damage, heme oxygenase (HO)‐1 plays a critical role in defending the lung against oxidative stress and inflammation. Therefore, we investigated whether pharmacological induction of HO‐1 by chronic hemin treatment attenuates senescence and improves dysfunctional mitochondria in COPD fibroblasts. Fibroblasts from smoker controls (S‐C) and COPD patients were isolated from lung biopsies. Fibroblasts were long‐term cultured in the presence or absence of hemin, and/or ZnPP or QC‐15 (HO‐1 inhibitors). Lung fibroblasts from smokers and COPD patients displayed in long‐term culture a senescent phenotype, characterized by a reduced replicative capacity, an increased senescence and inflammatory profile. These parameters were significantly higher in senescent COPD fibroblasts which also exhibited decreased mitochondrial activity (respiration, glycolysis, and ATP levels) which led to an increased production of ROS, and mitochondria biogenesis and impaired mitophagy process. Exposure to hemin increased the gene and protein expression level of HO‐1 in fibroblasts and diminished ROS levels, senescence, the inflammatory profile and simultaneously rescued mitochondria dysfunction by restoring mitophagy in COPD cells. The effects of hemin were abolished by a cotreatment with ZnPP or QC‐15. We conclude that HO‐1 attenuates senescence in COPD fibroblasts by protecting, at least in part, against mitochondria dysfunction and restoring mitophagy.
Multicenter Implementation of a Novel Management Protocol Increases the Outpatient Treatment of Pulmonary Embolism and Deep Vein Thrombosis
Authors: Kabrhel Christopher , Rosovsky Rachel , Baugh Christopher , Connors Jean , White Benjamin , Giordano Nicholas , Torrey Jasmine , Deadmon Erin , Parry Blair Alden , Hagan Sean , Zheng Hui
Published: October 2018

Objective

The objective was to determine whether a protocol combining risk stratification, treatment with the direct‐acting oral anticoagulant rivaroxaban, and defined follow‐up is associated with a greater proportion of patients with venous thromboembolism (VTE) treated as outpatients, without hospital admission.

Methods

We performed a multicenter study of patients diagnosed with VTE (pulmonary embolism [PE] or deep vein thrombosis [DVT]) in two urban EDs, 18 months before and 18 months after implementation of an outpatient VTE treatment protocol. Patients with radiographically confirmed acute VTE were eligible. Our primary outcome was the proportion of VTE patients discharged from the ED or observation unit (i.e., without hospital admission). We performed subgroup analyses according to hospital, DVT and PE, and low‐risk PE. We also assessed 7‐ and 30‐day mortality, major bleeding, and returns to the ED. We compared proportions using chi‐square and Fisher's exact tests.

Results

We enrolled 2,212 patients, 1,081 (49%) before protocol and 1,131 (51%) after protocol. Mean age (59 years vs. 60 years), female sex (49% vs. 49%), other demographics, comorbid illness, and PE risk stratification were similar before and after. After protocol, more VTE (35% from 26%, p < 0.001), PE (18% from 12%, p = 0.002), low‐risk PE (28% from 18%, p < 0.001), and DVT (60% from 49%, p = 0.002) patients were treated as outpatients. Mortality, bleeding, and returns to ED were rare and did not increase after protocol.

Conclusions

A treatment protocol combining risk‐stratification, rivaroxaban treatment and defined follow‐up is associated with an increase in PE and DVT patients treated as outpatients, with no increase in adverse outcomes.
Anticariogenic efficacy of a saliva biomimetic in head‐and‐neck cancer patients undergoing radiotherapy
Authors: Sim CPC , Walker GD , Manton DJ , Soong YL , Wee JTS , Adams GG , Reynolds EC
Published: October 2018

Background

The aim of this study was to investigate the effect of treatment with the saliva biomimetic, casein phosphopeptide‐amorphous calcium phosphate (CPP‐ACP) and SnF2/NaF compared with SnF2/NaF alone on coronal surface caries progression in head‐and‐neck cancer patients undergoing radiotherapy.

Methods

Twenty‐four participants were randomized into two groups. Both groups used 0.4% SnF2 gel and a 0.32% NaF toothpaste; the test group also applied a crème containing 10% CPP‐ACP three times daily while the control group used an identical crème without CPP‐ACP (placebo). Resting saliva flow rate and saliva fluoride concentrations were determined. Caries status was assessed using ICDASII at baseline and 12‐weeks postradiotherapy. Data were statistically analysed using a linear mixed effects model.

Results

Both groups showed significantly reduced resting saliva flow rate (P < 0.001) postradiotherapy. There were no significant differences in flow rates and fluoride concentration between groups. The CPP‐ACP group exhibited a significant (P < 0.05) 51% reduction in coronal surface caries progression compared with the placebo group.

Conclusion

Resting salivary flow rate was significantly reduced in head‐and‐neck cancer patients following radiotherapy and use of CPP‐ACP with SnF2/NaF significantly lowered caries progression compared with SnF2/NaF alone.
Cash Holdings Adjustment Speed and Managerial Ability
Authors: Cho Hyungjin , Choi Sera , Kim Mi‐Ok
Published: October 2018

Using the partial adjustment model of cash holding, we find that managerial ability is negatively related to adjustment speed of cash holdings toward the target, particularly when the firm has excess cash. We also find that the relation between managerial ability and cash holding adjustment speed is weaker in the presence of the internal capital market. Additionally, we provide evidence that firms with higher managerial ability are less likely to make inefficient investments when they have excess cash, implying that high‐ability managers are willing to hold a large amount of cash to make timely investments.
C5a receptor 1−/− mice are protected from the development of IgE‐mediated experimental food allergy
Authors: Kordowski Anna , Reinicke Anna T. , Wu David , Orinska Zane , Hagemann Philipp , Huber‐Lang Markus , Lee Jee‐Boong , Wang Yui‐Hsi , Hogan Simon P. , Köhl Jörg
Published: October 2018

Background

Food‐induced anaphylaxis is a serious allergic reaction caused by Fcε‐receptor activation on mast cells (MCs). The exact mechanisms breaking oral tolerance and the effector pathways driving food allergy remain elusive. As complement is activated in food‐induced anaphylaxis, we aimed to assess the role of C5a in disease pathogenesis.

Methods

Oral antigen‐induced food‐induced anaphylaxis was induced in BALB/c wild‐type (wt) and C5ar1−/− mice. Readouts included diarrhea development, changes in rectal temperature, hematocrit, antigen‐specific serum IgE, MCPT‐1, and intestinal MC numbers, as well as FcεR1‐mediated MC functions including C5a receptor 1 (C5aR1) regulation. Further, histamine‐mediated hypothermia and regulation of endothelial tight junctions were determined.

Results

Repeated oral OVA challenge resulted in diarrhea, hypothermia, increased hematocrit, high OVA‐specific serum IgE, and MCPT‐1 levels in wt mice. Male C5ar1−/− mice were completely whereas female C5ar1−/− mice were partially protected from anaphylaxis development. Serum MCPT‐1 levels were reduced gender‐independent, whereas IgE levels were reduced in male but not in female C5ar1−/− mice. Mechanistically, IgE‐mediated degranulation and IL‐6 production from C5ar1−/− BMMCs of both sexes were significantly reduced. Importantly, FcεR1 cross‐linking strongly upregulated C5aR1 MC expression in vitro and in vivo. Finally, C5ar1−/− male mice were largely protected from histamine‐induced hypovolemic shock, which was associated with protection from histamine‐induced barrier dysfunction in vitro following C5aR targeting.

Conclusions

Our findings identify C5aR1 activation as an important driver of IgE‐mediated food allergy through regulation of allergen‐specific IgE production, FcεR1‐mediated MC degranulation, and histamine‐driven effector functions preferentially in male mice.
Accepting the avoidable death: The philosophy of limiting intensive care
Authors: Sørensen Marc , Andersen Lars Willy
Published: October 2018

Limiting intensive care is paid increasing attention. In the echoing call for physicians’ ethical self‐restriction, it is easily overlooked, however, that ethics needs a critical epistemological analysis before it can suffice as an emergency brake to futile treatment. This analysis is provided by the present essay. The authors suggest that the difficulties of resolving moral dilemmas related to limiting intensive care may just be due to the unclarified epistemological status of moral claims. Even if normative ethics cannot prescribe right decisions, but only draw conclusions from defined premises, the premises may or may not be true. Their intertwined descriptive and normative evidence is endorsed in an academic and political discourse. There will necessarily be various demands for rationality in prudent decisions between physicians, their patients and society. These demands are formulated dialogically through critical questions and justified answers. A good argument is the convincing one that, finally and ideally, leads to the absence of open objections. Thus, in the end the rightness of a given decision does not depend on axiomatic moral principles, but is comparative and conditional, as it is given in an omnilateral argument. Neither is it the democratic process of shared decision making that we should evaluate, but rather the argumentative state itself, when we judge the morality of health politics and clinical practice.
Medical crowdfunding and the virtuous donor
Authors: Moore Bryanna
Published: October 2018

Patients and families are increasingly turning to crowdfunding to help them cover the cost of medical care. The ethics of crowdfunding has garnered some attention in the bioethical literature. In this paper I examine an ethical aspect of medical crowdfunding (MCF) that has received limited attention: the role of donors. I defend a virtue ethical approach to analyzing the role of donors in MCF. Vicious donation, where donors do not exercise the relevant virtues, can compound some of the ethical risks associated with MCF, as seen in the several recent, high‐profile cases. My primary contention in this paper is that encouraging donors to think about how donating to a particular campaign would measure against the virtues I outline could help to discourage acts of ethically problematic donation to MCF campaigns.
Ectogenesis and the case against the right to the death of the foetus
Authors: Blackshaw Bruce P. , Rodger Daniel
Published: October 2018

Ectogenesis, or the use of an artificial womb to allow a foetus to develop, will likely become a reality within a few decades, and could significantly affect the abortion debate. We first examine the implications for Judith Jarvis Thomson’s violinist analogy, which argues for a woman’s right to withdraw life support from the foetus and so terminate her pregnancy, even if the foetus is granted full moral status. We show that on Thomson’s reasoning, there is no right to the death of the foetus, and abortion is not permissible if ectogenesis is available, provided it is safe and inexpensive. This raises the question of whether there are persuasive reasons for the right to the death of the foetus that could be exercised in the context of ectogenesis. Eric Mathison and Jeremy Davis have examined several arguments for this right, doubting that it exists, while Joona Räsänen has recently criticized their reasoning. We respond to Räsänen’s analysis, concluding that his arguments are unsuccessful, and that there is no right to the death of the foetus in these circumstances.
Histamine pharmacology: from Sir Henry Dale to the 21st century
Authors: Tiligada Ekaterini , Ennis Madeleine
Published: October 2018

Histamine has been one of the most studied substances in medicine, playing a major role in diverse (patho)physiological processes. It elicits its multifaceted modulatory functions by activating four types of GPCRs, designated as H1–4. Despite the heterogeneity and the complexity of histamine receptor pharmacology, many discoveries over the past 100 years resulted in the development of H1 antihistamines and H2‐targeting ‘blockbuster’ therapeutics for the management of allergies and gastrointestinal disorders respectively. Recently, a first‐in‐class H3 inverse agonist was approved for the treatment of narcolepsy, whereas H4 antagonists are under clinical evaluation for their potential therapeutic exploitation in immune‐related diseases. This review critically presents the past successes and drawbacks in histamine research, complemented by the modern conceptual innovations in molecular and receptor pharmacology. It targets both young and experienced researchers in an ongoing effort to stimulate novel insights for the dissection of the translational potential of histamine pharmacology.

Linked Articles

This article is part of a themed section on New Uses for 21st Century. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.3/issuetoc
Modelling of drainage dynamics influence on sediment routing system in a fold‐and‐thrust belt
Authors: Viaplana‐Muzas Marc , Babault Julien , Dominguez Stéphane , Van Den Driessche Jean , Legrand Xavier
Published: October 2018

Drainage networks link erosional landscapes and sedimentary basins in a source‐to‐sink system, controlling the spatial and temporal distribution of sediment flux at the outlets. Variations of accumulation rates in a sedimentary basin have been classically interpreted as changes in erosion rates driven by tectonics and/or climate. We studied the interactions between deformation, rainfall rate and the intrinsic dynamics of drainage basins in an experimental fold‐and‐thrust belt subjected to erosion and sedimentation under constant rainfall and shortening rates. The emergence of thrust sheets at the front of a prism may divert antecedent transverse channels (perpendicular to the structural grain) leading to the formation of longitudinal reaches, later uplifted and incorporated in the prism by the ongoing deformation. In the experiments, transverse incisions appear in the external slopes of the emerging thrust sheets. Headward erosion in these transverse channels results in divide migration and capture of the uplifted longitudinal channels located in the inner parts of the prism, leading to drainage network reorganization and modification of the sediment routing system. We show that the rate of drainage reorganization increases with the rainfall rate. It also increases in a nonlinear way with the rate of uplift. We explain this behaviour by an exponent > 1 on the slope variable in the framework of the stream power erosion model. Our results confirm the view that early longitudinal‐dominated networks are progressively replaced by transverse‐dominated rivers during mountain building. We show that drainage network dynamics modulate the distribution of sedimentary fluxes at the outlets of experimental wedges. We propose that under constant shortening and rainfall rates the drainage network reorganization can also modulate the composition and the spatial distribution of clastic fluxes in foreland basins.
Does fatigue and distress in a clinical cohort of adolescents with chronic fatigue syndrome correlate with fatigue and distress in their parents?
Authors: Loades Maria E. , Rimes Katharine A. , Ali Sheila , Lievesley Kate , Chalder Trudie
Published: October 2018

Objectives

Previous studies have found that parents of children with chronic fatigue syndrome (CFS) are more fatigued, and mothers are more distressed than healthy controls. Managing the disabling symptoms of CFS can result in disruption and burden for the family. Most research has focused on mothers. This study sought to further explore the associations between adolescent fatigue and distress and parental fatigue and distress, as well as family functioning, including both mothers and fathers.

Design

Cross‐sectional study of a clinical cohort of consecutive attenders at a specialist chronic fatigue unit.

Methods

Questionnaires were completed by adolescents (N = 115, age 11–18) with a confirmed diagnosis of CFS and their mothers (N = 100) and fathers (N = 65).

Results

Maternal fatigue was significantly correlated with maternal distress, but not with adolescent fatigue, depression, anxiety, or functioning. This pattern held true for paternal fatigue. Maternal and paternal anxiety and depression were significantly correlated with family functioning. Paternal and maternal distress were correlated with each other. Mothers and fathers tended to have a consistent view of family functioning. Family functioning, specifically being overwhelmed by difficulties and scoring lower on strengths and adaptability, was positively associated with adolescent depression. Unexpectedly, higher levels of adolescent fatigue and poorer physical functioning were associated with better family functioning as rated by the mother.

Conclusions

Parents of adolescents with fatigue scored near to or within normative range for non‐clinical samples on distress, fatigue, and family functioning. Parental distress may contribute to or result from poorer family functioning. Family functioning, particularly building strengths and adaptability, may be clinically important in CFS, as well as attending to parental (particularly paternal) distress in families where adolescents are low in mood.
Changing trends in surgery for abdominal Crohn's disease
Authors: Mege D. , Garrett K. , Milsom J. , Sonoda T. , Michelassi F.
Published: October 2018

Aim

The introduction of biological agents and laparoscopy are, arguably, the most important developments for the treatment of Crohn's disease (CD) in the last two decades. Due to the efficacy of biological agents in treating mild disease, it is likely that the percentage of surgery for complex cases may have increased. The objective of this study was to analyse the changing characteristics and results of the surgical treatment of patients with CD over the past 13 years.

Methods

All patients who underwent abdominal surgery for CD between 2004 and 2016 were retrospectively identified. Data were compared between two periods (2004–2010 and 2011–2016).

Results

A total of 908 procedures were performed (48% men, mean age 43 ± 16 years). Demographic and CD characteristics changed significantly over time: comorbidities were more frequent (35% vs 46%, P < 0.0001), and preoperative steroids (28% vs 36%, P < 0.01) and anti‐tumour necrosis factor (20% vs 40%, P < 0.0001) treatments were more frequently used in the second period. Smoking (14% vs 8%, P < 0.0001) and use of immunosuppressors (32% vs 22%, P < 0.001) decreased significantly. More cases of penetrating disease (22% vs 32%, P < 0.001) were operated upon in the second period. The laparoscopic approach (49% vs 57%, P < 0.04) was more frequently performed and mean blood loss (167 ± 222 vs 123 ± 243 ml, P < 0.01) decreased significantly. Postoperative morbidity did not change between the two periods.

Conclusion

Despite a higher incidence of comorbidities and the use of biologics postoperative morbidity remained unchanged. An increased use of laparoscopy and a decreased intra‐operative blood loss may have contributed to offsetting the impact of increased comorbidity.
Novel Implementation of Genotype‐Guided Proton Pump Inhibitor Medication Therapy in Children: A Pilot, Randomized, Multisite Pragmatic Trial
Authors: Cicali Emily J. , Blake Kathryn , Gong Yan , Mougey Edward B. , Al‐Atrash Hadeel , Chambers Nancy , Denham Jolanda , Evans Jonathan , George Donald E. , Gomez Roberto , Palomo Pablo , Taufiq Salik , Johnson Julie A. , Lima John J. , Franciosi James P.
Published: October 2018

The efficacy of proton pump inhibitor (PPI) medications is highly dependent on plasma concentrations, which varies considerably due to cytochrome P450 (CYP2C19) genetic variation. We conducted a pragmatic, pilot study of CYP2C19 genotype‐guided pediatric dosing of PPI medications. Children aged 5–17 years old with gastric‐acid‐related conditions were randomized to receive either conventional dosing of a PPI or genotype‐guided dosing for a total of 12 weeks. Sixty children (30 in each arm) were enrolled and had comparable baseline characteristics. The mean daily omeprazole equivalent dose prescribed to participants across metabolizer phenotype groups was significantly different in the genotype‐guided dosing arm (P < 0.001), but not in the conventional dosing arm. Prescribers waited for the genotype result before prescribing the PPI medication for 90% of the participants in the genotype‐guided dosing arm. The number of participants who reported an infection was marginally lower in genotype‐guided dosing vs. conventional dosing (20% vs. 44%; P = 0.07). Sinonasal symptoms were higher in the conventional dosing arm as compared with genotype‐guided dosing arm: (2.6 (2.0, 3.4) vs. 1.8 (1.0, 2.3), P = 0.031). CYP2C19 genotype‐guided PPI therapy is feasible in a clinical pediatric setting, well accepted by providers, resulted in differential PPI dosing, and may reduce PPI‐associated infections. A future large scale randomized clinical trial of CYP2C19 genotype‐guided pediatric dosing of PPI medications in children is warranted.
Endoscopic submucosal dissection under D‐sorbitol solution in an animal model
Authors: Morishita Asahiro , Kobara Hideki , Masaki Tsutomu
Published: October 2018

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Pinus taedaL. response to differential inoculum density ofLeptographium terebrantiscolonized toothpicks
Authors: Devkota Pratima , Mensah John K. , Nadel Ryan L. , Matusick George , Eckhardt Lori G.
Published: October 2018

Bark beetle‐vectored ophiostomatoid fungi,Leptographium terebrantis, is inoculated on the roots and lower stems of stressedPinusspecies during the feeding activity of bark beetle. To determine the exact host response following inoculation, it is critical to challenge the host with a realistic amount of fungal inoculum. Thus, we designed a series of stepwise experiments usingL. terebrantiscolonized toothpicks which focused on the inoculum transfer from the toothpicks to excisedPinus taedastem segments and living saplings, respectively, at different inoculum densities. The toothpicks served as a substrate for fungal growth and sporulation and the inoculation showed their utility in eliciting host's response to the pathogen. The inoculated fungus caused blue‐stain and sapwood occlusions inP. taedastems and saplings, respectively. The volume of occluded, visually damaged sapwood increased by 1.96 cm3per radial inoculation point on average. Fungal colonized toothpicks can be used as a suitable alternative to agar discs for studying bark beetles vectored fungi and their host interactions.
Structural insight into Wnt signaling inhibition by Clostridium difficile toxin B
Authors: Chen Peng , Tao Liang , Liu Zheng , Dong Min , Jin Rongsheng
Published: October 2018

The incidence of Clostridium difficile infection (CDI) has increased significantly worldwide, causing substantial morbidity and mortality. One of the major virulence factor, TcdB, manages to enter the colonic epithelia via the human frizzled proteins (FZDs), which are physiological receptors for Wnt morphogens. Binding of TcdB to FZDs inhibits Wnt signaling, which may contribute to pathogenesis of CDI. Here, we review the structural mechanism by which TcdB exploits to recognize FZDs for cell entry and inhibiting Wnt signaling, which reveals new strategies to modulate Wnt signaling for therapeutic interventions.
Serum Vitamin D Status in a Group of Migraine Patients Compared With Healthy Controls: A Case–Control Study
Authors: Togha Mansoureh , Razeghi Jahromi Soodeh , Ghorbani Zeinab , Martami Fahimeh , Seifishahpar Maryam
Published: October 2018

Objective

The association between serum vitamin D and migraine is investigated in this research.s

Background

Although the pathogenesis of migraine headache is not fully understood, the possible role of inflammation and disturbed immune system has been proposed; thus, higher levels of vitamin D might reduce the risk of migraine. However, the results of related studies have been inconclusive.

Methods

Seventy healthy individuals and 70 age‐ and sex‐matched migraineurs (34 chronic and 36 episodic migraineurs), diagnosed according to the International Headache Society criteria (ICHD‐IIIβ), were recruited. After obtaining baseline data and assessing migraine disability, a 30‐day headache diary was given to the participants. Blood samples were obtained and 25(OH)D serum concentrations were determined using ELISA techniques. Serum 25(OH)D under 20, 20–29, and 30–100 ng/mL were considered deficient, insufficient, and sufficient, respectively. The applied statistical tests for between‐group comparisons include independent‐sample t‐test, chi‐square, and analysis of variance. Multiple regression analysis was also performed to identify the possible risk factors of migraine headache.

Results

Migraine patients had significantly lower mean (SD) of serum VitD (30 (16) ng/mL) than healthy subjects (43 (19) ng/mL) (P < .001). The number (%) of subjects with VitD deficiency and insufficiency was significantly higher among the migraineurs (36 (53.7%)) than the controls (18 (26.1%)) (P < .0001). A significant negative association between migraine headache and serum VitD was detected in the fully adjusted multiple regression models when comparing the third and the highest serum 25(OH)D quartiles with the lowest (OR = 0.20; 95% CI = 0.05–0.77; OR = 0.17; 95% CI = 0.04–0.64, respectively, P for trend = .009). For each 5 ng/mL increase in serum 25(OH)D, there was a 22% odds decrease in the odds of migraine (OR = 0.78; 95% CI = 0.68–0.90; P = .001).

Conclusion

We have found that a higher level of serum VitD (between 50 to less than 100 ng/mL) among a sample of the Iranian population is associated with 80–83% lower odds of migraine headache than those with serum 25(OH)D levels below 20 ng/mL. However, there is a need for well‐designed clinical trials to investigate beneficial effects of increased serum 25(OH)D on lower risk of migraine.
Microguided Endodontics: a case report of a maxillary lateral incisor with pulp canal obliteration and apical periodontitis
Authors: Torres A. , Shaheen E. , Lambrechts P. , Politis C. , Jacobs R.
Published: October 2018

Aim

To describe a minimally invasive method to create a 3D‐printed guide to gain access to obliterated root canals on the basis of CBCT data.

A 85‐year‐old female ASA III was referred for root canal treatment of tooth 22. Clinically, there were no complaints, no percussion pain or sinus tract. Radiologically, the tooth had an obliterated canal with an apical radiolucency. The tooth was diagnosed with asymptomatic apical periodontitis. Microguided Endodontic treatment was performed with the help of a 3D‐printed guide. The root canal was localized initially with the aid of the 3D‐printed guide using a round carbide bur with a head diameter of 0.8 mm. Then, the canal was shaped and cleaned using mechanical rotary files under copious irrigation with 5% NaOCl, 17% EDTA and passive ultrasonic activation. A completely healed apical area of tooth 22 was visible after 6 months on periapical radiographs and small field of view CBCT.

Key learning points

Using the Microguided Endodontics concept, a minimally invasive access was achieved up to the middle of the root, in a maxillary lateral incisor with pulp canal obliteration (PCO) and apical periodontitis.

This technique is a valuable tool for the negotiation of PCO, reducing chair time and risk of iatrogenic damage to the root.
The impact of International Financial Reporting Standards (IFRS) adoption and IFRS renouncement on audit fees: The case of Switzerland
Authors: Raffournier Bernard , Schatt Alain
Published: October 2018

Several studies have shown that International Financial Reporting Standards (IFRS) adoption is associated with higher audit fees. We provide additional evidence on this issue by analyzing the Swiss context, which is particularly suitable for two reasons. First, it allows a better estimation of the impact of IFRS adoption on audit fees because the choice of accounting standards (IFRS, US generally accepted accounting principles [GAAPs] or Swiss GAAPs) is left to companies. Accordingly, comparisons can be made within the same institutional context. Second, it is also possible to measure the impact of IFRS renouncement on audit fees because Swiss companies following IFRS can switch back to Swiss GAAPs at any time. Based on a hand‐collected database including 1,651 firm‐year observations over 15 years, we show that, with the exception of very large companies, firms using IFRS pay higher audit fees. We also find that firms switching to IFRS incur additional audit fees in the year preceding the change. By contrast, the return to local GAAPs does not result in lower audit fees, which confirms the stickiness of audit fees reported by several prior studies.
The role of auditors in merger and acquisition completion time
Authors: Chahine Salim , Hasan Iftekhar , Mazboudi Mohamad
Published: October 2018

Using a sample of 664 merger and acquisition (M&A) transactions and office‐level audit data, this study investigates the role of auditors in M&A completion time. We find that having a common auditor for both acquirer and target firms in M&A transactions increases the completion time of such transactions because the exposure to higher litigation and reputational costs outweighs the information‐access advantage of common auditors. However, auditors' past experience in M&A transactions helps reduce completion time and costs. These results are robust to having Big N auditors at both ends as well as to various acquirer, target, and deal characteristics.